FMGE 2026 - Pathology PYQs Practice Questions

Q: A child presents with hepatosplenomegaly, anemia, and bone pain. Histopathological examination reveals macrophages with a “crumpled tissue paper” appearance due to cerebroside accumulation. Deficiency of which enzyme is responsible for this condition?

β-Glucocerebrosidase. ***β-Glucocerebrosidase*** - This condition is **Gaucher disease**, which is caused by a deficiency of the **β-glucocerebrosidase** enzyme, leading to the accumulation of **glucocerebroside** in lysosomes. - The characteristic **Gaucher cells** demonstrate an accumulation of substrate giving them a pathognomonic **crumpled tissue paper** appearance in the spleen, liver, and bone marrow. *Hexosaminidase A* - Deficiency of this enzyme leads to **Tay-Sachs disease**, characterized by **progressive neurodegeneration** and a **cherry-red macula**. - Cells in Tay-Sachs exhibit **onion-skin** lysosomal inclusions, distinct from the Gaucher cell inclusions. *Sphingomyelinase* - Deficiency of sphingomyelinase leads to **Niemann-Pick disease** (Type A and B). - Patients with Niemann-Pick typically present with **hepatosplenomegaly** and **cherry-red macula**, but the cells demonstrate **foam cells** (lipid-laden macrophages) rather than crumpled tissue paper. *Arylsulfatase A* - Deficiency of arylsulfatase A results in **metachromatic leukodystrophy**, a demyelinating disease of the central and peripheral nervous system. - Clinical presentation involves **ataxia**, **dementia**, and **seizures** rather than the viseo-visceral manifestations like hepatosplenomegaly found in this patient. [Practice more Pathology PYQs on OnCourse]

Q: A child presents with hepatosplenomegaly. Histological examination shows foam cells due to lipid accumulation. What is the most likely diagnosis?

Niemann –Pick disease. ***Niemann–Pick disease*** - Niemann–Pick disease, specifically type A and B, is caused by a **deficiency of sphingomyelinase**, leading to the accumulation of **sphingomyelin** within lysosomes. - The hallmark histological finding is the presence of **foam cells** (lipid-laden macrophages) in organs like the spleen, liver, and bone marrow, which correlates with the clinical finding of **hepatosplenomegaly**. *Gaucher disease* - Gaucher disease involves the accumulation of **glucocerebroside** due to a deficiency of the enzyme **glucocerebrosidase**. - Histologically, this presents as **Gaucher cells**, which are described as having the appearance of **wrinkled tissue paper** or crumpled silk, rather than foam cells. *Tay–Sachs disease* - Tay–Sachs disease is characterized by a deficiency in **hexosaminidase A**, leading to the accumulation of **GM2 gangliosides**. - It primarily affects the **central nervous system**, causing a **cherry-red spot** in the macula and neurodegeneration, but does **not** cause hepatosplenomegaly. *Fabry disease* - Fabry disease is an X-linked recessive disorder caused by a deficiency of **alpha-galactosidase A**, leading to the accumulation of **globotriaosylceramide**. - Clinical features typically include peripheral neuropathy, **angiokeratomas**, and hypohidrosis, generally without hepatosplenomegaly. [Practice more Pathology PYQs on OnCourse]

Q: A patient presents with hepatomegaly and joint pain. Investigations suggest abnormal intracellular accumulation of macromolecules such as lipids or glycoconjugates. Which cellular organelle is primarily responsible for this accumulation?

Lysosome. ***Lysosome*** - **Lysosomes** contain hydrolytic enzymes responsible for breaking down complex macromolecules like lipids and glycosaminoglycans; their deficiency leads to **lysosomal storage diseases**. - Accumulation of undigested substrate in organs like the liver (**hepatomegaly**) and connective tissue (**joint pain**) is a hallmark feature of these disorders, such as **Gaucher disease** or **Mucopolysaccharidoses**. *Golgi apparatus* - The **Golgi apparatus** is primarily involved in the post-translational modification, packaging, and sorting of proteins and lipids for secretion or delivery to other organelles. - Defects here typically result in altered **protein trafficking** or secretion rather than the massive intracellular accumulation of undigested macromolecular substances. *Mitochondria* - **Mitochondria** are primarily responsible for **ATP production** via oxidative phosphorylation and the regulation of apoptosis. - Dysfunction commonly manifests as **myopathy**, lactic acidosis, or neurological deficits, rather than the storage of complex macromolecules. *Peroxisome* - **Peroxisomes** are responsible for the breakdown of **very-long-chain fatty acids (VLCFAs)** via beta-oxidation and the catabolism of hydrogen peroxide. - Accumulation here corresponds to conditions like **Zellweger syndrome** or **X-linked adrenoleukodystrophy**, which primarily cause severe neurological symptoms rather than the classic lysosomal storage pattern. [Practice more Pathology PYQs on OnCourse]

Q: A 40-year-old wom an presents with headache and undergoes evaluation for a brain tumor/ cerebellopontine angle. Histopathological examination reveals a tumor composed of Antoni A and Antoni B areas. Which of the following is the most sensitive immunohistochemical marker for this tumor?

S-100 protein. ***S-100 protein*** - S-100 is a protein expressed in cells of neural crest origin, and it serves as a highly **sensitive immunohistochemical marker** for **Schwannomas**. - The tumor described presents characteristic **Antoni A** (dense, hypercellular) and **Antoni B** (loose, hypocellular) areas, which are pathognomonic for Schwannoma. *Glial fibrillary acidic protein (GFAP)* - GFAP is an intermediate filament protein primarily found in **glial cells** like astrocytes and ependymal cells. - It is used to diagnose **gliomas** (e.g., astrocytoma, ependymoma) rather than nerve sheath tumors. *Epithelial membrane antigen (EMA)* - EMA is typically positive in **meningiomas**, which also frequently occur in the cerebellopontine angle. - While it is a useful marker in neuropathology, it is not the primary diagnostic marker for a Schwannoma. *c-KIT* - c-KIT (CD117) is the standard diagnostic marker for **gastrointestinal stromal tumors (GIST)**. - It is not a useful marker for tumors originating from Schwann cells or other neural sheath components. [Practice more Pathology PYQs on OnCourse]

Q: Which genetic abnormality is classically associated with Burkitt lymphoma?

t(8;14). ***t(8;14)*** - This translocation results in the **overexpression of the c-MYC oncogene** on chromosome 8 due to its placement next to the **immunoglobulin heavy chain (IgH) locus** on chromosome 14. - This specific genetic defect leads to high **cellular proliferation** rates, which is a hallmark of the diagnostically distinct **starry-sky appearance** seen in Burkitt lymphoma histology. *t(14;18)* - This translocation is characteristic of **follicular lymphoma**, resulting in the overexpression of the **BCL-2 anti-apoptotic protein**. - It prevents follicular center B-cells from undergoing apoptosis, leading to an expansion of these cells in the lymph nodes. *t(11;14)* - This translocation identifies **mantle cell lymphoma**, caused by the overexpression of **cyclin D1**. - Cyclin D1 promotes cell cycle progression from G1 to S phase, contributing to the aggressive growth of this subtype of non-Hodgkin lymphoma. *t(9;22)* - This is the famous **Philadelphia chromosome**, characterized by the formation of the **BCR-ABL fusion gene**. - It is the defining genetic abnormality in **chronic myeloid leukemia (CML)** and certain subsets of acute lymphoblastic leukemia (ALL). [Practice more Pathology PYQs on OnCourse]

Question 1

A child presents with hepatosplenomegaly, anemia, and bone pain. Histopathological examination reveals macrophages with a “crumpled tissue paper” appearance due to cerebroside accumulation. Deficiency of which enzyme is responsible for this condition?

Accepted Answer

β-Glucocerebrosidase

Answer

Hexosaminidase A

Answer

Sphingomyelinase

Answer

Arylsulfatase A

Question 2

A child presents with hepatosplenomegaly. Histological examination shows foam cells due to lipid accumulation. What is the most likely diagnosis?

Accepted Answer

Niemann –Pick disease

Answer

Gaucher disease

Answer

Tay–Sachs disease

Answer

Fabry disease

Question 3

A patient presents with hepatomegaly and joint pain. Investigations suggest abnormal intracellular accumulation of macromolecules such as lipids or glycoconjugates. Which cellular organelle is primarily responsible for this accumulation?

Accepted Answer

Lysosome

Answer

Golgi apparatus

Answer

Mitochondria

Answer

Peroxisome

Question 4

A 40-year-old wom an presents with headache and undergoes evaluation for a brain tumor/ cerebellopontine angle. Histopathological examination reveals a tumor composed of Antoni A and Antoni B areas. Which of the following is the most sensitive immunohistochemical marker for this tumor?

Accepted Answer

S-100 protein

Answer

Glial fibrillary acidic protein (GFAP)

Answer

Epithelial membrane antigen (EMA)

Answer

c-KIT

Question 5

Which genetic abnormality is classically associated with Burkitt lymphoma?

Accepted Answer

t(8;14)

Answer

t(14;18)

Answer

t(11;14)

Answer

t(9;22)

Question 6

A peripheral blood smear is given, blasts count more than 60%. Immunophenotyping reveals positivity for CD13 and CD33. Negative CD19. What is the most likely diagnosis?

Accepted Answer

AML

Answer

CML

Answer

ALL

Answer

CLL

Question 7

Testicular tumor on histopathology shows AFP negative and mildly elevated β -hCG. LDH? Most likely diagnosis is:

Accepted Answer

Seminoma

Answer

Choriocarcinoma

Answer

Embryonal carcinoma

Answer

Yolk sac tumor

FMGE 2026 — Pathology