NEET-PG 2025 — Pathology

Q: A lymphoma characterized by the presence of centrocytes and centroblasts, along with BCL2 positivity and CD10 expression, is most commonly associated with which chromosomal translocation?

t(14 ; 18). ***t(14 ; 18)*** [1], [2] - This translocation is the genetic hallmark of **Follicular Lymphoma (FL)**, characterized by the presence of **centrocytes** and **centroblasts**, **BCL2 positivity**, and **CD10 expression** [1], [2]. - It results in the juxtaposition of the **BCL2 gene** (on chromosome 18) with the **IgH locus** (on chromosome 14), leading to constitutive overexpression of the anti-apoptotic BCL2 protein [1], [2]. *t(2 ; 5)* - This translocation is characteristic of **Anaplastic Large Cell Lymphoma (ALCL)**, leading to the activation of the **ALK gene**. - ALCL is typically **CD30 positive** and lacks the centrocytes/centroblasts morphology and germinal center markers (like CD10) seen in the described B-cell lymphoma. *t(11 ; 14)* - This translocation is associated with **Mantle Cell Lymphoma (MCL)**, causing the overexpression of **Cyclin D1**. - While MCL cells are often BCL2 positive, they typically lack **CD10 expression**, which is a key feature of the described germinal center lymphoma. *t(8 ; 14)* - This translocation is the hallmark of **Burkitt Lymphoma**, resulting in **MYC gene** overexpression. - Burkitt Lymphoma is typically **CD10 positive** but shows a high proliferation index (Ki-67 ~100%) and lacks BCL2 expression [3], unlike the described follicular lymphoma. **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, pp. 602-604. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 561-562. [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. [Practice more Pathology PYQs on OnCourse]

Q: A 30-year-old man presents with a painless testicular mass. An ultrasound shows a well-circumscribed, homogeneous, non-hemorrhagic testicular tumor. Which of the following is the most likely diagnosis?

Seminoma. Seminoma - The clinical presentation (painless mass in a 30-year-old) combined with ultrasound findings (well-circumscribed, homogeneous, non-hemorrhagic tumor) strongly favors seminoma, the most common testicular germ cell tumor [1]. - Histologically, seminomas consist of large, clear cells separated by delicate fibrovascular septa infiltrated with lymphocytes, confirming this diagnosis [1]. Yolk sac tumor - This tumor is primarily the most common germ cell malignancy in infants and young children (under 3 years old) [1]. - It is classically associated with significantly elevated serum marker Alpha-fetoprotein (AFP). Choriocarcinoma - This highly aggressive tumor is characterized by significant hemorrhage, necrosis, and cavitation due to vascular invasion, which contradicts the 'non-hemorrhagic' description [2]. - It produces high levels of Human Chorionic Gonadotropin (hCG) due to the presence of syncytiotrophoblasts [1]. Teratoma - Teratomas are typically seen as heterogeneous or complex cystic masses on ultrasound due to the presence of various differentiated tissue elements (e.g., cartilage, bone, fat) [3]. - Pure teratomas are rare in adults; they usually form part of a mixed germ cell tumor [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 979-982. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 512-513. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 982-983. [Practice more Pathology PYQs on OnCourse]

Q: A child presents with visual disturbances and delayed growth. Imaging reveals a suprasellar mass, and histopathology shows the presence of "wet keratin" (compact, eosinophilic anucleate keratin). What is the most likely diagnosis?

Craniopharyngioma. ***Craniopharyngioma*** - This tumor is classically located in the **suprasellar region** and presents in children with visual field deficits and **endocrine dysfunction** (e.g., delayed growth, short stature) due to hypothalamic or pituitary stalk compression. - The histopathology description of **"wet keratin"** (or keratin nests with peripheral palisading of epithelial cells) is pathognomonic for the adamantinomatous subtype of craniopharyngioma. *Medulloblastoma* - This is primarily a **posterior fossa tumor** originating in the cerebellum, typically causing signs of increased intracranial pressure and **ataxia**, not primarily suprasellar syndromes. - Histologically, it is a small, round blue cell tumor of **primitive neuroectoderm (PNET)** origin; it does not exhibit keratin formation. *Glioma* - While gliomas (e.g., optic pathway gliomas) can involve the suprasellar area, the cellular morphology would consist of **astrocytic** or oligodendroglial cells. - Gliomas lack the epithelial components and definitive **keratin formation** that are characteristic of craniopharyngioma. *Pituitary adenoma* - Pituitary adenomas are typically **intrasellar** and are much more common in adults, causing symptoms associated with hormone excess or deficiency (hypopituitarism) [1]. - Histology shows sheets and cords of uniform **polygonal cells** derived from pituitary endocrinocytes [2]; they do not contain squamous elements or keratin. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1081. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 417-418. [Practice more Pathology PYQs on OnCourse]

Q: A patient presents with a mass in the front of the neck, along with odynophagia and dyspnea. Histopathology reveals tumor cells positive for TTF-1, synaptophysin, and chromogranin, and there is evidence of amyloid deposition. What is the most likely diagnosis?

Medullary thyroid carcinoma. ***Medullary thyroid carcinoma*** - The tumor cells are positive for **Synaptophysin** and **Chromogranin**, confirming their **neuroendocrine origin** from the parafollicular C cells [1][2]. - The characteristic finding of **amyloid deposition** is due to the precipitation of stored pro-hormone (primarily **calcitonin**) produced by these C cells, which is highly diagnostic for MTC [2]. *Papillary thyroid carcinoma* - While positive for TTF-1, it is characterized by distinctive nuclear features such as **Orphan Annie eye nuclei** and **nuclear grooves**. - It does **not** exhibit neuroendocrine differentiation (Synaptophysin/Chromogranin negative) or **amyloid deposition**. *Follicular thyroid carcinoma* - This tumor consists of follicular cells and is diagnosed by the demonstration of **capsular** or **vascular invasion**. - It is **negative** for neuroendocrine markers and **lacks** the pathognomonic **calcitonin-derived amyloid**. *Anaplastic thyroid carcinoma* - This is highly malignant and rapidly growing, often presenting with severe compression symptoms, but is histologically characterized by undifferentiated **spindle and giant cells**. - It is typically **negative** for specific neuroendocrine markers and TTF-1 expression is often lost; **amyloid deposits are not a feature**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 430-431. [Practice more Pathology PYQs on OnCourse]

17 Previous Year Questions with Answers & Explanations

Questions

A lymphoma characterized by the presence of centrocytes and centroblasts, along with BCL2 positivity and CD10 expression, is most commonly associated with which chromosomal translocation?

A 30-year-old man presents with a painless testicular mass. An ultrasound shows a well-circumscribed, homogeneous, non-hemorrhagic testicular tumor. Which of the following is the most likely diagnosis?

Which of the following laboratory techniques is most commonly used to compare and quantify CD markers on cells?

A child presents with visual disturbances and delayed growth. Imaging reveals a suprasellar mass, and histopathology shows the presence of "wet keratin" (compact, eosinophilic anucleate keratin). What is the most likely diagnosis?

A patient presents with a mass in the front of the neck, along with odynophagia and dyspnea. Histopathology reveals tumor cells positive for TTF-1, synaptophysin, and chromogranin, and there is evidence of amyloid deposition. What is the most likely diagnosis?

A middle-aged woman presents with dry eyes and dry mouth. Laboratory tests reveal positive anti-Ro (SSA) and anti-La (SSB) antibodies. What is the most likely underlying pathological mechanism?

Most common cause of squamous cell carcinoma at the base of the tongue is:

A 22-year-old tall male presents with long limbs, increased arm span, hypermobile joints, and high-arched palate. On examination, he has lens subluxation and a diastolic murmur suggestive of aortic root dilation. Which of the following genes is most likely mutated in this condition?

Which of the following types of cell death involves activation of caspase enzymes?

Q10

A 68-year-old man presents with bleeding manifestations. Peripheral smear shows the presence of cells shown below. Which of the following is the most common chromosomal abnormality seen in this condition?

NEET-PG 2025 - Pathology NEET-PG Practice Questions and MCQs

Question 1: A lymphoma characterized by the presence of centrocytes and centroblasts, along with BCL2 positivity and CD10 expression, is most commonly associated with which chromosomal translocation?

A. t(2 ; 5)
B. t(11 ; 14)
C. t(8 ; 14)
D. t(14 ; 18) (Correct Answer)

Explanation: ***t(14 ; 18)*** [1], [2] - This translocation is the genetic hallmark of **Follicular Lymphoma (FL)**, characterized by the presence of **centrocytes** and **centroblasts**, **BCL2 positivity**, and **CD10 expression** [1], [2]. - It results in the juxtaposition of the **BCL2 gene** (on chromosome 18) with the **IgH locus** (on chromosome 14), leading to constitutive overexpression of the anti-apoptotic BCL2 protein [1], [2]. *t(2 ; 5)* - This translocation is characteristic of **Anaplastic Large Cell Lymphoma (ALCL)**, leading to the activation of the **ALK gene**. - ALCL is typically **CD30 positive** and lacks the centrocytes/centroblasts morphology and germinal center markers (like CD10) seen in the described B-cell lymphoma. *t(11 ; 14)* - This translocation is associated with **Mantle Cell Lymphoma (MCL)**, causing the overexpression of **Cyclin D1**. - While MCL cells are often BCL2 positive, they typically lack **CD10 expression**, which is a key feature of the described germinal center lymphoma. *t(8 ; 14)* - This translocation is the hallmark of **Burkitt Lymphoma**, resulting in **MYC gene** overexpression. - Burkitt Lymphoma is typically **CD10 positive** but shows a high proliferation index (Ki-67 ~100%) and lacks BCL2 expression [3], unlike the described follicular lymphoma. **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, pp. 602-604. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 561-562. [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.

Question 2: A 30-year-old man presents with a painless testicular mass. An ultrasound shows a well-circumscribed, homogeneous, non-hemorrhagic testicular tumor. Which of the following is the most likely diagnosis?

A. Yolk sac tumor
B. Choriocarcinoma
C. Seminoma (Correct Answer)
D. Teratoma

Explanation: Seminoma - The clinical presentation (painless mass in a 30-year-old) combined with ultrasound findings (well-circumscribed, homogeneous, non-hemorrhagic tumor) strongly favors seminoma, the most common testicular germ cell tumor [1]. - Histologically, seminomas consist of large, clear cells separated by delicate fibrovascular septa infiltrated with lymphocytes, confirming this diagnosis [1]. Yolk sac tumor - This tumor is primarily the most common germ cell malignancy in infants and young children (under 3 years old) [1]. - It is classically associated with significantly elevated serum marker Alpha-fetoprotein (AFP). Choriocarcinoma - This highly aggressive tumor is characterized by significant hemorrhage, necrosis, and cavitation due to vascular invasion, which contradicts the 'non-hemorrhagic' description [2]. - It produces high levels of Human Chorionic Gonadotropin (hCG) due to the presence of syncytiotrophoblasts [1]. Teratoma - Teratomas are typically seen as heterogeneous or complex cystic masses on ultrasound due to the presence of various differentiated tissue elements (e.g., cartilage, bone, fat) [3]. - Pure teratomas are rare in adults; they usually form part of a mixed germ cell tumor [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 979-982. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 512-513. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 982-983.

Question 3: Which of the following laboratory techniques is most commonly used to compare and quantify CD markers on cells?

A. Western blot
B. Flow cytometry (Correct Answer)
C. ELISA
D. Immunohistochemistry

Explanation: ***Flow cytometry*** - It is the standard technique used to analyze and count cells based on their expression of **surface** and **intracellular** markers like CD markers [1]. - Cells are labeled with **fluorescent antibodies** specific to CD markers and passed through a laser beam to quantify fluorescence, which corresponds to marker expression [1]. *ELISA (Enzyme-linked immunosorbent assay)* - It is primarily used to detect and quantify the concentration of **soluble molecules** (e.g., antibodies, cytokines, antigens) in biological fluids [2]. - It is not designed for the simultaneous comparison and quantification of **membrane markers** on individual cells. *Western blot* - This technique separates **proteins** based on size (electrophoresis) and uses specific antibodies to detect their presence from a cell lysate. - It provides information about the protein's presence and size but does not assess the **cellular localization** or allow for single-cell quantification of surface markers. *Immunohistochemistry (IHC)* - IHC uses antibodies to detect antigens (including CD markers) within **tissue sections** (or immunocytochemistry for cell smears) [1]. - While it can demonstrate the presence of CD markers, it is used for **qualitative visualization** and anatomical localization, not for the high-throughput, quantitative comparison of markers on suspended single cells [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 341-342. [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. 259-260.

Question 4: A child presents with visual disturbances and delayed growth. Imaging reveals a suprasellar mass, and histopathology shows the presence of "wet keratin" (compact, eosinophilic anucleate keratin). What is the most likely diagnosis?

A. Medulloblastoma
B. Glioma
C. Craniopharyngioma (Correct Answer)
D. Pituitary adenoma

Explanation: ***Craniopharyngioma*** - This tumor is classically located in the **suprasellar region** and presents in children with visual field deficits and **endocrine dysfunction** (e.g., delayed growth, short stature) due to hypothalamic or pituitary stalk compression. - The histopathology description of **"wet keratin"** (or keratin nests with peripheral palisading of epithelial cells) is pathognomonic for the adamantinomatous subtype of craniopharyngioma. *Medulloblastoma* - This is primarily a **posterior fossa tumor** originating in the cerebellum, typically causing signs of increased intracranial pressure and **ataxia**, not primarily suprasellar syndromes. - Histologically, it is a small, round blue cell tumor of **primitive neuroectoderm (PNET)** origin; it does not exhibit keratin formation. *Glioma* - While gliomas (e.g., optic pathway gliomas) can involve the suprasellar area, the cellular morphology would consist of **astrocytic** or oligodendroglial cells. - Gliomas lack the epithelial components and definitive **keratin formation** that are characteristic of craniopharyngioma. *Pituitary adenoma* - Pituitary adenomas are typically **intrasellar** and are much more common in adults, causing symptoms associated with hormone excess or deficiency (hypopituitarism) [1]. - Histology shows sheets and cords of uniform **polygonal cells** derived from pituitary endocrinocytes [2]; they do not contain squamous elements or keratin. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1081. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 417-418.

Question 5: A patient presents with a mass in the front of the neck, along with odynophagia and dyspnea. Histopathology reveals tumor cells positive for TTF-1, synaptophysin, and chromogranin, and there is evidence of amyloid deposition. What is the most likely diagnosis?

A. Follicular thyroid carcinoma
B. Medullary thyroid carcinoma (Correct Answer)
C. Papillary thyroid carcinoma
D. Anaplastic thyroid carcinoma

Explanation: ***Medullary thyroid carcinoma*** - The tumor cells are positive for **Synaptophysin** and **Chromogranin**, confirming their **neuroendocrine origin** from the parafollicular C cells [1][2]. - The characteristic finding of **amyloid deposition** is due to the precipitation of stored pro-hormone (primarily **calcitonin**) produced by these C cells, which is highly diagnostic for MTC [2]. *Papillary thyroid carcinoma* - While positive for TTF-1, it is characterized by distinctive nuclear features such as **Orphan Annie eye nuclei** and **nuclear grooves**. - It does **not** exhibit neuroendocrine differentiation (Synaptophysin/Chromogranin negative) or **amyloid deposition**. *Follicular thyroid carcinoma* - This tumor consists of follicular cells and is diagnosed by the demonstration of **capsular** or **vascular invasion**. - It is **negative** for neuroendocrine markers and **lacks** the pathognomonic **calcitonin-derived amyloid**. *Anaplastic thyroid carcinoma* - This is highly malignant and rapidly growing, often presenting with severe compression symptoms, but is histologically characterized by undifferentiated **spindle and giant cells**. - It is typically **negative** for specific neuroendocrine markers and TTF-1 expression is often lost; **amyloid deposits are not a feature**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 430-431.

Question 6: A middle-aged woman presents with dry eyes and dry mouth. Laboratory tests reveal positive anti-Ro (SSA) and anti-La (SSB) antibodies. What is the most likely underlying pathological mechanism?

A. IgE-mediated hypersensitivity reaction
B. Lymphocytic infiltration and destruction of salivary and lacrimal glands (Correct Answer)
C. Destruction of exocrine glands by neutrophils
D. Deposition of amyloid in salivary glands

Explanation: ***Lymphocytic infiltration and destruction of salivary and lacrimal glands*** - Sjögren's syndrome (suggested by dry eyes, dry mouth, and **anti-Ro/SSA** & **anti-La/SSB** positivity) is pathologically defined by intense focal **lymphocytic infiltration** (primarily CD4+ T cells) within the affected exocrine glands [1]. - This chronic autoimmune damage, also known as focal glandular adenitis, leads to atrophy and functional abolition of the **salivary** and **lacrimal glands**, causing sicca symptoms [2]. *Destruction of exocrine glands by neutrophils* - **Neutrophils** are primarily involved in acute inflammation or bacterial infections; they are not the hallmark destructive cell type in this **chronic autoimmune disease**. - The characteristic lesion in Sjögren's syndrome involves extensive infiltration by **lymphocytes**, not neutrophils [1]. *IgE-mediated hypersensitivity reaction* - This type of reaction (Type I) involves mast cell degranulation and is responsible for **allergic responses** and anaphylaxis, which is clinically and pathologically distinct from Sjögren's syndrome. - Sjögren's syndrome involves **Type IV (cell-mediated)** and **Type III (immune complex)** pathology, evidenced by T-cell infiltration and autoantibodies [1]. *Deposition of amyloid in salivary glands* - **Amyloidosis** causing salivary gland enlargement is a rare cause of xerostomia and is characterized by misfolded protein deposition, not by profound **lymphocytic infiltration**. - The presence of specific autoantibodies (**anti-Ro/SSA, anti-La/SSB**) confirms a diagnosis of Sjögren's syndrome, making amyloidosis highly unlikely [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 234-236. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Head and Neck, pp. 749-750.

Question 7: Most common cause of squamous cell carcinoma at the base of the tongue is:

A. EBV
B. HCV
C. HPV (Correct Answer)
D. CMV

Explanation: ***HPV*** - **Human Papillomavirus**, particularly **HPV-16**, is the predominant etiological factor for **squamous cell carcinoma (SCC) of the oropharynx**, which includes the base of the tongue [1]. - **HPV-positive SCC** has rapidly increased in incidence and constitutes the majority of these cancers in non-smokers and non-drinkers [1]. *EBV* - **Epstein-Barr Virus (EBV)** is strongly associated with **Nasopharyngeal Carcinoma (NPC)**, endemic Burkitt's lymphoma, and post-transplant lymphoproliferative disorder [2]. - It is not considered the primary or most common oncogenic agent for **base of tongue SCC** [2]. *HCV* - **Hepatitis C Virus (HCV)** is the chief cause of viral **Hepatocellular Carcinoma (HCC)** and is also linked to certain **B-cell non-Hodgkin's lymphomas**. - There is no established role for HCV in the pathogenesis or high prevalence of **squamous cell carcinoma of the head and neck**. *CMV* - **Cytomegalovirus (CMV)** is a herpesvirus typically associated with opportunistic infections (e.g., retinitis, colitis) in **immunocompromised patients**. - While studies have investigated its oncogenic potential, CMV is not a significant or common causative agent for **oral or pharyngeal SCC**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lung, pp. 738-741. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Head and Neck, pp. 744-745.

Question 8: A 22-year-old tall male presents with long limbs, increased arm span, hypermobile joints, and high-arched palate. On examination, he has lens subluxation and a diastolic murmur suggestive of aortic root dilation. Which of the following genes is most likely mutated in this condition?

A. Fibrillin-1 (FBN1) (Correct Answer)
B. COL4A5
C. Elastin
D. COL1A1

Explanation: ***Fibrillin-1 (FBN1)*** - The clinical presentation (tall stature, long limbs, increased arm span, aortic root dilation, and lens subluxation/ectopia lentis) is characteristic of **Marfan Syndrome** [1]. - Marfan syndrome is caused by an autosomal dominant mutation in the **FBN1 gene** on chromosome 15, which codes for the microfibrillar protein **fibrillin-1** [1]. *COL4A5* - Mutations in **COL4A5** (Type IV collagen) are associated with **Alport Syndrome**. - Alport syndrome primarily presents with **progressive sensorineural hearing loss**, ocular abnormalities (not typically lens subluxation), and **nephropathy** (hematuria/proteinuria). *COL1A1* - Mutations in **COL1A1** (Type I collagen) are most commonly associated with **Osteogenesis Imperfecta (OI)**. - OI is characterized by **recurrent fractures**, often with blue sclerae, hearing loss, and joint laxity, but not the specific cardiovascular and ocular features seen here. *Elastin* - Mutations in the **Elastin gene (ELN)** are responsible for **Supravalvular Aortic Stenosis (SVAS)**, often seen in **Williams Syndrome**. - Williams syndrome also involves intellectual disability and a characteristic 'elfin' facies, which are not mentioned in this patient's presentation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154.

Question 9: Which of the following types of cell death involves activation of caspase enzymes?

A. Necrosis and Apoptosis
B. Apoptosis and Pyroptosis (Correct Answer)
C. Apoptosis only
D. Apoptosis and necroptosis

Explanation: ***Apoptosis and Pyroptosis*** - **Apoptosis** is the classic caspase-dependent programmed cell death pathway [1] - Involves **initiator caspases** (Caspase-8, Caspase-9) and **executioner caspases** (Caspase-3, -6, -7) - Characterized by cell shrinkage, chromatin condensation, and apoptotic body formation - **Pyroptosis** is an inflammatory form of programmed cell death that is strictly caspase-dependent [2] - Mediated by **inflammatory caspases** (Caspase-1, -4, -5, -11) [2] - Involves cleavage of Gasdermin-D leading to membrane pore formation - Triggered by inflammasome activation (particularly NLRP3) *Necrosis and Apoptosis* - **Necrosis** is caspase-independent and represents unregulated cell death from acute injury - Characterized by cell swelling, membrane rupture, and inflammatory response - Does not involve programmed activation of caspase enzymes *Apoptosis and necroptosis* - **Necroptosis** is a regulated form of necrotic cell death that occurs in a **caspase-independent** manner [2] - Executed through RIPK1-RIPK3-MLKL kinase pathway [2] - Typically occurs when caspase activity is inhibited or blocked *Apoptosis only* - Incomplete answer as **pyroptosis** is also inherently caspase-dependent - Pyroptosis uses inflammatory caspases (Caspase-1/4/5) distinct from apoptotic caspases - Both pathways represent distinct forms of caspase-mediated programmed cell death **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. 64-67. [2] 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, p. 71.

Question 10: A 68-year-old man presents with bleeding manifestations. Peripheral smear shows the presence of cells shown below. Which of the following is the most common chromosomal abnormality seen in this condition?

A. t(15 ; 17) (Correct Answer)
B. t(14 ; 18)
C. inv(16)
D. t(8 ; 21)

Explanation: The image displays a large blast cell containing numerous needle-like pink/red inclusions known as **Auer rods** (sometimes referred to as a "faggot cell") [2]. This morphology is pathognomonic for **Acute Promyelocytic Leukemia (APL)**, which is categorized as **AML M3** [3]. APL is frequently associated with severe **Disseminated Intravascular Coagulation (DIC)**, explaining the patient's bleeding manifestations [3]. ***t(15 ; 17)*** - This specific reciprocal translocation fuses the **PML** (Promyelocytic Leukemia) gene on chromosome 15 with the **RARA** (Retinoic Acid Receptor Alpha) gene on chromosome 17, defining APL [1]. - The resulting **PML-RARA fusion protein** blocks myeloid differentiation, and its presence guides therapeutic management, making APL highly responsive to **All-trans Retinoic Acid (ATRA)** [1]. *t(8 ; 21)* - This translocation is the most common cytogenetic abnormality seen in **AML M2** (AML with maturation), fusing the *RUNX1* and *RUNX1T1* genes [3]. - Although classified as core-binding factor leukemia, it lacks the characteristic morphology (multiple Auer rods/faggot cells) of APL. *t(14 ; 18)* - This is the defining translocation for **Follicular Lymphoma**, leading to the overexpression of the anti-apoptotic protein **BCL2**. - It is not associated with Acute Myeloid Leukemia (AML) subtypes. *inv(16)* - This chromosomal inversion is highly characteristic of **AML M4eo** (Acute Myelomonocytic Leukemia with marrow eosinophilia) [3]. - This aberration fuses the *CBFB* gene with *MYH11*, another type of core-binding factor leukemia with a largely favorable prognosis [3]. **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, pp. 620-621. [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, pp. 621-622. [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. 620.