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?
A patient presents with weight gain, thinning of hair, and dry skin. Diagnosis is Hashimoto’s thyroiditis. Which antibody is seen in this case?
In Myasthenia gravis, which of the following is the primary target of autoantibodies at the neuromuscular junction?
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?
What defect is seen in Bernard Soulier syndrome?
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?
Which among the following best describes 'Neuropraxia'?
Tau protein inclusions are involved in:
For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?
Which of the following is pro-apoptotic?
FMGE 2025 - Pathology FMGE Practice Questions and MCQs
Question 11: 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?
- A. Phyllodes tumor (Correct Answer)
- B. Fibroadenoma
- C. Paget's disease
- D. Galactocele
Explanation: ***Phyllodes tumor*** - The histology shows a classic **leaf-like (phyllodes)** architecture, which is pathognomonic [1]. This is a fibroepithelial lesion characterized by an overgrowth of the stromal component forming these projections [1]. - Clinically, these tumors often present as large, rapidly growing, bosselated masses [1]. Skin ulceration, as seen in this patient, can occur with larger or more aggressive (borderline/malignant) phyllodes tumors. *Galactocele* - A galactocele is a milk-filled cyst, typically occurring during or after lactation. Histologically, it would appear as a cyst lined by flattened epithelium containing **inspissated, eosinophilic material**, not a complex stromal proliferation. - Clinically, it presents as a smooth, mobile, and often tender cyst, which is inconsistent with the uneven, bosselated mass described. *Fibroadenoma* - While also a fibroepithelial tumor, a fibroadenoma has a less cellular stroma and lacks the prominent **leaf-like structures** and stromal overgrowth seen in the image [1]. The glands are typically compressed by a paucicellular stroma [2]. - Fibroadenomas are usually smaller, well-circumscribed, rubbery, and highly mobile masses (often called a **'breast mouse'**) that rarely cause skin changes like ulceration [2]. *Paget's disease* - Paget's disease is an adenocarcinoma affecting the epidermis of the nipple-areolar complex. Histology would show malignant **Paget cells** infiltrating the epidermis, which is not seen here. - The clinical presentation involves an eczematous, crusted, or ulcerating lesion of the **nipple and areola**, not a distinct lump in a breast quadrant [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, p. 1074. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 448-449. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 443-444.
Question 12: A patient presents with weight gain, thinning of hair, and dry skin. Diagnosis is Hashimoto’s thyroiditis. Which antibody is seen in this case?
- A. Anti TBG
- B. Long-acting thyroid-stimulating antibody
- C. Anti-TSH receptor antibody
- D. Anti-TPO antibody (Correct Answer)
Explanation: ***Anti-TPO antibody*** - **Anti-thyroid peroxidase (Anti-TPO)** antibodies are the classic serological marker for Hashimoto's thyroiditis, present in over 90% of cases. They target an enzyme essential for the synthesis of thyroid hormones. - The presence of these antibodies signifies an autoimmune process causing lymphocytic infiltration (as seen with **germinal centers** [2] in the image) and destruction of thyroid follicular cells [1], leading to **hypothyroidism** and characteristic **Hürthle cell** changes [2]. *Anti-TSH receptor antibody* - Antibodies against the **TSH receptor** are primarily associated with **Graves' disease**, where they typically stimulate the receptor, causing hyperthyroidism [3]. - While blocking anti-TSH receptor antibodies can cause hypothyroidism, they are much less common in Hashimoto's than **Anti-TPO** and **anti-thyroglobulin** antibodies. *Anti TBG* - **Thyroxine-binding globulin (TBG)** is a carrier protein for thyroid hormones in the blood, and its levels can be altered by various conditions or medications, but autoantibodies against it are not a standard marker for autoimmune thyroid disease. - Diagnosis of Hashimoto's relies on detecting antibodies against thyroid cellular components like **peroxidase** and **thyroglobulin**, not transport proteins like TBG. *Long-acting thyroid-stimulating antibody* - **Long-acting thyroid-stimulating antibody (LATS)** is an older term for a type of **TSH receptor antibody** (specifically a **Thyroid-Stimulating Immunoglobulin, TSI**) that is characteristic of **Graves' disease** [3]. - These antibodies cause hyperthyroidism by continuously stimulating the thyroid gland, which is the opposite pathophysiology of the hypothyroidism seen in Hashimoto's thyroiditis [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1089-1090. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1090-1091. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 424-426.
Question 13: In Myasthenia gravis, which of the following is the primary target of autoantibodies at the neuromuscular junction?
- A. Acetylcholinesterase
- B. Voltage-gated calcium channels at NMJ
- C. Presynaptic ACh receptor
- D. Post-synaptic ACh Receptor (Correct Answer)
Explanation: ***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.
Question 14: 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?
- A. Subdural hemorrhage
- B. Intraventricular bleeding
- C. Ischemic injury
- D. Diffuse axonal injury (Correct Answer)
Explanation: ***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 15: What defect is seen in Bernard Soulier syndrome?
- A. Deficiency of GpIIb/IIIa receptor
- B. Deficiency of ADP receptors
- C. Deficiency of GpIb receptors (Correct Answer)
- D. Deficiency of von Willebrand factor
Explanation: ***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.
Question 16: 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?
- A. Delayed wound healing
- B. Rejection due to recipient T8 cells
- C. Graft failure
- D. Graft-versus-host disease (Correct Answer)
Explanation: ***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 17: Which among the following best describes 'Neuropraxia'?
- A. Intact axon; Damaged nerve sheath (Correct Answer)
- B. None of the above
- C. Damaged axon and nerve sheath
- D. Damaged axon; Intact nerve sheath
Explanation: ***Intact axon; Damaged nerve sheath*** - This correctly describes **Neuropraxia**, the mildest form of nerve injury, where there is localized damage to the **myelin sheath** causing a temporary conduction block [1]. - The **axon** and connective tissue layers (**endoneurium**, **perineurium**, and **epineurium**) remain intact, allowing for complete and relatively rapid recovery once the compression is relieved. *Damaged axon; Intact nerve sheath* - This description corresponds to **Axonotmesis**, a more severe injury where the axon is disrupted, leading to **Wallerian degeneration** distal to the lesion [2]. - The surrounding connective tissue sheaths remain intact, which provides a scaffold for axonal regeneration, though recovery is slower and less complete than in neuropraxia. *Damaged axon and nerve sheath* - This describes **Neurotmesis**, the most severe type of nerve injury, involving complete transection of the axon and its surrounding connective tissue sheaths [2]. - Due to the disruption of the entire nerve trunk, spontaneous recovery is unlikely, and **surgical intervention** is often required to restore function. *None of the above* - This option is incorrect as the first option accurately defines **Neuropraxia** according to Seddon's classification of nerve injuries. - The other options describe the more severe forms of nerve injury, **Axonotmesis** and **Neurotmesis**, covering the primary classifications. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, p. 1232. [2] 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. 109-110.
Question 18: Tau protein inclusions are involved in:
- A. Amyotrophic lateral sclerosis
- B. Huntington's disease
- C. CNS lymphoma
- D. Alzheimer’s disease (Correct Answer)
Explanation: ***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.
Question 19: For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?
- A. Blue (Correct Answer)
- B. Gray
- C. Red
- D. Green
Explanation: ***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.
Question 20: Which of the following is pro-apoptotic?
- A. Bcl-2
- B. Bax (Correct Answer)
- C. Bcl-xL
- D. Mcl-1
Explanation: ***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.