Heme Onc Flashcards
ALL (acute lymphoblastic leukemia)
common in kids
associated w/ Down syndrome
TdT+ (marker of pre-T and pre-B cells), CD10+
most resposive to therapy, may spread to CNS and testes
t(12;21) = better prognosis
B-ALL and T-ALL:
T-ALL (15-17%) associated w/ mediastinal mass (presents as SVC-like syndrome; may compress esophagus, trachea –> dysphagia, dyspnea, stridor). B-ALL (70-80%) p/w fever, malaise, bleeding, HSM
Chronic lymphocytic leukemia/small lymphocytic lymphoma
Elderly, most common adult leukemia
CD20/23/5+ B cell neoplasm
Slow progression, often asymp.
Smudge cells ("Crushed Little Lymphocytes")
Richter transformation into DLBCLHairy cell leukemia
Old men, TRAP+ (“it’s a trap!”)
Fuzzy on LM
Marrow fibrosis (dry tap on aspiration), massive splenomegaly, pancytopenia
AML (acute myelogenous leukemia) and APML (acute promyelocytic leukemia)
Older people 65 yo
Auer rods pathognom, (myelo)peroxidase+
Increased myeloblasts on periph smear
Risks: prior alkylating chemo, XRT, myeloproliferative disorders, Down syndrome
APML: t(15;17) forming PML/RARa fusion product that codes for abnormal retinoic acid receptor. Responds to all-trans retinoic acid (vit A), inducing diff’ation of promyelocytes; abundant Auer rods; DIC common
CML
Peak 45-85 yo, median 64 yo
Philly chromosome (t(9;22), BCR-ABL)
Dysregulated granulocyte prodxn, splenomegaly
Can transform into AML or ALL (blast crisis)
LAP is low (vs. leukemoid rxn)
Tx w/ tyr kinase inhibitors like imatinib
Factor V Leiden deficiency
Inherited mutation to factor V that makes it resistant to degradation by protein C –> most common cause of inherited hypercoagulability in Caucasians. Increased risk of thrombotic events (DVT/PE, cerebral vein thromboses, recurrent pregnancy loss)
Protein C or S deficiency
Inability to inactivate factors 5 and 8
Protein C deficiency –> increased risk of warfarin skin necrosis (because warfarin inactivates vit K dependent factors 2, 7, 9, 10, C, S - and C is first to fall with initiation of therapy d/t short half life, causing transient hypercoagulable state –> microthrombi, skin necrosis
Hodgkin lymphoma + subtypes
Localized group of nodes Contiguous spread Better prognosis overall than NHL Reed-Sternberg cells (owl eyes) Bimodal (young adults and > 55 yrs); more common in men except NS type EBV-associated
Nodular sclerosing (NS) - most common
Lymphocyte rich - best prognosis
Mixed cellularity - eosinophils, immunocomp
Lymphocyte depleted - immunocomp
Non-Hodgkin lymphoma
Multiple LNs involved & extranodal involvement common
Noncontiguous spread
Mostly B cells involved; few T cell lineage
Adults and children affected
may be HIV/autoimmune-associated
Pyruvate kinase deficiency
AR disorder; results in decreased ATP –> rigid RBCs –> extravascular hemolysis / hemolytic anemia in a newborn
Increases levels of 2,3 BPG to reduce Hb affinity for O2 (release more O2 to tissues)
Pure red cell aplasia
Severe hypoplasia of erythroid marrow elements (causing anemia & low retics), but normal thrombopoiesis & granulopoiesis. Associated w/ thymoma, lymphocytic leukemias, & Parvo B19
Multiple myeloma vs. Waldenstrom macroglobulinemia
MM: Plasma cell cancer (fried egg appearance) arising in BM; produces lots of (mostly) IgG and (some) IgA. CRAB: hyperCa, Renal involvement, Anemia, Bone lytic lesions/Back pain.
WM: M spike (IgM) –> hyperviscosity syndrome (blurred vision, Raynaud’s). No CRAB sx.
ALK
Oncogene; receptor tyr kinase
Lung adenocarcinoma ("Adenocarcinoma of the Lung Kinase = ALK")BCR-ABL
Oncogene; tyrosine kinase
CML, ALL
BCL-2
Oncogene; antiapoptotic molecule
Follicular and DLBC lymphomas
BRAF
Oncogene; serine/threonine kinase (cytoplasmic signal transducer protein)
Melanoma (V600E), NHL, papillary thyroid carcinoma
c-KIT
Oncogene; cytokine receptor
GIST
c-MYC
Oncogene; transcription factor Burkitt lymphoma (t(8;14))
HER2/neu (c-erbB2)
Oncogene; receptor tyrosine kinase
Breast and gastric carcinomas
JAK2
Oncogene; cytoplasmic (non-receptor) tyrosine kinase
Chronic myeloproliferative disorders e.g. polycythemia vera
KRAS
Oncogene; GTPase
Colon, lung, pancreatic cancer
MYCL1
Oncogene; transcription factor
Lung tumor
N-myc (MYCN)
Oncogene; transcription factor
Neuroblastoma
RET
Oncogene; receptor tyr kinase
MEN 2A/2B, papillary thyroid carcinoma
APC
Tumor suppressor; negative regulator of beta-catenin/WNT pathway Colorectal cancer (FAP)
BRCA1/2
Tumor suppressor; DNA repair protein
BReast, ovarian and pancreatic CAncer (BRCA)
MEN1
Tumor suppressor; Menin
Multiple Endocrine Neoplasia 1 (pituitary, pancreas, parathyroid)
NF1
Tumor suppressor; neurofibromin (Ras GTPase activating protein)
NeuroFibromatosis 1
NF2
Tumor suppressor; Merlin (schwannomin) protein
NeuroFibromatosis 2
PTEN
Tumor suppressor; negatively regulates P13k/AKT pathway
Breast, prostate, endometrial cancer
Rb
Tumor suppressor; inhibits EF2, blocks G1 –> S phase
RetinoBlastoma, osteosarcoma
TP53
Tumor suppressor; p53, activates p21, blocks G1 –> S phase
Most human cancers, Li-Fraumeni syndrome (sarcoma, breast, leukemia, adrenal malignancies at early age)
TSC1
Tumor suppressor; hamartin protein
Tuberous sclerosis
TSC2
Tumor suppressor; tuberin protein
Tuberous sclerosis
VHL
Tumor suppressor; inhibits inducible factor 1a
Von Hippel-Lindau disease
WT1
Tumor suppressor; TF that regulates urogenital development Wilms Tumor (nephroblastoma)
TTP
ADAMSTS13 inhibition or deficiency –> unable to degrade vWF multimers. Large multimers cause increased platelet adhesion/aggregation/thrombosis.
FAT RN (w/ big TT’s): Fever, mahA, Thrombocytopenia, Renal failure, Neurologic symptoms
Labs: high BT; schistocytes & high LDH (hemolytic anemia). Tx w/ plasmapheresis, steroids
Adults: more neuro sx (TTP); kids: more renal sx (HUS) - on a spectrum
ITP
Anti-GpIIbIIIa antibodies –> splenic macrophages consume plt-antibody complex. Will have no fever, normal PT and PTT, high BT, high megakaryocytes on BM biopsy. Tx: steroids, IVIG, rituximab or splenectomy if refractory
Acute Intermittent Porphyria
Deficient porphobilinogen deaminase –> porphobilinogen and ALA build up.
No skin photosensitivity; painful abdomen, port-wine colored urine that darkens when exposed to sunlight, polyneuropathy, psych disturbances. Precipitated by drugs, alcohol, starvation. Tx: hemin and glc to inhibit ALA synthase
Porphyria cutanea tarda
Deficient uroporphyrinogen decarboxylase –> build up of uroporphyrin (tea colored urine). Causes blistering cutaneous photosensitivity, hyperpigmentation. Most common, assoc w/ alc consumption and Hep C
Paroxysmal nocturnal hemoglobinuria
PIGA gene defect leads to uncontrolled c’ mediated hemolysis; lack of CD55/CD59 c’ inhibitor proteins = RBC not protected against c’, so MAC forms. triad: hemolytic anemia (hemoglobinuria), pancytopenia, thrombosis in atypical sites. Chronic hemolysis can cause iron deposition in kidney (hemosiderosis). Tx: eculizumab (prevents MAC formation)
Main defect in:
- vWF disease
- Bernard-Soulier
- Glanzmann thrombasthenia
- ITP
- vWF disease: lack of vWF = can’t bind vWF to platelet to form plt plug. No ristocetin agglut (ristocetin brings Gp1b and vWF together)
- Bernard-Soulier: decreased Gp1b, large plts (Big Suckers); no ristocetin agglut
- Glanzmann: Defective GpIIbIIIa, can’t form plt plug. Normal risto but abnormal plt to plt clumping
- ITP: antibodies against GpIIbIIIa; increased megakaryocytes on BM biopsy
General lab findings with intravascular hemolysis
- increase bili, Hb, LDH (all released when RBCs lyse)
- increased reticulocyte count
- decreased haptoglobin (binds free Hb that spills out of lysed RBCs to promote uptake by reticulo-endothelial system)
Langerhans cell histiocytosis
Kids w/ lytic bone lesions, rash or recurrent otitis media w/ mastoid mass. Langerhans cells proliferate but are immature and can’t effectively stimulate T cells via Ag presentation. Cells are S100+, CD1a+, Birbeck (tennis racket/rod shaped) granules on EM
Sickle cell trait characteristics
Usually asymptomatic but may have priapism, increased UTI risk, hematuria. Relative protection from P. falciparum malaria
Hereditary spherocytosis + Tx
Extravascular hemolysis d/t defective RBC membrane proteins (ankyrin, spectrin). AD (structural defect). Small, round RBCs w/ less SA and no central pallor (high MCHC and RDW). Hemolysis/premature removal by spleen is what causes sx (splenomegaly); thus splenectomy is curative (often done w/ cholecystectomy bc assoc w/ cholecystitis, jaundice)
Treatment for DVT (prevention/short-term and maintenance), imaging
- Hep or LMWH for prophylaxis and acute management
- Oral anticoags (warfarin, rivaroxaban) for long-term maintenance
- Imaging: compression US w/ Doppler
HIT/treatment for HIT
Heparin induced thrombocytopenia: IgG forms against heparin-bound PF4; these complexes activate plts –> thrombosis and thrombocytopenia. Can use direct IIa inhibitors (Bivalrudin, Argatroban, Dabigatran) - when Hep is BAD for the patient
Polycythemia vera
Primary polycythemia: increased RBCs/RBC mass; intense itching after hot shower; erythromelalgia d/t episodic clots in extremity vessels; DECREASED EPO (vs. 2ndary polycythemia). Tx: phlebotomy, hydoxyurea, ruxolitinib (JAK inhibitor)
