Wednesday, February 15th Seth Wander sawander@med.miami.edu 2014 Step 1 Review Oncology Wednesday, February 15th Seth Wander sawander@med.miami.edu

Oncology General comments Lymphomas Leukemias Chemotherapeutics Sample questions

Hodgkin’s Lymphoma Low-grade fever, night sweats, weight loss Constitutional “B” symptoms Localized group of nodes, contiguous spread Mediastinal lymphadenopathy 50% associated with EBV Reed-Sternberg cells Good prognosis = ↑lymphocytes ↓RS CD30+, CD15+ B cell origin

Non-Hodgkin’s Lymphoma Neoplasms of mature B cells: Burkitt’s lymphoma: t(8;14) = c-myc:Ig Children “starry-sky” histology Associated with EBV Jaw lesion in Africa Diffuse large B-cell lymphoma: Most common adult NHL Most B cell (20% T cell) Mantle cell lymphoma: t(11;14) cyclin D1 overexpression Adults CD5+ B cells Peyer’s patches@ terminal ileum Follicular lymphoma: t(14;18) bcl2 overexpression Indolent, waxing + waning lymphadenopathy

Abnormal stem cells @ bone marrow Leukemias Abnormal stem cells @ bone marrow Acute Blasts Children Short course Chronic Mature cells Midlife Longer course Acute Lymphoblastic Lymphoblasts @ bone marrow Responsive to therapy May spread to CNS/testes Acute Myelogenous M3 t(15;17) = PML-RAR, all-trans retinoic acid Auer rods Myeloblasts Chronic Lymphocytic Asymptomatic, indolent Autoimmune hemolytic anemia Smudge cells Chronic Myelogenous t(9;22) = bcr-abl Neutrophils, basophils Blast crisis (AML) Low leukocyte alkaline phosphatase

Leukemias CML: t(9;22) Philadelphia chromosome bcr-abl fusion Abl = tyrosine kinase Imatinib (gleevac) = anti-bcr-abl antibody ** Oncogene addiction + Rational drug design

Chemotherapeutics Nucleotide synthesis DNA RNA Protein Cellular division Methotrexate, 5-FU: (↓ thymidine synthesis) 6-MP: (↓ purine synthesis) Cytarabine (ara-C) (inhibits DNA Pol) Alkylating agents, cisplatin: (cross-link DNA) Doxorubicin, dactinomycin: (intercalate DNA) Bleomycin: (free radical formation) Etoposide: (inhibits Topoisomerase II) Vinca alkaloids: (inhibits microtubule assembly) Paclitaxel: (inhibits microtubule disassembly)

1) Which of the following features represents a typical presentation for Non-Hodgkin’s lymphoma? A) Low-grade fever and night sweats B) Contiguous spread C) Extranodal involvement D) Reed-Sternberg cells

2) A young child in Africa presents to the clinic with the following lesion in his jaw. You suspect a certain type of lymphoma with which of the following characteristic translocations? A) t(14;18) B) t(9;22) C) t(11;22) D) t(8;14)

3) A patient with a history of testicular cancer returns to the clinic for a regular follow up. He reports increasing shortness of breath. Pulmonary function tests reveal a restrictive pattern. Which of the following drugs was likely included in his treatment protocol? A) Doxorubicin B) Bleomycin C) Etoposide D) Paclitaxel

4) An adult patient presents with a rapidly progressive history of infections and excessive bleeding. The peripheral blood smear demonstrates increased circulating myeloblasts. A representative image is shown below. This patient might benefit from which of the following treatments? A) All-trans retinoic acid B) Imatinib C) Vincristine D) Doxorubicin

5) An elderly patient presents with pancytopenia and splenomegaly but does not demonstrate lymphadenopathy. The peripheral blood smear is shown below. What is the likely diagnosis? A) CLL B) Hodgkin’s lymphoma C) CML D) Hairy cell leukemia

6) Which of the following best describes the molecular function of Imatinib/Gleevac, used to treat CML? A) Inhibitor of Topoisomerase II B) Tyrosine kinase inhibitor C) Alkylating agent D) Microtubule assembly inhibitor

7) Both vincristine and paclitaxel act at which stage of the cell cycle? B) S C) G2 D) M

8) An elderly patient presents following a wrist fracture 8) An elderly patient presents following a wrist fracture. X-rays demonstrate several “punched-out” lytic lesions. Urinalysis reveals elevated Ig light chains. What is the diagnosis? A) Metastatic breast cancer B) Osteosarcoma C) Multiple Myeloma D) CLL