INI-CET 2025 — Pathology

Q: Which of the following is an incorrect gene-disease association?

TP53 - Mucosal Neuroma. ***TP53 - Mucosal Neuroma*** - This is an **incorrect association**. Mucosal neuromas are a hallmark feature of **Multiple Endocrine Neoplasia type 2B (MEN 2B)** [2]. - MEN 2B is caused by a germline gain-of-function mutation in the **RET proto-oncogene**, not the TP53 tumor suppressor gene (which is associated with **Li-Fraumeni syndrome**). *STK11 - Breast Cancer* - This is a **correct association**. Mutations in the **STK11** gene cause **Peutz-Jeghers syndrome (PJS)**. - Patients with PJS have a significantly increased risk of developing several malignancies, including gastrointestinal cancers and non-GI cancers like **breast cancer**. *PTEN - Thyroid Carcinoma* - This is a **correct association**. Germline mutations in the **PTEN** gene are responsible for **Cowden Syndrome**. - Cowden Syndrome is characterized by hamartomas and a high lifetime risk of developing cancers, most notably **follicular thyroid carcinoma** and breast cancer. *BRCA2 - Prostate Carcinoma* - This is a **correct association**. Germline mutations in **BRCA2** are strongly linked to hereditary breast and ovarian cancer syndromes [1]. - Men with **BRCA2** mutations have a substantially elevated risk of developing **prostate carcinoma**, often presenting with high-grade, aggressive disease. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Pancreas, pp. 898-899. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1139-1140. [Practice more Pathology PYQs on OnCourse]

Q: HLA-mismatched transplant is not a problem in which of the following diseases?

Bare lymphocyte syndrome. **Bare lymphocyte syndrome (Correct)** - **Bare Lymphocyte Syndrome** (BLS) is characterized by a failure to express **MHC Class I (Type I)** or **MHC Class II (Type II)** molecules on the cell surface, crucial for antigen presentation. - The absence of functional MHC in the recipient means their cells cannot effectively present the donor's HLA antigens, minimizing host immune rejection (host-versus-graft rejection) and allowing for the successful use of **HLA-mismatched transplants**. *Wiskott-Aldrich syndrome (Incorrect)* - This X-linked immunodeficiency involves the **WASp gene** and affects the cytoskeleton of hematopoietic cells, leading to defects in **T-cell function** and a high risk of autoimmune disease. - Since the patient's capacity for MHC presentation is generally intact, standard severe **Graft-versus-Host Disease (GvHD)** is a major risk following mismatched transplant, necessitating stringent HLA matching. *Job's syndrome (Incorrect)* - Job's syndrome (Hyper-IgE syndrome) is typically caused by mutations in **STAT3**, impairing signal transduction necessary for Th17 cell differentiation and resulting in defective neutrophil chemotaxis. - This syndrome does not eliminate the ability of the recipient's cells to express and utilize MHC molecules; therefore, an **HLA-matched donor** is required to prevent transplant rejection and GvHD. *Chediak-Higashi syndrome (Incorrect)* - Caused by a mutation in the **LYST gene**, leading to defective lysosomal trafficking, which primarily affects phagocytes and pigment cells. - Although it is an immunodeficiency, the fundamental mechanisms for T-cell recognition of foreign alloantigens (such as mismatched HLA) are functional, making a severe **HLA mismatch** highly problematic and usually fatal. [Practice more Pathology PYQs on OnCourse]

Q: In renal transplant biopsy, which of the following stains is not used to identify organisms?

Congo red. ***Congo red*** - **Congo red** is a special stain primarily used to look for **amyloid deposition**, which appears as an apple-green birefringence under polarized light [1]. - It is a diagnostic stain for **amyloidosis** and has **no role in the identification of infectious organisms** (bacteria, fungi, or parasites) in tissue biopsies [2]. - This is the stain that is **NOT used to identify organisms** in renal transplant biopsies. *Gomori methenamine silver* - This stain, often abbreviated as **GMS**, is excellent for demonstrating the cell walls of **fungi** (e.g., *Pneumocystis*, *Aspergillus*, *Cryptococcus*) which appear as black structures. - It is frequently used in transplant pathology to rule out opportunistic fungal infections. *PAS (Periodic acid-Schiff) stain* - **PAS** stain is used to highlight mucopolysaccharides, basement membranes, and certain cell walls, making it useful for identifying various organisms. - It stains the cell walls of **fungi** and the capsules of some organisms, making it valuable in detecting infections. *Masson Fontana* - **Masson Fontana** stain is primarily used to identify **melanin** pigment in tissues. - While it is not a standard organism identification stain in routine renal transplant pathology, specialized silver-based modifications have been described for detecting certain fungal organisms in research settings. - However, it is not considered a primary stain for organism identification in clinical practice. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 268-269. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 533-534. [Practice more Pathology PYQs on OnCourse]

8 Previous Year Questions with Answers & Explanations

Questions

Which of the following is an incorrect gene-disease association?

Which of the following is not an aneuploidy?

HLA-mismatched transplant is not a problem in which of the following diseases?

Transplant rejection does not occur in which of the following conditions?

In renal transplant biopsy, which of the following stains is not used to identify organisms?

Histopathological features of granulosa cell tumor include all except:

Caspase-1 mediated cell death with inflammation is known as

Least common finding in diabetic kidney is

INI-CET 2025 - Pathology INI-CET Practice Questions and MCQs

Question 1: Which of the following is an incorrect gene-disease association?

A. BRCA2 - Prostate Carcinoma
B. STK11 - Breast Cancer
C. TP53 - Mucosal Neuroma (Correct Answer)
D. PTEN - Thyroid Carcinoma

Explanation: ***TP53 - Mucosal Neuroma*** - This is an **incorrect association**. Mucosal neuromas are a hallmark feature of **Multiple Endocrine Neoplasia type 2B (MEN 2B)** [2]. - MEN 2B is caused by a germline gain-of-function mutation in the **RET proto-oncogene**, not the TP53 tumor suppressor gene (which is associated with **Li-Fraumeni syndrome**). *STK11 - Breast Cancer* - This is a **correct association**. Mutations in the **STK11** gene cause **Peutz-Jeghers syndrome (PJS)**. - Patients with PJS have a significantly increased risk of developing several malignancies, including gastrointestinal cancers and non-GI cancers like **breast cancer**. *PTEN - Thyroid Carcinoma* - This is a **correct association**. Germline mutations in the **PTEN** gene are responsible for **Cowden Syndrome**. - Cowden Syndrome is characterized by hamartomas and a high lifetime risk of developing cancers, most notably **follicular thyroid carcinoma** and breast cancer. *BRCA2 - Prostate Carcinoma* - This is a **correct association**. Germline mutations in **BRCA2** are strongly linked to hereditary breast and ovarian cancer syndromes [1]. - Men with **BRCA2** mutations have a substantially elevated risk of developing **prostate carcinoma**, often presenting with high-grade, aggressive disease. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Pancreas, pp. 898-899. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1139-1140.

Question 2: Which of the following is not an aneuploidy?

A. Trisomy 13
B. Bloom Syndrome (Correct Answer)
C. Trisomy 21
D. Klinefelter Syndrome

Explanation: ***Bloom Syndrome*** - **Bloom syndrome** is a **rare autosomal recessive disorder** caused by a mutation in the *BLM* gene, leading to excessive sister chromatid exchange and chromosomal breakage (a form of **chromosomal instability syndrome**). - It is a **syndrome of gene mutation** and **chromosomal instability**, not an abnormal number of chromosomes (aneuploidy). ***Trisomy 21*** - This refers to having three copies of chromosome 21 (47, XX or XY, +21), which is the definition of a common **aneuploidy** known as **Down Syndrome** [1]. - Aneuploidy is the condition of having an abnormal number of chromosomes in a haploid set [3]. ***Trisomy 13*** - This involves having three copies of chromosome 13 (47, XX or XY, +13), which is a lethal **aneuploidy** known as **Patau Syndrome** [2]. - It results from meiotic non-disjunction, leading to severe developmental defects [1]. ***Klinefelter Syndrome*** - The genotype is typically 47, XXY, meaning there is an extra X chromosome [2]. - This is a form of sex chromosome **aneuploidy**, characterized by small testes, infertility, and gynecomastia [4]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 170-171. [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. 92-93. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 191-192.

Question 3: HLA-mismatched transplant is not a problem in which of the following diseases?

A. Job's syndrome
B. Wiskott-Aldrich syndrome
C. Chediak-Higashi syndrome
D. Bare lymphocyte syndrome (Correct Answer)

Explanation: **Bare lymphocyte syndrome (Correct)** - **Bare Lymphocyte Syndrome** (BLS) is characterized by a failure to express **MHC Class I (Type I)** or **MHC Class II (Type II)** molecules on the cell surface, crucial for antigen presentation. - The absence of functional MHC in the recipient means their cells cannot effectively present the donor's HLA antigens, minimizing host immune rejection (host-versus-graft rejection) and allowing for the successful use of **HLA-mismatched transplants**. *Wiskott-Aldrich syndrome (Incorrect)* - This X-linked immunodeficiency involves the **WASp gene** and affects the cytoskeleton of hematopoietic cells, leading to defects in **T-cell function** and a high risk of autoimmune disease. - Since the patient's capacity for MHC presentation is generally intact, standard severe **Graft-versus-Host Disease (GvHD)** is a major risk following mismatched transplant, necessitating stringent HLA matching. *Job's syndrome (Incorrect)* - Job's syndrome (Hyper-IgE syndrome) is typically caused by mutations in **STAT3**, impairing signal transduction necessary for Th17 cell differentiation and resulting in defective neutrophil chemotaxis. - This syndrome does not eliminate the ability of the recipient's cells to express and utilize MHC molecules; therefore, an **HLA-matched donor** is required to prevent transplant rejection and GvHD. *Chediak-Higashi syndrome (Incorrect)* - Caused by a mutation in the **LYST gene**, leading to defective lysosomal trafficking, which primarily affects phagocytes and pigment cells. - Although it is an immunodeficiency, the fundamental mechanisms for T-cell recognition of foreign alloantigens (such as mismatched HLA) are functional, making a severe **HLA mismatch** highly problematic and usually fatal.

Question 4: Transplant rejection does not occur in which of the following conditions?

A. Bare lymphocyte syndrome
B. Severe Combined Immunodeficiency (SCID) (Correct Answer)
C. Chronic granulomatous disease
D. DiGeorge syndrome

Explanation: The condition of Severe Combined Immunodeficiency (SCID) is characterized by a profound failure of adaptive immunity due to defects in the creation or function of both T-lymphocytes and B-lymphocytes [1]. Transplant rejection is a primarily cell-mediated process dependent on functional T-cells; since SCID recipients lack these critical immune cells, they cannot recognize or attack the donor graft, thus rejection does not occur [1]. Bare lymphocyte syndrome (BLS) is characterized by defective expression of MHC class I or MHC class II molecules, leading to severe immunodeficiency but typically not the complete and absolute absence of T-cell function like SCID. While severely immunocompromised, the mechanisms required for adaptive immunity are present, albeit impaired, and rejection risk is complex, making SCID the more definitive answer. Chronic granulomatous disease (CGD) involves an inherited deficiency of NADPH oxidase in phagocytes, impairing their ability to kill internalized microbes using oxidative burst [2]. CGD affects the innate immune system; the adaptive immune system (T-cells responsible for recognizing the graft) remains fully functional, meaning rejection will occur. DiGeorge syndrome causes variable degrees of T-cell deficiency due to the hypoplasia or aplasia of the thymus resulting from impaired development of the third and fourth pharyngeal pouches [2]. Though T-cell function is impaired, many patients retain residual or partial T-cell immunity, meaning a delayed or mild form of transplant rejection can still occur [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 246-248. [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. 167-168.

Question 5: In renal transplant biopsy, which of the following stains is not used to identify organisms?

A. Masson Fontana
B. PAS (Periodic acid-Schiff) stain
C. Congo red (Correct Answer)
D. Gomori methenamine silver

Explanation: ***Congo red*** - **Congo red** is a special stain primarily used to look for **amyloid deposition**, which appears as an apple-green birefringence under polarized light [1]. - It is a diagnostic stain for **amyloidosis** and has **no role in the identification of infectious organisms** (bacteria, fungi, or parasites) in tissue biopsies [2]. - This is the stain that is **NOT used to identify organisms** in renal transplant biopsies. *Gomori methenamine silver* - This stain, often abbreviated as **GMS**, is excellent for demonstrating the cell walls of **fungi** (e.g., *Pneumocystis*, *Aspergillus*, *Cryptococcus*) which appear as black structures. - It is frequently used in transplant pathology to rule out opportunistic fungal infections. *PAS (Periodic acid-Schiff) stain* - **PAS** stain is used to highlight mucopolysaccharides, basement membranes, and certain cell walls, making it useful for identifying various organisms. - It stains the cell walls of **fungi** and the capsules of some organisms, making it valuable in detecting infections. *Masson Fontana* - **Masson Fontana** stain is primarily used to identify **melanin** pigment in tissues. - While it is not a standard organism identification stain in routine renal transplant pathology, specialized silver-based modifications have been described for detecting certain fungal organisms in research settings. - However, it is not considered a primary stain for organism identification in clinical practice. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 268-269. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 533-534.

Question 6: Histopathological features of granulosa cell tumor include all except:

A. CA-125 positivity (Correct Answer)
B. Microfollicular pattern
C. Coffee bean nuclei
D. Call-Exner bodies

Explanation: ***CA-125 positivity*** - **CA-125** is a **serum marker** predominantly associated with **epithelial ovarian cancer** (especially serous carcinoma), not a histopathological feature visible on microscopy. - It is not typically expressed by granulosa cell tumors (GCTs), which are sex cord-stromal tumors that produce **Inhibin** as their characteristic serum marker [1]. - **This is NOT a histopathological feature** but rather a laboratory/serological test, making it the correct answer to this "EXCEPT" question. *Incorrect: Microfollicular pattern* - Granulosa cells arrange themselves in **microfollicular or macrofollicular patterns**, creating small cystic spaces that are a key architectural feature [1]. - This pattern of growth is one of the characteristic **histopathological findings** seen on routine microscopy of adult GCTs. *Incorrect: Coffee bean nuclei* - This describes the characteristic appearance of tumor cell nuclei with **longitudinal grooves or infoldings**, giving them a distinct **'coffee bean'** appearance [1]. - This unique **nuclear morphology** is a classic and essential **histopathological feature** observed on H&E staining for diagnosis of GCT [1]. *Incorrect: Call-Exner bodies* - These are **small rosette-like structures** with central cystic spaces filled with eosinophilic material, formed by granulosa cells arranged in a circular pattern [1]. - Their presence is a **pathognomonic microscopic feature** of adult GCTs and represents follicular differentiation seen in these sex cord-stromal tumors [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1036-1037.

Question 7: Caspase-1 mediated cell death with inflammation is known as

A. Pyroptosis (Correct Answer)
B. Necroptosis
C. Necrosis
D. Ferroptosis

Explanation: ***Pyroptosis*** - This form of programmed cell death is characterized by the formation of an **inflammasome** complex [2], activating **Caspase-1** [1]. - Caspase-1 activation leads to the cleavage of pro-IL-1$\beta$ and pro-IL-18 into their active forms, resulting in a highly **inflammatory** process and cell lysis [1]. *Necroptosis* - This programmed, but non-apoptotic, cell death is mediated by the **RIPK1/RIPK3/MLKL** signaling pathway, involving receptor-interacting protein kinases [1]. - It is morphologically similar to necrosis but can be pharmacologically inhibited; it is **Caspase-independent** [3]. *Ferroptosis* - Ferroptosis is a form of regulated necrosis driven by **iron-dependent lipid peroxidation**. - It is characterized by the accumulation of reactive oxygen species and is typically **Caspase-independent**. *Necrosis* - Necrosis is an uncontrolled, **non-programmed** form of cell death resulting from acute cellular injury or pathology (e.g., ischemia). - It involves cell swelling, rupture of the plasma membrane, and leakage of cellular contents, leading to massive local inflammation, but is **not directly mediated by Caspase-1**. **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, p. 71. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, p. 196. [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. 69-71.

Question 8: Least common finding in diabetic kidney is

A. Podocyte loss
B. GBM thickening
C. Armanni-Ebstein (Correct Answer)
D. Mesangial widening

Explanation: ***Armanni-Ebstein*** - **Armanni-Ebstein lesion** (also known as Armanni-Ebstein change) refers to severe **glycogen accumulation** in the tubular epithelial cells, typically the proximal tubules. - This finding is relatively rare and seen mainly in cases of **poorly controlled acute diabetes mellitus** or acute hyperglycemia, making it the least common routine finding compared to the other structural changes. ***Podocyte loss*** - **Podocyte injury (podocytopathy)** and subsequent loss are a central and early feature in the pathogenesis of diabetic nephropathy, leading to **proteinuria**. - Progressive effacement, detachment, and eventual depletion of these highly specialized cells are constant findings in established **diabetic kidney disease (DKD)**. ***Mesangial widening*** - **Mesangial expansion/widening** is considered the earliest and most specific histological change in **diabetic nephropathy**. - This pathology progresses, leading eventually to **diffuse or nodular glomerulosclerosis** (**Kimmelstiel-Wilson lesions**), making it a universal finding in established DKD. ***GBM thickening*** - **Glomerular basement membrane (GBM) thickening** occurs very early in **diabetic nephropathy**, often preceding clinical proteinuria [1]. - It is a consistent and measurable structural abnormality caused by increased synthesis and altered composition of **extracellular matrix** components in the GBM [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1119-1121. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 907-908.