MSK/Skin Pathology

Question 1

Achondroplasia

Answer 1

AD cause of dwarfism; cartilage proliferation in growth plate is impaired due to activating mutation of fibroblast growth factor receptor 3 (FGFR3)

Question 2

Osteogenesis imperfecta

Answer 2

AD defect in type 1 collagen synthesis; results in bone fractures, blue sclera, and hearing loss

Question 3

Osteopetrosis

Answer 3

Defect in osteoclast function resulting in abnormally thick heavy bone that fractures easily; may be associated with carbonic anhydrase 2 mutation

Characterized by bone fractures, pancytopenia, CN impingement, hydrocephalus, and renal tubular acidosis

Question 4

Paget disease of bone

Answer 4

Imbalance between osteoclast and osteoblast formation; usually seen in late adulthood; results in thick sclerotic bone that fractures easily.

Biopsy reveals mosaic pattern of lamellar bone. Features include bone pain, increased hat size, hearing loss, lion-like facies, isolated elevated Alk Phos (due to osteoblasts)

Complications: High-output cardiac failure, osteosarcoma

Question 5

Causes of osteomyelitis

Answer 5

S. auresus - most common cause

N. gonorrhea - sexually active young adults

Salmonella - sickle cell disease

Pseudomonas - diabetic or IV drug users

Pasteurella - cat or dog bite/scratches

M. tuberculosis - Pott disease (vertebrae)

Question 6

Osteoid osteoma vs. osteoblastoma

Answer 6

Both are benign tumors of osteoblasts

Osteoblastoma is larger (>2 cm), arises in vertebrae (OO arises in cortex of long bones), and is NOT relieved with aspirin (unlike OO).

Question 7

Osteosarcoma

Answer 7

Malignant proliferation of osteoblasts; peak incidences in teenagers in the elderly; airses in the metaphysis of long bones, usually surrounding the knee.

Imaging reveals “sunburst” appearance and lifting of periosteum by the tumor to form “Codman triangle”

Histology reveals pleomorphic cells that produce eosinophilic osteoid

Question 8

Giant cell tumor

Answer 8

Benign tumor of epiphyseal end of long bones, affecting adults between 20-40 yo

Often around the knee

“Soap-bubble” appearance on x-ray.

Multinucleated giant cells

Question 9

Ewing sarcoma

Answer 9

Malignant bone tumor in boys < 15 yo. Commonly affects diaphysis of long bones, pelvis, scapula, and ribs

Anaplastic small blue cells

“Onion-skin” appearance

Associated with t(11;22) translocation

Question 10

Cartilage tumors

Answer 10

Arise in the medullary

Chondromas arise in the small bones of the hands and feet

Chondrosarcomas arise in the pelvis or central skeleton

Question 11

Metastatic osteoblastic lesion

Answer 11

Caused by metastatic prostate cancer.

Most metastatic tumors are osteolytic (punched-out)

Question 12

Rheumatoid arthritis

Answer 12

Synovitis leading to formation fo a pannus, leading to destruction of cartilage and ankylosis (fusion) of joint; associated with HLA-DR4

Arthritis improves with activity and DIP is spared (unlike OA)

Rheumatoid factor: IgM autoantibodies against Fc portion of IgG

Anti-cyclic cintrullinated peptide antibody (more specific than RF)

Complications: anemia of chronic disease and secondary amyloidosis

Tx: NSAIDs, Glucocorticoids, DMARDs (methotrexate, sulfasalazine, TNF-alpha inhibitors)

Question 13

Ankylosing sponydloarthritis

Answer 13

Seronegative spondyloarthopathy (HLA-B27)

Involves sacroiliac joint and spine in young males (“bamboo spine”); associated with uveitis and aortitis (leading to AR)

Question 14

Reiter syndrome

Answer 14

Seronegative spondyloarthopathy (HLA-B27)

Triad of reactive arthritis, urethritis, and conjunctivitis (“can’t see, can’t pee, can’t climb a tree”)

Usually arises weeks after GI/chlamydia infection

Question 15

Psoriatic arthritis

Answer 15

Seronegative spondyloarthopathy (HLA-B27)

Involvement of DIP joints lead to sausage fingers/toes

Question 16

Lesch-Nyhan syndrome

Answer 16

X-linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which is required for hypoxanthine and guanine salvage. Loss of HGPRT results in hyperuricemia.

Characterized by hyperuricemia, mental retardation, and self-mutilation.

Question 17

Dermatomyositis

Answer 17

Progressive symmetric proximal muscle weakness with malar rash, Gottron papules, and heliotrophe (erythematous periorbital rash)

Perimysial inflammation and atrophy with CD4+ T cells

Increased risk of occult malignancy

+ANA, +anti-Jo-1, +anti-SRP, +anti-Mi2

Question 18

Polymyositis

Answer 18

Similar to dermatomyositis, but it does not involve the skin.

Biopsy reveals endomysial inflammation (CD8 cells) with necrotic muscle fibers (unlike perimysial inflammation with CD4 cells in dermatomyositis)

Question 19

Myasthenia gravis

Answer 19

Caused by autoantibodies against postsynaptic ACh receptor at NMJ; muscle weakness worsens with use

Symptoms improve with rest and anticholinesterase agents

Thymectomy improves symptoms

Question 20

Lambert-Eaton syndrome

Answer 20

Autoantibodies against presynaptic calcium channels of NMJ; arises as a paraneoplastic syndrome (SCC of lung)

Characterized by proximal muscle weakness that improves with use (eyes are usually spared)

Anticholinesterase agents do not improve symptoms

Question 21

Psoriasis

Answer 21

Well-circumscribed salmon-colored plaques with silvery scale on extensor surfaces and scalp; due to excessive keratinocyte proliferation; associated with HLA-C

Characterized by acanothosis (epidermal hyperplasia), parakeratosis (hyperkeratosis with retention of keratinocyte nuclei in stratum corneum, leading to silver scale), munro abscesses (neutrophils in stratum corneum), and Auspitz sign (bleeding when scale is picked off)

Question 22

Lichen planus

Answer 22

Pruiritic, planar, polygonal, purple papules with Wickham striae (reticular white lines on surface)

Characteristic saw-tooth appearance of dermal-epidermal junction

Associated with chronic HCV

Question 23

Pemphigus vulgaris

Answer 23

Autoimmune destruction of desmosomes between keratinocytes due to IgG antibody against desmoglein

Characterized by suprabasal bullae of the skin and oral mucosa that rupture easily (Nikolsky sign)

Immunofluorescence: “fish net” pattern of IgG surrounding keratinocytes

Question 24

Bullous pemphigoid

Answer 24

Autoimmune destruction of hemidesmosomes between basal cells and underlying BM due to IgG antibody against hemidesmosome (BP180)

Tense bullae do not rupture as easily as thin-walled bullae of pemphigus vulgaris, and the bullae of BP do not involve the oral mucosa (unlike in PV)

Immunofluorescence: linear pattern of IgG along BM

Question 25

Erythema multiforme (EM)

Answer 25

Hypersensitivity reaction characterized by targetoid erythematous rash and bullae

Associated with HSV (most common), Myoplasma, drugs (penicillin, sulfonamides), autoimmune disease

Stevens-Johnson syndrome (SJS) = EM + fever + oral mucosa involvement

Toxic epidermal necrolysis = SJS + diffuse sloughing of skin

Question 26

Risk factors for development of squamous cell carcinoma

Answer 26

• UVB-induced DNA damage (prolonged sunlight exposure, albinism, xeroderma pigmentosum)
• Immunosuppressive therapy
• Arsenic exposure
• Chronic inflammation

Question 27

Vitiligo

Answer 27

Localized autoimmune destruction of melanocytes

Question 28

Albinism

Answer 28

Congenital lack of tyrosinase (impairs melanin production)

Question 29

Staphylococcal scalded skin syndrome

Answer 29

S. aureus releases exfoliative A and B toxins, which cause epidermolysis of the stratum granulosum.

More superficial than toxic epidermal necrolysis, which causes skin separation at the dermal-epidermal junction

Question 30

Myotonic dystrophy

Answer 30

Autosomal dominant disorder caused by increased number of trinucleotide repeats on the myotonia-protein kinase gene

Sustained muscle contraction (myotonia), weakness, atrophy, cataracts, frontal balding, gonadal atrophy

Question 31

Guillain-Barre syndrome

Answer 31

Rapid-onset demylinating syndrome of the peripheral nerves characterized by ascending muscle weakness and paralysis

Often preceded by infection by Campylobacter jejuni

Question 32

Xeroderma pigmentosum

Answer 32

Defect in DNA excisional repair

Increased sensitivity to UV radiation and a high incidence of all forms of cutaneous malignancy.

Question 33

Pityriasis versicolor

Answer 33

Hypo- or hyperpigmented skin patches/papules caused by fungus Malassezia furfur. Infection localized to the stratum corneum fo the skin.

Spores and hyphae of M. furfur appear like “spaghetti and meatballs” on light microscopy. The hyphae also have a “cigar-butt” appearance