535
Figure 19.14 Pleomorphic adenoma. The epithelial element is comprised of ducts, acini, tubules, sheets and strands of cuboidal and myoepithelial
cells. These are seen randomly admixed with mesenchymal elements composed of pseudocartilage which is the matrix of myxoid, chondroid and
mucoid material.
solid but occasionally may show small cystic spaces. The adenoma may metastasise to distant sites which too will have
consistency is soft and mucoid. benign appearance as the original tumour. However, actual
Microscopically, the pleomorphic adenoma is charac- malignant transformation can also occur in a pleomorphic
terised by pleomorphic or ‘mixed’ appearance in which adenoma (vide infra). CHAPTER 19
there are epithelial elements present in a matrix of mucoid,
myxoid and chondroid tissue (Fig. 19.14): Monomorphic Adenomas
Epithelial component may form various patterns like These are benign epithelial tumours of salivary glands
ducts, acini, tubules, sheets and strands of cells of ductal without any evidence of mesenchyme-like tissues. Their
or myoepithelial origin. The ductal cells are cuboidal or various forms are as under:
columnar, while the underlying myoepithelial cells may
be polygonal or spindle-shaped resembling smooth WARTHIN’S TUMOUR (PAPILLARY CYSTADENOMA
muscle cells. The material found in the lumina of duct- LYMPHOMATOSUM, ADENOLYMPHOMA). It is a
like structures is PAS-positive epithelial mucin. Focal benign tumour of the parotid gland comprising about 8% of
areas of squamous metaplasia and keratinisation may be all parotid neoplasms, seen more commonly in men from
present. Immunohistochemically, the tumour cells are 4th to 7th decades of life. Rarely, it may arise in the submandi-
immunoreactive for epithelial (cytokeratin, EMA, CEA) bular gland or in minor salivary glands. Histogenesis of the
as well as myoepithelial (actin, vimentin and S-100) tumour has been much debated; most accepted theory is that The Oral Cavity and Salivary Glands
antibodies. the tumour develops from parotid ductal epithelium present
in lymph nodes adjacent to or within parotid gland.
Mesenchymal elements are present as loose
connective tissue, and as myxoid, mucoid and chondroid MORPHOLOGIC FEATURES. Grossly, the tumour is
matrix, which simulates cartilage (pseudocartilage) but is encapsulated, round or oval with smooth surface. The cut
actually connective tissue mucin. the matrix of the tumour surface shows characteristic slit-like or cystic spaces,
has been characterised as a product of myoepithelial cells containing milky fluid and having papillary projections.
as seen by S-100 immunostain positivity. However, true Microscopically, the tumour shows 2 components:
cartilage and even bone may also be observed in a small epithelial parenchyma and lymphoid stroma (Fig. 19.15):
proportion of these tumours. Epithelial parenchyma is composed of glandular and
The epithelial and mesenchymal elements are inter-
mixed and either of the two components may be dominant cystic structures having papillary arrangement and is
lined by characteristic eosinophilic epithelium. Variants
in any tumour.
of epithelial patterns include presence of mucous goblet
cells and sebaceous differentiation.
PROGNOSIS. Pleomorphic adenoma is notorious for Lymphoid stroma is present under the epithelium in
recurrences, sometimes after many years. The main factors the form of prominent lymphoid tissue, often with
responsible for the tendency to recur are incomplete surgical germinal centres.
removal due to proximity to the facial nerve, multiple foci of
tumour, pseudoencapsulation, and implantation in the OXYPHIL ADENOMA (ONCOCYTOMA). It is a benign
surgical field. Although the tumour is entirely benign, under slow-growing tumour of the major salivary glands. The
exceptionally rare circumstances, an ordinary pleomorphic tumour consists of parallel sheets, acini or tubules of large
536
Figure 19.15 Warthin’s tumour, showing eosinophilic epithelium forming glandular and papillary, cystic pattern with intervening stroma of
lymphoid tissue.
cells with glandular eosinophilic cytoplasm (oncocytes). It It is the most common example of radiation-induced malig-
is also called as mitochondrioma because of cytoplasmic nant tumour, especially therapeutic radiation.
granularity due to mitochondria.
MORPHOLOGIC FEATURES. Grossly, the tumour is
OTHER TYPES OF MONOMORPHIC ADENOMAS. usually circumscribed but not encapsulated. It varies in
There are some uncommon forms of monomorphic size from 1 to 4 cm.
adenomas: Microscopically, the tumour is classified into low, inter-
i) Myoepithelioma is an adenoma composed exclusively of mediate and high grade depending upon the degree of
myoepithelial cells which may be arranged in tubular, differentiation and tumour invasiveness. The tumour is
SECTION III
alveolar or trabecular pattern. composed of combination of 4 types of cells: mucin-
ii) Basal cell adenoma is characterised by the type and producing, squamous, intermediate and clear cells. Well-
arrangement of cells resembling basal cell carcinoma of the differentiated tumours have predominance of mucinous
skin. cells, while poorly differentiated have more solid and
iii) Clear cell adenoma has spindle-shaped or polyhedral cells infiltrative pattern (Fig. 19.16).
with clear cytoplasm.
MISCELLANEOUS BENIGN TUMOURS
A number of mesenchymal tumours can rarely occur in
salivary glands. These include: fibroma, lipoma, neurilem-
Systemic Pathology
momas, neurofibroma, haemangioma and lymphangioma.
B. MALIGNANT SALIVARY GLAND TUMOURS
Mucoepidermoid Carcinoma
The status of ‘mucoepidermoid tumour’ as an intermediate
grade tumour in the previous classification has undergone
upgradation to mucoepidermoid carcinoma now having the
following peculiar features:
It is the most common malignant salivary gland tumour
(both in the major and minor glands).
The parotid gland amongst the major salivary glands and
the minor salivary glands in the palate are the most common
sites.
Common age group affected is 30-60 years but it is also
the most common malignant salivary gland tumour affecting Figure 19.16 Mucoepidermoid carcinoma. The tumour shows
combination of mucinous, squamous and intermediate cells and having
children and adolescents. infiltrative border.
Malignant Mixed Tumour 537
Malignant mixed tumour comprises three distinct
clinicopathologic entities:
Carcinoma arising in benign mixed salivary gland tumour
(carcinoma ex pleomorphic adenoma);
Carcinosarcoma; and
Metastasising mixed salivary tumour.
Carcinoma ex pleomorphic adenoma is more common
while the other two are rare tumours. Approximately 2 to
5% of pleomorphic adenomas reveal areas of frank
malignancy. The slow-growing adenoma may have been
present for a number of years when suddenly it undergoes
rapid increase in its size, becomes painful and the individual
may develop facial palsy. Malignant transformation occurs
in later age (6th decade) than the usual age for pleomorphic
adenoma (4th to 6th decades). It may occur in primary
tumour but more often occurs in its recurrences.
Figure 19.17 Adenoid cystic carcinoma. It shows nests of tumour
MORPHOLOGIC FEATURES. Grossly, the tumour is cells having fenestrations containing basophilic material.
poorly-circumscribed with irregular infiltrating margin.
Cut section may show haemorrhages, necrosis and cystic Adenocarcinoma
degeneration. Adenocarcinoma of the salivary gland does not differ from
Microscopically, besides the typical appearance of adenocarcinoma elsewhere in the body. It may have some
pleomorphic adenoma, malignant areas show cytologic variants such as mucoid adenocarcinoma, clear-cell CHAPTER 19
features of carcinoma such as anaplasia, nuclear adenocarcinoma and papillary cystadenocarcinoma.
hyperchromatism, large nucleolisation, mitoses and
evidence of invasive growth. All types of usual salivary Epidermoid Carcinoma
gland carcinomas (described below) may develop in
pleomorphic adenoma. This rare tumour has features of squamous cell carcinoma
with keratin formation and has intercellular bridges. The
Adenoid Cystic Carcinoma (Cylindroma) tumour commonly infiltrates the skin and involves the facial
nerve early.
This is a highly malignant tumour due to its typical infil-
trative nature, especially along the nerve sheaths. Adenoid
cystic carcinoma is histologically characterised by cribriform Undifferentiated Carcinoma
appearance i.e. the epithelial tumour cells of duct-lining and This highly malignant tumour consists of anaplastic epithe-
myoepithelial cells are arranged in duct-like structures or lial cells which are too poorly differentiated to be placed in
masses of cells, having typical fenestrations or cyst-like any other known category. The Oral Cavity and Salivary Glands
spaces and hence the name ‘adenoid cystic’. These cystic
spaces contain PAS-positive basophilic material (Fig. 19.17).
Miscellaneous Malignant Tumours
Acinic Cell Carcinoma Some rare malignant tumour of epithelial and mesenchymal
origin are melanoma, sebaceous carcinoma, undifferentiated
This is a rare tumour composed of acinic cells resembling carcinoma, lymphoma, fibrosarcoma and leiomyosarcoma
serous cells of normal salivary gland. These cells are arranged and are similar in morphology to such tumours elsewhere
in sheets or acini and have characteristic basophilic granular in the body. Besides, metastatic involvement of major salivary
cytoplasm. The degree of atypia may vary from a benign glands or the adjacent lymph nodes is common, especially
cytologic appearance to cellular features of malignancy. from epidermoid carcinoma and malignant melanoma.
q
538
Chapter 20 The Gastrointestinal Tract
Chapter 20
OESOPHAGUS the muscularis propria). However, oesophageal atresia and
tracheooesophageal fistula are relatively more common.
NORMAL STRUCTURE OESOPHAGEAL ATRESIA AND TRACHEO-OESO-
The oesophagus is a muscular tube extending from the PHAGEAL FISTULA. In about 85% of cases, congenital
pharynx to the stomach. In an adult, this distance measures atresia of the oesophagus is associated with tracheo-
25 cm. However, from the clinical point of view, the distance oesophageal fistula, usually at the level of tracheal bifur-
from the incisor teeth to the gastro-oesophageal (GE) junction cation. For survival, the condition must be recognised and
is about 40 cm. The region of proximal oesophagus at the corrected surgically within 48 hours of birth of the newborn.
level of cricopharyngeus muscle is called the upper oesophageal Clinically, the condition is characterised by regurgitation of
sphincter, while the portion adjacent to the anatomic gastro- every feed, hypersalivation, attacks of cough and cyanosis.
oesophageal junction is referred to as lower oesophageal Death usually results from asphyxia, aspiration pneumonia
sphincter. and fluid-electrolyte imbalance.
Morphologically, the condition is recognised by cord-like
Histologically, the wall of the oesophagus consists of non-canalised segment of oesophagus having blind pouch
mucosa, submucosa, muscularis propria and adventitia/ at both ends.
serosa.
The mucosa is composed of non-keratinising stratified MUSCULAR DYSFUNCTIONS
squamous epithelium overlying lamina propria except at the
lower end for a distance of 0.5 to 1.5 cm. The basal layer of These are disorders in which there is motor dysfunction of
SECTION III
the epithelium may contain some melanocytes, argyrophil the oesophagus, manifested clinically by dysphagia. These
cells and Langerhans’ cells. At the lower end of the include achalasia, hiatus hernia, oesophageal diverticula, and
oesophagus, there is sudden change from stratified webs and rings.
squamous epithelium to mucin-secreting columnar
epithelium; this is called the junctional mucosa. Achalasia (Cardiospasm)
The submucosa consists of loose connective tissue with Achalasia of the oesophagus is a neuromuscular dysfunction
sprinkling of lymphocytes, plasma cells, and occasional due to which the cardiac sphincter fails to relax during
eosinophil and mast cell. Mucus-producing glands are swallowing and results in progressive dysphagia and
scattered throughout the submucosa.
The muscularis propria is composed of 2 layers of smooth dilatation of the oesophagus (mega-oesophagus).
muscle—an inner circular coat and an outer longitudinal coat. ETIOLOGY. There is loss of intramural neurons in the wall
Systemic Pathology
The proximal portion of oesophagus contains skeletal muscle of the oesophagus. Most cases are of primary idiopathic
fibres from cricopharyngeus muscle. The parasympathetic achalasia which may be congenital. Secondary achalasia may
nerve supply by the vagus nerve is in the form of extrinsic occur from some other causes which includes: Chagas’ disease
and intrinsic plexuses. (an epidemic parasitosis with Trypansoma cruzi), infiltration
The adventitia/serosa is the outer covering of into oesophagus by gastric carcinoma or lymphoma, certain
oesophagus. Serosa is present in intra-abdominal part of viral infections, and neurodegenerative diseases.
oesophagus only, while elsewhere the perioesophageal
adventitia covers it. MORPHOLOGIC FEATURES. There is dilatation above
The major functions of oesophagus are swallowing by the short contracted terminal segment of the oesophagus.
peristaltic activity and to prevent the reflux of gastric contents Muscularis propria of the wall may be of normal thickness,
into the oesophagus. hypertrophied as a result of obstruction, or thinned out
due to dilatation. Secondary oesophagitis may supervene
CONGENITAL ANOMALIES
and cause oesophageal ulceration and haematemesis.
Congenital anomalies of the oesophagus are uncommon and
are detected soon after birth. These include a few rare Hiatus Hernia
anomalies such as agenesis (congenital absence of
oesophagus) which is incompatible with life, duplication of Hiatus hernia is the herniation or protrusion of part of the
oesophagus (double oesophagus) and congenital stenosis (i.e. stomach through the oesophageal hiatus of the diaphragm.
fibrous thickening of the oesophageal wall and atrophy of Oesophageal hiatal hernia is the cause of diaphragmatic
hernia in 98% of cases. The condition is diagnosed radio- 539
logically in about 5% of apparently normal asymptomatic
individuals. In symptomatic cases, especially the elderly
women, the clinical features are heartburn (retrosternal
burning sensation) and regurgitation of gastric juice into the
mouth, both of which are worsened due to heavy work, lifting
weights and excessive bending.
ETIOLOGY. The basic defect is the failure of the muscle
fibres of the diaphragm that form the margin of the
oesophageal hiatus. This occurs due to shortening of the
oesophagus which may be congenital or acquired.
Congenitally short oesophagus may be the cause of
hiatus hernia in a small proportion of cases.
More commonly, it is acquired due to secondary factors
which cause fibrous scarring of the oesophagus as follows:
a) Degeneration of muscle due to aging. Figure 20.2 Oesophageal webs and rings.
b) Increased intra-abdominal pressure such as in pregnancy,
abdominal tumours etc. Congenital diverticula occur either at the upper end of
c) Recurrent oesophageal regurgitation and spasm causing the oesophagus or at the bifurcation of trachea.
inflammation and fibrosis. Acquired diverticula may be of 2 types:
d) Increase in fatty tissue in obese people causing decreased a) Pulsion (Zenker’s) type—is seen in the region of hypo-
muscular elasticity of diaphragm. pharynx and occurs due to oesophageal obstruction such as
due to chronic oesophagitis, carcinoma etc. The mucosa and
MORPHOLOGIC FEATURES. There are 3 patterns in submucosa herniate through the weakened area or through
hiatus hernia (Fig. 20.1): defect in the muscularis propria.
i) Sliding or oesophago-gastric hernia is the most b) Traction type—occurs in the lower third of oesophagus CHAPTER 20
common, occurring in 85% of cases. The herniated part of from contraction of fibrous tissue such as from pleural
the stomach appears as supradiaphragmatic bell due to adhesions, scar tissue of healed tuberculous lesions in the
sliding up on both sides of the oesophagus. hilum, silicosis etc.
ii) Rolling or para-oesophageal hernia is seen in 10% of Complications of diverticula include obstruction, infec-
cases. This is a true hernia in which cardiac end of the tion, perforation, haemorrhage and carcinoma.
stomach rolls up para-oesophageally, producing an
intrathoracic sac. Oesophageal Webs and Rings
iii) Mixed or transitional hernia constitutes the remain- Radiological shadows in the oesophagus resembling ‘webs’
ing 5% cases in which there is combination of sliding and and ‘rings’ are observed in some patients complaining of
rolling hiatus hernia. dysphagia. The Gastrointestinal Tract
WEBS. Those located in the upper oesophagus, seen more
Oesophageal Diverticula commonly in adult women, and associated with dysphagia,
Diverticula are the outpouchings of oesophageal wall at the iron deficiency anaemia and chronic atrophic glossitis
point of weakness. They may be congenital or acquired. (Plummer-Vinson syndrome) are called ‘webs’.
RINGS. Those located in the lower oesophagus, not
associated with iron-deficiency anaemia, nor occurring in
women alone, are referred to as ‘Schatzki’s rings’.
MORPHOLOGIC FEATURES. The rings and webs are
transverse folds of mucosa and submucosa encircling the
entire circumference, or are localised annular thickenings
of the muscle (Fig. 20.2). These give characteristic
radiological shadows.
HAEMATEMESIS OF OESOPHAGEAL ORIGIN
Massive haematemesis (vomiting of blood) may occur due
to vascular lesions in the oesophagus. These lesions are as
under:
1. OESOPHAGEAL VARICES. Oesophageal varices are
Figure 20.1 Patterns of hiatus hernia. tortuous, dilated and engorged oesophageal veins, seen along
540 the longitudinal axis of oesophagus. They occur as a result of chronic disease such as nodularity, strictures,
of elevated pressure in the portal venous system, most ulcerations and erosions.
commonly in cirrhosis of the liver (Chapter 22). Less common Microscopically, the reflux changes in the distal
causes are: portal vein thrombosis, hepatic vein thrombosis oesophagus include basal cell hyperplasia and deep
(Budd-Chiari syndrome) and pylephlebitis. The lesions occur elongation of the papillae touching close to the surface
as a result of bypassing of portal venous blood from the liver epithelium. Inflammatory changes vary according to the
to the oesophageal venous plexus. The increased venous stage of the disease. In early stage, mucosa and submucosa
pressure in the superficial veins of the oesophagus may result are infiltrated by some polymorphs and eosinophils; in
in ulceration and massive bleeding. chronic stage, there is lymphocytic infiltration and fibrosis
2. MALLORY-WEISS SYNDROME. In this condition, of all the layers of the oesophageal wall.
there is lacerations of mucosa at the gastro-oesophageal Barrett’s Oesophagus
junction following minor trauma such as by vomiting,
retching or vigorous coughing. Patients present with upper This is a condition in which, following reflux oesophagitis,
gastro-oesophageal bleeding. stratified squamous epithelium of the lower oesophagus is
replaced by columnar epithelium (columnar metaplasia). The
3. RUPTURE OF THE OESOPHAGUS. Rupture of the condition is seen more commonly in later age and is caused
oesophagus may occur following trauma, during by factors producing gastro-oesophageal reflux disease
oesophagoscopy, indirect injury (e.g. due to sudden accele- (described above). Barrett’s oesophagus is a premalignant
ration and deceleration of the body) and spontaneous rupture condition evolving sequentially from Barrett’s epithelium
(e.g. after overeating, extensive aerophagy etc). (columnar metaplasia) → dysplasia → carcinoma in situ →
4. OTHER CAUSES. Oesophageal haematemesis may also oesophageal adenocarcinoma.
occur in the following conditions:
i) Bursting of aortic aneurysm into the lumen of oesophagus MORPHOLOGIC FEATURES. Endoscopically, the
affected area is red and velvety. Hiatus hernia and peptic
ii) Vascular erosion by malignant growth in the vicinity ulcer at squamocolumnar junction (Barrett’s ulcer) are
iii) Hiatus hernia frequently associated.
iv) Oesophageal cancer Microscopically, the most common finding is the replace-
v) Purpuras ment of squamous epithelium by metaplastic columnar
vi) Haemophilia. cells. Barrett’s oesophagus may be composed of intestinal
SECTION III
epithelium, fundic gastric glands, or cardiac mucous
INFLAMMATORY LESIONS glands. Other cells present in the glands may be Paneth
cells (Fig. 20.3), goblet cells, chief cells, parietal cells,
Inflammation of the oesophagus, oesophagitis, occurs most
commonly from reflux, although a number of other clinical mucus-secreting cells and endocrine cells.
conditions and infections may also cause oesophagitis as Inflammatory changes, acute or chronic, are commonly
under: accompanied. Dysplastic changes of the columnar
epithelium or glands may be present.
Surveillance endoscopic biopsies are advised because
Reflux (Peptic) Oesophagitis
Barrett’s intestinal metaplasaia may develop dysplasia.
Reflux of the gastric juice is the commonest cause of
oesophagitis.
Systemic Pathology
PATHOGENESIS. Gastro-oesophageal reflux, to an extent,
may occur in normal healthy individuals after meals and in
early pregnancy. However, in some clinical conditions, the
gastro-oesophageal reflux is excessive, resulting in
inflammation of the lower oesophagus. These conditions are
as under:
i) Sliding hiatus hernia
ii) Chronic gastric and duodenal ulcers
iii) Nasogastric intubation
iv) Persistent vomiting
v) Surgical vagotomy
vi) Neuropathy in alcoholics, diabetics
vii) Oesophagogastrostomy.
MORPHOLOGIC FEATURES. Endoscopically, the
demarcation between normal squamous and columnar
epithelium at the junctional mucosa is lost. The affected
distal oesophageal mucosa is red, erythematous, friable Figure 20.3 Barrett’s oesophagus. Part of the oesophagus which
and bleeds on touch. In advanced cases, there are features is normally lined by squamous epithelium undergoes metaplastic change
to columnar epithelium of intestinal type.
High-grade dysplasia may progress to invasive men over 50 years of age. Prognosis is dismal: with standard 541
adenocarcinoma of the oesophagus in up to 20% cases. methods of therapy (surgical resection and/or irradiation),
70% of the patients die within one year of diagnosis. Five-
Infectious Oesophagitis year survival rate is 5-10%.
A number of opportunistic infections in immunosuppressed ETIOLOGY. Although exact etiology of carcinoma of the
individuals can cause oesophagitis. Some of these agents are oesophagus is not known, a number of conditions and factors
as follows: have been implicated as under:
i) Candida (Monilial) oesophagitis
ii) Herpes simplex (Herpetic) oesophagitis 1. Diet and personal habits:
iii) Cytomegalovirus i) Heavy smoking
iv) Tuberculosis. ii) Alcohol consumption
iii) Intake of foods contaminated with fungus
Other Causes of Oesophagitis iv) Nutritional deficiency of vitamins and trace elements.
i) Eosinophilic oesophagitis caused by radiation, corrosives 2. Oesophageal disorders:
ii) Intake of certain drugs (anticholinergic drugs, i) Oesophagitis (especially Barrett’s oesophagus in
doxycycline, tetracycline) adenocarcinoma)
iii) Ingestion of hot, irritating fluids ii) Achalasia
iv) Crohn’s disease iii) Hiatus hernia
v) Various vesiculobullous skin diseases. iv) Diverticula
v) Plummer-Vinson syndrome.
TUMOURS OF OESOPHAGUS 3. Other factors:
Benign tumours of the oesophagus are uncommon and small i) Race—more common in the Chinese and Japanese than
in size (less than 3 cm). The epithelial benign tumours project in Western races; more frequent in blacks than whites.
as intraluminal masses arising from squamous epithelium ii) Family history—association with tylosis (keratosis
(squamous cell papilloma), or from columnar epithelium palmaris et plantaris). CHAPTER 20
(adenoma). The stromal or mesenchymal benign tumours are iii) Genetic factors—predisposition with coeliac disease,
intramural masses such as leiomyoma and others like lipoma, epidermolysis bullosa, tylosis.
fibroma, neurofibroma, rhabdomyoma, lymphangioma and iv) HPV infection—is the recent addition in etiologic factors.
haemangioma. At molecular level, abnormality of p53 tumour suppressor
For all practical purposes, malignant tumours of the oeso- gene has been found associated with a number of above risk
phagus are carcinomas because sarcomas such as factors, notably with consumption of tobacco and alcohol,
leiomyosarcoma and fibrosarcoma occur with extreme rarity. and in cases having proven Barrett’s oesophagus.
Carcinoma of Oesophagus MORPHOLOGIC FEATURES. Carcinoma of the oeso-
Carcinoma of the oesophagus is diagnosed late, after phagus is mainly of 2 types—squamous cell (epidermoid)
symptomatic oesophageal obstruction (dysphagia) has and adenocarcinoma. The sites of predilection for each of The Gastrointestinal Tract
developed and the tumour has transgressed the anatomical these 2 forms is shown in Fig. 20.4,A.
limits of the organ. The tumour occurs more commonly in
Figure 20.4 A, Carcinoma oesophagus—sites of predilection for
squamous cell carcinoma and adenocarcinoma. B, Gross patterns of
squamous cell carcinoma of the oesophagus.
542
Figure 20.5 Squamous cell carcinoma oesophagus. A, Gross appearance. The tubular structure has thick muscle in its wall and has longitudinal
mucosal folds. There is a concentric circumferential thickening in the middle (arrow) causing narrowing of the lumen (arrow). The mucosal surface
is ulcerated. B, Photomicrograph shows whorls of anaplastic squamous cells invading the underlying soft tissues.
SQUAMOUS CELL (EPIDERMOID) CARCINOMA. and middle third of the oesophagus. These tumours have
Squamous cell or epidermoid carcinoma comprises 90% a strong and definite association with Barrett’s
of primary oesophageal cancers. It is exceeded in incidence oesophagus in which there are foci of gastric or intestinal
by carcinoma colon, rectum and stomach amongst all the type of epithelium.
SECTION III
gastrointestinal cancers. The disease occurs in 6th to 7th Grossly, oesophageal adenocarcinoma appears as
decades of life and is more common in men than women. nodular, elevated mass in the lower oesophagus.
The sites of predilection are the three areas of oesophageal Microscopically, adenocarcinoma of the oesophagus can
constrictions. Half of the squamous cell carcinomas of have 3 patterns:
oesophagus occur in the middle third, followed by lower i) Intestinal type—is the adenocarcinoma with a pattern
third, and the upper third of oesophagus in that order of similar to that seen in adenocarcinoma of intestine or
frequency. stomach.
Grossly, 3 types of patterns are recognised (Fig. 20.4,B): ii) Adenosquamous type—is the pattern in which there is
i) Polypoid fungating type—is the most common form. It an irregular admixture of adenocarcinoma and squamous
appears as a cauliflower-like friable mass protruding into cell carcinoma.
the lumen. iii) Adenoid cystic type—is an uncommon variety and is
Systemic Pathology
ii) Ulcerating type—is the next common form. It looks akin to similar growth in salivary gland i.e. a cribriform
grossly like a necrotic ulcer with everted edges (Fig. 20.5, appearance in an epithelial tumour.
A). Adenocarcinoma of the oesophagus must be
iii) Diffuse infiltrating type—appears as an annular, distinguished from adenocarcinoma of the gastric cardia.
stenosing narrowing of the lumen due to infiltration into This is done by identifying normal oesophageal mucosa
the wall of oesophagus. on distal as well as proximal margin of the tumour.
Microscopically, majority of the squamous cell carcinomas OTHER CARCINOMAS. Besides the two main
of the oesophagus are well-differentiated or moderately- histological types of oesophageal cancer, a few other
differentiated (Fig. 20.5, B). Prickle cells, keratin forma- varieties are occasionally encountered. These are as follow:
tion and epithelial pearls are commonly seen. However, i) Mucoepidermoid carcinoma is a tumour having
non-keratinising and anaplastic growth patterns can also characteristics of squamous cell as well as mucus-secreting
carcinomas.
occur. An exophytic, slow-growing, extremely well- ii) Malignant melanoma is derived from melanoblasts in
differentiated variant, verrucous squamous cell carcinoma, the epithelium of the oesophagus.
has also been reported in the oesophagus.
iii) Oat cell carcinoma arises from argyrophil cells in the
ADENOCARCINOMA. Adenocarcinoma of the basal layer of the epithelium.
oesophagus constitutes less than 10% of primary iv) Undifferentiated carcinoma is an anaplastic carcinoma
oesophageal cancer. It occurs predominantly in men in which cannot be classified into any recognisable type of
their 4th to 5th decades. The common locations are lower carcinoma.
v) Carcinosarcoma consists of malignant epithelial as well is inner concavity on the right, while the greater curvature is 543
as sarcomatous components. the outer convexity on the left side of the stomach.
vi) Secondary tumours rarely occur in the oesophagus from The stomach has 5 anatomical regions (Fig. 20.6):
carcinomas of the breast, kidney and adrenals. 1. Cardia is the oesophagogastric junction and lacks the
sphincter.
SPREAD. The oesophageal cancer spreads locally as well as 2. Fundus is the portion above the horizontal line drawn
to distant sites. across the oesophagogastric junction.
i) Local spread. This is the most important mode of spread 3. Body is the middle portion of the stomach between the
and is of great importance for surgical treatment. The local fundus and the pyloric antrum.
spread may occur in the transverse as well as longitudinal 4. Pyloric antrum is the distal third of the stomach.
direction. The tumour may invade below into the stomach,
above into the hypopharynx, into the trachea resulting in 5. Pylorus is the junction of distal end of the stomach with
tracheo-oesophageal fistula, and may involve larynx causing the duodenum. It has powerful sphincter muscle.
hoarseness. The tumour may invade the muscular wall of The mucosal folds in the region of the body and the
the oesophagus and involve the mediastinum, lungs, bronchi, fundus are loose (rugae), while the antral mucosa is
pleura and aorta. somewhat flattened. Gastric canal is the relatively fixed
portion of the pyloric antrum and the adjoining lesser
ii) Lymphatic spread. Submucosal lymphatic permeation curvature; it is the site for numerous pathological changes
may lead to multiple satellite nodules away from the main such as gastritis, peptic ulcer and gastric carcinoma.
tumour. Besides, the lymphatic spread may result in The stomach receives its blood supply from the left gastric
metastases to the cervical, para-oesophageal, tracheo- artery and the branches of the hepatic and splenic arteries
bronchial and subdiaphragmatic lymph nodes.
with widespread anastomoses. Numerous gastric lymphatics
iii) Haematogenous spread. Blood-borne metastases from which communicate freely with each other are also present.
the oesophageal cancer are rare, probably because the death The innervation of the stomach is by the vagi and branches
occurs early due to invasion of important structures by other of the sympathetic which are connected with ganglia in the
modes of spread. However, metastatic deposits by muscular and submucous layers.
haematogenous route can occur in the lungs, liver and Histologically, the wall of the stomach consists of 4 layers— CHAPTER 20
adrenals. serosa, muscularis, submucosa and mucosa.
1. Serosa is derived from the peritoneum which is deficient
STOMACH in the region of lesser and greater curvatures.
2. Muscularis consists of 3 layers of smooth muscle fibres—
NORMAL STRUCTURE the outer longitudinal, the middle circular and the inner
oblique. Nerve plexuses and ganglion cells are present
The stomach is ‘gland with cavity’, extending from its between the longitudinal and circular layers of muscle. The
junction with lower end of the oesophagus (cardia) to its pyloric sphincter is the thickened circular muscle layer at
junction with the duodenum (pylorus). The lesser curvature the gastroduodenal junction. The Gastrointestinal Tract
Figure 20.6 Anatomical subdivisions of the stomach correlated with histological appearance of gastric mucosa in different regions. D , D , D 3
2
1
and D 4 are the first to fourth parts of the duodenum.
544 3. Submucosa is a layer of loose fibroconnective tissue Hydrochloric acid is produced by the parietal (oxyntic) cells
binding the mucosa to the muscularis loosely and contains by the interaction of Cl’ ions of the arterial blood with water
branches of blood vessels, lymphatics and nerve plexuses and carbon dioxide in the presence of the enzyme, carbonic
and ganglion cells. anhydrase. The degree of gastric activity is correlated with
4. Mucosa consists of 2 layers—superficial and deep. the ‘total parietal cell mass’. Injection of histamine can
Between the two layers is the lamina propria composed of stimulate the production of acid component of the gastric
network of fibrocollagenic tissue with a few lymphocytes, juice, while the pepsin-secreting chief cells do not respond
plasma cells, macrophages and eosinophils. The mucosa is to histamine. Physiologically, the gastric secretions are
externally bounded by muscularis mucosae: stimulated by the food itself.
i) Superficial layer. It consists of a single layer of surface The control of gastric secretions chiefly occurs in one of the
epithelium composed of regular, mucin-secreting, tall following 3 ways:
columnar cells with basal nuclei. There is a very rapid 1. Cephalic phase—is stimulated by the sight, smell, taste
turnover of these cells. These dip down at places to form or even thought of food. A neural reflex is initiated via
crypts (or pits or foveolae). branches of the vagus nerve that promotes the release of
Cardiac mucosa is the transition zone between the oeso- hydrochloric acid, pepsinogen and mucus.
phageal squamous mucosa and the oxyntic mucosa of the 2. Gastric phase—is triggered by the mechanical and
fundus and body with which it gradually merges. chemical stimuli.
Oxyntic mucosa lines both gastric fundus and body. i) Mechanical stimulation comes from stretching of the wall
Antral mucosa lines the pyloric antrum. of the stomach and conveying neural messages to the medulla
ii) Deep layer: It consists of glands that open into the for gastric secretion.
bottom of the crypts. Depending upon the structure, these ii) Chemical stimulation is by digested proteins, amino acids,
glands are of 3 types: bile salts and alcohol which act on gastrin-producing G cells.
a) Glands of the cardia are simple tubular or compound Gastrin then passes into the blood stream and on return to
tubulo-racemose, lined by mucin secreting cells. A few the stomach promotes the release of gastric juice.
endocrine cells and occasional parietal and chief cells are also 3. Intestinal phase—is triggered by the entry of protein-
present. rich food in the small intestine. An intestinal hormone capable
b) Glands of the body-fundus are long, tubular and tightly of stimulating gastric secretion is probably released into the
packed which may be coiled or dilated. There are 4 types of blood stream.
cells present in the glands of body-fundic mucosa:
SECTION III
Parietal (Oxyntic) cells—are the most numerous and line GASTRIC ANALYSIS
the superficial (upper) part of the glands. Parietal cells In various diseases of the stomach, the laboratory tests to
are triangular in shape, have dark-staining nuclei and measure gastric secretions (consisting of gastric acid, pepsin,
eosinophilic cytoplasm. These cells are responsible for mucus and intrinsic factor) and serum gastrin are of
production of hydrochloric acid of the gastric juice and particular significance (Table 20.1).
the blood group substances.
Chief (Peptic) cells—are the dominant cells in the deeper A. TESTS FOR GASTRIC SECRETIONS
(lower) parts of the glands. Their basal nuclei are large
with prominent nucleoli and the cytoplasm is coarsely 1. Tests for Gastric Acid Secretions
granular and basophilic. These cells secrete pepsin of the The conventional fractional test meal (FTM) has been totally
gastric juice. superseded by newer tests. These tests are based on the
Systemic Pathology
Mucin-secreting neck cells—are small and fewer. These
cells are present in the region of the narrow neck of the TABLE 20.1: Gastric Analysis.
gastric glands i.e. at the junction of the glands with the
pits. A. TESTS FOR GASTRIC SECRETIONS
1. Tests for gastric acid secretions
Endocrine (Kulchitsky or Enterochromaffin) cells—are i) Histamine stimulation
widely distributed in the mucosa of all parts of the ii) Histalog stimulation
alimentary tract and are described later (page 561). iii) Pentagastrin (peptavlon) stimulation
c) Glands of the pylorus are much longer than the body-fundic iv) Insulin meal (Hollander test)
glands. These are simple tubular glands which are often v) Tubeless analysis
coiled. They are lined mainly by small, granular, mucin- 2. Tests for pepsin
secreting cells resembling neck cells and occasional parietal Pepsin inhibitors
cells but no chief cells. Gastrin-producing G-cells are present 3. Tests for mucus
Protein content of mucus
predominantly in the region of antropyloric mucosa, with a 4. Tests for intrinsic factor
small number of these cells in the crypts and Brunner’s glands
of the proximal duodenum. B. TESTS FOR GASTRIN
The secretory products of the gastric mucosa are the 1. Serum gastrin
gastric juice and the intrinsic factor, required for absorption of 2. Gastrin provocation tests
vitamin B . Gastric juice consists of hydrochloric acid, ii) i) Secretin test
Calcium infusion test
12
–
+
+
pepsin, mucin and electrolytes like Na , K , HCO’ and Cl .
3
principle of measuring basal acid output (BAO) and maximal 3. Tests for Mucus 545
acid output (MAO) produced by the stomach under the
influence of a variety of stimulants, and then comparing the Protein content of gastric mucus is measured, normal value
readings of BAO and MAO with the normal values. being 1.8 mg/ml. The level is increased in chronic
hypertrophic gastritis (Ménétrier’s disease).
Quantitative analysis is performed after an overnight fast.
The stomach is intubated and gastric secretion collected in 4 4. Test for Intrinsic Factor
consecutive 15-minute intervals. This unstimulated, one-hour
collection after titration for the acid concentration in it, is Intrinsic factor (IF) is essential for vitamin B absorption from
12
called BAO, expressed in mEq 1-hour. Subsequently, the the small intestine. In its absence, the absorption of vitamin
stomach is stimulated to secrete maximal acid which is B is impaired as occurs in chronic atrophic gastritis and
12
similarly collected for one hour and the acid content called gastric atrophy. Schilling test is used for evaluation of patients
as MAO, expressed in mEq-1-hour. Two highest 15-minute with suspected pernicious anaemia but can also be used as a
acid outputs are added and then multiplied by 2; this gives diagnostic test for pancreatic insufficiency resulting in
the peak acid output (PAO). impaired absorption of vitamin B since gastric R-binder
12
The tests for gastric acid secretion are named after the protein is not cleared from intrinsic factor due to reduced
stimulants used for MAO. Some of the commonly used pancreatic proteolytic activity. Schilling test is discussed on
substances are as under: page 308.
i) HISTAMINE. Histamine was the first standard stimulant B. TESTS FOR GASTRIN
used for gastric acid secretion test. Subcutaneous injection
of histamine phosphate (0.04 mg/kg body weight) is given Circulating gastrin secreted by G-cells present in the
with simultaneous administration of antihistaminic agent to antropyloric and proximal duodenal mucosa is normally
prevent the untoward side-effects of histamine. 0-200 pg/ml. It can be tested by the following methods:
ii) HISTALOG (BETAZOLE). Subcutaneous injection of
histalog (1-15 mg/kg body weight) is preferable over 1. Serum Gastrin Levels
histamine due to fewer undesired side-effects and no need Radioimmunoassay (RIA) is the commonly used method of
for administration of antihistaminic agent. measurement of serum gastrin levels. Normal fasting values CHAPTER 20
are 20-150 pg/ml. The levels are high in:
iii) PENTAGASTRIN (PEPTAVLON). Pentagastrin is
currently the most preferred agent administered in the dose atrophic gastritis (with low gastric acid secretion);
of 6 μg/kg body weight. Its activity is similar to gastrin. Zollinger-Ellison syndrome or gastrinoma (with high
iv) INSULIN MEAL (HOLLANDER TEST). This test is gastric acid secretion); and
based on the fact that in a state of hypoglycaemia, direct vagal following surgery on the stomach.
action on the parietal cell mass is responsible for acid
secretion. Hypoglycaemia induced by intravenous insulin 2. Gastrin Provocation Tests
(15 IU soluble insulin) can be used as a test for evaluating These tests are used to differentiate between hyper-
the completeness of vagotomy. No increase in acid gastrinaemia and gastric acid hypersecretion as follows:
production should occur if the vagal resection is complete. i) SECRETIN TEST. An intravenous injection of secretin
v) TUBELESS ANALYSIS. A resin-bound dye, diagnex (1 unit/kg body weight) is given. If the serum gastrin levels The Gastrointestinal Tract
blue, is given orally. The release of dye by the action of gastric rise by more than 50% of basal value in 5-15 minutes, it is
acid and its appearance in the urine indicates the presence diagnostic of Zollinger-Ellison syndrome (gastrinoma). This
of gastric acid. The test can be repeated after giving stimulant rise does not occur in other conditions.
of gastric secretion. ii) CALCIUM INFUSION TEST. Intravenous infusion of
SIGNIFICANCE calcium (5 mg/kg per hour) is given for 3 hour. Rise in serum
Normal value for BAO is 1.5-2.0 mEq 1-hour and for MAO is gastrin levels by more than 50% of basal value is diagnostic
12-40 mEq 1-hour. In gastric ulcer, the values of BAO and of Zollinger-Ellison syndrome (gastrinoma).
MAO are usually normal or slightly below normal. CONGENITAL ANOMALIES
Higher values are found in:
duodenal ulcer; Pancreatic Heterotopia
Zollinger-Ellison syndrome (gastrinoma); and Heterotopic pancreatic tissue may present clinically as a
anastomotic ulcer.
gastric mass or may be an incidental finding. Symptomatic
Low value or achlorhydria are observed in: cases may present in newborn or later in life.
pernicious anaemia (atrophic gastritis); and
achlorhydria in the presence of gastric ulcer is highly Grossly, it is seen as a mass projecting into the gastric
suggestive of gastric malignancy. lumen, generally in the region of submucosa and less often
in the muscular layer. In most cases, the mass is located in
2. Tests for Pepsin the region of antrum or pylorus.
Microscopically, both normal mature pancreatic acinar and
Pepsin inhibitors are used for analysis of pepsin derived from ductal tissue are seen. Islets are seen in about a third of
pepsinogen for research purposes. The levels of pepsin are cases.
low in atrophic gastritis.
546 Acute Dilatation
Sudden and enormous dilatation of the stomach by gas or
fluids due to paralysis of the gastric musculature may occur
after abdominal operations, generalised peritonitis, and, in
pyloric stenosis.
Gastric Rupture
The stomach may rupture rarely and prove fatal e.g. due to
blunt trauma, external cardiac massage, ingestion of heavy
meal or large quantity of liquid intake like beer.
INFLAMMATORY CONDITIONS
The two important inflammatory conditions of the stomach
are gastritis and peptic ulcer. Rarely, stomach may be involved
in tuberculosis, sarcoidosis and Crohn’s disease.
Figure 20.7 Pyloric stenosis, infantile type. Longitudinal and GASTRITIS
transverse section of the stomach showing hypertrophy of the circular The term ‘gastritis’ is commonly employed for any clinical
layer of the muscularis in the pyloric sphincter.
condition with upper abdominal discomfort like indigestion
Pyloric Stenosis or dyspepsia in which the specific clinical signs and
radiological abnormalities are absent. The condition is of
Hypertrophy and narrowing of the pyloric lumen occurs great importance due to its relationship with peptic ulcer
predominantly in male children as a congenital defect and gastric cancer. Broadly speaking, gastritis may be of 2
(infantile pyloric stenosis). The adult form is rarely seen, either types—acute and chronic. Chronic gastritis can further be of
as a result of late manifestation of mild congenital anomaly various types.
or may be acquired type due to inflammatory fibrosis or
invasion by tumours. A simple classification of various types of gastritis is
presented in Table 20.2.
ETIOLOGY. The exact cause of congenital (infantile) pyloric
stenosis is not known but it appears to have familial Acute Gastritis
SECTION III
clustering and recessive genetic origin. The acquired (adult) Acute gastritis is a transient acute inflammatory involvement
pyloric stenosis is related to antral gastritis, and tumours in of the stomach, mainly mucosa.
the region (gastric carcinoma, lymphoma, pancreatic
carcinoma). ETIOPATHOGENESIS. A variety of etiologic agents have
been implicated in the causation of acute gastritis. These are
MORPHOLOGIC FEATURES. Grossly and micros- as follows:
copically, there is hypertrophy as well as hyperplasia of 1. Diet and personal habits:
the circular layer of muscularis in the pyloric sphincter Highly spiced food
accompanied by mild degree of fibrosis (Fig. 20.7).
Excessive alcohol consumption
CLINICAL FEATURES. The patient, usually a first born Malnutrition
male infant 3 to 6 weeks old, presents with the following Heavy smoking.
Systemic Pathology
clinical features: 2. Infections:
1. Vomiting, which may be projectile and occasionally
contains bile or blood. Bacterial infections e.g. Helicobacter pylori, diphtheria,
2. Visible peristalsis, usually noticed from left to right side salmonellosis, pneumonia, staphylococcal food poisoning.
of the upper abdomen.
3. Palpable lump, better felt after an episode of vomiting. TABLE 20.2: Classification of Gastritis.
4. Constipation. A. ACUTE GASTRITIS
5. Loss of weight.
1. Acute H. pylori gastritis
MISCELLANEOUS ACQUIRED CONDITIONS 2. Other acute infective gastritis (bacteria, viruses, fungi,
parasites)
Bezoars 3. Acute non-infective gastritis
Bezoars are foreign bodies in the stomach, usually in patients B. CHRONIC GASTRITIS
with mental illness who chew these substances. Some of the 1. Type A (autoimmune) : Body-fundic predominant
common bezoars are as follows: 2. Type B (H. pylori-related) : Antral-predominant
Trichobezoars composed of a ball of hair. gastritis
Phytobezoars composed of vegetable fibres, seeds or fruit 3. Type AB (mixed environmental) : Antral-body gastritis
skin.
Trichophytobezoars combining both hair and vegetable 4. Chemical (reflux) gastritis : Antral-body predominant
matter. 5. Miscellaneous forms of gastritis
Viral infections e.g. viral hepatitis, influenza, infectious 3. Associated disease of the stomach and duodenum, such as 547
mononucleosis. gastric or duodenal ulcer, gastric carcinoma.
4. Chronic hypochromic anaemia, especially associated with
3. Drugs: atrophic gastritis.
Intake of drugs like non-steroidal anti-inflammatory
drugs (NSAIDs), aspirin, cortisone, phenylbutazone, 5. Immunological factors such as autoantibodies to gastric
parietal cells in atrophic gastritis and autoantibodies against
indomethacin, preparations of iron, chemotherapeutic intrinsic factor.
agents.
The mechanism of chronic gastric injury by any of the
4. Chemical and physical agents: etiologic agents is by cytotoxic effect of the injurious agent
Intake of corrosive chemicals such as caustic soda, phenol, on the gastric mucosal epithelium, thus breaking the barrier
lysol and then inciting the inflammatory response.
Gastric irradiation
Freezing. CLASSIFICATION. Based on the type of mucosa affected
(i.e. cardiac, body, pyloric, antral or transitional), a
5. Severe stress: clinicopathologic classification has been proposed
Emotional factors like shock, anger, resentment etc. (Table 20.2).
Extensive burns 1. Type A gastritis (Autoimmune gastritis). Type A gas-
Trauma tritis involves mainly the body-fundic mucosa. It is also called
Surgery.
autoimmune gastritis due to the presence of circulating
The mucosal injury and subsequent acute inflammation antibodies and is sometimes associated with other
in acute gastritis occurs by one of the following mechanisms: autoimmune diseases such as Hashimoto’s thyroiditis and
1. Reduced blood flow, resulting in mucosal hypoperfusion Addison’s disease. As a result of the antibodies against
due to ischaemia. parietal cells and intrinsic factor, there is depletion of parietal
cells and impaired secretion of intrinsic factor. These changes
2. Increased acid secretion and its accumulation due to H.
pylori infection resulting in damage to epithelial barrier. may lead to significant gastric atrophy where intestinal
metaplasia may occur, and a small proportion of these CHAPTER 20
3. Decreased production of bicarbonate buffer.
patients may develop pernicious anaemia. Due to depletion
MORPHOLOGIC FEATURES. Grossly, the gastric of gastric acid-producing mucosal area, there is hypo- or
mucosa is oedematous with abundant mucus and achlorhydria, and hyperplasia of gastrin-producing G cells
haemorrhagic spots. in the antrum resulting in hypergastrinaemia.
Microscopically, depending upon the stage, there is 2. Type B gastritis (H. pylori-related). Type B gastritis
variable amount of oedema and infiltration by neutrophils mainly involves the region of antral mucosa and is more
in the lamina propria. In acute haemorrhagic and erosive common. It is also called hypersecretory gastritis due to
gastritis, the mucosa is sloughed off and there are excessive secretion of acid, commonly due to infection with
haemorrhages on the surface. H. pylori. These patients may have associated peptic ulcer.
Unlike type A gastritis, this form of gastritis has no
Chronic Gastritis autoimmune basis nor has association with other The Gastrointestinal Tract
autoimmune diseases.
Chronic gastritis is the commonest histological change 3. Type AB gastritis (Mixed gastritis, Environmental
observed in biopsies from the stomach. The microscopic gastritis, Chronic atrophic gastritis). Type AB gastritis affects
change is usually poorly correlated to the symptomatology, the mucosal region of A as well as B types (body-fundic and
as the change is observed in about 35% of endoscopically antral mucosa). This is the most common type of gastritis in
normal mucosal biopsies. The condition occurs more all age groups. It is also called environmental gastritis
frequently with advancing age; average age for symptomatic because a number of unidentified environmental factors have
chronic gastritis being 45 years which corresponds well with been implicated in its etiopathogenesis. Chronic atrophic
the age incidence of gastric ulcer. gastritis is also used synonymously with type AB gastritis
because in advanced stage, there is progression from chronic
ETIOPATHOGENESIS. In the absence of clear etiology of superficial gastritis to chronic atrophic gastritis, characterised
chronic gastritis, a number of etiologic factors have been by mucosal atrophy and metaplasia of intestinal or
implicated. All the causative factors of acute gastritis pseudopyloric type.
described above may result in chronic gastritis too. Recurrent
attacks of acute gastritis may result in chronic gastritis. Some MORPHOLOGIC FEATURES. Grossly, the features of all
additional causes are as under: forms of gastritis are inconclusive. The gastric mucosa may
1. Reflux of duodenal contents into the stomach, especially in be normal, atrophied, or oedematous.
cases which have undergone surgical intervention in the Histologically, criteria for categorisation are based on the
region of pylorus. following:
2. Infection with H. pylori is strongly implicated in the i) Extent of inflammatory changes in the mucosa (i.e.
etiology of chronic gastritis and is more common. superficial or deep).
548
Figure 20.8 Histologic appearance of H. pylori chronic gastritis. A, Diagrammatic representation. B, H&E stained section. C, Demonstration of
H. pylori in Giemsa stain.
ii) Activity of inflammation (i.e. quiscent or active; acute causative for almost all active cases of chronic superficial
or chronic). gastritis and about 65% of quiscent cases. The organism
iii) Presence of and type of metaplasia (i.e. intestinal or is identified on the epithelial layer on the luminal surface
pseudopyloric). and does not invade the mucosa (Fig. 20.8). It is not seen
Based on above, following simple morphologic classi- on areas with intestinal metaplasia. H. pylori gastritis can
fication has been proposed: be diagnosed by the following techniques:
1. Chronic superficial gastritis i) Invasive tests (Endoscopic biopsy):
SECTION III
2. Chronic atrophic gastritis a) histologic examination combined with special stains for
3. Gastric atrophy identification of microorganism: Giemsa, Steiner silver or
4. Chronic hypertrophic gastritis (Ménétrier’s disease) Warthin-Starry stains;
5. Uncommon forms of chronic gastritis. b) biopsy urease test which is quick and simple but not
However, Sydney system of recording of histologic fully sensitive; and
changes in gastritis is more acceptable since it takes into c) culture of the microorganism that helps in determining
account following multiple parameters as well: specific antibiotic sensitivity.
i) Etiology (H. pylori, autoimmune, NSAIDs, infections). ii) Non-invasive tests:
ii) Location (pangastritis, predominant antral, predominant a) serologic tests (Immunoblot, ELISA) which are cheap
body-fundic). and convenient but may not be helpful in early follow-up
iii) Morphology (depth of inflammation—superficial or cases; and
Systemic Pathology
deep, severity of inflammation, type of inflammation, b) 14C urea breath test.
atrophy, metaplasia). Although most patients of chronic superficial gastritis
iv) Some special features (e.g. granulomas, eosinophilic due to H. pylori remain asymptomatic, they may develop
gastritis, erosions, necrosis, haemorrhages). chronic atrophic gastritis, gastric atrophy, peptic ulcer
disease. H. pylori infection is now considered an
1. CHRONIC SUPERFICIAL GASTRITIS. As the name independent risk factor for gastric cancer: 3-6 fold
suggests there is inflammatory infiltrate consisting of increased risk for gastric adenocarcinoma and 6-50 times
plasma cells and lymphocytes in the superficial layer of risk of MALT lymphoma (Fig. 20.9).
the gastric mucosa, but there are no histological changes in
the deep layer of mucosa containing gastric glands. Chronic 2. CHRONIC ATROPHIC GASTRITIS. In this stage,
superficial gastritis may resolve completely or may there is inflammatory cell infiltrate in the deeper layer of the
progress to chronic gastric atrophy. mucosa and atrophy of the epithelial elements including
H. pylori, a spiral-shaped bacteria, was first reported destruction of the glands. Two types of metaplasia are
by Warren and Marshall in Australia in 1984 as inhabitant commonly associated with atrophic gastritis:
of the acid environment of the stomach causing gastritis. i) Intestinal metaplasia. Intestinal metaplasia is more
After intial skepticism, numerous workers subsequently common and involves antral mucosa more frequently.
verified its association with gastritis and peptic ulcer Characteristic histologic feature is the presence of
(Warren and Marshall shared Nobel Prize in medicine in intestinal type mucus-goblet cells; Paneth cells and
2005 for their discovery). It is now known that H. pylori is endocrine cells may also be present. Parietal cells are very
muscularis mucosae may extend into the thickened folds. 549
Epithelium-lined cysts are commonly seen in the
glandular layer. Inflammatory infiltrate is usually mild
but lymphoid follicles may be present. The condition is
considered significant in view of the risk of developing
cancer.
5. MISCELLANEOUS FORMS OF CHRONIC GAS-
TRITIS. A few other types of gastritis which do not fit
into the description of the types of gastritis described
above are as under:
i) Eosinophilic gastritis. This condition is characterised
by diffuse thickening of the pyloric antrum due to oedema
and extensive infiltration by eosinophils in all the layers
of the wall of antrum. Eosinophilic gastritis probably has
Figure 20.9 Consequences of long-term H. pylori gastritis. an allergic basis.
iii) Chronic follicular gastritis. This is a variant of chronic
few or absent (Fig. 20.10). Intestinal metaplasia, focal or atrophic gastritis in which numerous lymphoid follicles
extensive, in atrophic gastritis is significant because its are present in the mucosa and submucosa of the stomach.
incidence is high in populations having high prevalence iv) Haemorrhagic (Erosive) gastritis. In this condition,
rate of gastric cancer like in Japan. However, areas of there are superficial erosions and mucosal haemorrhages,
intestinal metaplasia are not colonised by H. pylori. usually following severe haematemesis. The causes for
ii) Pseudopyloric metaplasia. It involves the body glands such erosions and haemorrhages are duodenal-gastric
which are replaced by proliferated mucus neck cells, reflux, administration of non-steroidal anti-inflammatory
conforming in appearance to normal pyloric glands. Its drugs (NSAIDs), portal hypertension.
significance is not known. v) Granulomatous gastritis. Rarely, granulomas may be CHAPTER 20
3. GASTRIC ATROPHY. In this, there is thinning of the present in the gastric mucosa such as in tuberculosis,
gastric mucosa with loss of glands but no inflammation sarcoidosis, Crohn’s disease, syphilis, various mycoses,
though lymphoid aggregates may be present. and as a reaction to endogenous substance or foreign
material.
4. CHRONIC HYPERTROPHIC GASTRITIS (MÉNÉ-
TRIER’S DISEASE). This is an uncommon condition
characterised pathologically by enormous thickening of PEPTIC ULCERS
gastric rugal folds resembling cerebral convolutions, Peptic ulcers are the areas of degeneration and necrosis of
affecting mainly the region of fundic-body mucosa and gastrointestinal mucosa exposed to acid-peptic secretions.
characteristically sparing antral mucosa. The patients Though they can occur at any level of the alimentary tract
present with dyspepsia, haematemesis, melaena or that is exposed to hydrochloric acid and pepsin, they occur The Gastrointestinal Tract
protein-losing enteropathy. most commonly (98-99%) in either the duodenum or the
Histologically, the gastric pits are elongated and are stomach in the ratio of 4:1. Each of the two main types may
tortuous. The mucosa is markedly thickened and parts of be acute or chronic.
Figure 20.10 A, Chronic atrophic gastritis (right) contrasted with normal pyloric mucosa (left). There is marked gastric atrophy with disappearance
of gastric glands and appearance of goblet cells (intestinal metaplasia). B, Photomicrograph showing chronic atrophic gastritis with intestinal
metaplasia.
550 Acute Peptic (Stress) Ulcers and duodenal peptic ulcers are described together below
while their contrasting features are presented in Table 20.3.
Acute peptic ulcers or stress ulcers are multiple, small
mucosal erosions, seen most commonly in the stomach but INCIDENCE. Peptic ulcers are more frequent in middle-aged
occasionally involving the duodenum. adults. The peak incidence for duodenal ulcer is 5th decade,
while for gastric ulcer it is a decade later (6th decade).
ETIOLOGY. These ulcers occur following severe stress. The Duodenal as well as gastric ulcers are more common in males
causes are as follows:
than in females. Duodenal ulcer is almost four times more
i) Psychological stress common than gastric ulcer; the overall incidence of
ii) Physiological stress as in the following: gastroduodenal ulcers being approximately 10% of the male
Shock population.
Severe trauma ETIOLOGY. The immediate cause of peptic ulcer disease is
Septicaemia disturbance in normal protective mucosal ‘barrier’ by acid-
Extensive burns (Curling’s ulcers in the posterior aspect pepsin, resulting in digestion of the mucosa. However, in
of the first part of the duodenum). contrast to duodenal ulcers, the patients of gastric ulcer have
Intracranial lesions (Cushing’s ulcers developing from low-to-normal gastric acid secretions, though true achlorhydria in
hyperacidity following excessive vagal stimulation). response to stimulants never occurs in benign gastric ulcer.
Drug intake (e.g. aspirin, steroids, butazolidine, Besides, 10-20% patients of gastric ulcer may have coexistent
indomethacin). duodenal ulcer as well. Thus, the etiology of peptic ulcers
Local irritants (e.g. alcohol, smoking, coffee etc). possibly may not be explained on the basis of a single factor
but is multifactorial. These factors are discussed below but
PATHOGENESIS. It is not clear how the mucosal erosions the first two—H. pylori gastritis and NSAIDs-induced injury
occur in stress ulcers because actual hypersecretion of gastric are considered most important.
acid is demonstrable in only Cushing’s ulcers occurring from 1. Helicobacter pylori gastritis. About 15-20% cases infected
intracranial conditions such as due to brain trauma, with H. pylori in the antrum develop duodenal ulcer in their
intracranial surgery and brain tumours. In all other etiologic life time while gastric colonisation by H. pylori never deve-
factors, gastric acid secretion is normal or below normal. In lops ulceration and remain asymptomatic. H. pylori can be
these conditions, the possible hypotheses for genesis of stress identified in mucosal samples by histologic examination,
ulcers are as under: culture and serology as discussed on page 548.
SECTION III
1. Ischaemic hypoxic injury to the mucosal cells.
2. Depletion of the gastric mucus ‘barrier’ rendering the 2. NSAIDs-induced mucosal injury. Non-steroidal anti-
mucosa susceptible to attack by acid-peptic secretions. inflammatory drugs are most commonly used medications
in the developed countries and are responsible for direct
MORPHOLOGIC FEATURES. Grossly, acute stress toxicity, endothelial damage and epithelial injury to both
ulcers are multiple (more than three ulcers in 75% of cases). gastric as well as duodenal mucosa.
They are more common anywhere in the stomach, 3. Acid-pepsin secretions. There is conclusive evidence that
followed in decreasing frequency by occurrence in the first some level of acid-pepsin secretion is essential for the
part of duodenum. They may be oval or circular in shape, development of duodenal as well as gastric ulcer. Peptic
usually less than 1 cm in diameter. ulcers never occur in association with pernicious anaemia in
Microscopically, the stress ulcers are shallow and do not which there are no acid and pepsin-secreting parietal and
Systemic Pathology
invade the muscular layer. The margins and base may chief cells respectively.
show some inflammatory reaction depending upon the 4. Gastritis. Some degree of gastritis is always present in
duration of the ulcers. These ulcers commonly heal by the region of gastric ulcer, though it is not clear whether it is
complete re-epithelialisation without leaving any scars. the cause or the effect of ulcer. Besides, the population
Complications such as haemorrhage and perforation may distribution pattern of gastric ulcer is similar to that of chronic
occur. gastritis.
5. Other local irritants. Pyloric antrum and lesser curvature
Chronic Peptic Ulcers (Gastric and Duodenal Ulcers) of the stomach are the sites most exposed for longer periods
If not specified, chronic peptic ulcers would mean gastric to local irritants and thus are the common sites for occurrence
and duodenal ulcers, the two major forms of ‘peptic ulcer of gastric ulcers. Some of the local irritating substances
disease’ of the upper GI tract in which the acid-pepsin implicated in the etiology of peptic ulcers are heavily spiced
secretions are implicated in their pathogenesis. Peptic ulcers foods, alcohol, cigarette smoking, unbuffered aspirin.
are common in the present-day life of the industrialised and 6. Dietary factors. Nutritional deficiencies have been
civilised world. regarded as etiologic factors in peptic ulcers e.g. occurrence
Gastric and duodenal ulcers represent two distinct of gastric ulcer in poor socioeconomic strata, higher incidence
diseases as far as their etiology, pathogenesis and clinical of duodenal ulcer in parts of South India. However,
features are concerned. However, morphological findings in malnutrition does not appear to have any causative role in
both are similar and quite diagnostic. The features of gastric peptic ulceration in European countries and the U.S.
TABLE 20.3: Distinguishing Features of Two Major Forms of Peptic Ulcers. 551
Feature Duodenal Ulcer Gastric Ulcer
1. Incidence i) Four times more common than gastric ulcers Less common than duodenal ulcers
ii) Usual age 25-50 years Usually beyond 6th decade
iii) More common in males than in females (4:1) More common in males than in females (3.5:1)
2. Etiology Most commonly as a result of H. pylori infection Gastric colonisation with H. pylori asymptomatic
Other factors—hypersecretion of acid-pepsin, but higher chances of development of duodenal ulcer.
association with alcoholic cirrhosis, tobacco, Disruption of mucus barrier most important factor.
hyperparathyroidism, chronic pancreatitis, Association with gastritis, bile reflux, drugs,
blood group O, genetic factors alcohol, tobacco
3. Pathogenesis i) Mucosal digestion from hyperacidity most Usually normal-to-low acid levels; hyperacidity
significant factor if present is due to high serum gastrin
ii) Protective gastric mucus barrier may be damaged Damage to mucus barrier significant factor
4. Pathologic changes i) Most common in the first part of duodenum Most common along the lesser curvature
and pyloric antrum
ii) Often solitary, 1-2.5 cm in size, round to oval, Grossly similar to duodenal ulcer
punched out
iii) Histologically, composed of 4 layers—necrotic, Histologically, indistinguishable from
superficial exudative, granulation tissue and duodenal ulcer
cicatrisation
5. Complications Commonly haemorrhage, perforation, Perforation, haemorrhage and at times
sometimes obstruction; malignant obstruction; malignant transformation in CHAPTER 20
transformation never occurs less than 1% cases
6. Clinical features i) Pain-food-relief pattern Food-pain pattern
ii) Night pain common No night pain
iii) No vomiting Vomiting common
iv) Melaena more common than haematemesis Haematemesis more common
v) No loss of weight Significant loss of weight
vi) No particular choice of diet Patients choose bland diet devoid of fried foods,
curries etc. The Gastrointestinal Tract
vii) Deep tenderness in the right hypochondrium Deep tenderness in the midline in epigastrium
viii) Marked seasonal variation No seasonal variation
ix) Occurs more commonly in people at greater stress More often in labouring groups
7. Psychological factors. Psychological stress, anxiety, alcoholic cirrhosis, chronic renal failure, hyperpara-
fatigue and ulcer-type personality may exacerbate as well thyroidism, chronic obstructive pulmonary disease, and
as predispose to peptic ulcer disease. chronic pancreatitis.
8. Genetic factors. People with blood group O appear to be
more prone to develop peptic ulcers than those with other PATHOGENESIS. Although the role of various etiologic
blood groups. Genetic influences appear to have greater role factors just described is well known in ulcerogenesis, two
in duodenal ulcers as evidenced by their occurrence in most important factors in peptic ulcer are as under:
families, monozygotic twins and association with HLA-B5 Exposure of mucosa to gastric acid and pepsin secretion.
antigen. Strong etiologic association with H. pylori infection.
9. Hormonal factors. Secretion of certain hormones by There are distinct differences in the pathogenetic
tumours is associated with peptic ulceration e.g. elaboration mechanisms involved in duodenal and gastric ulcers as
of gastrin by islet-cell tumour in Zollinger-Ellison syndrome, under:
endocrine secretions in hyperplasia and adenomas of Duodenal ulcer. There is conclusive evidence to support the
parathyroid glands, adrenal cortex and anterior pituitary. role of high acid-pepsin secretions in the causation of
10. Miscellaneous. Duodenal ulcers have been observed to duodenal ulcers. Besides this, a few other noteworthy
occur in association with various other conditions such as features in the pathogenesis of duodenal ulcers are as follows:
552 1. There is generally hypersecretion of gastric acid into the
fasting stomach at night which takes place under the
influence of vagal stimulation. There is high basal as well as
maximal acid output (BAO and MAO) in response to various
stimuli.
2. Patients of duodenal ulcer have rapid emptying of the
stomach so that the food which normally buffers and
neutralises the gastric acid, passes down into the small
intestine, leaving the duodenal mucosa exposed to the
aggressive action of gastric acid.
3. Helicobacter gastritis caused by H. pylori is seen in 95-100%
cases of duodenal ulcers. The underlying mechanisms are
as under:
i) Gastric mucosal defense is broken by bacterial elaboration
of urease, protease, catalase and phospholipase.
ii) Host factors: H. pylori-infected mucosal epithelium releases Figure 20.11 Distribution of peptic ulcers.
proinflammatory cytokines such as IL-1, IL-6, IL-8 and tumour
necrosis factor-α, all of which incite intense inflammatory duodenal ulcers are coexistent. Vast majority of the peptic
reaction. ulcers are benign. Chronic duodenal ulcer never turns
iii) Bacterial factors: Epithelial injury is also induced by malignant, while chronic gastric ulcer may develop
cytotoxin-associated gene protein (CagA), while vacuolating carcinoma in less than 1% of cases. Malignant gastric ulcers
cytotoxin (VacA) induces elaboration of cytokines. are larger, bowl-shaped with elevated and indurated
mucosa at the margin (Fig. 20.13).
Gastric ulcer. The pathogenesis of gastric ulcer is mainly
explained on the basis of impaired gastric mucosal defenses Microscopically, chronic peptic ulcers have 4 histological
against acid-pepsin secretions. Some other features in the zones. From within outside, these are as under (Fig. 20.14):
pathogenesis of gastric ulcer are as follows: 1. Necrotic zone—lies in the floor of the ulcer and is
composed of fibrinous exudate containing necrotic debris
1. Hyperacidity may occur in gastric ulcer due to increased and a few leucocytes.
SECTION III
serum gastrin levels in response to ingested food in an atonic 2. Superficial exudative zone—lies underneath the necrotic
stomach. zone. The tissue elements here show coagulative necrosis
2 However, many patients of gastric ulcer have low-to- giving eosinophilic, smudgy appearance with nuclear
normal gastric acid levels. Ulcerogenesis in such patients is debris.
explained on the basis of damaging influence of other factors 3. Granulation tissue zone—is seen merging into the necro-
such as gastritis, bile reflux, cigarette smoke etc. tic zone. It is composed of nonspecific inflammatory
3. The normally protective gastric mucus ‘barrier’ against infiltrate and proliferating capillaries.
acid-pepsin is deranged in gastric ulcer. There is depletion 4. Zone of cicatrisation—is seen merging into thick layer
in the quantity as well as quality of gastric mucus. One of of granulation tissue. It is composed of dense fibrocolla-
the mechanisms for its depletion is colonisation of the gastric genic scar tissue over which granulation tissue rests.
mucosa by H. pylori seen in 75-80% patients of gastric ulcer. Thrombosed or sclerotic arteries may cross the ulcer which
Systemic Pathology
on erosion may result in haemorrhage.
MORPHOLOGIC FEATURES. Gross and microscopic
changes in gastric and duodenal ulcers are similar and
quite characteristic. Gastric ulcers are found predominantly
along the lesser curvature in the region of pyloric antrum,
more commonly on the posterior than the anterior wall.
Most duodenal ulcers are found in the first part of the
duodenum, usually immediate post-pyloric, more
commonly on the anterior than the posterior wall.
Uncommon locations include ulcer in the cardia, marginal
ulcer and in the Meckel’s diverticulum (Fig. 20.11).
Grossly, typical peptic ulcers are commonly solitary (80%),
small (1-2.5 cm in diameter), round to oval and
characteristically ‘punched out’. Benign ulcers usually
have flat margins in level with the surrounding mucosa.
The mucosal folds converge towards the ulcer. The ulcers
may vary in depth from being superficial (confined to
mucosa) to deep ulcers (penetrating into the muscular Figure 20.12 Benign chronic peptic ulcer. Partial gastrectomy
layer) (Fig. 20.12). In about 10-20% of cases, gastric and specimen showing a punched out round to oval ulcer on the mucosa,
about 1 cm in diameter (arrow) and penetrating into muscularis layer.
i) On perforation the contents escape into the lesser sac or 553
into the peritoneal cavity, causing acute peritonitis.
ii) Air escapes from the stomach and lies between the liver
and the diaphragm giving the characteristic radiological
appearance of air under the diaphragm.
iii) Subphrenic abscess between the liver and the diaphragm
may develop due to infection.
iv) Perforation may extend to involve the adjacent organs e.g.
the liver and pancreas.
4. Malignant transformation. The dictum ‘cancers ulcerate
but ulcers rarely cancerate’ holds true for most peptic ulcers.
Figure 20.13 Chronic gastric ulcer (A) contrasted with malignant A chronic duodenal ulcer never turns malignant, while less
gastric ulcer (B).
than 1% of chronic gastric ulcers may transform into
carcinoma.
COMPLICATIONS. Acute and subacute peptic ulcers
usually heal without leaving any visible scar. However, CLINICAL FEATURES. Peptic ulcers are remitting and
healing of chronic, larger and deeper ulcers may result in relapsing lesions. Their chronic and recurrent behaviour is
complications. These are as follows: summed up the saying: ‘once a peptic ulcer patient, always a
peptic ulcer patient.’ The two major forms of chronic peptic
1. Obstruction. Development of fibrous scar at or near the ulcers show variations in clinical features which are as
pylorus results in pyloric stenosis. In the case of healed follows:
duodenal ulcer, it causes duodenal stenosis. Healed ulcers
along the lesser curvatures may produce ‘hourglass’ 1. Age. The peak incidence of duodenal ulcer is in 5th
deformity due to fibrosis and contraction. decade while that for gastric ulcer is a decade later.
2. Haemorrhage. Minor bleeding by erosion of small blood 2. People at risk. Duodenal ulcer occurs more commonly
vessels in the base of an ulcer occurs in all the ulcers and can in people faced with more stress and strain of life (e.g. CHAPTER 20
be detected by testing the stool for occult blood. Chronic executives, leaders), while gastric ulcer is seen more often in
blood loss may result in iron deficiency anaemia. Severe labouring groups.
bleeding may cause ‘coffee ground’ vomitus or melaena. A 3. Periodicity. The attacks in gastric ulcers last from 2-6
penetrating chronic ulcer may erode a major artery (e.g. left weeks, with interval of freedom from 1-6 months. The attacks
gastric, gastroduodenal or splenic artery) and cause a massive of duodenal ulcer, are classically worsened by ‘work, worry
and severe hematemesis and sometimes death. and weather.’
3. Perforation. A perforated peptic ulcer is an acute abdo- 4. Pain. In gastric ulcer, epigastric pain occurs immediately
minal emergency. Perforation occurs more commonly in or within 2 hours after food and never occurs at night. In
chronic duodenal ulcers than chronic gastric ulcers. duodenal ulcer, pain is severe, occurs late at night (‘hunger
Following sequelae may result: pain’) and is usually relieved by food. The Gastrointestinal Tract
Figure 20.14 Chronic peptic ulcer. Histologic zones of the ulcer are illustrated in the diagram. The photomicrograph on right shows necrotic
debris, ulceration and inflammation on the mucosal surface.
554 5. Vomiting. Vomiting which relieves the pain is a conspi- TABLE 20.4: Gastric Tumours and Tumour-like Lesions.
cuous feature in patients of gastric ulcer. Duodenal ulcer
patients rarely have vomiting but instead get heart-burn A. TUMOUR-LIKE LESIONS (POLYPS)
(retrosternal pain) and ‘water brash’ (burning fluid into the 1. Hyperplastic (inflammatory) polyps
2. Hamartomatous polyps
mouth).
B. BENIGN TUMOURS
6. Haematemesis and melaena. Haematemesis and 1. Epithelial
melaena occur in gastric ulcers in the ratio of 60:40, while in Adenomas (adenomatous or neoplastic polyps)
duodenal ulcers in the ratio of 40:60. Both may occur together 2. Non-epithelial
more commonly in duodenal ulcer than in gastric ulcer Gastrointestinal spindle cell (stromal) tumours (GIST)
patients. C. MALIGNANT TUMOURS
7. Appetite. The gastric ulcer patients, though have good 1. Epithelial (90%)
appetite but are afraid to eat, while duodenal ulcer patients (i) Adenocarcinoma
have very good appetite. (ii) Others
2. Non-epithelial (2%)
8. Diet. Patients of gastric ulcer commonly get used to a (i) Leiomyosarcoma
bland diet consisting of milk, eggs etc and avoid taking fried (ii) Leiomyoblastoma
foods, curries and heavily spiced foods. In contrast, duodenal (epithelioid leiomyoma)
ulcer patients usually take all kinds of diets. 3. Carcinoid tumour (3%)
4. Lymphoma (4%)
9. Weight. Loss of weight is a common finding in gastric
ulcer patients while patients of duodenal ulcer tend to gain
weight due to frequent ingestion of milk to avoid pain. Microscopically, they are composed of irregular
10. Deep tenderness. Deep tenderness is demonstrable in hyperplastic glands, which may show cystic change. The
both types of peptic ulcers. In the case of gastric ulcer it is in lining epithelium is mostly superficial gastric type but
the midline of the epigastrium, while in the duodenal ulcer antral glands, chief cells and parietal cells may be present.
it is in the right hypochondrium. These lesions do not have cellular atypia and do not have
malignant potential.
HAEMATEMESIS AND MELAENA OF GASTRIC ORIGIN
Hamartomatous Polyps
In continuity with the discussion on peptic ulcers which are
the commonest cause of haematemesis and melaena, it is Hamartomatous polyps are not true neoplasms but are
SECTION III
worthwhile listing various causes of haematemesis of gastric malformations. They are of various types such as gastric
origin (causes of haematemesis of oesophageal origin are polyps of the Peutz-Jeghers syndrome (page 582), juvenile
already given on page 539). polyp, pancreatic heterotopia, heterotopia of Brunner’s
i) Chronic peptic ulcers (gastric as well as duodenal) glands and inflammatory fibroid polyps (eosinophilic
ii) Acute peptic ulcers (stress ulcers) granulomatous polyps).
iii) Multiple gastric and duodenal erosions
iv) Carcinoma of the stomach B. BENIGN TUMOURS
v) Peptic ulcer in Meckel’s diverticulum Adenomas (Adenomatous or Neoplastic Polyps)
vi) Mallory-Weiss syndrome
vii) Anaemias Adenomas, also, referred to as adenomatous or neoplastic
Systemic Pathology
viii) Purpuras polyps, are true benign epithelial neoplasms and are much
ix) Haemophilia. rare in the stomach than in the large intestine. They are also
found more often in the region of pyloric antrum. They are
TUMOURS AND TUMOUR-LIKE LESIONS commonly associated with atrophic gastritis and pernicious
anaemia. Morphologically, adenomatous polyps of the
The various types of tumour-like lesions (polyps) and benign stomach resemble their counterparts in the large bowel and
and malignant tumours of the stomach are given in are described on page 583.
Table 20.4.
Stromal Tumours
A. TUMOUR-LIKE LESIONS (POLYPS)
Stomach may be the site for occurrence of various uncommon
Hyperplastic (Inflammatory) Polyps benign tumours of stromal cell origin e.g. leiomyomas (being
Hyperplastic or inflammatory polyps are regenerative, non- the most common); others are neurofibromas, schwannomas
neoplastic lesions which are the most common type (90%). and lipomas. They are usually firm, circumscribed nodules,
They may be single or multiple and are more often located less than 4 cm in size and appear as submucosal nodules.
in the pyloric antrum. They resemble in gross and microscopic appearance with
their counterparts in other parts of the body.
Grossly, the lesions may be sessile or pedunculated, 1 cm Currently, the term gastrointestinal stromal tumours
or larger in size, smooth and soft. The surface may be (GISTs) is used for a group of uncommon benign tumours
ulcerated or haemorrhagic. composed of spindle cells or stromal cells but lacking the
true phenotypic features of smooth muscle cells, neural cells 555
or Schwann cells. They are uncommon but as compared to
other sites in the GIT, are most common in the stomach. Their
behaviour is generally benign but may be recurrent,
aggressive or even metastasis may occur.
C. MALIGNANT TUMOURS
Gastric Carcinoma
INCIDENCE. Carcinoma of the stomach comprises more
than 90% of all gastric malignancies and is the leading cause
of cancer-related deaths in countries where its incidence is
high. The highest incidence is between 4th to 6th decades of
life and is twice more common in men than in women.
ETIOLOGY. A number of etiologic factors have been
implicated in causation of gastric cancer. These are as under:
1. H. pylori infection. H. pylori infection of the stomach is Figure 20.15 Distribution of gastric carcinoma in the anatomical
an important risk factor for the development of gastric cancer. subdivisions of the stomach. The serial numbers in the figure indicate
the order of frequency of occurrence of gastric cancer.
Epidemiologic studies throughout world have shown that a
seropositivity with H. pylori is associated with 3 to 6 times
higher risk of development of gastric cancer. It may be common in individuals with blood group O). A germ line
mentioned here that similar association of H. pylori infection mutation in E-cadherin gene inherited as a autosomal
exists with gastric lymphomas (MALT type) as well. dominant pattern has been linked to higher incidence of
occult gastric cancer in younger individuals.
2. Dietary factors. Epidemiological studies suggest that die-
tary factors are most significant in the etiology of gastric 6. Pre-malignant changes in the gastric mucosa. There are CHAPTER 20
cancer. The evidences in support of this are multifold: some conditions of gastric mucosa which have increased risk
i) Occurrence of gastric cancer in the region of gastric canal to development of gastric cancer:
(i.e. along the lesser curvature and the pyloric antrum) where i) Hypo- or achlorhydria in atrophic gastritis of gastric
irritating foods exert their maximum effect. mucosa with intestinal metaplasia.
ii) Populations consuming certain foodstuffs have high risk ii) Adenomatous (neoplastic) polyps of the stomach.
of developing gastric cancer e.g. ingestion of smoked foods, iii) Chronic gastric ulcer (ulcer-cancer), and its association
high intake of salt, pickled raw vegetables, high intake of with achlorhydria.
carcinogens as nitrates in foods and drinking water, nitrites iv) Stump carcinoma in patients who have undergone partial
as preservatives for certain meats etc. However, intake of gastrectomy.
green leafy vegetables, citrus fruits and animal fats has been MORPHOLOGIC FEATURES. Gastric carcinoma is most
reported to have protective role in gastric cancer. commonly located in the region of gastric canal (prepyloric The Gastrointestinal Tract
iii) Tobacco smoke, tobacco juice and consumption of alcohol region) formed by lesser curvature, pylorus and antrum.
have all been shown to have carcinogenic effect on gastric Other less common locations are the body, cardia and
mucosa.
fundus (Fig. 20.15).
3. Geographical factors. There are geographic variations Pathogenetically, a sequential evolution of all gastric
in the incidence of gastric cancer. Japan, Chile and Italy have carcinomas from an initial stage of in situ carcinoma
the highest recorded death rate from gastric cancer, while confined to mucosal layers called early gastric carcinoma
the incidence is considerably low in the US, UK and Canada. (EGC) has been found. EGC eventually penetrates the
The higher incidence in certain geographic regions is the muscularis or beyond, resulting in advanced gastric
result of environmental influences as observed from the carcinoma. Accordingly, gastric carcinomas are broadly
finding of incidence of gastric cancer in the next generation classified into 2 main groups:
of Japanese immigrants to the US which is comparable to I. Early gastric carcinoma (EGC).
that of native Americans. II. Advanced gastric carcinoma, which has 5 further major
4. Racial factors. Within the country, different ethnic groups gross subtypes:
may have variations in incidence of gastric cancer e.g. i) Ulcerative carcinoma
incidence is higher in Blacks, American Indians, Chinese in ii) Fungating (Polypoid) carcinoma
Indonesia, North Wales than other parts of Wales. iii) Scirrhous carcinoma (Linitis plastica)
iv) Colloid (Mucoid) carcinoma
5. Genetic factors. Genetic influences have some role in the v) Ulcer-cancer
etiology of gastric cancer. Not more than 4% of patients of In addition to the above classification, gastric
gastric cancer have a family history of this disease.
Individuals with blood group A have higher tendency to carcinomas have been classified, on the basis of extent of
invasion, into 2 groups:
develop gastric cancer (Recall that the peptic ulcer is more
556
Figure 20.16 Classifications of gastric carcinomas. A, Conventional classification, showing correlation of the macroscopic subtypes with the
main histological patterns. B, Classification based on the depth of invasion by the tumour.
I. Expanding (formerly intestinal type) carcinomas that Prognosis of EGC after surgical resection is quite good;
grow laterally by an invasive margin. The tumour cells 5-year survival rate being 93-99%.
are in the form of cohesive clusters. Early gastric carcinoma must be distinguished from
II. Infiltrating (formerly diffuse type) carcinomas have certain related terms as under:
poorly-defined invasive border. The tumour cells are loose Epithelial dysplasia is cellular atypia seen in intestinal
and invade singly or in small group. metaplasia such as in atrophic gastritis and pernicious
These classifications are summarised in Fig. 20.16 and anaemia.
comparative morphology of various types is shown Carcinoma in situ in the stomach is a state of severe
diagrammatically in Fig. 20.18. cellular atypia or dysplasia, without invasion across the
I. EARLY GASTRIC CARCINOMA (EGC) (Fig. basement membrane of the glands.
20.18,A). EGC is the term used to describe cancer limited II. ADVANCED GASTRIC CARCINOMA. When the
to the mucosa and submucosa. The diagnosis of this carcinoma crosses the basement membrane into the
SECTION III
condition has been made possible by extensive work on muscularis propria or beyond, it is referred to as advanced
histogenesis of gastric cancer by Japanese pathologists by gastric carcinoma. Advanced gastric carcinoma has
the use of fibreoptic endoscope and gastrocamera. In following 5 patterns:
Japan, EGC comprises 35% of newly-diagnosed cases of i) Ulcerative carcinoma (Fig. 20.18,B). This is the most
gastric cancer. common pattern. The tumour appears as a flat, infiltrating
Grossly, the lesion of EGC may have 3 patterns—polypoid and ulcerative growth with irregular necrotic base and
(protruded), superficial and ulcerated (Fig. 20.17): raised margin. It is seen more commonly in the region of
Type I : Polypoid type gastric canal (Fig. 20.19,A).
Type IIa : Superficial elevated Histologically, ulcerative carcinomas are poorly-
Type II b : Superficial flat differentiated adenocarcinomas, which invade deeply into
Systemic Pathology
Type II c : Superficial depressed the stomach wall. Tubular and acinar patterns are seen
more commonly (Fig. 20.19, B).
Type III : Ulcerated type ii) Fungating (polypoid) carcinoma (Fig. 20.18,C). The
Histologically, EGC is a typical glandular adeno- second common pattern is a cauliflower growth projecting
carcinoma, usually well-differentiated type. into the lumen, similar to what is commonly seen in the
Figure 20.17 Diagrammatic representation of gross patterns of early gastric carcinoma.
large intestine. It is seen more often in the fundus. The SPREAD. Carcinoma of the stomach may spread by the 557
tumour undergoes necrosis and infection commonly. following routes:
Histologically, fungating or polypoid carcinomas are 1. Direct spread. Direct spread by local extension is the most
well-differentiated adenocarcinomas, commonly papillary common feature of gastric carcinoma. The spread occurs
type. mainly from the loose submucosal layer but eventually
muscularis and serosa are also invaded. After the peritoneal
iii) Scirrhous carcinoma (Linitis plastica) (Fig. 20.18,D).
In this pattern, the stomach wall is thickened due to covering of the stomach has been invaded, transcoelomic
extensive desmoplasia giving the appearance as ‘leather- dissemination may occur in any other part of the peritoneal
bottle stomach’ or ‘linitis plastica’. The involvement may cavity but ovarian masses (one sided or both-sided) occur
be localised to pyloric antrum, or diffuse affecting whole more commonly, referred to as Krukenberg tumours (Chapter
of the stomach from the cardia to pylorus. The lumen of 24). Submucosal spread occurs more often upwards into the
the stomach is reduced. There are no ulcers but rugae are oesophagus due to continuity of the layers of stomach with
prominent (Fig. 20.19,C). those of oesophagus, while the spread downwards into the
Histologically, it may be an adenocarcinoma or signet- duodenum occurs less often due to the presence of pyloric
ring cell carcinoma, extensively infiltrating the stomach sphincter and submucosal Brunner’s glands. The tumour
wall, but due to marked desmoplasia cancer cells may be may directly involve other neighbouring structures and
difficult to find (Fig. 20.19,D). organs like lesser and greater omentum, pancreas, liver,
common bile duct, diaphragm, spleen and transverse colon.
iv) Colloid (Mucoid) carcinoma (Fig. 20.18,E). This 2. Lymphatic spread. Metastases to regional lymph nodes
pattern is usually seen in the fundus. The tumour grows occur early, especially in the scirrhous carcinoma. The groups
like masses having gelatinous appearance due to secretion of lymph nodes involved are along the lesser and greater
of large quantities of mucus. curvature around the cardia and suprapancreatic lymph
Histologically, mucoid carcinoma contains abundant nodes. Involvement of left supraclavicular lymph node,
pools of mucin in which are seen a small number of Virchow or Troisier’s sign, is sometimes the presenting feature
tumour cells, sometimes having signet-ring appearance.
of gastric carcinoma.
v) Ulcer-cancer (Fig. 20.18,F). Development of cancer in 3. Haematogenous spread. Blood spread of gastric CHAPTER 20
chronic gastric ulcer is a rare occurrence (less than 1%). carcinoma may occur to the liver, lungs, brain, bones, kidneys
Majority of ulcer-cancers are malignant lesions from the and adrenals. It occurs more commonly with the poorly-
beginning. For confirmation of cancer in a pre-existing differentiated carcinoma.
gastric ulcer, the characteristic microscopic appearance of The American Joint Committee on Cancer has developed
peptic ulcer should be demonstrable with one portion of TNM staging system for gastric carcinoma based on tumour
the base or the margin of the ulcer showing carcinomatous invasion (T), lymph node involvement (N) and distant
changes. metastasis (M) into earliest stage T N M (intraepithelial
0
Histologically, ulcer-cancers are adenocarcinomas tumour) to most advanced stage T is N 0 M .
without any specific features. The differences between a any any 1
benign and malignant gastric ulcer are summarised in CLINICAL FEATURES. Gastric carcinoma may have diverse
Table 20.5 (also see Fig. 20.13). presentations. The usual clinical features are as under: The Gastrointestinal Tract
i) Persistent abdominal pain
TABLE 20.5: Differences between Benign and Malignant Gastric Ulcers.
Feature Benign Ulcer Malignant Ulcer
1. Age Younger age Older age
2. Sex Markedly common in males Slightly common in males
3. Duration of symptoms Weeks to years Weeks to months
4. Location Commonly lesser curvature of pylorus and antrum Commonly greater curvature of pylorus and antrum
5. Gross features
a) Size Small Large
b) Shape Regular Irregular
c) Mucosal folds Radiating Interrupted
d) Ulcer bed Haemorrhagic Necrotic
6. Barium studies Punched out ulcer Irregular filling defect
7. Acidity Usually normal-to-low May be normal-to-even achlorhydria
8. Therapy Responds well to medical therapy Usually does not respond to medical therapy
558
SECTION III
Systemic Pathology
Figure 20.18 Gastric carcinoma, gross appearance of subtypes and their corresponding dominant histological patterns.
ii) Gastric distension and vomiting Gastric carcinoma remains undiagnosed until late when
iii) Loss of weight (cachexia) the symptoms appear. Therefore, the prognosis is generally
iv) Loss of appetite (anorexia) poor; 5-year survival rate being 5-15% from the time of
v) Anaemia, weakness, malaise. diagnosis of advanced gastric carcinoma. However, 5-year
The most common complication of gastric cancer is survival rate for early gastric carcinoma is far higher
haemorrhage (in the form of haematemesis and/or melaena); (93-99%) and hence the need for early diagnosis of the
others are obstruction, perforation and jaundice. condition.
559
Figure 20.18 contd... Gastric carcinoma, gross appearance of subtypes and their corresponding dominant histological patterns. CHAPTER 20
Other Carcinomas Carcinoid Tumour
Besides the various morphologic patterns of adenocarcinoma Carcinoid tumours are rare in the stomach and are usually
just described, other carcinomas that occur rarely in the non-argentaffin type but argentaffinomas also occur. Their
stomach are: adenosquamous carcinoma, squamous cell behaviour is usually malignant; they are described on
carcinoma and undifferentiated carcinoma, all of which are page 579.
morphologically similar to such tumours elsewhere.
Lymphomas of Gut
Leiomyosarcoma Primary gastrointestinal lymphomas are defined as
lymphomas arising in the gut without any evidence of The Gastrointestinal Tract
Leiomyosarcoma, though rare, is the commonest soft tissue systemic involvement at the time of presentation.
sarcoma, the stomach being the more common site in the Secondary gastrointestinal lymphomas, on the other hand,
gastrointestinal tract. appear in the gut after dissemination from other primary
site.
Grossly, the tumour may be of variable size but is usually
quite large, pedunculated and lobulated mass into the Gastric lymphomas constitute over 50% of all bowel
lumen. lymphomas; other sites being small and large bowel in
Microscopically, leiomyosarcoma is characterised by high decreasing order of frequency. Prognosis of primary gastric
cellularity and presence of mitotic figures. Tumour is lymphoma is better than for intestinal lymphomas. Primary
usually well-differentiated. lymphoma of stomach is the most common malignant gastric
tumour (4%) next to carcinoma.
Clinical manifestations of gastric lymphomas may be
Leiomyoblastoma (Epithelioid Leiomyoma) similar to gastric carcinoma. Age incidence for lymphomas
of the gastrointestinal tract is usually lower than that for
This is a rare tumour, the behaviour of which is intermediate
between clearly benign and malignant tumour. carcinoma (30-40 years as compared to 40-60 years in gastric
carcinoma) and may occur even in childhood. Relationship
with long-standing chronic H. pylori gastritis with lymphoid
Grossly, the tumour is large, circumscribed and projects
into the lumen. hyperplasia has been strongly suggested.
Microscopically, it is characterised by round to polygonal Grossly, gastric lymphomas have 2 types of appearances:
cells with clear perinuclear halos. The number of mitoses 1. Diffusely infiltrating type, producing thickening of the
determines the biological behaviour of the tumour. affected gut wall, obliteration of mucosal folds and
560
SECTION III
Figure 20.19 A, Ulcerative carcinoma stomach. The luminal surface of the stomach in the region of pyloric canal shows an elevated irregular
growth with ulcerated surface and raised margins. B, Malignant cells forming irregular glands with stratification are seen invading the layers of the
Systemic Pathology
stomach wall. C, Linitis plastica. The wall of the stomach in the region of pyloric canal is markedly thickened and fibrotic while the mucosal folds are
lost. D, Microscopy shows characteristic signet ring tumour cells having abundant mucinous cytoplasm positive for mucicarmine (inbox). The
stroma is desmoplastic.
ulcerations. Cut section shows lesions in the mucosa and Tissue). The term pseudolymphoma is sometimes used for
submucosa but in late stage whole thickness of the gut non-invasive stage of MALToma.
wall may be affected.
2. Polypoid type, which produces large protruding mass
into the lumen with ulcerated surface. SMALL INTESTINE
Lymph node involvement may occur in either of the
two patterns. NORMAL STRUCTURE
Microscopically, gastric lymphomas are most often non- Anatomically, the small bowel having a length of 550-650
Hodgkin’s lymphomas of the following types: cm, includes the duodenum, jejunum and ileum and tends
High-grade large cell immunoblastic lymphoma being to become narrower throughout its course.
the most common. Histologically, the small bowel is identified by recognition
Low-grade small lymphocytic well-differentiated B-cell of villi. The wall of the small intestine consists of 4 layers:
lymphoma referred to as MALToma is the next in 1. The serosa is the outer covering of the small bowel which
frequency (arising from Mucosa Associated Lymphoid is complete except over a part of the duodenum.
2. The muscularis propria is composed of 2 layers of smooth The blood supply of the whole of small intestine, except 561
muscle tissue—outer thinner longitudinal and inner thicker the first part of the duodenum, is by the superior mesenteric
circular layer. These muscles are functionally important for artery which supplies blood by mesenteric arterial arcades
peristalsis. Between the two layers of muscle lie ganglionated and the straight arteries.
plexus, myenteric plexus of Auerbach. The main functions of the small intestine are digestion
and absorption so that ultimately nutrients passing into the
3. The submucosa is composed of loose fibrous tissue with
blood vessels and lacteals in it. It contains a gangliated bloodstream are utilised by the cells in metabolism. The
plexus, Meissner’s plexus, having fewer and smaller cells mucosal layer of the small intestine has remarkable capacity
than the Auerbach’s plexus. for regeneration and new lining is laid every 3-4 days.
4. The mucosa consists of glandular epithelium overlying CONGENITAL ANOMALIES
the lamina propria composed of loose connective tissue and
contains phagocytic cells and abundance of lymphoid cells Intestinal Atresia and Stenosis
(Peyer’s patches in the ileum) and plasma cells. It is Intestinal atresia is congenital absence of lumen, most
supported externally by thin layer of smooth muscle fibres, commonly affecting the ileum or duodenum. The proximal
muscularis mucosae. The mucous membrane is thrown into segment has a blind end which is separated from distal
folds or plicae which are more in the jejunum and less in the segment freely, or the two segments are joined by a fibrous
ileum, thus increasing the absorptive surface enormously. cord. The condition must be recognised early and treated
The absorptive surface is further increased by the intestinal surgically, as otherwise it is incompatible with life.
villi. Villi are finger-like or leaf-like projections which contain
3 types of cells: Intestinal stenosis is congenital narrowing of the lumen
i) Simple columnar cells. They perform absorptive function affecting a segment of the small intestine. Intestinal segment
due to the presence of brush border consisting of large above the level of obstruction is dilated and that below it is
number of microvilli. collapsed.
ii) Goblet cells. These are mucus-secreting cells and are
interspersed between the columnar cells. Meckel’s Diverticulum CHAPTER 20
iii) Endocrine cells. These are scattered in the villi as well as Meckel’s diverticulum is the most common congenital
are widely distributed throughout the gastrointestinal tract. anomaly of the gastrointestinal tract, occurring in 2% of
These cells have various synonyms as under: population. It is more common in males. The anomaly is
Kulchitsky cells, after the name of its discoverer. commonly situated on the antimesenteric border of the ileum,
Enterochromaffin cells, due to their resemblance to about 1 meter above the ileocaecal valve. Like other true
chromaffin cells of the adrenal medulla. diverticula, Meckel’s diverticulum is an outpouching
Argentaffin cells, as the intracytoplasmic granules stain containing all the layers of the intestinal wall in their normal
positively with silver salts by reduction reaction (argyrophil orientation (Fig. 20.20). It is almost always lined by small
cells, on the other hand, require the addition of exogenous intestinal type of epithelium; rarely it may contain islands of
reducing substance for staining). gastric mucosa and ectopic pancreatic tissue. Embryologic
Endocrine cells, as these specialised cells are considered origin of Meckel’s diverticulum is from incomplete The Gastrointestinal Tract
to be part of APUD cell system (having common properties obliteration of vitellointestinal duct. (Other anomalies
as Amine content, amine Precursor Uptake and Decarboxy- resulting from the remnants of vitellointestinal duct are
lation). APUD cells are considered to be endodermal in origin, vitelline sinus and vitelline cyst).
while previously they were thought to be neural crest The common complications of Meckel’s diverticulum are
derivative. Other endocrine cells belonging to the APUD cell perforation, haemorrhage and diverticulitis.
system are C-cells of the thyroid, chromaffin cells of the In addition to congenital Meckel’s diverticulum, acquired
adrenal medulla, certain cells of the carotid body, bronchi, diverticula also occur in the small intestine. These are
hypothalamus, pituitary and sympathetic ganglia. commonly multiple (diverticulosis), frequently located on the
Endocrine cells are heavily populated in the proximal mesenteric border, and are sometimes associated with
small bowel as this is the most active site for absorption and malabsorption.
secretory activities. They are sparse in the colon which is
less active site for such functions. Intestinal Malrotation
The duodenum contains distinctively branched Brunner’s Malrotation is a developmental abnormality of the midgut
glands present in the submucosa and going up to muscularis (i.e. the portion of intestine between the duodenojejunal
mucosae. The deeper layer of the mucosa of the small flexure and the middle of transverse colon). Due to failure of
intestine elsewhere contains intestinal glands or crypts of normal rotation of midgut, the following consequences can
Lieberkuhn. They are lined by columnar cells, goblet cells, occur:
endocrine cells and Paneth cells. Paneth cells are normally i) Exomphalos i.e. intestinal eventration at the umbilicus.
exclusively found in the small intestine and occasionally in ii) Misplacement of the caecum, appendix and ascending
the caecum. These cells are characterised by the presence of colon.
supranuclear granules rich in lysozyme. iii) Mobile caecum.
562
Figure 20.20 Meckel’s diverticulum. A, Common location and gross appearance. B, Resected segment of the small intestine shows an
outpouching which on section is seen communicating with the intestinal lumen. The lumen contains necrotic debris.
INTESTINAL OBSTRUCTION Peritoneal Adhesions and Bands
Conditions which interfere with the propulsion of contents Adhesions and bands in the peritoneum composed of fibrous
in the intestine are considered under the heading of intestinal tissue result following healing in peritonitis. Rarely, such
obstruction. The causes of intestinal obstruction can be fibrous adhesions and bands may be without any preceding
classified under the following 3 broad groups: peritoneal inflammation and are of congenital origin. In either
case, peritoneal bands and adhesions result in partial or
1. Mechanical obstruction. It can occur as a result of the complete intestinal obstruction by outside pressure on the
following causes: bowel wall.
i) Internal obstruction (intramural and intraluminal):
SECTION III
Inflammatory strictures (e.g. Crohn’s disease) Hernias
Congenital stenosis, atresia, imperforate anus Hernia is protrusion of portion of a viscus through an
Tumours abnormal opening in the wall of its natural cavity.
Meconium in mucoviscidosis
External hernia is the protrusion of the bowel through a
Roundworms defect or weakness in the peritoneum.
Gallstones, faecoliths, foreign bodies
Ulceration induced by potassium chloride tablets Internal hernia is the term applied for herniation that
prescribed to counter hypokalaemia. does not present on the external surface.
Two major factors involved in the formation of a hernia
ii) External compression: are as under:
Peritoneal adhesions and bands i) Local weakness which may be congenital e.g. at the
Systemic Pathology
Strangulated hernias umbilicus, inguinal and femoral canals, and in surgical scars
Intussusception called ‘incisional hernia’.
Volvulus ii) Increased intra-abdominal pressure that is produced by
Intra-abdominal tumour. coughing, straining and exertion.
2. Neurogenic obstruction. It occurs due to paralytic ileus Inguinal hernias are more common, followed in
i.e. paralysis of muscularis of the intestine as a result of shock decreasing frequency, by femoral and umbilical hernias.
after abdominal operation or by acute peritonitis. Inguinal hernias may be of 2 types:
3. Vascular obstruction. Obstruction of the superior mesen- Direct when hernia passes medial to the inferior
teric artery or its branches may result in infarction causing epigastric artery and it appears through the external
paralysis. The causes are as under: abdominal ring.
Thrombosis Indirect when it follows the inguinal canal lateral to the
Embolism inferior epigastric artery.
Accidental ligation. When the contents of hernia such as loop of intestine can
Out of the various causes listed above, conditions be returned to the abdominal cavity, it is called reducible.
producing external compression on the bowel wall are the When it is not possible to reduce hernia due to large contents
most common causes of intestinal obstruction (80%). Some or due to adhesions in the hernial sac, it is referred to as
of these are described below. irreducible.
as ischaemic bowel disease. In either case, the cause of 563
ischaemia is compromised mesenteric circulation, while
ischaemic effect is less likely to occur in the stomach,
duodenum and rectum due to abundant collateral blood
supply.
Depending upon the extent and severity of ischaemia, 3
patterns of pathologic lesions can occur (Fig. 20.22):
1. Transmural infarction, characterised by full thickness
involvement i.e. transmural ischaemic necrosis and gangrene
of the bowel.
2 Mural infarction, characterised by haemorrhagic gastro-
enteropathy (haemorrhage and necrosis). The ischaemic
effect in mural infarction is limited to mucosa, submucosa
and superficial muscularis, while mucosal infarction is
confined to mucosal layers superficial to muscularis
mucosae.
Figure 20.21 Ileocaecal intussusception. 3. Ischaemic colitis, due to chronic colonic ischaemia causing
fibrotic narrowing of the affected bowel.
When the blood flow in the hernial sac is obstructed, it These pathologic patterns are described below:
results in strangulated hernia. Obstruction to the venous
drainage and arterial supply may result in infarction or Transmural Infarction
gangrene of the affected loop of intestine. The gross and Ischaemic necrosis of the full-thickness of the bowel wall is
microscopic appearance of strangulated intestine is the same more common in the small intestine than the large intestine.
as that of infarction of intestine.
ETIOPATHOGENESIS. The common causes of transmural CHAPTER 20
Intussusception infarction of small bowel are as under:
i) Mesenteric arterial thrombosis such as due to the following:
Intussusception is the telescoping of a segment of intestine
into the segment below due to peristalsis. The telescoped Atherosclerosis (most common)
segment is called the intussusceptum and lower receiving Aortic aneurysm
segment is called the intussuscipiens. The condition occurs Vasospasm
more commonly in infants and young children, more often Fibromuscular hyperplasia
in the ileocaecal region when the portion of ileum invaginates Invasion by the tumour
into the ascending colon without affecting the position of Use of oral contraceptives
the ileocaecal valve (Fig. 20.21). Less common forms are ileo- Arteritis of various types
ileal and colo-colic intussusception. ii) Mesenteric arterial embolism arising from the following
In children, the cause is usually not known though causes: The Gastrointestinal Tract
enlargement of the lymphoid tissue in the terminal ileum Mural thrombi in the heart
has been suggested by some. In the case of adults, the usual Endocarditis (infective and nonbacterial thrombotic)
causes are foreign bodies and tumours.
The main complications of intussusception are intestinal Atherosclerotic plaques
obstruction, infarction, gangrene, perforation and peritonitis. Atrial myxoma
iii) Mesenteric venous occlusion is less common cause of full-
Volvulus thickness infarction of the bowel. The causes are as under:
Volvulus is the twisting of loop of intestine upon itself
through 180° or more. This leads to obstruction of the
intestine as well as cutting off of the blood supply to the
affected loop. The usual causes are bands and adhesions
(congenital or acquired) and long mesenteric attachment. The
condition is more common in the sigmoid colon than the
small bowel.
ISCHAEMIC BOWEL DISEASE
(ISCHAEMIC ENTEROCOLITIS)
Ischaemic lesions of the gastrointestinal tract may occur in
the small intestine and/or colon; the latter is called ischaemic Figure 20.22 Schematic diagram to show the three types of
colitis or ischaemic enterocolitis and is commonly referred to ischaemic bowel disease depending upon the extent of involvement.
564
Figure 20.23 Haemorrhagic infarct of the small intestine. The Figure 20.24 Infarct small intestine, microscopic appearance. The
infarcted area is swollen, dark in colour and coated with fibrinous exudate. mucosa in the infarcted area shows coagulative necrosis and submucosal
A sharp line of demarcation separates infarcted area from the normal haemorrhages: muscularis is also partly affected. Inflammatory cell
bowel (arrow). infiltration is marked at the line of demarcation between the infarcted
and normal bowel.
Intestinal sepsis e.g. appendicitis
Portal venous thrombosis in cirrhosis of the liver Mural and Mucosal Infarction (Haemorrhagic
Tumour invasion Gastroenteropathy, Membranous Colitis)
Use of oral contraceptives Mural and mucosal infarctions are limited to superficial
iv) Miscellaneous causes: layers of the bowel wall, sparing the deeper layer of the
SECTION III
Strangulated hernia muscularis and the serosa. The condition is also referred to
Torsion as haemorrhagic gastroenteropathy, and in the case of colon as
Fibrous bands and adhesions. membranous colitis.
ETIOPATHOGENESIS. Haemorrhagic gastroenteropathy
MORPHOLOGIC FEATURES. Grossly, irrespective of results from conditions causing non-occlusive hypoperfusion
the underlying etiology, infarction of the bowel is (compared from transmural infarction which occurs from
haemorrhagic (red) type (page 126). A varying length of occlusive causes). These are as under:
the small bowel may be affected. In the case of colonic Shock
infarction, the distribution area of superior and inferior Cardiac failure
mesenteric arteries (i.e. splenic flexure) is more commonly Infections
involved. The affected areas become dark purple and
Systemic Pathology
markedly congested and the peritoneal surface is coated Intake of drugs causing vasoconstriction e.g. digitalis,
with fibrinous exudate. The wall is thickened, oedematous norepinephrine.
and haemorrhagic. The lumen is dilated and contains
blood and mucus. In arterial occlusion, there is sharp line MORPHOLOGIC FEATURES. Grossly, the lesions affect
of demarcation between the infarcted bowel and the variable length of the bowel. The affected segment of the
normal intestine, whereas in venous occlusion the bowel is red or purple but without haemorrhage and
infarcted area merges imperceptibly into the normal bowel exudation on the serosal surface. The mucosa is
(Fig. 20.23). oedematous at places, sloughed and ulcerated at other
Microscopically, there is coagulative necrosis and ulcera- places. The lumen contains haemorrhagic fluid.
tion of the mucosa and there are extensive submucosal Microscopically, there is patchy ischaemic necrosis of
haemorrhages. The muscularis is less severely affected by mucosa, vascular congestion, haemorrhages and
ischaemia. Subsequently, inflammatory cell infiltration inflammatory cell infiltrate. The changes may extend into
and secondary infection occur, leading to gangrene of the superficial muscularis but deeper layer of muscularis and
bowel (Fig. 20.24). serosa are spared. Secondary bacterial infection may
supervene resulting in pseudomembranous enterocolitis.
The condition is clinically characterised by ‘abdominal
angina’ in which the patient has acute abdominal pain, Clinically, as in transmural infarction, the features of
nausea, vomiting, and sometimes diarrhoea. The disease is abdominal pain, nausea, vomiting and diarrhoea are present,
rapidly fatal, with 50-70% mortality rate. but the changes are reversible and curable. With adequate
therapy, normal morphology is completely restored in In healed cases, stricture formation, malabsorption and 565
superficial lesions, while deeper lesions may heal by fibrosis short bowel syndrome are the usual complications.
leading to stricture formation.
INFLAMMATORY BOWEL DISEASE
Ischaemic Colitis (CROHN’S DISEASE AND ULCERATIVE COLITIS)
Although this condition affects primarily colon in the region DEFINITION. The term ‘inflammatory bowel disease (IBD)’
of splenic flexure, it is described here due to its apparent is commonly used to include 2 idiopathic bowel diseases
pathogenetic relationship with ischaemic injury. Ischaemic having many similarities but the conditions usually have
colitis is characterised by chronic segmental colonic distinctive morphological appearance. These 2 conditions are
ischaemia followed by chronic inflammation and healing by Crohn’s disease (regional enteritis) and ulcerative colitis:
fibrosis and scarring causing obstruction (ischaemic
stricture). 1. Crohn’s disease or Regional enteritis is an idiopathic
chronic ulcerative IBD, characterised by transmural, non-
Grossly, most frequently affected site is the splenic flexure; caseating granulomatous inflammation, affecting most
other site is rectum. Ischaemic colitis passes through 3 commonly the segment of terminal ileum and/or colon,
stages: infarct, transient ischaemia and ischaemic stricture. though any part of the gastrointestinal tract may be involved.
However, the surgical submitted specimens generally are 2. Ulcerative colitis is an idiopathic form of acute and
of the ischaemic stricture. External surface of the affected chronic ulcero-inflammatory colitis affecting chiefly the
area is fusiform or saccular. On cut section, there are mucosa and submucosa of the rectum and descending colon,
patchy, segmental and longitudinal mucosal ulcers. Thus, though sometimes it may involve the entire length of the
the gross appearance can be confused with either of the large bowel.
two types of inflammatory bowel disease. Both these disorders primarily affect the bowel but may
Microscopically, the ulcerated areas of the mucosa show have systemic involvement in the form of polyarthritis,
granulation tissue. The submucosa is characteristically uveitis, ankylosing spondylitis, skin lesions and hepatic
thickened due to inflammation and fibrosis. The involvement. Both diseases can occur at any age but are more
muscularis may also show inflammatory changes and frequent in 2nd and 3rd decades of life. Females are affected CHAPTER 20
patchy replacement by fibrosis. The blood vessels may slightly more often.
show atheromatous emboli, organising thrombi and ETIOPATHOGENESIS. The exact etiology of IBD remains
endarteritis obliterans.
unknown. However, multiple factors are implicated which
can be considered under the following 3 groups:
NECROTISING ENTEROCOLITIS
1. Genetic factors. Genetic factors are implicated in the
Necrotising enterocolitis is an acute inflammation of the etiopathogenesis of IBD is supported by the following
terminal ileum and ascending colon, occurring primarily in evidences:
premature and low-birth-weight infants within the first week i) There is about 3 to 20 times higher incidence of occurrence
of life and less commonly in full-term infants. of IBD in first-degree relatives. This is due to genetic defect
ETIOLOGY. The condition has been considered as a variant causing diminished epithelial barrier function. The Gastrointestinal Tract
of the spectrum of ischaemic bowel disease. Important factors ii) Overall, there is approximately 50% chance of develop-
in the etiology of this disorder, thus, are as follows: ment of IBD (Crohn’s disease about 60% concordance,
1. Ischaemia ulcerative colitis about 6% concordance) in monozygotic
2. Hypoxia/anoxia of the bowel due to bypassing of blood twins.
from the affected area iii) Although no specific and consistent gene association with
3. Bacterial infection and endotoxins IBD has been seen, genome wide search has revealed that
4. Establishment of feeding disease-predisposing loci are present in chromosomes 16q,
5. Infants fed on commercial formulae than breast-fed, 12p, 6p, 14q and 5q. In particular, CARD15 (caspase-
implying the role of immunoprotective factors. associated recruitment domain containing protein 15) on
chromosome 16q is expressed by several cells in the intestinal
MORPHOLOGIC FEATURES. Grossly, the affected mocosa which in mutated form results in loss of its function
segment of the bowel is dilated, necrotic, haemorrhagic and renders an individual about 50-times higher risk to
and friable. Bowel wall may contain bubbles of air develop Crohn’s disease.
(pneumatosis intestinalis). iv) HLA studies show that ulcerative colitis is more common
Microscopically, the changes are variable depending upon in HLA-DRB1-alleles while Crohn’s disease is more common
the stage. Initial changes are confined to mucosa and show in HLA-DR7 and DQ4 alleles.
oedema, haemorrhage and coagulative necrosis. A 2. Immunologic factors. Defective immunologic regulation
pseudomembrane composed of necrotic epithelium, fibrin in IBD has been shown to play significant role in the
and inflammatory cells may develop. As the ischaemic pathogenesis of IBD:
process extends to the subjacent layers, muscle layer is i) Defective regulation of immune suppression. In a normal
also involved and may lead to perforation and peritonitis. individual, there is lack of immune responsiveness to dietary
566 antigens and commensal flora in the intestinal lumen. The peripheral blood. These cells either activate other
mechanism responsible for this is by activation of CD4+ T inflammatory cells (e.g. macrophages and B cells), or recruit
cells secreting cytokines inhibitory to inflammation (IL-10, more inflammatory cells by stimulation of homing receptor
TGF-β) which suppress inflammation in the gut wall. In IBD, on leucocytes and vascular endothelium. There are two main
this immune mechanism of suppression of inflammation is types of CD4+ T cells in IBD:
defective and thus results in uncontrolled inflammation. TH1 cells secrete proinflammatory cytokines IFN-γ and
ii) Transgenic mouse experimental model studies. Gene ‘knock TNF which induce transmural granulomatous inflammation
out’ studies on colitis in mice have revealed that multiple seen in Crohn’s disease. IL-12 initiates TH1 cytokine
immune abnormalities may be responsible for IBD as under: pathway.
a) Deletion of inflammation inhibitory cytokines (e.g. IL-2, TH2 cells secrete IL-4, IL-5 and IL-13 which induce
IL-10, TGF-β) or their receptors. superficial mucosal inflammation characteristically seen in
ulcerative colitis.
b) Deletion of molecules responsible for T cell recognition
(e.g. T cell antigen receptors, MHC class II). 3. Exogenous factors. In addition to role of genetic factors
and deranged T-cell mediated immunity, a role for several
c) Interference with normal epithelial barrier function in the exogenous and environmental factors has been assigned:
intestine (e.g. blocking N-cadherin, deletion of multi-drug i) Microbial factors: At different times, role of a variety of
resistance MDR gene). microbes in initiation of inflammatory response by the body
iii) Type of inflammatory cells. In both types of IBD, activated has been suspected. Accordingly, several microorganism
CD4+ T cells are present in the lamina propria and in the species (bacteria, viruses, protozoa and fungi) have been
TABLE 20.6: Distinguishing Features of Crohn’s Disease and Ulcerative Colitis.
Feature Crohn’s Disease Ulcerative Colitis
A. MACROSCOPIC FEATURES
1. Distribution Segmental with skip areas Continuous without skip areas
2. Location Commonly terminal ileum and/or Commonly rectum, sigmoid colon and
ascending colon extending upwards
3. Extent Usually involves the entire thickness Usually superficial, confined to mucosal
SECTION III
of the affected segment of bowel wall layers
4. Ulcers Serpiginous ulcers, may develop Superficial mucosal ulcers without fissures
into deep fissures
5. Pseudopolyps Rarely seen Commonly present
6. Fibrosis Common Rare
7. Shortening Due to fibrosis Due to contraction of muscularis
B. MICROSCOPIC FEATURES
1. Depth of inflammation Typically transmural Mucosal and submucosal
2. Type of inflammation Non-caseating granulomas and infiltrate Crypt abscess and non-specific acute and
of mononuclear cells (lymphocytes, chronic inflammatory cells (lymphocytes,
plasma cells and macrophages) plasma cells, neutrophils, eosinophils, mast
Systemic Pathology
cells)
3. Mucosa Patchy ulceration Haemorrhagic mucosa with ulceration
4. Submucosa Widened due to oedema and lymphoid Normal or reduced in width
aggregates
5. Muscularis Infiltrated by inflammatory cells Usually spared except in cases of toxic
megacolon
6. Fibrosis Present Usually absent
C. IMMUNOLOGIC FEATURES
1. Lymphocyte type CD4+ TH1 CD4+ TH2
2. Cytokines INF-γ, TNF, IL-12 TGF-β, IL-4, IL-5, IL-13
3. ANCA-P antibodies Positive in a few Positive in most
D. COMPLICATIONS
1. Fistula formation Internal and external fistulae in 10% cases Extremely rare
2. Malignant changes Rare May occur infrequently in disease of more than
10 years’ duration
3. Type of malignancy Lymphoma more than carcinoma Carcinoma more than lymphoma
4. Fibrous strictures Common Never
567
Figure 20.25 Crohn’s disease of the terminal ileum. A, The lesions
are characteristically segmental with intervening uninvolved ‘skip areas’.
The bowel wall is thickened and the lumen narrowed, giving hose-pipe
appearance. Serpiginous ulcers, some deep fissures and swollen
intervening surviving mucosa giving ‘cobblestone appearance’, are present.
B, The specimen of small intestine is shown in longitudinal section along
with a segment in cross section. External surface shows increased
mesenteric fat, thickened wall and narrow lumen. Luminal surface of
longitudinal cut section shows segment of thickened wall with narrow lumen
which is better appreciated in cross section (arrow) while intervening areas
of the bowel are uninvolved or skipped.
suspect but without definite evidence: Mycobacterium commonly 15-25 cm of the terminal ileum which may extend CHAPTER 20
paratuberculosis, Salmonella, Shigella, Helicobacter, Clostridia, into the caecum and sometimes into the ascending colon:
bacteroides, Escherichia, Measles virus etc.
ii) Psychosocial factors: It has been observed that individuals Grossly, characteristic feature is the multiple, well-
who are unduly sensitive, dependent on others and unable demarcated segmental bowel involvement with
to express themselves, or some major life events such as intervening uninvolved ‘skip areas’. The wall of the
illness or death in the family, divorce, interpersonal conflicts affected bowel segment is thick and hard, resembling a
etc, suffer from irritable colon or have exacerbation of ‘hose pipe’. Serosa may be studded with minute granu-
symptoms. Patients of IBD in the West have been found to lomas. The lumen of the affected segment is markedly
suffer from greater functional impairment than the general narrowed. The mucosa shows ‘serpiginous ulcers’, while
population, as assessed by sickness impact profile which is a intervening surviving mucosa is swollen giving The Gastrointestinal Tract
measure of overall psychological and physical functioning. ‘cobblestone appearance’. There may be deep fissuring
iii) Smoking: Role of smoking in causation of Crohn’s disease into the bowel wall (Fig. 20.25).
has been reported. Histologically, the characteristic features are as follows
iv) Oral contraceptives: An increased risk to develop Crohn’s (Fig. 20.26):
disease with long-term use of oral contraceptives has been 1. Transmural inflammatory cell infiltrate consisting of
found in some studies but there is no such increased risk for chronic inflammatory cells (lymphocytes, plasma cells and
ulcerative colitis. macrophages) is the classical microscopic feature.
Consensus hypothesis in pathogenesis of IBD combines 2. Non-caseating, sarcoid-like granulomas are present in all
the role of above three major groups of etiologic factors: i.e. the layers of the affected bowel wall in 60% of cases and
in a genetically predisposed individual, the effects of exogenous may even be seen in the regional lymph nodes.
and endogenous host factors result in dysregulation of 3. There is patchy ulceration of the mucosa which may take
mucosal immune function, which gets further modified by the form of deep fissures, accompanied by inflammatory
certain environmental factors. infiltrate of lymphocytes and plasma cells.
4. There is widening of the submucosa due to oedema and
MORPHOLOGIC FEATURES. The morphologic features foci of lymphoid aggregates.
of Crohn’s disease and ulcerative colitis are sufficiently 5. In more chronic cases, fibrosis becomes increasingly
distinctive so as to be classified separately. These features prominent in all the layers disrupting muscular layer.
are presented below; the distinguishing features of the
two conditions are summarised in Table 20.6. ULCERATIVE COLITIS. Classically, ulcerative colitis
begins in the rectum, and in continuity extends upwards into
CROHN’S DISEASE. Crohn’s disease may involve any the sigmoid colon, descending colon, transverse colon, and
portion of the gastrointestinal tract but affects most sometimes may involve the entire colon. The colonic contents
568
Figure 20.26 Crohn’s disease of the ileum. The histological features present are: transmural chronic inflammatory cell infiltration, deep fissures
into the bowel wall, submucosal widening due to oedema, some prominent lymphoid follicles and a few non-caseating epithelioid cell granulomas
in the bowel wall.
may rarely backflow into the terminal ileum in continuity, affected colon with loss of normal haustral folds giving
causing ‘back-wash ileitis’ in about 10% of cases. ‘garden-hose appearance’ (Fig. 20.27).
Histologically, ulcerative colitis because of remission and
Grossly, the characteristic feature is the continuous exacerbations, is characterised by alternating ‘active
involvement of the rectum and colon without any uninvol- disease process’ and ‘resolving colitis.’ The changes in the
ved skip areas compared to Crohn’s disease. The ‘active disease process’ are as under (Fig. 20.28):
appearance of colon may vary depending upon the stage 1. Crypt distortion, cryptitis and focal accumulations of
and intensity of the disease because of remissions and neutrophils forming crypt abscesses.
SECTION III
exacerbations. Mucosa shows linear and superficial ulcers, 2. Marked congestion, dilatation and haemorrhages from
usually not penetrating the muscular layer. The mucosal capillaries.
intervening intact mucosa may form inflammatory 3. Superficial mucosal ulcerations, usually not penetrating
‘pseudopolyps.’ The muscle layer is thickened due to into the muscle coat, except in severe cases, and is
contraction, producing shortening and narrowing of the accompanied by nonspecific inflammatory cell infiltrate
Systemic Pathology
Figure 20.27 Ulcerative colitis. Continuous involvement of the
rectum and colon without any uninvolved skip areas. The ulcers are
superficial with intervening inflammatory pseudopolyps. The lumen is
narrow and the haustral folds are lost giving ‘garden-hose appearance’.
569
Figure 20.28 Ulcerative colitis in active phase. The microscopic features seen are superficial ulcerations, with mucosal infiltration by inflammatory
cells and a ‘crypt abscess’.
of lymphocytes, plasma cells, neutrophils, some 2. Perianal fistula formation may occur rarely.
eosinophils and mast cells in the lamina propria. 3. Carcinoma may develop in long-standing cases of CHAPTER 20
4. Goblet cells are markedly diminished in cases of active ulcerative colitis of more than 10 years duration.
disease. 4. Stricture formation almost never occurs in ulcerative colitis.
5. Areas of mucosal regeneration and mucodepletion of lin-
ing cells. OTHER INFLAMMATORY LESIONS OF THE BOWEL
6. In long-standing cases, epithelial cytologic atypia Besides IBD, a variety of other acute and chronic inflam-
ranging from mild to marked dysplasia and sometimes matory conditions affect small bowel (enteritis), large bowel
developing into carcinoma in situ and frank adeno- (colitis), or both (enterocolitis); the last named being more
carcinoma.
common. Hence, all these conditions involving small bowel
and/or large bowel are described together here for better
COMPLICATIONS. Complications of Crohn’s disease and correlation of features.
ulcerative colitis are as under: The various forms of inflammations of the bowel after The Gastrointestinal Tract
excluding IBD can be categorised broadly into ‘infective
Crohn’s disease: enterocolitis’ and ‘pseudomembranous enterocolitis.’
1. Malabsorption due to impaired absorption of fat, vitamin
B , proteins and electrolytes from the diseased small bowel. INFECTIVE ENTEROCOLITIS
12
2. Fistula formation may occur in long-standing cases. These
may be internal fistulae between the loops of the intestine, These are a group of acute and chronic inflammatory lesions
or external fistulae such as enterocutaneous, rectal and anal of small intestine and/or colon caused by microorganisms
fistulae. (bacteria, viruses, fungi, protozoa and helminths). All these
3. Stricture formation may occur in chronic cases due to are characterised by diarrhoeal syndromes. Pathogenetically
speaking, these microorganisms can cause enterocolitis by 2
extensive fibrosis in the affected bowel wall. mechanisms—by enteroinvasive bacteria producing ulcerative
4. Development of malignancy in the small intestine as a late lesions, and by enterotoxin-producing bacteria resulting in non-
complication of Crohn’s disease is rarer than that in ulcerative ulcerative lesions.
colitis, but lymphoma may develop more often in Crohn’s A list of common microorganisms producing enterocolitis
disease than adenocarcinoma (seen in some long-standing is presented in Table 20.7. A few important forms are
cases of ulcerative colitis).
described below.
Ulcerative colitis: Intestinal Tuberculosis
1. Toxic megacolon (Fulminant colitis) is the acute fulminating
colitis in which the affected colon is thin-walled and dilated Intestinal tuberculosis can occur in 3 forms—primary,
and is prone to perforation and faecal peritonitis. There is secondary and hyperplastic caecal tuberculosis.
deep penetration of the inflammatory cell infiltrate into 1. PRIMARY INTESTINAL TUBERCULOSIS. Though an
muscle layer which is disrupted. uncommon disease in the developed countries of the world,
570
TABLE 20.7: Micro-organisms Causing Infective Microscopically, in the initial stage, there is primary
Enterocolitis. complex or Ghon’s focus in the intestinal mucosa as occurs
A. BACTERIAL ENTEROCOLITIS elsewhere in primary tuberculous infection (page 153).
Subsequently, the mesenteric lymph nodes are affected
1. Entero-invasive bacteria which show typical tuberculous granulomatous
(i) Tuberculosis inflammatory reaction with caseation necrosis.
(ii) Salmonella Tuberculous peritonitis may occur due to spread of the
(iii) Campylobacter jejuni infection.
(iv) Shigella
(v) Escherichia coli 2. SECONDARY INTESTINAL TUBERCULOSIS. Self-
(vi) Yersinia enterocolitica
swallowing of sputum in patients with active pulmonary
2. Enterotoxin-producing bacteria tuberculosis may cause secondary intestinal tuberculosis,
(i) Vibrio cholerae most commonly in the terminal ileum and rarely in the colon.
B. VIRAL ENTEROCOLITIS
Grossly, the intestinal lesions are prominent than the
C. FUNGAL ENTEROCOLITIS
lesions in regional lymph nodes as in secondary
(i) Candidiasis pulmonary tuberculosis (Fig. 20.29,B). The lesions begin
(ii) Mucormycosis
in the Peyer’s patches or the lymphoid follicles with
D. PROTOZOAL AND METAZOAL INFESTATIONS formation of small ulcers that spread through the
(i) Giardia lamblia lymphatics to form large ulcers which are transverse to the
(ii) Entamoeba histolytica long axis of the bowel, (c.f. typhoid ulcers of small intestine,
(iii) Balantidium coli described below). These ulcers may be coated with caseous
(iv) Taenia solium material. Serosa may be studded with visible tubercles.
(v) Ascaris lumbricoides In advanced cases, transverse fibrous strictures and
(vi) Ancylostoma duodenale intestinal obstruction are seen (Fig. 20.30,A, B).
(vii) Strongyloides stercoralis Histologically, the tuberculous lesions in the intestine are
similar to those observed elsewhere i.e. presence of
primary tuberculosis of the ileocaecal region is quite common tubercles. Mucosa and submucosa show ulceration and
SECTION III
in developing countries including India. In the pre- the muscularis may be replaced by variable degree of
pasteurisation era, it used to occur by ingestion of unpas- fibrosis (Fig. 20.30,C). Tuberculous peritonitis may be
teurised cow’s milk infected with Mycobacterium bovis. But observed.
now-a-days due to control of tuberculosis in cattle and
pasteurisation of milk, virtually all cases of intestinal 3. HYPERPLASTIC CAECAL TUBERCULOSIS. This is a
tuberculosis are caused by M. tuberculosis. The predominant variant of occurring secondary to pulmonary tuberculosis.
changes are in the mesenteric lymph nodes without any
significant intestinal lesion. Grossly, the caecum and/or ascending colon are thick-
walled with mucosal ulceration. Clinically, the lesion is
Grossly, the affected lymph nodes are enlarged, matted palpable and may be mistaken for carcinoma
and caseous (tabes mesenterica). Eventually, there is (Fig. 20.29,C).
healing by fibrosis and calcification (Fig. 20.29,A).
Systemic Pathology
Figure 20.29 Intestinal tuberculosis, three patterns.
571
Figure 20.30 Intestinal tuberculosis. A, The external surface of small intestine shows stricture and a lymph node in section having caseation
necrosis (arrows). B, The lumen shows characteristic transverse ulcers and two strictures (arrow). The wall of intestine in the area of narrowed
lumen is thickened. C, Microscopy of intestine shows caseating epithelioid cell granulomas in the intestinal wall.
Microscopically, the presence of caseating tubercles and colon. Peyer’s patches show oval typhoid ulcers with
distinguishes the condition from Crohn’s disease in which their long axis along the length of the bowel, (c.f. tuberculous CHAPTER 20
granulomas are non-caseating. Besides, bacteriological ulcers of small intestine, described above). The base of
evidence by culture or animal inoculation and Mantoux the ulcers is black due to sloughed mucosa. The margins
test are helpful in differential diagnosis of the two of the ulcers are slightly raised due to inflammatory
conditions. oedema and cellular proliferation. There is never signifi-
cant fibrosis and hence fibrous stenosis seldom occurs in
Enteric Fever healed typhoid lesions. The regional lymph nodes are
invariably enlarged (Fig. 20.31,A).
The term enteric fever is used to describe acute infection Microscopically, there is hyperaemia, oedema and cellular
caused by Salmonella typhi (typhoid fever) or Salmonella proliferation consisting of phagocytic histiocytes (showing
paratyphi (paratyphoid fever). Besides these 2 salmonellae,
Salmonella typhimurium causes food poisoning. characteristic erythrophagocytosis), lymphocytes and
plasma cells. Though enteric fever is an example of acute The Gastrointestinal Tract
PATHOGENESIS. The typhoid bacilli are ingested through inflammation, neutrophils are invariably absent from the
contaminated food or water. During the initial asymptomatic cellular infiltrate and this is reflected in the leucopenia
incubation period of about 2 weeks, the bacilli invade the with neutropenia and relative lymphocytosis in the
lymphoid follicles and Peyer’s patches of the small intestine peripheral blood (Fig. 20.31,B).
and proliferate. Following this, the bacilli invade the blood- The main complications of the intestinal lesions of
stream causing bacteraemia, and the characteristic clinical typhoid are perforation of the ulcers and haemorrhage.
features of the disease like continuous rise in temperature 2. OTHER LESIONS. Besides the intestinal involvement,
and ‘rose spots’ on the skin are observed. Immunological various other organs and tissues showing pathological
reactions (Widal’s test) begin after about 10 days and peak changes in enteric fever are as under:
titres are seen by the end of the third week. Eventually, the
bacilli are localised in the intestinal lymphoid tissue i) Mesenteric lymph nodes—haemorrhagic lymph-
(producing typhoid intestinal lesions), in the mesenteric adenitis.
lymph nodes (leading to haemorrhagic lymphadenitis), in ii) Liver—foci of parenchymal necrosis.
the liver (causing foci of parenchymal necrosis), in the gall iii) Gallbladder—typhoid cholecystitis.
bladder (producing typhoid cholecystitis), and in the spleen iv) Spleen—splenomegaly with reactive hyperplasia.
(resulting in splenic reactive hyperplasia). v) Kidneys—nephritis.
vi) Abdominal muscles—Zenker’s degeneration.
MORPHOLOGIC FEATURES. The lesions are observed vii) Joints—arthritis.
in the intestines as well as in other organs.
viii) Bones—osteitis.
1. INTESTINAL LESIONS. Grossly, terminal ileum is ix) Meninges—Meningitis.
affected most often, but lesions may be seen in the jejunum x) Testis—Orchitis.
572 described below. Staphylococcal food poisoning occurs due
to liberation of enterotoxins by the bacteria.
2. Clostridial food poisoning. Infection with anaerobic
organisms Clostridium welchii, following consumption of
contaminated meat results in acute food poisoning (page 181).
The illness occurs both by bacterial invasion as well as by
toxins.
3. Botulism. This is a severe form of paralysing illness
caused by ingestion of organism, Clostridium botulinum,
which produces neurotoxin.
4. Salmonella food poisoning (Salmonellosis). This is an
infection (and not caused by toxins) occurring due to food
contaminated by S. typhimurium or S. enteritidis. The condition
manifests with fever, vomiting, and diarrhoea. Death may
result from depletion of water and electrolytes.
Dysenteries
The term ‘dysentery’ is used to mean diarrhoea with
abdominal cramps, tenesmus and passage of mucus in the
stools, from any cause. There are 2 main forms of dysen-
teries—bacillary and amoebic.
1. BACILLARY DYSENTERY. Bacillary dysentery is the
term used for infection by shigella species: S. dysenteriae, S.
flexneri, S. boydii and S. sonnei. Infection occurs by foeco-oral
route and is seen with poor personal hygiene, in densely
populated areas, and with contaminated food and water. The
common housefly plays a role in spread of infection.
Grossly, the lesions are mainly found in the colon and
SECTION III
occasionally in the ileum. Superficial transverse
ulcerations of mucosa of the bowel wall occur in the region
of lymphoid follicles but perforation is seldom seen. The
intervening intact mucosa is hyperaemic and oedematous.
Following recovery from the acute attack, complete
healing usually takes place.
Figure 20.31 A, Typhoid ulcers in the small intestine appear Microscopically, the mucosa overlying the lymphoid
characteristically oval with their long axis parallel to the long axis of the
bowel. B, Blood picture in typhoid fever showing neutropenia and relative follicles is necrosed. The surrounding mucosa shows
lymphocytosis. congestion, oedema and infiltration by neutrophils and
lymphocytes. The mucosa may be covered by greyish-
Persistence of organism in the gallbladder or urinary tract yellow ‘pseudomembrane’ composed of fibrinosuppurative
Systemic Pathology
may result in passage of organisms in the faeces or urine exudate.
creating a ‘carrier state’ which is a source of infection to The complications of bacillary dysentery are haemorrhage,
others. perforation, stenosis, polyarthritis and iridocyclitis.
2. AMOEBIC DYSENTERY. This is due to infection by
Bacterial Food Poisoning
Entamoeba histolytica. It is more prevalent in the tropical
This is a form of acute bacterial illness that occurs following countries and primarily affects the large intestine. Infection
ingestion of food or water contaminated with bacteria other occurs from ingestion of cyst form of the parasite. The cyst
than those that cause specific acute intestinal infections like wall is dissolved in the small intestine from where the
typhoid, paratyphoid, cholera or dysentery bacilli. The illness liberated amoebae pass into the large intestine. Here, they
results from either bacterial invasion or bacterial toxigenic invade the epithelium of the mucosa, reach the submucosa
effect on the bowel. and produce the characteristic flask-shaped ulcers.
The commonest causes of bacterial food poisoning
resulting in enteritis or enterocolitis are as under: Grossly, early intestinal lesions appear as small areas of
elevation on the mucosal surface. In advanced cases,
1. Staphylococcal food poisoning. Staphylococcus aureus typical flask-shaped ulcers having narrow neck and broad
infection acquired from contaminated food produces either base are seen. They are more conspicuous in the caecum,
mild food poisoning by enterotoxins, or may cause more severe rectum and in the flexures (Fig. 20.32).
form of the illness called pseudomembranous enterocolitis
573
Figure 20.32 Amoebic ulcers large intestine. A, The luminal surface
shows multiple ulcers some of which are deep and are flask-shaped
with narrow neck and broad base (arrow) containing necrotic tissue and
undermined margins. B, Trophozoites of Entamoeba histolytica are seen
at the margin of ulcer (arrow).
Microscopically, the ulcerated area shows chronic MORPHOLOGIC FEATURES. Grossly, the lesions may CHAPTER 20
inflammatory reaction consisting of lymphocytes, plasma be confined, to the large intestine or small intestine, or
cells, macrophages and eosinophils. The trophozoites of both may be involved. The mucosa of the bowel is covered
Entamoeba are seen in the inflammatory exudate and are by patchy, raised yellow-white plaques. Elsewhere, the
concentrated at the advancing margin of the lesion. mucosa is congested and may show small mucosal
Intestinal amoebae characteristically have ingested red ulcerations.
cells in their cytoplasm. Oedema and vascular congestion Microscopically, the ‘pseudomembrane’ is composed of
are present in the area surrounding the ulcers. network of fibrin and mucus, in which are entangled
inflammatory cells and mucosal epithelial cells. There is
Complications of intestinal amoebic ulcers are: amoebic focal necrosis of surface epithelial cells. The lamina propria
liver abscess or amoebic hepatitis, perforation, haemorrhage contains inflammatory cell infiltrate, mainly neutrophils. The Gastrointestinal Tract
and formation of amoeboma which is a tumour-like mass. The submucosa has congested capillaries and may show
microthrombi. The inflammation spreads laterally rather
PSEUDOMEMBRANOUS ENTEROCOLITIS than deeply.
(ANTIBIOTIC-ASSOCIATED DIARRHOEA)
MALABSORPTION SYNDROME
Pseudomembranous enterocolitis is a form of acute
inflammation of colon and/or small intestine characterised DEFINITION AND CLASSIFICATION
by formation of ‘pseudomembrane’ over the site of mucosal The malabsorption syndrome (MAS) is characterised by
injury. impaired intestinal absorption of nutrients especially of fat;
ETIOLOGY. Numerous studies have established the some other substances are proteins, carbohydrates, vitamins
overgrowth of Clostridium difficile with production of its toxin and minerals. MAS is subdivided into 2 broad groups:
in the etiology of antibiotic-associated diarrhoea culminating Primary MAS, which is due to primary deficiency of the
in pseudomembranous colitis. Oral antibiotics such as absorptive mucosal surface and of the associated enzymes.
clindamycin, ampicillin and the cephalosporins are more Secondary MAS, in which mucosal changes result
often (20%) associated with antibiotic-associated diarrhoea, secondary to other factors such as diseases, surgery, trauma
while development of pseudomembranous colitis may occur and drugs.
in 1-10% cases. Each of the two main groups has a number of causes listed
Pseudomembrane formation may also occur in various in Table 20.8.
other conditions as under: CLINICAL FEATURES
Staphylococcal enterocolitis The clinical manifestations of MAS vary according to the
Bacillary (Shigella) dysentery underlying cause. However, some common symptoms are
Candida enterocolitis as follows:
574 TABLE 20.8: Classification of Malabsorption Syndrome. INVESTIGATIONS
I. PRIMARY MALABSORPTION When MAS is suspected on clinical grounds, the following
1. Coeliac sprue investigations (laboratory tests) and endoscopic biopsy) may
2. Collagenous sprue be carried out to confirm it:
3. Tropical sprue I. LABORATORY TESTS:
4. Whipple’s disease
5. Disaccharidase deficiency 1. Tests for fat malabsorption:
6. Allergic and eosinophilic gastroenteritis i) Faecal analysis for fat content
ii) Microscopic analysis for faecal fat
II. SECONDARY MALABSORPTION iii) Blood lipid levels after a fatty meal
1. Impaired digestion iv) Tests based on absorption of radioactive-labelled fat.
(i) Mucosal damage e.g. in tuberculosis, Crohn’s disease, lymphoma,
amyloidosis, radiation injury, systemic sclerosis 2. Tests for protein malabsorption:
(ii) Hepatic and pancreatic insufficiency i) Bile acid malabsorption
(iii) Resection of bowel ii) Radioactive-labelled glycine breath test.
(iv) Drugs e.g. methotrexate, neomycin, phenindione etc. iii) Prothrombin time (vitamin K deficiency)
iv) Secretin and other pancreatic tests.
2. Impaired absorption
(i) Short or stagnant bowel (blind loop syndrome) from surgery or 3. Tests for carbohydrate malabsorption:
disease resulting in abnormal proliferation of microbial flora i) D-xylose tolerance test
(ii) Acute infectious enteritis ii) Lactose tolerance test
(iii) Parasitoses e.g. Giardia, Strongyloides, hookworms iii) Hydrogen breath test
iv) Bile acid breath test
3. Impaired transport
(i) Lymphatic obstruction e.g. in lymphoma tuberculosis, lymph- 4. Vitamin B , malabsorption:
12
angiectasia i) Schilling test (page 308).
(ii) Abetalipoproteinaemia
II. INTESTINAL MUCOSAL BIOPSY:
Mucosal biopsy of small intestine is essential for making the
1. Steatorrhoea (pale, bulky, foul-smelling stools)
2. Chronic diarrhoea diagnosis of MAS and also evaluation of a patient on follow-
3. Abdominal distension up. The availability of endoscopes has enabled easy viewing
of affected mucosa directly and taking mucosal biopsy under
4. Barborygmi and flatulence vision; this has largely replaced the earlier per-oral Crosby-
SECTION III
5. Anorexia Kugler capsule biopsy of small intestine. The biopsy should
6. Weight loss first be examined under dissecting microscope before
7. Muscle wasting histologic sectioning.
8. Dehydration
9. Hypotension Normal villous (Fig. 20.33,A). Under the dissecting
10. Specific malnutrition and vitamin deficiencies depending microscope, the normal jejunal mucosa has tall, slender,
upon the cause.
Systemic Pathology
Figure 20.33 Jejunal biopsy diagrammatic appearance in malabsorption syndrome.
finger-shaped or leaf-shaped villi. It is lined by tall colum- 575
nar absorptive epithelium and has scattered lymphocytes
in the lamina propria.
Villous atrophy. Variable degree of flattening of intestinal
mucosa in MAS is the commonest pathological change in
mucosal pattern and is referred to as villous atrophy. It
may be of 2 types—partial and subtotal/total type.
Partial villous atrophy is the mild form of the lesion
in which villi fuse with each other and thus become short
and broad, commonly called as convolutions and irregular
ridges (Fig. 20.33,B). The epithelial cells show compen-
satory hyperplasia suggesting a turnover of these cells
(Fig. 20.34,A). Lamina propria shows increased cellular
infiltrate, predominantly of plasma cells.
Partial villous atrophy is commonly found in children
and adults with diarrhoea, parasitic infestations, Crohn’s
disease, ulcerative colitis and malabsorption due to drugs Figure 20.34 A, Partial villus atrophy. There is shortening and
and radiation injury. blunting of the villi with reduction in their height. There is crypt hyperplasia.
B, Subtotal villous atrophy. There is near total flattening of the villi and
Subtotal/Total villous atrophy is the severe form of the crypt hyperplasia.
lesion in which there is flattening of mucosa due to more
advanced villous fusion (Fig. 20.33,C). The surface Histologically, there are no differences in the pathological
epithelium is cuboidal and there is increased plasma cell findings in children and adults. There is variable degree
infiltrate in the lamina propria (Fig. 20.34,B). of flattening of the mucosa, particularly of the upper
Subtotal and total villous atrophy is exhibited by a jejunum, and to some extent of the duodenum and ileum. CHAPTER 20
number of conditions such as nontropical sprue, tropical The surface epithelial cells are cuboidal or low columnar
sprue, intestinal lymphomas, carcinoma, protein-calorie type. There may be partial villous atrophy which is
malnutrition etc. replacement of normal villous pattern by convolutions,
or subtotal villous atrophy characterised by flat mucosal
IMPORTANT TYPES OF MAS surface. Lamina propria shows increased number of
Coeliac Sprue (Non-tropical Sprue, Gluten-Sensitive plasma cells and lymphocytes (Fig. 20.34).
Enteropathy, Idiopathic Steatorrhoea) The major sequela of long-term coeliac sprue is increased
This is the most important cause of primary malabsorption incidence of intestinal carcinoma in these cases.
occurring in temperate climates. The condition is
characterised by significant loss of villi in the small intestine Collagenous Sprue
and thence diminished absorptive surface area. The condition This entity is regarded as the end-result of coeliac sprue in The Gastrointestinal Tract
occurs in 2 forms: which the villi are totally absent (total villous atrophy) and
Childhood form, seen in infants and children and is there are unique and diagnostic broad bands of collagen
commonly referred to as coeliac disease. under the basal lamina of surface epithelium. The condition
Adult form, seen in adolescents and early adult life and used is refractory to any treatment and the course is generally fatal.
to be called idiopathic steatorrhoea. Some workers consider collagenous sprue as a variant of
In either case, there is genetic abnormality resulting in coeliac sprue without classifying it separately.
sensitivity to gluten (a protein) and its derivative, gliadin,
present in diets such as grains of wheat, barley and rye. Tropical Sprue
Serum antibodies—IgA antigliadin and IgA antiendomysial,
have been found but is not known whether these antibodies This disease, as the name suggests, occurs in individuals
are primary or appear secondary to tissue damage. living in or visiting tropical areas such as Caribbean
The symptoms are usually relieved on elimination of countries, South India, Sri Lanka and Hong Kong.
gluten from the diet. The role of heredity is further supported Pathogenesis of the condition is not clear but there is evidence
by the observation of familial incidence and HLA association to support enterotoxin production by some strains of E. coli
of the disease. Exact pathogenesis of the condition is not clear. which causes the intestinal injury. Severe cases are
However, following hypotheses are significant in causing characterised by additional features such as macrocytic
mucosal cell damage: anaemia, glossitis and emaciation due to intestinal
1. Hypersensitivity reaction as seen by gluten-stimulated malabsorption of vitamin B and folate.
12
antibodies.
2. Toxic effect of gluten due to inherited enzyme deficiency in Histologically, there is usually partial villous atrophy and
the mucosal cells. sometimes subtotal atrophy.
576 The lesions are relieved by removal of the patient from
the tropical area and by oral administration of antibiotics
but gluten-free diet has no role in improvement.
Whipple’s Disease (Intestinal Lipodystrophy)
This is an uncommon bacterial disease involving not only
the intestines but also various other systems such as central
nervous system, heart, blood vessels, skin, joints, lungs, liver,
spleen and kidneys. The disease is more common in males
in 4th to 5th decades of life. Patients may present with
features of malabsorption or may have atypical presentation
in the form of migratory polyarthritis, neurological
disturbances and focal hyperpigmentation of the skin.
Histologically, the affected tissues show presence of
characteristic macrophages containing PAS-positive
granules and rod-shaped micro-organisms (Whipple’s
bacilli). These macrophages are predominantly present in
the lamina propria of the small intestine and mesenteric
lymph nodes.
Patients respond very well to oral antibiotic therapy.
Figure 20.35 Lymphoma small intestine. The polypoid growth is
Protein-Losing Enteropathies seen projecting into lumen while the covering mucosa is ulcerated.
A number of disorders of the gastrointestinal tract are
accompanied by excessive protein loss without concomitant agent (non-argentaffin or argyrophil granules). Accordingly,
increase in protein synthesis, thus resulting in hypo- carcinoid tumour may be argentaffin or argyrophil type.
proteinaemia. These diseases are listed below: Depending upon the embryologic derivation of the tissues
i) Whipple’s disease where the tumour is located, these are classified as foregut,
SECTION III
ii) Crohn’s disease midgut, and hindgut carcinoids.
iii) Ulcerative colitis Midgut carcinoids, seen in terminal ileum and appendix
iv) Sprue are the most common (60-80%) and are more often argentaffin
v) Intestinal lymphangiectasia positive.
vi) Ménétrier’s disease (Hypertrophic gastritis).
Hindgut carcinoids, occurring in rectum and colon are
SMALL INTESTINAL TUMOURS more commonly argyrophil type, and comprise about 10-
20% of carcinoids.
Although small intestine is about 6 meter long, but for Foregut carcinoids, located in the stomach, duodenum
obscure reasons, benign as well as malignant tumours in it and oesophagus are also argyrophil type and are encoun-
are surprisingly rare. Most common benign tumours, in tered as frequently as in the hindgut (10-20%).
Systemic Pathology
descending order of frequency, are: leiomyomas, adenomas Other uncommon locations are the bronchus, trachea,
and vascular tumours (haemangioma, lymphangioma). gallbladder, and Meckel’s diverticulum.
Amongst the malignant tumours, the most frequently Appendix and terminal ileum, the two most common
encountered, in descending frequency, are: carcinoid sites for carcinoids, depict variation in their age and sex
tumours, lymphomas (Fig. 20.35) and adenocarcinoma. All incidence and biologic behaviour:
these tumours are identical in morphology to those seen
elsewhere in the alimentary tract. Carcinoid tumour, a Appendiceal carcinoids, occur more frequently in 3rd
peculiar neoplasm most common in the midgut, is described and 4th decades of life without any sex predilection, are often
below. solitary and behave as locally malignant tumours.
Ileal carcinoids, on the other hand, are seen more often
Carcinoid Tumour (Argentaffinoma) in later age (7th decade) with female preponderance, are more
commonly multiple and behave like metastasising
Carcinoid tumour or argentaffinoma is a generic term applied carcinomas.
to tumours originating from endocrine cells (synonyms:
argentaffin cells, Kulchitsky cells, enterochromaffin cells) MORPHOLOGIC FEATURES. Grossly, all carcinoids are
belonging to APUD cell system and are therefore also called small, button-like submucosal elevations with intact or
as apudomas (page 561). The endocrine cells are distributed ulcerated overlying mucosa. They are usually small; those
throughout the mucosa of GI tract. These cells have secretory larger than 2 cm are more often metastasising. Ileal and
granules which stain positively with silver salts (argentaffin gastric carcinoids are commonly multiple, whereas
granules) or many stain after addition of exogenous reducing
3. Abdominal pain 577
4. Attacks of dyspnoea due to bronchospasm
5. Right-sided heart failure due to involvement of tricuspid
and pulmonary valves and endocardium (page 451).
A number of secretory products in a functioning carcinoid
tumour have been demonstrated:
i) 5-Hydroxytryptamine (5-HT, serotonin)
ii) 5-Hydroxytryptophan
iii) 5-Hydroxy-indole acetic acid (5-HIAA)
iv) Histamine
v) Kallikrein
vi) Bradykinin
However, 5-HT and its degradation product, 5-HIAA, are
particularly significant in the production of carcinoid
Figure 20.36 Carcinoid tumour. Gross appearance at common
locations in longitudinal section. syndrome. 5-HT, a potent vasodilator and smooth muscle
stimulant, is normally synthesised in the endocrine cells of
the gut from dietary tryptophan. Tryptophan is first
appendiceal carcinoids commonly involve the tip of the hydroxylated to 5-hydroxytryptophan, then decarboxylated
organ and are solitary (Fig. 20.36). Cut section of all the to 5-HT and further oxidised to 5-HIAA by the monoamine
carcinoids is bright yellow. oxidase in the liver cells. It is then excreted in the urine. This
Histologically, the tumour cells may be arranged in a capacity to synthesise 5-HT and 5-HIAA is markedly elevated
variety of patterns—solid nests, sheets, cords, trabeculae in primary and hepatic metastatic carcinoids. Midgut
and clusters, all of which show characteristic palisading carcinoids have rich decarboxylating enzymes and are thus
of the peripheral cells. Acinar arrangement and rosettes able to produce large quantities of 5-HT and 5-HIAA,
are rarely seen. The tumour cells are classically small, accounting for high frequency of carcinoid syndrome in them.
monotonous, having uniform nuclei and poorly-defined Foregut and hindgut carcinoids, on the other hand, lack CHAPTER 20
cell boundaries (Fig. 20.37). The argentaffin carcinoids decarboxylating enzymes and, therefore, are less often
show eosinophilic granules in the cytoplasm which stain associated with carcinoid syndrome.
positively by the argentaffin reaction. Mitotic figures are
rare. However, the cytologic features are a poor guide for
distinguishing clinically benign from malignant behaviour APPENDIX
of the tumour, but all carcinoids infiltrate the bowel wall.
NORMAL STRUCTURE
CARCINOID SYNDROME. Carcinoid tumours that meta-
stasise, especially to the liver, are sometimes associated with Appendix is a vestigial organ which serves no useful purpose
the carcinoid syndrome. The syndrome consists of the in human beings but instead becomes the site of trouble at
following features: times. It is like a diverticulum of the caecum, usually lying The Gastrointestinal Tract
1. Intermittent attacks of flushing of the skin of face behind the caecum and varies in length from 4 to 20 cm
2. Episodes of watery diarrhoea (average 7 cm).
Figure 20.37 Microscopic appearance showing solid masses and trabeculae of uniform, monotonous, small cells with palisading of the peripheral
cells.
578
Histologically, appendix has four layers in its wall—
mucosa, submucosa, muscularis and serosa. The mucosa has
patchy distribution of crypts and the submucosa has
abundant lymphoid tissue. Argentaffin and non-
argentaffin endocrine cells are present in the base of
mucosal glands just as in the small intestine. The muscu-
laris of the appendix has two layers (inner circular and
outer longitudinal) as elsewhere in the alimentary tract.
Two important diseases involving the appendix are
appendicitis and appendiceal carcinoids.
APPENDICITIS
Acute inflammation of the appendix, acute appendicitis, is
the most common acute abdominal condition confronting the Figure 20.38 Acute appendicitis. Gross appearance of longitudinally
surgeon. The condition is seen more commonly in older opened appendix showing impacted faecolith in the lumen and exudate
children and young adults, and is uncommon at the extremes on the serosa.
of age. The disease is seen more frequently in the West and
in affluent societies which may be due to variation in diet— MORPHOLOGIC FEATURES. Grossly, the appearance
a diet with low bulk or cellulose and high protein intake more depends upon the stage at which the acutely-inflamed
often causes appendicitis. appendix is examined. In early acute appendicitis, the organ
ETIOPATHOGENESIS. The most common mechanism is is swollen and serosa shows hyperaemia. In well-
obstruction of the lumen from various etiologic factors that developed acute inflammation called acute suppurative
leads to increased intraluminal pressure. This presses upon appendicitis, the serosa is coated with fibrinopurulent
the blood vessels to produce ischaemic injury which in turn exudate and engorged vessels on the surface. In further
favours the bacterial proliferation and hence acute advanced cases called acute gangrenous appendicitis, there
appendicitis. The common causes of appendicitis are as is necrosis and ulcerations of mucosa which extend
under: through the wall so that the appendix becomes soft and
A. Obstructive: friable and the surface is coated with greenish-black
SECTION III
1. Faecolith gangrenous necrosis (Fig. 20.38).
2. Calculi Microscopically, the most important diagnostic histological
3. Foreign body criterion is the neutrophilic infiltration of the muscularis. In
4. Tumour early stage, the other changes besides acute inflammatory
changes, are congestion and oedema of the appendiceal
5. Worms (especially Enterobius vermicularis) wall. In later stages, the mucosa is sloughed off, the wall
6. Diffuse lymphoid hyperplasia, especially in children.
becomes necrotic, the blood vessels may get thrombosed
B. Non-obstructive: and there may be neutrophilic abscesses in the wall. In
1. Haematogenous spread of generalised infection either case, an impacted foreign body, faecolith, or con-
2. Vascular occlusion cretion may be seen in the lumen (Fig. 20.39).
3. Inappropriate diet lacking roughage.
Systemic Pathology
Figure 20.39 Acute appendicitis. Microscopic appearance showing diagnostic neutrophilic infiltration into the muscularis. Other changes
present are necrosis of mucosa and periappendicitis.
Thus, there is good correlation between macroscopic PSEUDOMYXOMA PERITONEI. Pseudomyxoma peritonei 579
and microscopic findings in acute appendicitis. is appearance of gelatinous mucinous material around the
appendix admixed with epithelial tumour cells. It is generally
CLINICAL COURSE. The patient presents with features of due to mucinous collection from benign mucinous
acute abdomen as under: cystadenoma of the ovary or mucin-secreting carcinoma of
1. Colicky pain, initially around umbilicus but later localised the appendix.
to right iliac fossa ADENOCARCINOMA. It is an uncommon tumour in the
2. Nausea and vomiting appendix and is morphologically similar to adenocarcinoma
3. Pyrexia of mild grade elsewhere in the alimentary tract.
4. Abdominal tenderness
5. Increased pulse rate
6. Neutrophilic leucocytosis. LARGE INTESTINE
An attack of acute appendicitis predisposes the appendix
to repeated attacks (recurrent acute appendicitis) and thus NORMAL STRUCTURE
surgery has to be carried out. If appendicectomy is done at a
later stage following acute attack (interval appendicectomy), The large bowel consists of 6 parts—the caecum, ascending
pathological changes of healing by fibrosis of the wall and colon, transverse colon, descending colon, sigmoid colon and
chronic inflammation are observed. rectum, and in all measures about 1.5 meters in length. The
serosal surface of the large intestine except the rectum is
COMPLICATIONS. If the condition is not adequately studded with appendices epiploicae which are small, rounded
managed, the following complications may occur:
collections of fatty tissue covered by peritoneum.
1. Peritonitis. A perforated appendix as occurs in
gangrenous appendicitis may cause localised or generalised Histologically, the wall of large bowel consists of 4 layers as
peritonitis. elsewhere in the alimentary tract—serosa, muscularis,
submucosa and mucosa.
2. Appendix abscess. This is due to rupture of an appendix
giving rise to localised abscess in the right iliac fossa. This The mucosa lacks villi and there is preponderance of CHAPTER 20
abscess may spread to other sites such as between the liver goblet cells over columnar epithelial cells. The lymphoid
and diaphragm (subphrenic abscess), into the pelvis between tissue is less abundant than in the small bowel but lymphoid
the urinary bladder and rectum, and in the females may follicles are seen in the caecum and rectum.
involve uterus and fallopian tubes. The muscularis propria of the large intestine is quite
peculiar—the inner circular muscle layer ensheaths whole
3. Adhesions. Late complications of acute appendicitis are length of the intestine, while the outer longitudinal muscle
fibrous adhesions to the greater omentum, small intestine
and other abdominal structures. layer is concentrated into 3 muscle bands called taenia coli.
The length of outer muscle layer is shorter than the length of
4. Portal pylephlebitis. Spread of infection into mesenteric the intestine and therefore, it forms the sacculations or haustra
veins may produce septic phlebitis and liver abscess. of the large intestine. At the rectosigmoid junction, the three
5. Mucocele. Distension of distal appendix by mucus muscle bands fuse to form a complete covering. The Gastrointestinal Tract
following recovery from an attack of acute appendicitis is The blood supply to the right colon is from the superior
referred to as mucocele. It occurs generally due to proximal mesenteric artery which also supplies blood to the small
obstruction but sometimes may be due to a benign or bowel. The remaining portion of large bowel except the lower
malignant neoplasm in the appendix. An infected mucocele part of rectum receives blood supply from inferior mesenteric
may result in formation of empyema of the appendix. artery. The lower rectum is supplied by haemorrhoidal
branches.
TUMOURS OF APPENDIX The innervation of the large bowel consists of 3 plexuses
of ganglion cells—Auerbach’s or myenteric plexus lying
Tumours of the appendix are quite rare. These include: between the two layers of muscularis, Henle’s plexus lying in
carcinoid tumour (the most common), pseudomyxoma the deep submucosa inner to circular muscle layer, and
peritonei and adenocarcinoma.
Meissner plexus that lies in the superficial mucosa just beneath
CARCINOID TUMOUR. It is already described on page 576. the muscularis mucosae. These are interconnected by non-
Both argentaffin and argyrophil types are encountered, the myelinated nerve fibres.
former being more common. Anal canal, 3-4 cm long tubular structure, begins at the
lower end of the rectum, though is not a part of large bowel,
Grossly, carcinoid tumour of the appendix is mostly but is included here to cover simultaneously lesions
situated near the tip of the organ and appears as a pertaining to this region. It is lined by keratinised or
circumscribed nodule, usually less than 1 cm in diameter, nonkeratinised stratified squamous epithelium. Anal verge
involving the wall but metastases are rare. is the junction between the anal canal and perineal skin, while
Histologically, carcinoid tumour of the appendix pectinate line is the squamo-columnar junction between the
resembles other carcinoids of the midgut. anal canal and the rectum.
580 CONGENITAL MALFORMATIONS
Hirschsprung’s Disease (Congenital Megacolon)
The term ‘megacolon’ is used for any form of marked
dilatation of the entire colon or its segment and may occur
as a congenital or acquired disorder. Congenital form
characterised by congenital absence of ganglion cells in the
bowel wall (enteric neurons) is called Hirschsprung’s disease.
As a result, the aganglionic segment remains contracted.
Genetically, Hirschsprung’s disease is a heterogeneous
disorder as under:
1. Autosomal dominant inheritance with mutation in RET
proto-oncogene in some cases.
2. Autosomal recessive form with mutation in endothelin-B
receptor gene in many other cases.
Clinically, the condition manifests shortly after birth with
constipation, gaseous distension and sometimes with acute Figure 20.40 Hirschsprung’s disease, diagrammatic representation
intestinal obstruction. Its frequency is 1 in 5,000 live-births, of the pathologic changes.
has familial tendency in about 4% of cases and has
predilection for development in Down’s syndrome. 5. Zonal colonic aganglionosis: A short segment is nvolved in
Pathogenesis lies in the failure of neuroblasts to migrate to agnaglionosis in which the ganglia cells are absent both above
the rectum which normally occurs at about 12 weeks of and below the aganglionic segment.
gestation.
In addition to congenital megacolon discussed above,
megacolon may occur from certain acquired causes as under:
MORPHOLOGIC FEATURES. Two types of biopsies may i. Obstructive e.g. due to tumour, post-inflammatory
be done on infants suspected of having Hirschsprung’s strictures.
disease—full-thickness rectal biopsy, and suction biopsy ii. Endocrine e.g. in myxoedema, cretinism.
that includes mucosa and submucosa. iii. CNS disorders e.g. spina bifida, paraplegia, parkinsonism.
SECTION III
Grossly, typical case of Hirschsprung’s disease shows 2 iv. Psychogenic e.g. emotional disturbances, psychiatric
segments—a distal narrow segment that is aganglionic and disorders.
a dilated proximal segment that contains normal number of v. Chagas’ disease due to infection with Trypanosoma cruzi is
ganglion cells (Fig. 20.40). the only example resulting in acquired loss of ganglion cells.
Microscopically, the distal narrow segment shows total In all other acquired causes listed above, the bowel
absence of ganglion cells of all the three plexuses innervation is normal.
(Auerbach’s or myenteric plexus present between the two
layers of muscularis, deep submucosal or Henle’s plexus, COLITIS
and superficial mucosal or Meissner’s plexus) and
prominence of non-myelinated nerve fibres. Histo- Colitis may occur in isolation but more commonly
involvement of small intestine is also present (enterocolitis).
chemical staining for acetylcholine esterase activity In view of the considerable overlapping of enteritis and
Systemic Pathology
provides confirmation for identifying ganglion cells and colitis, these lesions have already been described under small
nerve trunks.
intestine (page 578). Table 20.9 presents a classification of
the various types of colitis/enterocolitis.
Depending upon the length of the segment affected by
aganglionosis in Hirschsprung’s disease, following patterns
are recognised: TABLE 20.9: Classification of Colitis/Enterocolitis.
1. Classic form: Anganglionosis from distal colorectal region I. ISCHAEMIC BOWEL DISEASE
to proximal dilated colon. Ischaemic colitis (‘Membranous’ colitis)
2. Short segment (rectal and recto-sigmoid) form: Aganglionosis II. INFLAMMATORY BOWEL DISEASE
involving a few centimeters of the rectum and rectosigmoid 1. Ulcerative colitis
only. 2. Crohn’s disease
3. Ultra-short form: Aganglionosis is in a very small segment III. OTHER INFLAMMATORY LESIONS
which can be missed in a biopsy. 1. Infective enterocolitis (Dysenteries—bacillary, amoebic, other
4. Long segment (subtotal colonic) form: Aganglionosis parasitic)
involves most of the colon from rectosigmoid to the ileo- 2. ‘Pseudomembranous’ enterocolitis (Antibiotic-associated
caecal valve, and sometimes may even extend into smll 3. diarrhoea)
Necrotising enterocolitis
bowel.
MISCELLANEOUS LESIONS Haemorrhoids (Piles) 581
Diverticulosis Coli Haemorrhoids or piles are the varicosities of the haemorrhoi-
dal veins. They are called ‘internal piles’ if dilatation is of
Diverticula are the outpouchings or herniations of the mucosa superior haemorrhoidal plexus covered over by mucous
and submucosa of the colon through the muscle wall. membrane, and ‘external piles’ if they involve inferior
Diverticular disease, as it is commonly known, is rare under haemorrhoidal plexus covered over by the skin. They are
30 years of age and is seen more commonly as the age common lesions in elderly and pregnant women. They
advances. Multiple diverticula of the colon are very common commonly result from increased venous pressure. The
in the Western societies, probably due to ingestion of low- possible causes include the following:
fibre diet but is seen much less frequently in tropical countries 1. Portal hypertension
and in Japan. Diverticulosis is often asymptomatic and may 2. Chronic constipation and straining at stool
be detected as an incidental finding at autopsy. However, a 3. Cardiac failure
proportion of patients develop clinical symptoms such as 4. Venous stasis of pregnancy
low abdominal pain, distension, constipation and sometimes 5. Hereditary predisposition
intermittent bleeding. 6. Tumours of the rectum.
Based on the etiologic role of low fibre diet, pathogenesis
of diverticular disease of the colon can be explained as under: Microscopically, thin-walled and dilated tortuous veins
1. Increased intraluminal pressure such as due to low fibre are seen under the rectal mucosa (internal piles) or anal
content of the diet causing hyperactive peristalsis and thereby skin (external piles). Secondary changes and complications
sequestration, of mucosa and submucosa. that may occur include: thrombosis, haemorrhage,
inflammation, scarring and strangulation (prolapsed piles).
2. Muscular weakness of the colonic wall at the junction of
the muscularis with submucosa. Angiodysplasia
MORPHOLOGIC FEATURES. Grossly, diverticulosis is Angiodysplasia is a submucosal telangiectasia affecting
seen most commonly in the sigmoid colon (95%) but any caecum and right colon that causes recurrent acute and
other part of the entire colon may be involved. They may chronic haemorrhage. The condition is more common in the CHAPTER 20
vary in number from a few to several hundred. They elderly past 6th decade. The pathogenesis is obscure but is
appear as small, spherical or flask-shaped outpouchings, possibly due to mechanical obstruction of the veins.
usually less than 1 cm in diameter, commonly extend into
appendices epiploicae and may contain inspissated faeces. MISCELLANEOUS INFLAMMATORY CONDITIONS
They are connected to the intestinal lumen by a narrow ‘Fistula-in-ano’ is a well known and common condition
neck.
in which one or more fistulous tracts pass from the internal
Histologically, the flask-shaped structures extend from opening at the pectinate line through the internal sphincter
the intestinal lumen through the muscle layer. The colonic on to the skin surface. The condition probably results from
wall in the affected area is thin and is composed of atrophic infection of the anal glands.
mucosa, compressed submucosa and thin or deficient Histologically, nonspecific inflammatory changes are seen. The Gastrointestinal Tract
muscularis. However, muscularis propria in between the
diverticular protrusions is hypertrophied. While diverti- ‘Anal fissure’ is an ulcer in the anal canal below the level
cular disease may remain asymptomatic, inflammatory of the pectinate line, mostly in midline and posteriorly. The
changes in the diverticula (diverticulitis) produce clinical common cause is trauma due to passage of hard stools,
symptoms. followed by chronic infection.
‘Solitary rectal ulcer syndrome’ is a condition charac-
The complications of diverticulosis and diverticulitis are terised usually by solitary, at times multiple, rectal ulcers
perforation, haemorrhage, intestinal obstruction and fistula with prolapse of rectal mucosa and development of proctitis.
formation. The histological appearance is quite characteristic. Besides
ulceration and inflammation of the rectal mucosa, lamina
Melanosis Coli propria is occupied by spindle-shaped fibroblasts and smooth
muscle cells. The condition is also called as ‘localised form of
Melanosis coli is a peculiar condition in which mucosa of
the large intestine acquires brown-black colouration. The colitis cystica profunda’ and must be differentiated from ‘diffuse
form of colitis cystica profunda’ seen in cases of ulcerative colitis.
condition is said to occur in individuals who are habitual Submucosal cysts lined by foreign body giant cells and
users of cathartics of anthracene type.
containing gas are also seen in ‘pneumatosis cystoides
Grossly, the mucosal surface is intact and is pigmented intestinalis’.
brown-black.
Microscopically, large number of pigment-laden LARGE INTESTINAL POLYPS AND TUMOURS
macrophages are seen in the lamina propria. The nature Large bowel is the most common site for a variety of benign
of this pigment is found to be both melanin and lipofuscin. and malignant tumours, majority of which are of epithelial
582 rectosigmoid. They are called ‘hyperplastic’ because there is
TABLE 20.10: Polyps and Tumours of the Large Intestine.
epithelial hyperplasia at the base of the crypts, and
I. COLORECTAL POLYPS ‘metaplastic’ as there are areas of cystic metaplasia. They may
A. Non-neoplastic polyps be seen at any age but are more common in the elderly
1. Hyperplastic (metaplastic) polyps (6th-7th decade).
2. Hamartomatous polyps
(i) Peutz-Jeghers polyps and polyposis Grossly, hyperplastic polyps are generally multiple,
(ii) Juvenile (Retention) polyps and polyposis
3. Inflammatory polyps (Pseudopolyps) sessile, smooth-surfaced and small (less than 0.5 cm).
4. Lymphoid polyps Microscopically, they are composed of long and cystically
dilated glands and crypts lined by normal epithelial cells.
B. Neoplastic polyps (Adenomas)
Their lining is partly flat and partly papillary. The luminal
1. Tubular adenoma (Adenomatous polyp) border of the lining epithelium is often serrated or saw-
2. Villous adenoma (Villous papilloma)
3. Tubulovillous adenoma (Papillary adenoma, villoglandular toothed.
adenoma)
Hyperplastic polyps are usually symptomless and have
C. Familial polyposis syndromes
no malignant potential unless there is a coexistent adenoma.
1. Familial polyposis coli (Adenomatosis)
2. Gardner’s syndrome
3. Turcot’s syndrome Hamartomatous Polyps
4. Juvenile polyposis syndrome These are tumour-like lesions composed of abnormal mixture
II. OTHER BENIGN COLORECTAL TUMOURS of tissues indigenous to the part. They are further of 2 types:
(Leiomyomas, leiomyoblastoma, neurilemmoma, lipoma and PEUTZ-JEGHERS POLYPS AND POLYPOSIS. Peutz-
vascular tumours)
Jeghers syndrome is autosomal dominant defect, charac-
III. MALIGNANT COLORECTAL TUMOURS
terised by hamartomatous intestinal polyposis and melanotic
A. Carcinoma pigmentation of lips, mouth and genitalia. The polyps may
1. Adenocarcinoma be located in the stomach, small intestine or colon but are
2. Other carcinomas most common in the jejunum and ileum. The most common
(Mucinous adenocarcinoma, signet-ring cell carcinoma, age is adolescence and early childhood.
adenosquamous carcinoma, undifferentiated carcinoma)
B. Other malignant tumours Grossly, these polyps are of variable size but are often
SECTION III
(Leiomyosarcoma, malignant lymphoma, carcinoid tumours)
large, multiple and pedunculated and more commonly
IV. TUMOURS OF THE ANAL CANAL situated in the small intestine.
A. Benign (viral warts or condyloma acuminata) Microscopically, the most characteristic feature is the tree-
B. Malignant (squamous cell carcinoma, basaloid carcinoma, like branching of muscularis mucosae. The lining
mucoepidermoid carcinoma, adenocarcinoma, undifferentiated epithelium is by normal-appearing epithelial cells. The
carcinoma, malignant melanoma)
glands may show hyperplasia and cystic change
(Fig. 20.41).
origin. Most of the benign tumours present clinically as
polyps. A classification of polyps, alongwith benign tumours Peutz-Jeghers polyps do not undergo malignant
and malignant tumours, is presented in Table 20.10. transformation unless a coexistent adenoma is present.
However, patients with Peutz-Jeghers syndrome are more
Systemic Pathology
COLORECTAL POLYPS prone to certain other cancers such as of pancreas, lung,
A polyp is defined as any growth or mass protruding from breast, ovary and uterus.
the mucous membrane into the lumen. Polyps are much more JUVENILE (RETENTION) POLYPS. Juvenile or retention
common in the large intestine than in the small intestine and polyps, another form of hamartomatous polyps, occur more
are more common in the rectosigmoid colon than the commonly in children below 5 years of age. Solitary juvenile
proximal colon. Polyps are broadly classified into 2 groups— polyps occur more often in the rectum, while juvenile
non-neoplastic and neoplastic. Non-neoplastic polyps have polyposis may be present anywhere in the large bowel.
further subtypes indicating their mode of origin. Neoplastic
polyps, on the other hand, include epithelial tumours, both Grossly, juvenile polyps are spherical, smooth-surfaced,
benign and malignant (Table 20.10). about 2 cm in diameter and are often pedunculated.
Microscopically, the classical appearance is of cystically
A. NON-NEOPLASTIC POLYPS dilated glands containing mucus and lined by normal
Non-neoplastic polyps are more common and include the mucus-secreting epithelium. The stroma may show
following 4 subtypes: inflammatory cell infiltrate if there is chronic ulceration
of the surface (Fig. 20.42).
Hyperplastic (Metaplastic) Polyps
Most cases, on becoming symptomatic in the form of
The hyperplastic or metaplastic polyps are the most common rectal bleeding, are removed. In common with other non-
amongst all epithelial polyps, particularly in the neoplastic polyps, they are also not precancerous.
583
Figure 20.41 Hamartomatous polyps: Peutz-Jeghers polyp.
Inflammatory Polyps (Pseudopolyps) Lymphoid Polyps
Inflammatory polyps or pseudopolyps appear due to re- Reactive hyperplasia of lymphoid tissue that is normally also
epithelialisation of the undermined ulcers and overhanging more prominent in the rectum and terminal ileum, gives rise
margins in inflammatory bowel disease, most frequently in to localised or diffuse lymphoid polyps, also called rectal
ulcerative colitis (colitis polyposa) and sometimes in Crohn’s tonsils. Localised form occurs more often in the rectum in
disease. elderly, while diffuse form is seen at younger age and in CHAPTER 20
children.
Grossly, they are usually multiple, cylindrical to rounded
overgrowths of mucosa and may vary from minute Grossly, they are solitary or multiple, tiny elevated lesions.
nodules to several centimeters in size. Microscopically, they are composed of prominent
Microscopically, the centre of inflammatory polyp lymphoid follicles with germinal centres located in the
consists of connective tissue core that shows some submucosa and mucosa, and are covered by epithelium
inflammatory cell infiltrate and is covered superficially that may be inflamed.
by regenerating epithelial cells and some cystically-dilated They are benign lesions and have to be distinguished from
glands. malignant lymphoma.
These lesions have no malignant potential; carcinomas B. NEOPLASTIC POLYPS (ADENOMAS) The Gastrointestinal Tract
seen in long-standing cases of ulcerative colitis arise in the
region of epithelial dysplasia and not from the polyps. Neoplastic polyps are colorectal adenomas which have
potential for malignant change while polypoid carcinoma is
Figure 20.42 Juvenile polyp.
584
Figure 20.43 Adenomas (neoplastic polyps)—three main varieties.
the term used for invasive epithelial tumours. Adenomas Malignant transformation is present in about 5% of
have 3 main varieties (tubular, villous and tubulovillous), tubular adenomas; the incidence being higher in larger
SECTION III
each of which represents a difference in the growth pattern adenomas.
of the same neoplastic process and variable biological
behaviour. Villous Adenoma (Villous Papilloma)
Villous adenomas or villous papillomas of the colon are much
Tubular Adenoma (Adenomatous Polyp) less common than tubular adenomas. The mean age at which
they appear is 6th decade of life with approximatey equal
Tubular adenomas or adenomatous polyps are the most sex incidence. They are seen most often in the distal colon
common neoplastic polyps (75%). They are common beyond and rectum, followed in decreasing frequency, by rest of the
3rd decade of life and have slight male preponderance. They colon.
occur most often in the distal colon and rectum. They may
be found singly as sporadic cases, or multiple tubular Grossly, villous adenomas are round to oval exophytic
adenomas as part of familial polyposis syndrome with masses, usually sessile, varying in size from 1 to 10 cm or
Systemic Pathology
autosomal dominant inheritance pattern. Tubular adenomas more in diameter. Their surface may be haemorrhagic or
may remain asymptomatic or may manifest by rectal ulcerated.
bleeding. Microscopically, the characteristic histologic feature is the
presence of many slender, finger-like villi, which appear
Grossly, adenomatous polyps may be single or multiple, to arise directly from the area of muscularis mucosae. Each
sessile or pedunculated, vary in size from less than 1 cm of the papillae has fibrovascular stromal core that is
to large, spherical masses with an irregular surface. covered by epithelial cells varying from apparently benign
Usually, the larger lesions have recognisable stalks. to anaplastic cells. Excess mucus secretion is sometimes
Microscopically, the usual appearance is of benign seen (Fig. 20.43,B).
tumour overlying muscularis mucosa and is composed Villous adenomas are invariably symptomatic; rectal
of branching tubules which are embedded in the lamina bleeding, diarrhoea and mucus being the common features.
propria. The lining epithelial cells are of large intestinal The presence of severe atypia, carcinoma in situ and invasive
type with diminished mucus secreting capacity, large carcinoma are seen more frequently. Invasive carcinoma has
nuclei and increased mitotic activity (Fig. 20.43,A). been reported in 30% of villous adenomas.
However, tubular adenomas may show variable degree
of cytologic atypia ranging from atypical epithelium Tubulovillous Adenoma
restricted within the glandular basement membrane called (Papillary Adenoma, Villoglandular Adenoma)
as ‘carcinoma in situ’ to invasion into the fibrovascular Tubulovillous adenoma is an intermediate form of pattern
stromal core termed as frank adenocarcinoma.
between tubular adenoma and villous adenoma. It is also
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