INI-CET 2021 — Pathology

Q: Which of the following causes aplastic crisis in hereditary spherocytosis?

Parvovirus. ***Parvovirus*** - **Parvovirus B19** specifically targets and destroys **erythroid precursors** in the bone marrow, leading to a temporary cessation of red blood cell production [1]. - In patients with conditions like **hereditary spherocytosis** who already have chronic hemolysis and increased erythropoiesis, this interruption can cause a sudden and severe drop in hemoglobin, known as an **aplastic crisis** [1]. *Poxvirus* - Poxviruses primarily cause **skin lesions** and systemic symptoms like fever and malaise, with diseases such as smallpox or molluscum contagiosum. - They are not known to directly cause **aplastic crisis** by targeting erythroid progenitors. *Adenovirus* - Adenoviruses commonly cause **respiratory tract infections**, gastroenteritis, and conjunctivitis. - While they can cause various symptoms, they are not typically associated with **aplastic crisis** in the context of hereditary spherocytosis. *Epstein-Barr virus* - **Epstein-Barr virus (EBV)** is known to cause **infectious mononucleosis** and is associated with certain lymphomas and nasopharyngeal carcinoma. - Although it can rarely cause **hemophagocytic lymphohistiocytosis** leading to pancytopenia, it does not typically induce **aplastic crisis** in hereditary spherocytosis by directly targeting erythroid precursors. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 641-642. [Practice more Pathology PYQs on OnCourse]

Q: Which is the cell of origin of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma?

Naïve B cells. ***Naïve B cells*** - Chronic Lymphocytic Leukaemia (CLL) and Small Lymphocytic Lymphoma (SLL) originate from **CD5-positive B lymphocytes** arrested in a mature but **naïve differentiation stage** [1]. - These cells express both **B-cell markers (CD19, CD20, CD23)** and a T-cell marker (CD5), which is characteristic of the clone [4]. *Mature B cells* - While CLL/SLL are derived from B cells, they are specifically from **naïve, not fully mature, B cells**. - **Other B-cell lymphomas** like follicular lymphoma or mantle cell lymphoma originate from distinct stages of mature B-cell differentiation [2]. *Progenitor T cells* - **Progenitor T cells** are the cells of origin for **T-cell acute lymphoblastic leukaemia (T-ALL)**, not CLL/SLL [3]. - T-ALL involves immature T lymphocytes and presents with different clinical and immunophenotypic features [3]. *Mature T cells* - **Mature T cells** can give rise to various **peripheral T-cell lymphomas**, like peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) or cutaneous T-cell lymphoma (Mycosis Fungoides). - These are distinct from CLL/SLL, which is a B-cell neoplasm [4]. **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. 596-598. [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. 610-612. [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, pp. 598-599. [4] 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. [Practice more Pathology PYQs on OnCourse]

Q: Arrange the following cellular events of inflammation in the correct sequence: 1. Rolling 2. Cytokine-mediated integrin activation 3. Adhesion 4. Migration

1,2,3,4. ***1,2,3,4*** - The correct sequence of cellular events for leukocyte recruitment during inflammation begins with **rolling** [1], followed by **cytokine-mediated integrin activation** [2], then firm **adhesion** to the endothelium [1], and finally **migration** (diapedesis) into the tissues [3]. - This step-by-step process ensures effective targeting of leukocytes to the site of injury or infection [1]. *3,4,1,2* - This sequence is incorrect as **adhesion** cannot occur before **rolling**, and **migration** is the final step after adhesion, not an early one. - **Cytokine-mediated integrin activation** must precede firm adhesion [1]. *2,1,4,3* - This order is incorrect because **rolling** (1) is the initial interaction that allows leukocytes to slow down on the endothelium [2], and it occurs before **cytokine-mediated integrin activation** (2) which strengthens the binding. - **Migration** (4) is also misplaced as it should be the last step after firm adhesion (3). *4,1,2,3* - This sequence is incorrect as **migration** (4) is the last step in the process, not the first. - **Rolling** (1) initiates the process by transiently interacting with endothelial cells, followed by activation and adhesion. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 87. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Migration in the tissues toward a chemotactic stimulus, pp. 86-87. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 87-89. [Practice more Pathology PYQs on OnCourse]

12 Previous Year Questions with Answers & Explanations

Questions

Which of the following causes aplastic crisis in hereditary spherocytosis?

Which cell acts as the primary effector cell in type IV (delayed-type) hypersensitivity reactions?

Which is the cell of origin of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma?

Arrange the following cellular events of inflammation in the correct sequence: 1. Rolling 2. Cytokine-mediated integrin activation 3. Adhesion 4. Migration

A 5 year old child who presented with proptosis of one of the eyes was found to have a desmin positive tumour. What is the probable diagnosis?

Which of the following is true? 1. BRCA1 is an oncogene 2. HER2neu is amplified only in a fraction of breast cancer 3. EGFR (+) is seen in non-small cell lung cancer 4. N-MYC is a tumor suppressor gene

A patient with lytic lesions on the skull is suspected of a diagnosis of Langerhans cell histiocytosis. Which of the following is a characteristic finding on electron microscopy?

A person was brought to the emergency department with facial swelling, itching, and hypotension following a bee sting. The mentioned clinical features are due to the increase in which immunoglobulin?

A 42 year-old female patient presents with cough, low-grade fever, and hemoptysis. Investigations reveal a cavitary lesion on her right lung apex, which on biopsy reveals caseous necrosis. The underlying pathophysiology is:

Q10

A boy presents with fever, night sweats, and neck swelling. The biopsy of swelling showed a starry sky appearance. What is the most likely genetic abnormality seen in this case?

INI-CET 2021 - Pathology INI-CET Practice Questions and MCQs

Question 1: Which of the following causes aplastic crisis in hereditary spherocytosis?

A. Poxvirus
B. Parvovirus (Correct Answer)
C. Adenovirus
D. Epstein-Barr virus

Explanation: ***Parvovirus*** - **Parvovirus B19** specifically targets and destroys **erythroid precursors** in the bone marrow, leading to a temporary cessation of red blood cell production [1]. - In patients with conditions like **hereditary spherocytosis** who already have chronic hemolysis and increased erythropoiesis, this interruption can cause a sudden and severe drop in hemoglobin, known as an **aplastic crisis** [1]. *Poxvirus* - Poxviruses primarily cause **skin lesions** and systemic symptoms like fever and malaise, with diseases such as smallpox or molluscum contagiosum. - They are not known to directly cause **aplastic crisis** by targeting erythroid progenitors. *Adenovirus* - Adenoviruses commonly cause **respiratory tract infections**, gastroenteritis, and conjunctivitis. - While they can cause various symptoms, they are not typically associated with **aplastic crisis** in the context of hereditary spherocytosis. *Epstein-Barr virus* - **Epstein-Barr virus (EBV)** is known to cause **infectious mononucleosis** and is associated with certain lymphomas and nasopharyngeal carcinoma. - Although it can rarely cause **hemophagocytic lymphohistiocytosis** leading to pancytopenia, it does not typically induce **aplastic crisis** in hereditary spherocytosis by directly targeting erythroid precursors. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 641-642.

Question 2: Which cell acts as the primary effector cell in type IV (delayed-type) hypersensitivity reactions?

A. Neutrophil
B. Dendritic cell
C. Macrophage (Correct Answer)
D. Cytotoxic T cell

Explanation: ***Macrophage*** - **Macrophages** are the **principal effector cells** in type IV hypersensitivity reactions, responsible for the characteristic tissue damage and inflammation [1]. - They are activated by **IFN-γ and other cytokines** released by sensitized CD4+ Th1 cells upon antigen re-exposure [2]. - Activated macrophages release **inflammatory mediators, lysosomal enzymes, and reactive oxygen species** that cause tissue damage [3]. - They are central to **granuloma formation** (e.g., tuberculosis, sarcoidosis) and the classic tuberculin skin test reaction [1]. *Neutrophil* - **Neutrophils** are the hallmark of acute inflammation and type III hypersensitivity (immune complex reactions). - While neutrophils can be recruited in some type IV reactions (subtype IVd), they are **not the defining effector cells** of classic delayed-type hypersensitivity [1]. *Dendritic cell* - **Dendritic cells** function as **antigen-presenting cells (APCs)** in the sensitization/afferent phase [1]. - They capture and present antigens to naive T cells but do **not serve as effector cells** causing tissue damage in the efferent phase. *Cytotoxic T cell* - **CD8+ cytotoxic T cells** are involved in a specific subtype of type IV hypersensitivity (type IVc) where they directly kill antigen-bearing target cells. - However, in **classic delayed-type hypersensitivity** (type IVa, e.g., tuberculin reaction, contact dermatitis), **macrophages are the predominant effector cells** mediating tissue damage through inflammatory mediators rather than direct cytotoxicity [1]. **Note:** Type IV hypersensitivity is T cell-mediated, with CD4+ Th1 cells initiating the response, but macrophages execute the effector function as the primary tissue-damaging cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 216-218. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 109. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 105-106.

Question 3: Which is the cell of origin of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma?

A. Mature B cells
B. Progenitor T cells
C. Mature T cells
D. Naïve B cells (Correct Answer)

Explanation: ***Naïve B cells*** - Chronic Lymphocytic Leukaemia (CLL) and Small Lymphocytic Lymphoma (SLL) originate from **CD5-positive B lymphocytes** arrested in a mature but **naïve differentiation stage** [1]. - These cells express both **B-cell markers (CD19, CD20, CD23)** and a T-cell marker (CD5), which is characteristic of the clone [4]. *Mature B cells* - While CLL/SLL are derived from B cells, they are specifically from **naïve, not fully mature, B cells**. - **Other B-cell lymphomas** like follicular lymphoma or mantle cell lymphoma originate from distinct stages of mature B-cell differentiation [2]. *Progenitor T cells* - **Progenitor T cells** are the cells of origin for **T-cell acute lymphoblastic leukaemia (T-ALL)**, not CLL/SLL [3]. - T-ALL involves immature T lymphocytes and presents with different clinical and immunophenotypic features [3]. *Mature T cells* - **Mature T cells** can give rise to various **peripheral T-cell lymphomas**, like peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) or cutaneous T-cell lymphoma (Mycosis Fungoides). - These are distinct from CLL/SLL, which is a B-cell neoplasm [4]. **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. 596-598. [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. 610-612. [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, pp. 598-599. [4] 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.

Question 4: Arrange the following cellular events of inflammation in the correct sequence: 1. Rolling 2. Cytokine-mediated integrin activation 3. Adhesion 4. Migration

A. 1,2,3,4 (Correct Answer)
B. 3,4,1,2
C. 2,1,4,3
D. 4,1,2,3

Explanation: ***1,2,3,4*** - The correct sequence of cellular events for leukocyte recruitment during inflammation begins with **rolling** [1], followed by **cytokine-mediated integrin activation** [2], then firm **adhesion** to the endothelium [1], and finally **migration** (diapedesis) into the tissues [3]. - This step-by-step process ensures effective targeting of leukocytes to the site of injury or infection [1]. *3,4,1,2* - This sequence is incorrect as **adhesion** cannot occur before **rolling**, and **migration** is the final step after adhesion, not an early one. - **Cytokine-mediated integrin activation** must precede firm adhesion [1]. *2,1,4,3* - This order is incorrect because **rolling** (1) is the initial interaction that allows leukocytes to slow down on the endothelium [2], and it occurs before **cytokine-mediated integrin activation** (2) which strengthens the binding. - **Migration** (4) is also misplaced as it should be the last step after firm adhesion (3). *4,1,2,3* - This sequence is incorrect as **migration** (4) is the last step in the process, not the first. - **Rolling** (1) initiates the process by transiently interacting with endothelial cells, followed by activation and adhesion. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 87. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Migration in the tissues toward a chemotactic stimulus, pp. 86-87. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 87-89.

Question 5: A 5 year old child who presented with proptosis of one of the eyes was found to have a desmin positive tumour. What is the probable diagnosis?

A. Neuroblastoma
B. Retinoblastoma
C. Rhabdomyosarcoma (Correct Answer)
D. Ewing's sarcoma

Explanation: ***Rhabdomyosarcoma*** - **Desmin positivity** is a characteristic immunohistochemical feature of **rhabdomyosarcoma**, as desmin is an intermediate filament found in muscle cells [1]. - In a 5-year-old child presenting with **proptosis**, rhabdomyosarcoma of the orbit is a highly probable diagnosis, as it is the most common primary malignant orbital tumor in childhood [3]. *Neuroblastoma* - Neuroblastoma is typically a tumor of neural crest origin, with classic immunohistochemical markers being **neuron-specific enolase (NSE)** and **chromogranin**, not desmin [2]. - While it can manifest with orbital metastases leading to proptosis, the desmin positivity rules it out as the primary diagnosis [3]. *Retinoblastoma* - Retinoblastoma is a malignant tumor of the retina, presenting with **leukocoria** (white pupillary reflex) and occasionally proptosis in advanced stages [4]. - It arises from neuroectodermal cells, and its characteristic markers include **synaptophysin** and **neuron-specific enolase (NSE)**, not desmin [4]. *Ewing's sarcoma* - Ewing's sarcoma is a primary malignant small round blue cell tumor of bone and soft tissue, typically marked by expression of **CD99** and a characteristic **t(11;22) translocation**. - While it can occur in the orbit, it is not desmin positive, making rhabdomyosarcoma a more likely diagnosis given the immunohistochemical findings. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1224-1225. [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. 211-212. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1323-1324. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 737-738.

Question 6: Which of the following is true? 1. BRCA1 is an oncogene 2. HER2neu is amplified only in a fraction of breast cancer 3. EGFR (+) is seen in non-small cell lung cancer 4. N-MYC is a tumor suppressor gene

A. 1,3
B. 1,2
C. 2,3 (Correct Answer)
D. All of the options

Explanation: ***Correct Option: 2,3*** - **Statement 2 is TRUE**: HER2neu amplification occurs in only a fraction (~15-20%) of breast cancers, making it a specific subset requiring targeted therapy with trastuzumab (Herceptin) [1]. - **Statement 3 is TRUE**: EGFR (epidermal growth factor receptor) mutations or overexpression are commonly seen in non-small cell lung cancer (NSCLC) and serve as important therapeutic targets for tyrosine kinase inhibitors. *Incorrect Option: 1,3* - Statement 1 is **FALSE**: BRCA1 is a **tumor suppressor gene**, not an oncogene. It functions in DNA double-strand break repair, and loss-of-function mutations increase the risk of breast and ovarian cancers. - Statement 3 is TRUE, but the inclusion of the false statement about BRCA1 makes this option incorrect. *Incorrect Option: 1,2* - Statement 1 is **FALSE**: BRCA1 is a **tumor suppressor gene**, not an oncogene. - Statement 2 is TRUE [1], but the false classification of BRCA1 invalidates this option. *Incorrect Option: All of the options* - Statement 1 is **FALSE**: BRCA1 is a tumor suppressor gene, not an oncogene. - Statement 4 is **FALSE**: N-MYC is an **oncogene** that is amplified in neuroblastoma and other cancers, not a tumor suppressor gene. - Since two of the four statements are incorrect, "All of the options" cannot be true. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1059-1060.

Question 7: A patient with lytic lesions on the skull is suspected of a diagnosis of Langerhans cell histiocytosis. Which of the following is a characteristic finding on electron microscopy?

A. Eosinophils
B. Histiocytes
C. Birbeck granules (Correct Answer)
D. Giant cells

Explanation: ***Birbeck granules*** - **Birbeck granules** are rod-shaped organelles with a striated core and a dilated end, resembling a "tennis racket," which are pathognomonic for **Langerhans cells** and, by extension, **Langerhans cell histiocytosis** [1]. - Their presence on **electron microscopy** is a definitive diagnostic feature for LCH [1]. *Eosinophils* - While **eosinophils** are often seen infiltrating lesions in **Langerhans cell histiocytosis**, they are not the diagnostic cellular component or ultrastructural finding on electron microscopy [1]. - **Eosinophils** are granulocytes involved in allergic reactions and parasitic infections; their appearance on EM is distinct from Birbeck granules. *Histiocytes* - **Histiocytes** (macrophages) are present in various inflammatory and neoplastic conditions and are the cell lineage from which **Langerhans cells** are derived, but their general presence on **electron microscopy** is not specific enough for diagnosing **LCH** [1]. - Without the characteristic **Birbeck granules**, a generic histiocyte would not distinguish LCH from other histiocytic disorders [1]. *Giant cells* - **Giant cells**, such as **multinucleated giant cells** or **osteoclasts**, can be found in association with bone lesions including **lytic lesions**, but they are not specific to **Langerhans cell histiocytosis** and do not possess Birbeck granules. - Their presence points to bone destruction or inflammation but not the underlying cellular pathology of LCH. **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. 630.

Question 8: A person was brought to the emergency department with facial swelling, itching, and hypotension following a bee sting. The mentioned clinical features are due to the increase in which immunoglobulin?

A. IgE (Correct Answer)
B. IgG
C. IgA
D. IgM

Explanation: IgE - The symptoms of **facial swelling, itching, and hypotension** following a bee sting are characteristic of an immediate hypersensitivity reaction, specifically **anaphylaxis**, which is predominantly mediated by **IgE antibodies** [1]. - **IgE** binds to mast cells and basophils, and upon re-exposure to the allergen (bee venom), triggers the release of potent inflammatory mediators like **histamine**, causing vasodilation, increased vascular permeability, and smooth muscle contraction [1], . *IgG* - **IgG** antibodies are primarily involved in secondary immune responses, conferring long-term immunity, and neutralizing toxins and viruses [1]. - While IgG can be involved in some hypersensitivity reactions (Type II and Type III), it is not the primary immunoglobulin responsible for the acute, systemic symptoms of **anaphylaxis** from a bee sting [1]. *IgA* - **IgA** is the main immunoglobulin found in mucosal secretions, such as those in the gastrointestinal, respiratory, and genitourinary tracts, providing mucosal immunity. - It does not play a significant role in immediate hypersensitivity reactions or the systemic symptoms described in this scenario. *IgM* - **IgM** is the first antibody produced during a primary immune response and is important for activating the complement system and agglutinating antigens [1]. - It is not directly implicated in the pathogenesis of **Type I hypersensitivity reactions** like the anaphylactic response to a bee sting. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 208-213.

Question 9: A 42 year-old female patient presents with cough, low-grade fever, and hemoptysis. Investigations reveal a cavitary lesion on her right lung apex, which on biopsy reveals caseous necrosis. The underlying pathophysiology is:

A. Type 4 hypersensitivity reaction (Correct Answer)
B. Sudden cut off of blood supply
C. Enzyme degradation
D. Fibrinoid deposition

Explanation: ***Type 4 hypersensitivity reaction*** - **Caseous necrosis**, characteristic of **tuberculosis**, is mediated by a **Type 4 hypersensitivity reaction** to the mycobacterial antigens [1], [3]. - This delayed-type hypersensitivity involves activated **macrophages** and **T-lymphocytes** forming **granulomas** with central caseous necrosis [2], [4]. *Sudden cut off of blood supply* - This mechanism typically leads to **coagulative necrosis** (e.g., in myocardial infarction), where the tissue architecture is preserved for some time. - **Infarction** due to loss of blood supply generally does not result in the distinct cheesy, crumbly appearance of caseous necrosis. *Enzyme degradation* - This mechanism describes **liquefactive necrosis**, where dead cells are digested by hydrolytic enzymes, resulting in a viscous fluid. - Liquefactive necrosis is common in bacterial infections and central nervous system infarcts, which is not consistent with the morphology of caseous necrosis. *Fibrinoid deposition* - **Fibrinoid necrosis** involves immune complex deposition in arterial walls, leading to leakage of plasma proteins and fibrin. - This type of necrosis is characteristic of **vasculitis** and immunologic reactions in vessels, not the widespread tissue destruction seen in caseous necrosis. **References:** [1] 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. 173-174. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 109. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, p. 380. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 383-384.

Question 10: A boy presents with fever, night sweats, and neck swelling. The biopsy of swelling showed a starry sky appearance. What is the most likely genetic abnormality seen in this case?

A. RAS
B. BCR-ABL
C. p53
D. MYC (Correct Answer)

Explanation: ***MYC*** - The clinical presentation of **fever, night sweats, and neck swelling** in a child, coupled with a **starry sky appearance** on biopsy, is highly suggestive of **Burkitt lymphoma** [2, 3]. - **Burkitt lymphoma** is characterized by a **translocation involving the *MYC* gene** on chromosome 8, most commonly t(8;14), which leads to its overexpression and uncontrolled cell proliferation [1]. *RAS* - Mutations in the **RAS family of genes (HRAS, KRAS, NRAS)** are commonly found in a wide variety of cancers, including **leukemias, pancreatic cancer, and colorectal cancer**. - While *RAS* mutations drive proliferation, they are **not the primary genetic driver** of Burkitt lymphoma, nor are they linked to the characteristic starry sky appearance. *BCR-ABL* - The **BCR-ABL fusion gene**, resulting from the **Philadelphia chromosome (t(9;22))**, is the defining genetic abnormality of **chronic myeloid leukemia (CML)**. - CML presents with different symptoms and a distinct peripheral blood and bone marrow morphology, **not the "starry sky" appearance** seen in Burkitt lymphoma. *p53* - The **p53 tumor suppressor gene** is frequently mutated or inactivated in over half of all human cancers, leading to a loss of cell cycle control and apoptosis. - While **p53 mutations can occur in aggressive lymphomas**, including Burkitt lymphoma, the **primary and characteristic genetic abnormality** associated with Burkitt lymphoma and its presentation is the *MYC* translocation, not solely *p53* mutations. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [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. 605-606. [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.