70 clinical MCQs in Oncopathology. A 33-year-old woman with breast cancer is found to have HER2/neu gene amplification. Which. Kenya, Africa and global...
Q1. A 33-year-old woman with breast cancer is found to have HER2/neu gene amplification. Which of the following best describes the mechanism by which HER2/neu promotes oncogenesis? Amplification means extra copies of a normal receptor, driving excess growth signaling. ---
Answer: Overexpressed growth factor receptor causing increased proliferative signaling
Q2. A 28-year-old man presents with bilateral retinoblastomas. Genetic analysis reveals a germline mutation in one allele of the RB gene, followed by somatic loss of the second allele. This exemplifies which principle? Both copies of a tumor-suppressor gene (R ---
Answer: Knudson's two-hit hypothesis
Q3. A point mutation in the RAS gene that locks it in an active GTP-bound state results in which cellular effect? RAS normally self-inactivates by hydrolyzing GTP to GDP. Locked "on," it fires proliferative signals continuously without needing upstream growth factor input. ---
Answer: Continuous cell proliferation independent of growth factors
Q4. The ERBB2 (HER2/neu) oncogene contributes to tumorigenesis primarily by ---
Answer: Overexpression of a growth factor receptor
Q5. Autocrine stimulation of growth factor receptors is best exemplified by: Autocrine means the tumor cell makes the growth factor and also expresses its receptor, stimulating itself. ---
Answer: Glioblastoma producing PDGF
Q6. Mutation of the RB1 gene promotes cancer development by: RB normally holds the cell at the G1/S checkpoint until it's ready to divide. Losing it removes the brake. ---
Answer: Removing a checkpoint that blocks G1/S transition
Q7. Loss of function of the TGF-β signaling pathway contributes to tumorigenesis by: TGF-β is normally a growth inhibitor in most epithelial cells; losing this pathway removes that brake. ---
Answer: Removing inhibition of cell proliferation
Q8. The anti-apoptotic effect of BCL-2 overexpression in follicular lymphoma occurs due to: BCL-2 keeps the mitochondrial membrane intact, preventing cytochrome c release and blocking the intrinsic apoptotic pathway. ---
Answer: Stabilization of mitochondrial membrane and inhibition of cytochrome c release
Q9. Which genetic alteration would favour resistance to apoptosis? p53, BAX, and caspases are all pro-apoptotic; losing p53 removes a key trigger for apoptosis, favoring cell survival. ---
Answer: Loss of p53
Q10. Activation of telomerase contributes to cancer progression by: Telomerase rebuilds telomeres, bypassing the normal limit on cell division (replicative senescence) — this is how cancer cells achieve immortality. ---
Answer: Allowing indefinite cell divisions despite chromosomal shortening
Q11. Which of the following is most directly linked to cellular senescence escape? p16 enforces the RB-mediated senescence checkpoint; losing it allows cells to bypass senescence. ---
Answer: p16INK4A loss
Q12. Tumor hypoxia stimulates VEGF expression through stabilization of which transcription factor? Under normoxia HIF-1α is degraded; hypoxia stabilizes it, and it then drives VEGF transcription. ---
Answer: HIF-1α
Q13. Inhibition of angiogenesis is best achieved experimentally by blocking which pathway? ---
Answer: VEGF–VEGFR signalling
Q14. Loss of E-cadherin expression in epithelial tumors facilitates: E-cadherin holds epithelial cells together; losing it is a key step in EMT and local invasion. ---
Answer: Loss of cell adhesion and increased invasiveness
Q15. The degradation of extracellular matrix during tumor invasion is mainly mediated by ---
Answer: Matrix metalloproteinases (MMPs)
Q16. The Warburg effect refers to: Cancer cells favor "aerobic glycolysis" even when oxygen is available, because it supports rapid biomass production, not just ATP. ---
Answer: Preferential use of glycolysis even in presence of oxygen
Q17. Which molecule regulates metabolic reprogramming by promoting glycolytic enzyme expression? MYC upregulates glycolytic enzymes and glucose transporters, driving the Warburg phenotype. ---
Answer: MYC
Q18. Tumour cells escape immune surveillance most commonly by: PD-L1 engages PD-1 on T cells, delivering an inhibitory signal that shuts down the anti-tumor immune response. ---
Answer: Upregulating PD-L1 expression
Q19. Which immune cell type plays the major role in tumour immune editing and elimination? ---
Answer: CD8+ cytotoxic T lymphocytes
Q20. Defects in DNA mismatch repair genes (MLH1, MSH2) are associated with ---
Answer: Hereditary nonpolyposis colorectal cancer (Lynch syndrome)
Q21. BRCA1 and BRCA2 mutations predispose to cancer because they: BRCA1/2 normally repair double-strand DNA breaks accurately; loss forces cells to rely on error-prone repair, accumulating mutations. ---
Answer: Impair homologous recombination DNA repair
Q22. Chronic Helicobacter pylori infection contributes to gastric carcinoma mainly by ---
Answer: Inducing chronic inflammation and reactive oxygen species production
Q23. Which cytokine produced in chronic inflammation promotes tumour growth and survival? Chronically, TNF-α can promote a tumor-supportive inflammatory microenvironment rather than clearing damaged cells. ---
Answer: TNF-α
Q24. Which of the following best describes how inflammatory cells enhance metastasis? ---
Answer: They secrete proteases and growth factors facilitating invasion
Q25. A tumour showing MYC amplification, VEGF overexpression, and p53 loss demonstrates which combination of hallmarks? MYC → growth signal independence; p53 loss → apoptosis resistance; VEGF → angiogenesis. Three separate hallmarks of cancer together. ---
Answer: Self-sufficiency in growth + resistance to death + angiogenesis
Q26. Which of the following is a benign tumour? A benign smooth muscle tumor. All the others are malignant. # GENETICS ---
Answer: Leiomyoma
Q27. A 25-year-old man presents with progressive muscle weakness. Genetic testing reveals a mutation in the dystrophin gene on the X chromosome. Which best explains why this mutation leads to disease? Dystrophin anchors the cytoskeleton to the membrane; without it, muscle fibers tear during contraction. ---
Answer: Defective structural protein disrupting muscle cell membrane stability
Q28. A 4-year-old girl presents with recurrent lung infections and pancreatic insufficiency. Sweat chloride test is positive. This autosomal recessive disorder is caused by mutations in which gene? Classic cystic fibrosis presentation. ---
Answer: CFTR (chloride channel regulator)
Q29. A 16-year-old boy is tall, with long extremities and hyperflexible joints. Echocardiography shows aortic root dilatation. Which genetic defect best explains this patient's condition? Marfan syndrome. ---
Answer: Mutation in fibrillin-1 leading to defective microfibrils
Q30. A 52-year-old woman with obesity and hypertension develops type 2 diabetes mellitus. Which of the following best describes the genetic basis of this disorder? ---
Answer: Polygenic inheritance with environmental influence
Q31. A 34-year-old woman with a strong family history of early-onset breast cancer seeks genetic counseling. Which of the following is the most appropriate indication for genetic testing in this patient? ---
Answer: Multiple relatives with BRCA-associated cancers at young ages
Q32. Gene therapy aims to ---
Answer: Replace or repair defective genes in somatic cells
Q33. A child born to phenotypically normal parents develops cystic fibrosis. The inheritance pattern is most consistent with: Two unaffected carrier parents having an affected child is the hallmark of autosomal recessive inheritance. ---
Answer: Autosomal recessive
Q34. If a couple are carriers of an autosomal recessive trait, what is the probability that all their four children will be homozygous for the disease? Each pregnancy independently has a 1/4 chance; probability of all four being affected multiplies the independent probabilities. ---
Answer: ¼ × ¼ × ¼ × ¼
Q35. Which of the following features distinguishes autosomal dominant from autosomal recessive inheritance? This vertical pattern is classic for AD; AR instead shows generation skipping (e is a description of AR, not a distinguishing feature stated as such). ---
Answer: Vertical transmission with affected parent in each generation
Q36. A 40-year-old man develops progressive choreiform movements and dementia. His father had similar symptoms. Which mutation is most likely? Huntington disease (autosomal dominant, CAG repeat expansion). ---
Answer: Trinucleotide repeat expansion in HTT gene
Q37. Which of the following best characterizes complex (multifactorial) genetic disorders? ---
Answer: Involve interaction of multiple genes and environmental factors
Q38. Type 2 diabetes mellitus is an example of a ---
Answer: Multifactorial polygenic disorder
Q39. Which statement regarding multifactorial inheritance is true? Recurrence risk correlates with degree of genetic relatedness — closer relatives share more risk alleles. ---
Answer: First-degree relatives have higher recurrence risk than distant relatives
Q40. A karyotype showing 47,XX,+13 indicates: Trisomy 13. ---
Answer: Patau syndrome
Q41. Which of the following features is least characteristic of Down syndrome? Down syndrome (trisomy 21) is associated with short stature, not tall. ---
Answer: Tall stature
Q42. Trisomy 18 is most often associated with: Edwards syndrome. ---
Answer: Micrognathia, clenched fists, and congenital heart disease
Q43. A 15-year-old girl presents with short stature, streak ovaries, and webbed neck. Karyotype shows 45,X. The diagnosis is ---
Answer: Turner syndrome
Q44. A tall, infertile male with gynecomastia and small testes likely has which karyotype? Klinefelter syndrome. ---
Answer: 47,XXY
Q45. The most consistent hormonal abnormality in Klinefelter syndrome is: Testicular failure gives low testosterone with compensatory high LH/FSH. ---
Answer: Elevated gonadotropins with low testosterone
Q46. Which of the following is X-linked recessive? ---
Answer: Duchenne muscular dystrophy
Q47. In X-linked recessive inheritance, carrier females ---
Answer: Can transmit the mutation to sons (affected) or daughters (carriers)
Q48. Fragile X syndrome results from ---
Answer: CGG trinucleotide repeat expansion in FMR1 gene
Q49. Which clinical feature is most characteristic of Fragile X syndrome? ---
Answer: Macroorchidism and large ears
Q50. Genomic imprinting refers to ---
Answer: Selective silencing of one parental allele by DNA methylation
Q51. Deletion of paternal chromosome 15q11–13 results in: Loss of the paternally-expressed genes at 15q11-13 → Prader-Willi. Loss of maternal copy → Angelman. ---
Answer: Prader–Willi syndrome
Q52. Deletion of the maternal 15q11–13 allele causes ---
Answer: Angelman syndrome
Q53. Which statement regarding mitochondrial inheritance is correct? Mitochondrial DNA comes entirely from the egg cytoplasm, so it is maternally inherited to all children (though severity varies with heteroplasmy). ---
Answer: Affected mothers transmit to all offspring
Q54. Leber hereditary optic neuropathy (LHON) is due to ---
Answer: Mutation in mitochondrial genes encoding oxidative phosphorylation enzymes
Q55. A 35-year-old woman presents with heavy menstrual bleeding and pelvic pressure. Ultrasound reveals multiple well-circumscribed masses in the uterus composed of smooth muscle cells arranged in whorled patterns. Which diagnosis is most likely? The classic "whorled" smooth-muscle bundle appearance of a benign fibroid. ---
Answer: Leiomyoma
Q56. A 52-year-old postmenopausal woman presents with vaginal bleeding. Endometrial biopsy shows atypical glandular proliferation with nuclear atypia. Which condition is most strongly associated with progression to endometrial carcinoma? ---
Answer: Endometrial hyperplasia with atypia
Q57. A 27-year-old woman presents with amenorrhea and galactorrhea. Pregnancy test is negative. Elevated prolactin is detected. Which organ pathology is most likely responsible? Most likely a prolactinoma. ---
Answer: Pituitary gland
Q58. A 30-year-old woman presents with lower abdominal pain and positive pregnancy test. Ultrasound reveals no intrauterine pregnancy but shows a mass in the fallopian tube. Which condition is most likely? ---
Answer: Ectopic pregnancy
Q59. A 40-year-old woman presents with dysmenorrhea and enlarged uterus. Histology reveals endometrial glands within the myometrium. Which diagnosis is most likely? Endometrial glands within the myometrium — distinguishes it from endometriosis (outside the uterus entirely). ---
Answer: Adenomyosis
Q60. A 60-year-old woman presents with abdominal distension and weight loss. Imaging reveals bilateral ovarian masses. Histology shows papillary structures with psammoma bodies. Which tumour is most likely? Psammoma bodies (concentric calcifications) with papillary architecture is classic for serous tumors. ---
Answer: Serous cystadenocarcinoma
Q61. A 22-year-old woman presents with abdominal pain. Imaging shows an ovarian tumour containing hair, teeth, and sebaceous material. Which tumour is most likely? A germ cell tumor containing tissue from all three germ layers (a "dermoid cyst"). ---
Answer: Mature cystic teratoma
Q62. A 45-year-old woman presents with abnormal uterine bleeding. Histology reveals granulosa cells forming Call-Exner bodies. Which tumour is most likely? Call-Exner bodies are the histologic hallmark; these tumors also secrete estrogen, causing the abnormal bleeding. ---
Answer: Granulosa cell tumour
Q63. A 24-year-old woman presents with primary infertility. Laparoscopy shows fibrous adhesions and dilated fallopian tubes filled with fluid. Which condition is most likely? Usually from prior pelvic inflammatory disease scarring the tube shut, causing fluid accumulation. ---
Answer: Hydrosalpinx
Q64. A 33-year-old woman presents with persistent vaginal bleeding after a miscarriage. Very high β-hCG levels are detected. Imaging shows uterine mass with no foetal tissue. Which condition is most likely? ---
Answer: Hydatidiform mole
Q65. A patient with gestational trophoblastic disease develops lung metastases and extremely high β-hCG levels. Which diagnosis is most likely? A malignant, highly vascular trophoblastic tumor that metastasizes early (classically to lung) and produces very high β-hCG. ---
Answer: Choriocarcinoma
Q66. A 36-year-old woman presents with postcoital bleeding. Cervical biopsy reveals dysplastic squamous cells involving full epithelial thickness without invasion. Which condition is this? Full-thickness dysplasia but no invasion through the basement membrane. ---
Answer: CIN III (carcinoma in situ)
Q67. A 50-year-old woman develops invasive cervical carcinoma. Which virus is most strongly associated with this malignancy? HPV 16 and 18 are the high-risk oncogenic types. HPV 6 and 11 cause genital warts but are low-risk for malignancy. ---
Answer: Human papillomavirus 16
Q68. A 55-year-old woman presents with vaginal bleeding. Imaging shows a tumour arising from the cervix and invading surrounding tissue. Which histologic type is most common? The majority of cervical cancers are squamous cell. ---
Answer: Squamous cell carcinoma
Q69. A 38-year-old woman presents with pelvic mass and ascites. CA-125 is elevated. Which condition is most likely? CA-125 is the classic (though nonspecific) ovarian cancer marker. ---
Answer: Ovarian carcinoma
Q70. A 30-year-old woman presents with infertility and cyclic pelvic pain. Endometrial tissue is found on the ovaries and pelvic peritoneum. Which hormone primarily stimulates growth of this tissue? Ectopic endometrial tissue in endometriosis is estrogen-dependent, just like normal endometrium.
Answer: Oestrogen