Section A (Depth, mechanisms) Practice exam questions Flashcards
Discuss the molecular and environmental factors contributing to the development of hepatocellular carcinoma in the context of chronic liver disease.
Chronic hepatitis B and C as underlying viral causes.
Role of cirrhosis and aflatoxin exposure in carcinogenesis.
Key genetic mutations (e.g., TP53, CTNNB1) in hepatocarcinogenesis.
Clinical implications for screening and targeted therapy.
Compare and contrast the mechanisms by which high-risk and low-risk HPV subtypes contribute to epithelial neoplasia.
Differences in E6/E7 oncogene activity.
Integration into host genome in high-risk HPV.
Morphological and histopathological progression.
Role in cancer screening and vaccine development.
Evaluate the utility and limitations of molecular classification systems in guiding the management of endometrial carcinoma.
Four subtypes in TCGA classification.
Prognostic and therapeutic implications of molecular vs. histologic classification.
Role of MMR testing and POLE mutations.
Impact on clinical decision-making.
Describe the spectrum of glomerular diseases and evaluate how structural changes relate to proteinuria and clinical outcome.
Key examples: Minimal Change Disease, Membranous Nephropathy, FSGS.
Podocyte injury and basement membrane thickening.
Diagnostic significance of light, immunofluorescent, and electron microscopy.
Therapeutic implications based on underlying mechanism.
Explain the pathogenesis of colorectal adenocarcinoma with reference to both sporadic and hereditary pathways.
Chromosomal instability vs. microsatellite instability pathways.
APC, KRAS, p53 mutations in sporadic cases.
Lynch syndrome and familial adenomatous polyposis.
Clinical importance of screening and surveillance.
Discuss the interplay between chronic inflammation and carcinogenesis using examples from Helicobacter pylori-induced gastric cancer and HPV-related cervical neoplasia.
Chronic inflammation promotes genomic instability and cellular proliferation.
H. pylori induces a chronic gastritis that can progress to intestinal metaplasia and adenocarcinoma.
High-risk HPV types produce E6 and E7 oncoproteins disrupting p53 and Rb.
Inflammatory cytokines and immune evasion contribute to neoplastic progression in both.
Compare and contrast the molecular pathogenesis, histological subtypes, and prognosis of lung adenocarcinoma and squamous cell carcinoma of the lung.
Lung adenocarcinomas often involve EGFR, ALK, or KRAS mutations and arise peripherally.
Squamous cell carcinomas are linked to smoking and often show p53 mutations, arising centrally.
Histological differences impact biopsy interpretation and treatment eligibility.
Targeted therapies exist for adenocarcinomas, contributing to differing prognoses.
Explain how histological, molecular, and clinical findings converge to classify soft tissue tumours and guide management decisions.
WHO classification integrates morphology and genetic markers (e.g., SYT-SSX fusion in synovial sarcoma).
Some tumours require molecular confirmation due to overlapping histological features.
Molecular findings can influence treatment, e.g., tyrosine kinase inhibitors in GIST.
Risk stratification affects decisions around surgical margins, chemo, and follow-up.
Evaluate how next-generation sequencing technologies have reshaped our understanding of tumour heterogeneity and patient stratification in systemic pathology.
Enables comprehensive detection of somatic/germline mutations in a single assay.
Reveals clonal evolution and intra-tumoural heterogeneity.
Facilitates personalised treatment decisions based on actionable mutations.
Provides insights into prognosis, recurrence risk, and familial implications.
Discuss the diagnostic and prognostic implications of integrating histological grading with molecular classifications in endometrial and ovarian carcinomas.
Histology remains essential for initial classification (e.g., endometrioid vs. serous types).
Molecular classification stratifies cases by mutations (e.g., POLE, p53 abnormal).
Prognostic value: p53 mutant tumours typically have poor prognosis; POLE-mutant, better.
Helps in treatment selection and eligibility for trials targeting specific pathways.
Describe the mechanisms by which aflatoxin exposure contributes to hepatocarcinogenesis.
Induces mutations in TP53 (especially codon 249)
Synergistic effect with chronic hepatitis B infection
Promotes oxidative stress and DNA adduct formation
Geographic correlation with high HCC incidence
Explain how endometrial intraepithelial carcinoma differs from serous carcinoma of the endometrium in pathogenesis and clinical implications.
EIC is a precursor to serous carcinoma
Both commonly associated with TP53 mutations
Serous carcinoma is aggressive, often stage-advanced
Usually arises in atrophic endometrium, not linked to estrogen
Discuss the role of mismatch repair deficiency in colorectal carcinoma and its diagnostic and therapeutic implications.
Associated with Lynch syndrome (MLH1, MSH2, etc.)
Causes microsatellite instability (MSI)
Identified by IHC or PCR-based tests
Predicts response to immunotherapy
Describe the role of Helicobacter pylori in gastric carcinogenesis, including its interaction with host immune responses and progression to malignancy.
Virulence factors (e.g., CagA, VacA) disrupt epithelial cells
Chronic gastritis leading to intestinal metaplasia, dysplasia, carcinoma
Immune evasion mechanisms
Importance of eradication in prevention strategies
Compare and contrast Minimal Change Disease and Membranous Nephropathy in terms of pathogenesis, histology, and response to treatment.
MCD: podocyte foot process effacement, steroid-responsive
MN: immune complex deposition, basement membrane thickening
Diagnostic tools: EM, IF, LM
Clinical course and complications
Explain the molecular events and histological features associated with the adenoma-carcinoma sequence in colorectal cancer.
APC mutation as an early event
KRAS mutation promoting growth
p53 mutation in late transformation
Microsatellite-stable pathway
Discuss the significance of HER2 amplification and estrogen receptor status in the diagnosis and treatment of breast cancer.
HER2 positivity associated with aggressive phenotype
ER/PR status predicts hormone therapy response
IHC and FISH as diagnostic tools
Impact on targeted therapy (e.g., trastuzumab)
Outline the key pathological features and genetic drivers of melanoma, and how they relate to novel therapeutic approaches.
BRAF, NRAS, and KIT mutations
Histology: asymmetry, atypical melanocytes, mitotic rate
Targeted therapies and immunotherapy options
Prognostic markers and staging
Describe the mechanisms by which germline mutations in tumour suppressor genes contribute to hereditary cancer syndromes, using two examples.
Loss of heterozygosity model (e.g., two-hit hypothesis)
TP53 mutation in Li-Fraumeni syndrome: diverse early-onset cancers
RB1 mutation in retinoblastoma: risk of bilateral eye tumours and secondary cancers
Implications for family screening and surveillance programs
Compare the pathogenesis and clinical implications of Lynch syndrome-associated endometrial cancer with sporadic endometrial cancer.
Lynch: MMR deficiency, microsatellite instability, earlier onset
Sporadic: more often associated with estrogen exposure and PTEN mutations
Morphological differences may be subtle
Importance of screening in women with family history
