Neoplasia — MCQs

A 3-year-old boy is admitted to the hospital with signs of acute renal failure. Radiologic studies reveal that the boy has bilateral masses involving both kidneys. Examination of biopsy material confirms the diagnosis of Wilms tumor. Which of the following gene mutations is the most common in Wilms tumor?

Neoplasia Indian Medical PG Practice Questions and MCQs

Question 41: A malignant tumor of childhood that metastasizes to bone most often is:

A. Wilms' tumor
B. Neuroblastoma (Correct Answer)
C. Adrenal gland tumor
D. Granulosa cell tumor of ovary

Explanation: **Explanation:** **Neuroblastoma** is the most common extracranial solid tumor of childhood, arising from primordial neural crest cells [1]. It is notorious for its aggressive nature and early hematogenous spread. 1. **Why Neuroblastoma is correct:** Approximately 70% of patients have metastatic disease at the time of diagnosis. The most common sites of metastasis are the **bone (specifically the skull and orbit)** and bone marrow, followed by the liver and skin. A classic clinical presentation is "Proptosis and Periorbital Ecchymosis" (Raccoon eyes) due to orbital bone metastasis. 2. **Why the other options are incorrect:** * **Wilms’ tumor (Nephroblastoma):** While it is the most common renal tumor in children [1], it primarily metastasizes to the **lungs**. Bone metastasis is extremely rare in Wilms’ tumor (unlike Clear Cell Sarcoma of the Kidney, which is known as the "Bone-seeking tumor"). * **Adrenal gland tumor:** While neuroblastoma often arises in the adrenal medulla [1][2], "adrenal gland tumor" is a broad term. Adrenocortical carcinomas are rare in children and do not share the same high predilection for bone metastasis as neuroblastoma. * **Granulosa cell tumor:** This is a sex cord-stromal tumor. In children (juvenile type), it usually presents with precocious puberty due to estrogen secretion and rarely metastasizes to bone. **High-Yield NEET-PG Pearls:** * **Homer-Wright Rosettes:** Characteristic histological finding (also seen in Medulloblastoma and Ewing’s Sarcoma). * **Markers:** Elevated urinary catecholamines (VMA and HVA) and Neuron-Specific Enolase (NSE) [1][2]. * **Genetic Marker:** **N-myc amplification** is the most important poor prognostic factor. * **Opsoclonus-Myoclonus Syndrome:** A classic paraneoplastic syndrome associated with neuroblastoma ("dancing eyes, dancing feet"). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 483-484, 486. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 419-420.

Question 42: Infantile polycythemia is seen in which of the following conditions?

A. Cerebellar hemangioma (Correct Answer)
B. Retinoblastoma
C. Hepatoblastoma
D. All of the above

Explanation: **Explanation:** The correct answer is **Cerebellar hemangioma** (specifically, Capillary Hemangioblastoma). **1. Why Cerebellar Hemangioma is correct:** Cerebellar hemangioblastomas are highly vascular tumors often associated with **von Hippel-Lindau (VHL) syndrome** [2]. These tumors have the unique ability to produce **Erythropoietin (EPO)** ectopically. This leads to secondary polycythemia (erythrocytosis), characterized by an increased red blood cell count [1]. When these tumors occur in infants or young children, they present as infantile polycythemia. **2. Why the other options are incorrect:** * **Retinoblastoma:** While also a common childhood ocular tumor (and associated with the RB1 gene), it does not secrete erythropoietin and is not associated with polycythemia. * **Hepatoblastoma:** This is the most common liver tumor in children. While some liver tumors (like Hepatocellular Carcinoma in adults) can cause paraneoplastic polycythemia, it is not a classic or defining feature of infantile hepatoblastoma. **3. Clinical Pearls for NEET-PG:** * **Paraneoplastic Polycythemia (The "Potentially High" mnemonic):** Remember the tumors that secrete EPO: **P**heochromocytoma, **R**enal Cell Carcinoma (RCC), **H**epatocellular Carcinoma (HCC), and **H**emangioblastoma. * **VHL Syndrome:** Always look for the triad of Cerebellar hemangioblastoma, Retinal angiomas, and Renal Cell Carcinoma (clear cell type) [2]. * **Histology:** Hemangioblastomas are characterized by "foamy cells" (stromal cells) and a rich network of thin-walled capillaries. * **Differential:** If a question mentions polycythemia with a renal mass in a child, think of **Wilms Tumor** (though rare, it can also secrete EPO). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 663-664. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 724-725.

Question 43: What is the wasting syndrome associated with cancer?

A. Achalasia
B. Cachexia (Correct Answer)
C. Atelectasis
D. Cacogeusia

Explanation: **Explanation:** **Cancer Cachexia** is a paraneoplastic syndrome characterized by a progressive loss of body fat and lean muscle mass, accompanied by profound weakness, anorexia, and anemia [1]. Unlike simple starvation, cachexia cannot be reversed by increased caloric intake because it is driven by a systemic inflammatory response [2]. * **Mechanism:** It is primarily mediated by cytokines like **TNF-alpha** (historically called 'Cachectin'), **IL-6**, and **PIF (Proteolysis Inducing Factor)** [2]. These factors increase the basal metabolic rate and activate the **ubiquitin-proteasome pathway**, leading to the degradation of skeletal muscle proteins. **Analysis of Incorrect Options:** * **Achalasia:** A failure of the lower esophageal sphincter to relax, leading to difficulty swallowing (dysphagia). * **Atelectasis:** The collapse or closure of a lung resulting in reduced or absent gas exchange. * **Cacogeusia:** A bad taste in the mouth, often described as metallic or foul, which can be a side effect of chemotherapy but is not a wasting syndrome. **NEET-PG High-Yield Pearls:** * **TNF-alpha** is the chief mediator of cachexia (produced by macrophages) [2]. * Cachexia is most commonly associated with **Pancreatic** and **Gastric** cancers. * It is responsible for approximately **20-30% of cancer-related deaths**, often due to the failure of respiratory muscles. * **Key distinction:** In starvation, the body preserves muscle and loses fat; in cachexia, both are lost simultaneously due to metabolic derangement [2]. **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. 235-236. [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, pp. 47-49.

Question 44: Which of the following is NOT a characteristic of breast papilloma?

A. Myoepithelial cells present
B. Apocrine metaplasia is seen
C. Hyperplasia of adjacent ducts
D. Regular polarized gland pattern (Correct Answer)

Explanation: **Explanation:** The core concept in differentiating benign from malignant breast lesions is the preservation of the **dual cell layer**. **Why Option D is the Correct Answer:** A **"Regular polarized gland pattern"** is a hallmark of **well-differentiated adenocarcinoma** (malignancy), not benign papilloma. In benign lesions like intraductal papilloma, the architecture consists of branching fibrovascular cores covered by two layers of cells (epithelial and myoepithelial) [1]. The growth is often complex and crowded, lacking the organized, uniform, and polarized glandular arrangement seen in low-grade carcinomas. **Analysis of Incorrect Options:** * **A. Myoepithelial cells present:** This is a defining feature of benign breast lesions. The presence of a basal myoepithelial layer (highlighted by p63 or SMA stains) excludes malignancy [1]. * **B. Apocrine metaplasia:** This is a common reactive change seen in benign breast conditions, including papillomas and fibrocystic changes. Its presence strongly favors a benign diagnosis. * **C. Hyperplasia of adjacent ducts:** Intraductal papillomas are frequently associated with other proliferative breast changes, such as usual ductal hyperplasia (UDH) in the surrounding terminal duct lobular units. **High-Yield NEET-PG Pearls:** * **Clinical Presentation:** Intraductal papilloma is the most common cause of **bloody nipple discharge**. * **Location:** Solitary papillomas are usually **subareolar** (large ducts), while multiple papillomas are peripheral and carry a higher risk of subsequent carcinoma. * **Key Diagnostic Marker:** Loss of the myoepithelial layer is the "gold standard" for diagnosing invasive carcinoma. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 446-447.

Question 45: Which of the following oncogenes functions as a growth factor?

A. fos
B. myc
C. jun
D. sis (Correct Answer)

Explanation: **Explanation:** The correct answer is **D. sis**. To understand this, one must categorize oncogenes based on their functional role in the cell signaling pathway: growth factors, growth factor receptors, signal transducers, or nuclear transcription factors [1]. **1. Why 'sis' is correct:** The **sis oncogene** (derived from Simian Sarcoma Virus) encodes the **Platelet-Derived Growth Factor (PDGF)-β chain** [1]. When this oncogene is overexpressed, the cell produces excessive amounts of PDGF, which acts in an autocrine fashion to stimulate continuous cell proliferation. This is classically associated with tumors like **astrocytomas** and **osteosarcomas** [1]. **2. Why other options are incorrect:** * **A, B, and C (fos, myc, jun):** These are all **nuclear transcription factors**. They act at the final stage of the signaling pathway, binding to DNA to initiate the cell cycle (transition from G0/G1 to S phase). * **myc** is the most high-yield transcription factor, associated with Burkitt Lymphoma (c-myc), Neuroblastoma (n-myc), and Small Cell Carcinoma of the Lung (l-myc) [2]. * **fos and jun** often dimerize to form the AP-1 transcription factor complex. **Clinical Pearls for NEET-PG:** * **Growth Factor Receptor:** *ERBB2* (HER2/neu) in breast cancer and *RET* in MEN 2A/2B [1]. * **Signal Transducers:** *RAS* (GTP-binding protein) is the most common mutated proto-oncogene in human tumors. *ABL* (non-receptor tyrosine kinase) is seen in CML (t:9,22). * **Cell Cycle Regulators:** *Cyclin D1* (Mantle cell lymphoma) and *CDK4* (Melanoma) [2]. * **Rule of Thumb:** If the oncogene name is short (3 letters) and starts with 'm', 'f', or 'j', it is usually a transcription factor. If it is *sis*, think "Secreted" (Growth Factor). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 292. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 296-297.

Question 46: Which of the following sites are predisposed to carcinoma due to smoking?

A. Bladder, Buccal mucosa, Stomach (Correct Answer)
B. Bladder, Buccal mucosa, Breast
C. Bladder, Ovary, Breast
D. Ovary, Buccal mucosa, Stomach

Explanation: **Explanation:** Tobacco smoking is a potent multi-organ carcinogen containing over 60 known carcinogens (such as polycyclic aromatic hydrocarbons and nitrosamines) [1]. The correct answer is **A** because smoking has a well-established causal relationship with malignancies in these three systems: 1. **Buccal Mucosa:** Direct contact with tobacco smoke and chewing tobacco causes field cancerization, leading to squamous cell carcinoma [2]. 2. **Bladder:** Carcinogens (specifically **Beta-naphthylamine**) are absorbed into the bloodstream, filtered by the kidneys, and stored in the bladder, leading to **Urothelial (Transitional Cell) Carcinoma** [1], [2]. 3. **Stomach:** Smoking is a recognized risk factor for gastric adenocarcinoma (particularly the intestinal type) as nitrosamines are swallowed and irritate the gastric mucosa [1]. **Analysis of Incorrect Options:** * **Breast Cancer:** While some studies suggest a marginal link, smoking is not considered a primary or definitive "predisposing" risk factor for breast cancer in the same way it is for the respiratory or urinary tracts [4]. * **Ovarian Cancer:** Most subtypes of ovarian cancer are not linked to smoking. The only exception is **Mucinous ovarian carcinoma**, but it is not a generalized risk for all ovarian malignancies. **NEET-PG High-Yield Pearls:** * **Most common site** associated with smoking: **Lung** (Small cell and Squamous cell carcinoma) [3], [4]. * **Pancreas:** Smoking is the most common environmental risk factor for pancreatic cancer [2]. * **Kidney:** Smoking doubles the risk of Renal Cell Carcinoma (RCC). * **Cervix:** Smoking is a co-factor with HPV for Squamous Cell Carcinoma of the cervix. * **Key Carcinogen:** Polycyclic aromatic hydrocarbons (like Benzopyrene) are primarily responsible for lung cancer, while Arylamines are linked to bladder cancer [1], [2]. **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. 217-218. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 423-424. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lung, pp. 720-721. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lung, pp. 719-720.

Question 47: Somatic mutation E17K in the PH domain of the AKT-1 gene is associated with which type of cancer?

A. Stomach cancer
B. Breast cancer (Correct Answer)
C. Ovarian cancer
D. Pancreatic cancer

Explanation: ### Explanation **Correct Option: B (Breast cancer)** The **AKT1** gene encodes a serine-threonine kinase that plays a pivotal role in the **PI3K/AKT/mTOR pathway**, which regulates cell growth, proliferation, and survival [1]. The specific somatic mutation **E17K** involves a substitution of glutamic acid (E) with lysine (K) at position 17 within the **Pleckstrin Homology (PH) domain**. This mutation results in the constitutive recruitment of AKT1 to the plasma membrane, leading to its permanent activation independent of upstream growth factor signaling [1]. While this mutation is found in various solid tumors, it is most characteristically associated with **Breast cancer** (specifically ER-positive/ductal subtypes), as well as endometrial and colorectal cancers. **Analysis of Incorrect Options:** * **A. Stomach cancer:** Gastric cancers are more frequently associated with mutations in *CDH1* (E-cadherin), *HER2/neu* amplification, or microsatellite instability (MSI). * **C. Ovarian cancer:** While the PI3K pathway is often altered in ovarian cancer, it usually occurs via *PIK3CA* mutations or *PTEN* loss rather than the specific AKT1 E17K mutation. * **D. Pancreatic cancer:** The hallmark mutation in >90% of pancreatic adenocarcinomas is in the **KRAS** oncogene [2]. **High-Yield Clinical Pearls for NEET-PG:** * **PI3K/AKT Pathway:** This is the most frequently mutated pathway in human neoplasia [1]. * **PTEN:** A key tumor suppressor that acts as a "brake" on this pathway by dephosphorylating PIP3 [1]. Loss of PTEN is common in **Endometrial carcinoma**. * **Cowden Syndrome:** Germline mutations in *PTEN* lead to this syndrome, characterized by multiple hamartomas and an increased risk of breast and thyroid cancer. * **Targeted Therapy:** AKT inhibitors are currently being researched as therapeutic agents for tumors harboring the E17K mutation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 294-295. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Pancreas, pp. 898-899.

Question 48: All are malignant tumors, except:

A. Chloroma
B. Fibromatosis (Correct Answer)
C. Askin's tumor
D. Liposarcoma

Explanation: **Explanation:** The core concept tested here is the distinction between **locally aggressive/borderline lesions** and **frankly malignant tumors**. **Why Fibromatosis is the correct answer:** **Fibromatosis** (specifically Desmoid tumors) is a group of fibroblastic proliferations that are **locally aggressive** and infiltrative but **do not metastasize** [2]. In pathology, they are classified as "intermediate" or "borderline" lesions rather than malignant. They lack the cellular features of malignancy (like high mitotic figures or nuclear pleomorphism) but are notorious for high local recurrence rates after excision. **Analysis of Incorrect Options:** * **Chloroma (Granulocytic Sarcoma):** This is a solid collection of leukemic cells (Myeloblasts) occurring outside the bone marrow. It is a **malignant** manifestation of Acute Myeloid Leukemia (AML) [1]. * **Askin’s Tumor:** This is a **malignant** small round blue cell tumor belonging to the Ewing Sarcoma family, specifically occurring in the chest wall. It is highly aggressive. * **Liposarcoma:** This is the most common soft tissue **malignancy** in adults [2]. It is a malignant tumor of adipocytes (fat cells) [3]. **NEET-PG High-Yield Pearls:** * **The "Oma" Trap:** While most malignant tumors end in "-sarcoma" or "-carcinoma," remember the exceptions that end in "-oma" but are **malignant**: Lymphoma, Melanoma, Mesothelioma, Seminoma, and Chloroma [1]. * **Fibromatosis Associations:** Deep fibromatosis (Desmoid tumor) is strongly associated with **Gardner Syndrome** (a variant of FAP) and mutations in the **APC or CTNNB1 (β-catenin)** genes. * **Askin's Tumor Marker:** Like Ewing Sarcoma, it typically shows **t(11;22)** translocation and expresses **CD99 (MIC2)**. **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. 208-209. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1222. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1222-1223.

Question 49: Which of the following is the best example of a proto-oncogene activated by point mutation?

A. Ras (Correct Answer)
B. N-myc
C. L-myc
D. Abl

Explanation: **Explanation:** **Correct Answer: A. Ras** The **Ras gene family** (H-ras, K-ras, N-ras) is the most common example of a proto-oncogene activated by **point mutations**. In its normal state, Ras flips between an active (GTP-bound) and inactive (GDP-bound) state. A single point mutation (most commonly at codons 12, 13, or 61) interferes with GTP hydrolysis, trapping Ras in a permanent "on" position. This leads to continuous mitogenic signaling to the nucleus. **Why the other options are incorrect:** * **B & C. N-myc and L-myc:** These members of the *myc* family are typically activated by **gene amplification** (increased copy number), not point mutations [1]. *N-myc* amplification is a classic prognostic marker in Neuroblastoma, while *L-myc* is associated with Small Cell Carcinoma of the lung. * **D. Abl:** The *c-Abl* proto-oncogene is activated by **balanced translocation**, specifically t(9;22), which forms the BCR-ABL fusion protein (Philadelphia chromosome) characteristic of Chronic Myeloid Leukemia (CML) [1], [2]. **High-Yield Clinical Pearls for NEET-PG:** * **K-ras mutations** are highly associated with **Pancreatic adenocarcinoma** (90%) and Colon cancer. * **H-ras mutations** are linked to Bladder tumors. * **N-ras mutations** are frequently seen in Melanomas and Hematologic malignancies. * **Mechanism Summary:** Ras activation = Point mutation; Myc activation = Amplification/Translocation; Abl activation = Translocation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 292. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 295-296.

Question 50: A 3-year-old boy is admitted to the hospital with signs of acute renal failure. Radiologic studies reveal that the boy has bilateral masses involving both kidneys. Examination of biopsy material confirms the diagnosis of Wilms tumor. Which of the following gene mutations is the most common in Wilms tumor?

A. The gene responsible for WT1 (Correct Answer)
B. The gene responsible for HGF
C. The gene responsible for VEGF
D. The gene responsible for GDNF

Explanation: **Explanation:** **Wilms Tumor (Nephroblastoma)** is the most common primary renal tumor of childhood. The pathogenesis is linked to the disruption of normal renal development, specifically the transformation of the metanephric blastema. **Why Option A is Correct:** The **WT1 gene**, located on chromosome **11p13**, is the most frequently implicated gene in the development of Wilms tumor [1]. It encodes a transcription factor essential for normal renal and gonadal development. Mutations or deletions of WT1 are found in approximately 20% of sporadic Wilms tumors and are classically associated with syndromic cases such as **WAGR syndrome** (Wilms tumor, Aniridia, Genitourinary anomalies, and Range of developmental delays) and **Denys-Drash syndrome** [1]. **Why Incorrect Options are Wrong:** * **HGF (Hepatocyte Growth Factor):** While involved in mesenchymal-epithelial interactions during kidney development, it is not a primary driver mutation for Wilms tumor. * **VEGF (Vascular Endothelial Growth Factor):** This is a pro-angiogenic factor. While tumors utilize VEGF for blood supply, it is not the causative genetic mutation for nephroblastoma. * **GDNF (Glial Cell Line-Derived Neurotrophic Factor):** GDNF plays a role in ureteric bud branching during embryogenesis, but mutations are not a standard feature of Wilms tumor pathogenesis. **High-Yield Clinical Pearls for NEET-PG:** * **Triphasic Histology:** Characterized by Blastemal, Stromal, and Epithelial cells. * **Beckwith-Wiedemann Syndrome (BWS):** Associated with the **WT2** locus (11p15.5), characterized by macroglossia, organomegaly, and hemihypertrophy. * **Clinical Presentation:** Usually presents as a large, palpable abdominal mass that **does not cross the midline** (unlike Neuroblastoma). * **Prognostic Marker:** The presence of **anaplasia** (TP53 mutation) is the most important indicator of poor prognosis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 487-488.

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