Neuropathology Practice Questions

Q: In Von Hippel-Lindau Syndrome, retinal vascular tumors are often associated with intracranial hemangioblastomas. Which one of the following regions is associated with such vascular abnormalities in this syndrome?

Cerebellum. **Explanation:** **Von Hippel-Lindau (VHL) Syndrome** is an autosomal dominant multisystem disorder caused by a mutation in the **VHL gene on chromosome 3p25**. This gene normally acts as a tumor suppressor by degrading Hypoxia-Inducible Factor (HIF). Its loss leads to the overproduction of angiogenic factors like VEGF, resulting in highly vascular tumors. **Why the Correct Answer is Right:** The hallmark CNS lesion in VHL is the **hemangioblastoma**. These are benign but highly vascular tumors that most commonly occur in the **Cerebellum (60-80%)**, followed by the spinal cord and brainstem. In this question, the association of retinal angiomas (von Hippel tumors) with cerebellar hemangioblastomas (Lindau tumors) defines the classic presentation of the syndrome. **Why the Incorrect Options are Wrong:** * **Optic radiation, Optic tract, and Pulvinar:** While VHL affects the visual system via retinal hemangioblastomas, it does not typically cause vascular tumors in the retro-chiasmal pathways (tracts/radiations) or the thalamic nuclei (pulvinar). Hemangioblastomas in VHL have a predilection for the **infratentorial compartment** (posterior fossa) rather than the supratentorial white matter or deep gray matter. **High-Yield Clinical Pearls for NEET-PG:** * **VHL Gene:** Chromosome **3**. * **Classic Triad:** Retinal hemangioblastomas, Cerebellar hemangioblastomas, and Renal Cell Carcinoma (RCC). * **Associated Findings:** Pheochromocytoma (Type 2 VHL), Pancreatic cysts/NETs, and Endolymphatic sac tumors (causing hearing loss). * **RCC Type:** Clear cell variant (often bilateral and multifocal). * **Most common cause of death:** Renal Cell Carcinoma or complications from CNS hemangioblastomas.

Q: Which CNS tumor is typically associated with calcification?

Oligodendroglioma. **Explanation:** **1. Why Oligodendroglioma is Correct:** Oligodendroglioma is the classic CNS tumor associated with **calcification**, occurring in approximately **70–90%** of cases. These are slow-growing tumors typically located in the cortical gray matter of the frontal lobes. On imaging (CT scan), the presence of "clumpy" or "popcorn" calcification is a hallmark feature. Histologically, these tumors exhibit a "fried-egg" appearance (clear cytoplasm with central nuclei) and a "chicken-wire" vascular pattern. **2. Why the Other Options are Incorrect:** * **Astrocytoma:** While some subtypes (like Pilocytic Astrocytoma) can occasionally show calcification, it is much less frequent (approx. 10–20%) compared to oligodendrogliomas. * **Medulloblastoma:** This is a highly malignant primitive neuroectodermal tumor (PNET) found in the posterior fossa of children. It typically presents as a solid, enhancing mass in the cerebellum; calcification is rare. * **Pheochromocytoma:** This is not a CNS tumor. It is a catecholamine-secreting tumor of the adrenal medulla (or extra-adrenal paraganglia). **3. High-Yield Clinical Pearls for NEET-PG:** * **Most common CNS tumor to calcify:** Oligodendroglioma. * **Other CNS tumors with calcification:** Craniopharyngioma (90% in children), Meningioma (Psammoma bodies), and Ependymoma. * **Genetic Marker:** 1p/19q co-deletion is the diagnostic molecular hallmark of oligodendroglioma and predicts a better response to chemotherapy. * **Clinical Presentation:** Seizures are the most common presenting symptom due to the tumor's cortical location.

Q: Which of the following is not seen in Tuberous sclerosis?

McCollum plaques. **Explanation:** **Tuberous Sclerosis Complex (TSC)** is an autosomal dominant neurocutaneous syndrome (phakomatosis) caused by mutations in the **TSC1 (Hamartin)** or **TSC2 (Tuberin)** genes. It is characterized by the development of benign tumors (hamartomas) in multiple organs [1]. **Why McCollum Plaques is the correct answer:** **McCollum plaques** are irregular endocardial thickenings usually found in the **left atrium**, resulting from jet lesions in **Mitral Regurgitation** (Rheumatic Heart Disease). They have no association with Tuberous Sclerosis. The characteristic cardiac finding in TSC is actually **Cardiac Rhabdomyoma** [1]. **Analysis of Incorrect Options (Features seen in TSC):** * **Shagreen patches:** These are leathery, thickened, "orange-peel" textured skin patches typically found on the lower back (lumbosacral region). They represent connective tissue nevi. * **Adenoma sebaceum:** A misnomer, as these are actually **facial angiofibromas** [1]. They appear as reddish papules in a malar distribution (butterfly area of the face). * **Depigmented nevi:** Also known as **Ash-leaf spots**. These are often the earliest clinical sign of TSC and are best visualized using a **Wood’s lamp**. **High-Yield Clinical Pearls for NEET-PG:** * **Vogt’s Triad:** Seizures, Mental retardation, and Adenoma sebaceum (seen in only ~30% of cases). * **CNS findings:** Cortical tubers, Subependymal nodules (SEN), and **Subependymal Giant Cell Astrocytoma (SEGA)** [1]. * **Renal findings:** Bilateral **Renal Angiomyolipomas** (risk of hemorrhage) [1]. * **Pulmonary findings:** Lymphangioleiomyomatosis (LAM), primarily in females [1]. * **Ungual fibromas:** Also known as Koenen tumors (flesh-colored growths around nails). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1318-1319.

Q: Antoni A and Antoni B patterns are seen in which of the following?

Schwannoma. **Explanation:** **Schwannoma** (also known as Neurilemmoma) is a benign nerve sheath tumor derived from Schwann cells. Histologically, it is characterized by a distinct biphasic pattern consisting of **Antoni A** and **Antoni B** areas: * **Antoni A:** Highly cellular areas with spindle cells arranged in fascicles. A hallmark feature here is the **Verocay body**, which consists of two compact rows of well-aligned nuclei separated by an acellular zone. * **Antoni B:** Hypocellular, loosely arranged myxoid stroma with fewer cells and cystic changes. **Why other options are incorrect:** * **Neurofibroma:** Unlike Schwannomas, these are unencapsulated and contain a mixture of cell types (Schwann cells, fibroblasts, and perineural cells) in a "shredded carrot" collagenous background. They do not exhibit the Antoni A/B biphasic pattern. * **Meningioma:** Characterized histologically by whorled patterns and **Psammoma bodies** (laminated calcifications), not Antoni patterns. * **Teratoma:** A germ cell tumor containing tissues from all three germ layers (ectoderm, endoderm, mesoderm). Its histology shows a disorganized mixture of various tissues like hair, muscle, and epithelium. **High-Yield Clinical Pearls for NEET-PG:** * **S-100 Protein:** Schwannomas show strong and diffuse positivity for S-100 (immunohistochemistry). * **Nerve Relationship:** Schwannomas usually arise from the side of the nerve and are **encapsulated**, making them surgically separable from the nerve (unlike neurofibromas). * **Acoustic Neuroma:** The most common location is the Vestibulocochlear nerve (CN VIII) at the cerebellopontine angle. Bilateral acoustic neuromas are pathognomonic for **Neurofibromatosis Type 2 (NF2)**.

Q: A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Amyotrophic lateral sclerosis (ALS). ***Amyotrophic lateral sclerosis (ALS)*** - **SOD1 (Superoxide dismutase 1)** gene mutations are responsible for approximately **20% of familial ALS** cases and 1-2% of sporadic cases - SOD1 enzyme normally protects cells from oxidative damage by converting superoxide radicals to hydrogen peroxide - Mutations lead to **toxic gain of function** causing motor neuron degeneration, affecting both upper and lower motor neurons [1] - Clinical features include progressive muscle weakness, fasciculations, spasticity, and bulbar symptoms [1] - This is one of the **most well-established genetic associations** in neurodegenerative disease *Parkinson's disease* - Associated with mutations in **SNCA (α-synuclein), LRRK2, and Parkin** genes, not SOD1 - Characterized by dopaminergic neuron loss in substantia nigra - Presents with bradykinesia, rigidity, resting tremor, and postural instability *Multiple sclerosis* - An **autoimmune demyelinating disease** with complex genetic susceptibility involving HLA-DRB1 and other immune-related genes - Not linked to SOD1 mutations - Presents with relapsing-remitting neurological symptoms and white matter lesions *Huntington's disease* - Caused by **CAG trinucleotide repeat expansion** in the huntingtin (HTT) gene on chromosome 4 - Autosomal dominant inheritance with anticipation - Presents with chorea, cognitive decline, and psychiatric symptoms

Q: Tau protein inclusions are involved in:

Alzheimer’s disease. ***Alzheimer's disease*** - **Tau protein** aggregation leads to the formation of **neurofibrillary tangles (NFTs)**, which are characteristic pathological hallmarks of Alzheimer's disease, particularly in the hippocampus and cortex [1]. - Hyperphosphorylation of Tau causes it to dissociate from microtubules, destabilizing the neuronal cytoskeleton and ultimately leading to **synaptic dysfunction** and cell death [2]. *Huntington's disease* - This disorder is caused by an expansion of a **CAG triplet repeat** in the *HTT* gene, leading to the accumulation of misfolded **Huntingtin protein**. - It is characterized by atrophy of the **caudate nucleus** and putamen (striatum) and is not primarily linked to Tauopathies. *Amyotrophic lateral sclerosis* - ALS is primarily characterized by the aggregation of **TDP-43** (Tar DNA-binding protein 43) in motor neurons, a distinct type of proteinopathy. - While some cases of ALS overlap with Frontotemporal Dementia (FTD) which can involve Tauopathies, classic ALS pathology is defined by **TDP-43 inclusions**. *CNS lymphoma* - CNS lymphoma is a **primary central nervous system (CNS) tumor**, usually a non-Hodgkin B-cell lymphoma. - Diagnosis relies on identifying atypical lymphoid cells and is not associated with misfolded Tau protein inclusions, which are features of **neurodegenerative diseases** [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1292-1295. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 721-722. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1288-1289.

Q: A patient had a road traffic accident (RTA). NCCT head was normal on admission. The patient later died after several days in the ICU due to coma. Brain biopsy revealed multiple punctate hemorrhages. What is the diagnosis?

Diffuse axonal injury. ***Diffuse axonal injury*** - This condition is caused by **traumatic shearing forces** due to sudden acceleration-deceleration, as seen in RTAs, leading to widespread axonal damage [1][2]. - A key feature is a discrepancy between clinical severity (e.g., coma) and initial imaging, as non-contrast CT scans are often normal [2]. The presence of **multiple punctate hemorrhages** on biopsy or sensitive MRI sequences (like the one shown) is characteristic [2]. *Ischemic injury* - This results from reduced blood flow causing a stroke, not direct trauma, and presents with focal neurological deficits corresponding to an arterial territory [3]. - Pathologically, it leads to **liquefactive necrosis** in a specific vascular distribution, not diffuse punctate hemorrhages [3]. *Intraventricular bleeding* - This refers to hemorrhage within the ventricular system and would be clearly visible as a **hyperdensity** on an initial NCCT head scan [3]. - It is a distinct type of intracranial bleed and does not present as microscopic, diffuse parenchymal hemorrhages [3]. *Subdural hemorrhage* - This involves bleeding into the space between the dura and arachnoid mater, usually from torn bridging veins. - It appears as a **crescent-shaped** hyperdensity on a CT scan and is typically evident immediately after trauma. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 700-701. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 701-702. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 706-707.

Question 1

In Von Hippel-Lindau Syndrome, retinal vascular tumors are often associated with intracranial hemangioblastomas. Which one of the following regions is associated with such vascular abnormalities in this syndrome?

Accepted Answer

Cerebellum

Answer

Optic radiation

Answer

Optic tract

Answer

Pulvinar

Question 2

Which of the following is not a finding in viral encephalitis?

Accepted Answer

Astroglial proliferation

Answer

Perivascular mononuclear infiltrate

Answer

Intranuclear and intracytoplasmic inclusion bodies

Answer

None of the above

Question 3

Lisch nodules (Pigmented Iris hamartomas) are seen in which condition?

Accepted Answer

Neurofibromatosis

Answer

Niemann Pick disease

Answer

Ochronosis

Answer

Glycogen storage disease

Question 4

Which CNS tumor is typically associated with calcification?

Accepted Answer

Oligodendroglioma

Answer

Astrocytoma

Answer

Medulloblastoma

Answer

Pheochromocytoma

Question 5

Which of the following is not seen in Tuberous sclerosis?

Accepted Answer

McCollum plaques

Answer

Shagreen patch

Answer

Adenoma sebaceum

Answer

Depigmented nevi

Question 6

Antoni A and Antoni B patterns are seen in which of the following?

Accepted Answer

Schwannoma

Answer

Neurofibroma

Answer

Meningioma

Answer

Teratoma

Question 7

A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Accepted Answer

Amyotrophic lateral sclerosis (ALS)

Answer

Parkinson's disease

Answer

Multiple sclerosis

Answer

Huntington's disease

Question 8

Tau protein inclusions are involved in:

Accepted Answer

Alzheimer’s disease

Answer

Amyotrophic lateral sclerosis

Answer

Huntington's disease

Answer

CNS lymphoma

Question 9

Which among the following best describes 'Neuropraxia'?

Accepted Answer

Intact axon; Damaged nerve sheath

Answer

None of the above

Answer

Damaged axon and nerve sheath

Answer

Damaged axon; Intact nerve sheath

Question 10

A patient had a road traffic accident (RTA). NCCT head was normal on admission. The patient later died after several days in the ICU due to coma. Brain biopsy revealed multiple punctate hemorrhages. What is the diagnosis?

Accepted Answer

Diffuse axonal injury

Answer

Subdural hemorrhage

Answer

Intraventricular bleeding

Answer

Ischemic injury

Neuropathology — MCQs

Neuropathology — MCQs

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