FMGE 2025 - Pathology Practice Questions

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: For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?

Blue. ***Blue*** - The blue-coded vacutainer contains **Sodium Citrate** (3.2% or 3.8%), which is the required anticoagulant for performing coagulation studies, such as **PT** (Prothrombin Time) and **aPTT** (Activated Partial Thromboplastin Time) [1]. - **Sodium Citrate** works by binding and sequestering **calcium ions** (Factor IV), thereby reversibly preventing the coagulation cascade from proceeding until calcium is added back in the lab [1]. *Red* - The Red top tube typically contains **no anticoagulant** (or a clot activator) and is used to obtain **serum** after the blood clots naturally. - It is utilized for chemistry, serology, and blood bank tests, where the natural clotting process is required or coagulation factors are not needed. *Green* - The Green top tube contains **Heparin** (Lithium or Sodium Heparin), which inhibits clotting by augmenting the activity of **antithrombin III** [2]. - Although it provides plasma, it is unsuitable for routine coagulation assays because heparin itself significantly interferes with most coagulation factor tests. *Gray* - The Gray top tube contains **Potassium Oxalate** as an anticoagulant and **Sodium Fluoride** as a preservative. - It is specifically reserved for **glucose** and sometimes **lactate** measurements, as sodium fluoride inhibits enolase, thereby preventing glycolysis (glucose breakdown) by blood cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, pp. 128-130. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 583-584.

Q: Which of the following is pro-apoptotic?

Bax. ***Bax*** - Bax is a key **pro-apoptotic** effector protein from the Bcl-2 family [1]. Upon activation by stress signals, it translocates to the mitochondria and forms pores in the outer membrane [2]. - This pore formation, along with Bak, leads to **Mitochondrial Outer Membrane Permeabilization (MOMP)**, which releases **cytochrome c** and initiates the intrinsic caspase cascade of apoptosis [3]. *Bcl-2* - Bcl-2 is the prototypical **anti-apoptotic** protein that prevents apoptosis by binding to and inhibiting pro-apoptotic proteins like Bax and Bak [2]. - By preventing MOMP, it maintains mitochondrial integrity and is often overexpressed in cancers, such as follicular lymphoma, contributing to cell survival [2]. *Bcl-xL* - Bcl-xL is another major **anti-apoptotic** protein in the Bcl-2 family, with a function very similar to Bcl-2 [2]. - It promotes cell survival by sequestering pro-apoptotic BH3-only proteins and preventing the activation of Bax and Bak. *Mcl-1* - Mcl-1 (Myeloid cell leukemia-1) is a critical **anti-apoptotic** protein that is essential for the survival of various cell types [2]. - Its primary role is to inhibit apoptosis by neutralizing pro-apoptotic proteins, and its high levels are often associated with tumor progression and resistance to chemotherapy [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 65-67. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 310. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 64-65.

Q: A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?

Hemophilia. ***Hemophilia***- The presentation of joint swelling after trauma (suggesting **hemarthrosis**) in a young boy is highly characteristic of hemophilia, which is an X-linked recessive disorder [1].- Hemophilia A (Factor VIII deficiency) or B (Factor IX deficiency) affects the **intrinsic coagulation pathway**, leading to an isolated prolongation of the **aPTT** while the PT remains normal. *Von Willebrand Disease*- VWD primarily causes defects in **platelet adhesion** and mild to moderate mucocutaneous bleeding (e.g., epistaxis, menorrhagia), not typically severe spontaneous hemarthrosis [1].- While severe VWD can lower Factor VIII and mildly prolong aPTT, it generally presents differently and often affects both males and females (autosomal pattern) [2].*Iron Deficiency Anaemia (IDA)*- IDA is a nutritional deficiency resulting in **microcytic, hypochromic anemia** and is not a primary bleeding disorder.- It does not involve defects in the coagulation cascade; therefore, PT and aPTT levels would be within the **normal reference range**.*Platelet function disorder*- These disorders (e.g., Glanzmann's or Bernard-Soulier) affect **primary hemostasis** (platelet plug formation), leading mainly to mucocutaneous bleeding [2].- In platelet disorders, the **PT and aPTT** are typically normal, as the coagulation cascade (secondary hemostasis) is intact.

Q: Which CD markers are typically positive in Chronic Lymphocytic Leukaemia (CLL)?

CD19, CD20, CD23, CD5. CD19, CD20, CD23, CD5 [1] - Chronic Lymphocytic Leukemia (CLL) is a malignancy of mature B-lymphocytes, which typically express the pan-B-cell markers CD19 and CD20 (often dimly), along with CD23 [1]. - A hallmark of CLL is the aberrant co-expression of the T-cell marker CD5 [2], which is crucial for differentiating it from other B-cell lymphomas. The peripheral smear in the image shows mature lymphocytes and a characteristic smudge cell, supporting the diagnosis of CLL [1]. CD3, CD5, CD8 - This profile is characteristic of a T-cell malignancy, as CD3 is a pan-T-cell marker and CD8 is a marker for cytotoxic T-cells [2]. - While CD5 is present in CLL, its combination with CD3 and CD8 excludes a B-cell disorder like CLL. CD10, CD19, CD22 - This combination of markers is more suggestive of other B-cell neoplasms like Follicular Lymphoma or Burkitt Lymphoma, which are characteristically CD10 positive [2]. - Typical CLL is negative for CD10 and positive for CD5 and CD23, which are key distinguishing features [1]. CD13, CD33, CD117 - These are markers associated with the myeloid lineage. CD13 and CD33 are classic myeloid antigens often seen in Acute Myeloid Leukemia (AML). - CD117 (c-kit) is a marker for hematopoietic progenitors and is also frequently positive in AML, making this immunophenotype inconsistent with a lymphoid neoplasm. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 602. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 598.

Q: 2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?

t(2;5). ***Correct: t(2;5)*** - This is the **most common and classic translocation** found in systemic **Anaplastic Large Cell Lymphoma (ALCL)**, especially in children [1] - Occurs in approximately **60-85% of systemic ALCL cases** - Fuses the **NPM (Nucleophosmin)** gene on chromosome 5 with the **ALK** gene on chromosome 2 [1] - Results in constitutively active **ALK tyrosine kinase** that drives cell proliferation [1] - **ALK-positive ALCL** has a better prognosis, particularly in pediatric patients [1] *Incorrect: t(8;14)* - This is the hallmark translocation of **Burkitt Lymphoma (BL)**, not ALCL [2] - Juxtaposes the **MYC oncogene** on chromosome 8 to the **IgH promoter** on chromosome 14 [2] - Burkitt Lymphoma presents with rapidly growing masses and characteristic **"starry sky"** microscopic appearance [3] - Distinct from ALCL's hallmark cells (large cells with eccentric horseshoe/kidney-shaped nuclei) *Incorrect: t(8;22)* - A variant translocation associated with **Burkitt Lymphoma (BL)** [2] - Translocates **MYC gene** to the **kappa light chain locus** on chromosome 22 [2] - Results in MYC overexpression, which is pathognomonic for Burkitt Lymphoma - Not associated with Anaplastic Large Cell Lymphoma *Incorrect: t(14;18)* - Characteristic translocation of **Follicular Lymphoma (FL)** - Leads to overexpression of the **BCL2 anti-apoptotic protein** - Follicular Lymphoma is typically seen in adults and is a **B-cell lymphoma** - ALCL is a **T-cell/null-cell lymphoma**, making this translocation irrelevant **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 565-566. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 606.

Q: In Barrett's oesophagus, which of the following epithelial transformations occurs?

Squamous to intestinal columnar epithelium. ***Squamous to intestinal columnar epithelium*** - Barrett's esophagus is a complication of chronic **gastroesophageal reflux disease (GERD)**, where the normal stratified **squamous epithelium** of the lower esophagus is replaced by metaplastic columnar epithelium [1]. - This metaplastic epithelium is specifically an **intestinal type**, characterized by the presence of **goblet cells**, which is considered a premalignant condition for esophageal adenocarcinoma [1]. *Columnar to squamous epithelium* - This describes the reverse process of what happens in Barrett's esophagus. - This type of metaplasia can occur in other organs, for example, in the endocervix (squamous metaplasia) or the bronchi of chronic smokers. *Transitional to squamous epithelium* - **Transitional epithelium** (urothelium) is the characteristic lining of the urinary tract (e.g., bladder, ureters) and is not found in the esophagus. - This type of metaplastic change is seen in the bladder in response to chronic irritation, such as from stones or **Schistosoma haematobium** infection. *Cuboidal to columnar epithelium* - The normal esophageal lining is stratified squamous epithelium, not cuboidal epithelium. - While metaplasia involving cuboidal cells can occur in glandular ducts or bronchioles, it is not the transformation that defines Barrett's esophagus. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Alimentary System Disease, pp. 347-349.

Q: Bernard-Soulier syndrome is caused by a defect in which of the following platelet glycoproteins?

GpIb/IX complex. ***GpIb/IX complex***- Bernard-Soulier syndrome (BSS) is a rare, autosomal recessive bleeding disorder caused by a quantitative or qualitative defect in the **platelet GpIb/IX/V complex** [1].- This complex acts as the essential high-affinity receptor for **von Willebrand factor (vWF)**, mediating initial **platelet adhesion** to the injured vessel wall, which is impaired in BSS [1], [2].*GpIIb/IIIa*- A defect in **GpIIb/IIIa** (integrin $\alpha_{IIb}\beta_3$) causes **Glanzmann thrombasthenia**, which presents with impaired **platelet aggregation**, not adhesion [1].- GpIIb/IIIa is the receptor for **fibrinogen**, which is necessary to link aggregating platelets [1], [2].*GpIa/IIa*- **GpIa/IIa** (integrin $\alpha_2\beta_1$) is primarily a receptor for **collagen** on the platelet surface, mediating adhesion in parallel with GpIb/vWF.- While important for hemostasis, defects in this receptor generally cause only mild bleeding and not the characteristic **giant platelets** or severe adhesion defect seen in BSS.*GpIV*- **GpIV** (also known as CD36) is a scavenger receptor that binds to **thrombospondin** and sometimes collagen.- Platelet defects related to GpIV are rare and usually involve mild aggregation defects, distinct from the severe adhesion failure defined by BSS. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128.

Q: A patient with renal disease undergoes a biopsy. On Congo red staining, the deposits show apple-green birefringence under polarised light. What is the most likely diagnosis?

Amyloidosis. ***Amyloidosis***- This feature is the **pathognomonic microscopic manifestation** of amyloid deposition, where the Congo red stain binds specifically to the parallel **cross-beta sheet** configuration of amyloid fibrils [1].- When viewed under **polarized light**, this interaction results in the classic **apple-green birefringence** due to the ordering of the deposited protein [1], [2]. *Minimal change disease*- The diagnosis of minimal change disease relies primarily on **electron microscopy**, which shows **effacement of podocyte foot processes**.- On **light microscopy**, the glomeruli appear virtually normal, and there are no deposits present that would stain positively with Congo red. *Diabetic nephropathy*- Characteristic findings on light microscopy include **diffuse mesangial expansion** and the formation of **Kimmelstiel-Wilson nodules** (nodular glomerulosclerosis).- The thickening of the glomerular basement membrane and mesangial expansion are due to hyperglycemia and associated metabolic changes, not amyloid deposition. *Membranous nephropathy*- This nephropathy is defined by the presence of **subepithelial immune complex deposits** that result in a uniformly thickened glomerular basement membrane (GBM).- Silver stains often reveal a classic **"spike and dome"** pattern on the GBM, which is distinct from amyloid fibrils. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 268-269. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 533-534.

Question 1

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 2

Tau protein inclusions are involved in:

Accepted Answer

Alzheimer’s disease

Answer

Amyotrophic lateral sclerosis

Answer

Huntington's disease

Answer

CNS lymphoma

Question 3

For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?

Accepted Answer

Blue

Answer

Gray

Answer

Red

Answer

Green

Question 4

Which of the following is pro-apoptotic?

Accepted Answer

Bax

Answer

Bcl-2

Answer

Bcl-xL

Answer

Mcl-1

Question 5

A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?

Accepted Answer

Hemophilia

Answer

Von Willebrand Disease

Answer

Platelet function disorder

Answer

Iron Deficiency Anaemia (IDA)

Question 6

Which CD markers are typically positive in Chronic Lymphocytic Leukaemia (CLL)?

Accepted Answer

CD19, CD20, CD23, CD5

Answer

CD10, CD19, CD22

Answer

CD13, CD33, CD117

Answer

CD3, CD5, CD8

Question 7

2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?

Accepted Answer

t(2;5)

Answer

t(14;18)

Answer

t(8;22)

Answer

t(8;14)

Question 8

In Barrett's oesophagus, which of the following epithelial transformations occurs?

Accepted Answer

Squamous to intestinal columnar epithelium

Answer

Cuboidal to columnar epithelium

Answer

Transitional to squamous epithelium

Answer

Columnar to squamous epithelium

Question 9

Bernard-Soulier syndrome is caused by a defect in which of the following platelet glycoproteins?

Accepted Answer

GpIb/IX complex

Answer

GpIV

Answer

GpIa/IIa

Answer

GpIIb/IIIa

Question 10

A patient with renal disease undergoes a biopsy. On Congo red staining, the deposits show apple-green birefringence under polarised light. What is the most likely diagnosis?

Accepted Answer

Amyloidosis

Answer

Diabetic nephropathy

Answer

Membranous nephropathy

Answer

Minimal change disease

FMGE 2025 — Pathology