A 44-year-old man with nodular sclerosis Hodgkin lymphoma has polyuria and confusion. Serum calcium is 12.9 mg/dL (reference 8.5-10.5), phosphate 4.2 mg/dL, intact PTH 6 pg/mL (reference 10-65), PTH-related protein undetectable and 1,25-dihydroxyvitamin D 120 pg/mL (reference 20-75). Bone scan shows no metastases. What is the mechanism of his hypercalcaemia?

Calcitriol made in the tumour tissue

Osteolysis by bone marrow metastases

PTHrP secretion by Reed-Sternberg cells

Parathyroid adenoma with lymphoma

Neoplasia: oncogenes, tumour suppressors and markers

33 NEET-PG practice questions on Neoplasia: oncogenes, tumour suppressors and markers, 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.

Question 1 · Easy
A 63-year-old bidi smoker from rural Bihar has a central hilar mass on chest X-ray. Serum calcium is 13.2 mg/dL and serum PTH is suppressed. There are no bone metastases on the bone scan. Which tumour type is most likely?
1. ASquamous cell carcinoma
2. BAdenocarcinoma
3. CBronchial carcinoid tumour
4. DSmall cell carcinoma
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Answer: A · Squamous cell carcinoma
Squamous cell carcinoma of the lung is the tumour classically linked with humoral hypercalcaemia of malignancy. It secretes PTH-related protein (PTHrP), which acts on PTH receptors in bone and kidney, so calcium rises while the patient's own PTH is suppressed. It is usually central and strongly linked to smoking. Small cell carcinoma is also central but its paraneoplastic syndromes are SIADH, ectopic ACTH and Lambert-Eaton syndrome.
- B: Adenocarcinoma is usually peripheral and is not the classic PTHrP-secreting tumour.
- C: Carcinoids cause carcinoid syndrome or ectopic ACTH, not PTHrP hypercalcaemia.
- D: Small cell carcinoma causes SIADH, ectopic ACTH and Lambert-Eaton syndrome, not PTHrP hypercalcaemia.
Question 2 · Hard
A 64-year-old man has multiple liver masses but no known primary. Biopsy shows adenocarcinoma forming glands with 'dirty' central necrosis. Immunohistochemistry: CK7 negative, CK20 positive, CDX2 positive, TTF-1 negative. Which site is the most likely primary?
1. APancreas
2. BStomach
3. CColorectum
4. DLung
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Answer: C · Colorectum
The CK7-negative, CK20-positive pattern with nuclear CDX2 staining is characteristic of colorectal adenocarcinoma, and glands with dirty (garland) necrosis support it. Lung adenocarcinoma is usually CK7-positive, CK20-negative and TTF-1-positive. Upper GI and pancreatic adenocarcinomas usually express CK7, often with CK20. Colonoscopy is therefore the next step, and RAS, BRAF and mismatch repair testing of the tumour guide treatment.
- A: Pancreatic adenocarcinoma is usually CK7-positive.
- B: Gastric adenocarcinoma usually expresses CK7, unlike this tumour.
- D: Lung adenocarcinoma is typically CK7-positive and TTF-1-positive.
Question 3 · Hard
A 44-year-old man with nodular sclerosis Hodgkin lymphoma has polyuria and confusion. Serum calcium is 12.9 mg/dL (reference 8.5-10.5), phosphate 4.2 mg/dL, intact PTH 6 pg/mL (reference 10-65), PTH-related protein undetectable and 1,25-dihydroxyvitamin D 120 pg/mL (reference 20-75). Bone scan shows no metastases. What is the mechanism of his hypercalcaemia?
1. ACalcitriol made in the tumour tissue
2. BOsteolysis by bone marrow metastases
3. CPTHrP secretion by Reed-Sternberg cells
4. DParathyroid adenoma with lymphoma
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Answer: A · Calcitriol made in the tumour tissue
Hypercalcaemia with suppressed PTH means the parathyroids are not the cause. PTHrP is undetectable and the bone scan is clear, so humoral PTHrP and local osteolysis are unlikely. A high 1,25-dihydroxyvitamin D points to extra-renal 1-alpha-hydroxylase activity in the lymphoma tissue (tumour cells and associated macrophages), the same mechanism seen in sarcoidosis; it raises intestinal calcium absorption. Steroids reduce this calcitriol production, along with hydration and treatment of the lymphoma.
- B: Osteolytic metastases do not raise calcitriol, and the bone scan is clear.
- C: PTHrP is undetectable here, so humoral hypercalcaemia by PTHrP is excluded.
- D: A parathyroid adenoma would give a raised or inappropriately normal PTH, not a suppressed one.
Question 4 · Easy
A 49-year-old man has worked for 20 years in a factory making polyvinyl chloride pipes. He now has weight loss and hepatomegaly, and CT shows multiple vascular liver masses. Biopsy shows malignant endothelial cells forming irregular vascular channels. What is the most likely diagnosis?
1. AHepatocellular carcinoma
2. BHepatic angiosarcoma
3. CMetastatic carcinoid
4. DHepatic haemangioma
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Answer: B · Hepatic angiosarcoma
Long exposure to vinyl chloride monomer in the PVC industry is the classic occupational cause of angiosarcoma of the liver. The biopsy shows a malignant vascular tumour, with atypical endothelial cells lining anastomosing channels. Arsenic and the old contrast agent Thorotrast are other recognised causes. The tumour is aggressive and the prognosis is poor, so it is a notifiable occupational disease in many countries.
- A: Hepatocellular carcinoma is made of malignant hepatocytes, not endothelial cells.
- C: Carcinoid metastases are nests of neuroendocrine cells, not vascular channels.
- D: Haemangioma is a benign vascular tumour without atypia.
Question 5 · Medium
A 29-year-old woman is diagnosed with breast carcinoma. Her younger brother had a rhabdomyosarcoma at 12, and her mother died of an adrenocortical carcinoma at 38. Her cousin has a brain tumour. Which gene is most likely mutated in this family?
1. ABRCA1
2. BTP53
3. CPTEN
4. DCDH1
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Answer: B · TP53
Early breast cancer with childhood sarcoma, adrenocortical carcinoma and brain tumours across one family is the pattern of Li-Fraumeni syndrome, caused by a germline mutation of TP53. Losing the remaining normal copy removes the cell's main guardian against DNA damage, so many tissue types develop cancers at young ages. Affected people should avoid unnecessary radiation, which adds DNA damage; surveillance often uses whole-body MRI. Relatives should be offered genetic counselling and testing.
- A: BRCA1 causes breast and ovarian cancer, not childhood sarcoma and adrenocortical carcinoma.
- C: PTEN mutations cause Cowden syndrome, with breast, thyroid and endometrial cancers.
- D: CDH1 mutations cause diffuse gastric and lobular breast cancer.
Question 6 · Easy
A 34-year-old man with untreated HIV infection and a CD4 count of 90 cells/µL has several violaceous plaques on his legs and palate. Biopsy shows spindle cells forming slit-like vascular spaces with extravasated red cells. Which virus is responsible for this tumour?
1. AHuman papillomavirus 16
2. BEpstein-Barr virus
3. CCytomegalovirus
4. DHuman herpesvirus 8
Answer and explanation in LearnFree account
Question 7 · Medium
A 38-year-old woman's cervical screening shows a high-grade squamous intraepithelial lesion, and HPV 16 DNA is detected. Colposcopic biopsy confirms CIN 3. How does the viral E7 protein promote proliferation of the infected cells?
1. AIt targets p53 for degradation
2. BIt amplifies the cellular MYC gene
3. CIt binds RB and releases E2F
4. DIt mutates the cellular KRAS gene
Answer and explanation in LearnFree account
Question 8 · Medium
A 50-year-old groundnut farmer from a humid district stores his crop in damp sacks for months. He has no history of alcohol use and is negative for HBsAg and anti-HCV. He now has a large hepatocellular carcinoma. Which molecular change is characteristic of the carcinogen most likely involved?
1. AAmplification of the MYC gene
2. BLoss of both APC alleles
3. CTranslocation involving the ABL gene
4. DG to T mutation at codon 249 of TP53
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Question 9 · Medium
A 54-year-old woman from a surgical OPD has an enlarged, firm left inguinal lymph node. Excision shows sheets of large epithelioid cells with prominent nucleoli and no visible pigment. Immunohistochemistry: pan-cytokeratin negative, CD45 negative, S-100 diffusely positive, HMB-45 positive, SOX10 positive. What is the most likely tumour type?
1. AMalignant peripheral nerve sheath tumour
2. BDiffuse large B-cell lymphoma
3. CMetastatic carcinoma
4. DMetastatic melanoma
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Question 10 · Medium
A 66-year-old retired shipyard worker who smoked for 40 years has calcified pleural plaques on chest X-ray from asbestos exposure in the 1980s. He asks which cancer he is now at greatest risk of. Which malignancy is most common in people with this exposure?
1. ABronchogenic carcinoma
2. BLaryngeal carcinoma
3. CMalignant mesothelioma
4. DPeritoneal mesothelioma
Answer and explanation in LearnFree account
Question 11 · Medium
A 45-year-old woman receiving radiotherapy for carcinoma of the cervix has DNA damage in the normal cells within the field. In these normal cells, p53 levels rise and the cells pause in G1 to repair the damage. Which protein induced by p53 mainly causes this arrest?
1. AMDM2, a ubiquitin ligase
2. BCyclin D1, a G1 cyclin
3. Cp21, a CDK inhibitor
4. DBAX, a pro-apoptotic protein
Answer and explanation in LearnFree account
Question 12 · Medium
A 46-year-old woman with a 3 cm invasive ductal carcinoma of the breast has HER2 staining of 3+ on immunohistochemistry, and FISH shows many extra copies of the ERBB2 gene. She is started on trastuzumab with chemotherapy. By which mechanism is this oncogene activated?
1. APoint mutation
2. BGene amplification
3. CPromoter hypermethylation
4. DChromosomal translocation
Answer and explanation in LearnFree account
Question 13 · Medium
A 31-year-old man has a gastric carcinoma made of scattered signet-ring cells that infiltrate the wall and thicken the stomach without forming a mass. His father died of stomach cancer at 40, and his aunt had lobular carcinoma of the breast. A germline mutation in which gene is most likely?
1. AMLH1
2. BCDH1 (E-cadherin)
3. CSMAD4
4. DAPC
Answer and explanation in LearnFree account
Question 14 · Medium
A 62-year-old bidi smoker in a medicine OPD has 3 months of weakness climbing stairs and a dry mouth. Proximal leg muscles are weak, but strength improves briefly after repeated effort, and the ankle reflexes are absent. Chest CT shows a central lung mass with mediastinal nodes. Antibodies against which target are most likely present?
1. AMuscle-specific kinase
2. BVoltage-gated calcium channels
3. CAcetylcholine receptors
4. DVoltage-gated sodium channels
Answer and explanation in LearnFree account
Question 15 · Medium
A 58-year-old man has painless haematuria and a dull ache in the left flank. His Hb is 19.2 g/dL and haematocrit 58%, with normal oxygen saturation and no splenomegaly. CT shows a 7 cm solid, enhancing mass in the left kidney. Which tumour product best explains his blood count?
1. ARenin
2. BPTH-related protein
3. CErythropoietin
4. DInterleukin-6
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Question 16 · Easy
In a tumour board meeting at a regional cancer centre, a postgraduate lists four pairings of a serum marker with the tumour it is mainly used to follow: 1. Calcitonin with papillary carcinoma of the thyroid. 2. Alpha-fetoprotein with yolk sac tumour. 3. CA 19-9 with pancreatic adenocarcinoma. 4. Prostate-specific antigen with prostatic adenocarcinoma. Which pairings are correct?
1. A1 and 3 only
2. B2, 3 and 4 only
3. C1, 3 and 4 only
4. D2 and 3 only
Answer and explanation in LearnFree account
Question 17 · Medium
A 48-year-old man from a village in a delta district of West Bengal, where tube-well water is untreated, has hard keratotic papules on his palms and soles and spotty 'raindrop' hyper- and hypopigmentation of the trunk. A non-healing ulcer on his back is biopsied and shows invasive squamous cell carcinoma. Which carcinogen is most likely responsible?
1. AAflatoxin
2. BCadmium
3. CArsenic
4. DBenzene
Answer and explanation in LearnFree account
Question 18 · Medium
A 22-year-old woman undergoes colonoscopy because her mother died of colon cancer at 38. More than 300 adenomatous polyps carpet the colon, and a germline APC mutation is found. How does the normal APC protein restrain cell growth?
1. AIt repairs DNA base-pair mismatches
2. BIt inactivates RAS by hydrolysing GTP
3. CIt promotes degradation of beta-catenin
4. DIt inhibits cyclin D-CDK4 complexes
Answer and explanation in LearnFree account
Question 19 · Hard
A 58-year-old postmenopausal woman with hormone receptor-positive, HER2-negative metastatic breast carcinoma is started on letrozole with palbociclib. On review she has neutropenia but feels well. Through which cell-cycle mechanism does palbociclib slow tumour growth?
1. AInhibits topoisomerase II during S phase
2. BKeeps RB hypophosphorylated, blocking G1 to S
3. CActivates p53 and induces apoptosis directly
4. DBlocks microtubules and stops cells in mitosis
Answer and explanation in LearnFree account
Question 20 · Easy
A 56-year-old man with hepatitis B-related cirrhosis on 6-monthly surveillance in a gastroenterology OPD has a new 3 cm arterially enhancing liver nodule with washout on triple-phase CT. Which serum tumour marker is most useful to measure now?
1. ACA 19-9
2. BCarcinoembryonic antigen
3. CAlpha-fetoprotein
4. DBeta-hCG
Answer and explanation in LearnFree account
Question 21 · Medium
A 52-year-old woman with dyspepsia has gastric biopsies showing a low-grade marginal zone (MALT) lymphoma confined to the stomach, with Helicobacter pylori organisms on the surface epithelium. Staging shows no spread. What is the most appropriate first treatment?
1. ATotal gastrectomy
2. BGastric radiotherapy
3. CR-CHOP chemotherapy
4. DEradication therapy for H. pylori
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Question 22 · Hard
A 17-year-old boy has more than ten cafe-au-lait macules, axillary freckling, several soft cutaneous neurofibromas and Lisch nodules on slit-lamp examination. His mother has similar skin lesions. Which signalling change best explains tumour formation in this disorder?
1. ARAS gene undergoes direct point mutation
2. BMerlin no longer suppresses cell growth
3. CRAS stays active as its GAP is lost
4. DBeta-catenin fails to be degraded
Answer and explanation in LearnFree account
Question 23 · Medium
A 62-year-old man in a surgical OPD has a hard 2 cm lump beneath the left nipple with nipple retraction; core biopsy shows invasive ductal carcinoma. His sister had ovarian cancer and his brother has prostate cancer diagnosed at 55. Which gene is most likely mutated?
1. ABRCA2
2. BTP53
3. CSTK11
4. DPTEN
Answer and explanation in LearnFree account
Question 24 · Medium
A 64-year-old man has had painful, tender cords appearing on his arm, then his thigh, then his chest wall over 6 weeks. Each clears and another appears elsewhere. He has lost 8 kg and has new-onset diabetes. Which underlying malignancy is most likely?
1. APapillary carcinoma of thyroid
2. BPancreatic adenocarcinoma
3. CHepatocellular carcinoma
4. DSquamous carcinoma of oesophagus
Answer and explanation in LearnFree account
Question 25 · Hard
A 26-year-old man has a right testicular mass. Before surgery, serum AFP is 820 ng/mL (reference below 10 ng/mL), beta-hCG is mildly raised and LDH is normal. After high inguinal orchiectomy, the pathologist's initial report on the sections examined is pure seminoma. What is the best interpretation?
1. AThe AFP rise is a laboratory artefact
2. BA non-seminomatous component is present
3. CAFP is secreted by the seminoma cells
4. DThe raised AFP is from syncytiotrophoblast
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Neoplasia: oncogenes, tumour suppressors and markers

A 63-year-old bidi smoker from rural Bihar has a central hilar mass on chest X-ray. Serum calcium is 13.2 mg/dL and serum PTH is suppressed. There are no bone metastases on the bone scan. Which tumour type is most likely?

A 64-year-old man has multiple liver masses but no known primary. Biopsy shows adenocarcinoma forming glands with 'dirty' central necrosis. Immunohistochemistry: CK7 negative, CK20 positive, CDX2 positive, TTF-1 negative. Which site is the most likely primary?

A 49-year-old man has worked for 20 years in a factory making polyvinyl chloride pipes. He now has weight loss and hepatomegaly, and CT shows multiple vascular liver masses. Biopsy shows malignant endothelial cells forming irregular vascular channels. What is the most likely diagnosis?

A 29-year-old woman is diagnosed with breast carcinoma. Her younger brother had a rhabdomyosarcoma at 12, and her mother died of an adrenocortical carcinoma at 38. Her cousin has a brain tumour. Which gene is most likely mutated in this family?

A 34-year-old man with untreated HIV infection and a CD4 count of 90 cells/µL has several violaceous plaques on his legs and palate. Biopsy shows spindle cells forming slit-like vascular spaces with extravasated red cells. Which virus is responsible for this tumour?

A 38-year-old woman's cervical screening shows a high-grade squamous intraepithelial lesion, and HPV 16 DNA is detected. Colposcopic biopsy confirms CIN 3. How does the viral E7 protein promote proliferation of the infected cells?

A 50-year-old groundnut farmer from a humid district stores his crop in damp sacks for months. He has no history of alcohol use and is negative for HBsAg and anti-HCV. He now has a large hepatocellular carcinoma. Which molecular change is characteristic of the carcinogen most likely involved?

A 66-year-old retired shipyard worker who smoked for 40 years has calcified pleural plaques on chest X-ray from asbestos exposure in the 1980s. He asks which cancer he is now at greatest risk of. Which malignancy is most common in people with this exposure?

A 45-year-old woman receiving radiotherapy for carcinoma of the cervix has DNA damage in the normal cells within the field. In these normal cells, p53 levels rise and the cells pause in G1 to repair the damage. Which protein induced by p53 mainly causes this arrest?

A 46-year-old woman with a 3 cm invasive ductal carcinoma of the breast has HER2 staining of 3+ on immunohistochemistry, and FISH shows many extra copies of the ERBB2 gene. She is started on trastuzumab with chemotherapy. By which mechanism is this oncogene activated?

A 31-year-old man has a gastric carcinoma made of scattered signet-ring cells that infiltrate the wall and thicken the stomach without forming a mass. His father died of stomach cancer at 40, and his aunt had lobular carcinoma of the breast. A germline mutation in which gene is most likely?

A 58-year-old man has painless haematuria and a dull ache in the left flank. His Hb is 19.2 g/dL and haematocrit 58%, with normal oxygen saturation and no splenomegaly. CT shows a 7 cm solid, enhancing mass in the left kidney. Which tumour product best explains his blood count?

A 22-year-old woman undergoes colonoscopy because her mother died of colon cancer at 38. More than 300 adenomatous polyps carpet the colon, and a germline APC mutation is found. How does the normal APC protein restrain cell growth?

A 58-year-old postmenopausal woman with hormone receptor-positive, HER2-negative metastatic breast carcinoma is started on letrozole with palbociclib. On review she has neutropenia but feels well. Through which cell-cycle mechanism does palbociclib slow tumour growth?

A 56-year-old man with hepatitis B-related cirrhosis on 6-monthly surveillance in a gastroenterology OPD has a new 3 cm arterially enhancing liver nodule with washout on triple-phase CT. Which serum tumour marker is most useful to measure now?

A 52-year-old woman with dyspepsia has gastric biopsies showing a low-grade marginal zone (MALT) lymphoma confined to the stomach, with Helicobacter pylori organisms on the surface epithelium. Staging shows no spread. What is the most appropriate first treatment?

A 17-year-old boy has more than ten cafe-au-lait macules, axillary freckling, several soft cutaneous neurofibromas and Lisch nodules on slit-lamp examination. His mother has similar skin lesions. Which signalling change best explains tumour formation in this disorder?

A 62-year-old man in a surgical OPD has a hard 2 cm lump beneath the left nipple with nipple retraction; core biopsy shows invasive ductal carcinoma. His sister had ovarian cancer and his brother has prostate cancer diagnosed at 55. Which gene is most likely mutated?

A 64-year-old man has had painful, tender cords appearing on his arm, then his thigh, then his chest wall over 6 weeks. Each clears and another appears elsewhere. He has lost 8 kg and has new-onset diabetes. Which underlying malignancy is most likely?