Neoplasia — MCQs

Neoplasia Indian Medical PG Practice Questions and MCQs

Question 221: Malignancies associated with BRCA 1 and 2 include all of the following except?

A. Breast cancer
B. Prostate cancer
C. Papillary serous carcinoma of peritoneum
D. Mesothelioma (Correct Answer)

Explanation: **Explanation:** The **BRCA1 and BRCA2** genes are tumor suppressor genes involved in the repair of double-stranded DNA breaks via **homologous recombination**. Mutations in these genes lead to genomic instability, significantly increasing the risk of various malignancies. **Why Mesothelioma is the correct answer:** **Mesothelioma** is primarily associated with **asbestos exposure** [1] and mutations in the **BAP1 gene** (BRCA1-associated protein 1), not the BRCA1/2 genes themselves. While BAP1 is part of the same molecular pathway, standard BRCA1/2 germline mutations are not established risk factors for mesothelioma. **Analysis of other options:** * **Breast Cancer:** This is the most common association. BRCA1 carries a higher lifetime risk (up to 80%) [3] and is often associated with "triple-negative" tumors, while BRCA2 is associated with ER-positive tumors and **male breast cancer**. * **Prostate Cancer:** BRCA2 mutations, in particular, are linked to an increased risk of aggressive, high-grade prostate cancer in men. * **Papillary Serous Carcinoma of Peritoneum:** BRCA mutations predispose individuals to serous carcinomas of the "Müllerian" spectrum, which includes the ovaries, fallopian tubes, and the primary peritoneum. **High-Yield Clinical Pearls for NEET-PG:** * **Chromosome Locations:** BRCA1 is on **Ch 17q**, and BRCA2 is on **Ch 13q**. * **Pancreatic Cancer:** BRCA2 is a significant risk factor for familial pancreatic adenocarcinoma [2]. * **Ovarian Cancer:** BRCA1 carries a higher risk (approx. 40%) compared to BRCA2 (approx. 15%). * **Synthetic Lethality:** Tumors with BRCA mutations are highly sensitive to **PARP inhibitors** (e.g., Olaparib). **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. 221-222. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Pancreas, pp. 898-899. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1058-1060.

Question 222: Which gene is involved in Retinoblastoma?

A. 12P13
B. 13P14
C. 12Q13
D. 13Q14 (Correct Answer)

Explanation: **Explanation:** The **RB1 gene**, the first tumor suppressor gene ever discovered, is located on the long arm of **chromosome 13 at region 1, band 4 (13q14)** [1]. **1. Why 13q14 is correct:** The RB1 gene encodes the pRB protein, which acts as a critical "brake" on the cell cycle [3]. It prevents the transition from the G1 to the S phase by binding and sequestering the **E2F transcription factor** [4]. When both alleles of the RB1 gene are inactivated (Knudson’s "Two-Hit" Hypothesis), E2F is released, leading to uncontrolled cell proliferation and the development of Retinoblastoma [1], [2]. **2. Analysis of Incorrect Options:** * **12p13:** This locus is associated with the *ETV6* gene, often involved in leukemias (e.g., ETV6-RUNX1 translocation in ALL). * **13p14:** This refers to the short arm (p) of chromosome 13. The RB1 gene is specifically located on the long arm (q). * **12q13:** This locus is associated with the *MDM2* gene (an inhibitor of p53) and is frequently amplified in well-differentiated liposarcomas. **3. High-Yield Clinical Pearls for NEET-PG:** * **Knudson’s Two-Hit Hypothesis:** In familial cases, the first hit is germline (inherited), and the second is somatic. In sporadic cases, both hits are somatic [1]. * **Histology:** Look for **Flexner-Wintersteiner rosettes** (pathognomonic) and **Homer Wright rosettes**. * **Clinical Sign:** The most common presenting sign is **Leukocoria** (white pupillary reflex). * **Secondary Tumors:** Patients with germline RB1 mutations have a high risk of developing **Osteosarcoma** later in life. * **Trilateral Retinoblastoma:** Bilateral retinoblastoma associated with a pineal tumor (Pineoblastoma). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 300. [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. 227-228. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 297-298. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 300-301.

Question 223: Russel bodies are seen in which of the following conditions?

A. Multiple Myeloma (Correct Answer)
B. Rabies
C. Parkinsonism
D. Intracranial neoplasm

Explanation: **Explanation:** **Russell bodies** are large, eosinophilic, homogeneous immunoglobulin inclusions found within the cytoplasm of plasma cells. They represent an accumulation of newly synthesized immunoglobulins in the **Rough Endoplasmic Reticulum (RER)**, occurring when the rate of protein synthesis exceeds the cell's capacity to secrete them. This is a classic example of intracellular protein accumulation. * **Option A (Correct):** In **Multiple Myeloma**, there is a neoplastic proliferation of plasma cells producing excessive monoclonal antibodies [1]. These cells frequently exhibit Russell bodies. When these inclusions are found within the nucleus, they are termed **Dutcher bodies**. * **Option B (Incorrect):** Rabies is characterized by **Negri bodies**, which are eosinophilic cytoplasmic inclusions found in pyramidal cells of the hippocampus and Purkinje cells of the cerebellum. * **Option C (Incorrect):** Parkinsonism is associated with **Lewy bodies**, which are eosinophilic cytoplasmic inclusions containing alpha-synuclein found in the neurons of the substantia nigra. * **Option D (Incorrect):** While various inclusions exist in CNS tumors (e.g., Psammoma bodies in Meningiomas), Russell bodies are not a characteristic feature of intracranial neoplasms. **High-Yield Clinical Pearls for NEET-PG:** * **Mott Cells:** A plasma cell containing multiple Russell bodies is called a "Mott cell" or "Grape cell." * **Dutcher vs. Russell:** Remember: **R**ussell = **R**ER (Cytoplasm); **D**utcher = **D**irectly in nucleus. * **Flame Cells:** Bright red cytoplasm in plasma cells (seen in IgA Myeloma) [2]. * **Bence-Jones Proteins:** Free light chains excreted in the urine of Myeloma patients, which precipitate at 40-60°C and redissolve at 100°C [1], [2]. **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. 606-608. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 616-619.

Question 224: Which of the following is the most common tumor of the fetus and newborn?

A. Neuroblastoma
B. Wilm's tumor
C. Leukemia
D. Sacrococcygeal teratoma (Correct Answer)

Explanation: **Explanation:** **Sacrococcygeal Teratoma (SCT)** is the most common tumor of the fetus and newborn [1], occurring in approximately 1 in 20,000 to 40,000 live births [1]. These tumors arise from the **totipotent cells** of the primitive streak (Hensen’s node) that fail to migrate or involute. They are more common in females (4:1 ratio) [1]. While most are benign (mature), the risk of malignancy increases with age at diagnosis. **Analysis of Incorrect Options:** * **Neuroblastoma:** This is the most common **extracranial solid tumor of childhood** and the most common malignancy in infants (under 1 year), but it is not more frequent than SCT in the immediate neonatal/fetal period. * **Wilms Tumor (Nephroblastoma):** This is the most common **primary renal tumor of childhood**, typically presenting between ages 2 and 5. It is rare in the neonatal period. * **Leukemia:** While leukemia is the most common childhood cancer overall, it is not the most common tumor at birth. Congenital leukemia is a rare entity. **High-Yield Clinical Pearls for NEET-PG:** * **Altman Classification:** Used for SCT based on the location (Type I is predominantly external; Type IV is entirely presacral/internal). * **Tumor Markers:** Elevated **Alpha-fetoprotein (AFP)** in a teratoma often suggests a yolk sac component (malignancy). * **Associated Complication:** Large fetal SCTs can cause **high-output cardiac failure** and hydrops fetalis due to significant vascular shunting (steal phenomenon). * **Most common malignancy in infants:** Neuroblastoma. * **Most common childhood cancer:** Acute Lymphoblastic Leukemia (ALL). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 482-483.

Question 225: Tumor arising from a totipotent cell is:

A. Teratoma (Correct Answer)
B. Seminoma
C. Myoma
D. Lipoma

Explanation: **Explanation:** **1. Why Teratoma is the Correct Answer:** A **Teratoma** is a germ cell tumor derived from **totipotent cells** (typically found in the ovary or testis) [1]. Totipotent cells have the unique capacity to differentiate into any of the three germ layers: **ectoderm, mesoderm, and endoderm** [3]. Consequently, a teratoma characteristically contains a variety of tissues foreign to the organ in which it arises, such as hair, teeth (ectoderm), muscle, bone (mesoderm), and gut epithelium (endoderm) [2]. **2. Analysis of Incorrect Options:** * **Seminoma (Option B):** While this is also a germ cell tumor, it is composed of a single, uniform population of undifferentiated germ cells [5]. It does not exhibit the multi-lineage differentiation characteristic of totipotent cells. * **Myoma (Option C):** This is a benign tumor of muscle tissue (e.g., Leiomyoma from smooth muscle). It is a specialized mesenchymal tumor, not derived from totipotent cells. * **Lipoma (Option D):** This is a benign tumor of adipocytes (fat cells). Like myoma, it is a differentiated mesenchymal tumor. **3. NEET-PG High-Yield Pearls:** * **Classification:** Teratomas are classified into **Mature** (well-differentiated, usually benign in females) and **Immature** (contains fetal/neuroepithelial tissue, potentially malignant) [3]. * **Monodermal Teratomas:** Highly specialized forms include **Struma ovarii** (composed of thyroid tissue) and **Carcinoid** [4]. * **Most Common Site:** The most common location for a teratoma in infants is the **sacrococcygeal region**. * **Dermoid Cyst:** A common term for a mature cystic teratoma of the ovary, typically lined by skin-like structures [1]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Female Genital Tract Disease, pp. 480-481. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 276. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1033-1034. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, p. 1034. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 979-980.

Question 226: Which of the following malignancies is associated with the characteristic Zellballen pattern on histopathology?

A. Gastrointestinal stromal tumor
B. Astrocytoma
C. Carotid body tumor (Correct Answer)
D. Retinoblastoma

Explanation: **Explanation:** The correct answer is **C. Carotid body tumor**. **1. Why Carotid Body Tumor is correct:** A carotid body tumor is a type of **paraganglioma** (extra-adrenal pheochromocytoma) [1]. The characteristic histopathological hallmark of paragangliomas is the **Zellballen pattern**. This consists of nests or clusters of round-to-oval neuroendocrine cells (Chief cells) surrounded by a delicate vascular stroma and peripheral spindle-shaped sustentacular cells. The term "Zellballen" is German for "cell balls." **2. Why other options are incorrect:** * **A. Gastrointestinal stromal tumor (GIST):** Characterized by bundles of spindle cells or epithelioid cells. The diagnostic marker is **CD117 (c-KIT)**. * **B. Astrocytoma:** Low-grade astrocytomas show a fibrillary background; high-grade (GBM) shows pseudopalisading necrosis. They do not form nested patterns. * **C. Retinoblastoma:** Characterized by **Flexner-Wintersteiner rosettes** (true rosettes with a central lumen) and Homer Wright rosettes. **3. High-Yield Clinical Pearls for NEET-PG:** * **Location:** Carotid body tumors occur at the bifurcation of the common carotid artery [1]. * **Clinical Sign:** **Fontaine’s Sign** – The mass is mobile horizontally but fixed vertically (due to its attachment to the carotid artery). * **Immunohistochemistry (IHC):** Chief cells are positive for **Synaptophysin/Chromogranin**, while Sustentacular cells are positive for **S-100**. * **Rule of 10s:** While traditionally associated with pheochromocytoma, remember that carotid body tumors are the most common head and neck paragangliomas [1]. * **Salt and Pepper Chromatin:** A common feature of neuroendocrine tumors, including the cells within the Zellballen nests. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Head and Neck, pp. 748-749.

Question 227: Which tumor suppressor gene is primarily responsible for lung squamous cell carcinoma?

A. p53 (Correct Answer)
B. Rb
C. PTEN
D. p63

Explanation: **Explanation:** **Correct Answer: A. p53** The **TP53 gene** (located on chromosome 17p) is the most frequently mutated gene in human cancers [3]. In the context of lung cancer, p53 mutations are strongly associated with exposure to tobacco smoke [2]. It is found in over **90% of Small Cell Lung Carcinomas (SCLC)** and approximately **50-80% of Squamous Cell Carcinomas (SCC)** [1]. The mutation often occurs early in the pathogenesis of squamous cell carcinoma, following the initial stages of squamous metaplasia and dysplasia [1]. **Analysis of Incorrect Options:** * **B. Rb (Retinoblastoma gene):** While Rb mutations are nearly universal in **Small Cell Lung Carcinoma (SCLC)** (approx. 90%), they are less frequent in Squamous Cell Carcinoma compared to p53 [1]. * **C. PTEN:** This tumor suppressor is more classically associated with **Endometrial carcinoma**, Glioblastoma, and Prostate cancer. In the lung, it is less common than p53 or CDKN2A mutations. * **D. p63:** This is not a tumor suppressor gene responsible for the *initiation* of the cancer; rather, it is a **diagnostic immunohistochemical (IHC) marker**. p63 (along with CK5/6 and P40) is used to confirm the squamous lineage of a poorly differentiated lung tumor. **High-Yield Clinical Pearls for NEET-PG:** * **Squamous Cell Carcinoma (SCC):** Centrally located, associated with smoking, and may cause **Hypercalcemia** (due to PTHrP production). * **Adenocarcinoma:** Most common type in **non-smokers** and females; typically peripheral; associated with **EGFR** and **ALK** mutations. * **Small Cell Carcinoma:** Strongest link to smoking; neuroendocrine origin; associated with **p53 and Rb** mutations [1]. * **Molecular Marker for SCC:** Loss of **CDKN2A (p16)** is also a very common early event in lung SCC [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lung, p. 721. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 331-332. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 301-302.

Question 228: Microdeletion leading to instability of DNA, causing the cell to undergo degeneration, is seen as a marker in which of the following cancers?

A. Medullary carcinoma of thyroid
B. Small cell lung cancer
C. Gastric lymphoma
D. Colon carcinoma (Correct Answer)

Explanation: ### Explanation The correct answer is **Colon carcinoma**. The question refers to **Microsatellite Instability (MSI)**, a hallmark of the **Mismatch Repair (MMR) pathway** defect [1]. Microsatellites are short, repetitive DNA sequences prone to errors (insertions or deletions) during replication. Normally, MMR genes (MLH1, MSH2, MSH6, PMS2) correct these errors [1]. A deficiency in these genes leads to the accumulation of mutations (microdeletions/instability), driving oncogenesis [1]. This is the underlying mechanism in **Lynch Syndrome** (Hereditary Non-Polyposis Colorectal Cancer - HNPCC) and approximately 15% of sporadic colorectal cancers [1], [2]. #### Analysis of Options: * **Colon Carcinoma (Correct):** MSI is a classic molecular marker for colorectal cancer [1]. These tumors often arise in the right colon, show a mucinous histology, and paradoxically have a better prognosis despite being high-grade [1]. * **Medullary Carcinoma of Thyroid:** This is associated with **RET proto-oncogene** mutations (MEN 2A/2B), not DNA repair instability. * **Small Cell Lung Cancer:** Characterized by strong associations with smoking and mutations/deletions in **RB1** and **TP53** genes. * **Gastric Lymphoma:** Most commonly MALToma, which is associated with *H. pylori* infection and specific translocations like **t(11;18)**. #### NEET-PG High-Yield Pearls: * **Lynch Syndrome:** Autosomal dominant; most common mutated genes are **MSH2** and **MLH1** [3]. * **Screening:** MSI status is now routinely tested in colon cancers via immunohistochemistry (IHC) for MMR proteins [1]. * **Prognostic Value:** MSI-High (MSI-H) colorectal cancers generally have a better prognosis but respond poorly to 5-Fluorouracil (5-FU) monotherapy [1]. * **Amsterdam Criteria:** Used clinically to identify families at risk for Lynch Syndrome (3-2-1 rule: 3 relatives, 2 generations, 1 diagnosed before age 50). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 819-821. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Alimentary System Disease, pp. 373-374. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, p. 817.

Question 229: MIC-2 is a marker of?

A. Ewing sarcoma (Correct Answer)
B. Chronic lymphocytic leukemia
C. Mantle cell lymphoma
D. All of these

Explanation: **Explanation:** **MIC-2** (also known as **CD99**) is a cell surface glycoprotein that is highly characteristic of the **Ewing Sarcoma/Primitive Neuroectodermal Tumor (PNET)** family. It is encoded by the *MIC2* gene located on the pseudoautosomal region of the X and Y chromosomes. 1. **Why Ewing Sarcoma is Correct:** In Ewing Sarcoma, MIC-2/CD99 shows a distinctive **strong, diffuse, membranous staining** pattern on immunohistochemistry (IHC). While not 100% specific, it is a highly sensitive marker used to differentiate Ewing sarcoma from other "small round blue cell tumors" of childhood. 2. **Why Other Options are Incorrect:** * **Chronic Lymphocytic Leukemia (CLL):** The hallmark markers for CLL are **CD5, CD19, CD20, and CD23**. MIC-2 is not used for its diagnosis. * **Mantle Cell Lymphoma (MCL):** MCL is characterized by the overexpression of **Cyclin D1** (due to t(11;14)) and markers like **CD5** and **SOX11** [1]. 3. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** Ewing Sarcoma is most commonly associated with **t(11;22)(q24;q12)**, leading to the **EWS-FLI1** fusion gene. * **Radiology:** Classically presents with an **"onion-skin"** periosteal reaction. * **Morphology:** Small round blue cells with scant cytoplasm; **Homer-Wright rosettes** may be seen (indicating neural differentiation). * **Differential Diagnosis:** Other CD99-positive tumors include lymphoblastic lymphoma and synovial sarcoma, but in the context of bone tumors, it strongly points to Ewing's. **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. 610-612.

Question 230: Smoking is most commonly associated with which of the following carcinomas?

A. Liver carcinoma
B. Gall bladder carcinoma
C. Urinary bladder carcinoma (Correct Answer)
D. Stomach carcinoma

Explanation: **Explanation:** **1. Why Urinary Bladder Carcinoma is correct:** Smoking is the most significant risk factor for **Urothelial (Transitional Cell) Carcinoma** of the bladder, accounting for approximately 50% of cases [1]. Cigarettes contain aromatic amines (such as **beta-naphthylamine**) and polycyclic aromatic hydrocarbons [3]. These carcinogens are absorbed into the bloodstream, filtered by the kidneys, and concentrated in the urine [1]. Prolonged contact between these metabolites and the bladder mucosa leads to field cancerization and malignant transformation. **2. Why the other options are incorrect:** * **Liver Carcinoma:** The primary risk factors are chronic Hepatitis B/C infections, cirrhosis, and Aflatoxin exposure. While smoking is a minor cofactor, it is not the primary association. * **Gallbladder Carcinoma:** This is most strongly associated with **cholelithiasis** (gallstones) and "porcelain gallbladder." * **Stomach Carcinoma:** The strongest associations are with *H. pylori* infection, dietary nitrosamines (smoked/salted foods), and genetic factors (CDH1 mutation) [2]. **3. NEET-PG High-Yield Pearls:** * **Most common type:** Smoking specifically increases the risk of **Transitional Cell Carcinoma (TCC)** [1]. * **Occupational Risk:** Workers in the **dye, rubber, and leather industries** are at high risk due to aniline dye exposure [2]. * **Schistosomiasis:** Infection with *S. haematobium* is specifically associated with **Squamous Cell Carcinoma** of the bladder, not TCC [1]. * **Field Cancerization:** This concept explains why patients with bladder cancer are also at risk for synchronous or metachronous tumors in the ureter or renal pelvis. **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. 968-970. [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. 217-218. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 423-424.

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