FMGE 2025 - Pathology Practice Questions

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.

Q: HPV infection is most commonly associated with which type of cancer?

Oropharyngeal cancer. ***Oropharyngeal cancer*** - HPV (particularly HPV-16 and HPV-18) is strongly associated with oropharyngeal cancers, especially those affecting the **base of tongue and tonsils** [2], [3] - HPV-positive oropharyngeal cancers represent a distinct epidemiological entity with **better prognosis** compared to tobacco/alcohol-related cases - Among the options listed, oropharyngeal cancer is the **only HPV-associated malignancy** [3] - Note: Cervical cancer is the **most common HPV-related cancer overall** (not listed in options) [1], [3] *Incorrect: Esophageal cancer* - Primarily associated with **tobacco, alcohol, Barrett's esophagus, and chronic GERD** - Not significantly associated with HPV infection *Incorrect: Lung cancer* - Main risk factors include **smoking, radon exposure, asbestos, and air pollution** - No established HPV association *Incorrect: Stomach cancer* - Associated with **H. pylori infection, dietary factors (nitrosamines), and chronic gastritis** - Not linked to HPV infection **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1007-1008. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lung, pp. 739-741. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 219-220.

Q: A 25-year-old man presents with headaches, visual disturbances, and hypertension. MRI brain shows a cerebellar hemangioblastoma, and abdominal imaging reveals multiple cysts in the kidneys along with a solid renal mass suggestive of renal cell carcinoma. His father had similar findings and died from a brain tumor in his 40s. Which of the following chromosomal abnormalities is most likely associated with his condition?

Deletion on chromosome 3p. ***Deletion on chromosome 3p*** - This clinical presentation of **cerebellar hemangioblastoma**, **renal cell carcinoma (clear cell type)**, and multiple renal and pancreatic cysts in a familial context is highly characteristic of **Von Hippel-Lindau (VHL) disease**. [1] - VHL disease is caused by an inherited or sporadic inactivation (deletion or mutation) of the **VHL tumor suppressor gene** located on the short arm of chromosome 3 (**3p25.3**). [2] *Deletion on chromosome 13q* - Deletion of the **RB1 gene** on chromosome 13q is associated with **retinoblastoma** and an increased risk of **osteosarcoma**, not VHL disease. - The clinical picture of headaches, cerebellar mass, and renal cell carcinoma is distinct from the typical presentation of RB1-associated disorders. *Deletion on chromosome 17p* - Deletion or mutation of the **TP53 gene** on chromosome 17p is primarily associated with **Li-Fraumeni syndrome**, which increases the risk for a variety of cancers, including sarcomas, breast cancer, and adrenocortical carcinoma, but less commonly VHL-related tumors. - This deletion is not the genetic locus for the VHL tumor suppressor gene. *Trisomy of chromosome 12* - Trisomy 12 is a common chromosomal anomaly found in B-cell chronic lymphocytic leukemia (**CLL**) and some benign tumors like **uterine leiomyomas**. - It is an inappropriate anomaly for a familial syndrome presenting with hemangioblastoma and renal cell carcinoma. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 724-725. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 958-959.

Q: Mutation in which of the following genes is most commonly associated with medullary thyroid carcinoma?

RET. ***RET***- The **RET proto-oncogene** mutation is the defining genetic feature of medullary thyroid carcinoma (MTC), which arises from parafollicular C-cells. [1] - Germline mutations in **RET** are responsible for hereditary forms of MTC, including **Multiple Endocrine Neoplasia type 2 (MEN 2A and 2B)**, making it the most critical diagnostic marker. [1] *RAS* - Mutations in the **RAS family** of genes (NRAS, HRAS, KRAS) are highly prevalent in **follicular thyroid carcinoma (FTC)** and follicular variants of papillary thyroid carcinoma (PTC). - These mutations are typically associated with a less aggressive tumor phenotype compared to RET or BRAF alterations. *BRAF* - The **BRAF V600E mutation** is the most common genetic alteration found in **papillary thyroid carcinoma (PTC)**, specifically the classical and tall cell variants. - The presence of **BRAF V600E** often correlates with increased risk of aggressive features, such as lymph node metastasis and extrathyroidal extension in PTC. *TP53* - **TP53** is a tumor suppressor gene whose mutations are primarily seen in highly aggressive, **anaplastic (undifferentiated) thyroid carcinoma (ATC)**. - Mutations in **TP53** indicate a progression from well-differentiated tumors and are associated with a very poor prognosis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1139-1140.

Q: Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is caused by mutations in which type of genes?

MMR. ***MMR*** - Hereditary non-polyposis colorectal cancer (**HNPCC**), also known as **Lynch syndrome**, is caused by germline mutations in **DNA Mismatch Repair (MMR)** genes [1]. - Defective MMR function, most commonly due to mutations in **MLH1**, **MSH2**, **MSH6**, or **PMS2**, leads to an accumulation of mutations throughout the genome, a state known as **microsatellite instability (MSI)**. *APC* - Mutations in the **APC** gene, a tumor suppressor, are the cause of **Familial Adenomatous Polyposis (FAP)**, a different hereditary colorectal cancer syndrome [1]. - FAP is characterized by the development of hundreds to thousands of colonic polyps, whereas HNPCC typically presents with fewer polyps that rapidly progress to carcinoma [1]. *MYC* - **MYC** is a **proto-oncogene** involved in cell cycle control and proliferation; its dysregulation contributes to the development of many cancers, but it is not the primary genetic cause of HNPCC. - It is not a DNA repair gene, but rather a transcription factor that, when overexpressed, promotes uncontrolled cell growth. *TERT1* - This likely refers to the **TERT** gene, which encodes **telomerase reverse transcriptase**, an enzyme essential for maintaining telomere length. - While reactivation of **telomerase** is a critical step for cellular immortalization in many cancers, inherited mutations in this gene are not the cause of Lynch syndrome. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 817, 821-822.

Question 1

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 2

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 3

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 4

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 5

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

Question 6

A 25-year-old presents with painful vesicular lesions on the lips. A Tzanck smear from the lesion base shows multinucleated giant cells. What is the most likely causative agent?

Accepted Answer

Herpes simplex virus

Answer

Coxsackievirus A16

Answer

Human papillomavirus

Answer

Varicella-zoster virus

Question 7

HPV infection is most commonly associated with which type of cancer?

Accepted Answer

Oropharyngeal cancer

Answer

Esophageal cancer

Answer

Lung cancer

Answer

Stomach cancer

Question 8

A 25-year-old man presents with headaches, visual disturbances, and hypertension. MRI brain shows a cerebellar hemangioblastoma, and abdominal imaging reveals multiple cysts in the kidneys along with a solid renal mass suggestive of renal cell carcinoma. His father had similar findings and died from a brain tumor in his 40s. Which of the following chromosomal abnormalities is most likely associated with his condition?

Accepted Answer

Deletion on chromosome 3p

Answer

Trisomy of chromosome 12

Answer

Deletion on chromosome 17p

Answer

Deletion on chromosome 13q

Question 9

Mutation in which of the following genes is most commonly associated with medullary thyroid carcinoma?

Accepted Answer

RET

Answer

RAS

Answer

BRAF

Answer

TP53

Question 10

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is caused by mutations in which type of genes?

Accepted Answer

MMR

Answer

APC

Answer

TERT1

Answer

MYC

FMGE 2025 — Pathology