Molecular pathology, IHC markers and WHO tumour classifications

53 NEET-PG practice questions on Molecular pathology, IHC markers and WHO tumour classifications, part of Pathology. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Medium

   Biopsy of an orbital mass that has pushed the eye forward over 4 weeks in a boy of 6: sheets of small round blue cells, some with eosinophilic cytoplasm. CD45 and CD99 are negative and cytokeratin is negative. Which nuclear immunostain confirms skeletal muscle differentiation?

   1. ADesmin
   2. BSmooth muscle actin
   3. CS100 protein
   4. DMyogenin

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   Answer: D · Myogenin

   Rhabdomyosarcoma is the commonest soft tissue sarcoma of childhood, and the orbit is a classic site. Desmin is a sensitive cytoplasmic muscle marker, but nuclear myogenin (MYF4) and MyoD1 are specific for skeletal muscle and confirm the diagnosis; diffuse strong myogenin suggests the alveolar type.

   • A: Desmin is cytoplasmic and also positive in smooth muscle tumours, so it is not specific.
   • B: SMA marks smooth muscle and myofibroblasts.
   • C: S100 marks melanocytic and neural tumours.

   Remember this

   Nuclear myogenin and MyoD1 confirm rhabdomyosarcoma; desmin is sensitive but not specific.

2. Question 2 · Medium

   Liver biopsy from a man with hepatitis B cirrhosis, a 4 cm arterially enhancing nodule and an AFP of 24 ng/mL: a trabecular tumour of polygonal cells with bile production in some areas. The pathologist wants to separate hepatocellular carcinoma from metastatic adenocarcinoma. Which panel supports hepatocellular origin?

   1. ATTF-1, napsin A and CK7
   2. BArginase-1, HepPar-1 and glypican-3
   3. CCK7, CK20 and CDX2
   4. DSynaptophysin, chromogranin and CD56

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   Answer: B · Arginase-1, HepPar-1 and glypican-3

   Arginase-1 and HepPar-1 mark hepatocytic differentiation, and glypican-3 is positive in most HCCs but not in benign hepatocytes; canalicular polyclonal CEA or CD10 also supports HCC. Adenocarcinoma metastases express CK7/CK20 and site-specific markers instead.

   • A: TTF-1 and napsin A suggest lung adenocarcinoma.
   • C: CK7, CK20 and CDX2 suggest metastatic gastrointestinal adenocarcinoma or cholangiocarcinoma.
   • D: Neuroendocrine markers suggest a neuroendocrine tumour.

   Remember this

   Hepatocellular carcinoma: arginase-1, HepPar-1 and glypican-3 positive.

3. Question 3 · Medium

   Plasma ctDNA testing by next-generation sequencing is reported as 'no actionable mutation detected' for a man newly diagnosed with lung adenocarcinoma. He has a single 2.2 cm peripheral lesion and two small bone metastases on PET-CT; the earlier bronchoscopic biopsy had too little tumour for molecular testing. He has never smoked. What should the team do next?

   1. AStart erlotinib empirically
   2. BRebiopsy for tissue genotyping
   3. CTreat as driver-negative disease
   4. DRepeat the plasma test in 6 months

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   Answer: B · Rebiopsy for tissue genotyping

   A negative liquid biopsy does not exclude a driver mutation, because small or low-volume tumours shed little DNA into the blood and the false-negative rate is significant. A negative plasma result should therefore be followed by tissue testing, while a positive result can be acted upon. A never-smoker with adenocarcinoma has a high pretest probability of EGFR, ALK or other drivers.

   • A: Empirical TKI therapy without a proven mutation is not recommended.
   • C: Calling it driver-negative risks missing targetable EGFR or ALK alterations.
   • D: Waiting 6 months delays first-line treatment of stage IV disease.

   Remember this

   Liquid biopsy: a positive result is actionable; a negative result needs tissue genotyping before calling a tumour driver-negative.

4. Question 4 · Easy

   Pleural fluid cell block from a non-smoker with a lung mass: adenocarcinoma cells positive for TTF-1 and napsin A. The primary site is:

   1. AThyroid
   2. BLung
   3. CBreast
   4. DStomach

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   Answer: B · Lung

   Nuclear TTF-1 with cytoplasmic napsin A is the standard pair for lung adenocarcinoma. Thyroid tumours are also TTF-1-positive but napsin-negative and thyroglobulin-positive, and the clinical picture of a lung mass with effusion fits lung. Breast and stomach are TTF-1-negative.

   • A: Thyroid carcinoma is TTF-1 positive but napsin A negative and thyroglobulin positive.
   • C: Breast carcinoma is GATA3 and mammaglobin positive, TTF-1 negative.
   • D: Gastric adenocarcinoma is TTF-1 negative and often CDX2 positive.

   Remember this

   TTF-1 plus napsin A positive adenocarcinoma: primary lung adenocarcinoma.

5. Question 5 · Medium

   Peritoneal biopsy from a woman with ascites and an omental cake: a high-grade papillary carcinoma with psammoma bodies, positive for PAX8 and WT1, with diffuse strong p53 staining. CA-125 is 1,240 U/mL. Besides the Müllerian tract, PAX8 positivity in a carcinoma can also point to which other organs?

   1. AColon and pancreas
   2. BLung and breast
   3. CLiver and stomach
   4. DKidney and thyroid

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   Answer: D · Kidney and thyroid

   PAX8 is a nuclear marker of Müllerian (ovary, tube, endometrium), renal and thyroid epithelium. With WT1 and aberrant p53, this picture fits high-grade serous carcinoma of tubo-ovarian origin. In a metastasis of unknown primary, PAX8 positivity narrows the search to these three systems.

   • A: Colon and pancreas are PAX8-negative.
   • B: Lung and breast carcinomas are PAX8-negative (TTF-1 and GATA3 respectively).
   • C: Liver and stomach are PAX8-negative.

   Remember this

   PAX8 marks Müllerian, renal and thyroid carcinomas; PAX8 with WT1 favours serous carcinoma.

6. Question 6 · Hard

   Metastatic adenocarcinoma of the ascending colon in a pharmacist has progressed on first-line FOLFOX with bevacizumab. Tumour testing shows BRAF V600E, KRAS and NRAS wild-type, and proficient mismatch repair. Her nephew, a medical student, points out that vemurafenib alone works well in BRAF V600E melanoma and asks why it is not given here. Which regimen is preferred, and for what reason?

   1. ACetuximab alone, as RAS is wild-type
   2. BPembrolizumab, as BRAF predicts immune response
   3. CEncorafenib with cetuximab, as BRAF block reactivates EGFR
   4. DVemurafenib alone, as in BRAF-mutant melanoma

   Answer and explanation in LearnFree account

7. Question 7 · Easy

   For a liquid biopsy to genotype a lung adenocarcinoma, which component of the patient's blood is most often analysed?

   1. ASerum tumour markers
   2. BCirculating tumour cells
   3. CCirculating tumour DNA in plasma
   4. DTumour-educated platelet RNA profiles

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8. Question 8 · Easy

   An undifferentiated tumour in an axillary node is negative for cytokeratin and CD45. Which panel suggests metastatic melanoma?

   1. ASynaptophysin, chromogranin and INSM1
   2. BDesmin, myogenin and MyoD1
   3. CCD20, CD3 and CD30
   4. DS100, SOX10 and HMB-45

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9. Question 9 · Easy

   Acute promyelocytic leukaemia with t(15;17) PML::RARA. Which drug acts directly on the fusion protein to induce differentiation?

   1. AImatinib
   2. BRituximab
   3. CAll-trans retinoic acid
   4. DCytarabine

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10. Question 10 · Medium

    CT-guided biopsy of a peripheral lung mass in a beedi roller from Tirunelveli: a poorly differentiated non-small cell carcinoma with no glands, no keratin pearls and no mucin on special stains. The oncologist needs the subtype because some drugs are chosen by histology. Which nuclear immunostain is most specific for squamous differentiation?

    1. Ap40
    2. BNapsin A
    3. CTTF-1
    4. DCDX2

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11. Question 11 · Hard

    MRI of a baby girl of 14 months with vomiting for 2 weeks, irritability, loss of head control and a bulging fontanelle shows a large heterogeneous mass in the cerebellum with hydrocephalus; an external ventricular drain is placed and the mass is resected. Histology shows sheets of small blue cells mixed with large cells that have eccentric nuclei, prominent nucleoli and glassy eosinophilic cytoplasmic inclusions. The pathologist first suspects medulloblastoma, but an immunostain shows complete loss of nuclear staining in the tumour cells, with retained staining in the vessels. Which protein has been lost?

    1. Ap53
    2. BSynaptophysin
    3. CINI1 (SMARCB1)
    4. DGFAP

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12. Question 12 · Medium

    Next-generation sequencing of a lung adenocarcinoma from a non-smoking accountant, aged 38, with brain metastases shows an EML4::ALK fusion, and ALK (D5F3) immunostaining is strongly positive. EGFR and KRAS are wild-type. Which drug is preferred first-line?

    1. ACetuximab
    2. BOsimertinib
    3. CAlectinib
    4. DSotorasib

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13. Question 13 · Medium

    Endoscopic ultrasound-guided biopsy of a 7 cm submucosal gastric mass in a retired railway guard with melaena: uniform spindle cells in fascicles with perinuclear vacuoles, 3 mitoses per 5 mm2. Desmin and S100 are negative. Which pair of stains confirms the diagnosis?

    1. ACD34 and CD31
    2. BS100 and SOX10
    3. CDesmin and SMA
    4. DCD117 (KIT) and DOG1

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14. Question 14 · Medium

    A woman who had a mastectomy 6 years ago now has a bone lesion; she also passed blood in her urine last month, and cystoscopy is pending. The bone biopsy shows a poorly differentiated carcinoma that is CK7-positive, CK20-negative, ER-negative and GATA3-positive. Which two primaries does GATA3 positivity mainly point to?

    1. AKidney and ovary
    2. BColon and stomach
    3. CBreast and urothelium
    4. DLung and thyroid

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15. Question 15 · Easy

    Bronchoscopic biopsy from a heavy smoker with a central hilar mass and hyponatraemia shows small cells with scant cytoplasm, nuclear moulding, finely granular chromatin and crush artefact. Which pair of immunostains confirms neuroendocrine differentiation?

    1. Ap40 and CK5/6
    2. BSynaptophysin and chromogranin A
    3. CCalretinin and WT1
    4. DCD45 and CD20

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16. Question 16 · Medium

    Relapsed acute myeloid leukaemia in a retired postmaster, 8 months after induction: sequencing of the marrow shows an IDH1 R132H mutation. The oncometabolite produced by the mutant enzyme blocks myeloid differentiation. Which drug inhibits the mutant enzyme?

    1. AVenetoclax
    2. BMidostaurin
    3. CIvosidenib
    4. DEnasidenib

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17. Question 17 · Easy

    Haemoglobin 20.1 g/dL with itching after a hot bath and splenomegaly. Which acquired mutation is found in about 95% of such patients?

    1. AJAK2 V617F
    2. BCALR exon 9
    3. CMPL W515L
    4. DBCR::ABL1

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18. Question 18 · Medium

    Bronchoscopic biopsy from a never-smoking schoolteacher in Chennai with a lung mass and bone metastases: adenocarcinoma, EGFR exon 19 deletion on next-generation sequencing, and PD-L1 tumour proportion score 60%. The family has read that immunotherapy is best for high PD-L1. Which first-line treatment is preferred?

    1. AOsimertinib
    2. BDocetaxel
    3. CCrizotinib
    4. DPembrolizumab

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19. Question 19 · Easy

    In chronic myeloid leukaemia, imatinib acts by inhibiting which protein?

    1. ABCR::ABL1 tyrosine kinase
    2. BBruton tyrosine kinase
    3. CJAK2 kinase
    4. DFLT3 receptor

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20. Question 20 · Medium

    Needle biopsy of the prostate in a farmer with a PSA of 14 ng/mL: a small focus of crowded small glands with prominent nucleoli, and the pathologist is unsure between a small carcinoma and benign atrophy. Which staining pattern supports carcinoma?

    1. AAMACR positive with intact p63 basal cells
    2. BAMACR negative with intact p63 basal cells
    3. CPSA negative with intact HMWCK basal cells
    4. DAMACR positive with absent p63 basal cells

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21. Question 21 · Medium

    Resection report of a 2 cm well-differentiated neuroendocrine tumour of the ileum: synaptophysin and chromogranin positive, mitotic count 1 per 2 mm2, and a Ki-67 index of 12% in the hotspot. The patient, an auto-rickshaw driver with flushing and diarrhoea, asks what this means for his tumour. Under the WHO grading of gastroenteropancreatic NETs, this tumour is:

    1. AGrade 3 NET
    2. BGrade 1 NET
    3. CGrade 2 NET
    4. DNeuroendocrine carcinoma

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22. Question 22 · Medium

    Core biopsy of a breast lump at a cancer centre in Thiruvananthapuram: invasive ductal carcinoma, with ER positive in 6% of tumour nuclei, PR negative and HER2 IHC 1+. Consider: 1. The tumour is reported as ER-low positive. 2. It is treated as ER-negative and endocrine therapy is never offered. 3. Its behaviour often resembles ER-negative tumours. 4. Cold ischaemia time over 1 hour can cause false-negative ER. Which statements are correct?

    1. A1, 2, 3 and 4
    2. B1 and 2 only
    3. C1, 3 and 4 only
    4. D2 and 4 only

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23. Question 23 · Hard

    Pleural biopsy from a retired shipyard worker in Visakhapatnam with a recurrent right pleural effusion and mild pleural thickening on CT, with no mass: a dense mesothelial proliferation with mild atypia, but the pathologist cannot see definite invasion into fat. He worked for 25 years lagging pipes with asbestos, and thoracoscopy showed only diffuse thickening without nodules. Calretinin and WT1 are positive in the cells, and claudin-4 is negative. The clinician asks whether this is reactive mesothelial hyperplasia or an early epithelioid mesothelioma. Which result best supports malignancy?

    1. APositive cytoplasmic D2-40 staining
    2. BNegative claudin-4 staining
    3. CStrong calretinin positivity in the cells
    4. DLoss of nuclear BAP1 in the mesothelial cells

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24. Question 24 · Easy

    Under the WHO CNS5 classification (2021), the term glioblastoma in an adult is reserved for a diffuse astrocytic glioma that is:

    1. AIDH-mutant and ATRX-lost
    2. BIDH-wildtype
    3. CH3 K27M-mutant
    4. D1p/19q-codeleted

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25. Question 25 · Hard

    A neurosurgeon at a regional cancer centre sends a tumour from a software engineer with headaches for 6 months; MRI showed a 4 cm non-enhancing left frontal mass. He is right-handed and has had two focal seizures. Histology shows a moderately cellular diffuse astrocytic glioma with occasional mitoses, but no necrosis and no microvascular proliferation. IHC: IDH1 R132H positive, ATRX lost, p53 strongly positive in most nuclei. Molecular tests: 1p/19q intact, MGMT promoter methylated, and CDKN2A/B homozygous deletion. According to the WHO CNS5 (2021) classification, what is the integrated diagnosis?

    1. AAstrocytoma, IDH-mutant, CNS WHO grade 2
    2. BOligodendroglioma, IDH-mutant, grade 3
    3. CAstrocytoma, IDH-mutant, CNS WHO grade 4
    4. DGlioblastoma, IDH-mutant, grade 4

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