485
MORPHOLOGIC FEATURES. The disease charac-
teristically affects distal bronchi and bronchioles beyond
the segmental bronchi.
Grossly, the lungs may be involved diffusely or
segmentally. Bilateral involvement of lower lobes occurs
most frequently. More vertical air passages of left lower
lobe are more often involved than the right. The pleura is
usually fibrotic and thickened with adhesions to the chest
wall. The dilated airways, depending upon their gross or
bronchographic appearance, have been subclassified into
the following different types (Fig. 17.22):
i) Cylindrical: the most common type characterised by
tube-like bronchial dilatation.
ii) Fusiform: having spindle-shaped bronchial dilatation.
iii) Saccular: having rounded sac-like bronchial distension.
iv) Varicose: having irregular bronchial enlargements.
Cut surface of the affected lobes, generally the lower
zones, shows characteristic honey-combed appearance. The
bronchi are extensively dilated nearly to the pleura, their
walls are thickened and the lumina are filled with mucus or
Figure 17.22 Types of bronchial dilatations in bronchiectasis. muco-pus. The intervening lung parenchyma is reduced and
fibrotic (Fig. 17.23).
v) Atopic bronchial asthma patients have often positive family
history of allergic diseases and may rarely develop diffuse Microscopically, fully-developed cases show the CHAPTER 17
bronchiectasis. following histologic features (Fig. 17.24):
i) The bronchial epithelium may be normal, ulcerated
2. Obstruction. Post-obstructive bronchiectasis, unlike the or may show squamous metaplasia.
congenital-hereditary forms, is of the localised variety, ii) The bronchial wall shows infiltration by acute and
usually confined to one part of the bronchial system. The chronic inflammatory cells and destruction of normal
causes of endobronchial obstruction include foreign bodies, muscle and elastic tissue with replacement by fibrosis.
endobronchial tumours, compression by enlarged hilar
lymph nodes and post-inflammatory scarring (e.g. in healed iii) The intervening lung parenchyma shows fibrosis,
while the surrounding lung tissue shows changes of
tuberculosis) all of which favour the development of post- interstitial pneumonia.
obstructive bronchiectasis.
iv) The pleura in the affected area is adherent and shows The Respiratory System
3. As secondary complication. Necrotising pneumonias such bands of fibrous tissue between the bronchus and the
as in staphylococcal suppurative pneumonia and tuberculosis pleura.
may develop bronchiectasis as a complication.
Figure 17.23 Bronchiectasis of the lung. Sectioned surface shows honey-combed appearance of the lung in the lower lobe where many thick-
walled dilated cavities with cartilaginous wall are seen (arrow).
486
Figure 17.24 Microscopic appearance of a dilated distal bronchiole in bronchiectasis. The bronchial wall is thickened and infiltrated by acute
and chronic inflammatory cells. The mucosa is sloughed off at places with exudate of muco-pus in the lumen (arrow).
CLINICAL FEATURES. The clinical manifestations of 3. Severe obesity
bronchiectasis typically consist of chronic cough with foul- 4. Pleural diseases.
smelling sputum production, haemoptysis and recurrent As a group, these conditions cause restriction to
pneumonia. Sinusitis is a common accompaniment of diffuse expansion of lungs due to alterations in chest wall, pleura
bronchiectasis. Late complications occurring in cases and neuromuscular apparatus, but are primarily not lung
uncontrolled for years include development of clubbing of parenchymal diseases.
the fingers, metastatic abscesses (often to the brain), B. Restriction due to interstitial and infiltrative diseases.
amyloidosis and cor pulmonale.
SECTION III
Commonly called as ‘interstitial lung diseases (ILDs)’, these
are diseases characterised by non-infectious diffuse
CHRONIC RESTRICTIVE PULMONARY DISEASE parenchymal involvement of the lung i.e. the alveolar lumina
and alveolar epithelium, capillary basement membrane, the
The second large group of diffuse lung disease is ‘chronic intervening space, perivascular tissue and lymphatic tissue.
restrictive pulmonary disease’ characterised by reduced Diffuse lung parenchymal involvement may be primary, or
expansion of lung parenchyma with decreased total lung it may be involved secondarily as a part of some other multi-
capacity. This group of diseases must be distinguished from organ disease process. The term ‘infiltrative’ is used here to
the foregoing COPD (Table 17.7). denote the radiologic appearance of lungs in chest
Restrictive lung disease includes 2 types of conditions: radiographs which show characteristic diffuse interstitial
A. Restriction due to chest wall disorder: It includes ground-glass opacities. The ILDs consist of more than 200
Systemic Pathology
following conditions: heterogeneous conditions which have common clinical,
1. Kyphoscoliosis radiologic, and functional manifestations but diverse
2. Poliomyelitis pathological features. As a group, ILDs have high mortality
TABLE 17.7: Obstructive versus Restrictive Pulmonary Diseases.
Feature Obstructive Restrictive
1. Airways Obstructed at any level from Reduced expansion of lung parenchyma
trachea to respiratory bronchiole
2. Pulmonary Increased pulmonary resistance and Decreased total lung capacity
function test obstruction of maximal expiratory airflow
3. X-ray chest Variable appearance depending Typically bilateral infiltrates giving ground-glass
upon the cause shadows
4. Examples • Chronic bronchitis • Chest cage disorders (e.g. kyphoscoliosis, poliomyelitis, severe
• Emphysema obesity and pleural disease)
• Bronchial asthma • Interstitial lung diseases (ILDs) (e.g. pneumoconioses,
• Bronchiectasis idiopathic pulmonary fibrosis, immunologic lung diseases,
collagen-vascular disease and sarcoidosis)
TABLE 17.8. Classification of Interstitial Lung Diseases (ILDs). The major common clinical manifestations of restrictive 487
lung diseases are exertional dyspnoea, non-persistent
I. WITH PREDOMINANT FIBROSIS productive cough, tachypnoea, cyanosis and sometimes
1. Pneumoconiosis with inorganic minerals: coal, asbestos, haemoptysis but no wheezing so characteristic of COPD.
fumes, gases
2. Idiopathic pulmonary fibrosis (Idiopathic interstitial pneumonias) Important and common examples of ILDs are discussed
3. Nonspecific interstitial pneumonia below.
4. Acute interstitial pneumonia (Hamman-Rich syndrome)
5. Cryptogenic organising pneumonia PNEUMOCONIOSES
6. Therapy related-ILD (radiation, antibiotics, chemotherapy) Pneumoconiosis is the term used for lung diseases caused
7. Connective tissue diseases by inhalation of dust, mostly at work (pneumo = lung; conis =
8. Residual effects of ARDS dust in Greek). These diseases are, therefore, also called ‘dust
II. WITH PREDOMINANT GRANULOMATOUS REACTION diseases’ or ‘occupational lung diseases’.
1. Sarcoidosis (Chapter 6) The type of lung disease varies according to the nature
2. Pneumoconiosis with inorganic dusts: silica, beryllium of inhaled dust. Some dusts are inert and cause no reaction
3. Granulomatous vasculitis and no damage at all, while others cause immunologic
4. Wegener’s granulomatosis damage and predispose to tuberculosis or to neoplasia. The
III. IMMUNOLOGIC LUNG DISEASES factors which determine the extent of damage caused by
(EOSINOPHILIC PNEUMONIAS) inhaled dusts are as under:
1. Hypersensitivity pneumonitis: with organic dusts 1. size and shape of the particles;
2. Pulmonary infiltrates with eosinophilia (PIE) 2. their solubility and physicochemical composition;
3. Pulmonary haemorrhage syndromes (Goodpasture’s 3. the amount of dust retained in the lungs;
syndrome) 4. the additional effect of other irritants such as tobacco
4. Pulmonary alveolar proteinosis
smoke; and
IV. SMOKING- ASSOCIATED ILDs 5. host factors such as efficiency of clearance mechanism
1. Desquamative interstitial pneumonia (DIP) and immune status of the host.
2. Respiratory bronchiolitis-associated ILD In general, most of the inhaled dust particles larger than CHAPTER 17
3. Pulmonary Langerhans cell histiocytosis (eosinophilic 5 μm reach the terminal airways where they are ingested by
granuloma of the lung)
and morbidity. Depending upon the underlying pathologic
findings, ILDs have been broadly classified into 2 groups,
each further subdivided into those with known and unknown
causes:
Conditions with predominant non-specific inflammation The Respiratory System
(alveolitis, interstitial inflammation, and fibrosis).
Conditions with predominant granulomatous inflam-
mation.
Based on this, an abbreviated classification of ILDs is
given in Table 17.8.
The exact pathogenesis of ILDs from injury to fibrosis is
not known. However, it can be explained on immune basis
as under (Fig. 17.25):
i) There is local inflammatory reaction in the alveoli in response
to various exogenous and endogenous stimuli in the form of
lymphocytes (both B and T) and macrophages.
ii) Activated macrophages cause recruitment of neutrophils
and also produce fibrogenic and chemotactic cytokines.
Neutrophils liberate proteases and oxidants which injure the
type I pneumocytes resulting in initial microscopic alveolitis,
while cytokines cause subsequent proliferation of type II
pneumocytes and fibrosis.
iii) The result is inflammatory destruction of the pulmonary
parenchyma followed by fibrosis. Eventually, there is
widespread destruction of alveolar capillary walls resulting
in end-stage lung or ‘honeycomb lung’. Figure 17.25 Schematic evolution of interstitial lung disease (ILD).
488 asymptomatic accumulation of carbon dust in the lungs of
TABLE 17.9: Classification of Pneumoconioses.
most urban dwellers due to atmospheric pollution and
Agent Diseases
cigarette smoke (anthacite refers to coal). Anthracotic pigment
A. INORGANIC (MINERAL) DUSTS is deposited in the macrophages in the alveoli and around
1. Coal dust Simple coal-workers’ the respiratory bronchioles and into the draining lymph
pneumoconiosis nodes but does not produce any respiratory difficulty or
Progressive massive radiologic changes.
fibrosis PATHOGENESIS. Pathogenetically, it appears that
Caplan’s syndrome
anthracosis, simple coal-workers’ pneumoconiosis and
2. Silica Silicosis progressive massive fibrosis are different stages in the evolu-
Caplan’s syndrome
tion of fully-developed coal-workers’ pneumoconiosis.
3. Asbestos Asbestosis However, progressive massive fibrosis develops in a small
Pleural diseases proportion of cases (2-8%) of simple coal-workers’ pneumo-
Tumours
coniosis. A number of predisposing factors have been
4. Beryllium Acute berylliosis implicated in this transformation as follows:
Chronic berylliosis
1. Older age of the miners.
5. Iron oxide Pulmonary siderosis 2. Severity of coal dust burden engulfed by macrophages.
B. ORGANIC (BIOLOGIC) DUSTS 3. Prolonged exposure (20 to 30 years) to coal dust.
4. Concomitant tuberculosis.
1. Mouldy hay Farmer’s lungs
5. Additional role of silica dust.
2. Bagasse Bagassosis
Activation of alveolar macrophage plays the most
3. Cotton, flax, hemp dust Byssinosis significant role in the pathogenesis of progressive massive
4. Bird droppings Bird-breeders’ (bird fibrosis by release of various mediators (Fig. 17.26,A):
fancier’s) lung i) Free radicals which are reactive oxygen species which
5. Mushroom compost dust Mushroom-workers’ lung damage the lung parenchyma.
6. Mouldy barley, malt dust Malt-workers’ lung ii) Chemotactic factors for various leucocytes (leukotrienes,
TNF, IL-8 and IL-6) resulting in infiltration into pulmonary
7. Mouldy maple bark Maple-bark disease
tissues by these inflammatory cells which on activation cause
8. Silage fermentation Silo-fillers’ disease
further damage.
SECTION III
iii) Fibrogenic cytokines such as IL-1, TNF and platelet derived
growth factor (PDGF) which stimulate healing by fibrosis
alveolar macrophages. Most of these too are eliminated by due to proliferation of fibroblasts at the damaged tissue site.
expectoration but the remaining accumulate in alveolar
tissue. Of particular interest are the particles smaller than MORPHOLOGIC FEATURES. In life, the pathologic
1 μm which are deposited in the alveoli most efficiently. Most changes in lung in coal-workers’ pneumoconiosis are
of the dust-laden macrophages accumulated in the alveoli graded by radiologic appearance according to the size and
die leaving the dust, around which fibrous tissue is formed. extent of opacities. The pathologic findings at autopsy of
Some macrophages enter the lymphatics and reach regional lungs in the major forms of coal-workers’ pneumoconiosis
lymph nodes. The tissue response to inhaled dust may be are considered below under 3 headings: simple coal-
one of the following three types: workers’ pneumoconiosis, progressive massive fibrosis
Fibrous nodules e.g. in coal-workers’ pneumoconiosis and and rheumatoid pneumoconiosis (Caplan’s syndrome).
Systemic Pathology
silicosis. SIMPLE COAL-WORKERS’ PNEUMOCONIOSIS.
Interstitial fibrosis e.g. in asbestosis. Grossly, the lung parenchyma shows small, black focal
Hypersensitivity reaction e.g. in berylliosis. lesions, measuring less than 5 mm in diameter and evenly
A comprehensive list of various types of occupational distributed throughout the lung but have a tendency to
lung diseases caused by inorganic (mineral) dusts and orga- be more numerous in the upper lobes. These are termed
nic dusts is presented in Table 17.9. The more common coal macules, and if palpable are called nodules. The air
examples of pneumoconioses are described here. spaces around coal macules are dilated with little
destruction of alveolar walls (Fig. 17.26,A). Though some
Coal-Workers’ Pneumoconiosis workers have called it centrilobular emphysema of coal-
miners (page 481), others prefer not to consider it
This is the commonest form of pneumoconiosis and is defined emphysema because there is no significant destruction of
as the lung disease resulting from inhalation of coal dust alveolar walls. Similar blackish pigmentations are found
particles, especially in coal-miners engaged in handling soft on the pleural surface and in the regional lymph nodes
bituminous coal for a number of years, often 20 to 30 years. (Fig. 17.27).
It exists in 2 forms—a milder form of the disease called simple
coal workers’ pneumoconiosis and an advanced form termed Histologically, the following features are seen (Fig. 17.28):
progressive massive fibrosis (complicated coal-miners’ 1. Coal macules are composed of aggregates of dust-
pneumoconiosis). Anthracosis, on the other hand, is not a lung laden macrophages. These are present in the alveoli and
disease in true sense but is the common, benign and in the bronchiolar and alveolar walls.
489
Figure 17.26 Pathogenesis of three common forms of pneumoconiosis. A, Coal-workers’ pneumoconiosis. The macrophages phagocytose CHAPTER 17
large amount of coal dust particles which are then passed into the interstitial tissue of the lung and aggregate around respiratory bronchiole and The Respiratory System
cause focal dust emphysema. B, Silicosis. The tiny silica particles are toxic to macrophages. The dead macrophages release fibrogenic factor and
eventually result in silicotic nodule. C, Asbestosis. Asbestos fibres initiate lot of interstitial fibrosis and also form asbestos bodies.
2. There is some increase in the network of reticulin and 2. The wall of respiratory bronchioles and pulmonary
collagen in the coal macules. vessels included in the massive scars are thickened and
3. Respiratory bronchioles and alveoli surrounding the their lumina obliterated.
macules are distended without significant destruction of
the alveolar walls.
PROGRESSIVE MASSIVE FIBROSIS. Grossly, besides
the coal macules and nodules of simple pneumoconiosis,
there are larger, hard, black scattered areas measuring
more than 2 cm in diameter and sometimes massive. They
are usually bilateral and located more often in the upper
parts of the lungs posteriorly. Sometimes, these masses
break down centrally due to ischaemic necrosis or due to
tuberculosis forming cavities filled with black semifluid
resembling India ink. The pleura and the regional lymph
nodes are also blackened and fibrotic (Fig. 17.27).
Histologically, the following features are present:
1. The fibrous lesions are composed almost entirely of
dense collagen and carbon pigment. Figure 17.27 Gross appearance of the lungs in simple coal-workers’
pneumoconiosis (A) and progressive massive fibrosis (B).
490 probably due to swallowing of coal dust containing
carcinogens. But bronchogenic carcinoma does not appear
to be more common in coal-miners than in other groups.
Silicosis
Historically, silicosis used to be called ‘knife grinders’ lung.
Silicosis is caused by prolonged inhalation of silicon dioxide,
commonly called silica. Silica constitutes about one-fourth
of earth’s crust. Therefore, a number of occupations engaged
in silceous rocks or sand and products manufactured from
them are at increased risk. These include miners (e.g. of
granite, sandstone, slate, coal, gold, tin and copper), quarry
workers, tunnellers, sandblasters, grinders, ceramic workers,
foundry workers and those involved in the manufacture of
abrasives containing silica. Peculiar to India are the occu-
pational exposure to pencil, slate and agate-grinding industry
carrying high risk of silicosis (agate = very hard stone
containing silica). According to an Indian Council of Medical
Figure 17.28 Histologic appearance of the lung in coal-workers’ Research report, it is estimated that about 3 million workers
pneumoconiosis. Coal macules composed of aggregates of dust-laden in India are at high potential risk of silica exposure employed
macrophages and collagens are seen surrounding respiratory in a variety of occupations including construction workers.
bronchioles. The alveoli and respiratory bronchioles surrounding the coal
macule are distended. An infrequent acute form of silicosis called accelerated silicosis
produces irregular fibrosis adjoining the alveoli which is
filled with lipoproteinaceous exudate and resembles alveolar
3. There is scanty inflammatory infiltrate of lymphocytes proteinosis (page 494). However, if not specified, silicosis
and plasma cells around the areas of massive scars. refers to the common chronic form of the disease characterised
4. The alveoli surrounding the scars are markedly by formation of small collagenous silicotic nodules.
dilated.
SECTION III
Progressive massive fibrosis probably has immuno- PATHOGENESIS. Silicosis appears after prolonged
logical pathogenetic basis as described above. exposure to silica dust, often a few decades. Besides, it
depends upon a number of other factors such as total dose,
RHEUMATOID PNEUMOCONIOSIS (CAPLAN’S duration of exposure, the type of silica inhaled and individual
SYNDROME). The development of rheumatoid arthritis host factors. The mechanisms involved in the formation of
in a few cases of coal-workers’ pneumoconiosis, silicosis silicotic nodules are not clearly understood. The following
or asbestosis is termed rheumatoid pneumoconiosis or sequence of events has been proposed and schematically
Caplan’s syndrome. illustrated in Fig. 17.26, B:
Grossly, the lungs have rounded, firm nodules with 1. Silica particles between 0.5 to 5 μm size on reaching the
central necrosis, cavitation or calcification. alveoli are taken by the macrophages which undergo
Histologically, the lung lesions are modified rheumatoid necrosis. New macrophages engulf the debris and thus a
nodules with central zone of dust-laden fibrinoid necrosis repetitive cycle of phagocytosis and necrosis is set up.
Systemic Pathology
enclosed by palisading fibroblasts and mononuclear cells. 2. Some silica-laden macrophages are carried to the respi-
The lung lesions in Caplan’s syndrome have immuno- ratory bronchioles, alveoli and in the interstitial tissue. Some
logical basis for their origin as evidenced by detection of of the silica dust is transported to the subpleural and
rheumatoid factor and antinuclear antibodies. interlobar lymphatics and into the regional lymph nodes. The
cellular aggregates containing silica become associated with
CLINICAL FEATURES. Simple coal-workers’ pneumo-
coniosis is the mild form of disease characterised by chronic lymphocytes, plasma cells, mast cells and fibroblasts.
cough with black expectoration. The radiological findings of 3. Silica dust is fibrogenic. Crystalline form, particularly
nodularities in the lungs appear after working for several quartz, is more fibrogenic than non-crystalline form of silica.
years in coal-mines. Progressive massive fibrosis is, however, 4. Simultaneously, there is activation of T and B lymphocytes.
a serious disabling condition manifested by progressive This results in increased serum levels of immunoglobulins
dyspnoea and chronic cough with jet-black sputum. (IgG and IgM), antinuclear antibodies, rheumatoid factor and
Recurrent bacterial infections may produce purulent sputum. circulating immune complexes as well as proliferation of T
More advanced cases develop pulmonary hypertension and cells.
right ventricular hypertrophy (cor pulmonale). The radio- 5. As noted above, silica is cytotoxic and kills the macro-
logical appearance may suggest tuberculosis or cancer. phages which engulf it. The released silica dust activates
Tuberculosis and rheumatoid arthritis are more common in viable macrophages leading to secretion of macrophage-
coal miners than the general population. Coal workers have derived growth factors such as interleukin-1 that favour
increased risk of developing carcinomas of the stomach, fibroblast proliferation and collagen synthesis.
1. The silicotic nodules are located in the region of 491
respiratory bronchioles, adjacent alveoli, pulmonary
arteries, in the pleura and the regional lymph nodes.
2. The silicotic nodules consist of central hyalinised
material with scanty cellularity and some amount of dust.
The hyalinised centre is surrounded by concentric
laminations of collagen which is further enclosed by more
cellular connective tissue, dust-filled macrophages and a
few lymphocytes and plasma cells. Some of these nodules
may have calcium deposits.
3. The collagenous nodules have cleft-like spaces
between the lamellae of collagen which when examined
polariscopically may demonstrate numerous birefringent
particles of silica.
4. The severe and progressive form of the disease may
result in coalescence of adjacent nodules and cause
complicated silicosis similar to progressive massive
Figure 17.29 Gross appearance of the lung in silicosis, diagram- fibrosis of coal-workers’ pneumoconiosis (described
matic appearance. above).
5. The intervening lung parenchyma may show
MORPHOLOGIC FEATURES. Grossly, the chronic silico- hyperinflation or emphysema.
tic lung is studded with well-circumscribed, hard, fibrotic 6. Cavitation when present may be due to ischaemic
nodules, 1 to 5 mm in diameters. They are scattered necrosis in the nodules, or may reveal changes of tuber-
throughout the lung parenchyma but are initially more culosis or rheumatoid pneumoconiosis (Caplan’s
often located in the upper zones of the lungs. These syndrome), discussed already. CHAPTER 17
nodular lesions frequently have simultaneous deposition
of coal-dust and may develop calcification. The pleura is CLINICAL FEATURES. The functional effects of silicosis
grossly thickened and adherent to the chest wall. There develop slowly and insidiously. The main presenting
may be similar fibrotic nodules on the pleura and within complaint is dyspnoea. In time, the patient may develop
the regional lymph nodes. The nodular lesions are features of obstructive or restrictive pattern of disease. Other
detectable as egg-shell shadows in chest X-rays. The complications such as pulmonary tuberculosis, rheumatoid
lesions may undergo ischaemic necrosis and develop arthritis (Caplan’s syndrome) and cor pulmonale may occur.
cavitation, or be complicated by tuberculosis and The chest radiograph initially shows fine nodularity, while
rheumatoid pneumoconiosis (Fig. 17.29). later there are larger and coalescent nodules. Silicosis does
Histologically, the following features are observed not carry increased risk of developing bronchogenic
(Fig. 17.30): carcinoma. The Respiratory System
Figure 17.30 Microscopic picture of the lung in silicosis. The silicotic nodule consists of hyaline centre surrounded by concentric layers of
collagen which are further enclosed by fibroblasts and dust-laden macrophages. Polarising microscopy in photomicrograph on right shows bright
fibres of silica.
492 Asbestos Disease
Asbestos as a mineral is known to mankind for more than
4000 years but its harmful effects have come to light during
the last few decades. Asbestos is a Greek word meaning
‘unquenchable’. In general, if coal is lot of dust and little fibrosis,
asbestos is little dust and a lot of fibrosis. Prolonged exposure
for a number of years to asbestos dust produces three types
of severe diseases: asbestosis of lungs, pleural disease and
tumours. In nature, asbestos exists as long thin fibrils which
are fire-resistant and can be spun into yarns and fabrics
suitable for thermal and electrical insulation and has many
applications in industries. Particularly at risk are workers
engaged in mining, fabrication and manufacture of a number
of products from asbestos such as asbestos pipes, tiles, roofs,
textiles, insulating boards, sewer and water conduits, brake Figure 17.31 Gross appearance of the lung in asbestosis, diagram-
matic appearance.
lining, clutch castings etc.
There are two major geometric forms of asbestos:
Serpentine consisting of curly and flexible fibres. It 6. Asbestos fibres are carcinogenic, the most carcinogenic
includes the most common chemical form chrysotile (white being crocidolite. There is high incidence of bronchogenic
asbestos) comprising more than 90% of commercially used carcinoma in asbestosis which is explained on the basis of
asbestos. the role of asbestos fibres as tumour promoters or by causing
Amphibole consists of straight, stiff and rigid fibres. It cell death of the airways so that it is exposed to the
includes the less common chemical forms crocidolite (blue carcinogenic effect of cigarette smoke. The development of
asbestos), amosite (brown asbestos), tremolite, anthophyllite and pleural mesothelioma in these cases is probably by carrying
actinolyte. However, the group of amphibole, though less of asbestos fibres via lymphatics to the pleura.
common, is more important since it is associated with MORPHOLOGIC FEATURES. As stated already, over-
induction of malignant pleural tumours, particularly in exposure to asbestos is associated with 3 types of lesions:
association with crocidolite. asbestosis, pleural disease and certain tumours.
However, in view of long term harmful effects of asbestos
SECTION III
exposure, it has been mostly replaced with synthetic mineral A. ASBESTOSIS. The gross pulmonary fibrosis caused
fibres such as fiberglass in developed countries since 1975 by asbestos exposure and histologic demonstration of
but it continues to be used in developing countries of the asbestos bodies on asbestos fibres is termed asbestosis.
world. Grossly, the affected lungs are small and firm with
cartilage-like thickening of the pleura. The sectioned
PATHOGENESIS. Overexposure to asbestos for more than surface shows variable degree of pulmonary fibrosis,
a decade may produce asbestosis of the lung, pleural lesions especially in the subpleural areas and in the bases of lungs
and certain tumours. How asbestos causes all these lesions (Fig. 17.31). The advanced cases may show cystic changes.
is not clearly understood but the following mechanisms have Histologically, the following changes are observed:
been suggested (Fig. 17.26,C): 1. There is non-specific interstitial fibrosis.
1. The inhaled asbestos fibres are phagocytosed by alveolar 2. There is presence of characteristic asbestos bodies in the
Systemic Pathology
macrophages from where they reach the interstitium. Some of involved areas (Fig. 17.32). These are asbestos fibres coated
the engulfed dust is transported via lymphatics to the pleura with glycoprotein and haemosiderin and appear beaded
and regional lymph nodes. or dumbbell-shaped. The coating stains positively for
2. The asbestos-laden macrophages release chemo-attractants Prussian blue reaction.
for neutrophils and for more macrophages, thus inciting
cellular reaction around them.
3. Asbestos fibres are coated with glycoprotein and
endogenous haemosiderin to produce characteristic beaded
or dumbbell-shaped asbestos bodies.
4. All types of asbestos are fibrogenic and result in interstitial
fibrosis. Fibroblastic proliferation may occur via macrophage-
derived growth factor such as interleukin-1. Alternatively,
fibrosis may occur as a reparative response to tissue injury
by lysosomal enzymes released from macrophages and
neutrophils or by toxic free radicals.
5. A few immunological abnormalities such as antinuclear
antibodies and rheumatoid factor have been found in cases Figure 17.32 Microscopic appearance of asbestos body. An
of asbestosis but their role in the genesis of disease is not asbestos body is an asbestos fibre coated with glycoprotein and
haemosiderin giving it beaded or dumbbell-shaped appearance with
clear. bulbous ends.
3. There may be changes of emphysema in the principally used in nuclear and aerospace industries and in 493
pulmonary parenchyma between the areas of interstitial the manufacture of electrical and electronic equipments. Two
fibrosis. forms of pulmonary berylliosis are recognised—acute and
4. The involvement of hilar lymph nodes in asbestosis is chronic.
not as significant as in silicosis. ACUTE BERYLLIOSIS. Acute berylliosis occurs in
B. PLEURAL DISEASE. Pleural disease in asbestos individuals who are unusually sensitive to it and are heavily
exposure may produce one of the following 3 types of exposed to it for 2 to 4 weeks. The pulmonary reaction is in
lesions: the form of an exudative chemical pneumonitis in which the
alveoli are filled with protein-rich fluid with formation of
1. Pleural effusion. It develops in about 5% of asbestos
workers and is usually serious type. Pleural effusion is hyaline membrane. The patient develops sudden dyspnoea,
generally accompanied by subpleural asbestosis. hyperapnoea and substernal pain. Most patients recover
completely.
2. Visceral pleural fibrosis. Quite often, asbestosis is
associated with dense fibrous thickening of the visceral CHRONIC BERYLLIOSIS. Chronic berylliosis develops in
pleura encasing the lung. individuals who are sensitised to it for a number of years,
often after a delay of 20 or more years. The disease is a cell-
3. Pleural plaques. Fibrocalcific pleural plaques are the
most common lesions associated with asbestos exposure. mediated hypersensitivity reaction in which the metal
Grossly, the lesions appear as circumscribed, flat, small beryllium acts as a hapten. The condition is characterised by
(upto 1 cm in diameter), firm or hard, bilateral nodules. development of non-caseating epithelioid granulomas like
They are seen more often on the posterolateral part of those of sarcoidosis. These granulomas are diffusely scattered
parietal pleura and on the pleural surface of the throughout the lung parenchyma. The granulomas have
diaphragm. giant cells which frequently contain 3 types of inclusions:
Microscopically, they consist of hyalinised collagenous 1. Birefringent crystals.
tissue which may be calcified so that they are visible on 2. Concentrically-laminated haematoxyphilic Schaumann or
chest X-ray. Asbestos bodies are generally not found conchoid bodies.
within the plaques. 3. Acidophilic stellate-shaped asteroid bodies. CHAPTER 17
These inclusions are described in giant cells of
C. TUMOURS. Asbestos exposure predisposes to a granulomas in sarcoidosis too (Chapter 6). Similar sarcoid-
number of cancers, most importantly bronchogenic like granulomas can occur in other organs such as in the liver,
carcinoma (page 496) and malignant mesothelioma (page kidneys, spleen or lymph nodes in chronic berylliosis.
505). A few others are: carcinomas of oesophagus,
stomach, colon, kidneys and larynx and various lymphoid ILD ASSOCIATED WITH IMMUNOLOGIC LUNG DISEASES
malignancies.
1. Bronchogenic carcinoma is the most common Hypersensitivity (Allergic) Pneumonitis
malignancy in asbestos workers. Its incidence is 5 times
higher in non-smoker asbestos workers than the non- Hypersensitivity pneumonitis is a group of immunologically- The Respiratory System
smoker general population and 10 times higher in smoker mediated ILDs occurring in workers inhaling a variety of
asbestos workers than the other smokers. organic (biologic) antigenic materials. The condition may
have an acute onset due to isolated exposure or may be chronic
2. Malignant mesothelioma is an uncommon tumour due to repeated low-dose exposure.
but association with asbestos exposure is present in 30 to
80% of cases with mesothelioma. The exposure need not ETIOPATHOGENESIS. A list of important organic
be heavy because mesothelioma is known to develop in (biologic) dusts which may be inhaled to produce hyper-
people living near asbestos plants or in wives of asbestos sensitivity pneumonitis is already given in Table 17.9. The
workers. immunologic mechanisms underlying hypersensitivity
pneumonitis from any of these causes appear to be either
CLINICAL FEATURES. Asbestosis is a slow and insidious type III immune-complex disease or type IV delayed-
illness. The patient may remain asymptomatic for a number hypersensitivity reaction.
of years in spite of radiological evidence of calcific pleural 1. Farmers’ lung is the classic example resulting from
plaques and parenchymatous changes. However, onset of exposure to thermophilic actinomycetes generated by humid
interstitial fibrosis brings about dyspnoea with dry or and warm mouldy hay.
productive cough. More advanced cases show development 2. Bagassosis occurs in individuals engaged in manufacture
of Caplan’s syndrome, pulmonary hypertension, cor of paper and cardboard from sugarcane bagasse. Spores of
pulmonale and various forms of cancers. thermophilic actinomycetes grow rapidly in mouldy
sugarcane bagasse which are inhaled.
Berylliosis
3. Byssinosis is an occupational lung disease occurring in
Berylliosis is caused by heavy exposure to dust or fumes of workers exposed to fibres of cotton, flex and hemp for a
metallic beryllium or its salts. Beryllium was used in the past number of years. The role of immunologic mechanisms in
in fluorescent tubes and light bulbs but currently it is byssinosis is not as clear as in exposure to other organic dusts.
494 4. Bird-breeders’ (Bird-fanciers’) lung occurs in pigeon 3. Secondary chronic pulmonary eosinophilia occurs
breeders, parrot breeders, chicken farmers and bird-fanciers secondary to adverse drug reactions; infection with fungi,
who are exposed to bird-droppings and danders from their bacteria, and helminths; allergic bronchopulmonary
feathers. aspergillosis and in association with asthma.
5. Mushroom-workers’ lung is found in mushroom 4. Idiopathic chronic eosinophilic pneumonia is
cultivators exposed to mushroom compost dust. characterised by prominent focal areas of consolidation of
6. Malt-workers’ lung is seen in distillery and brewery the lung. The condition is clinically diagnosed by excluding
workers who are exposed to mouldy barley and malt dust. other known causes of pulmonary eosinophilia.
7. Maple-bark disease occurs in those involved in stripping 5. Hypereosinophilic syndrome is occurrence of eosino-
of maple bark and inhale mouldy maple bark (maple tree is philia of over 1500/μl for more than 6 months without any
grown in northern hemisphere for timber and its leaf is the identifiable cause and without eosinophilic infiltrates in the
national emblem of Canada). lungs and other organs.
8. Silo-fillers’ disease occurs in individuals who enter the
silo (silo is an airtight store-house of fodder for farm animals) MORPHOLOGIC FEATURES. The lesions in the lungs
in which toxic fumes of nitric oxide and nitrogen dioxide are are similar in all cases of hypersensitivity pneumonitis.
formed due to fermentation of silage. The condition is Grossly, the lungs usually show patchy consolidation.
generally rapidly fatal; less often it may lead to ILD. Microscopically, there is thickening of the alveolar walls
by oedema and exudate, chiefly of eosinophils, and some
MORPHOLOGIC FEATURES. The pathologic changes lymphocytes and plasma cells. The alveolar lumina also
primarily involve the alveoli in contrast to bronchiolar contain eosinophils. Occasionally, small granulomas may
involvement in asthma. The changes vary depending upon be present.
whether the biopsy is examined in early stage or in late
stage. Goodpasture’s Syndrome
In early stage, the alveolar walls are diffusely infiltrated
with lymphocytes, plasma cells and macrophages. A Goodpasture’s syndrome or pulmonary haemorrhage
proportion of cases show granulomas consisting of syndrome is combination of necrotising haemorrhagic
histiocytes and giant cells of foreign body or Langhans’ interstitial pneumonitis and rapidly progressive
type. glomerulonephritis. The renal lesions of Goodpasture’s
SECTION III
In chronic cases, the lungs show interstitial fibrosis with syndrome are described in Chapter 22.
some inflammatory infiltrate. Honeycombing of the lung ETIOPATHOGENESIS. The condition results from
may be present. immunologic damage produced by anti-basement membrane
antibodies formed against antigens common to the
CLINICAL FEATURES. The clinical features vary according glomerular and pulmonary basement membranes. The
to the stage. In acute cases, there is generally sudden attack trigger for initiation of this autoimmune response is not clear;
of fever, myalgia, dyspnoea, cough and leucocytosis. In more it could be virus infection, exposure to hydrocarbons and
chronic cases, there are signs of slowly progressive smoking.
respiratory failure, dyspnoea and cyanosis as seen in other
interstitial lung diseases. MORPHOLOGIC FEATURES. Grossly, the lungs are
heavy with red-brown areas of consolidation.
Pulmonary Infiltrates with Eosinophilia Microscopically, the features vary according to the stage
Systemic Pathology
Pulmonary eosinophilia, eosinophilic pneumonias or of the disease:
pulmonary infiltration with eosinophilia (PIE) syndrome are In acute stage, there are focal areas of haemorrhages in
a group of immunologically-mediated lung diseases the alveoli and focal necrosis in the alveolar walls.
characterised by combination of 2 features: In more chronic cases, there is organisation of the
Infiltration of the lungs in chest radiographs. haemorrhage leading to interstitial fibrosis and filling of
Elevated eosinophil count in the peripheral blood. alveoli with haemosiderin-laden macrophages.
ETIOPATHOGENESIS. PIE syndrome has a number of CLINICAL FEATURES. The condition occurs commonly in
diverse causes and pathogenesis. These are as under: 2nd or 3rd decades of life with preponderance in males. The
1. Löeffler’s syndrome is characterised by eosinophilia in pulmonary manifestations generally precede the renal
the blood and typical wandering radiologic shadows, disease. Most cases present with haemoptysis accompanied
appearing in some part of the lung for a few days, and then with dyspnoea, fatigue, weakness and anaemia. Renal
disappearing to appear again somewhere else in the lung. manifestations soon appear which include haematuria,
The condition is generally self-limiting and mild, associated proteinuria, uraemia and progressive renal failure.
with slight fever and a few respiratory symptoms. The
etiology is unknown. Pulmonary Alveolar Proteinosis
2. Tropical pulmonary eosinophilia is caused by the Pulmonary alveolar proteinosis is a rare chronic disease in
passage of larvae of worms through the lungs e.g. in filariasis, which the distal airspaces of the lungs are filled with
ascariasis, strongyloidosis, toxocariasis and ancylostomiasis. granular, PAS-positive, eosinophilic material with abundant
lipid in it. The condition can occur at any age from infancy 3. SYSTEMIC LUPUS ERYTHEMATOSUS. Patients with 495
to old age. systemic lupus erythematosus (SLE) commonly develop
some form of lung disease during the course. The most
ETIOPATHOGENESIS. The etiology and pathogenesis of common manifestation of SLE is pleurisy with small amount
alveolar proteinosis are unknown. A number of possibilities of pleural effusion that may contain LE cells. Other
have been suggested: pulmonary lesions in SLE are interstitial pneumonitis,
Since the alveolar material is combination of lipid and
protein, it is not simply an overproduction of surfactant. pulmonary haemorrhage and vasculitis.
Alveolar proteinosis may have an occupational etiology 4. SJÖGREN’S SYNDROME. Patients with Sjögren’s
as seen in patients heavily exposed to silica. syndrome often have rheumatoid arthritis and associated
It may have an etiologic association with haematologic pulmonary changes. Involvement of the bronchial mucous
malignancies. gland by a process similar to that in the salivary glands can
There may be defective alveolar clearance of debris. lead to inadequate bronchial clearance and repeated
infections.
MORPHOLOGIC FEATURES. Grossly, usually both
lungs are involved, particularly the lower lobes. The lungs 5. DERMATOMYOSITIS AND POLYMYOSITIS.
are heavier with areas of consolidation. Sectioned surface Interstitial pneumonitis and interstitial fibrosis commonly
exudes abundant turbid fluid. accompany dermatomyositis and polymyositis.
Histologically, the hallmark of the condition is presence 6. WEGENER’S GRANULOMATOSIS. Wegener’s
of homogeneous, granular, eosinophilic material which granulomatosis is an necro-inflammatory lesion having
stains brightly with PAS. Often, the material contains 4 components—granulomas of the upper respiratory tract,
cholesterol clefts. There is no significant inflammatory granulomas of the lungs, systemic vasculitis (page 403) and
infiltrate in the affected alveoli. Biochemically, the material focal necrotising glomerulonephritis. Localised or limited form
consists of serum proteins of low molecular weight, of the disease occurs in the lungs without involvement of
cholesterol and phospholipids similar to surfactant. other organs. Pulmonary involvement is in the form of single
Electron microscopy reveals that the material consists of or multiple granulomas.
necrotic alveolar macrophages and desquamated alveolar CHAPTER 17
epithelial cells. Microscopically, these granulomas have foci of fibrinoid
necrosis and intense infiltrate of lymphocytes, plasma cells
CLINICAL FEATURES. The condition is manifested and macrophages with scattered multinucleate giant cells.
clinically by dyspnoea, cough, chest pain, pyrexia, fatigue Besides necrotising granulomas, there is associated
and loss of weight. Chest X-ray shows confluent areas of vasculitis.
consolidation. Occasionally, alveolar proteinosis may recover
spontaneously but more often it is a fatal condition.
IDIOPATHIC PULMONARY FIBROSIS
ILD ASSOCIATED WITH Idiopathic pulmonary fibrosis is the most common form of
CONNECTIVE TISSUE DISEASES diffuse interstitial pneumonia and has bad prognosis The Respiratory System
compared with other forms of lung fibrosis. Diffuse inter-
A number of connective tissue diseases or collagen diseases
may result in chronic interstitial fibrosis and destruction of stitial fibrosis can occur as a result of a number of pathologic
blood vessels. These diseases are described in detail in entities such as pneumoconiosis, hypersensitivity
Chapter 4 but the lung involvement in important forms of pneumonitis and collagen-vascular disease. However, in half
collagen diseases is briefly considered here. the cases of diffuse interstitial fibrosis, no apparent cause or
underlying disease is identifiable. Such cases are included
1. SCLERODERMA (PROGRESSIVE SYSTEMIC under the entity ‘idiopathic pulmonary fibrosis’ in the United
SCLEROSIS). The lungs are involved in 80% cases of States and ‘cryptogenic fibrosing alveolitis’ in Britain.
scleroderma. Interstitial pulmonary fibrosis is the most
common form of pulmonary involvement. The disease PATHOGENESIS. The pathogenesis of idiopathic pulmo-
usually involves the lower lobes and subpleural regions of nary fibrosis is unknown and the condition is diagnosed by
the lungs and may lead to honeycombing of the lung. There excluding all known causes of interstitial fibrosis. However,
is increased risk of development of cancer of the lung in a few evidences point toward immunologic mechanism:
pulmonary fibrosis in scleroderma. 1. High levels of autoantibodies such as rheumatoid factor
2. RHEUMATOID ARTHRITIS. Pulmonary involvement and antinuclear antibodies.
in rheumatoid arthritis may result in pleural effusion, 2. Elevated titres of circulating immune complexes.
interstitial pneumonitis, necrobiotic nodules and rheumatoid 3. Immunofluorescent demonstration of the deposits of
pneumoconiosis (Caplan’s syndrome, page 490). The immunoglobulins and complement on the alveolar walls in
parenchymatous lesions in rheumatoid arthritis are most biopsy specimens.
commonly seen in the lower lobe. Necrobiotic nodules are
the most specific manifestations of rheumatoid disease and MORPHOLOGIC FEATURES. The lung involvement in
closely resemble the subcutaneous nodules commonly found idiopathic pulmonary fibrosis is often bilateral and
in rheumatoid arthritis. widespread.
496 Microscopically, the features are as under:
Grossly, the lungs are firm, heavier with reduced volume.
Honeycombing (i.e. enlarged, thick-walled air spaces) i) Hallmark finding is collections of large number of
develops in parts of lung, particularly in the subpleural intraalveolar macrophages having abundant cytoplasm
region. and containing brown-black pigment and are termed as
Histologically, the changes vary according to the stage smokers’ macrophages.
of the disease. ii) The intervening septa contain a few lymphocytes,
In early stage, there is widening of the alveolar septa plasma cells and an occasional eosinophil.
by oedema and cellular infiltrate by mononuclear iii) Late cases show mild interstitial fibrosis.
inflammatory cells. The alveolar lining cells may show RESPIRATORY BRONCHIOLITIS-ASSOCIATED ILD.
hyperplasia at places and are flattened at other places. Respiratory bronchiolitis is a far more common lesion in
There is often formation of hyaline membranes. The chronic smokers than DIP and is considered a milder form
alveolar spaces contain exudate consisting of of DIP having similar clinical presentation. Respiratory
macrophages, lymphocytes and neutrophils. Many of the bronchiolitis-associated ILD is the term used for advanced
macrophages contain lamellar bodies derived from cases who develop impaired pulmonary function and
surfactant of the necrotic alveolar lining epithelial cells. radiologic features.
Based on the observation of desquamative component in The condition resolves following cessation of smoking.
the cellular exudate, some authors label the early stage of
idiopathic pulmonary fibrosis as ‘desquamative interstitial Microscopically, it is characterised by following features:
pneumonitis’. i) Patchy and bronchiolocentric location of similar
In advanced stage, there is organisation of the alveolar smokers’ macrophages as are seen in DIP.
exudate and replacement fibrosis in the alveoli as well as ii) Peribronchial infiltrate of lymphocytes and histiocytes.
in the interstitial septal wall with variable amount of iii) There may be mild peribronchial fibrosis.
inflammation. Eventually, there are small cystic areas iv) Centriacinar emphysema may coexist.
(honeycomb lung) with alternating areas of fibrosis
containing thick-walled and narrowed vessels. This stage PULMONARY LANGERHANS CELL HISTIOCYTOSIS.
is often referred to as ‘chronic interstitial pneumonitis’ or This is an uncommon smoking-related ILD occurring in
‘usual interstitial pneumonitis’. younger men (20-40 years). Clinically, the features may vary
from an asymptomatic state to a rapidly progressive course.
SECTION III
CLINICAL FEATURES. Middle-aged males are affected Symptomatic cases present with cough, dyspnoea, weight
more frequently. The usual features are of respiratory loss and fever. CT scan shows presence of ill-defined stellate
difficulty beginning with dry cough and slowly progressing nodules and thin-walled cysts.
dyspnoea. More advanced cases may develop clubbing of Discontinuation of smoking leads to reversal of the
fingers and cor pulmonale. A rapidly progressive form of condition.
the idiopathic pulmonary fibrosis with death within 6 weeks Microscopically, the features are as under:
to 6 months is termed Hamman-Rich syndrome.
i) There is presence of poorly-defined nodules distributed
in peribronchiolar location while intervening lung
ILD ASSOCIATED WITH SMOKING parenchyma is uninvolved.
ii) Characteristically, these nodules are sclerosing and
Long-term consequences of smoking is associated with contain Langerhans cells along with other inflammatory
Systemic Pathology
following non-neoplastic respiratory insufficiency:
cells.
Smoking-related COPD: due to chronic bronchitis and iii) Progressive cases have fibrosis with concomitant cystic
emphysema. change.
Smoking-related ILD: i.e. chronic restrictive pulmo-
nary disease due to desquamative interstitial pneumonia TUMOURS OF LUNGS
(DIP), respiratory bronchiolitis-associated ILD, and
pulmonary Langerhans cell histiocytosis (eosinophilic A number of benign and malignant tumours occur in the
granuloma of the lung). lungs but the primary lung cancer, commonly termed
bronchogenic carcinoma, is the most common (95% of all
DESQUAMATIVE INTERSTITIAL PNEUMONIA (DIP). primary lung tumours). The lung is also the commonest site
It is an uncommon condition occurring exclusively in for metastasis from carcinomas and sarcomas. A histologic
smokers in 4th to 5th decades of life and is more common in classification of various benign and malignant tumours of
males. Most patients present with dyspnoea and cough. lungs as recommended by the World Health Organisation is
Chest X-ray shows peculiar diffuse hazy opacities which given in Table 17.10.
characterize all ILDs. DIP was earlier thought to represent
forerunner lesion in the sequence of development of
idiopathic pulmonary fibrosis. However, DIP has minimal BRONCHOGENIC CARCINOMA
fibrosis and has a far better prognosis on cessation of smoking The term bronchogenic carcinoma is commonly used for
compared to idiopathic pulmonary fibrosis. cancer of the lungs which includes carcinomas arising from
TABLE 17.10: WHO Classification of Lung Tumours. There are 5 main histologic types of lung cancer: 497
i) Squamous cell or epidermoid carcinoma
I. EPITHELIAL TUMOURS
ii) Small cell carcinoma
A. Benign iii) Adenocarcinoma (including bronchioalveolar
1. Papilloma carcinoma)
2. Adenoma
iv) Large cell carcinoma
B. Dysplasia and carcinoma in situ
v) Combined squamous cell carcinoma and adeno-
C. Malignant carcinoma (adenosquamous carcinoma).
Bronchogenic carcinoma As per reports on international data for the last 25
1. Squamous cell (epidermoid) carcinoma years, while there has been decline in the incidence of
2. Small cell carcinoma small cell carcinoma, incidence of adenocarcinoma of the
i) Oat cell carcinoma lung has risen and has surpassed squamous cell carcinoma
ii) Intermediate cell carcinoma
iii) Combined oat cell carcinoma as the most frequent histologic subtype of lung cancer.
3. Adenocarcinoma However, for therapeutic purposes, bronchogenic
i) Acinar adenocarcinoma carcinoma can be classified into 3 groups:
ii) Papillary adenocarcinoma 1. Small cell carcinomas, SCC (20-25%)
iii) Bronchiolo-alveolar carcinoma 2. Non-small cell carcinomas, NSCC (70-75%) (includes
iv) Solid carcinoma with mucus formation
4. Large cell carcinoma squamous cell carcinoma, adenocarcinoma, and large cell
5. Adenosquamous carcinoma carcinoma)
3. Combined/mixed patterns (5-10%).
Other carcinomas
1. Pulmonary neuroendocrine tumour (carcinoid tumour) ETIOLOGY. The high incidence of lung cancer is associated
2. Bronchial gland carcinomas with a number of etiologic factors, most important of which
i) Adenoid cystic carcinoma
ii) Mucoepidermoid carcinoma is cigarette smoking.
1. Smoking. The most important factor for high incidence
II. SOFT TISSUE TUMOURS
of all forms of bronchogenic carcinoma is tobacco smoking. CHAPTER 17
(Fibroma, fibrosarcoma; leiomyoma, leiomyosarcoma; lipoma,
chondroma, haemangioma, lymphangioma, granular cell About 80% of the lung cancer occurs in active smokers. A
myoblastoma) number of evidences support the positive relationship of lung
cancer with tobacco smoking (see page 237):
III. PLEURAL TUMOURS
A. Benign mesothelioma i) Total dose: There is a direct statistical correlation between
B. Malignant mesothelioma death rate from lung cancer and the total amount of cigarettes
smoked e.g.
IV. MISCELLANEOUS TUMOURS An average regular smoker has 10 times greater risk of
1. Carcinosarcoma developing lung cancer than a non-smoker.
2. Pulmonary blastoma
3. Malignant melanoma The risk of smokers of more than 2 packs (40 cigarettes)
4. Malignant lymphoma per day for 20 years is 60-70 times greater than a non-smoker. The Respiratory System
Cessation of smoking by a regular smoker results in
V. SECONDARY TUMOURS
gradual decline in the chances of developing lung cancer.
After 10 years of abstinence from smoking, the risk declines
the respiratory epithelium lining the bronchi, bronchioles and but never returns to the non-smoker level.
alveoli. Pipe and cigar smokers, though have higher risk than
non-smokers but are at lesser risk than cigarette smokers.
INCIDENCE AND CLASSIFICATION. Lung cancer is the
most common primary malignant tumour in men and ii) Histologic alterations: The association of tobacco
accounts for nearly 30% of all cancer deaths in both sexes in smoking is strongest for squamous cell carcinoma and small
developing countries. Currently, the incidence of lung cancer cell carcinoma of the lung. More than 90% of smokers have
in females in the United States has already exceeded breast sequential epithelial changes in the respiratory tract in the
cancer as a cause of death in women. Cancer of the lung is a form of squamous metaplasia, dysplasia and carcinoma in
disease of middle and late life with peak incidence in 55-65 situ (Fig. 17.33).
years of age, after which there is gradual fall in its incidence. iii) Mechanism: How tobacco smoking causes lung cancer
Of late, there has been slight decline in lung cancer deaths in is not quite clear. However, following facts have been
males due to smoking cessation efforts which started in the observed:
West 4 decades back and has started yielding results. Analysis of the tar from cigarette smoke has revealed a
However, worldwide the scene on its incidence and number of known carcinogens (e.g. polycyclic aromatic
prognosis are quite grim; data from International Agency hydrocarbons, nitrosamines) and tumour promoters (e.g.
for Research on Cancer estimate that worldwide by the year phenol derivatives).
2030 there would be about 10 million deaths per year from In experimental animal studies, it has been possible to
lung cancer. induce cancer by skin painting experiments with smoke-tar.
498
Figure 17.33 Schematic representation of sequential development of squamous cell carcinoma of the lung.
However, it has not been possible to reproduce pattern of MYC family, and overexpression of bcl-2 and other
human respiratory tract cancer, probably because of the antiapoptotic proteins.
difficulty in reproducing human smoking methods in 2. Inactivation of tumour-suppressor genes. Inactivation of
animals. tumour suppressor genes has been found as another
2. Other factors. Although smoking is the dominant molecular mechanism in lung cancer. Many tumour
etiologic factor in lung cancer, 15% cases of lung cancer occur suppressor genes have been found on chromosome 3p in lung
in non-smokers, more so in women probably related to cancer cases. These include inactivation of p53 and Rb gene.
hormonal factors. A few other factors implicated in lung Besides, some tumour-acquired promoter genes have been
cancer are as follows: identified in lung cancer e.g. p16, RASSFIA etc, which cause
i) Atmospheric pollution. There is increased risk of developing loss of normal function of growth-regulatory tumour
bronchogenic carcinoma in non-smokers living in suppressor genes.
industrialised and smoky cities than in the less polluted rural 3. Autocrine growth factors. Studies have shown that lung
SECTION III
areas. It is possible that specific industrial pollutants may be cancer is a multistep process—initiator carcinogen causing
at fault as evidenced by high rates for lung cancer in people mutation, followed by action of tumour promoters. Nicotine
living in the neighbourhood of petrochemical industries. acts as both initiator as well as promoter carcinogen.
ii) Occupational causes. There are a number of well-esta- Derivatives of nicotine in smoke unmask and expresses
blished occupational causes of lung cancer. These include nicotine acetylcholine receptors which activate the signaling
workers exposed to asbestos, radiation of all types, bis-ethers, pathway in tumour, blocking the apoptosis. Promoters also
nickel, beryllium, arsenic, metallic iron and iron-oxide. Some include several hormones which are elaborated by lung
industrial carcinogens and cigarette smoking have cancer by autocrine pathway as part of paraneoplastic
cocarcinogenic effect, particularly in uranium mines and syndrome.
asbestos workers. 4. Inherited predisposition. Although not common, but there
iii) Dietary factors. Susceptibility to respiratory cancers is are a few examples of inheritance of lung cancer as under:
Systemic Pathology
increased in vitamin A deficiency. Smokers with low vitamin
A intake have a greater risk of lung cancer than those with i) Patients of Li-Fraumeni syndrome who inherit p53
mutation may develop lung cancer.
vitamin A-rich diet. The incidence of lung cancer is inversely
related to socioeconomic level reflecting their dietary pattern. ii) Clinical cases of retinoblastoma having mutation in Rb
gene are predisposed to develop lung cancer if they live up
iv) Chronic scarring. Peripheral adenocarcinomas occur more to adulthood.
frequently in areas of chronic scarring caused by chronic iii) First-degree relatives of lung cancer patients have a 2-3
inflammatory changes, old tuberculosis, asbestosis, chronic fold higher risk of developing lung cancer in their lifetime.
interstitial fibrosis, old infarcts and in scleroderma.
iv) Mutations of cytochrome P450 system have been
MOLECULAR PATHOGENESIS. Molecular studies have identified in lung cancer patients; P450 metabolises chemical
revealed that there are several genetic alterations in cancer carcinogen in tobacco smoke (page 216).
stem cells which produce clones of malignant cells to form 5. Molecular targets for therapy and survival prediction.
tumour mass. Following genetic changes have been found: Knowledge on the insight into molecular biology and
1. Activation of growth-promoting oncogenes: Mutation in pathogenesis of lung cancer has applications in discovering
K-RAS oncogene has been seen as the dominant change in newer molecules for targeted therapy, predicting response
lung cancer. Besides, there is mutation in tyrosine kinase to treatment and survival:
domain of EGFR oncogene in cases of adenocarcinoma lung i) EGFR mutations and NSCC therapy: It has been reported
in non-smokers. Other mutations include BRAF, PIK3CA and that 70% cases of NSCC have overexpression of EGFR protein
or amplification of the EGFR gene. EGFR belonging to ERBB 499
(HER) family of protooncogenes through mutation in its
tyrosine kinase (TK) domain plays a role in both extracelluar
and intracellular signaling resulting in tumour cell
proliferation, metastasis and antiapoptotic action. Targeted
molecular therapy against these mutations in EGFR include
EGFR-TK inhibitor oral therapy.
ii) VEGF and monoclonal therapy: Although not mutated, VEGF
is excessively produced in lung cancer and contributes to
tumour angiogenesis. Monoclonal antibody therapy against
EGFR in conjunction with chemotherapy has been used for
curtailing tumour angiogenesis in lung caner.
iii) Molecular signature gene for prediction: Recent proteomic
studies at research level have shown that each patient has
unique protein pattern in the serum (i.e. molecular
signatures) which may be used for early diagnosis, predict Figure 17.34 The two main gross patterns of bronchogenic
drug resistance, response to treatment and survival, but these carcinoma.
are yet to be applied in clinical settings.
MORPHOLOGIC FEATURES. Bronchogenic carcinoma during the course of different lung diseases). It is common
can occur anywhere in the lung but the most common to find secondary changes in bronchogenic carcinoma of
location is hilar, followed in descending frequency by lung such as bronchopneumonia, abscess formation and
peripheral type. bronchiectasis as a result of obstruction and intercurrent
Grossly, these 2 main types show variation in appearance: infections. The tumour soon spreads within the lungs by
1. Hilar type (Fig. 17.34,A): Most commonly, the lung direct extension or by lymphatics, and to distant sites by
cancer arises in the main bronchus or one of its segmental lymphatic or haematogenous routes, as described later. CHAPTER 17
branches in the hilar parts of the lung, more often on the 2. Peripheral type (Fig. 17.34,B): A small proportion of
right side. The tumour begins as a small roughened area lung cancers, chiefly adenocarcinomas including
on the bronchial mucosa at the bifurcation. As the tumour bronchioloalveolar carcinomas, originate from a small
enlarges, it thickens the bronchial mucosa producing peripheral bronchiole but the exact site of origin may not
nodular or ulcerated surface. As the nodules coalesce, the be discernible. The tumour may be a single nodule or
carcinoma grows into a friable spherical mass, 1 to 5 cm multiple nodules in the periphery of the lung producing
in diameter, narrowing and occluding the lumen. The cut pneumonia-like consolidation of a large part of the lung.
surface of the tumour is yellowish-white with foci of The cut surface of the tumour is greyish and mucoid.
necrosis and haemorrhages which may produce cavitary Histologically, as per the WHO classification outlined in
lesions (Table 17.11 sums up a list of common conditions Table 17.10, five main histologic types of bronchogenic
having pulmonany cavitary lesions or ‘honey-comb lung’ carcinoma are distinguished which is important because The Respiratory System
of prognostic and therapeutic considerations. However,
from clinical point of view, distinction between small cell
TABLE 17.11: Conditions Producing Pulmonary Cavities (SCC) and non-small cell carcinomas (NSCC) is important
(Honeycomb Lung). because the two not only differ in morphology, but there
A. INFECTIONS are major differences in immunophenotyping and
1. Pulmonary tuberculosis response to treatment discussed above. The major
2. Primary lung abscess (e.g. due to aspiration) differences between SCC and NSCC of the lung are
3. Secondary lung abscess (e.g. preceding pneumonia, pyaemia, summed up in Table 17.12.
sepsis) 1. Squamous cell (epidermoid) carcinoma: This has been
4. Bronchiectasis
5. Fungal infections (e.g. aspergillosis, mucormycosis) the most common histologic subtype of bronchogenic
6. Actinomycosis carcinoma until recently and is found more commonly in
7. Nocardiosis men, often with history of tobacco smoking. These
tumours usually arise in a large bronchus and are prone
B. NON-INFECTIOUS CAUSES to massive necrosis and cavitation (Fig. 17.35). The tumour
1. Pneumoconiosis (e.g. simple coal-workers’ pneumoconiosis, is diagnosed microscopically by identification of either
silicosis, asbestosis) intercellular bridges or keratinisation. The tumour may
2. Bronchogenic carcinoma show varying histologic grades of differentiation such as
3. Metastatic lung tumours well-differentiated, moderately-differentiated and poorly-
4. Wegener’s granulomatosis
5. Pulmonary infarction differentiated (Fig. 17.36). Occasionally, a variant of
6. Congenital cysts squamous cell carcinoma, spindle cell carcinoma, having
7. Idiopathic pulmonary fibrosis biphasic pattern of growth due to the presence of a
500
TABLE 17.12: Comparison of Features of Small Cell and Non-small Cell Carcinoma of the Lung.
Feature Small Cell Carcinoma Non-small Cell Carcinoma
1. Etiologic relationship Strongly related to tobacco smoking Smoking implicated, other factors:
pollution, chronic scars, asbestos exposure
2. Morphology
i) Pattern Diffuse sheets Squamous or glandular pattern
ii) Nuclei Hyperchromatic, fine chromatin Pleomorphic, coarse chromatin
iii) Nucleoli Indistinct Prominent
iv) Cytoplasm Scanty Abundant
3. Neuroendocrine markers Present Absent
(e.g. dense-core granules on EM,
chromogranin, synaptophysin,
neuron-specific enolase, CD56, CD57)
4. Epithelial markers Present Present
(e.g. epithelial membrane antigen,
carcinoembryonic antigen, cytokeratin)
5. Mucin Absent Present in adenocarcinoma
6. HLA, β2 microglobulin Absent to low Present
7. Peptide hormone production Gastrin, ACTH, ADH, calcitonin Parathormone
8. Genetic abnormalities 3p allele loss, RB and 3p allele loss, EGFR and K-RAS
p53 mutations mutations
9. Treatment type Radiotherapy and/or Surgical resection possible, limited
chemotherapy response to radiotherapy and/or
chemotherapy
10. Prognosis Poor Better
component of squamous cell carcinoma and the other bronchi show squamous metaplasia, epithelial dysplasia
SECTION III
sarcoma-like spindle cell component, is found. and carcinoma in situ.
Usually the spread of squamous cell carcinoma is more 2. Small cell carcinoma: Small cell carcinomas are
rapid than the other histologic types of NSCC. Frequently, frequently hilar or central in location, have strong
the edge of the growth and the adjoining uninvolved relationship to cigarette smoking and are highly malignant
tumours. They are most often associated with ectopic
hormone production because of the presence of
neurosecretory granules in majority of tumour cells which
are similar to those found in argentaffin or Kulchitsky cells
normally found in bronchial epithelium. By immuno-
histochemistry, these tumour cells are positive for
neuroendocrine markers: chromogranin, neuron-specific
Systemic Pathology
enolase (NSE) and synaptophysin. Small cell carcinomas
have 3 subtypes:
i) Oat cell carcinoma is composed of uniform, small cells,
larger than lymphocytes with dense, round or oval nuclei
having diffuse chromatin, inconspicuous nucleoli and very
sparse cytoplasm (oat = a form of grain). These cells are
organised into cords, aggregates and ribbons or around
small blood vessels forming pseudorosettes (Fig. 17.37).
ii) Small cell carcinoma, intermediate cell type is composed of
cells slightly larger than those of oat cell carcinoma and
have similar nuclear characteristics but have more
abundant cytoplasm. These cells are organised into lobules.
iii) Combined oat cell carcinoma is a tumour in which there
is a definite component of oat cell carcinoma with
squamous cell and/or adenocarcinoma.
3. Adenocarcinoma: Adenocarcinoma, also called
Figure 17.35 Squamous cell carcinoma lung, hilar type. Sectioned peripheral carcinoma due to its location and scar carcinoma
surface shows grey-white fleshy tumour in the bronchus at its bifurcation due to its association with areas of chronic scarring, is the
and occluding the lumen partly (arrow). The tumour is seen extending
directly into adjacent lung parenchyma and hilar nodes. most common bronchogenic carcinoma in women and is
501
Figure 17.36 Squamous cell carcinoma of the lung. Islands of invading malignant squamous cells are seen. A few well-developed cell nests
with keratinisation are evident.
slow-growing. Recent estimates on adenocarcinoma place 4. Large cell carcinoma: These are undifferentiated
this as the most frequent histologic subtype of lung cancer. carcinomas which lack the specific features by which they
Adenocarcinoma is further subclassified into 4 types: could be assigned into squamous cell carcinoma or
i) Acinar adenocarcinoma which has predominance of adenocarcinoma. Large cell carcinomas are more common
glandular structure and often occurs in the larger bronchi. in men, have strong association with cigarette smoking
ii) Papillary adenocarcinoma which has a pronounced and are highly malignant tumours. The tumour cells have CHAPTER 17
papillary configuration and is frequently peripherally large nuclei, prominent nucleoli, abundant cytoplasm and
located in the lungs and is found in relation to pulmonary well-defined cell borders. Variants of large cell
scars (scar carcinoma). undifferentiated carcinomas include giant cell carcinoma
with prominence of highly pleomorphic multinucleate
iii) Bronchiolo-alveolar carcinoma is characterised by cells and clear cell carcinoma composed of cells with clear
cuboidal to tall columnar and mucus-secreting epithelial or foamy cytoplasm without mucin.
cells growing along the existing alveoli and forming 5. Adenosquamous carcinoma: These are a small
numerous papillary structures (Fig. 17.38). Ultrastruc- proportion of peripheral scar carcinomas having clear
turally, these tumour cells resemble Clara cells or less often evidence of both keratinisation and glandular
type II pneumocytes. differentiation.
iv) Solid carcinoma is a poorly-differentiated adenocarci- The Respiratory System
noma lacking acini, tubules or papillae but having mucus- SPREAD. Bronchogenic carcinoma can invade the adjoin-
containing vacuoles in many tumour cells. ing structures directly, or may spread by lymphatic and
haematogenous routes.
Figure 17.37 Oat cell carcinoma of the lung. The tumour cells are arranged in sheets, cords or aggregates and at places form pseudorosettes.
The individual tumour cells are small, uniform, lymphocyte-like with scanty cytoplasm.
502
Figure 17.38 Bronchioloalveolar carcinoma. The alveolar walls are lined by cuboidal to tall columnar and mucin-secreting tumour cells with
papillary growth pattern.
1. Direct spread. The tumour extends directly by invading caval syndrome, painful bony lesions, paralysis of recurrent
through the wall of the bronchus and destroys and replaces nerve and other neurologic manifestations resulting from
the peribronchial lung tissue. As it grows further, it spreads brain metastases.
to the opposite bronchus and lung, into the pleural cavity, 4. Paraneoplastic syndromes. A number of paraneoplastic
the pericardium and the myocardium and along the great syndromes (page 231) are associated with lung cancer. These
vessels of the heart causing their constriction. Extension of include the following:
the cancer located at the apex of the lung into the thoracic
cage may involve brachial plexus and the sympathetic chain i) Ectopic hormone production: Different hormonal
causing pain and sensory disturbances, so called Pancoast’s syndromes are characteristic of different histologic types of
SECTION III
lung cancer. Small cell carcinomas are associated most often
syndrome.
with ectopic hormone production. The various hormones
2. Lymphatic spread. Initially, hilar lymph nodes are elaborated by lung cancer are as follows:
affected. Later, lymphatic metastases occur to the other a) ACTH, producing Cushing’s syndrome.
groups leading to spread to mediastinal, cervical, b) ADH, inducing hyponatraemia.
supraclavicular and para-aortic lymph nodes. Invasion of the c) Parathormone, causing hypercalcaemia.
thoracic duct may produce chylous ascites.
d) Calcitonin, producing hypocalcaemia.
3. Haematogenous spread. Distant metastases via blood e) Gonadotropins, causing gynaecomastia.
stream are widespread and early. The sites affected, in f) Serotonin, associated with carcinoid syndrome.
descending order of involvement, are: the liver, adrenals,
bones, pancreas, brain, opposite lung, kidneys and thyroid.
Systemic Pathology
CLINICAL FEATURES. Symptoms of lung cancer are quite TABLE 17.13: Causes of Haemoptysis.
variable and result from local effects, effects due to occlusion A. INFLAMMATORY
of a bronchus, direct and distant metastases, and 1. Bronchitis
paraneoplastic syndromes. Diagnostic aids include radiologic 2. Bronchiectasis
examination and CT scan of the chest, cytologic examination 3. Tuberculosis
of the sputum, bronchial washings and bronchioalveolar 4. Lung abscess
lavage. 5. Pneumonias
1. Local symptoms. Most common local complaints are B. NEOPLASTIC
cough, chest pain, dyspnoea and haemoptysis. (A list of 1. Primary and metastatic lung cancer
various causes of haemoptysis is summed up in Table 17.13). 2. Bronchial adenoma
2. Bronchial obstructive symptoms. Occlusion of a C. OTHERS
bronchus may result in bronchopneumonia, lung abscess and 1. Pulmonary thromboembolism
bronchiectasis in the lung tissue distal to the site of 2. Left ventricular failure
obstruction and cause their attendant symptoms like fever, 3. Mitral stenosis
productive cough, pleural effusion and weight loss. 4. Trauma
3. Symptoms due to metastases. Distant spread may 5. Foreign bodies
produce varying features and sometimes these are the first 6. Primary pulmonary hypertension
7.
Haemorrhagic diathesis
manifestation of lung cancer. These include: superior vena
ii) Other systemic manifestations: These include the 503
following:
a) Neuromuscular e.g. polymyositis, myopathy, peripheral
neuropathy and subacute cerebellar degeneration.
b) Skeletal e.g. clubbing and hypertrophic osteoarthro-
pathy.
c) Cutaneous e.g. acanthosis nigricans and dermato-
myopathy.
d) Cardiovascular e.g. migratory thrombophlebitis
(Trousseau’s syndrome), nonbacterial thrombotic
endocarditis.
e) Haematologic e.g. abnormalities in coagulation and
leukaemoid reaction.
STAGING AND PROGNOSIS. The widely accepted clinical
staging of lung cancer is according to the TNM classification,
combining features of primary Tumours, Nodal involvement
and distant Metastases. TNM staging divides all lung cancers Figure 17.39 Central carcinoid of the lung. The tumour shows a
into the following 4 stages: characteristic nested of cells separated by fibrovascular septa. These
nests are composed of uniform cuboidal cells having granular cytoplasm.
Occult: Malignant cells in the bronchopulmonary secretions
but no evidence of primary tumour or metastasis.
MORPHOLOGIC FEATURES. Bronchial carcinoids
Stage I: Tumour less than 3 cm, with or without ipsilateral
nodal involvement, no distant metastasis. resemble their intestinal counterparts described in
Chapter 20.
Stage II: Tumour larger than 3 cm, with ipsilateral hilar lymph Grossly, bronchial carcinoids most commonly arise from
node involvement, no distant metastasis. a major bronchus and project into the bronchial lumen as CHAPTER 17
Stage III: Tumour of any size, involving adjacent structures, a spherical polypoid mass, 3-4 cm in diameter. Less
involving contralateral lymph nodes or distant metastasis. commonly, the tumour may grow into the bronchial wall
In general, tumour size larger than 5 cm has worse and produce collar-button like lesion. The overlying
prognosis. Symptomatic patients, particularly with systemic bronchial mucosa is usually intact. Cut surface of the
symptoms, fare far badly than the nonsymptomatic patients. tumour is yellow-tan in colour.
The overall prognosis of bronchogenic carcinoma is dismal. Histologically, the tumour is composed of uniform
However, 5-year survival rate with surgery combined with cuboidal cells forming aggregates, trabeculae or ribbons
radiotherapy or chemotherapy in the last 30 years has separated by fine fibrous septa. The tumour cells have
doubled from its earlier rate of about 9% to present rate of abundant, finely granular cytoplasm and oval central
15%. Adenocarcinoma and squamous cell carcinoma which nuclei with clumped nuclear chromatin. Mitoses are rare The Respiratory System
are localised, are resectable and have a slightly better and necrosis is uncommon (Fig. 17.39). The secretory
prognosis. Small cell carcinoma has the worst prognosis since granules of bronchial carcinoids resemble those of other
surgical treatment is ineffective though the tumour is foregut carcinoids and stain positively with argyrophilic
sensitive to radiotherapy and chemotherapy. stains in which exogenous reducing agent is added for
the reaction. Immunohistochemically, markers for
BRONCHIAL CARCINOID AND neuroendocrine stain positive and include NSE,
OTHER NEUROENDOCRINE TUMOURS chromogranin, synaptophysin and neurofilaments.
Neuroendocrine tumours of the lung represent a continuum CLINICAL FEATURES. Bronchial carcinoids occur at a
spectrum of lung tumours with progressively increasing relatively early age and have equal sex incidence. Most of
aggressiveness which include: typical carcinoid (least the symptoms in bronchial carcinoids occur as a result of
aggressive), atypical carcinoid, and large cell endocrine bronchial obstruction such as cough, haemoptysis, atelectasis
carcinoma, and also small cell carcinoma (most aggressive). and secondary infection. About 5-10% of bronchial carcinoids
All these tumours arise from neuroendocrine (Kulchitsky) metastasise to the liver and these cases are capable of
cells of bronchial mucosa. Formerly, bronchial carcinoids producing carcinoid syndrome (Chapter 20).
used to be classified as ‘bronchial adenomas’ but now it is
known that they are locally invasive and have the capacity
to metastasise. Bronchial carcinoids tend to occur at a HAMARTOMA
younger age than bronchogenic carcinoma, often appearing Hamartoma is a tumour-like lesion composed of an abnormal
below the age of 40 years, and are not related to cigarette admixture of pulmonary tissue components and is
smoking. discovered incidentally as a coin-lesion in the chest-X-ray.
504 Pulmonary hamartomas are of 2 types: chondromatous and PLEURA
leiomyomatous.
Chondromatous hamartoma is more common and NORMAL STRUCTURE
usually asymptomatic. It forms a solitary, spherical mass, Visceral pleura covers the lungs and extends into the fissures
2-5 cm in diameter, usually at the periphery of the lung. while the parietal pleura limits the mediastinum and covers
Typically, it shows nodules of cartilage associated with the dome of the diaphragm and inner aspect of the chest wall.
fibrous and adipose tissue admixed with bronchial The two layers between them enclose pleural cavity which
epithelium.
contains less than 15 ml of clear serous fluid.
Leiomyomatous hamartoma has a prominent smooth
muscle component and bronchiolar structures. They are Microscopically, both the pleural layers are lined by a single
frequently multiple, 1-2 mm in diameter and are more layer of flattened mesothelial cells facing each other.
commonly located near the pleura. Underneath the lining cells is a thin layer of connective tissue.
Diseases affecting the pleura are nearly always secondary
to some other underlying disease. Broadly, they fall into
METASTATIC LUNG TUMOURS
inflammations, non-inflammatory pleural effusions,
Secondary tumours of the lungs are more common than the pneumothorax, and tumours.
primary pulmonary tumours. Metastases from carcinomas
as well as sarcomas arising from anywhere in the body may INFLAMMATIONS
spread to the lung by haematogenous or lymphatic routes, Inflammatory involvement of the pleura is commonly termed
or by direct extension. Blood-borne metastases are the most pleuritis or pleurisy. Depending upon the character of resultant
common since emboli of tumour cells from any malignant exudate, it can be divided into serous, fibrinous and
tumour entering the systemic venous circulation are likely serofibrinous, suppurative or empyema, and haemorrhagic
to be lodged in the lungs. Metastases are most common in pleuritis.
the peripheral part of the lung forming single or multiple,
discrete nodular lesions which appear radiologically as 1. SEROUS, FIBRINOUS AND SEROFIBRINOUS
‘cannon-ball secondaries’ (Fig. 17.40). Less frequently, the PLEURITIS. Acute inflammation of the pleural sac (acute
metastatic growth is confined to peribronchiolar and pleuritis) can result in serous, serofibrinous and fibrinous
perivascular locations which is due to spread via lymphatics. exudate. Most of the causes of such pleuritis are infective in
SECTION III
Most common sources of metastases in the lungs are: origin, particularly within the lungs, such as tuberculosis,
carcinomas of the bowel, breast, thyroid, kidney, pancreas, pneumonias, pulmonary infarcts, lung abscess and
lung (ipsilateral or contralateral) and liver. Other tumours bronchiectasis. Other causes include a few collagen diseases
which frequently metastasise to the lungs are osteogenic (e.g. rheumatoid arthritis and disseminated lupus
sarcoma, neuroblastoma, Wilms’ tumour, melanoma, erythematosus), uraemia, metastatic involvement of the
lymphomas and leukaemias. pleura, irradiation of lung tumours and diffuse systemic
infections (e.g. typhoid fever, tularaemia, blastomycosis and
coccidioidomycosis).
Pleurisy causes pain in the chest on breathing and a
friction rub is audible on auscultation. In most patients, the
exudate is minimal and is resorbed resulting in resolution.
Repeated attacks of pleurisy may result in organisation
Systemic Pathology
leading to fibrous adhesions and obliteration of the pleural
cavity.
2. SUPPURATIVE PLEURITIS (EMPYEMA THORACIS).
Bacterial or mycotic infection of the pleural cavity that
converts a serofibrinous effusion into purulent exudate is
termed suppurative pleuritis or empyema thoracis. The most
common cause is direct spread of pyogenic infection from
the lung. Other causes are direct extension from subdia-
phragmatic abscess or liver abscess and penetrating injuries
to the chest wall. Occasionally, the spread may occur by
haematogenous or lymphatic routes.
In empyema, the exudate is yellow-green, creamy pus
that accumulates in large volumes. Empyema is eventually
replaced by granulation tissue and fibrous tissue. In time,
tough fibrocollagenic adhesions develop which obliterate the
Figure 17.40 Metastatic deposits in the lung. Large parts of the cavity, and with passage of years, calcification may occur.
lung parenchyma are replaced by multiple, variable-sized, circumscribed The effect of these is serious respiratory difficulty due to
nodular masses which are grey-white in colour. Some of these show
areas of haemorrhage and necrosis. inadequate pulmonary expansion.
3. HAEMORRHAGIC PLEURITIS. Haemorrhagic with emphysema, asthma and tuberculosis. Other causes 505
pleuritis differs from haemothorax in having inflammatory include chronic bronchitis in an old patient, bronchiectasis,
cells or exfoliated tumour cells in the exudate. The causes of pulmonary infarction and bronchial cancer. In young
haemorrhagic pleuritis are metastatic involvement of the patients, recurrent spontaneous rupture of peripheral
pleura, bleeding disorders and rickettsial diseases. subpleural blebs may occur without any cause resulting in
disabling condition termed spontaneous idiopathic
NON-INFLAMMATORY PLEURAL EFFUSIONS pneumothorax.
These include fluid collections in the pleural cavity such as ii) Traumatic pneumothorax is caused by trauma to the
hydrothorax, haemothorax and chylothorax. chest wall or lungs, ruptured oesophagus or stomach, and
surgical operations of the thorax.
1. HYDROTHORAX. Hydrothorax is non-inflammatory iii) Therapeutic (artificial) pneumothorax used to be
accumulation of serous fluid within the pleural cavities. employed formerly in the treatment of chronic pulmonary
Hydrothorax may be unilateral or bilateral depending upon tuberculosis in which air was introduced into the pleural sac
the underlying cause. Occasionally, an effusion is limited to so as to collapse the lung and limit its respiratory movements.
part of a pleural cavity by preexisting pleural adhesions. The effects of pneumothorax due to any cause depend
The most common cause of hydrothorax, often bilateral,
is congestive heart failure. Other causes are renal failure, upon the amount of air collected in the pleural cavity. If the
quantity of air in the pleura is small, it is resorbed. Larger
cirrhosis of liver, Meig’s syndrome (Chapter 24), pulmonary volume of air collection in the pleural cavity causes dyspnoea
oedema and primary and secondary tumours of the lungs. and pain in the chest. Pneumothorax causes lung collapse
The non-inflammatory serous effusion in hydrothorax is
clear and straw-coloured and has the characteristics of and pulls the mediastinum to the unaffected side.
Occasionally, the defect in the lungs is such that it acts as
transudate with a specific gravity of under 1.012, protein flap-valve and allows entry of air during inspiration but does
content below 1 gm/dl and little cellular content.
If the fluid collection in pleural cavity is less than 300 ml not permit its escape during expiration, creating tension
(normal is less than 15 ml), no signs or symptoms are pneumothorax which requires urgent relief of pressure so as
to relieve severe dyspnoea and circulatory failure.
produced and may be apparent in chest X-ray in standing CHAPTER 17
posture as obliterated costodiaphragmatic angle. If the TUMOURS OF PLEURA
pleural cavity contains abundant fluid, it imparts a
characteristic opaque radiographic appearance to the affected Pleural tumours may be primary or secondary. In line with
side with deviation of trachea to the opposite side. In such pulmonary tumours, the secondary tumours in the pleura
cases, symptoms such as respiratory embarrassment and are more common. The only important primary tumour of
dyspnoea are produced which are promptly relieved on pleura is mesothelioma.
withdrawal of fluid.
MESOTHELIOMA
2. HAEMOTHORAX. Accumulation of pure blood in the
pleural cavity is termed as haemothorax. The most common Mesothelioma is an uncommon tumour arising from
causes of haemothorax are trauma to the chest wall or to the mesothelial lining of serous cavities, most often in pleural The Respiratory System
thoracic viscera and rupture of aortic aneurysm. It is cavity, and rarely in peritoneal cavity and pericardial sac.
important to remove the blood from the pleural cavity as Mesotheliomas are of 2 types—benign (solitary) and malignant
early as possible. Otherwise the blood will clot and organise, (diffuse). The biologic behaviour of pleural mesotheliomas is
resulting in fibrous adhesions and obliteration of the pleural usually predicted by their gross appearance—those forming
cavity. solitary, discrete masses are generally benign, whereas those
which grow diffusely are usually malignant.
3. CHYLOTHORAX. Chylothorax is an uncommon
condition in which there is accumulation of milky fluid of Benign (Solitary) Mesothelioma
lymphatic origin into the pleural cavity. Chylothorax results
most commonly from rupture of the thoracic duct by trauma Benign or solitary mesothelioma is also called as pleural
or obstruction of the thoracic duct such as by malignant fibroma. Asbestos exposure plays no role in etiology of benign
tumours, most often malignant lymphomas. Chylothorax is mesothelioma.
more often confined to the left side. Chylous effusion is milky Grossly, it consists of a solitary, circumscribed, small, firm
due to high content of finely emulsified fats in the chyle. mass, generally less than 3 cm in diameter. Cut surface
shows whorls of dense fibrous tissue.
PNEUMOTHORAX Microscopically, the tumour is predominantly composed
An accumulation of air in the pleural cavity is called of whorls of collagen fibres and reticulin with interspersed
pneumothorax. It may occur in one of the three circum- fibroblasts. Rarely, mesothelial-lined clefts are seen in the
stances: spontaneous, traumatic and therapeutic. tumour.
i) Spontaneous pneumothorax occurs due to spontaneous Benign mesothelioma causes no symptoms and is
rupture of alveoli in any form of pulmonary disease. Most detected as an incidental radiologic finding. Sometimes the
commonly, spontaneous pneumothorax occurs in association tumour is associated with systemic syndrome of
506
Figure 17.42 Malignant mesothelioma, showing biphasic pattern
of growth.
Microscopically, malignant mesothelioma may have
epithelial, sarcomatoid or biphasic patterns.
Figure 17.41 Malignant (diffuse) mesothelioma, gross appearance.
The tumour is seen to form a thick, white, fleshy coat over the parietal i) Epithelial pattern resembles an adenocarcinoma,
and visceral surfaces.
consisting of tubular and tubulo-papillary formations. The
tumour cells are usually well-differentiated, cuboidal,
osteoarthropathy or hypoglycaemia. Removal of the tumour flattened or columnar cells.
is generally curative. ii) Sarcomatoid pattern consists of spindle cell sarcoma
resembling fibrosarcoma. The tumour cells are arranged
Malignant (Diffuse) Mesothelioma in a storiform pattern with abundant collagen between
SECTION III
them.
Malignant or diffuse mesothelioma is rare. It is a highly
malignant tumour associated with high mortality. The iii) Biphasic pattern shows mixed growth having
tumour is significant in view of its recognised association with epithelial as well as sarcomatoid pattern. Usually, there
occupational exposure to asbestos (particularly crocidolite) for are slit-like or gland-like spaces lined by neoplastic
a number of years, usually 20 to 40 years (page 492). About mesothelial cells separated by proliferating spindle-
90% of malignant mesotheliomas are asbestos-related. shaped tumour cells (Fig. 17.42).
Mechanism of carcinogenicity by asbestos is not quite clear Asbestos bodies are found in the lungs of most patients
but it appears that prolonged exposure of amphibole type of with malignant mesothelioma of any histologic type.
asbestos is capable of inducing oncogenic mutation in the Clinical manifestations include chest pain, dyspnoea,
mesothelium. However, prolonged asbestos-exposure is pleural effusion and infections. The tumour spreads rapidly
considered more significant rather than heavy exposure as by direct invasion into lung and by lymphatic spread into
Systemic Pathology
documented by occurrence of malignant mesothelioma in the hilar lymph nodes and pericardium. Sometimes distant
family members of asbestos workers. Although combination metastases, particularly to the liver, occur. The prognosis is
of cigarette smoking and asbestos exposure greatly increases poor; 50% of patients die within one year of diagnosis.
risk to develop bronchogenic carcinoma, there is no such
extra increased risk of developing mesothelioma in asbestos
workers who smoke. Recently, SV40 (simian vacuolating SECONDARY PLEURAL TUMOURS
virus) antigen has also been implicated in the etiology of Metastatic malignancies in the pleura are more common than
mesothelioma. the primary tumours and appear as small nodules scattered
over the lung surface. The most frequent primary malignant
Grossly, the tumour is characteristically diffuse, forming tumours metastasising to the pleura are of the lung and breast
a thick, white, fleshy coating over the parietal and visceral through lymphatics, and ovarian cancers via haematogenous
surfaces (Fig. 17.41). route.
❑
507
Chapter 18 The Eye, ENT and Neck
Chapter 18
EYE
NORMAL STRUCTURE
The structure of the eye is shown diagrammatically in
Fig. 18.1. The eyelids are covered externally by the skin and
internally by conjunctiva which is reflected over the globe of
the eye. The lacrimal glands which are compound racemose
glands are situated at the outer upper angle of the orbit. The
globe of the eye is composed of 3 layers: the cornea-sclera,
choroid-iris, and retina.
The cornea consists of stratified epithelium which may
be regarded as continuation of the conjunctiva over the
cornea. The subepithelial stroma consists of fibrous
connective tissue, and the posterior endothelium-lined thin Figure 18.1 Schematic diagram of longitudinal section of the eyeball.
elastic membrane called Descemet’s membrane.
The sclera is composed of dense fibrous tissue which is CHAPTER 18
thickest at the back of the eyeball. The vitreous chamber is the large space behind the lens
The choroid is the vascular membrane in contact with containing gelatinous material, the vitreous humour.
the sclera. The choroid becomes thickened anteriorly forming The main function of the eye is visual acuity which
ciliary body, ciliary processes and contains ciliary muscle. depends upon a transparent focussing system comprised by
The iris is the continuation of the choroid which extends the cornea, lens, transparent media consisting of aqueous
in front of the lens. It is similar in structure to the choroid and vitreous humours, and a normal retinal and neural
but contains pigment cells. conduction system. The cornea and lens receive their nutrient
The uveal tract consists of 3 parts—the choroid and ciliary demands from the aqueous humour produced by the ciliary
body posteriorly, and the iris anteriorly. processes. The intraocular pressure is normally 15-20 mmHg
The retina is part of the central nervous system and and depends upon the rate of aqueous production and on The Eye, ENT and Neck
corresponds in extent to the choroid which it lines internally. the resistance in the outflow system.
The retina is composed of a number of layers of cells and
their synapses which are of 3 types—external photoreceptor CONGENITAL LESIONS
cells (rods and cones), intermediate relay layer of bipolar
cells, and internal layer of ganglion cells with their axons RETROLENTAL FIBROPLASIA (RETINOPATHY OF
running into the central nervous system. The central fovea is PREMATURITY). This is a developmental disorder occur-
a specially differentiated spot in the retina posteriorly which ring in premature infants who have been given oxygen-
consists only of photosensitive cones but is devoid of therapy at birth. The basic defect lies in the developmental
photoreceptor rods and blood vessels. Macula lutea or yellow prematurity of the retinal blood vessels which are extremely
spot surrounds the central fovea and though not as sensitive sensitive to high dose of oxygen-therapy. The peripheral
as central fovea, it is more so than the other parts of the retina. retina is incompletely vascularised in such infants and
At the optic disc, the fibres of the nerve fibre layer of the exposure to oxygen results in vaso-obliteration. On stoppage
retina pass into the optic nerve. of oxygen-therapy, vasoproliferation begins leading to
The lens is the biconvex mass of laminated transparent neovascularisation, cicatrisation and retinal detachment.
tissue with elastic capsule. RETINITIS PIGMENTOSA. Retinitis pigmentosa is a group
The anterior chamber is the space filled with the aqueous of systemic and ocular diseases of unknown etiology,
humour, and is bounded by the cornea in front and the iris characterised by degeneration of the retinal pigment
behind, with anterior surface of the lens exposed in the pupil. epithelium. The condition can have various inheritance
The posterior chamber containing aqueous humour is patterns—autosomal dominant, autosomal recessive trait, or
the triangular space between the back of the iris, the anterior sex-linked recessive trait. The earliest clinical finding is night
surface of the lens and ciliary body forming its apex at the blindness due to loss of rods and may progress to total
pupillary margin. blindness.
508
Histologically, there is disappearance of rods and cones
of the photoreceptor layer of the retina, degeneration of
retinal pigment epithelium and ingrowth of glial
membrane on the optic disc.
INFLAMMATORY CONDITIONS
Inflammatory conditions of the eye are designated according
to the tissue affected. ‘Uveitis’ is the commonly used term
for the ocular inflammation of the uveal tract which is the
most vascular tissue of the eye. However, specific designation
is used for the type of tissue of eye inflamed. Some of the
important types are described below.
STYE (HORDEOLUM). Stye or ‘external hordeolum’ is an
acute suppurative inflammation of the sebaceous glands of
Zeis, the apocrine glands of Moll and the eyelash follicles.
The less common ‘internal hordeolum’ is an acute
suppurative inflammation of the meibomian glands.
CHALAZION. Chalazion is a very common lesion and is Figure 18.2 Chalazion of the eyelid. There is presence of a
the chronic inflammatory process involving the meibomian lipogranuloma having central pool of fat and surrounded by mixed
glands. It occurs as a result of obstruction to the drainage of inflammatory cells and foreign body type multinucleated giant cells.
secretions. The inflammatory process begins with destruction
of meibomian glands and duct and subsequently involves formed by the proliferating microorganisms within the cells.
tarsal plate. Later, the conjunctiva thickens due to dense chronic
inflammatory cell infiltrate alongwith lymphoid follicles and
Histologically, the chalazion gives the appearance of a macrophages. The end-result is extensive corneal and
chronic inflammatory granuloma located in the tarsus and conjunctival cicatrisation accounting for blindness in
contains fat globules in the centre of the granulomas i.e. trachoma. Inclusion conjunctivitis, though caused by an
SECTION III
appearance of a lipogranuloma (Fig. 18.2). organism closely related to trachoma agent, is a much less
severe disease and causes mild keratoconjunctivitis.
ENDOPHTHALMITIS. Endophthalmitis is an acute
suppurative intraocular inflammation which may be of GRANULOMATOUS UVEITIS. A number of chronic
exogenous or endogenous origin. The exogenous agents may granulomatous conditions may cause granulomatous uveitis.
be bacteria, viruses or fungi introduced into the eye during These include bacteria (e.g. tuberculosis, leprosy, syphilis),
an accidental or surgical perforating wound. The endogenous viruses (e.g. CMV disease, herpes zoster), fungi (e.g.
agents include opportunistic infections which may cause aspergillosis, blastomycosis, phycomycosis, histoplasmosis),
endophthalmitis via haematogenous route e.g. candidiasis, and certain parasites (e.g. toxoplasmosis, onchocerciasis).
toxoplasmosis, nocardiosis, aspergillosis and cryptococcosis. Granulomatous uveitis is common in sarcoidosis as well.
CONJUNCTIVITIS AND KERATOCONJUNCTIVITIS. SYMPATHETIC OPHTHALMIA (SYMPATHETIC
Systemic Pathology
Conjunctiva and cornea are constantly exposed to various UVEITIS). This is an uncommon condition in which there is
types of physical, chemical, microbial (bacteria, fungi, bilateral diffuse granulomatous uveitis following penetrating
viruses) and allergic agents and hence prone to develop acute, injury to one eye. The condition probably results from an
subacute and chronic inflammations. In the acute stage, there autosensitivity reaction to injured uveal tissue. It leads to a
is corneal oedema and infiltration by inflammatory cells, severe visual loss in both the eyes if not diagnosed and
affecting the transparency of the cornea. In the more chronic treated early.
form of inflammation, there is proliferation of small blood Histologically, there is granulomatous uveal inflamma-
vessels in the normally avascular cornea and infiltration by tion consisting of epithelioid cells and lymphocytes
lymphocytes and plasma cells (pannus formation).
affecting both the eyes. There is no necrosis and no
TRACHOMA AND INCLUSION CONJUNCTIVITIS. neutrophilic or plasma cell infiltration. If lens is also
Both these conditions are caused by Chlamydia or TRIC injured, it results in phacoanaphylactic endophthalmitis.
agents. Trachoma is caused by C. trachomatis while inclusion
conjunctivitis is caused by C. oculogenitalis. Trachoma is VASCULAR LESIONS
widely prevalent in the underdeveloped and developing
countries of the world and is responsible for blindness on a DIABETIC RETINOPATHY. Diabetic retinopathy is an
large scale. In the early stage of infection, the trachoma agent important cause of blindness. It is related to the degree and
that infects the conjunctival epithelium, can be recognised duration of glycaemic control. The condition develops in
in the smears by the intracytoplasmic inclusion bodies more than 60% of diabetics 15-20 years after the onset of
509
Figure 18.3 Schematic diagram showing the effects of diabetes mellitus on eye in causing blindness.
disease, and in about 2% of diabetics causes blindness. Other ii) Friability of newly-formed blood vessels causes them
ocular complications of diabetes include glaucoma, cataract to bleed easily and results in vitreous haemorrhages.
and corneal disease. Most cases of diabetic retinopathy occur iii) Proliferation of astrocytes and fibrous tissue around
over the age of 50 years. The risk is greater in type 1 diabetes the new blood vessels.
mellitus than in type 2 diabetes mellitus, although in clinical iv) Fibrovascular and gliotic tissue contracts to cause CHAPTER 18
practice there are more patients of diabetic retinopathy due retinal detachment and blindness.
to type 2 diabetes mellitus because of its higher prevalence. In addition to the changes on retina, severe diabetes
Women are more prone to diabetes as well as diabetic may cause diabetic iridopathy with formation of adhesions
retinopathy. Diabetic retinopathy is directly correlated with between iris and cornea (peripheral anterior synechiae)
Kimmelstiel-Wilson nephropathy (page 678).
and between iris and lens (posterior synechiae). Diabetics
also develop cataract of the lens at an earlier age than the
Histologically, two types of changes are described in
diabetic retinopathy—background (non-proliferative) and general population.
proliferative retinopathy. The pathogenesis of blindness in diabetes mellitus is
1. Background (non-proliferative) retinopathy. This is schematically outlined in Fig. 18.3.
the initial retinal capillary microangiopathy. The following HYPERTENSIVE RETINOPATHY. In hypertensive The Eye, ENT and Neck
changes are seen: retinopathy, the retinal arterioles are reduced in their
i) Basement membrane shows varying thickness due to diameter leading to retinal ischaemia. In acute severe hyper-
increased synthesis of basement membrane substance. tension as happens at the onset of malignant hypertension
ii) Degeneration of pericytes and some loss of endothelial and in toxaemia of pregnancy, the vascular changes are in
cells are found. the form of spasms, while in chronic hypertension the
iii) Capillary microaneurysms appear which may develop changes are diffuse in the form of onion-skin thickening of
thrombi and get occluded. the arteriolar walls with narrowing of the lumina (page 391).
iv) ‘Waxy exudates’ accumulate in the vicinity of Features of hypertensive retinopathy include the
microaneurysms especially in the elderly diabetics following (Fig. 18.4):
because of hyperlipidaemia. i) Variable degree of arteriolar narrowing due to
v) ‘Dot and blot haemorrhages’ in the deeper layers of arteriolosclerosis.
retina are produced due to diapedesis of erythrocytes. ii) ‘Flame-shaped’ haemorrhages in the retinal nerve fibre
vi) Soft ‘cotton-wool spots’ appear on the retina which layer.
are microinfarcts of nerve fibre layers. ‘Scotomas’ appear iii) Macular star i.e. exudates radiating from the centre of
from degeneration of nerve fibres and ganglion cells. macula.
iv) Cotton-wool spots i.e. fluffy white bodies in the
2. Proliferative retinopathy (retinitis proliferans). After superficial layer of retina.
many years, retinopathy becomes proliferative. Severe v) Microaneurysms.
ischaemia and chronic hypoxia for long period leads to vi) Arteriovenous nicking i.e. kinking of veins at sites where
secretion of angiogenic factor by retinal cells and results sclerotic arterioles cross veins.
in the following changes: vii) Hard exudates due to leakage of lipid and fluid into
i) Neovascularisation of the retina at the optic disc. macula.
510 choroid, exudation and haemorrhage under the retina
which may eventually get organised and heal by fibrosis
and result in permanent loss of central vision.
RETINAL DETACHMENT. Retinal detachment is the
separation of the neurosensory retina from the retinal
pigment epithelium. It may occur spontaneously in older
individuals past 50 years of age, or may be secondary to
trauma in the region of head and neck. Normally, the rods
and cones of the photoreceptor layer are interdigitated with
projections of the retinal pigment epithelium, but the two
can separate readily in some disease processes. There are 3
pathogenetic mechanisms of retinal detachment:
i) Pathologic processes in the vitreous or anterior segment,
causing traction on the retina.
Figure 18.4 Ocular lesions in hypertension.
ii) Collection of serous fluid in the sub-retinal space from
inflammation or tumour in the choroid.
Hypertensive retinopathy is classified according to the iii) Accumulation of vitreous under the retina through a hole
severity of above lesions from grade I to IV. More serious or a tear in the retina.
and severe changes with poor prognosis occur in higher PHTHISIS BULBI. Phthisis bulbi is the end-stage of
grades of hypertensive retinopathy. Malignant hypertension advanced degeneration and disorganisation of the entire
is characterised by necrotising arteriolitis and fibrinoid eyeball in which the intraocular pressure is decreased and
necrosis of retinal arterioles.
the eyeball shrinks. The causes of such end-stage blind eye
RETINAL INFARCTS. Infarcts of the retina may result from are trauma, glaucoma and intraocular inflammations.
thrombosis or embolism in central artery of the retina,
causing ischaemic necrosis of the inner two-third of the retina Histologically, there is marked atrophy and disorga-
while occlusion of the posterior ciliary arteries causes nisation of all the ocular structures, and markedly
ischaemia of the inner photoreceptor layer only. The usual thickened sclera. Even osseous metaplasia may occur.
SECTION III
causes of thrombosis and embolism are atherosclerosis,
hypertension and diabetes. Occlusion of the central retinal CATARACT. The cataract is the opacification of the normally
vein produces haemorrhagic infarction of the entire retina. crystalline lens which leads to gradual painless blurring of
vision. The various causes of cataract are: senility, congenital
(e.g. Down syndrome, rubella, galactosaemia), traumatic (e.g.
MISCELLANEOUS CONDITIONS
penetrating injury, electrical injury), metabolic (e.g. diabetes,
PINGUECULA AND PTERYGIUM. Pinguecula is a hypoparathyroidism), and associated with drugs (e.g. long-
degenerative condition of the collagen of the bulbar term corticosteroid therapy), smoking and heavy alcohol
conjunctiva. Clinically, the condition appears as raised consumption. The most common is, however, idiopathic
yellowish lesions on the interpalpebral bulbar conjunctiva senile cataract.
of both eyes in middle-aged and elderly patients.
Histologically, the changes in the cataractous lens are
Systemic Pathology
Histologically, there is characteristic basophilic similar irrespective of the underlying cause. The lens fibres
degeneration of the subepithelial collagen of the undergo degeneration, fragmentation and liquefaction but
conjunctiva. The overlying epithelium may show the central nucleus remains intact because it is quite
acanthosis, hyperkeratosis or dyskeratosis. sclerotic.
Pterygium is a lesion closely related to pinguecula but differs GLAUCOMA. Glaucoma is a group of ocular disorders that
from the latter by being located at the limbus and often have in common increased intraocular pressure. Glaucoma
involves the cornea; hence the lesion is more important is one of the leading causes of blindness because of the
clinically.
ocular tissue damage produced by raised intraocular
SENILE MACULAR DEGENERATION. Age-related pressure. In almost all cases, glaucoma occurs due to
degeneration of the macular region of the retina is an impaired outflow of aqueous humour, though there is a
important cause of bilateral central visual loss in the elderly theoretical possibility of increased production of aqueous
people. by the ciliary body causing glaucoma. The obstruction to
the aqueous flow may occur as a result of developmental
Histologically, in the early stage, there is irregular malformations (congenital glaucoma); or due to
thickening of the Bruch’s membrane that separates retinal complications of some other diseases such as uveitis,
pigment epithelium from the choroid, and there is trauma, intraocular haemorrhage and tumours (secondary
degeneration of the photoreceptor and pigment glaucoma); or may be primary glaucoma which is typically
epithelium. Later, there is ingrowth of capillaries into the bilateral and is the most common type.
There are 2 types of primary glaucoma—primary open- TABLE 18.1: Tumours and Tumour-like Lesions of the Eye 511
angle (chronic simple glaucoma) and primary angle-closure and Adnexal Structures.
(acute congestive glaucoma). Primary open-angle glaucoma
is more common type and is usually a genetically-determined Benign Malignant
disease. Primary angle-closure glaucoma occurs due to I. EYELID
shallow anterior chamber and hence narrow angle causing Squamous cell papilloma Squamous cell carcinoma
blockage to aqueous outflow. Basal cell papilloma Basal cell carcinoma
In all types of glaucoma, degenerative changes appear Sebaceous adenoma Sebaceous adenocarcinoma
after some duration and eventually damage to the optic nerve Naevi Malignant melanoma
and retina occurs. II. CONJUNCTIVA-CORNEA
Squamous cell papilloma Squamous cell carcinoma
PAPILLOEDEMA. Papilloedema is oedema of the optic disc Pseudoepitheliomatous Mucoepidermoid carcinoma
resulting from increased intracranial pressure. This is due hyperplasia
to anatomic continuation of the subarachnoid space of the Naevi Malignant melanoma
brain around the optic nerve so that raised intracranial Haemangioma
III. LACRIMAL GLAND
pressure is passed onto the optic disc area. In acute
papilloedema, there is oedema, congestion and haemorrhage Pleomorphic adenoma Carcinoma in pleomorphic
adenoma
at the optic disc. In chronic papilloedema, there is degene- IV. ORBIT
ration of nerve fibres, gliosis and optic atrophy.
Glioma Malignant glioma
SJÖGREN’S SYNDROME. Sjögren’s syndrome is charac- Inflammatory ‘pseudotumour’ Malignant lymphoma
terised by triad of keratoconjunctivitis sicca, xerostomia (sicca Meningioma Rhabdomyosarcoma
syndrome) and rheumatoid arthritis. The condition occurs V. INTRAOCULAR
due to immunologically-mediated destruction of the lacrimal Naevi Malignant melanoma
and salivary glands along- with another autoimmune disease Neurofibroma Retinoblastoma
(Chapter 4).
is seen more commonly in the upper eyelid (basal cell
MIKULICZ’S SYNDROME. This is characterised by
inflammatory enlargement of lacrimal and salivary glands carcinoma is seen more frequently in the lower eyelid). CHAPTER 18
(Chapter 19). The condition may occur with Sjögren’s MORPHOLOGIC FEATURES. Grossly, the tumour
syndrome, or with some diseases like sarcoidosis, leukaemia, appears as a localised or diffuse swelling of the tarsus, or
lymphoma and macroglobulinaemia. may be in the form of ulcerated or papillomatous tumour
at the lid margin.
TUMOURS AND TUMOUR-LIKE LESIONS Microscopically, the tumour may show well-differen-
The eye and its adnexal structures are the site of a variety of tiated lobules of tumour cells with sebaceous differen-
benign and malignant tumours as well as tumour-like lesions. tiation, or may be poorly-differentiated tumour requiring
A brief list of such lesions is given in Table 18.1. The confirmation by fat stains (Fig. 18.5). These tumours can
morphology of many of these tumours and tumour-like
lesions is identical to similar lesions elsewhere in the body. The Eye, ENT and Neck
However, a few examples peculiar to the eye are described
below.
Inflammatory Pseudotumours
These are a group of inflammatory enlargements, especially
in the orbit, which clinically look like tumours but surgical
exploration and pathologic examination fail to reveal any
evidence of neoplasm.
MORPHOLOGIC FEATURES. Grossly, these lesions are
circumscribed and sometimes have fibrous capsule.
Microscopically, many of the lesions can be placed in well-
established categories such as tuberculous, syphilitic,
mycotic, parasitic, foreign-body granuloma etc, while
others show non-specific histologic appearance having
abundant fibrous tissue, lymphoid follicles and
inflammatory infiltrate with prominence of eosinophils.
Sebaceous Carcinoma
This is the most frequent tumour of the eyelid next only to basal
cell carcinoma, although it is very rare tumour elsewhere in Figure 18.5 Sebaceous carcinoma. The tumour cells are arranged
as lobules with peripheral basaloid cells and pale cells in the centre. The
the body. It arises either from the meibomian glands in the cells have sebaceous differentiation appreciated by foamy, vacuolated
tarsus or from Zeis’ glands of eyelash follicles. The tumour cytoplasm.
512
Figure 18.6 Choroidal melanoma appearing as a pigmented mass
pushing the retina forward over it.
metastasise to the regional lymph nodes as well as to Figure 18.7 Uveal melanoma. The tumour cells are epithelioid in
distant sites. appearance having prominent nucleoli and contain black finely granular
melanin pigment in the cytoplasm.
Uveal Malignant Melanoma
melanomas spread via haematogenous route and liver is
Malignant melanomas arising from neural crest-derived eventually involved in 90% of cases. Various indicators of
pigment epithelium of the uvea is the most common primary bad prognosis include large tumour size and epithelioid cell
ocular malignancy in the white adults in North America and type.
Europe. It is discussed in detail in Chapter 26.
Retinoblastoma
MORPHOLOGIC FEATURES. Grossly, the malignant
SECTION III
melanoma appears as a pigmented mass, most commonly This is the most common malignant ocular tumour in
in the posterior choroid, and less often in the ciliary body children. It may be present at birth or recognised in early
and iris. The mass projects into the vitreous cavity with childhood before the age of 4 years. Retinoblastoma has some
retina covering it (Fig. 18.6). peculiar features. About 60% cases of retinoblastoma are
Microscopically, age-old classification of Callender (1931) sporadic and the remaining 40% are familial. Familial
which has prognostic significance is still followed with tumours are often multiple and multifocal and transmitted
some modifications: as an autosomal dominant trait by retinoblastoma
1. Spindle A melanoma is composed of uniform, susceptibility gene (RB) located on chromosome 13. Such
spindle-shaped cells containing spindled nuclei. Nucleoli individuals have a higher incidence of bilateral tumours and
are indistinct and mitotic figures are rare. Tumours of this have increased risk of developing second primary tumour,
type have the most favourable prognosis (85% 10-year particularly osteogenic sarcoma. Retinoblastoma may occur
Systemic Pathology
survival).
2. Spindle B melanoma is composed of larger and plump
spindle-shaped cells with ovoid nuclei. Nucleoli are
conspicuous and a few mitotic figures are present. These
tumours carry slightly worse prognosis (80% 10-year
survival).
3. Epithelioid melanoma consists of larger, irregular and
pleomorphic cells with larger nuclei and abundant
acidophilic cytoplasm (Fig. 18.7). These tumours are the
most malignant of the uveal melanomas and have poor
prognosis (35% 10-year survival).
4. Mixed cell type melanomas have features of spindle
cell type as well as of epithelioid cell type. These are more
common tumours and carry an intermediate prognosis
(45% 10-year survival).
In general, uveal malignant melanomas are usually slow-
growing, late metastasising and have a better prognosis than Figure 18.8 Retinoblastoma, showing white mass growing
malignant melanoma of the skin (Chapter 26). Uveal extensively within the posterior part of the eye.
513
Figure 18.9 Retinoblastoma. The tumour arising from the retina (arrow) shows undifferentiated retinal cells and the typical rosettes.
as a congenital tumour too. Clinically, the child presents with The tumour can spread widely via haematogenous route
leukokoria i.e. white pupillary reflex. as well. Prognosis is determined by the extent of local
invasion and distant metastasis.
MORPHOLOGIC FEATURES. Grossly, the tumour Salient features of retinoblastoma are contrasted with
characteristically appears as a white mass within the retina those of uveal melanoma in Table 18.2.
which may be partly solid and partly necrotic. The tumour CHAPTER 18
may be endophytic when it protrudes into the vitreous, or Metastatic Tumours
exophytic when it grows between the retina and the Ocular metastatic tumours are far more common than
pigment epithelium (Fig. 18.8). primary ocular malignant tumours, choroid and iris being
Microscopically, the tumour is composed of the preferential site for metastasis. Common primary
undifferentiated retinal cells with tendency towards tumours that metastasise in the eye are cancers of the breast
formation of photo-receptor elements. In the better in women and lung in men. Leukaemia and malignant
differentiated area, the tumour cells are characteristically lymphoma also commonly invade ocular tissues.
arranged in rosettes. The rosettes may be of 2 types—
Flexner-Wintersteiner rosettes characterised by small EAR
tumour cells arranged around a lumen with their nuclei The Eye, ENT and Neck
away from the lumen, and Homer-Wright rosettes having NORMAL STRUCTURE
radial arrangement of tumour cells around the central
neurofibrillar structure (Fig. 18.9). The tumour shows The ear is divided into 3 parts—the external, middle and
wide areas of necrosis and calcification and dissemination inner ear.
in all directions—into the vitreous, under the retina, into The external ear comprises the auricle or pinna composed
the optic nerve and even into the brain. of cartilage, the external cartilaginous meatus and the
external bony meatus. The external meatus is lined by
TABLE 18.2: Uveal Malignant Melanoma versus Retinoblastoma.
Feature Melanoma Retinoblastoma
1. Inheritance Rare About 40% cases
2. Age >50 years Birth to 4 years
3. Race Common in Caucasians, uncommon in blacks No predisposition
4. Location Most commonly choroid Retina
5. Bilaterality Rare Common (30%)
6. Cell of origin Melanocytes Retinal neurons
7. Colour of tumour Grey-black Creamy
8. Spread Haematogenous common, rarely via optic nerve Common via both haematogenous
and optic nerve
514 stratified epithelium which is continued on to the external inflammatory cell infiltrate, vascular proliferation and
layer of the tympanic membrane. The tympanic membrane fibrosis.
has middle layer of elastic fibrous tissue and the inner layer
of mucous membrane and is supported around the periphery
by the annulus. MISCELLANEOUS CONDITIONS
The middle ear consists of 3 parts—the uppermost CAULIFLOWER EAR. This is an acquired deformity of the
portion is the attic, the middle portion is mesotympanum, and external ear due to degeneration of cartilage as a result of
the lowermost portion is the hypotympanum. Besides, the repeated trauma as occurs in boxers and wrestlers.
middle ear has an opening, eustachian tube, the mastoid
antrum and cells, and the three ossicles (the malleus, incus Histologically, there is destruction of cartilage forming
and stapes). The middle ear is lined by a single layer of flat homogeneous matrix (chondromalacia) and fibrous
ciliated and nonciliated epithelium. replacement.
The inner ear or labyrinth consists of bony capsule
embedded in the petrous bone and contains the membranous OTOSCLEROSIS. This is a dystrophic disease of labyrinth
labyrinth. The bony capsule consists of 3 parts—posteriorly of the temporal bone. The footplate of stapes first undergoes
three semicircular canals, in the middle is the vestibule, and fibrous replacement and is subsequently replaced by sclerotic
anteriorly contains snail-like cochlea. bone. The exact etiology is not known but the condition has
Besides the function of hearing, the stimulation of familial preponderance and autosomal dominant trait. It is
vestibular labyrinth can cause vertigo, nausea, vomiting and seen more commonly in young males as a cause for sensori-
nystagmus. neural type of deafness.
INFLAMMATORY LESIONS TUMOURS AND TUMOUR-LIKE LESIONS
OTITIS MEDIA. This is the term used for inflammatory Tumours and tumour-like conditions are relatively more
involvement of the middle ear. It may be acute or chronic. common in the external than the middle and inner ear. The
The usual source of infection is via the eustachian tube and lesions seen in the external ear are similar to those seen in
the common causative organisms are Streptococcus the skin e.g. tumour-like lesions such as epidermal cyst; benign
pneumoniae, Haemophilus influenzae and β-Streptococcus tumours like naevi and squamous cell papilloma; and
haemolyticus. Otitis media may be suppurative, serous or malignant tumours such as basal cell carcinoma, squamous
SECTION III
mucoid. Acute suppurative otitis media (SOM) clinically cell carcinoma and malignant melanoma. However, tumours
presents as tense and hyperaemic tympanic membrane along and tumour-like lesions which are specific to the ear are
with pain and tenderness and sometimes mastoiditis as well. described below. These include the following:
Chronic SOM manifests clinically as draining ear with In the external ear—aural (otic) polyps and cerumen-
perforated tympanic membrane and partially impaired gland tumours.
hearing. Serous or mucoid otitis media refers to non- In the middle ear—cholesteatoma (keratoma) and jugular
suppurative accumulation of serous or thick viscid fluid in paraganglioma (glomus jugulare tumour).
the middle ear. These collections of fluid are encountered In the inner ear—acoustic neuroma.
more often in children causing hearing problems and occur AURAL (OTIC) POLYPS. Aural or otic polyps are tumour-
due to obstruction of the eustachian tube. like lesions arising from the middle ear as a complication of
Systemic Pathology
RELAPSING POLYCHONDRITIS. This is an uncommon the chronic otitis media and project into the external auditory
autoimmune disease characterised by complete loss of canal.
glycosaminoglycans resulting in destruction of cartilage of
the ear, nose, eustachian tube, larynx and lower respiratory Histologically, they are composed of chronic inflamma-
tract. tory granulation tissue and are often covered by
metaplastic squamous epithelium or pseudostratified
columnar epithelium.
Histologically, the perichondral areas show acute
inflammatory cell infiltrate and destruction and vasculari- CERUMEN-GLAND TUMOURS. Tumours arising from
sation of the cartilage. Late stage shows lymphocytic cerumen-secreting apocrine sweat glands of the external
infiltration and fibrous replacement.
auditory canal are cerumen-gland adenomas or cerumen-
gland adenocarcinomas and are counter-parts of sweat gland
CHONDRODERMATITIS NODULARIS CHRONICA tumours (hideradenoma and adenocarcinoma) of the skin
HELICIS. This condition involves the external ear discussed in Chapter 26. Both these tumours may invade the
superficially and presents as a ‘painful nodule of the ear’. temporal bone.
The skin in this location is in direct contact with the cartilage
without protective subcutaneous layer. CHOLESTEATOMA (KERATOMA). This is a post-
inflammatory ‘pseudotumour’ found in the middle ear or
Histologically, the nodule shows epithelial hyperplasia mastoid air cells. There is invariable history of acute or
with degeneration of the underlying collagen, chronic chronic otitis media. A marginal perforation is generally
NOSE AND PARANASAL SINUSES 515
NORMAL STRUCTURE
The external nose and the septum are composed of bone and
cartilage. On the lateral wall of the nasal cavity, there is a
system of 3 ridges on each side known as conchae or
turbinates—the inferior, middle and superior. The nasal
accessory sinuses are air spaces in the bones of the skull and
communicate with the nasal cavity. They are the frontal air
sinus, maxillary air sinus and the anterior ethmoid air cells,
comprising the anterior group, while posterior ethmoidal cells
and sphenoidal sinus form the posterior group. The anterior
group drains into the middle meatus while the posterior
group drains into the superior meatus and the spheno-
ethmoidal recess. Nasal mucous membranes as well as the
lining of the nasal sinus are lined by respiratory epithelium
(pseudostratified columnar ciliated cells). Mucous and serous
glands underlie the mucous membrane. Besides, the upper
Figure 18.10 Cholesteatoma middle ear. There is chronic and middle turbinate processes and the upper third of the
inflammatory granulation tissue and foreign body giant cells around the septum are covered with olfactory mucous membrane.
cholesterol clefts and some pink keratinous material.
The main physiologic functions of the nose are smell,
filtration, humidification and warming of the air being
present through which the squamous epithelium enters the breathed.
middle ear and results in exfoliation of squamous and
formation of the keratin. Rarely, it may be a primary lesion INFLAMMATORY CONDITIONS
arising from embryonal rests of squamous epithelium in the CHAPTER 18
temporal bone. ACUTE RHINITIS (COMMON COLD). Acute rhinitis or
common cold is the common inflammatory disorder of the
Histologically, the lesion consists of cyst containing nasal cavities that may extend into the nasal sinuses. It begins
abundant keratin material admixed with cholesterol with rhinorrhoea, nasal obstruction and sneezing. Initially,
crystals and large number of histiocytes (Fig. 18.10). In the nasal discharge is watery, but later it becomes thick and
advanced cases, there may be pressure erosion of the bone. purulent. The etiologic agents are generally adenoviruses that
evoke catarrhal discharge. Chilling of the body is a
JUGULAR PARAGANGLIOMA (GLOMUS JUGULARE contributory factor. Secondary bacterial invasion is common.
TUMOUR, NON-CHROMAFFIN PARAGANGLIOMA). The nasal mucosa is oedematous, red and thickened.
Tumours originating from parasympathetic ganglia are The Eye, ENT and Neck
called ‘paraganglioma’ and are named according to the Microscopically, there are numerous neutrophils,
location of the tissue of origin. The one arising from glomus lymphocytes, plasma cells and some eosinophils with
jugulare bodies of the middle ear (jugulotympanic bodies) abundant oedema.
is called jugular paraganglioma or chemodectoma or non- ALLERGIC RHINITIS (HAY FEVER). Allergic rhinitis
chromaffin paraganglioma and is the most common benign occurs due to sensitivity to allergens such as pollens. It is an
tumour of the middle ear. Histologically similar tumours are IgE-mediated immune response consisting of an early acute
seen in the carotid bodies and vagus (Chapter 27). response due to degranulation of mast cells, and a delayed
prolonged response in which there is infiltration by
Microscopically, the tumour cells containing neuro- leucocytes such as eosinophils, basophils, neutrophils and
secretory granules are arranged in typical organoid macrophages accompanied with oedema.
pattern or nests. The tumour may extend locally to involve
the skull and brain but may rarely metastasise. SINUSITIS. Acute sinusitis is generally a complication of
acute or allergic rhinitis and rarely secondary to dental sepsis.
ACOUSTIC NEUROMA (ACOUSTIC SCHWANNOMA). The ostia are occluded due to inflammation and oedema and
This is a tumour of Schwann cells of 8th cranial nerve the sinuses are full. ‘Mucocele’ is filling up of the sinus with
(page 893). It is usually located in the internal auditory canal mucus while ‘empyema’ of the sinus occurs due to collection
and cerebellopontine angle. It is a benign tumour similar to of pus. Acute sinusitis may become chronic due to incomplete
other schwannomas but by virtue of its location and large resolution of acute inflammation and from damage to the
size, may produce compression of the important mucous membrane. Sinusitis may rarely spread to produce
neighbouring tissues leading to deafness, tinnitus, paralysis osteomyelitis and intracranial infections.
of 5th and 7th nerves, compression of the brainstem and NASAL POLYPS. Nasal polyps are common and are
hydrocephalus. pedunculated grape-like masses of tissue. They are the end-
516 respiratory epithelium which may show squamous
metaplasia (Fig. 18.11). Nasal polyps may have
superimposed fungal infection.
RHINOSPORIDIOSIS. Rhinosporidiosis is caused by a
fungus, Rhinosporidium seeberi. Typically it occurs in a nasal
polyp but may be found in other locations like nasopharynx,
larynx and conjunctiva. The disease is common in India and
Sri Lanka and sporadic in other parts of the world.
Microscopically, besides the structure of inflammatory
or allergic polyp, large number of organisms of the size
of erythrocytes with chitinous wall are seen in the thick-
walled sporangia. Each sporangium may contain a few
thousand spores. On rupture of a sporangium, the spores
are discharged into the submucosa or on to the surface of
the mucosa. The intervening tissue consists of inflam-
matory granulation tissue (plasma cells, lymphocytes,
histiocytes, neutrophils) while the overlying epithelium
Figure 18.11 Allergic polyp nose. The overlying mucosa is covered shows hyperplasia, focal thinning and occasional
partly by respiratory and partly by squamous metaplastic epithelium. ulceration (Fig. 18.12).
The underlying stroma is oedematous and contains inflammatory cells
with prominence of eosinophils.
RHINOSCLEROMA. This is a chronic destructive
result of prolonged chronic inflammation causing poly- inflammatory lesion of the nose and upper respiratory
poid thickening of the mucosa. They may be allergic or inflam- airways caused by diplobacilli, Klebsiella rhinoscleromatis. The
matory. They are frequently bilateral and the middle turbinate condition is endemic in parts of Africa, America, South Asia
is the common site. Antrochoanal polyps originate from the and Eastern Europe. The condition begins as a common cold
mucosa of the maxillary sinus and appear in the nasal cavity. and progresses to atrophic stage, and then into the nodular
Morphologically, nasal and antro-choanal polyps are stage characterised by small tumour-like submucosal masses.
SECTION III
identical.
Histologically, there is extensive infiltration by foamy
Grossly, they are gelatinous masses with smooth and histiocytes containing the organisms (Mikulicz cells) and
shining surface. other chronic inflammatory cells like lymphocytes and
Microscopically, they are composed of loose oedematous plasma cells.
connective tissue containing some mucous glands and
varying number of inflammatory cells like lymphocytes, GRANULOMAS. Many granulomatous inflammations may
plasma cells and eosinophils. Allergic polyps have plenty involve the nose. These include: tuberculosis, leprosy,
of eosinophils and hyperplasia of mucous glands. Both syphilis, aspergillosis, mucormycosis, Wegener’s
inflammatory and allergic polyps are covered by granulomatosis and lethal midline granuloma.
Systemic Pathology
Figure 18.12 Rhinosporidiosis in a nasal polyp. The spores are present in sporangia as well as are intermingled in the inflammatory cell
infiltrate.
1. Tuberculosis or lupus of the nose is uncommon and other small cell malignancies like rhabdomyosarcoma, 517
occurs secondary to pulmonary tuberculosis and usually undifferentiated carcinoma, lymphoma or Ewing’s sarcoma.
produces ulcerative lesions on the anterior part of the septum Rosettes are found in about 10% of tumours.
of the nose.
2. CARCINOMAS. Majority of carcinomas of the nasal cavity
2. Leprosy begins as a nodule that may ulcerate and and paranasal sinuses are squamous cell carcinomas,
perforate the septum. commonly called sinonasal carcinomas. They are seen more
3. Syphilis may involve the nose in congenital form causing commonly in the elderly with history of heavy smoking and
destruction of the septum, or in acquired tertiary syphilis in severe chronic sinusitis, in nickel refinery workers and in
the form of gummas perforating the septum. In either case, wood workers. The tumour extends locally to involve the
characteristic saddle-nose deformity occurs due to collapse surrounding bone and soft tissues and also metastasises
of bridge of the nose. widely. Other types of malignancies found uncommonly in
4. Aspergillosis may involve the paranasal sinuses where this location are: adenocarcinoma, adenoid cystic carcinoma,
the septate hyphae grow to form a mass called aspergilloma. mucoepidermoid carcinoma, small cell carcinoma,
lymphoma and malignant melanoma.
5. Mucormycosis is an opportunistic infection caused by
Mucorales which are non-septate hyphae and involve the
nerves and blood vessels. PHARYNX
6. Wegener’s granulomatosis is a form of necrotising NORMAL STRUCTURE
vasculitis with granuloma formation affecting the upper
respiratory tract, lungs and kidneys. In 15-50% of cases, the The pharynx has 3 parts—the nasopharynx, oropharynx
condition may evolve into malignant lymphoma. (pharynx proper) and the laryngopharynx. The whole of
pharynx is lined by stratified squamous epithelium. The
7. Lethal midline granuloma or polymorphic reticulosis lymphoid tissue of the pharynx is comprised by the tonsils
is a rare and lethal lesion of the upper respiratory tract that and adenoids.
causes extensive destruction of cartilage and necrosis of
tissues and does not respond to antibiotic treatment. Besides
the necrosis, lymphoid infiltrates of pleomorphic and atypical INFLAMMATORY CONDITIONS CHAPTER 18
cells admixed with small lymphocytes, plasma cells and LUDWIG’S ANGINA. This is a severe, acute streptococcal
macrophages are seen. Currently, the condition is considered cellulitis involving the neck, tongue and back of the throat.
to be a T cell lymphoma that may respond to chemotherapy The condition was more common in the pre-antibiotic era as
and radiotherapy (page 380). a complication of compound fracture of the mandible and
periapical infection of the molars. The condition often proves
TUMOURS fatal due to glottic oedema, asphyxia and severe toxaemia.
The tumours of nose, nasal cavity and paranasal sinuses are VINCENT’S ANGINA. Vincent’s angina is a painful
uncommon. However, benign and malignant tumours of condition of the throat characterised by local ulceration of
epithelial as well as mesenchymal origin can occur. the tonsils, mouth and pharynx. The causative organism is The Eye, ENT and Neck
Vincent’s bacillus. The condition may occur as an acute illness
Benign Tumours involving the tissues diffusely, or as chronic form consisting
1. CAPILLARY HAEMANGIOMA. Capillary haeman- of ulceration of the tonsils.
gioma of the septum of nose is a common benign lesion. If DIPHTHERIA. Diphtheria is an acute communicable disease
the surface is ulcerated and the lesion contains inflammatory caused by Corynebacterium diphtheriae. It usually occurs in
cell infiltrate, it resembles inflammatory granulation tissue children and results in the formation of a yellowish-grey
and is called ‘haemangioma of granulation tissue type’ or pseudomembrane in the mucosa of nasopharynx, oropharynx,
‘granuloma pyogenicum’. tonsils, larynx and trachea. C. diphtheriae elaborates an
2. SINONASAL PAPILLOMAS. Papillomas may occur in exotoxin that causes necrosis of the epithelium which is
the nasal vestibule, nasal cavity and paranasal sinuses. They associated with abundant fibrinopurulent exudate resulting
are mainly of 2 types—fungiform papilloma with exophytic in the formation of pseudomembrane. Absorption of the
growth, and inverted papilloma with everted growth, also exotoxin in the blood may lead to more distant injurious
called Schneiderian pailloma. Each of these may be lined with effects such as myocardial necrosis, polyneuritis,
various combinations of epithelia: respiratory, squamous and parenchymal necrosis of the liver, kidney and adrenals. The
mucous type. constitutional symptoms such as fever, chills, malaise,
obstruction of the airways and dyspnoea are quite marked.
Malignant Tumours The condition has to be distinguished from the membrane
of streptococcal infection.
1. OLFACTORY NEUROBLASTOMA OR ESTHESIO-
NEUROBLASTOMA. It occurs over the olfactory mucosa TONSILLITIS. Tonsillitis caused by staphylococci or
as a polypoid mass that may invade the paranasal sinuses streptococci may be acute or chronic. Acute tonsillitis is charac-
or skull. It is a highly malignant small cell tumour of neural terised by enlargement, redness and inflammation. Acute
crest origin that may, at times, be indistinguishable from tonsillitis may progress to acute follicular tonsillitis in which
518 crypts are filled with debris and pus giving it follicular
appearance. Chronic tonsillitis is caused by repeated attacks
of acute tonsillitis in which case the tonsils are small and
fibrosed. Acute tonsillitis may pass on to tissues adjacent to
tonsils to form peritonsillar abscess or quinsy.
PERITONSILLAR ABSCESS (QUINSY). Peritonsillar
abscess or quinsy occurs as a complication of acute tonsil-
litis. The causative organisms are staphylococci or
streptococci which are associated with infection of the tonsils.
The patient complains of acute pain in the throat, trismus,
difficulty in speech and inability to swallow. The glands
behind the angle of the mandible are enlarged and tender.
Besides the surgical management of the abscess, the patient
must be advised tonsillectomy because quinsy is frequently
recurrent.
RETROPHARYNGEAL ABSCESS. Formation of abscess in
the soft tissue between the posterior wall of the pharynx and
the vertebral column is called retropharyngeal abscess. It
occurs due to infection of the retropharyngeal lymph nodes. Figure 18.13 Angiofibroma nose. There is admixture of thin-walled
blood vessels and spindled stroma. The blood vessels are variable-sized,
It is found in debilitated children. A chronic form of the some having incomplete muscle coat and there is absence of elastic
abscess in the same location is seen in tuberculosis of the tissue. The stroma has stellate fibroblasts and mast cells.
cervical spine (cold abscess).
Non-keratinising and keratinising squamous cell
TUMOURS carcinomas are identical in morphology to typical tumours
There are 4 main tumours of note in the pharynx, one in other locations. The undifferentiated carcinoma, also
benign—nasopharyngeal angiofibroma, and three called as transitional cell carcinoma, is characterised by
malignant— nasopharyngeal carcinoma, embryonal masses and cords of cells which are polygonal to spindled
SECTION III
rhabdomyosarcoma and malignant lymphoma. and have large vesicular nuclei. A variant of undiffe-
rentiated carcinoma is ‘lymphoepithelioma’ in which
NASOPHARYNGEAL ANGIOFIBROMA. This is a undifferentiated carcinoma is infiltrated by abundant non-
peculiar tumour that occurs exclusively in adolescent males neoplastic mature lymphocytes (Fig. 18.14).
(10-20 years of age) suggesting the role of testosterone
hormone in its production. Though a benign tumour of the
nasopharynx, it may grow into paranasal sinuses, cheek and
orbit but does not metastasise.
Microscopically, the tumour is composed of 2 components
as the name suggests—numerous small endothelium-
lined vascular spaces and the stromal cells which are
Systemic Pathology
myofibroblasts (Fig. 18.13). The androgen-dependence of
the tumour is confirmed by demonstration by
immunostaining for androgen receptors in 75% cases.
NASOPHARYNGEAL CARCINOMA. Nasopharyngeal
carcinoma is a common cancer in South-East Asia, especially
prevalent in people of Chinese descent under 45 years of age.
Genetic susceptibility and role of Epstein-Barr virus are consi-
dered important factors in its etiology (page 225). In fact,
EBV-genome is found virtually in all cases of nasopharyngeal
carcinoma. The primary tumour is generally small and
undetected, while the metastatic deposits in the cervical
lymph nodes may be large.
Microscopically, nasopharyngeal carcinoma has
3 histologic variants:
i) Non-keratinising squamous cell carcinoma
ii) Keratinising squamous cell carcinoma
iii) Undifferentiated (transitional cell) carcinoma Figure 18.14 Nasopharyngeal carcinoma, non-keratinising. The
tumour is composed of undifferentiated anaplastic cells arranged in nests.
The prognosis is usually fatal. Undifferentiated TUMOURS 519
carcinoma is radiosensitive.
Both benign and malignant tumours occur in the larynx. The
EMBRYONAL RHABDOMYOSARCOMA. Also termed as common examples of benign tumours are papillomas and
botyroid rhabdomyosarcoma, this is one of the common polyps, while laryngeal carcinoma is an important example
malignant tumours in children but can also occur in adults. amongst malignant tumours.
The lesion is highly cellular and mitotically active. Other LARYNGEAL PAPILLOMA AND PAPILLOMATOSIS.
locations include vagina, orbit, middle ear, oral cavity, Juvenile laryngeal papillomas are found in children or
retroperitoneum and bile duct. It is discussed in detail on adolescents and are often multiple, while the adults have
page 867.
usually a single lesion. Multiple juvenile papillomas may
MALIGNANT LYMPHOMA. The lymphoid tissue of the undergo spontaneous regression at puberty. Human
nasopharynx and tonsils may be the site for development of papilloma virus (HPV type 11 and 6) has been implicated in
malignant lymphomas which resemble similar tumours the etiology of papillomas of the larynx.
elsewhere in the body.
Grossly, the lesions appear as warty growths on the true
vocal cords, epiglottis and sometimes extend to the trachea
LARYNX and bronchi.
Microscopically, papillomas are composed of finger-like
NORMAL STRUCTURE
papillae, each papilla contains fibrovascular core covered
The larynx is composed of cartilages which are bound by stratified squamous epithelium (Fig. 18.15).
together by ligaments and muscles and is covered by mucous
membrane. The cartilages of the larynx are of 2 types— LARYNGEAL NODULES. Laryngeal nodules or polyps are
unpaired and paired. seen mainly in adults and are found more often in heavy
The unpaired laryngeal cartilages are epiglottis, thyroid smokers and in individuals subjected to vocal abuse.
cartilage (Adam’s apple) and cricoid cartilage. Therefore, they are known by various synonyms like singers’
The paired cartilages are the arytenoid cartilages which nodes, preachers’ node, and screamers’ nodes. The patients
play important part in the movement of vocal cords. have characteristic progressive hoarseness. CHAPTER 18
The larynx as well as trachea are lined by respiratory Grossly, it is a small lesion, less than 1 cm in diameter,
epithelium, except over the true vocal cords and the rounded, smooth, usually sessile and polypoid swelling
epiglottis, which are lined by stratified squamous epithelium.
on the true vocal cords.
Microscopically, the nodules have prominent oedema
INFLAMMATORY CONDITIONS
with sparse fibrous tissue and numerous irregular and
ACUTE LARYNGITIS. This may occur as a part of the
upper or lower respiratory tract infection. Atmospheric
pollutants like cigarette smoke, exhaust fumes, industrial
and domestic smoke etc predispose the larynx to acute The Eye, ENT and Neck
bacterial and viral infections. Streptococci and H. influenzae
cause acute epiglottitis which may be life-threatening. Acute
laryngitis may occur in some other illnesses like typhoid,
measles and influenza. Acute pseudomembranous
(diphtheric) laryngitis occurs due to infection with C.
diphtheriae.
CHRONIC LARYNGITIS. Chronic laryngitis may occur
from repeated attacks of acute inflammation, excessive
smoking, chronic alcoholism or vocal abuse. The surface is
granular due to swollen mucous glands. There may be
extensive squamous metaplasia due to heavy smoking,
chronic bronchitis and atmospheric pollution.
TUBERCULOUS LARYNGITIS. Tuberculous laryngitis
occurs secondary to pulmonary tuberculosis. Typical
caseating tubercles are present on the surface of the larynx.
ACUTE OEDEMA OF THE LARYNX. This hazardous
condition is an acute inflammatory condition, causing
swelling of the larynx that may lead to airway obstruction
and death by suffocation. Acute laryngeal oedema may occur Figure 18.15 Squamous cell papilloma. There is papillomatosis;
due to trauma, inhalation of irritants, drinking hot fluids or papillae are covered with well oriented and orderly layers of squamous
may be infective in origin. cells.
520 sarcoma (pseudosarcoma) at the other extreme of
prognosis.
Cervical lymph node metastasis of laryngeal carcinoma
are found in a good proportion of cases at the time of
diagnosis. Death from laryngeal cancer occurs due to local
extension of growth into vital structures like trachea and
carotid artery; other causes are bacterial infection, aspiration
pneumonia, debility and disseminated metastases.
NECK
NORMAL STRUCTURE
The neck is the region from where important structures like
oesophagus, trachea, carotid arteries, great veins and nerve
trunks pass down. Besides, the neck has structures such as
carotid body, sympathetic ganglia, larynx, thyroid,
parathyroids and lymph nodes. Only the tumours and cysts
Figure 18.16 Laryngeal nodule. The lesion has intact surface of the neck are considered here while the lesions pertaining
epithelium. The subepithelium has fibromyxoid appearance and contains to other anatomic structures are described elsewhere in the
proliferating blood vessels some of which are hyalinised. textbook.
dilated vascular channels. Sometimes, the subepithelial CYSTS OF NECK
basement membrane is thickened, resembling amyloid The cysts of neck may be medial (midline) or lateral
material (Fig. 18.16).
(Table 18.3).
LARYNGEAL CARCINOMA. Cancer of the larynx in 99%
of cases is squamous cell carcinoma. Rarely, adenocarcinoma Medial (Midline) Cervical Cysts
and sarcoma are encountered. Squamous carcinoma of the THYROGLOSSAL CYST. Thyroglossal cyst arises from the
SECTION III
larynx occurs in males beyond 4th decade of life. Important vestiges of thyroglossal duct that connects the foramen
etiologic factor is heavy smoking of cigarettes, cigar or pipe; caecum at the base of the tongue with the normally located
other factors include excessive alcohol consumption, thyroid gland. The cyst is located in the midline, generally
radiation and asbestos exposure. Carcinoma of the larynx is at the level of hyoid bone, and rarely at the base of the tongue.
conventionally classified into extrinsic that arises or extends
outside the larynx, and intrinsic that arises within the larynx. Microscopically, the cyst is lined by respiratory and/or
However, based on the anatomic location, laryngeal stratified squamous epithelium.
carcinoma is classified as under:
1. Glottic is the most common location, found in the region MIDLINE DERMOID CYST. Dermoid cyst located in the
of true vocal cords and anterior and posterior commissures. midline of the neck occurs due to sequestration of dermal
2. Supraglottic involving ventricles and arytenoids. cells along the lines of closure of embryonic clefts. The cyst
Systemic Pathology
3. Subglottic in the walls of subglottis. contains paste-like pultaceous material.
4. Marginal zone between the tip of epiglottis and ary- Microscopically, it is lined by epidermis and may contain
epiglottic folds. skin adnexal structures.
5. Laryngo-(hypo-) pharynx in the pyriform fossa, postcricoid
fossa and posterior pharyngeal wall. Lateral Cervical Cysts
Grossly, the glottic carcinoma is the most common form BRANCHIAL (LYMPHOEPITHELIAL) CYST. Branchial or
and appears as a small, pearly white, plaque-like lymphoepithelial cyst arises from incomplete closure of 2nd
thickening that may be ulcerated or fungated.
Microscopically, keratinising and non-keratinising TABLE 18.3: Cysts of the Neck.
squamous carcinomas of varying grades are found.
Generally, carcinoma of the supraglottic and subglottic I. MEDIAL (MIDLINE) CYSTS
regions tends to be more poorly-differentiated than the 1. Thyroglossal cyst
glottic tumour. Besides the keratinising and non- 2. Midline dermoid cyst
keratinising squamous carcinoma, 2 special varieties of II. LATERAL CERVICAL CYSTS
squamous carcinoma in the larynx are: verrucous carcinoma 1. Branchial (lymphoepithelial) cyst
(or Ackerman’s tumour) which is a variant of well- 2. Parathyroid cyst
differentiated squamous carcinoma, and spindle cell 3. Cervical thymic cyst
carcinoma which has elongated tumour cells resembling 4. Cystic hygroma
or 3rd branchial clefts. The cyst is generally located anterior bifurcation of the common carotid arteries. Carotid bodies 521
to the sternocleidomastoid muscle near the angle of the are normally part of the chemoreceptor system and the cells
mandible. The cyst is 1-3 cm in diameter and is filled with of this system are sensitive to changes in the pH and arterial
serous or mucoid material. oxygen tension and are also the storage site for catechola-
mines. Histologically similar tumours are found in other
Microscopically, the cyst is lined by stratified squamous parasympathetic ganglia represented by the vagus and
or respiratory epithelium, covering subepithelial glomus jugulare (jugulotympanic bodies, Chapter 27).
lymphoid tissue aggregates or follicles with germinal Carotid body paragangliomas, as they are currently called,
centres.
are rare tumours and occur between 3rd and 6th decades of
life with slight female preponderance. A few (5%) are bilateral
PARATHYROID CYST. Parathyroid cyst is a lateral cyst of and some show familial incidence.
the neck usually located deep to the sternocleidomastoid
muscle at the angle of the mandible. These may be Grossly, they are small, firm, dark tan, encapsulated
microscopic cysts or larger. They are generally thin-walled, nodules.
filled with clear watery fluid.
Microscopically, well-differentiated tumour cells form
Microscopically, parathyroid cyst is lined by flattened characteristic organoid or alveolar pattern, as is the case
cuboidal to low columnar epithelium and the cyst wall with all other neuroendocrine tumours. The tumour cells
may contain any type of parathyroid cells. contain dark neurosecretory granules containing
catecholamines.
CERVICAL THYMIC CYST. Cervical thymic cyst originates These tumours are mostly benign but recurrences are
from cystic degeneration of Hassall’s corpuscles. It is frequent; about 10% may metastasise widely.
generally located in the left lateral side of the neck.
TORTICOLLIS (FIBROMATOSIS COLLI, WRY NECK).
Microscopically, the cyst is lined by stratified squamous This is a deformity in which the head is bent to one side while
epithelium and the cyst wall may contain thymic the chin points to the other side. The deformity may occur as
structures. congenital torticollis or may be an acquired form. The acquired CHAPTER 18
form may occur secondary to fracture dislocation of the
CYSTIC HYGROMA. Cystic hygroma is a lateral swelling cervical spine, Pott’s disease of the cervical spine, scoliosis,
at the root of the neck, usually located behind the spasm of the muscles of neck, exposure to chill causing
sternocleidomastoid muscle. It may be present congenitally myositis, and contracture following burns or wound healing.
or may manifest in the first 2 years of life. It is usually The congenital or primary torticollis appears at birth or within
multilocular and may extend into the mediastinum and the first few weeks of life as a firm swelling in the lower
pectoral region. third of the sternocleidomastoid muscle. The etiology is
unknown but about half the cases are associated with breech
Microscopically, cystic hygroma is a diffuse lymphan- delivery.
gioma containing large cavernous spaces lined by
endothelium and containing lymph fluid (page 412). Grossly, the muscle is contracted, shortened and fibrous. The Eye, ENT and Neck
Microscopically, abundant dense fibrous tissue separates
TUMOURS the muscle fibres.
Tumours of the neck may be primary or metastatic in cervical MALIGNANT LYMPHOMAS. Various forms of non-
lymph nodes. Hodgkin’s lymphomas and Hodgkin’s disease occur in the
cervical lymph nodes which are described in Chapter 14.
Primary Tumours
Secondary Tumours
A few important examples of primary tumours in the neck
are carotid body tumour, torticollis and malignant Cervical lymph nodes are common site for metastases of a
lymphomas. large number of carcinomas. These include: squamous cell
carcinoma of the lips, mouth, tongue, larynx and oesophagus;
CAROTID BODY TUMOUR (CHEMODECTOMA, transitional cell carcinoma of the pharynx and nasopharynx;
CAROTID BODY PARAGANGLIOMA). Carotid body thoracic and abdominal cancers such as of the stomach, lungs,
tumour arises in the carotid bodies which are situated at the ovaries, uterus and testis.
❑
522
The Oral Cavity and
Chapter 19
Chapter 19
Salivary Glands
ORAL SOFT TISSUES iv) Bifid tongue is a rare condition occurring due to failure
of the two lateral halves of the tongue to fuse in the midline.
v) Tongue tie occurs when the lingual fraenum is quite
NORMAL STRUCTURE
short, or when the fraenum is attached near the tongue tip.
The oral cavity is the point of entry for digestive and vi) Hairy tongue is not a true developmental defect, but is
respiratory tracts. The mucous membrane of the mouth mentioned here because of its similarity with other
consists of squamous epithelium covering vascularised conditions discussed here. The filiform papillae are
connective tissue. The epithelium is keratinised over the hard hypertrophied and elongated. These ‘hairs’ (papillae) are
palate, lips and gingiva, while elsewhere it is non-keratinised. stained black, brown or yellowish-white by food, tobacco,
Mucous glands (minor salivary glands) are scattered oxidising agents or by oral flora.
throughout the oral mucosa. Sebaceous glands are present
in the region of the lips and the buccal mucosa only. MUCOCUTANEOUS LESIONS
Lymphoid tissue is present in the form of tonsils and
adenoids. Lesions of the oral mucosa occur in many diseases of the
The oral cavity is the site of numerous congenital and skin (Chapter 26) and they are similar in morphology. Some
acquired diseases. Besides, many systemic diseases have oral of these are listed as under:
manifestations. Some of the commonly occurring conditions LICHEN PLANUS. Characteristically, oral lichen planus
are discussed here. appears as interlacing network of whitening or keratosis on
the buccal mucosa but other oral tissues such as gingival,
SECTION III
DEVELOPMENTAL ANOMALIES tongue and palate may also be involved.
1. FACIAL CLEFTS. Cleft upper lip (harelip) and cleft palate, VESICULAR LESIONS. A number of vesicular or bullous
alone or in combination, are the commonest developmental diseases of the skin have oral lesions.
anomalies of the face. These occur from the failure of fusion i) Pemphigus vulgaris. Vesicular oral lesions appear
of facial processes.
invariably in all cases at some time in the course of
2. FORDYCE’S GRANULES. Fordyce’s granules are pemphigus vulgaris. In about half the cases oral lesions are
symmetric, small, light yellow macular spots on the lips and the initial manifestations.
buccal mucosa and represent collections of sebaceous glands. ii) Pemphigoid. Vesicles or bullae appear on oral mucosa
They remain undeveloped until puberty but occur quite as well as on conjunctiva in pemphigoid and are seen more
commonly in adults. often in older women.
Systemic Pathology
3. LEUKOEDEMA. This is an asymptomatic condition iii) Erythema multiforme. Subepithelial vesicles may occur
occurring in children and is characterised by symmetric, grey- on the skin as well as mucosae.
white areas on the buccal mucosa. Histologically, there is iv) Stevens-Johnson syndrome is a rather fatal and severe
pronounced intracellular oedema. There is no increased form of erythema multiforme involving oral and other
malignant potential compared to leukoplakia discussed mucous membranes occurring following ingestion of sulfa
below. drugs.
4. DEVELOPMENTAL DEFECTS OF THE TONGUE. v) Epidermolysis bullosa is a hereditary condition having
These are as under: subepidermal bullae on the skin as well as has oral lesions.
i) Macroglossia is the enlargement of the tongue, usually
due to lymphangioma or haemangioma, and sometimes due INFLAMMATORY DISEASES
to amyloid tumour. STOMATITIS. Inflammation of the mucous membrane of
ii) Microglossia and aglossia are rare congenital anomalies the mouth is called stomatitis. It can occur in the course of
representing small-sized and absence of tongue respectively. several different diseases.
iii) Fissured tongue (scrotal, furrowed or grooved tongue) i) Aphthous ulcers (Canker sores) is the commonest form
is a genetically-determined condition characterised by of oral ulceration. The etiology is unknown but may be
numerous small furrows or grooves on the dorsum of the precipitated by emotional factors, stress, allergy, hormonal
tongue. It is often associated with mild glossitis. imbalance, nutritional deficiencies, gastrointestinal
disturbances, trauma etc. The condition is characterised by TABLE 19.1: Oral Manifestations of AIDS. 523
painful oral ulcers, 1 cm or more in size. Recurrent aphthae
may form a part of Behcet’s syndrome and inflammatory A. OPPORTUNISTIC INFECTIONS
bowel disease. Fungal : Candidiasis (oral thrush)
Histoplasmosis
ii) Herpetic stomatitis is an acute disease occurring in Cryptococcosis
infants and young children. It is the most common Bacterial : Dental caries and periodontitis
manifestation of primary infection with herpes simplex virus. Mycobacterial infections
The lesions are in the form of vesicles around the lips. Similar Viral : Herpetic stomatitis
lesions may appear on the genital skin. Recurrent attacks Cytomegalovirus
Human papillomavirus
occur due to stress, emotional upsets and upper respiratory
infections. B. TUMOURS Kaposi’s sarcoma
iii) Necrotising stomatitis (Noma or Cancrum oris) occurs Squamous cell carcinoma
more commonly in poorly-nourished children like in Non-Hodgkin’s lymphoma
kwashiorkor; infectious diseases such as measles, immuno- C. OTHERS
deficiencies and emotional stress. The lesions are Hairy leukoplakia
characterised by necrosis of the marginal gingiva and may Recurrent aphthous ulcers
extend on to oral mucosa, causing cellulitis of the tissue of
the cheek. The condition may progress to gangrene of the PIGMENTARY LESIONS
cheek.
Oral and labial melanotic pigmentation may be observed in
iv) Mycotic infections commonly involving the oral mucosa certain systemic and metabolic disorders such as Addison’s
are actinomycosis and candidiasis. disease, Albright syndrome, Peutz-Jeghers syndrome and
Cervicofacial actinomycosis is the commonest form of the haemochromatosis. All types of pigmented naevi as well as
disease developing at the angle of the mandible (Chapter 6). malignant melanoma can occur in oral cavity. Exogenous
Candidiasis (moniliasis or thrush) is caused by Candida pigmentation such as due to deposition of lead sulfide can
albicans which is a commensal in the mouth. It appears as an also occur. CHAPTER 19
opportunistic infection in immunocompromised host. There
are erythematous lesions on the palate and angular cheilitis. TUMOURS AND TUMOUR-LIKE LESIONS
GLOSSITIS. Acute glossitis characterised by swollen Benign and malignant tumours as also a number of tumour-
papillae occurs in eruptions of measles and scarlet fever. In like lesions and premalignant lesions are encountered in the
chronic glossitis, the tongue is raw and red without swollen oral soft tissues. A list of such lesions is presented in
papillae and is seen in malnutrition such as in pellagra, Table 19.2.
ariboflavinosis and niacin deficiency. In iron deficiency
anaemia, pernicious anaemia and sprue, there is chronic TABLE 19.2: Classification of Tumours and Tumour-like
atrophic glossitis characterised by atrophied papillae and Lesions of the Oral Soft Tissues.
smooth raw tongue. A. TUMOUR-LIKE LESIONS
SYPHILITIC LESIONS. Oral lesions may occur in primary, 1. Fibrous growths
secondary, tertiary and congenital syphilis (Chapter 6). (Fibroepithelial polyps, fibrous epulis, denture The Oral Cavity and Salivary Glands
i) Extragenital chancre of primary syphilis occurs most 2. hyperplasia)
Pyogenic granuloma
commonly on the lips. 3. Mucocele
ii) Secondary syphilis shows maculopapular eruptions and 4. Ranula
mucous patches in the mouth. 5. Dermoid cyst
iii) In the tertiary syphilis, gummas or diffuse fibrosis may be B. BENIGN TUMOURS
seen on the hard palate and tongue. 1. Squamous papilloma
iv) Oral lesions of the congenital syphilis are fissures at the 2. Haemangioma
angles of mouth and characteristic peg-shaped notched 3. Lymphangioma
Hutchinson’s incisors. 4. Fibroma
5. Fibromatosis gingivae
TUBERCULOUS LESIONS. Involvement of the mouth in 6. Tumours of minor salivary glands
tuberculosis is rare. The lesions are in the form of ulcers or (e.g. Pleomorphic adenoma)
elevated nodules. 7. Granular cell myoblastoma
8. Other rare benign tumours
HIV INFECTION. HIV infection of low grade as well as full- C. PREMALIGNANT LESIONS
blown acquired immunodeficiency syndrome (AIDS) are
associated with oral manifestations such as opportunistic 1. Hyperkeratotic leukoplakia
2.
Dysplastic leukoplakia
infections, malignancy, hairy leukoplakia and others; these
are listed in Table 19.1. About half the cases of Kaposi’s D. MALIGNANT TUMOURS
sarcoma have intraoral lesions as part of systemic 1. Squamous cell (Epidermoid) carcinoma
involvement (Chapter 6). 2. Other malignant tumours
524 is lined by stratified squamous epithelium. The cyst wall
contains sebaceous glands, sweat glands, hair follicles and
other mature tissues.
B. BENIGN TUMOURS
Different parts of the mouth have a variety of mesodermal
tissues and keratinising and non-keratinising epithelium.
Therefore, majority of neoplasms arising from the oral tissues
are just like their counterparts in other parts of the body.
Some of the common benign tumours of the mouth are as
under:
SQUAMOUS PAPILLOMA. Papilloma can occur anywhere
in the mouth and has the usual papillary or finger-like
projections.
Microscopically, each papilla is composed of vascularised
connective tissue covered by squamous epithelium.
HAEMANGIOMA. Haemangioma can occur anywhere in
the mouth; when it occurs on the tongue it may cause
macroglossia. It is most commonly capillary type, although
cavernous and mixed types may also occur.
Figure 19.1 Fibrous epulis in gingival.
LYMPHANGIOMA. Lymphangioma may develop most
A. TUMOUR-LIKE LESIONS commonly on the tongue producing macroglossia; on the lips
producing macrocheilia, and on the cheek. Cystic hygroma
A number of proliferative lesions arising from the oral tissues is a special variety of lymphangioma occurring in children
are tumour-like masses which clinically may resemble on the lateral side of neck.
neoplasms. Some of these are as under:
FIBROUS GROWTHS. Fibrous growths of the oral soft Microscopically, lymphangioma is characterised by large
SECTION III
tissues are very common. These are not true tumours (unlike lymphatic spaces lined by endothelium and containing
intraoral fibroma and papilloma), but are instead lymph (Chapter 15).
inflammatory or irritative in origin. A few common varieties
are as under: FIBROMA. Although most common benign oral mucous
i) Fibroepithelial polyps occur due to irritation or chronic membrane mass is fibroma appearing as a discrete superficial
trauma. These are composed of reparative fibrous tissue, pedunculated mass, it appears to be nonneoplastic in nature.
covered by a thin layer of stratified squamous epithelium. It probably arises as a response physical trauma (discussed
ii) Fibrous epulis is a lesion occurring on the gingiva and is above).
localised hyperplasia of the connective tissue following
trauma or inflammation in the area (Fig. 19.1). Giant cell epulis
Systemic Pathology
is a variant seen more commonly in females as reactive
change to trauma; the lesion shows numerous osteoclast-like
giant cells and vascular stroma.
iii) Denture hyperplasia occurs in edentulous or partly
edentulous patients. The lesion is an inflammatory
hyperplasia in response to local irritation by ill-fitting denture
or an elongated tooth.
PYOGENIC GRANULOMA. This is an elevated, bright red
swelling of variable size occurring on the lips, tongue, buccal
mucosa and gingiva. It is a vasoproliferative inflammatory
lesion. Pregnancy tumour is a variant of pyogenic granuloma.
MUCOCELE. Also called mucous cyst or retention cyst, it is
a cystic dilatation of the mucous glands of the oral mucosa.
The cyst often ruptures on distension and incites inflam-
matory reaction due to mucous extravasation (Fig. 19.2).
RANULA. It is a large mucocele located on the floor of the
mouth. The cyst is lined by true epithelial lining.
DERMOID CYST. This tumour-like mass in the floor of the Figure 19.2 Mucous retention cyst (mucocele). There is inflamma-
mouth represents a developmental malformation. The cyst tory reaction around extravasated mucus.
Microscopically, fibroma is composed of collagenic INCIDENCE. It occurs more frequently in males than 525
fibrous connective tissue covered by stratified squamous females. The lesions may be of variable size and appearance.
epithelium. The sites of predilection, in descending order of frequency,
are: cheek mucosa, angles of mouth, alveolar mucosa, tongue,
FIBROMATOSIS GINGIVAE. This is a fibrous overgrowth lip, hard and soft palate, and floor of the mouth. In about 4-
of unknown etiology involving the entire gingiva. Sometimes 6% cases of leukoplakia, carcinomatous change is reported.
the fibrous overgrowth is so much that the teeth are covered However, it is difficult to decide which white lesions may
by fibrous tissue. undergo malignant transformation, but speckled or nodular
TUMOURS OF MINOR SALIVARY GLANDS. Minor form is more likely to progress to malignancy. Therefore, it
salivary glands present in the oral cavity may sometimes be is desirable that all oral white patches be biopsied to exclude
the site of origin of salivary tumours similar to those seen in malignancy.
the major salivary glands (page 533). Pleomorphic adenoma ETIOLOGY. The etiological factors are similar to those
is a common example. suggested for carcinoma of the oral mucosa (discussed
GRANULAR CELL TUMOUR. Earlier called as granular cell below). It has the strongest association with the use of tobacco in
myoblastoma, it is benign tumour which now by electron various forms, e.g. in heavy smokers (especially in pipe and
microscopic studies is known to be mesenchymal in origin cigar smokers) and improves when smoking is discontinued,
than odontogenic. The most common location is the tongue and in those who chew tobacco as in paan, paan masaala,
but may occur in any other location on the oral cavity. It zarda, gutka etc. The condition is also known by other names
occurs exclusively in females. A similar lesion seen in infants such as smokers keratosis and stomatitis nicotina. Other
is termed as congenital epulis. etiological factors implicated are chronic friction such as with
ill-fitting dentures or jagged teeth, and local irritants like
Microscopically, the tumour is composed of large excessive consumption of alcohol and very hot and spicy
polyhedral cells with granular, acidophilic cytoplasm. The foods and beverages. A special variety of leukoplakia called
covering epithelium usually shows pronounced ‘hairy leukoplakia’ has been described in patients of AIDS and
pseudoepitheliomatous hyperplasia. has hairy or corrugated surface but is not related to CHAPTER 19
development of oral cancer.
OTHER RARE BENIGN TUMOURS. Some other rare
benign tumours which can occur in the oral soft tissues are:
neurilemmoma, neurofibroma, lipoma, giant cell granuloma, MORPHOLOGIC FEATURES. Grossly, the lesions of
rhabdomyoma, leiomyoma, solitary plasmacytoma, osteoma, leukoplakia may appear white, whitish-yellow, or red-
chondroma, naevi and vascular oral lesions seen in hereditary velvety of more than 5 mm diameter and variable in
haemorrhagic telangiectasia (Osler-Rendu-Weber syndrome) appearance. They are usually circumscribed, slightly
and encephalofacial angiomatosis (Sturge-Weber syndrome). elevated, smooth or wrinkled, speckled or nodular.
Histologically, leukoplakia is of 2 types:
C. ORAL LEUKOPLAKIA (WHITE LESIONS)
1. Hyperkeratotic type. This is characterised by an
DEFINITION. Leukoplakia (white plaque) may be clinically orderly and regular hyperplasia of squamous epithelium
defined as a white patch or plaque on the oral mucosa, with hyperkeratosis on the surface (Fig. 19.3, A).
exceeding 5 mm in diameter, which cannot be rubbed off 2. Dysplastic type. When the changes such as irregular The Oral Cavity and Salivary Glands
nor can be classified into any other diagnosable disease. A stratification of the epithelium, focal areas of increased
number of other lesions are characterised by the formation and abnormal mitotic figures, hyperchromatism,
of white patches listed in Table 19.3. However, from the pleomorphism, loss of polarity and individual cell
pathologist’s point of view, the term ‘leukoplakia’ is reserved keratinisation are present, the lesion is considered as
for epithelial thickening which may range from completely epithelial dysplasia. The subepithelial tissues usually
benign to atypical and to premalignant cellular changes. show an inflammatory infiltrate composed of lymphocytes
and plasma cells. The extent and degree of the epithelial
TABLE 19.3: Causes of White Lesions in the Oral Mucosa.
changes indicate the degree of severity of the epithelial
A. BENIGN dysplasia. Usually, mild dysplasia may revert back to
1. Fordyce’s granules normal if the offending etiologic factor is removed,
2. Hairy tongue
3. Leukoedema whereas severe dysplasia indicates that the case may
4. Lupus erythematosus progress to carcinoma. Erythroplasia is a form of dysplastic
5. White sponge naevus leukoplakia in which the epithelial atypia is more marked
B. PREMALIGNANT and thus has higher risk of developing malignancy. If the
1. Leukoplakia epithelial dysplasia is extensive so as to involve the entire
2. Oral lichen planus thickness of the epithelium, the lesion is called carcinoma
in situ which may progress to invasive carcinoma
C. MALIGNANT
Squamous cell carcinoma (Fig. 19.3, B).
526
Figure 19.3 Leukoplakia oral mucosa. A, Hyperkeratosis type. There is keratosis and orderly arrangement of increased number of layers of
stratified mucosa. B, Dysplastic type. The number of layers is increased and the individual cells in layers show features of cytologic atypia and
mitosis but there is no invasion across the basement membrane.
D. MALIGNANT TUMOURS It can occur anywhere in the mouth but certain sites are more
commonly involved. These sites, in descending order of
Squamous Cell (Epidermoid) Carcinoma
SECTION III
frequency, are: the lips (more commonly lower), tongue,
Oral cancer is a disease with very poor prognosis because it anterior floor of mouth, buccal mucosa in the region of
is not recognised and treated when small and early. alveolar lingual sulcus, and palate (Fig. 19.4).
INCIDENCE. Squamous cell (epidermoid) carcinoma ETIOLOGY. As with other forms of cancer, the etiology of
comprises 90% of all oral malignant tumours and 5% of all squamous cell carcinoma is unknown. But a number of
human malignancies. The peak incidence in the UK and the etiological factors have been implicated:
USA is from 55 to 75 years of age, whereas in India it is from Strong association:
40 to 45 years of age. Oral cancer is a very frequent i) Tobacco smoking and tobacco chewing causing
malignancy in India, Sri Lanka and some Eastern countries, leukoplakia is the most important factor as discussed above.
probably related to habits of betel-nut chewing and reversed ii) Chronic alcohol consumption.
smoking (Chapter 8). There is a definite male preponderance. iii) Human papilloma virus infection, particularly HPV 16,
Systemic Pathology
18 and 33 types.
Weak association:
i) Chronic irritation from ill-fitting denture or jagged teeth.
ii) Submucosal fibrosis as seen in Indians consuming excess
of chillies.
iii) Poor orodental hygiene.
iv) Nutritional deficiencies.
v) Exposure to sunlight (in relation to lip cancer).
vi) Exposure to radiation.
vii) Plummer-Vinson syndrome, characterised by atrophy of
the upper alimentary tract.
The most common molecular alterations in oncogenes
seen in squamous cell carcinoma of the oral cavity are in p16,
p53, cyclin D, p63, PTEN, and EGFR.
MORPHOLOGIC FEATURES. Grossly, squamous cell
carcinoma of oral cavity may have the following types
Figure 19.4 Frequency of occurrence of squamous cell carcinomas (Fig. 19.5):
in the oral cavity.
527
Figure 19.5 Squamous cell (Epidermoid) carcinoma of oral cavity, patterns of gross appearance.
i) Ulcerative type—is the most frequent type and is of very well-differentiated squamous epithelium with
characterised by indurated ulcer and firm everted or rolled minimal atypia and hence has very good prognosis.
edges.
ii) Papillary or verrucous type—is soft and wart-like OTHER MALIGNANT TUMOURS
growth. Other less common malignant neoplasms which may be
iii) Nodular type—appears as a firm, slow growing encountered in the oral cavity are: malignant melanoma,
submucosal nodule. lymphoepithelial carcinoma, malignant lymphoma,
iv) Scirrhous type—is characterised by infiltration into malignant tumours of minor salivary glands, and various
deeper structures. sarcomas like rhabdomyosarcoma, liposarcoma, alveolar soft
All these types may appear on a background of part sarcoma, Kaposi’s sarcoma and fibrosarcoma. Metastatic
leukoplakia or erythroplasia of the oral mucosa. Enlarged tumours can also occur in the soft tissues of the mouth.
cervical lymph nodes may sometimes be present.
Histologically, squamous cell carcinoma ranges from TEETH AND PERIODONTAL TISSUES
well-differentiated keratinising carcinoma to highly- Although care of the teeth belongs to the field of dental CHAPTER 19
undifferentiated neoplasm (Chapter 26). Changes of profession, the fully educated medical doctor should be
epithelial dysplasia are often present in the surrounding familiar with certain principal diseases of teeth and
areas of the lesion. Carcinoma of the lip and intraoral periodontal tissues, especially about dental caries, periapical
squamous carcinoma are usually always well- abscess and periodontitis, and common cysts and
differentiated (Fig. 19.6).
odontogenic tumours of the jaw. But first, a brief account of
normal structure of these tissues is presented.
Carcinoma of the lip has a more favourable prognosis
due to visible and easily accessible location and less frequent NORMAL STRUCTURE
metastasis to the regional lymph nodes. However, intraoral
squamous carcinomas have poor prognosis because they are The teeth are normally composed of 3 calcified tissues,
detected late and metastasis to regional lymph nodes occur namely: enamel, dentin and cementum; and the pulp which is
early, especially in the case of carcinoma of tongue and soft composed of connective tissue. The teeth are peculiar than
palate. Verrucous carcinoma, on the other hand, is composed other calcified tissues of the body by being surrounded by The Oral Cavity and Salivary Glands
Figure 19.6 Oral mucosa showing epithelial dysplasia progressing to invasive squamous cell carcinoma. There is keratosis, irregular stratification,
cellular pleomorphism, increased and abnormal mitotic figures and individual cell keratinisation, while a few areas show superficial invasive islands
of malignant cells in the subepithelial soft tissues.
528 Cementum is the portion of tooth which covers the dentin at
the root of tooth and is the site where periodontal ligament
is attached. Cementum is similar to bone in morphology and
composition.
Dental pulp is inner to dentine and occupies the pulp cavity
and root canal. It consists of connective tissue, blood vessels
and nerves.
Nests of odontogenic epithelium are normally present in
the jaw and may develop into cysts and tumours.
DENTAL CARIES
Dental caries is the most common disease of dental tissues,
causing destruction of the calcified tissues of the teeth.
ETIOPATHOGENESIS. Dental caries is essentially a
disease of modern society, associated with diet containing
high proportion of refined carbohydrates. It has been known
for almost 100 years that mixture of sugar or bread with
saliva in the presence of acidogenic bacteria of the mouth,
especially streptococci, produces organic acids which can
decalcify enamel and dentin. Enamel is largely composed
of inorganic material which virtually disintegrates. Dentin
contains organic material also which is left after
decalcification. Bacteria present in the oral cavity cause
proteolysis of the remaining organic material of dentin,
completing the process of destruction. Diets rich in
Figure 19.7 The normal structure of tooth in longitudinal section carbohydrates do not require much chewing and thus the
embedded in the jaw.
soft and sticky food gets clung to the teeth rather than being
cleared away, particularly in the areas of occlusal pits and
the portion of oral mucosa called the gingiva or gum, and fissures. ‘Bacterial plaques’ are formed in such stagnation
SECTION III
that they are part of a highly specialised odontogenic areas. If these plaques are not removed by brushing or by
apparatus; other parts of this apparatus being the mandible vigorous chewing of fibrous foods, the process of tooth
and maxilla. decay begins. There is evidence that consumption of water
Embryologically, odontogenic development takes place containing one part per million (ppm) fluoride is sufficient
from primitive structure, the dental lamina or primitive oral to reduce the rate of tooth decay in children.
cavity, as follows: MORPHOLOGIC FEATURES. Caries occurs chiefly in the
Inner epithelial layer of the dental lamina is ectoderm-
derived columnar to cuboidal oral epithelium called areas of pits and fissures, mainly of the molars and
premolars, where food retention occurs, and in the cervical
ameloblasts which secrete enamel matrix, also called enamel part of the tooth.
organ. Grossly, the earliest change is the appearance of a small,
Mesoderm-derived connective tissue gives rise to
Systemic Pathology
structures in the dental papilla (i.e. dental pulp or core of chalky-white spot on the enamel which subsequently
enlarges and often becomes yellow or brown and breaks
loose connective tissue, blood vessels and nerves). down to form carious cavity. Eventually, the cavity
Outer margin of the dental papilla differentiates into becomes larger due to fractures of enamel. Once the lesion
odontoblasts, which continue with ameloblastsic epithelium;
odontoblasts secrete dentin.
The normal structure of tooth in an adult is as follows
(Fig. 19.7):
Enamel is the outer covering of teeth composed almost
entirely of inorganic material (as in bone) which can be
demonstrated in ground sections only as it is lost in
decalcified section.
Dentin lies under the enamel and comprises most of the tooth
substance. It is composed of organic material in the form of
collagen fibrils as well as inorganic material in the form of
calcium phosphates as in bone. Dentin is composed of
odontoblasts or dentin cells which are counterparts of
osteocytes in bone but differ from the latter in having
odontoblast processes. Dentin in the crown of tooth is covered Figure 19.8 Dental caries. There is complete destruction of enamel,
with thicker layer of enamel. deposition of secondary dentine and evidence of pulpitis.
reaches enamel-dentin junction, destruction of dentine periodontal pocket from which purulent discharge can be 529
also begins. expressed by digital pressure.
Microscopically, inflammation (pulpitis) and necrosis of Microscopically, chronic marginal gingivitis is charac-
pulp take place. There is evidence of reaction of the tooth terised by heavy chronic inflammatory cell infiltrate,
to the carious process in the form of secondary dentin, which destruction of collagen, and epithelial hyperplasia so as
is a layer of odontoblasts laid down under the original to line the pocket. Untreated chronic marginal gingivitis
dentine (Fig. 19.8). slowly progresses to chronic periodontitis or pyorrhoea in
which there is inflammatory destruction of deeper tissues.
SEQUELAE OF CARIES. Carious destruction of dental hard At this stage, progressive resorption of alveolar bone
tissues frequently produces pulpitis and other inflammatory occurs and the tooth ultimately gets detached.
lesions like apical granuloma and apical abscess. Less
common causes of these lesions are fracture of tooth and EPITHELIAL CYSTS OF THE JAW
accidental exposure of pulp by the dentist. The epithelium-lined cysts of dental tissue can have
1. Pulpitis. Pulpitis may be acute or chronic. inflammatory or developmental origin. A classification of
Acute pulpitis is accompanied by severe pain which may such cysts is given in Table 19.4.
be continuous, throbbing or dull, and is accentuated by heat
or cold. It is often accompanied by mild fever and A. INFLAMMATORY CYSTS
leucocytosis. Radicular Cyst
Chronic pulpitis occurs when pulp is exposed widely. It is
often not associated with pain. Chronically inflamed pulp Radicular cyst, also called as apical, periodontal or simply
dental cyst, is the most common cyst originating from the
tissue may protrude through the cavity forming polyp of the dental tissues. It arises consequent to inflammation following
pulp. It may be partly covered by implanted squamous destruction of dental pulp such as in dental caries, pulpitis,
epithelium.
and apical granuloma. The epithelial cells of Mallasez, which
2. Apical granuloma. Pulpitis may lead to spread of are nests of odontogenic epithelium embedded in the CHAPTER 19
infection through the apical foramen into the tissues periodontium, proliferate within apical granuloma under the
surrounding the root of the tooth. influence of inflammation, leading to the formation of an
epithelium-lined cystic cavity. Most often, radicular cyst is
Histologically, there is chronic inflammatory reaction observed at the apex of an erupted tooth and sometimes
with formation of granulation tissue and inclusion of nests contains thick pultaceous material.
or strands of squamous epithelium derived from remnants
of odontogenic epithelium normally present in the Histologically, the radicular cyst is lined by nonkera-
periodontal membrane. An apical granuloma may tinised squamous epithelium. Epithelial rete processes
develop into a dental (radicular) cyst as discussed below. may penetrate the underlying connective tissues.
Radicular cyst of the maxilla may be lined by respiratory
3. Apical abscess. An apical granuloma or acute pulpitis epithelium. The cyst wall is fibrous and contains chronic
may develop into apical abscess. Acute abscess is very inflammatory cells (lymphocytes, plasma cells with
painful, while pus in chronic abscess may escape through Russell bodies and macrophages) hyaline bodies and
root canal and cause further complications like osteomyelitis, deposits of cholesterol crystals which may be associated The Oral Cavity and Salivary Glands
cellulitis, cerebral abscess, meningitis and cavernous sinus with foreign body giant cells (Fig. 19.9).
thrombosis.
PERIODONTAL DISEASE
TABLE 19.4: Classification of Epithelial Cysts of Jaw.
Chronic inflammation and degeneration of the supporting A. INFLAMMATORY
tissues of teeth resulting in teeth loss is a common condition. Radicular (apical, periodontal, dental) cyst
Besides inflammation, other diseases associated with gingi-
val swelling are leukaemia, scurvy, fibrous hyperplasia and B. DEVELOPMENTAL
epulis. 1. Odontogenic cysts
(i) Dentigerous (follicular) cyst
The inflammatory periodontal disease affects adults more (ii) Eruption cyst
commonly. Pregnancy, puberty and use of drugs like dilantin (iii) Gingival cyst
are associated with periodontal disease more often. The (iv) Primordial cyst (odontogenic keratocyst)
disease begins as chronic marginal gingivitis, secondary to 2. Non-odontogenic and fissural cysts
bacterial plaques around the teeth such as due to calculus (i) Nasopalatine duct (Incisive canal, Median anterior
(tartar) on the tooth surface, impacted food, uncontrolled maxillary) cyst
diabetes, tooth-decay and ill-fitting dental appliances. The (ii) Nasolabial (nasoalveolar) cyst
gingival sulcus acts as convenient site for lodgement of food (iii) Globulomaxillary cyst
debris and bacterial plaque leading to formation of (iv) Dermoid cyst
530
Figure 19.9 Dental (Radicular) cyst. The cyst wall is composed of fibrous
tissue and is lined by non-keratinised squamous epithelium. The cyst wall is
densely infiltrated by chronic inflammatory cells, chiefly lymphocytes, plasma
cells and macrophages.
B. DEVELOPMENTAL CYSTS Non-odontogenic and Fissural Cysts
Odontogenic Cysts NASOPALATINE DUCT (INCISIVE CANAL, MEDIAN,
DENTIGEROUS (FOLLICULAR) CYST. Dentigerous cyst ANTERIOR MAXILLARY) CYST. This is the most common
arises from enamel of an unerupted tooth. The mandibular non-odontogenic (fissural) cyst and arises from the epithelial
SECTION III
third molars and the maxillary canines are most often remnants of the nasopalatine duct.
involved. Dentigerous cysts are less common than radicular Histologically, the cyst is lined by stratified squamous
cysts and occur more commonly in children and young epithelium, respiratory epithelium, or both.
individuals. These cysts are more significant because of
reported occurrence of ameloblastoma and carcinoma in NASOLABIAL (NASOALVEOLAR) CYST. This cyst is
them. situated in the soft tissues at the junction of median nasal,
lateral nasal and maxillary processes, at the ala of the nose,
Histologically, dentigerous cyst is composed of a thin and sometimes extending into the nostril.
fibrous tissue wall lined by stratified squamous
epithelium. Thus, the cyst may resemble radicular cyst, Histologically, the cyst is lined by squamous or
except that chronic inflammatory changes so characteristic respiratory epithelium, or both.
of radicular cyst, are usually absent in dentigerous cyst
Systemic Pathology
(Fig. 19.10).
ERUPTION CYST. This is a cyst lying over the crown of an
unerupted tooth and is lined by stratified squamous
epithelium. It is thus a form of dentigerous cyst.
GINGIVAL CYST. It arises from the epithelial rests in the
gingiva and is lined by keratinising squamous epithelium.
PRIMORDIAL CYST (ODONTOGENIC KERATOCYST).
Primordial cyst, like dentigerous cyst, also arises from tooth-
forming epithelium. The common location is mandibular
third molar.
Histologically, the cyst wall is thin and is lined by regular
layer of keratinising stratified squamous epithelium.
Inflammatory changes are normally absent. Primordial
cysts have a marked tendency to recur (50%). Multiple Figure 19.10 Dentigerous (Follicular) cyst. The cyst is composed
primordial cysts occur in association with naevoid basal of thin fibrous tissue wall and is lined by stratified squamous epithelium.
cell carcinoma syndrome. A partly formed unerupted tooth is also seen in the wall. Inflammatory
changes are conspicuously absent.
GLOBULOMAXILLARY CYST. This is an intraosseous cyst TABLE 19.5: Classification of Odontogenic Tumours. 531
and is rare.
A. BENIGN
DERMOID CYST. The dermoid cyst is common in the region a) Epithelial origin
of head or neck, especially in the floor of the mouth. The cyst 1. Ameloblastoma
arises from remains in the midline during closure of 2. Adenomatoid odontogenic tumour
mandibular and branchial arches. (Adenoameloblastoma)
3. Calcifying epithelial odontogenic tumour
ODONTOGENIC TUMOURS b) Mesenchymal origin
1. Odontogenic myxoma
Odontogenic tumours are a group of uncommon lesions of 2. Odontogenic fibroma
the jaw derived from the odontogenic apparatus. These 3. Cementoma
tumours are usually benign but some have malignant c) Mixed epithelial-mesenchymal origin
counterparts. An abbreviated WHO classification is 1. Ameloblastic fibroma
presented in Table 19.5. 2. Ameloblastic fibro-odontoma
3.
Complex odontomas
A. BENIGN ODONTOGENIC TUMOURS B. MALIGNANT
a) Epithelial origin
Ameloblastoma 1. Malignant ameloblastoma
2. Ameloblastic carcinoma
Ameloblastoma is the most common benign but locally b) Mesenchymal origin
invasive epithelial odontogenic tumour. It is most frequent Ameloblastic fibrosarcoma
in the 3rd to 5th decades of life. Preferential sites are the
mandible in the molar-ramus area and the maxilla. The
tumour originates from dental epithelium of the enamel itself i) Follicular pattern is the most common. The tumour
or its epithelial residues. Sometimes, the tumour may arise consists of follicles of variable size and shape and
from the epithelial lining of a dentigerous cyst or from basal separated from each other by fibrous tissue. The structure
layer of oral mucosa. Radiologically, typical picture is of a of follicles is similar to that of enamel organ consisting of CHAPTER 19
multilocular destruction of the bone. Rare instances of an central area of stellate cells resembling stellate reticulum,
extraosseous example, presence of an embedded tooth, or and peripheral layer of cuboidal or columnar cells
unilocular ameloblastoma can occur. Tumour with histologic resembling epithelium. The central stellate areas may
resemblance to ameloblastoma can occur occasionally in the show cystic changes (Fig. 19.11).
long bone, like adamantinoma of the tibia (Chapter 28). ii) Plexiform pattern is the next common pattern after folli-
cular pattern. The tumour epithelium is seen to form
Grossly, the tumour is greyish-white, usually solid, irregular plexiform masses or network of strands. The
sometimes cystic, replacing and expanding the affected stroma is usually scanty. Microcyst formation can occur
bone. in the stroma.
Histologically, ameloblastoma can show different iii) Acanthomatous pattern is squamous metaplasia within
patterns as follows:
the islands of tumour cells. The Oral Cavity and Salivary Glands
Figure 19.11 Ameloblastoma, follicular and plexiform patterns. Epithelial follicles are composed of central area of stellate cells and peripheral
layer of cuboidal or columnar cells. Plexiform areas show irregular plexiform masses and network of strands of epithelial cells. A few areas show
central cystic change.
532 Odontomas
iv) Basal cell pattern of ameloblastoma is similar to basal
cell carcinoma of the skin. Odontomas are hamartomas that contain both epithelial and
v) Granular cell pattern is characterised by appearance of mesodermal dental tissue components. There are 3 subtypes:
acidophilic granularity in the cytoplasm of tumour cells. i) Complex odontoma is always benign and consists of
Combination of more than one morphologic pattern enamel, dentin and cementum which are not differentiated,
may also be seen. so that the structure of actual tooth is not identifiable.
Tumour cells in ameloblastoma exhibit positive
immunostaining for cytokeratin and laminin as are seen ii) Compound odontoma is also benign and is comprised
in developing tooth. of differentiated dental tissue elements forming a number of
denticles in fibrous tissue.
Odontogenic Adenomatoid Tumour iii) Ameloblastic fibro-odontoma is a lesion that resembles
(Adeno-ameloblastoma) ameloblastic fibroma with odontoma formation.
This is a benign tumour seen more often in females in their Cementomas
2nd decade of life. The tumour is commonly associated with
an unerupted tooth and thus closely resembles dentigerous Cementomas are a variety of benign lesions which are charac-
cyst radiologically. Unlike ameloblastoma, adenomatoid terised by the presence of cementum or cementum-like tissue.
odontogenic tumour is not invasive nor does it recur after Five types of cementomas are described:
enucleation. i) Benign cementoblastoma (true cementoma) is a solitary
lesion of jaw, characterised by features comparable to those
Histologically, the lesion has extensive cyst formations. of osteoid osteoma and osteoblastoma.
The wall of cyst contains scanty fibrous connective tissue
in which are present characteristic tubule-like structures ii) Cementifying fibroma consists of cellular fibrous tissue
composed of epithelial cells and hence the name containing calcified masses of cementum-like tissue.
‘adenomatoid’ (gland-like). iii) Periapical cemental dysplasia (Periapical fibrous
dysplasia) is most common and resembles cementifying
fibroma except that it contains more fibrous tissue as well as
Calcifying Epithelial Odontogenic Tumour
cementum-like tissue.
This is a rare lesion which is locally invasive and recurrent iv) Multiple apical cementomas are found on the apical
SECTION III
like ameloblastoma. It is seen commonly in 4th and 5th region of teeth and detected incidentally in postmenopausal
decades and occurs more commonly in the region of women.
mandible.
v) Gigantiform cementoma is a large lobulated mass of
Histologically, the tumour consists of closely packed cementum-like tissue. Sometimes, there are multiple such
polyhedral epithelial cells having features of nuclear masses in the jaw.
pleomorphism, giant nuclei and rare mitotic figures. The
stroma is often scanty and appears homogeneous and B. MALIGNANT ODONTOGENIC TUMOURS
hyalinised in which small calcified deposits are seen which
are a striking feature of this tumour. Malignant odontogenic tumours are rare.
Systemic Pathology
Odontogenic Myxoma (Myxofibroma) Odontogenic Carcinoma
Odontogenic myxoma is a locally invasive and recurring i) Malignant ameloblastoma is the term used for the
tumour. uncommon metastasising ameloblastoma.
ii) Ameloblastic carcinoma is the term employed for the
Microscopically, it is characterised by abundant mucoid ameloblastic tumour having cytologic features of malignancy
stroma and loose stellate cells in which are seen a few in the primary tumour.
strands of odontogenic epithelium.
iii) Primary intraosseous carcinoma may develop within the jaw
from the rests of odontogenic epithelium.
Ameloblastic Fibroma
iv) Rarely, carcinomas may arise from the odontogenic
This is a benign tumour consisting of epithelial and connec- epithelium lining the odontogenic cysts.
tive tissues derived from odontogenic apparatus. It resembles
ameloblastoma but can be distinguished from it because
ameloblastic fibroma occurs in younger age group (below Odontogenic Sarcomas
20 years) and the clinical behaviour is always benign. The only example of odontogenic sarcoma is a rare
ameloblastic fibrosarcoma. This tumour resembles amelo-
Histologically, it consists of epithelial follicles similar to blastic fibroma but the mesodermal component in it is
those of ameloblastoma, set in a very cellular connective malignant (sarcomatous) whereas the ameloblastic
tissue stroma. epithelium remains differentiated and benign.
SALIVARY GLANDS 533
NORMAL STRUCTURE
There are two main groups of salivary glands—major and
minor. The major salivary glands are the three paired glands:
parotid, submandibular and sublingual. The minor salivary
glands are numerous and are widely distributed in the
mucosa of oral cavity. The main duct of the parotid gland
drains into the oral cavity opposite the second maxillary
molar, while the ducts of submandibular and sublingual
glands empty in the floor of the mouth. At times, heterotopic
salivary gland tissue may be present in lymph nodes near or
within the parotid gland.
Histologically, the salivary glands are tubuloalveolar glands
and may contain mucous cells, serous cells, or both. The
parotid gland is purely serous. The submandibular gland is
mixed type but is predominantly serous, whereas the
sublingual gland though also a mixed gland is predominantly
mucous type. Similarly, minor salivary glands may also be
serous, mucous or mixed type. Figure 19.12 Lesions in mumps.
The secretory acini of the major salivary glands are
drained by ducts lined by: atrophy. Less commonly, cytomegalovirus infection may
low cuboidal epithelium in the intercalated portion, occur in parotid glands of infants and young children.
tall columnar epithelium in the intralobular ducts, and 2. Bacterial and mycotic infections. Bacterial infections may CHAPTER 19
simpler epithelium in the secretory ducts. cause acute sialadenitis more often. Sometimes there are
recurrent attacks of acute parotitis when parotitis becomes
The product of major salivary glands is saliva which
performs various functions such as lubrication for swallow- chronic.
ing and speech, and has enzyme amylase and antibacterial i) Acute sialadenitis: The causes are as follows:
properties too. a) Acute infectious fevers
b) Acute postoperative parotitis (ascent of microorganisms
SALIVARY FLOW DISTURBANCES up the parotid duct from the mouth)
SIALORRHOEA (PTYALISM). Increased flow of saliva is c) General debility
termed sialorrhoea or ptyalism. It occurs commonly due to: d) Old age
stomatitis, teething, mentally retarded state, schizophrenia, e) Dehydration.
neurological disturbances, increased gastric secretion and ii) Chronic sialadenitis. This may result from the following
sialosis (i.e. uniform, symmetric, painless hypertrophy of causes: The Oral Cavity and Salivary Glands
salivary glands). a) Recurrent obstructive type. Recurrent obstruction due to
calculi (sialolithiasis), stricture, surgery, injury etc. may cause
XEROSTOMIA. Decreased salivary flow is termed xero-
stomia. It is associated with the following conditions: repeated attacks of acute sialadenitis by ascending infection
Sjögren’s syndrome, sarcoidosis, mumps parotitis, Mikulicz’s and then chronicity.
syndrome, megaloblastic anaemia, dehydration, drug intake b) Recurrent non-obstructive type. Recurrent mild ascending
(e.g. antihistamines, antihypertensives, antidepressants). infection of the parotid gland may occur due to non-
obstructive causes which reduce salivary secretion like due
to intake of drugs causing hyposalivation (e.g. antihista-
SIALADENITIS
mines, antihypertensives, antidepressants), effect of
Inflammation of salivary glands, sialadenitis, may be acute irradiation and congenital malformations of the duct system.
or chronic; the latter being more common. c) Chronic inflammatory diseases. Tuberculosis, actinomycosis
and other mycoses may rarely occur in the salivary glands.
ETIOLOGY. Sialadenitis can occur due to the following
causes: 3. Autoimmune disease. Inflammatory changes are seen in
salivary glands in 2 autoimmune diseases:
1. Viral infections. The most common inflammatory lesion
of the salivary glands particularly of the parotid glands, is i) Sjögren’s syndrome characterised by triad of dry eyes
mumps occurring in children of school-age. It is characterised (keratoconjunctivitis sicca), dry mouth (xerostomia) and
by triad of pathological involvement—epidemic parotitis rheumatoid arthritis (Chapter 4).
(mumps), orchitis-oophoritis, and pancreatitis (Fig. 19.12). ii) Mikulicz’s syndrome is the combination of inflammatory
Involvement of the testis and pancreas may lead to their enlargement of salivary and lacrimal glands with xerostomia.
534 MORPHOLOGIC FEATURES. Irrespective of the under- TABLE 19.6: Classification of Salivary Gland Tumours.
lying etiology of sialadenitis, there is swelling of the A. BENIGN
affected salivary gland, usually restricted by the fibrous
capsule. Acute stage is generally associated with local 1. Adenomas
Pleomorphic adenoma (Mixed tumour) (65-80%)
i)
redness, pain and tenderness with purulent ductal ii) Monomorphic adenoma
discharge. Late chronic cases may be replaced by firm (a) Warthin’s tumour (Papillary cystadenoma
fibrous swelling. lymphomatosum, Adenolymphoma) (5-10%)
Microscopically, acute viral sialadenitis in mumps shows (b) Oxyphil adenoma (Oncocytomas) (< 1%)
swelling and cytoplasmic vacuolation of the acinar (c) Other types (Myoepithelioma, Basal cell
adenoma, Clear cell adenoma) (uncommon)
epithelial cells and degenerative changes in the ductal 2. Mesenchymal tumours (rare)
epithelium. There is interstitial oedema, fibrinoid degene-
ration of the collagen and dense infiltration by mono- B. MALIGNANT
nuclear cells (lymphocytes, plasma cells and macro- 1. Mucoepidermoid carcinoma (5-10%)
phages). Chronic and recurrent sialadenitis is characterised 2. Malignant mixed tumour
by increased lymphoid tissue in the interstitium, ii) i) Carcinoma in pleomorphic adenoma (2%)
Carcinosarcoma (rare)
progressive loss of secretory tissue and replacement by iii) Metastasising mixed salivary tumour (rare)
fibrosis. 3. Adenoid cystic carcinoma (cylindroma) (3-10%)
4. Acinic cell carcinoma (2-3%)
TUMOURS OF SALIVARY GLANDS 5. Adenocarcinoma (1-3%)
6. Epidermoid carcinoma (1-3%)
The major as well as minor salivary glands can give rise to a 7. Undifferentiated carcinoma (< 1%)
variety of benign and malignant tumours (Table 19.6). The 8. Miscellaneous (rare)
major glands, particularly the parotid glands (85%), are the
most common sites. Majority of parotid gland tumour (65- Pleomorphic Adenoma (Mixed Salivary Tumour)
85%) are benign, while in the other major and minor salivary This is the most common tumour of major (60-75%) and
glands 35-50% of the tumours are malignant. Most of the minor (50%) salivary glands. Pleomorphic adenoma is the
salivary gland tumours originate from the ductal lining commonest tumour in the parotid gland and occurs less often
epithelium and the underlying myoepithelial cells; a few arise in other major and minor salivary glands. The tumour is
from acini. Recurrent tumours of the parotid glands, due to commoner in women and is seen more frequently in 3rd to
SECTION III
their location, are often associated with facial palsy and 5th decades of life. The tumour is solitary, smooth-surfaced
obvious scarring following surgical treatment.
but sometimes nodular, painless and slow-growing. It is often
located below and in front of the ear (Fig. 19.13).
A. BENIGN SALIVARY GLAND TUMOURS
MORPHOLOGIC FEATURES. Grossly, pleomorphic
ADENOMAS
adenoma is a circumscribed, pseudoencapsulated,
The adenomas of the salivary glands are benign epithelial rounded, at times multilobulated, firm mass, 2-5 cm in
tumours. They are broadly classified into 2 major groups— diameter, with bosselated surface. The cut surface is grey-
pleomorphic and monomorphic adenomas. white and bluish, variegated, semitranslucent, usually
Systemic Pathology
Figure 19.13 Pleomorphic adenoma (mixed salivary tumour) of the
parotid gland. A, Diagrammatic location. B, Sectioned surface of the parotid
gland shows lobules of grey-white circumscribed tumour having
semitranslucent parenchyma (arrow).
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