A 6-year-old girl from Indore has had early-morning vomiting, headache and a wide-based gait for 6 weeks. MRI shows a midline mass arising from the cerebellar vermis and filling the fourth ventricle, with hydrocephalus. Histology shows sheets of densely packed small round blue cells with scant cytoplasm and Homer Wright rosettes, positive for synaptophysin. Why must the whole spine be imaged as part of staging?

It seeds through the CSF as drop metastases

It spreads through the blood to the vertebrae

It compresses the cord by direct downward growth

It often has a separate spinal cord primary

Endocrine, bone and CNS pathology

40 NEET-PG practice questions on Endocrine, bone and CNS pathology, 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 · Medium
A 6-year-old girl from Indore has had early-morning vomiting, headache and a wide-based gait for 6 weeks. MRI shows a midline mass arising from the cerebellar vermis and filling the fourth ventricle, with hydrocephalus. Histology shows sheets of densely packed small round blue cells with scant cytoplasm and Homer Wright rosettes, positive for synaptophysin. Why must the whole spine be imaged as part of staging?
1. AIt spreads through the blood to the vertebrae
2. BIt compresses the cord by direct downward growth
3. CIt often has a separate spinal cord primary
4. DIt seeds through the CSF as drop metastases
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Answer: D · It seeds through the CSF as drop metastases
A midline vermian tumour of small round blue cells with Homer Wright rosettes in a child is medulloblastoma, an embryonal tumour (WHO grade 4). Its cells are shed into the CSF and settle on the leptomeninges of the spinal cord and cauda equina as 'drop' metastases, so staging includes MRI of the whole neuraxis and CSF cytology. Extraneural spread is rare. It is highly radiosensitive, and molecular groups (WNT, SHH, group 3 and group 4) guide prognosis, with WNT the most favourable.
- A: Blood-borne spread to bone is rare in medulloblastoma.
- B: Its spinal deposits come from CSF seeding, not direct growth down the canal.
- C: Medulloblastoma arises in the cerebellum, not as multifocal spinal primaries.
Question 2 · Medium
A 28-year-old woman has had early-morning episodes of sweating, confusion and odd behaviour that improve after eating; during one episode her plasma glucose was 38 mg/dL with inappropriately high insulin and C-peptide. CT shows a 1.5 cm lesion in the tail of the pancreas. She also has galactorrhoea with a raised prolactin, and serum calcium is 11.4 mg/dL with a raised PTH. Mutation of which gene is most likely?
1. ARET
2. BNF1
3. CMEN1 (menin)
4. DVHL
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Answer: C · MEN1 (menin)
An insulinoma, a prolactinoma and primary hyperparathyroidism together make multiple endocrine neoplasia type 1, caused by inactivating mutation of the MEN1 tumour suppressor gene, which encodes menin. Parathyroid hyperplasia is the commonest and usually the first feature; pancreatic and duodenal neuroendocrine tumours (gastrinoma, insulinoma) and pituitary adenomas complete the syndrome. First-degree relatives are offered genetic testing and screening.
- A: RET mutations cause MEN2 (medullary carcinoma, phaeochromocytoma), not insulinoma or prolactinoma.
- B: NF1 causes neurofibromas and occasionally duodenal somatostatinoma, not this triad.
- D: VHL causes haemangioblastoma, renal cell carcinoma and phaeochromocytoma; its pancreatic tumours are not usually insulinomas with pituitary disease.
Question 3 · Medium
A 71-year-old man from Ludhiana has had low back pain for 3 months and difficulty starting micturition. X-ray of the spine and pelvis shows multiple dense, sclerotic lesions in the vertebral bodies and iliac bones. Serum alkaline phosphatase is raised and serum calcium is normal. The most likely primary tumour is:
1. AFollicular thyroid carcinoma
2. BCarcinoma of the prostate
3. CMultiple myeloma
4. DRenal cell carcinoma
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Answer: B · Carcinoma of the prostate
Metastases are the commonest malignant tumours of bone, and dense osteoblastic (sclerotic) deposits in an elderly man with urinary symptoms point to prostatic carcinoma. Tumour cells stimulate osteoblasts, so alkaline phosphatase rises while calcium usually stays normal. Serum PSA and a prostatic biopsy confirm the diagnosis, and androgen deprivation is the basis of treatment for metastatic disease.
- A: Thyroid carcinoma metastases are lytic and expansile.
- C: Myeloma gives punched-out lytic lesions with a normal alkaline phosphatase.
- D: Renal cell carcinoma gives lytic, often expansile, vascular metastases.
Question 4 · Easy
A 9-year-old boy has had morning headaches, vomiting and an unsteady gait for 2 months. MRI shows a well-circumscribed cystic mass in the right cerebellar hemisphere with an enhancing mural nodule. Histology shows bipolar cells with long hair-like processes, Rosenthal fibres and eosinophilic granular bodies. What is the diagnosis?
1. AHaemangioblastoma
2. BEpendymoma
3. CMedulloblastoma
4. DPilocytic astrocytoma
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Answer: D · Pilocytic astrocytoma
A cystic cerebellar mass with a mural nodule in a child, with hair-like (piloid) cells and Rosenthal fibres, is pilocytic astrocytoma, a WHO grade 1 tumour. Most carry a KIAA1549::BRAF fusion that activates the MAPK pathway. Complete surgical removal is usually curative.
- A: Haemangioblastoma also forms a cyst with a nodule but occurs mainly in adults and shows capillaries with lipid-laden stromal cells.
- B: Ependymoma arises from the fourth ventricle floor and shows perivascular pseudorosettes.
- C: Medulloblastoma is a solid midline tumour of small round blue cells.
Question 5 · Medium
A 32-year-old woman has medullary thyroid carcinoma, and CT shows masses in both adrenal glands; plasma metanephrines are raised. Germline testing shows a RET mutation, and she has a normal body habitus. A postgraduate lists four statements about her syndrome: 1. Her thyroid tumour was preceded by C-cell hyperplasia. 2. Pituitary adenomas are a core feature. 3. Phaeochromocytomas in this syndrome are often bilateral. 4. Parathyroid hyperplasia may develop. Which statements are correct?
1. A1, 2 and 3 only
2. B1 and 3 only
3. C3 and 4 only
4. D1, 3 and 4 only
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Answer: D · 1, 3 and 4 only
Statements 1, 3 and 4 are correct. Medullary carcinoma with bilateral phaeochromocytomas and a germline RET mutation is MEN2A. Its medullary carcinomas are multifocal and arise from bilateral C-cell hyperplasia, its phaeochromocytomas are often bilateral, and parathyroid hyperplasia with hyperparathyroidism occurs in a minority. Pituitary adenomas belong to MEN1, not MEN2. The phaeochromocytomas must be removed, after alpha-blockade, before the thyroid operation.
- A: Includes statement 2 (pituitary adenoma, an MEN1 feature) and leaves out statement 4.
- B: Leaves out statement 4; parathyroid hyperplasia is a recognised feature of MEN2A.
- C: Leaves out statement 1; medullary carcinoma in MEN2A arises from C-cell hyperplasia.
Question 6 · Hard
A 41-year-old woman had a total thyroidectomy and radioiodine ablation for a 3 cm papillary thyroid carcinoma 3 years ago and takes levothyroxine (TSH 0.3 mIU/L). One year after ablation her serum thyroglobulin was undetectable, with negative anti-thyroglobulin antibodies. Now thyroglobulin is 9 ng/mL, the antibodies are still negative, and neck ultrasound shows a 1.4 cm round, hypoechoic left lateral neck node with microcalcifications and no fatty hilum. What is the next best step?
1. ARaise levothyroxine; repeat thyroglobulin in a year
2. BSerum calcitonin and CEA levels
3. CFNAC of the node with thyroglobulin washout
4. DExternal beam radiotherapy to the neck
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Question 7 · Medium
A 36-year-old schoolteacher has her first generalised seizure. CT shows a calcified mass in the right frontal lobe involving the cortex. Histology shows uniform round cells with perinuclear clearing ('fried-egg' appearance) and a delicate branching capillary network. Which molecular result is needed to confirm the diagnosis?
1. AH3 K27M mutation
2. BIDH mutation with 1p/19q codeletion
3. CIDH-wildtype with EGFR amplification
4. DBRAF V600E mutation alone
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Question 8 · Hard
A 35-year-old man with HIV who stopped antiretroviral therapy a year ago has had 3 weeks of confusion and right-sided weakness. His CD4 count is 38 cells/µL. MRI shows a single 3 cm enhancing periventricular lesion in the left hemisphere, abutting the ependyma. Toxoplasma IgG is positive, but after 2 weeks of pyrimethamine and sulfadiazine there is no clinical or radiological improvement. CSF cytology is negative, and CSF PCR detects Epstein-Barr virus DNA. What is the most likely diagnosis?
1. APrimary CNS lymphoma
2. BTuberculoma
3. CCerebral toxoplasmosis
4. DProgressive multifocal leukoencephalopathy
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Question 9 · Easy
A 27-year-old woman has had a dull ache and swelling just above the right knee for 4 months. X-ray shows an eccentric, expansile, lytic lesion in the epiphysis and metaphysis of the distal femur, reaching the subchondral bone, with a 'soap-bubble' appearance and no periosteal reaction. Biopsy shows many multinucleated osteoclast-like giant cells evenly scattered among mononuclear stromal cells. What is the diagnosis?
1. AGiant cell tumour of bone
2. BAneurysmal bone cyst
3. CChondroblastoma
4. DOsteosarcoma
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Question 10 · Easy
A 48-year-old man has had gradually worsening hearing loss and tinnitus in the left ear for 2 years, with recent unsteadiness. Audiometry shows a left sensorineural loss, and MRI shows an enhancing mass in the left cerebellopontine angle extending into the internal acoustic meatus. Histology shows S-100-positive spindle cells in alternating compact and loose areas, with nuclear palisades around pink fibrillary zones. What is the diagnosis?
1. AVestibular schwannoma
2. BMeningioma
3. CNeurofibroma
4. DEpidermoid cyst
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Question 11 · Medium
A 14-year-old boy, who had both eyes treated for retinoblastoma in infancy, has 2 months of pain and swelling above the left knee that wakes him at night. X-ray shows a destructive metaphyseal lesion of the distal femur with a sunburst periosteal reaction and a Codman triangle. Biopsy shows malignant pleomorphic cells directly forming lace-like osteoid. A germline mutation in which gene links his two tumours?
1. ATP53
2. BRB1
3. CEXT1
4. DEWSR1
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Question 12 · Medium
A 62-year-old man has had headaches, a change in personality and left-sided weakness for 5 weeks. MRI shows an irregular ring-enhancing mass crossing the corpus callosum, with central necrosis and surrounding oedema. Histology shows an infiltrating astrocytic tumour with pseudopalisading necrosis and microvascular proliferation, and IDH sequencing shows no mutation. Consider four statements under the WHO 2021 (CNS5) classification: 1. Necrosis or microvascular proliferation makes this a grade 4 tumour. 2. An IDH mutation is required for this diagnosis. 3. Even without necrosis, a TERT promoter mutation, EGFR amplification or +7/-10 would make an adult IDH-wildtype diffuse astrocytic glioma a glioblastoma. 4. Most such tumours arise from a pre-existing low-grade astrocytoma. Which statements are correct?
1. A1 and 2 only
2. B1 and 3 only
3. C2, 3 and 4 only
4. D3 and 4 only
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Question 13 · Medium
A 12-year-old girl has had pain in the right thigh with intermittent fever for 6 weeks; ESR is 68 mm/h and the total leucocyte count is 12,400/µL. X-ray shows a permeative lesion in the diaphysis of the femur with a lamellated ('onion-peel') periosteal reaction and a soft-tissue mass. Biopsy shows sheets of small round blue cells with glycogen-rich cytoplasm and strong membranous CD99 staining. Which genetic change defines this tumour?
1. At(11;22) EWSR1::FLI1 fusion
2. Bt(2;13) PAX3::FOXO1 fusion
3. Ct(X;18) SS18::SSX fusion
4. DMYCN amplification
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Question 14 · Medium
A 44-year-old man has a 5 cm right adrenal phaeochromocytoma removed after alpha-blockade. Histology shows nests (Zellballen) of polygonal cells with granular basophilic cytoplasm surrounded by sustentacular cells, with some nuclear pleomorphism and focal capsular invasion. His wife asks whether the tumour was benign or malignant. What finding establishes that a phaeochromocytoma is malignant (metastatic)?
1. ACapsular and vascular invasion on histology
2. BTumour size of more than 5 cm
3. CMarked nuclear pleomorphism
4. DTumour deposits where chromaffin tissue is absent
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Question 15 · Medium
A 38-year-old man has a total thyroidectomy for a 3 cm papillary thyroid carcinoma with central neck node metastases at a tertiary centre in Chennai. The oncologist requests molecular testing of the tumour. Which mutation is found most often in this type of thyroid carcinoma?
1. APAX8::PPARG fusion
2. BBRAF V600E
3. CGermline RET point mutation
4. DTP53 mutation
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Question 16 · Medium
A 52-year-old woman has headaches and a recent focal seizure. MRI shows a 4 cm extra-axial, homogeneously enhancing mass attached to the falx, with a 'dural tail'. It is removed completely. Histology shows whorls of meningothelial cells with laminated calcified bodies, and the cells are positive for EMA and progesterone receptor. Which gene is most often mutated in sporadic tumours of this type?
1. AVHL
2. BTSC2
3. CNF1
4. DNF2
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Question 17 · Medium
A 34-year-old woman who had a total thyroidectomy for medullary carcinoma is found to carry a germline RET mutation (MEN2A). Her 4-year-old son is well; after counselling, the parents agree to testing, and he carries the same mutation. His serum calcitonin and neck ultrasound are being arranged. What is the definitive way to prevent thyroid cancer in this child?
1. AHemithyroidectomy when a nodule appears
2. BProphylactic total thyroidectomy, timed by RET codon
3. CLifelong TSH suppression with levothyroxine
4. DRadioiodine ablation of the thyroid
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Question 18 · Medium
A 45-year-old woman has a solitary 3.5 cm thyroid nodule that is cold on scintigraphy; she is clinically and biochemically euthyroid. FNAC shows a cellular smear of follicular cells arranged in microfollicles, with scant colloid and no nuclear features of papillary carcinoma. Why can FNAC not tell a follicular adenoma from a follicular carcinoma in her?
1. ACarcinoma smears show more colloid
2. BCarcinoma produces less thyroglobulin
3. CCarcinoma cells always show more nuclear atypia
4. DCarcinoma is defined by capsular or vascular invasion
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Question 19 · Hard
A 10-year-old boy has been falling behind his classmates in height for 2 years and now has headaches, bumps into objects on both sides, and drinks and passes large amounts of water. Visual fields show bitemporal hemianopia. CT shows a suprasellar mass with cysts and calcification. At surgery the cysts contain thick brownish fluid like machinery oil. Histology shows epithelial cords with peripheral palisading, loose stellate reticulum and nodules of 'wet' keratin. Mutation of which gene is characteristic of this tumour subtype?
1. ABRAF V600E
2. BIDH1
3. CGNAS
4. DCTNNB1 (beta-catenin)
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Question 20 · Hard
Pelvic X-ray of a man in his fifties with deep, aching left hip pain for 8 months, worse at night: a 9 cm lesion in the ilium with ring-and-arc calcification, endosteal scalloping over two-thirds of the cortical thickness and a focal breach of the cortex. MRI shows a small soft tissue component, and there is no other bone lesion on a skeletal survey. A needle biopsy shows lobules of hyaline cartilage with mildly enlarged, occasionally binucleate chondrocytes, and the pathologist asks for the radiology before signing out. Which feature best separates this tumour from a benign enchondroma?
1. ABinucleate chondrocytes in the lacunae
2. BPermeation of host bone with cortical destruction
3. CRing-and-arc calcification
4. DIDH1 mutation in the tumour cells
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Question 21 · Medium
Brain MRI of a retired schoolteacher with 6 weeks of headache and left-sided weakness: a ring-enhancing mass with a necrotic centre that crosses the corpus callosum. Histology shows pleomorphic astrocytic cells, glomeruloid microvascular proliferation and serpiginous necrosis rimmed by densely packed tumour nuclei; IDH sequencing is wild-type. What does the rim of nuclei around the necrosis represent?
1. ATumour cells arranged around blood vessels
2. BTumour cells migrating away from hypoxic necrosis
3. CNeoplastic cells around a central neuropil core
4. DReactive astrocytes walling off an abscess
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Question 22 · Hard
FNAC of a thyroid nodule in a schoolteacher shows medullary carcinoma, and her serum calcitonin is 980 pg/mL. She mentions episodes of pounding headache, sweating and palpitations for a year, and her BP is 168/104 mmHg. Her brother was found to have a germline RET mutation. Plasma free metanephrines are four times the upper limit of normal, and CT shows a 3 cm right and a 2 cm left adrenal mass. The surgeon has listed her for total thyroidectomy with central neck dissection next week. What should be done first?
1. AThyroidectomy and adrenalectomy together without blockade
2. BThyroidectomy first, then adrenal surgery later
3. CAlpha-blockade, then adrenalectomy before thyroid surgery
4. DBeta-blocker alone, then thyroidectomy
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Question 23 · Hard
Haemoglobin 19.2 g/dL (normal 13-17) and haematocrit 58% are found in a young driver admitted with headache, vomiting and an unsteady gait. MRI shows a cystic right cerebellar mass with a brightly enhancing mural nodule. His father died of a kidney cancer at 45, and a paternal uncle was treated with laser for retinal 'blood vessel tumours'. The excised nodule shows many thin-walled capillaries with large, lipid-laden, vacuolated stromal cells between them, and his haemoglobin returns to normal after surgery. Which tumour must be watched for most carefully during his long-term surveillance?
1. APancreatic ductal adenocarcinoma
2. BMedullary thyroid carcinoma
3. CHepatocellular carcinoma
4. DClear cell renal cell carcinoma
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Question 24 · Medium
MRI of the lumbosacral spine in a retired postman with buttock pain, constipation and saddle numbness for a year: a lobulated, destructive midline sacral mass with a large presacral soft tissue component. Biopsy shows lobules of large cells with bubbly, vacuolated cytoplasm in a myxoid matrix. Which nuclear immunostain confirms the diagnosis?
1. ABrachyury
2. BSOX10
3. CMyogenin
4. DSTAT6
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Question 25 · Medium
Genetic counselling clinic: a family carries a germline RET mutation at codon 634, and three members have had medullary thyroid carcinoma. About this syndrome: 1. Primary hyperparathyroidism occurs. 2. Phaeochromocytomas are often bilateral. 3. Marfanoid habitus and mucosal neuromas are typical. 4. Cutaneous lichen amyloidosis can occur. Which statements are correct?
1. A2, 3 and 4 only
2. B1 and 3 only
3. C1, 2, 3 and 4
4. D1, 2 and 4 only
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Endocrine, bone and CNS pathology

A 38-year-old man has a total thyroidectomy for a 3 cm papillary thyroid carcinoma with central neck node metastases at a tertiary centre in Chennai. The oncologist requests molecular testing of the tumour. Which mutation is found most often in this type of thyroid carcinoma?