Neoplasia for NEET PG Pathology: Oncogenes, Tumour Suppressors, Carcinogens, Paraneoplastic Syndromes, Tumour Markers, Grade vs Stage

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🎯 Exam priority: Very high. Expect: which gene goes with which cancer, the two-hit hypothesis, carcinogen–cancer pairs, cancer viruses, paraneoplastic syndromes from lung cancer, tumour markers and their limits, and grade versus stage.

CBME mapping: PA 6.1–6.7, 7.1.

Oncogenes and tumour suppressor genes with their cancers, and serum tumour markers. Drawn by TrackNation.

The Words That Get Tested

• Hyperplasia: more cells that look normal. Metaplasia: cells change to a type not normally found in that tissue. Dysplasia: abnormal cells, not yet cancer, graded mild to severe. Carcinoma in situ: cancer-like cells that have not spread beyond where they formed.

• Cancer (MSD): lack of differentiation, local invasion and metastasis. Benign tumours may grow but do not spread. Most cancer deaths are from metastases, not the primary. Tumours release VEGF to grow new vessels.

• Carcinoma arises from skin or the linings of organs; sarcoma from bone and soft tissue (fat, muscle, cartilage, vessels, fibrous tissue). A teratoma is a germ cell tumour with several tissues such as hair, muscle and bone.

• Grade = how abnormal the cells look (nuclei, nucleoli, mitoses, necrosis). Stage = extent of disease; TNM: T = size and local spread, N = regional nodes, M = distant metastasis. Stage guides treatment and prognosis.

Genes: Accelerators and Brakes

• Oncogenes are abnormal forms of proto-oncogenes, activated by point mutation (e.g. chemicals), amplification or translocation. RAS is abnormal in about 25% of cancers; HER2 is amplified in breast and gastric cancer; BCR::ABL1 in CML; CMYC in Burkitt; NMYC in neuroblastoma and small cell lung cancer; EGFR and EML4-ALK in lung adenocarcinoma; KRAS in pancreatic cancer; RET (chromosome 10) in MEN 2.

• Tumour suppressors: p53 stops replication of damaged DNA and triggers apoptosis; BRCA1/2 loss raises breast and ovarian cancer risk; MEN1 (menin) loss causes MEN 1.

• Two-hit model (RB1, 13q14): in hereditary retinoblastoma one allele is mutated in every cell and a later somatic hit knocks out the other. Children present with leukocoria; survivors of the hereditary form can get second cancers such as osteosarcoma.

• Step-wise carcinogenesis: in familial polyposis, hyperproliferation starts with loss of a suppressor gene on chromosome 5, then RAS activation and losses on 18 and 17. FAP is autosomal dominant with ≥ 100 polyps; nearly all get colon cancer by 40.

• Telomerase lets cancer cells divide without limit. DNA-repair defects (Bloom, Fanconi, Down syndrome; xeroderma pigmentosum for UV) raise cancer risk.

• MEN syndromes (all autosomal dominant): MEN 1 = parathyroid, pancreatic islet, pituitary; MEN 2A = medullary thyroid, phaeochromocytoma, parathyroid; MEN 2B = medullary thyroid, phaeochromocytoma, mucosal neuromas, marfanoid habitus.

Carcinogens

UV light causes thymidine dimers. Co-carcinogens have little effect alone but boost another carcinogen. Chronic inflammation (e.g. ulcerative colitis) raises cancer risk. IARC groups: 1 = carcinogenic to humans, 2A = probably, 2B = possibly, 3 = not classifiable.

Effects on the Host: Paraneoplastic Syndromes

Up to 20% of cancer patients get paraneoplastic syndromes; lung cancer, especially small cell, is the commonest cause. Peripheral neuropathy is the commonest neurological one; anti-Hu is found in some lung cancer patients. Lambert-Eaton weakness improves with repeated nerve stimulation (CMAP amplitude rises > 200% at > 10 Hz).

Diagnosis, Markers and Immunity

• Diagnosis needs biopsy and histology. Lymphoma needs a core or excision biopsy to keep the node architecture. Bone scans miss purely lytic tumours such as myeloma.

• Markers: no marker is specific or sensitive enough for screening. AFP — liver cancer, non-seminomatous germ cell tumours; β-hCG — gestational trophoblastic disease; PSA — prostate, but also BPH and prostatitis; CA 125 — ovary; CA 19-9 — pancreas; CEA — colon, also raised in heavy smokers, best for recurrence after surgery; calcitonin — medullary thyroid; chromogranin A — neuroendocrine tumours; thyroglobulin — after thyroidectomy; β2-microglobulin — myeloma prognosis.

• Immunity: immune surveillance removes early cancers; T cells, macrophages and NK cells kill tumour cells. Tumours escape via PD-L1 binding PD-1 on T cells — checkpoint inhibitors block this. CAR-T works best in B-cell cancers.

Traps the Examiner Sets

• Grade = microscopy; stage = spread.

• Small cell lung: ACTH, vasopressin, Lambert-Eaton. Squamous lung: PTHrP hypercalcaemia.

• CEA and PSA are not screening tests for everyone; CEA rises in smokers, PSA in BPH.

• RB1 is a tumour suppressor (two hits); RET is an oncogene (one activating hit).

Memory Hooks & Shortcuts

Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.

• 🧠 Grade = Gaze down the microscope; Stage = Spread — grade vs stage

• 🧠 Two hits to blind the eye — RB1 two-hit, retinoblastoma

• 🧠 RET Raises the thyroid's Calcitonin — RET, MEN 2, medullary thyroid, calcitonin

• 🧠 Small cell is the Sly cell: ACTH, ADH, Lambert-Eaton — small cell paraneoplastic syndromes

• 🧠 Squamous = Stones (calcium) — PTHrP hypercalcaemia

• 🧠 Yo-Yo for the ladies' cerebellum — anti-Yo, breast/ovary

• 🧠 Vinyl in the Veins of the liver — vinyl chloride, angiosarcoma

Rapid-Revision Cards

• Metaplasia

  Cells change to a type not normal for that tissue.

• Carcinoma in situ

  Cancer-like cells that have not spread beyond where they formed.

• Grade vs stage

  Grade = microscopy; stage = extent (TNM).

• Carcinoma vs sarcoma

  Linings/skin vs bone and soft tissue.

• Teratoma

  Germ cell tumour with hair, muscle, bone.

• HER2

  Amplified — breast, gastric.

• EML4-ALK / EGFR

  Lung adenocarcinoma.

• KRAS

  Pancreas, lung.

• MYCN

  Neuroblastoma (2p24); poor prognosis if amplified.

• RB1

  13q14; two hits; leukocoria; later osteosarcoma.

• p53

  Stops damaged-DNA replication; triggers apoptosis.

• FAP

  AD; ≥ 100 polyps; cancer by 40; chromosome 5 suppressor first.

• MEN 1

  Parathyroid, pancreas, pituitary — menin.

• MEN 2A / 2B

  Medullary thyroid + phaeo (+ parathyroid / + neuromas, marfanoid) — RET.

• Vinyl chloride

  Hepatic angiosarcoma.

• Aromatic amines

  Bladder.

• UV

  Thymidine dimers; xeroderma pigmentosum.

• Small cell lung paraneoplastic

  ACTH, vasopressin, Lambert-Eaton.

• Squamous lung

  PTHrP hypercalcaemia.

• Anti-Yo

  Cerebellar degeneration — breast/ovary.

• AFP / β-hCG

  Liver, non-seminoma / trophoblastic disease.

• CA 125 / CA 19-9 / CEA

  Ovary / pancreas / colon recurrence.

• Checkpoint inhibitors

  Block PD-1/PD-L1 or CTLA-4.

Sources

Facts in this article were checked against these documents.

• MSD Manual Professional: Overview of Cancer; Cellular and Molecular Basis of Cancer; Paraneoplastic Syndromes; Cancer Diagnosis — Merck & Co. (MSD Manuals), reviewed 2024–26 (link)

• MSD Manual Professional: Tumor Antigens; Tumor Immunodiagnosis; Host Response to Tumors; MEN syndromes; Retinoblastoma; Neuroblastoma; FAP — Merck & Co. (MSD Manuals), reviewed 2024–26 (link)

• NCI Dictionary of Cancer Terms — National Cancer Institute, accessed 2026 (link)

• Agents Classified by the IARC Monographs — International Agency for Research on Cancer (WHO), accessed 2026 (link)

• Competency Based Undergraduate Curriculum, Pathology (PA 6, 7) — National Medical Commission, 2024

Test Yourself: Practice Questions

Forty-six questions in NEET PG style, most of them clinical vignettes.

Practice Questions (NEET PG pattern)

Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.

Q1. Biopsy shows a change of cells into a type that does not normally occur in that tissue, with no atypia. This is

• (a) metaplasia

• (b) hyperplasia

• (c) dysplasia

• (d) carcinoma in situ

Q2. A biopsy shows cells that look like cancer cells but are confined to where they formed, without spread into nearby tissue. This is

• (a) carcinoma in situ

• (b) metaplasia

• (c) invasive carcinoma

• (d) hyperplasia

Q3. The three prominent properties of cancer listed by MSD are

• (a) hyperplasia, metaplasia and atrophy

• (b) lack of differentiation, local invasion and metastasis

• (c) fever, weight loss and anaemia

• (d) encapsulation, slow growth and no spread

Q4. A pathology report grades a tumour as 'high grade'. Grade is based on

• (a) distant metastasis

• (b) tumour size

• (c) how abnormal the cells look — nuclei, nucleoli, mitoses and necrosis

• (d) lymph node spread

Q5. In TNM staging, 'N' describes

• (a) number of mitoses

• (b) spread to nearby lymph nodes

• (c) tumour size

• (d) nuclear grade

Q6. A malignant tumour arising from skeletal muscle, fat or bone is called a

• (a) sarcoma

• (b) carcinoma

• (c) lymphoma

• (d) teratoma

Q7. An ovarian mass contains hair, muscle and bone. This is a

• (a) carcinoma in situ

• (b) lymphoma

• (c) sarcoma

• (d) teratoma (germ cell tumour)

Q8. Most patients with cancer die from

• (a) paraneoplastic syndromes

• (b) tumour markers

• (c) metastases

• (d) the primary tumour itself

Q9. A woman's breast cancer shows amplification of a growth factor receptor gene. The gene most likely amplified is

• (a) TP53

• (b) HER2

• (c) BRCA1

• (d) RB1

Q10. A lung adenocarcinoma carries a chimeric fusion gene. The likely fusion is

• (a) BCR::ABL1

• (b) EML4-ALK

• (c) PML::RARA

• (d) CMYC-IGH

Q11. The oncogene most associated with pancreatic cancer is

• (a) KRAS

• (b) RET

• (c) NMYC

• (d) HER2

Q12. A young child has an abdominal mass and raised urinary catecholamine breakdown products. Amplification of which gene correlates with poor outcome?

• (a) MYCN (chromosome 2p24)

• (b) RET

• (c) BRCA2

• (d) RB1

Q13. A baby has a white pupillary reflex; the father had the same tumour as a child. The gene and model are

• (a) TP53 — one hit

• (b) RET — one activating mutation

• (c) RB1 on 13q14 — germline first hit, somatic second hit

• (d) BRCA1 — X-linked

Q14. A survivor of hereditary retinoblastoma is at particular risk later of

• (a) osteosarcoma and other sarcomas

• (b) hepatocellular carcinoma

• (c) CML

• (d) no further cancers

Q15. The normal function of p53 is to

• (a) stimulate cell division

• (b) stop replication of damaged DNA and trigger apoptosis

• (c) activate RAS

• (d) lengthen telomeres

Q16. Cancer cells avoid the normal limit on the number of cell divisions by activating

• (a) telomerase

• (b) caspases

• (c) BRCA1

• (d) p53

Q17. A 20-year-old has hundreds of adenomatous polyps carpeting the colon; his mother had the same condition. The inheritance and risk are

• (a) sporadic; no risk

• (b) autosomal recessive; risk only after 70

• (c) autosomal dominant; nearly all develop colon cancer by 40

• (d) X-linked; low risk

Q18. A young man has medullary thyroid carcinoma, a phaeochromocytoma, multiple mucosal neuromas and a marfanoid build. The syndrome and gene are

• (a) FAP — APC

• (b) MEN 2B — RET proto-oncogene

• (c) MEN 2A — RB1

• (d) MEN 1 — menin

Q19. A patient has hyperparathyroidism, a pancreatic islet tumour and a pituitary adenoma. The gene involved encodes

• (a) RET (oncogene)

• (b) p53

• (c) menin (MEN1, tumour suppressor)

• (d) HER2

Q20. A worker with long industrial chemical exposure develops angiosarcoma of the liver. The likely carcinogen is

• (a) aromatic amines

• (b) asbestos

• (c) benzene

• (d) vinyl chloride (hepatic angiosarcoma)

Q21. Occupational exposure to aromatic amines increases the risk of

• (a) hepatic angiosarcoma

• (b) mesothelioma

• (c) bladder cancer

• (d) nasopharyngeal carcinoma

Q22. A patient with chronic urinary schistosomiasis is at increased risk of

• (a) colon cancer

• (b) bladder cancer

• (c) lymphoma

• (d) liver cancer

Q23. Which pairing of virus and cancer is correct?

• (a) HTLV-1 — adult T-cell lymphoma

• (b) HPV — hepatocellular carcinoma

• (c) EBV — Kaposi sarcoma

• (d) HBV — cervical cancer

Q24. A child with xeroderma pigmentosum develops multiple skin cancers at a young age. The UV damage that cannot be repaired is

• (a) RAS activation

• (b) telomere shortening

• (c) chromosome translocation

• (d) thymidine dimers

Q25. In the IARC classification, 'Group 2A' means the agent is

• (a) carcinogenic to humans

• (b) probably carcinogenic to humans

• (c) possibly carcinogenic

• (d) not classifiable

Q26. A patient with lung cancer has hypokalaemia, hypertension and a moon face. The likely tumour and mechanism are

• (a) small cell lung cancer — ectopic ACTH

• (b) carcinoid — serotonin

• (c) adenocarcinoma — erythropoietin

• (d) squamous cell lung cancer — PTHrP

Q27. A patient with lung cancer has calcium of 13.5 mg/dL, constipation and polyuria, without bone metastases. The tumour type and mediator are most likely

• (a) small cell — ACTH

• (b) carcinoid — VIP

• (c) adenocarcinoma — calcitonin

• (d) squamous cell carcinoma — PTH-related peptide

Q28. A man with proximal leg weakness, dry mouth and absent reflexes has a small cell lung cancer. Repetitive nerve stimulation increases CMAP amplitude by 250%. The defect is

• (a) postsynaptic receptor loss (myasthenia gravis)

• (b) presynaptic — impaired acetylcholine release (Lambert-Eaton)

• (c) demyelination

• (d) muscle necrosis

Q29. A woman develops progressive ataxia and dysarthria; serum shows anti-Yo antibodies. Search for a cancer of the

• (a) breast or ovary

• (b) lung

• (c) pancreas

• (d) kidney

Q30. A patient with a kidney tumour has a haematocrit of 58%. The mechanism is

• (a) iron overload

• (b) ectopic erythropoietin production

• (c) dehydration only

• (d) JAK2 mutation

Q31. A young man has a testicular mass and raised serum alpha-fetoprotein. This favours

• (a) a non-seminomatous germ cell tumour

• (b) Leydig cell tumour

• (c) pure seminoma

• (d) lymphoma

Q32. A heavy smoker with no cancer has a mildly raised CEA. This shows that CEA

• (a) measures smoking dose

• (b) proves colon cancer

• (c) is a screening test for everyone

• (d) is non-specific and best used to watch for recurrence after surgery

Q33. The marker more sensitive for pancreatic than colorectal cancer, used mainly to judge treatment response, is

• (a) CA 19-9

• (b) CA 125

• (c) PSA

• (d) AFP

Q34. After total thyroidectomy for differentiated thyroid cancer, recurrence is monitored with serum

• (a) thyroglobulin

• (b) chromogranin A

• (c) calcitonin

• (d) CEA

Q35. Tumour cells evade T-cell attack by expressing a ligand that binds PD-1 on T cells. Drugs that block this are called

• (a) alkylating agents

• (b) checkpoint inhibitors

• (c) tyrosine kinase inhibitors

• (d) antimetabolites

Q36. A patient with suspected lymphoma has an enlarged node. The preferred sample is

• (a) fine-needle aspiration only

• (b) a blood smear

• (c) serum LDH

• (d) a core biopsy or whole-node excision to keep the architecture

Q37. A woman with a pelvic mass has a raised serum CA 125. The marker is used mainly for

• (a) colon cancer screening

• (b) diagnosing and monitoring ovarian cancer (also raised by peritoneal inflammation)

• (c) screening all women for cancer

• (d) liver cancer

Q38. A 66-year-old man has a raised PSA. Which statement is correct?

• (a) a raised PSA proves prostate cancer

• (b) PSA is made by the bladder

• (c) PSA also rises in benign prostatic hyperplasia, prostatitis and after instrumentation

• (d) PSA is less sensitive than acid phosphatase

Q39. After evacuation of a molar pregnancy, the marker followed to detect gestational trophoblastic neoplasia is

• (a) CA 125

• (b) CEA

• (c) β-hCG

• (d) AFP

Q40. A patient with MEN 2A is being followed for medullary thyroid carcinoma. The tumour marker is

• (a) calcitonin

• (b) chromogranin A only

• (c) thyroglobulin

• (d) CA 19-9

Q41. A patient with flushing and diarrhoea has a suspected neuroendocrine (carcinoid) tumour. A useful serum marker is

• (a) CA 125

• (b) chromogranin A

• (c) PSA

• (d) AFP

Q42. In multiple myeloma, serum β2-microglobulin is used mainly for

• (a) prognosis

• (b) diagnosis of the M-protein

• (c) screening

• (d) detecting bone lesions

Q43. A patient with small cell lung cancer has a serum sodium of 118 mmol/L. The paraneoplastic mechanism is

• (a) erythropoietin

• (b) insulin-like growth factor

• (c) ectopic PTHrP

• (d) tumour production of vasopressin

Q44. An older man suddenly develops dozens of 'stuck-on' seborrhoeic keratoses. This Leser-Trélat sign should prompt a search for

• (a) lymphoma or gastrointestinal cancer

• (b) diabetes only

• (c) kidney stones

• (d) melanoma only

Q45. A toddler develops chaotic, rapid eye movements (opsoclonus). The associated tumour is

• (a) medulloblastoma

• (b) neuroblastoma

• (c) Wilms tumour

• (d) retinoblastoma

Q46. The commonest neurological paraneoplastic syndrome is

• (a) Lambert-Eaton syndrome

• (b) peripheral neuropathy

• (c) cerebellar degeneration

• (d) opsoclonus

Active Recall

From memory: define metaplasia, dysplasia and carcinoma in situ; contrast grade and stage; name the oncogene or suppressor in breast, lung, pancreatic cancer, neuroblastoma, retinoblastoma and MEN; pair carcinogens and viruses with cancers; list the paraneoplastic syndromes of lung cancer; and give the use and limits of the main tumour markers.