FMGE 2025 - Pathology Practice Questions

Q: Which gene mutation is most commonly associated with Burkitt's lymphoma?

C-myc. ***C-myc*** - Burkitt's lymphoma is characterized by the **t(8;14) translocation** in 80% of cases [1] - This translocation juxtaposes the **C-myc oncogene (chromosome 8)** with the **immunoglobulin heavy chain locus (chromosome 14)** [1] - Results in **constitutive overexpression of C-myc**, driving uncontrolled cell proliferation [1] - This is a **pathognomonic molecular feature** of Burkitt's lymphoma [1] - Variants include t(2;8) and t(8;22) involving immunoglobulin light chain loci [1] *p53* - Tumor suppressor gene involved in many cancers - Not the characteristic mutation defining Burkitt's lymphoma - May be involved in disease progression but not the hallmark feature *Rb* - Retinoblastoma gene, another tumor suppressor - Associated with retinoblastoma and osteosarcoma - Not characteristic of Burkitt's lymphoma *p21* - Cyclin-dependent kinase inhibitor (CDKN1A) - Involved in cell cycle regulation - Not the defining genetic alteration in Burkitt's lymphoma **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325.

Q: A child presents with a right transverse palmar crease, a cardiac defect, survival into childhood, and mild intellectual impairment. What chromosomal mechanism is most likely associated with these findings?

Mosaicism. ***Mosaicism*** - **Mosaicism** is the presence of two or more cell lines with different genetic constitutions in a single individual, allowing for a **milder phenotype** of chromosomal syndromes like Trisomy 21. - The combination of classic Down syndrome features (transverse palmar crease, cardiac defect) with relatively **mild intellectual impairment** and survival into childhood with better outcomes suggests **Mosaic Down Syndrome** (mosaic Trisomy 21). - In mosaicism, only a proportion of cells carry the extra chromosome 21, resulting in **less severe manifestations** compared to complete trisomy. *Incorrect: Trisomy* - While **complete Trisomy 21** (Down syndrome) presents with similar features, it typically causes **more severe intellectual disability** and greater phenotypic expression. - The emphasis on **"mild" intellectual impairment** in this case points toward mosaicism rather than complete trisomy. *Incorrect: Haploid* - **Haploid** refers to a cell having only one set of chromosomes (n=23), a state that is **incompatible with human survival** beyond early embryonic development. - A complete haploid individual cannot survive into **childhood**. *Incorrect: Monosomy* - **Monosomy** (loss of one chromosome, 2n-1) for autosomes is typically **lethal in utero**, making survival into childhood impossible. - The only viable monosomy is **Monosomy X** (Turner syndrome), which presents with distinct features (short stature, webbed neck, ovarian dysgenesis) without the characteristic Down syndrome features described.

Q: A 50 year old female presented with a breast mass that was operated and the microscopic examination in given. What is the diagnosis?

Mucinous carcinoma breast. ***Mucinous carcinoma breast*** - The micrograph shows clusters and nests of relatively uniform tumor cells floating in abundant extracellular **mucin**, which is the hallmark of this diagnosis. - This subtype of invasive ductal carcinoma is typically well-differentiated, hormone receptor-positive (**ER/PR positive**), and carries a more favorable prognosis than conventional invasive ductal carcinoma. *Lobular carcinoma breast* - This carcinoma is characterized by small, discohesive tumor cells infiltrating the stroma individually or in a **single-file** or **“Indian file”** pattern, which is not seen here [1]. - A key feature is the loss of **E-cadherin** expression, leading to the discohesive nature of the cells [3]. *Medullary carcinoma* - Histologically, this tumor presents as poorly differentiated cells arranged in solid, **syncytial sheets** with a prominent **lymphoplasmacytic infiltrate** [2]. - The image lacks both the syncytial growth pattern and the dense inflammatory background characteristic of medullary carcinoma [2]. *Phyllodes tumour* - This is a biphasic **fibroepithelial tumor**, characterized by a hypercellular stromal component and an epithelial component arranged in a **leaf-like** (phyllodes) architecture. - The defining feature is the proliferating stroma, whereas the image shows a carcinoma defined by its epithelial cells and extracellular mucin. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 454-455. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 455-456. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1068-1069.

Q: In Myasthenia gravis, which of the following is the primary target of autoantibodies at the neuromuscular junction?

Post-synaptic ACh Receptor. ***Post-synaptic ACh Receptor*** - Myasthenia gravis is an autoimmune disorder where **IgG autoantibodies** are produced against the nicotinic **acetylcholine receptors (AChR)** on the post-synaptic muscle membrane [1], [2]. - These antibodies block acetylcholine from binding and also cause **complement-mediated destruction** and accelerated degradation of the receptors, leading to fatigable muscle weakness [1]. *Presynaptic ACh receptor* - Presynaptic acetylcholine receptors are involved in modulating the release of acetylcholine, but they are not the primary target of autoantibodies in Myasthenia Gravis. - Conditions targeting presynaptic components, like **Lambert-Eaton Myasthenic Syndrome**, involve a different pathophysiology. *Voltage-gated calcium channels at NMJ* - Autoantibodies against presynaptic **P/Q-type voltage-gated calcium channels (VGCCs)** are the hallmark of **Lambert-Eaton Myasthenic Syndrome (LEMS)**, not Myasthenia Gravis. - The blockade of these channels impairs the presynaptic release of acetylcholine, leading to a distinct clinical picture of weakness that often improves with activity. *Acetylcholinesterase* - **Acetylcholinesterase** is the enzyme that breaks down acetylcholine in the synaptic cleft; it is not the target of autoantibodies in this disease [3]. - **Acetylcholinesterase inhibitors**, such as pyridostigmine, are a primary treatment for Myasthenia Gravis because they increase the availability of acetylcholine at the neuromuscular junction [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 213-214. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1237-1238. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1238-1239.

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.

Q: What defect is seen in Bernard Soulier syndrome?

Deficiency of GpIb receptors. ***Deficiency of GpIb receptors***- **Bernard-Soulier syndrome (BSS)** is an autosomal recessive disorder caused by defective or deficient **Glycoprotein Ib (GpIb)** [1]; this receptor is necessary for platelet adhesion to the subendothelium via **von Willebrand factor (vWF)** [1], [2]. - This defect results in dysfunctional primary **hemostasis**, causing bleeding and characteristic findings like **giant platelets** (macrothrombocytopenia) and mild to severely prolonged **bleeding time**. *Deficiency of GpIIb/IIIa receptor*- Deficiency or dysfunction of the **GpIIb/IIIa receptor** (fibrinogen receptor) causes **Glanzmann thrombasthenia** [1], which impairs platelet aggregation, not initial adhesion. - In Glanzmann thrombasthenia, platelets fail to aggregate in response to most agonists (like ADP or thrombin), but the initial adhesion mediated by GpIb is preserved [1]. *Deficiency of von Willebrand factor*- Deficiency of **von Willebrand factor (vWF)** causes **von Willebrand disease (vWD)**, the most common inherited bleeding disorder. - vWF is the ligand that links GpIb on the platelet to the exposed collagen in the vessel wall [2]; its deficiency is distinct from the receptor deficiency seen in BSS. *Deficiency of ADP receptors*- Deficiency of **ADP receptors** (specifically the P2Y12 receptor) impairs the signal transduction critical for sustained platelet aggregation and granule release [2]. - While affecting primary hemostasis, this congenital receptor deficiency is separate from BSS and is rarely reported; the most common interference with this receptor is therapeutic (**clopidogrel**). **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 skin graft was performed on an immunocompromised patient using tissue from another immunocompromised individual. Weeks later, the patient developed contractures and systemic symptoms. What is the most likely cause?

Graft-versus-host disease. ***Correct: Graft-versus-host disease (GVHD)*** - GVHD occurs when **immunocompetent donor T lymphocytes** from the graft recognize recipient tissues as foreign and mount an immune attack [1] - Key scenario: **Immunocompromised recipient** receiving tissue from another person (even if donor is immunocompromised, donor T cells in the graft can still be functional) - The recipient's compromised immune system **cannot eliminate donor lymphocytes**, allowing them to engraft and attack host tissues [1] - **Contractures** are characteristic of chronic GVHD affecting skin and connective tissue - **Systemic symptoms** (fever, diarrhea, hepatitis) reflect multi-organ involvement typical of GVHD - Timeline of **weeks** fits both acute (2-100 days) and chronic (>100 days) GVHD *Incorrect: Delayed wound healing* - Would present as local wound complications, not systemic symptoms - Does not explain contractures or multi-organ involvement - Typically occurs within days, not weeks *Incorrect: Rejection due to recipient T8 cells* - This describes **host-versus-graft** (rejection), not graft-versus-host - Patient is **immunocompromised**, so recipient T cells are impaired and unlikely to mount effective rejection - Would cause graft loss, not systemic symptoms in the recipient *Incorrect: Graft failure* - Non-specific term that doesn't explain the clinical presentation - Would present as loss of graft function/wound dehiscence, not systemic symptoms - Does not account for contractures or multi-organ disease **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 244-245.

Question 1

Which gene mutation is most commonly associated with Burkitt's lymphoma?

Accepted Answer

C-myc

Answer

p53

Answer

Rb

Answer

p21

Question 2

A child presents with a right transverse palmar crease, a cardiac defect, survival into childhood, and mild intellectual impairment. What chromosomal mechanism is most likely associated with these findings?

Accepted Answer

Mosaicism

Answer

Haploid

Answer

Monosomy

Answer

Trisomy

Question 3

A 50 year old female presented with a breast mass that was operated and the microscopic examination in given. What is the diagnosis?

Accepted Answer

Mucinous carcinoma breast

Answer

Medullary carcinoma

Answer

Lobular carcinoma breast

Answer

Phyllodes tumour

Question 4

The CSF findings in bacterial meningitis would include which of the following?

Accepted Answer

Elevated protein and decreased glucose

Answer

Elevated WBC count with normal glucose

Answer

Decreased protein and elevated glucose

Answer

Normal white blood cell count

Question 5

A 30-year-old female presents to the OPD with a 3 cm breast lump in the upper medial quadrant. The lump has an uneven, bosselated surface, and the overlying skin is mildly ulcerated. Microscopic examination reveals the given findings. What is the most likely diagnosis?

Accepted Answer

Phyllodes tumor

Answer

Fibroadenoma

Answer

Paget's disease

Answer

Galactocele

Question 6

A patient presents with weight gain, thinning of hair, and dry skin. Diagnosis is Hashimoto’s thyroiditis. Which antibody is seen in this case?

Accepted Answer

Anti-TPO antibody

Answer

Anti TBG

Answer

Long-acting thyroid-stimulating antibody

Answer

Anti-TSH receptor antibody

Question 7

In Myasthenia gravis, which of the following is the primary target of autoantibodies at the neuromuscular junction?

Accepted Answer

Post-synaptic ACh Receptor

Answer

Acetylcholinesterase

Answer

Voltage-gated calcium channels at NMJ

Answer

Presynaptic ACh receptor

Question 8

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

Question 9

What defect is seen in Bernard Soulier syndrome?

Accepted Answer

Deficiency of GpIb receptors

Answer

Deficiency of GpIIb/IIIa receptor

Answer

Deficiency of ADP receptors

Answer

Deficiency of von Willebrand factor

Question 10

A skin graft was performed on an immunocompromised patient using tissue from another immunocompromised individual. Weeks later, the patient developed contractures and systemic symptoms. What is the most likely cause?

Accepted Answer

Graft-versus-host disease

Answer

Delayed wound healing

Answer

Rejection due to recipient T8 cells

Answer

Graft failure

FMGE 2025 — Pathology