Paraneoplastic Syndrome/Skin Cancers Flashcards
what are endocrinopathies associated with paraneoplastic syndrome?
cushing syndrome, ADH, hypercalcemia, hypoglycemia, polycythemia
what cancers do you see cushing syndrome in?
SCLC, pancreatic carcinoma, neural tumors, ACTH is high and includes high serum pro-opiomelanocortin
when is ADH secretion seen?
SCLC, intracranial neoplasms
when is hypercalcemia seen?
parathyroid hormone related protein is released, TGFalpha, IL-1, seen in squamous cell carcinoma, breast, renal, adult T cell leukemia, lymphoma
what is hypoglycemia seen in ?
ovarian carcinoma, fibrosarcoma, other mesenchymal sarcomas
what is polycythemia seen in
renal, cerebellar hemangioma, hepatocellular carcinoma
what is myasthenia gravis seen in
bronchogenic carcinoma, thymic neoplasms
what CNS/PNS disorders are likely seen in breast cancers?
peripheral neuropathies, cortical cerebrallar degeneration, polymyopathy resembling polymitosis
what is acanthosis nigricans?
derm disorder associated with paraneoplastic syndrome, seen in gastric carcinoma, lung and uterine, grey/black thickened keratotic, velvety skin
what is dermatomyositis seen in?
bronchogenic, thymic neoplasms
when would you see finger clubbing?
liver disease, diffuse lung disease, congenital cyanotic heart disease, ulcerative colitis
what is hypertrophic osteoarthropathy?
periosteal new bone formation at distal end of long bones, metacarpals, metatarsals, proximal phalanges, and arthritis of adjacent joints
when is trousseau phenomenon/venous thrombosis seen?
pancreatic, bronchogenic, when tumor products/mucins activate clotting
what is red cell aplasia associated with?
thymic neoplasms
what is thrombotic endocarditis associtaed with?
not bacterial, causes hypercoagulability, seen in advanced cancers
when is disseminated intravascular coagulation caused by tumor products that activate clotting seen?
acute promyelocytic leukemia, and prostatic cancer
what is melanoma linked with?
acquired mutations caused by UV radiation/periodic sunburns early in life
what gene is commonly mutated in melanoma?
familial form: CDKN2A, which encodes p15ink4b (loss of this is indicated in melanoma), p16/innk4a, and p14/ARF, sporadic form: activation in BRAF and NRAF is seen in sporadic form, activation of TERT
what is p16/ink4a
tumor suppressor, inhibits cdk4 and cdk6, reinforces RB tumor suppressor to block cells in G1 phase of cell cycle - if this is lost, cdk binds and inactivates RB, sends E2F
what is p14/ARF
enhances activity of p53 tumor suppressor by inhibiting MDM2 - if lost, MDM2 not inhibited, and p53 is degraded
what are the 7 prognostic factors of melanoma
- tumor depth (breslow thickness)
- number of mitoses
- evidence of tumor regression (absence is good)
- ulceration of underlying skin (lack is good)
- presence and number of tumor infiltrating lymphocytes
- gender
- location
usual location of melanoma on male and female
males usually on back and upper trunk, females on legs
what are the ABCDE of melanoma
asymmetry, irregular borders, color, increasing diameter over 6mm, evolution over time
what treatment is best and worst for melanoma
RAS and P13K/AKT pathway blockers, melanoma is resistant to chemo and radiation
what is the most common non-melanoma skin cancer?
basal cell
pathogenesis of squamous cell carcinoma?
degree of lifetime sun exposure, immunosuppression, industrial carcinogens, usually p53 is mutated leading to increased RAS and decreased notch
what skin cancer is commonly seen in immunocompromised/immunosuppressive people and those with disorders of dna repair?
basal cell carcinoma
pathogenesis of basal cell carcinoma
unbridled SHH signaling due to PTCH mutation
indications for RAF blockers
familial melanoma is mutated in p16INK4a, so raf is wild type. treating with RAF blocker may actually induce growth of a tumor, so only treat sporadic melanoma with RAF inhibitor
