Step 1 - Oncology (Path/Pharm)
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40 terms
Terms | Definitions |
|---|---|
 Hodgkin's lymphoma | B-cell lymphoma -Affects localized, single group of nodes (extranodal is rare); contiguous spread (stage is strongest predictor of prognosis) -Constitutional B symptoms: low-grade fever, night sweats, weight loss -Mediastinal lymphadenopathy -50% of cases associated with EBV (young & old people) -Reed-Sternberg cells: B-cell origin, CD30+, CD15+; binucleate or bilobed with 2 halves as mirror images ("owl eyes") -Prognosis worsens with dec. lymphocytes and inc. RS cells |
| Hodgkin's lymphoma: nodular sclerosing type | Nodules of mixed inflammatory cells -Some RS cells & lacunar cells surrounded by bands of sclerotic fibrous tissue (collagen banding) -Excellent prognosis |
| Hodgkin's lymphoma: mixed cellularity type | Numerous RS cells, more aggressive, usually found in older patients -EBV+ (60-70%) -Intermediate prognosis |
| Hodgkin's lymphoma: lymphocyte predominant type | Found in males 30-50 years of age -Originate in germinal center -Large nodules of small lymphocytes & macrophages ("popcorn" cells) -Excellent prognosis |
| Non-Hodgkin's lymphoma | May be associated with HIV and immunosuppression -Multiple, peripheral nodal involvement; extranodal involvement is common; non-contiguous spread -Majority involve B-cells -Fewer constitutional S/S -Peak incidence 20-40 y.o. |
| Burkitt's lymphoma | Non-Hodgkin's B-cell lymphoma -Occurs in adolescents or young adults -t(8;14): C-MYC gene moves next to heavy-chain IgG gene -"Starry-sky" appearance (sheets of lymphocytes with interspersed macrophages) -Associated with EBV: infectious mononucleosis (high fever, cervical lymphadenopathy, splenomegaly) -Jaw lesion in endemic form in Africa; pelvis or abdomen in sporadic form |
| Diffuse large B-cell lymphoma | Non-Hodgkin's B-cell lymphoma -Usually affects older adults, but 20% in children -Most common adult NHL -May be mature T-cell in origin (20%) |
| Mantle cell lymphoma | Non-Hodgkin's B-cell lymphoma -Occurs in older males -t(11;14): overexpression of cyclin D1/Bcl-1 protein -Poor prognosis -CD5+ |
| Follicular lymphoma | Non-Hodgkin's B-cell lymphoma -Occurs in adults, most common indolent Non-Hodgkin's lymphoma -t(14;18): overexpression of bcl-2 -> inhibition of apoptosis -Indolent course with remissions and recurrence -> size fluctuates over time, difficult to cure -S/S: painless lymph node enlargement, abdominal discomfort |
| Adult T-cell lymphoma | Non-Hodgkin's T-cell lymphoma -Occurs in adults, especially in Japan, West Africa, and the Caribbean -Caused by HTLV-1 infection: retrovirus integrates into T-cell DNA -Presents with cutaneous lesions -Aggressive course |
| Sezary syndrome | Non-Hodgkin's T-cell lymphoma -Leukemic form of mycosis fungoides (cutaneous T-cell lymphoma) -Generalized erythroderma ("red man syndrome"): hyperkeratosis of palms and soles, pruritis |
| Multiple myeloma | Malignant proliferation of plasma cells that replace bone marrow and secrete monoclonal IgG & IgA antibodies -Cells have a "fried-egg" appearance & M-spike on protein electrophoresis 1. Signs/symptoms ("CRAB") -hyperCalcemia: secondary to bone destruction -Renal insufficiency: "myeloma kidney" with waxy Ab casts depositing in renal tubules and Ig light chains in urine (Bence-Jones proteins) -Anemia: infiltration of marrow, dec. EPO secretion, hemolysis (rouleaux formation) -Bone lytic lesions & Back pain: pathologic fractures, diffuse bone loss, osteoporosis (punched-out lesions on X-ray) 2. Associated with: -Increased susceptibility to infx (encapsulated organisms) -Primary amyloidosis (AL) |
| Waldenstrom's macroglobulinemia | Lymphoplasmacytic cells invade bone marrow and secrete IgM antibody (vs. IgG/IgA in MM) -B-cell proliferation causes B-symptoms, infiltration of BM, lymph nodes, and organs -M-protein production by plasma cells -> hyperviscosity syndrome, neuropathy, cold agglutinin disease, and Raynaud's phenomenon -NO lytic bone lesions! |
| Acute lymphoblastic leukemia (ALL) | Lymphoid leukemia -Homogeneous proliferation of precursor B-cells or T-cells (lymphoblasts) with very high mitotic activity -> bone marrow is replaced by lymphoblasts -Bone marrow involvement in childhood (B-cells) -Mediastinal mass in adolescent males (T-cells): compresses great vessels, esophagus, and trachea -> superior vena cava syndrome, dysphagia, dyspnea/stridor -Markers: TdT+ (blast marker), CALLA+ (CD10), CD19+ (B-cell), CD5+ (T-cell) -May spread to testes or CNS -t(12;21) -> better prognosis -Most responsive to therapy |
| Chronic lymphocytic leukemia (CLL) | Lymphoid leukemia -Mature B or T-cell lymphocytosis in peripheral blood and bone marrow -Often asymptomatic, affects older adults -Blood smear: smudge cells -Labs: increased neutrophil alkaline phosphatase levels (vs. CML) -Immune complications (warm antibody autoimmune hemolytic anemia) |
| Hairy cell leukemia | Lymphoid leukemia -Mature B-cell tumor in the elderly, more often in males -Pancytopenia and splenomegaly in an elderly man -Labs: low leukocyte count, "hairy cells" on blood smear -Stains TRAP+ (tartrate-resistant acid phosphatase) -Indolent, slowly progressive disease w/bleeding and infection complications -Tx: cladribine (purine analog; resistant to adenosine deaminase -> can reach high intracellular concentrations) |
| Acute myelogenous leukemia (AML) | Myeloid leukemia -Malignancy of immature hematopoietic cells that also inhibit normal hematopoietic maturation -Commonly affects adults -Blood smear: increased number of circulating myeloblasts with Auer rods (stain with peroxidase) |
| Acute promyelocytic leukemia (APL) | Myeloid leukemia -M3 variant of ALL -t(15,17): PML-RAR-alpha fusion protein inhibits DNA transcription via abnormal retinoic acid receptor -Blood smear: myeloblasts w/Auer rods -Tx: all-trans retinoic acid (ATRA) -Treatment may release Auer rods from cells -> DIC |
| Chronic myelogenous leukemia (CML) | Myeloid leukemia -All levels of maturation of granulocytic cells are represented (neutrophils, basophils, eosinophils) -t(9;22): Philadelphia chromosome -> bcr-abl tyrosine kinase fusion protein -Splenomegaly -May accelerate and transform into AML or ALL -> "blast crisis" -Labs: very low leukocyte alkaline phosphatase (vs. CLL) -Tx: Imatinib |
| Langerhans cell histiocytosis (histiocytosis X) | Proliferative disorder of dendritic (Langerhans) cells -Defective cells express S-100 and CD1a -EM: Birbeck granules ("tennis rackets") |
| Polycythemia vera | Chronic myeloproliferative disorder -Absolute erythrocytosis; slight male predominance -JAK2 V617F mutation -> tyrosine kinase is constitutively active -> BM trilineage proliferation -> hypercellular BM (erythrocytes, platelets, and leukocytes) -S/S: aquagenic pruritus, gout, bleeding, erythromelalgia (burning, redness of the hands & feet) -May cause abdominal vein thrombosis -> Budd Chiari Syndrome |
| Essential thrombocytosis | Chronic myeloproliferative disorder -Proliferation of megakaryocytes and platelets; slight female predominance -JAK2 V617F mutation -> tyrosine kinase is constitutively active -Persistent thrombocytosis (>450k) -BM: proliferating megakaryocytes with hyperlobated nuclei -S/S: often asymptomatic; may have large vessel thrombosis, bleeding, splenomegaly, erythromelalgia |
| Myelofibrosis | Chronic myeloproliferative disorder -Proliferation of megakaryocytes, granulocytes, and fibroblasts -> marrow fibrosis and angiogenesis -JAK2 V617F mutation -> tyrosine kinase is constitutively active -S/S: fatigue, weight loss, fever, night sweats, bone pain, marrow failure -> extramedullary hematopoiesis (splenomegaly) -Blood smear: "tear-drop" RBCs (dacryocytes), hypercellularity and clustering of atypical megakaryocytes, reticulin |
| Methotrexate (MTX) | Antimetabolite -Mech: folic acid analog that inhibits dihydrofolate reductase -> dec. dTMP synthesis -> dec. DNA and protein synthesis -Clinical: cancer (leukemia, lymphoma, choriocarcinoma, sarcoma), abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis -Tox: myelosuppression, macrovesicular fatty liver, mucositis/stomatitis, teratogenic -Leucovorin (folinic acid) rescue: replaces THF that was lost to MTX; used to treat myelosuppression |
| 5-fluorouracil (5-FU) | Antimetabolite -Mech: pyrimidine analog that is bioactivated to 5F-dUMP, which covalently complexes with folic acid -> inhibits thymidylate synthase -> dec. dTMP -> dec. DNA and protein synthesis -Clinical: colon cancer and other solid tumors, basal cell carcinoma (topical); synergy with MTX -Tox: myelosuppression (NOT reversible with leucovorin; treat overdose with thymidine); photosensitivity |
| 6-mercaptopurine (azathioprine) | Antimetabolite -Mech: purine analog -> decreases de novo purine synthesis; activated by HGPRTase -Clinical: leukemia, lymphoma (NOT CLL or Hodgkin's) -Tox: bone marrow, GI, liver; metabolized by xanthine oxidase, so has increased toxicity with allopurinol -6-thioguanine (6-TG): can be given with allopurinol |
| Dactinomycin | Antitumor antibiotic -Mech: intercalates into DNA -Clinical: Wilms tumor, Ewing's sarcoma, rhabdomyosarcoma ("children ACT out") -Tox: myelosuppression |
| Doxorubicin (adriamycin) | Antitumor antibiotic -Mech: noncovalently intercalates into DNA and generate free radicals -> DNA breaks -> dec. replication -Clinical: Hodgkin's lymphoma, myelomas, sarcomas, solid tumors -Tox: dilated cardiomyopathy, myelosuppression, alopecia |
| Bleomycin | Antitumor antibiotic -Mech: induces free radical formation -> causes breaks in DNA strands -Clinical: testicular cancer, Hodgkin's lymphoma -Tox: pulmonary fibrosis, skin changes; minimal myelosuppression |
| Etoposide | Antitumor antibiotic -Mech: inhibits DNA topoisomerase II -> increased DNA degradation -Clinical: small cell carcinoma of lung and prostate, testicular carcinoma -Tox: myelosuppression, GI irritation, alopecia |
| Cyclophosphamide | Alkylating agents -Mech: covalently cross-link DNA at guanine N-7; requires bioactivation by the liver -Clinical: non-Hodgkin's lymphoma, breast/ovarian carcinomas, immunosuppression -Tox: myelosuppression, hemorrhagic cystitis -Partially prevented with mesna |
| Nitrosureas | Alkylating agents (carmustine, lomustine, semustine, streptozocin) -Mech: require bioactivation; can cross the BBB into the CNS -Clinical: brain tumors (e.g. glioblastoma multiforme) -Tox: CNS toxicity (dizziness, ataxia) |
| Vincristine, vinblastine | Microtubule inhibitors -Mech: bind to tubulin in M-phase and block formation of mitotic spindle -Clinical: Hodgkin's lymphoma, Wilms' tumor, choriocarcinoma -Tox: neurotoxicity (areflexia, peripheral neuritis) and paralytic ileus (vincristine); BM suppression (vinblastine) |
| Paclitaxel | Microtubule inhibitor -Mech: hyperstabilize polymerized microtubules in M-phase to prevent breakdown of the mitotic spindle -Clinical: ovarian and breast carcinomas -Tox: myelosuppression, hypersensitivity |
| Cisplatin, carboplatin | Platinums -Mech: cross-link DNA -Clinical: testicular, bladder, ovary, and lung carcinomas -Tox: nephrotoxicity, ototoxicity (high-frequency hearing loss, tinnitus) -Prevent with amifostine |
| Hydroxyurea | Inhibits ribonucleotide reductase -> decreased pyrimidine synthesis -> decreased DNA synthesis (S-phase specific) -Clinical: melanoma, CML, sickle cell disease (increases HbF synthesis) -Tox: bone marrow suppression, GI upset |
| Prednisone | Most commonly used glucocorticoid in cancer chemotherapy -Clinical: CLL, Hodgkin's lymphoma (MOPP regimen), immunosuppression -Tox: Cushing-like symptoms, immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis |
| Trastuzumab (Herceptin) | Monoclonal antibody -Mech: binds and kills breast cancer cells that overexpress HER-2 (antibody-dependent cytotoxicity) -Clinical: metastatic breast cancer -Tox: cardiotoxicity |
| Imatinib (Gleevec) | Tyrosine kinase inhibitor -Mech: inhibits Philadelphia chromosome bcr-abl tyrosine kinase fusion protein -Clinical: CML, GI stromal tumors -Tox: fluid retention |
| Rituximab | Monoclonal antibody -Mech: binds to CD20 on neoplastic B-cells -Clinical: Non-Hodgkin's lymphoma, rheumatoid arthritis (w/MTX) |
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