# USMLE Step 1 & 2 — General Pathology, Neoplasia, Hemostasis & Oncologic Markers > Cellular adaptation, cell injury/death, tumor genetics, hallmarks of cancer, coagulation cascades, thrombophilia, and oncologic diagnostic markers. - **Canonical URL:** https://flashcards.world/flashcards/sets/ef5ca334-b750-4c25-aab1-b37285152fcc/ - **Markdown URL:** https://flashcards.world/flashcards/sets/ef5ca334-b750-4c25-aab1-b37285152fcc.md - **Level:** intermediate - **Languages:** en → en - **Total Cards:** 32 ## Flashcards (32 Cards) | # | Front (Term / Prompt) | Back (Definition / Answer) | Example | Multiple-Choice Options | | :--- | :--- | :--- | :--- | :--- | | 1 | Why does Warfarin induce a transient hypercoagulable state during the first 24–48 hours of administration? | Protein C has a very short half-life (~6 hours) compared to procoagulant factors (e.g., prothrombin ~60 hours). Early Protein C depletion leads to unopposed coagulation before procoagulant factors fall, risking Warfarin-induced skin necrosis unless bridged with heparin. | | | | 2 | What serum tumor marker is elevated in Pancreatic adenocarcinoma and cholangiocarcinoma? | CA 19-9 (Carbohydrate Antigen 19-9). Correlates with tumor burden and response to chemotherapy/surgical resection in pancreatic adenocarcinoma. | | | | 3 | What is the function of the Retinoblastoma (Rb) protein at the G1 to S phase checkpoint? | Hypophosphorylated Rb binds and sequesters the E2F transcription factor, blocking transcription of S-phase genes. Cyclin D/CDK4/6 hyperphosphorylates Rb, releasing E2F and driving entry into S phase. | | | | 4 | What chromosomal translocation is pathognomonic for Burkitt lymphoma, and what oncogene is upregulated? | t(8;14)(q24;q32), placing the c-MYC proto-oncogene under the control of the highly active immunoglobulin heavy chain (IGH) promoter on chromosome 14, driving constitutive cellular proliferation with a 'starry sky' histology. | | | | 5 | What chromosomal translocation and fusion protein define Chronic Myelogenous Leukemia (CML)? | t(9;22)(q34;q11), creating the Philadelphia chromosome with BCR-ABL1 fusion gene encoding a constitutively active tyrosine kinase; treated with Imatinib. | | | | 6 | What serum marker is used to monitor recurrence in Colorectal Carcinoma after resection? | Carcinoembryonic Antigen (CEA). Useful for monitoring therapeutic response and detecting disease recurrence, but not for initial screening. | | | | 7 | What is the immediate management for a patient diagnosed with Heparin-Induced Thrombocytopenia? | Immediately discontinue all heparin products (including flushes) and initiate non-heparin anticoagulation with a direct thrombin inhibitor (Argatroban, Bivalirudin) or Fondaparinux. Warfarin is contraindicated initially due to risk of venous limb gangrene. | | | | 8 | What is the molecular defect in Hemophilia A versus Hemophilia B, their inheritance, and their coagulation profile? | Hemophilia A: Factor VIII deficiency. Hemophilia B (Christmas disease): Factor IX deficiency. Both are X-linked recessive. Both show isolated prolonged aPTT with normal PT, normal platelet count, and normal bleeding time. | | | | 9 | What tumor marker is produced by Choriocarcinoma and Hydatidiform moles, as well as testicular seminomas/non-seminomas? | Beta-hCG (human chorionic gonadotropin). Produced by syncytiotrophoblastic cells; can cause hyperthyroidism due to homology with TSH. | | | | 10 | What is the function of the KRAS proto-oncogene and what downstream signaling pathway does it belong to? | GTPase that acts as an intracellular molecular switch in the EGFR/MAPK signaling cascade. Activating point mutations (common in colon, pancreatic, and lung cancers) prevent GTP hydrolysis, causing permanent downstream signaling; resistant to anti-EGFR mAbs (Cetuximab). | | | | 11 | What type of necrosis is pathognomonic for ischemic cerebral infarction? | Liquefactive necrosis: Brain tissue hydrolytic enzymes and microglial digestion liquefy dead parenchymal tissue into a cystic cavity, unlike coagulative necrosis seen in solid organs. | | | | 12 | What translocation characterizes Follicular Lymphoma, and what anti-apoptotic protein is overexpressed? | t(14;18)(q32;q21), placing the BCL-2 oncogene under the control of the immunoglobulin heavy chain (IGH) locus, overexpressing Bcl-2 which blocks apoptotic mitochondrial cytochrome c release. | | | | 13 | What is the most common inherited cause of hypercoagulability (thrombophilia) in Caucasian populations? | Factor V Leiden mutation (G1691A substitution replacing arginine with glutamine at position 506). Makes Factor Va resistant to inactivation by Activated Protein C (APC). | | | | 14 | What is the most common inherited bleeding disorder, and what laboratory findings are characteristic? | von Willebrand Disease (vWD; usually autosomal dominant). Causes impaired platelet adhesion and stabilization of Factor VIII. Labs: Prolonged bleeding time/PFA-100, normal or prolonged aPTT (due to low Factor VIII), normal PT, and abnormal Ristocetin cofactor assay. | | | | 15 | What enzyme deficiency causes Thrombotic Thrombocytopenic Purpura (TTP), and what is the classic clinical pentad? | Severe deficiency or autoantibody against ADAMTS13 (vWF-cleaving metalloprotease), causing ultra-large vWF multimers that shear platelets and RBCs. Pentad: Thrombocytopenia, Microangiopathic hemolytic anemia (schistocytes), Neurologic symptoms, Renal dysfunction, and Fever ('FAT RN'). | | | | 16 | What translocation is diagnostic of Ewing Sarcoma, and what is the typical histological appearance? | t(11;22)(q24;q12), creating the EWS-FLI1 fusion transcript. Histology demonstrates sheets of small round blue cells with Homer-Wright pseudorosettes and positive CD99 staining. | | | | 17 | What is the definition of Dysplasia and how does it differ from Metaplasia? | Metaplasia: Reversible reprogramming of one differentiated adult cell type into another (e.g., Barrett esophagus: squamous to columnar). Dysplasia: Disordered growth with loss of cellular uniformity, architecture, pleomorphism, and hyperchromatic nuclei, considered premalignant. | | | | 18 | What translocation is characteristic of Mantle Cell Lymphoma, and what cell cycle protein is overexpressed? | t(11;14)(q13;q32), juxtaposing the Cyclin D1 (CCND1) gene with the Ig heavy chain promoter, causing constitutive Cyclin D1 overexpression and driving G1 to S phase transition. | | | | 19 | What is the Prothrombin G20210A mutation and how does it predispose to venous thromboembolism? | A point mutation in the 3' untranslated region (UTR) of the prothrombin gene that increases mRNA stability and translation, resulting in elevated plasma prothrombin levels and a ~2- to 3-fold higher risk of VTE. | | | | 20 | What is the role of p53 in cell cycle arrest and apoptosis, and what syndrome arises from germline TP53 mutations? | p53 arrests the cell cycle at G1/S transition by upregulating p21 (CDK inhibitor) in response to DNA damage, or induces apoptosis via BAX/BAK. Germline TP53 mutation causes Li-Fraumeni syndrome (SBLA: Sarcoma, Breast, Leukemia, Adrenal tumors). | | | | 21 | What translocation defines Acute Promyelocytic Leukemia (APL / AML M3), and what targeted therapy induces remission? | t(15;17)(q24;q21), creating PML-RARA fusion which blocks myeloid differentiation at the promyelocyte stage. Treated with All-trans retinoic acid (ATRA) and Arsenic trioxide, preventing fatal DIC. | | | | 22 | What are the three factors in Virchow's Triad of thrombosis? | 1. Endothelial injury/damage; 2. Stasis or turbulent blood flow; 3. Hypercoagulability of blood. | | | | 23 | What tumor marker is used to monitor non-seminomatous germ cell tumors and Hepatocellular Carcinoma (HCC)? | Alpha-fetoprotein (AFP). Markedly elevated in yolk sac (endodermal sinus) tumors and hepatocellular carcinoma; also elevated in cirrhosis and ataxia-telangiectasia. | | | | 24 | What serum tumor marker is elevated in Medullary Thyroid Carcinoma? | Calcitonin, secreted by neoplastic parafollicular C cells (associated with MEN 2A and MEN 2B syndromes due to RET proto-oncogene mutations). | | | | 25 | What are the coagulation profile differences between Disseminated Intravascular Coagulation (DIC) and TTP? | DIC: Clotting cascade is consumptively activated; Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) are prolonged, fibrinogen is low, and D-dimer is markedly elevated. TTP: Platelet-only consumption; PT and aPTT are completely NORMAL, with normal fibrinogen. | | | | 26 | What is Knudson's 'two-hit' hypothesis and which tumor suppressor gene served as the classic paradigm? | Both alleles of a tumor suppressor gene must be inactivated for oncogenesis. In hereditary retinoblastoma (RB1 gene on 13q14), one allele is mutated in the germline ('first hit') and a somatic mutation disables the second allele ('second hit'). | | | | 27 | What morphological and biochemical features differentiate Apoptosis from Necrosis? | Apoptosis: Programmed, ATP-dependent, cellular shrinkage, intact cell membrane, pyknosis, karyorrhexis, apoptotic bodies, no inflammatory reaction. Necrosis: Unregulated, ATP-depleted, cellular swelling, disrupted membrane, nuclear lysis, marked acute inflammation. | | | | 28 | What immunohistochemical marker stains positive in malignant melanoma, and what other markers are sensitive? | S100 (neural crest origin), HMB-45, and Melan-A (MART-1). | | | | 29 | What serum tumor marker is used to monitor epithelial Ovarian cancer recurrence? | CA 125 (Cancer Antigen 125). Used for post-treatment monitoring of serous ovarian carcinoma (not recommended for general population screening due to low specificity in premenopausal women). | | | | 30 | What immunohistochemical marker stains positive in neoplasms of mesenchymal origin (e.g., sarcomas)? | Vimentin (intermediate filament characteristic of mesenchymal tissue, distinguishing sarcomas from carcinomas which stain positive for cytokeratins). | | | | 31 | What is the pathophysiology of Heparin-Induced Thrombocytopenia (HIT Type 2)? | IgG antibodies form against Heparin-Platelet Factor 4 (PF4) complexes. The Fc portion of the antibody cross-links Fc-gamma-RIIa receptors on platelets, causing massive platelet activation, paradoxically leading to widespread arterial and venous thrombosis with moderate thrombocytopenia. | | | | 32 | What is the mechanism of action of Heparin versus Warfarin on the coagulation cascade? | Heparin: Binds antithrombin III (ATIII) causing a conformational change that accelerates its inactivation of Thrombin (IIa) and Factor Xa (monitored via aPTT). Warfarin: Inhibits Vitamin K epoxide reductase (VKORC1), blocking gamma-carboxylation of Factors II, VII, IX, X and Proteins C and S (monitored via PT/INR). | | | --- Study this deck interactively with FSRS-6 spaced repetition, audio review, and multiple-choice mode at [Flashcards World](https://flashcards.world/flashcards/sets/ef5ca334-b750-4c25-aab1-b37285152fcc/).