Pathoma-Lecture-Notes

Fig: bottom right- perivascular pseudorosette; top left: true ependymal rosette .

3. Medullobastoma

Defn - Malignant tumor of neuroectoderm cells of cerebellum (granular cells)

Presentation - Histology:
• Homer-Wright rosettes may be present (type of true rosette)
• Small, round, blue cells on biopsy

Prognosis - Poor; tumor rapidly grows and spreads via CSF giving 'drop metastasis in cauda equina
4. Craniopharyngioma

Defn - Benign tumor that arises from epidermal remnant of Rathke's pouch (makes parts of pituitary
gland)

Presentation - Supratentorial mass in child or young adult (only supratentorial kid tumor we study)
- Can cause bitemporal hemianopsia due to compression of optic chiasm
- Calcifications can be seen - derived from 'teeth like' tissue

Neurology Page 2.4

Calcifications can be seen - derived from 'teeth like' tissue

Prognosis Fig: calcified craniopharyngioma
- Tends to recur after resection

Malignant brain tumor

Epidem. - Represent 50% of brain tumors

Source - Most common are breast, lung and kidney (BLacK mnemonic)

Appearance - Multiple and well circumcised at gray-white junction

Fig: metastatic melanoma; note the dark color tumors

Neurology Page 2.5

Virtigo

virtigo - room spinning around or you spinning in the room

CNS vertigo : originates in CNS
- no hearing loss
- vertical nystagmus
- focal neuro deficit
- associated CNS symptom (difficulty walking)

peripheral virtigo: originates in ears because they moved their head)
- hearing loss
- no vertical nystagmus
- extremely nauseous (CNS vertigo has less nausea)
- head movement can trigger (wake up midnight
- BPPV

Ddx for peripheral virtigo: minutes)
- ex - Meniere disease (vertigo that lasts 20
- labyrinthitis (days
- ototoxicity

Ddx for central virtigo:
- MS
- tumor

age old male with PMH of ..... presents with .... most concerning with...

Neurology Page 9.1

Chapter 18: Musculoskeletal
Pathology

18.1 Skeletal System

Achondroplasia (without cartilage formation)

Defn - Impaired cartilage proliferation in growth plate that leads to dwarfism

Epidemiolog - Most common cause of short limbed dwarfism
y

Cause - Activating mutation in fibroblast growth factor receptor 3 (FGFR3) (autosomal d.)
- Most cases are sporadic (80%) and related to increased parental age

Presen. - Presentation based on impaired endochondral ossification; intramembranous
bone formation not affected
- Short extremities with normal sized head and chest
- Mental function, life span, and fertility not affected

Osteogenesis imprefecta (brittle bone disease)

Defn - Mutation in collagen type 1 leads to congenital bone defects

Presen. - Multiple bone fractures (can mimic child abuse)
- Blue sclera - due to thinning of scleral collagen revealing underlying choroidal veins
- Hearing loss - due to fracture of middle ear bones
- Dental imperfection due to lack of dentin (blue or brown teeth that easily rots)

Osteopetrosis (bone-that-is-like-stone)

Defn - Poor osteoclast function leading to abnormally thick and heavy bone that fractures

Musculoskeletal Page 1.1

Defn - Poor osteoclast function leading to abnormally thick and heavy bone that fractures
easily like a piece of chalk

Pathophy - Multiple pathways but one is mutation in carbonic anhydrase II that leads to loss of
s. acidic microenviroment required for bone reabsorption

Presen. - Bone fractures
- Anemia, thrombocytopenia, leukopenia with extramedullary hematopoiesis - due to
bony replacement of marrow (myelophthisic process)
- Hepatosplenomegaly - extramedullary hematopoiesis
- Vision and hearing impairment - due to impingement of cranial nerves
- Hydrocephalous - due to narrowing of foramen magnum
- Renal tubular acidosis - seen if carbonic anhydrase mutation present; CA important
for tubular reabsorption of HCO3- in tubules

Fig: osteopetrosis (left), normal head x-ray (right)

Treatmen - Bone marrow transplant
t

Rickets/Osteomalacia (kids vs adult form of disease)

Defn - Poor mineralization of osteoid (bone matrix produced by osteoblast) with Ca and
PO4 due to Vit D deficiency

Vit D - Derived from sunlight in skin - 85%, diet - 15%
biochem - Vit D2 (ergocalciferol)- ingested from plants; Vit D3 (cholecalciferol) - ingested from
milk or converted from 7-dehydrocholesterol by UV in skin
- Activation requires 25 hydroxylase activity in liver (becomes 25-OH-vit D) followed
by 1-alpha-hydroxylase activity in PCT of kidney (becomes 1,25-OH-vit D - active
form).

Vit D - Increase absorption of Ca and PO4 from kidney and intestine
function - Increase reabsorption of Ca and PO4 from bone

Picmonic

Musculoskeletal Page 1.2

Picmonic

Vitamin D = viking daisy
1st step of activation = 25 hydroxylase action in liver = liver giving 25 cents
2nd step of activation = 1 alpha hydroxylase action in kidney = kidney giving cent

Vit D - Liver or kidney failure

deficiency - Poor diet, lack of sun exposure

causes

Rickets - Pectus craniatum (pigeon breast)
presentati - Frontal bossing (enlarged forehead)
on - Rachitic rosary - osteoid deposition in costochondral junction
- Harrison sulcus - strong diaphragm pull the last ribs inward
- Bowing of legs

Osteomala - Increased risk for fracture

cia - Labs:

presentati • Low serum calcium and phosphate

on • High serum PTH

• High alkaline phosphatase (creates alkaline environment that is required for

osteoblast function)

Osteoporosis - Reduction of bone density due to loss of trabecular (spongy) bone that increases risk
Defn of fracture

Musculoskeletal Page 1.3

-

Risk - Risk based on peak bone mass (attained ~30 years) and rate of bone loss after that
- Peak bone mass depends on genetics (Vit D receptor variation), diet and exercise
- Rate of bone loss is <1% per year after that. Bone loss increases due to lack of
exercise (space travel), poor diet and lack of estrogen

Clinic. - Reduced bone density on DEXA scan
features - Normal serum Ca, PO4, PTH - distinguish from osteomalacia (presentation of both
may be similar otherwise)
- Fracture in weight bearing bones - vertebra (ht loss and kyphosis), hip and distal
radius

Treatmen - Bisphosphonates - induce apoptosis of osteoclast
t - Exercise, Vit D, and Ca

- Estrogen replacement therapy debated (increases risk of breast and endometrium
cancer)
- Glucocorticoid speeds up bone loss

Paget disease of bone

Defn - thick, sclerotic bone that fractures easily due to imbalance between osteoblast and
osteoclast activity; first osteoclast overactive, then both equal activity, then
osteoblast overactive.

Epid - Mostly seen in >60 year olds (most common cause of isolated increase in alk
phosphate in >40 year olds)

Etiology - Unknown, maybe viral

Clinic - Skull is commonly affected
features • Hearing and vision loss - impengement of cranial nerves
• Lion like face and increased hat size

- Bone pain - due to micro fractures
- Biopsy - mosaic pattern of lamellar bone

Treatment - Bisphosphonate - induce apoptosis of osteoclasts
- Calcitonin - inhibit osteoclast function (to tone down blood calcium)

Musculoskeletal Page 1.4

- Calcitonin - inhibit osteoclast function (to tone down blood calcium)

Complicati - Risk of osteosarcoma during osteoblast overactivity phase
on - High output cardiac failure due to formation of AV shunt in bone

Osteomyelitis - Infection of marrow and bone
Defn
Types - Transient bacteremia - seen in kids - affects metaphysis
- Open wound bacteremia - seen in adults - affects epiphysis
Causes
Most common cause (90%) - Staph aurues

Sexually active young adult - Neisseria gonorrhoeae

Sickle cell disease - Salmonella

Diabetics and IV drug users - Pseudomonas

Dog or cat bite/scratch - Pasteurella

Vertebral osteomyelitis (Pott disease) - Mycobacterium TB

Present. - Bone pain with systemic sign of infection (fever, leukocytosis)
- X-ray - shows lytic focus (abscess) - aka sequestrum, with surrounding sclerosis - aka
involucrum

Diagnosis - Blood culture

Treatmen - Antibiotics
t

Avascular necrosis (aseptic necrosis)

Defn - Ischemic necrosis of bone and bone marrow

Causes - Fracture (most common) - ex: avascular necrosis of femoral head
- Steroids
- Sickle cell anemia - vasoocclusive crisis n bone of hands and feet (presents as
dactylitis)
- Caisson disease (decompression sickness) - gas bubbles form in blood with
depressurization

Complicatio - Osteoarthritis and fracture
n

Musculoskeletal Page 1.5

18.2 Bone Tumors

Benign tumors - benign tumor most commonly seen on face
Osteoma - Associated with garderner's synrome (osteoma + FAP (familial adenomatous polyposis) +
retroperitoneal fibrosis)

Chondroma - Divided as enchondroma (seen on medulla, mainly on small bones of hand and feet) or juxtacortical
chondroma (seen on bone surface)

Osteoid Fig: enchondroma (left); juxtacortical chondroma (right)
osteoma
- Benign tumor of osteoblast with osteoid core (radiolucent) most commonly seen on diaphysis
- Size <2cm
- Localized pain, most severe at night, is an almost universal complaint
- Pain is relieved by asprin

Fig: osteoid osteoma (left); osteoblastoma (middle); oxteochondroma (right)
Osteoblasto - Similar to Osteoid osteoma
ma - Differences:

• Most commonly seen on vertebra
• Size >2cm

Musculoskeletal Page 2.1

• Size >2cm
• Pain not relieved by asprin

Osteochond - Most common benign tumor of bone

roma - Tumor of bone with overlying cartilage cap; arises from lateral part of metaphysis and bone is

contineous with marrow space

- Overlying cartilage can rarely transform to chondrosarcoma

Giant cell - Biopsy shows multinucleated giant cells and sromal cells
tumor - Soap bubble lesions seen most commonly in epiphysis of long bones - mostly distal femur or proximal
tibia
- Locally aggressive and may recur

Malignant tumors

Osteosarco Defn - Malignant tumor of osteoblast that has two peak incidence - most common in teenagers,
ma then in elderly

Risk - Familial retinoblastoma
factors - Paget disease (during the osteolbastic hyperactivity phase)
- Radiation exposure

Presentati - Occurs mostly in metaphysis of long bones (distal femur or proximal tibia mainly)
on - Imaging shows destructive mass with 'sunbrust' appearance due to periosteal reaction

and lifting of periosteum by adjacent tumor(codman triangle)

Musculoskeletal Page 2.2

Biopsy Fig: sunburst appearance (left) and codman triangle (right)
- Pleomorphic cells that produce osteoid

Chondrosa - Malignant tumor of cartilage seen in medulla that can grow out through cortex to make sessile

rcoma paracortical mass

- Seen mostly in central skeleton or pelvis

-

Ewing Defn - Malignant tumor of poorly differentiated neuroectodermal cells seen most commonly in
sarcoma diaphysis of males <15 years

Imaging - Onion skin appearance on X-ray
- Tumor arises in medullary cavity and comes outside the cortex to make soft tan-white
mass

Biopsy - Small round blue cells that resemble lymphocytes (can be confused with lymphoma or
chronic osteomyelitis) (presence of homer wright rosettes indicate neural differentiation)

Cause - Often associated with 11;22 translocation (ewing sarcoma gene (EWS) on ch 22 merges
with transcripton factor gene; precise pathophys unknown)

Musculoskeletal Page 2.3

Prognos - Often metastasizes but responsive to chemotherapy
i

Malignant -
tumors
- Most common malignant bone tumors
- Classic site of origin (lead kettle - PB KTL) - Prostate>breast>kidney>thyroid>lung
- Usually causes osteolytic (punched out) lesion except prostate that cause oseoblastic (sclerotic) leison

Musculoskeletal Page 2.4

18.3 Joint

DJD RA Spondyloarthropathy

+ve Rheumatic factor Negative rheumatic factor

Affects both DIP and PIP Affects mainly PIP symmetrically Affects mainly DIP (sausage

(heubordin-bouchard nodes) fingers)- for psoriatic only

Pain worsens during day Pain gets better during day

Associated with HLA-DR4 Associated with HLA-B27

Degenerative joint disease

Defn - progressive degeneration of articular cartilage
- aka non-inflammatory arthritis (no redness or swelling in joints). Synovial fluid accumulates but
lymphocyte infiltrate are not seen. Lymphocyte infiltrate are hallmark in inflammatory
arthritis - gout and RA.

Risk factors - Obesity
- Age
- Trauma

Clinical ○ Commonly affects hip, lower lumbar, DIP and PIP joints
features ○ Symptoms worsen during day (HY)

Pathologic ○ Eburnation (bone rub) of subchondral bone
features ○ Pieces of bone might fall off in joint space (aka joint mice)
○ Enlarged DIP and PIP joints (heubordin-bouchard nodes) due to osteophyte formation (bone

spurs) (HY)

Fig: from left to right - characterstic fibrillation of articular cartilage; 1=bone eburnation, 2
=subchondral cyst, 3 = normal articular cartilate; joint mice; osteophytes

Fig - osteophytes leading to heubordin-bouchard notes on the left x-ray. Right is normal hand x-
ray

Rheumatoid arthritis

Defn - chronic systemic autoimmune joint disease that causes symmetrical polyarthritis and mainly

Musculoskeletal Page 3.1

Defn - chronic systemic autoimmune joint disease that causes symmetrical polyarthritis and mainly
affects PIP and MCP joints
- Classically seen in middle age woman

Genetics - Associated with HLA-DR4

Pathogene ○ Synovitis leading to formation of pannus (granulation tissue)
sis ▪ Contraction of pannus by myofibroblast can lead to

• ankylosis,
• joint distortion,
• damage of cartilage,
• osteopenia (wearing away of bone due to inflammatory processes)

Presentati - morning stiffness that improves with day
on - Symmetric PIP involvement
- DIP spared (HY) - both DIP and PIP involved in DJD.
- Fever, malaise, myalgia, wt loss (systemic autoimmune signs)
- Others:

- Rheumatoid nodules
- Vasculitis
- Baker cyst (swollen bursa behind knee)
- Pleural effusion, LAD, interstitial lung disease

Labs (HY) - Positive rheumatoid factor (IgM against Fc of IgG)
- Presence of neutrophils and protein in synovial fluid.

Complicaio - Anaemia -
ns ○ chronic inflammatory state produces hepsydin (acute phase protein). Hepsydin blocks ability

to use iron that's stored in macrophage. Results in anemia
- Secondary amyloidosis (liver makes acute phase protein SAA that gets converted to AA amyloid
deposition)

Seronegative Spondyloarthropathy
7. What are clinical features of spondyloarthropathy? Explain its types.
- Negative rheumatoid factor (aka seronegative)
- Affects axial skeleton
- Associated with HLA-B27
- Types
○ Ankylosing spondyloarthritis
 Seen in young adult males
 Presents with sacroiliitis and ankylosis of spine (bamboospine)
 Uveitis - eye inflammation
 Aortitis (weak aorta can lead to aortic regurgitation)
○ Reiter syndrome (reactive arthritis)
 Can't see (conjuctivitis)
 Can't pee (urethritis - pains with urination)
 Can't climb tree (arthritis)
 Usually seen in young males a week after GI or C trachomatis infection.
○ Psoriatic arthritis
 Affects 10% of psoriatic patients
 Affects axial and peripheral joints
 Affects DIP of hands and feet (leads to sausage finger and toes) (HY)

○ Infectious arthritis
 Most commonly seen with Neisseria gonorrhea (young adults)
 Staph aureus (old people or kids).
 Pt usually have only one joint affected - only the knee

Musculoskeletal Page 3.2

 Pt usually have only one joint affected - only the knee
 Pt have systemic signs like fever, increased WBC and elevated ESR
 Can be easily treated with antibiotics

Gout

8. What causes gout?

- Caused due to deposition of MSU (mono sodium urate) crystals in joint.

- Crystals arise due to hyperuricemia (uric acid is nucleotide breakdown product)
○ Occurs either by too much uric acid in blood
○ Or not enough filtration by kidney (more common cause)

9. What are some etiologies of hyperuricemia?

Overproduction Underexcretion (more common)

Psoriasis (increased skin turnover) Renal insufficiency

Strenous exercise Competition for excretion by
- Drugs (thiazides, salicylate)
- EtOH
- Lactic acid
- Ketosis
- Glycogen storage disease

10. What is presentation of acute gout?
- Most commonly seen as highly inflammatory monoarticular arthritis in great toe (podegra)
- Acute inflammation (crystals activate macrophage)

9. What are secondary causes of gout?
- Lukemia and Myeloproliferative Disorder - lots of cell turnover
- Lesch-Nyhan syndrome -
○ breakdown product of purine (xanthine and hypoxanthine) can be recycled. Patients who lack
hypoxanthine guanine phosphoribosyl transferase (HGPRT) (enzyme that recycles these breakdown
products) have high uric acid in blood. Uric acid is end product of purine breakdown.
- Renal insufficiency

11. Why do alcohol and meat exacerbate acute gout?
- EtOH compete with uric acid excretion in kidney.
- Meat has lots of DNA/RNA and the purine metabolism increases uric acid.

12. What is presentation of chronic gout?
- Tophi - UA crystals in soft tissue and joints
- Renal failure -
○ UA deposition in tubules
○ See white chalky deposits in kidney tubules with pink fibrosis
- Lab-
○ Hyperuricemia
○ Needle shaped crystals without birefringence with plane light in synovial fluid

13. What is pseudogout?
- It resembles gout but it's deposition of calcium pyrophosphate (not MSU)
- Knee is to pseudogout (some involvement of wrist) as big toe is to gout.
- Synovial fluid has weak positive birefringence under polarized light

14. What constitutes a positive birefringence?
- Crystals that are horizontal are yellow (low crystals are yellow)

Musculoskeletal Page 3.3

15. What lubricating substance is secreted by synovium?
- Synovial fluid (rich in hyaluronic acid)

Musculoskeletal Page 3.4

18.4-18.5 Muscle and Neuromuscular Junction

Dearmatomyositis vs polymysosits Polymyositis
- Inflammation of skeletal muscle only
Dermatomyositis
- Other than skin involvement, mimics
Defn - Inflammation of skin and skeletal muscle dermatomyositis (bilateral proximal muscle
weakness
Cause - Unknown; some associated with carcinoma

Presentati - Bilateral proximal muscle weakness; distal
on muscles can be affected late

- Rash on upper eyelids (heliotrope rash); malar
rash
- Red papules on elbows, knuckles and knees
(Gottron papules)

Lab - Increased creatine kinase - Endomysial inflammation (CD8+) with necrotic
Biopsy - +ve ANA and anti-Jo-1 Ab muscle fibers

- Perimysial inflammation (CD4+) with
perifascicular atrophy on biopsy

-

X-linked muscular dystrophy

Defn - Degenerative disease with muscle wasting due to bad dystrophin protein and replacement of
muscle by fat

Pathophy - Dystrophin protein is important in anchoring muscle cytoskeleton to extracellular matrix
s - Most mutations are sporadic; large gene size predisposes to high mutation rate - DMD largest

human gene

Types Duchenne muscular dystrophy Becker muscular dystrophy

- Caused due to Deletion of dystrophin gene - Caused due to mutation of
dystrophin gene

Musculoskeletal Page 4.1

- Presents as proximal muscle weakness at 1 year age; distal dystrophin gene
muscles involved later - Clinically milder disease

• Calf pseudohypertrophy characteristic finding (filled
with fat)

- Death due to cardiac or respiratory failure; myocardium
commonly involved

- Elevated serum creatine kinase

Neuromuscular junction
Myasthenia gravis vs Lambert-Eaton syndrome

Myasthenia gravis Lambert-Eaton syndrome

Defn - Ab against postsynaptic Ach receptor at NM - Ab against presynaptic Ca channel at NM
junction junction

Pt popn - Commonly seen in women - Seen as paraneoplastic syndrome; commonly
- 15% of cases associated with thymic hyperplasia in small cell carcinoma of lung
or thymoma

Presentati - Muscle weakness that worsens with use and - Muscle weakness that improves with use and

on improves with rest worsens with rest

- Early eye involvement - ptosis and diplopia (MOST

MUSCULAR DISEASE SPARE EYES)

Treatment - Thymectomy improves symptoms - Resection of cancer resolves disease

- Use anti-cholinesterase agents to increase Ach in - Anti-cholinesterase don't help

synapse

Musculoskeletal Page 4.2

18.6 Soft Tissue Tumor

Lipoma - Benign tumor of adipose tissue
- Most common benign soft tissue tumor in adult

Liposarcoma - Malignant tumor of adipose tissue
- Most common malignant soft tissue tumor in adults
- Lipoblast is characteristic cell - immature fat cell with multiple fat vacuole that create
scalloped appearance of nucleus

Fig: Top left - arrow points to scalloped nucleus in liposacoma; bottom left -
scalloped definition; right - normal adipose tissue biopsy

Rhabdomyoma - Benign tumor of skeletal muscle
- Cardiac rhabdomyoma is associated with tuberous sclerosis

Rhabdomyosarc - Malignant tumor of skeletal muscle
oma - Most common soft tissue tumor in children

- Rhabdomyoblast is characterstic cell - desmin positive
- Most common site is eyes, head and neck; vagina is classic site in young girls

Musculoskeletal Page 5.1

Chapter 19: Skin Pathology

19.1 Inflammatory Dermatoses

1. Describe the histology of epidermis.

Layer Character

Stratum basalis Stem cell layer

Statum spinosum Appears spinous due to desmosomes between keratinocytes

Stratum granulosum See granules in keratinocytes

Stratum corneum See keratin and anucleate cells

INFLAMMATORY DERMATOSES
Atopic dermatitis and contact dermatitis

1. Differentiate atopic dermatitis and contact dermatitis.

Atopic dermatitis Contact dermatitis
Same presentation
Pruritic, erythematous, oozing rash with vesicles
and edema

Skin pathology Page 1.1

and edema Type IV hypersensitivity. Some causes:
- Poison ivy, nickel jewelry
- Type I hypersensitivity reaction; associated with - Irritant chemical (ex- detergent)
asthma and allergic rhinitis - Drugs (ex- penicillin)
- Usually start in face in infancy; seen mostly on
flexor surface afterwards Treatment: topical glucocorticoid and
remove offending agent

Acne vulgaris

Presentation - Comedones (whitehead and blackheads), pustules, and nodules
- Very common in adolescents

Cause - Chronic inflammation of hair follicle and associated sebaceous gland

Pathophysiol - Propionibacterium acnes - infection produces lipases that break sebum to
ogy proinflammatory fatty acids which results in pustules or nodule

- Hormone mediated - androgens increase sebum and excess keratin production.
They block follicles and produce comedones

Treatment - Benzoyl peroxide (antimicrobial)
- Vit A derivatives (reduce keratin production) - ex- isotretinoin

Psoriasis

Presentation - Well-circumscribed salmon-colored plaques with silvery scale, usually on
extensor surface and scales
- Pitting of nails

Pathophysiolo - Excess keratinocyte proliferation
gy

Etiology - Autoimmune: associated with HLA - C
- Environmental trigger may be present: ex - trauma

Histology - Acanthosis- epidermal hyperplasia
- Parakeratosis - retention of nuclei in stratum corneum
- Munro microabscess - neutrophil collection in stratum corneum
- Auspitz sign - thinning of epidermis above elongated dermal paiillae - results in
bleeding when scale is picked off

Treatment - Corticosteroids
- UV-A light with psoralen
- Immune modulating therapy

Lichen planus

Presentation - Pruritic, purple papules with reticular white lines on surface (wickham striae)
- Commonly seen on wrists, elbow, and oral mucosa

Histology - Inflammation of dermal-epidermal junction with a saw tooth appearance

Etiology - Unknown
- Associated with Hep C infection

Skin pathology Page 1.2

19.2 Blistering Dermatoses

Pemphigus vulgaris Bullous pemphigoid

• IgG mediated attack to desmosomes • IgG mediated attack to hemidesmosome

• Cell separate somewhere in stratum • Cells separate in dermal-epidermal junction -
spinosum - vesicles rupture easily vesicles don't rupture easily

• Fish net immunofluorecence • Linear immunofluorescence

• Histology - tombsonte cells, acantholysis • Histology -
(suprabasal vesicle), Nikolky sign

• Oral mucosa involved Oral mucosa spared

Pemphigus vulgaris (pemphigus = watery blister)

Cause IgG mediated attack to desmosomes (desmoglein) (type II hypersensitivity)
between keratinocytes

Presentation - Skin and oral mucosa bullae

Acantholysis Seperation of stratum spinosum keratinocytes (connected by
desmosome) results in suprabasal bullae

Tombstone Basal cells are still attached to dermus and appear as
cells tombstones

Nikolky sign Bullae are thin walled and rupture easily making shallow
erosions with dried crust

- Potentially fatal

Immunofluorec Fish net immunofluorescence pattern- IgG surrounding keratinocytes
ence

Bullous Pemphigod (pemphigoid = similar to pemphigus)

Cause - IgG mediated attack to hemidesmosomes (BP180) between basal cell and
basement membrane

Presentaiton - Blisters on skin, usually in elderly (bullae don't rupture easily - contrast to
pemphigus vulgaris)
- Oral mucosa is spared
- Clinically milder than pemphigus vulgaris

Immunofluoresce Linear pattern
nce

Skin pathology Page 2.1

Immunofluoresce
nce

Dermatitis herpetiformis

Cause - IgA deposition at tip of dermal papillae

Presentation - Grouped pruritic papule, vesicles and bullae

Association Strong association with celiac disease
Treatment Gluten free diet

Erythema Multiforme, Stevens-Johnson syndrome, and Toxic epidermal necrolysis

Erythema Presentatio - Hypersensitivity reaction with targetoid rash (target with
multiforme n multiple rings) and bullae

- Targetoid rash is due to central epidermal necrosis
surrounded by erythema

Cause - HSV (most common)
- Mycoplasma
- Drugs (penicillin and sulfonamides)
- Autoimmune (SLE)
- Malignancy

Stevens-Johnson • Erythema multiforme,bullae,necrosis,sloughing of skin with fever and
syndrome (SJS) mucous membrane involvement

Toxic epidermal • Typically 2 mucous membrane involved - lips, eyes
necrolysis • Mostly associated with adverse drug reaction

Presentati - SJS that occupies >30% of body surface with diffuse
on sloughing of skin resembling large burn

- Separation of cells at dermal-epidermal junction (scalded

Skin pathology Page 2.2

- Separation of cells at dermal-epidermal junction (scalded
skin syndrome separates at stratum granulosum)
Cause - Most commonly due to adverse drug reaction

Skin pathology Page 2.3

19.3 Epithelial Tumors

Seborrheic keratosis

Presentation - Benign squamous proliferation; common in elderly
- Keratin filled cysts (horn cysts) - on extremities or face, coin like stuck on
appearance

Histology Keratin pseudocyst on histology

Leser-Trelat - Sudden onset multiple seborrheic keratoses
sign - Suggests underlying carcinoma of GI tract

Acanthosis nigricans
Presentation - Epidermal hyperplasia with symmetric darkening of skin (velvet like skin)
- Often presents in axilla, neck, groin

Association - Hyperinsulinemia - diabetes, obesity, Cushing
- Visceral carcinoma - ex - gastric carcinoma

Basal cell carcinoma vs squamous cell carcinoma

Skin pathology Page 3.1

Basal cell carcinoma vs squamous cell carcinoma Squamous cell carcinoma
Basal cell carcinoma
Malignant proliferation of supra-basal
Definiti Malignant proliferation of basal cell (stem cell) cell of epidermis - that’s why
on of epidermis presentation is crusty

Epidemi Most common HUMAN CANCER; locally 2nd most common skin cancer
ology invasive but rarely metastasize
- Risk factor related to UVB exposure
• 75% of non-melanoma skin cancer - Others:
- Seen from 50s-70s
• Immunosupressive therapy
Risk Risk factors related to UVB exposure: • Arsenic exposure
- Albinism • Chronic inflammation (burn
- Xeroderma pigmentosum (nucleotide
excision repair damage) scar or draining sinus tract)
- Prolonged sun exposure
- Has stepwise progression like colon
Progres cancer.
sion - Actinic keratosis - precursor lesion of
SCC and presents as hyperkeratotic
scaly plaque (0.07% of AK progress to
SCC per year)
- In Xeroderma pigmentosum, you see
tons of actinic keratosis at very early
age

Present - Pearly and shiny - Crusty, nodular mass
ation - Dialated (telangiectatic) vessel - Classic location is lower lip

- Classic location is upper lip

Histolog - Nodules of basal cell with peripheral palisading • Keratin pearls
y

Skin pathology Page 3.2

Histolog
y

Treatm - Excision - Excision
ent - Metastasis is uncommon - Metastasis is uncommon

- Keratoacanthoma - well differentiated SCC that develops rapidly and regress spontaneously;
presents as cup shaped tumor filled with keratin debris

Skin pathology Page 3.3

19.4 Disorders of Pigmentation and Melanocytes

Melanocytes basic

Melanocyte location Basal layer

Embryogenic development From neural crest cells

Melanin production - Make melanin from tyrosine in melanosomes
- Pass melanosomes to keratinocytes

Vitiligo, albinism, freckle (ephelis), and mesalma

Vitiligo Albinism Freckle Mesalma

- Localized loss of - Mass like
skin hyperpigmentation of
pigmentation cheeks

- Due to - Congenital enzyme - Due to increased number - Associated with
autoimmune defect (tyrosinase) of
damage of melanin production of melanosomes pregnancy and oral
melanocytes pathway
- May involve eyes only (melanocytes number contraceptives
or eye and skin
stay the same
- Increased risk for SCC,
basal cell carcinoma,
and melanoma (sun
damage)

Nevus

Definition - Benign neoplasm of melanocytes

Presentatio - Flat macule or raised papule
n - Symmetric with sharp borders, evenly distributed

Types - Junctional nevus - melanocyte at dermal-epidermal junction; most common in kids
- Compound (intradermal) nevus - melanocyte extension into dermis; most
common in adults

Prognosis - Most common acquired nevi appear in early childhood; evaluate lesions after 20
years age
- Nevi changes is normal. Ex - hormones, pregnancy
- Dysplasia is precursor to melanoma

Melanoma
Definition - Malignant neoplasm of melanocytes - often fatal

Epidemiology - Significant risk of metastasis (contrast to basal cell carcinoma and SCC of skin)

Skin pathology Page 4.1

Epidemiology - Significant risk of metastasis (contrast to basal cell carcinoma and SCC of skin)

Risk - UVB induced DNA damaged
- Dysplastic nevus syndrome (autosomal dominant disorder characterized by
formation of dysplastic nevi that may progress to melanoma)
• >50 nevi; usually appear around puberty and continue to develop beyond
40
- De novo melanoma is more common than dysplasia from nevus

Fig: dysplastic nevus syndrome

Presentation - S-100 tumor marker
- Mole with ABCDE-

• A = asymmetry
• B = borders are irregular
• C = color is non-uniform
• D = diameter>6mm
• E = evolution over time

Growth types - Radial - horizontal growth across epidermis; low risk for metastasis
- Vertical - growth to deep dermis
• Depth of extension (Breslow thickness) most important prognostic factor
for metastasis

Genetics • Often associated with BRAF V600E kinase mutation (55% of cases) (HY)

Treatment • Vemurafenib (BRAF kinase inhibitor) for BRAF +ve tumors
• Surgical excision

Variant of

Skin pathology Page 4.2

Variant of Superficial spreading - Most common subtype
melanoma - Dominant early radiant growth
- Good prognosis

Lentigo maligna melanoma - Lentiginous proliferation (radial growth)
- Good prognosis

Nodular - Early vertical growth
- Poor prognosis

Acral lentiginous - Arises on palm or soles, often in dark skin
individuals
- Acral = affecting limbs

Skin pathology Page 4.3

19.5 Infectious Disorders

Impetigo and cellulitis

Impetigo Cellulitis

Presentati - Erythematous macules that progress to - Red, tender, swollen rash with fever
on pustules; rupture of pustules causes

honey crusted skin

Cause - Superficial bacterial infection: Staph - Deeper dermal and subcutaneous
aureus, Strep pyogenes infection S aureus or S pyogenes

Epidemiol - Commonly affects children - Risk for necrotizing fascitis due to
ogy infection with anaerobic 'flesh eating'
bacteria (surgical emergency)

Staphylococcal scalded skin syndrome

Presentation - Sloughing of skin with red rash and fever

Pathophysiology - Exfoliative A and B toxin results in epidermolysis of stratum
granulosum
Difference from toxic
epidermal necrolysis - Skin separation in TEN occurs at dermal-epidermal junction;
separation in scalded skin junction occurs in stratum granulosum

Molluscum contagiosum
Presentation - Firm, pink, umbilicated papules

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-

Cause - Poxvirus infection
Histology
Classic pt - Affected cells show molluscum bodies (cytoplasmic inclusion)

- Kids
- Sexually active adults
- Immunecompromised individuals

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Dermatologic morphology

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