MSK/Skin Pathology Flashcards
Achondroplasia
AD cause of dwarfism; cartilage proliferation in growth plate is impaired due to activating mutation of fibroblast growth factor receptor 3 (FGFR3)
Osteogenesis imperfecta
AD defect in type 1 collagen synthesis; results in bone fractures, blue sclera, and hearing loss
Osteopetrosis
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
Paget disease of bone
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
Causes of osteomyelitis
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)
Osteoid osteoma vs. osteoblastoma
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).
Osteosarcoma
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
Giant cell tumor
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
Ewing sarcoma
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
Cartilage tumors
Arise in the medullary
Chondromas arise in the small bones of the hands and feet
Chondrosarcomas arise in the pelvis or central skeleton
Metastatic osteoblastic lesion
Caused by metastatic prostate cancer.
Most metastatic tumors are osteolytic (punched-out)
Rheumatoid arthritis
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)
Ankylosing sponydloarthritis
Seronegative spondyloarthopathy (HLA-B27)
Involves sacroiliac joint and spine in young males (“bamboo spine”); associated with uveitis and aortitis (leading to AR)
Reiter syndrome
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
Psoriatic arthritis
Seronegative spondyloarthopathy (HLA-B27)
Involvement of DIP joints lead to sausage fingers/toes
Lesch-Nyhan syndrome
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.
Dermatomyositis
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
Polymyositis
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)
Myasthenia gravis
Caused by autoantibodies against postsynaptic ACh receptor at NMJ; muscle weakness worsens with use
Symptoms improve with rest and anticholinesterase agents
Thymectomy improves symptoms
Lambert-Eaton syndrome
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
Psoriasis
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)
Lichen planus
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
Pemphigus vulgaris
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
Bullous pemphigoid
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
Erythema multiforme (EM)
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
Risk factors for development of squamous cell carcinoma
- UVB-induced DNA damage (prolonged sunlight exposure, albinism, xeroderma pigmentosum)
- Immunosuppressive therapy
- Arsenic exposure
- Chronic inflammation
Vitiligo
Localized autoimmune destruction of melanocytes
Albinism
Congenital lack of tyrosinase (impairs melanin production)
Staphylococcal scalded skin syndrome
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
Myotonic dystrophy
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
Guillain-Barre syndrome
Rapid-onset demylinating syndrome of the peripheral nerves characterized by ascending muscle weakness and paralysis
Often preceded by infection by Campylobacter jejuni
Xeroderma pigmentosum
Defect in DNA excisional repair
Increased sensitivity to UV radiation and a high incidence of all forms of cutaneous malignancy.
Pityriasis versicolor
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
