Neoplasia Practice Questions

Q: BRAF acts as a main proto-oncogene in which of the following conditions?

All of the above. **Explanation:** The **BRAF gene** encodes a protein belonging to the RAF family of serine/threonine kinases. It is a vital component of the **MAPK/ERK signaling pathway**, which regulates cell growth, proliferation, and survival. Mutations in BRAF, most commonly the **V600E mutation** (substitution of valine by glutamic acid at codon 600) [2], lead to constitutive activation of this pathway, driving oncogenesis [1]. **Why "All of the Above" is correct:** * **Hairy Cell Leukemia (HCL):** The BRAF V600E mutation is considered a "defining" genetic event in HCL, present in nearly **100% of cases** [2]. It serves as a critical diagnostic marker to differentiate HCL from other B-cell lymphoproliferative disorders. * **Melanoma:** BRAF mutations are found in approximately **40-60% of cutaneous melanomas** [1]. This discovery led to the development of targeted therapies like Vemurafenib and Dabrafenib. * **Langerhans Cell Histiocytosis (LCH):** BRAF V600E mutations are identified in about **50-60% of LCH cases** [2], establishing it as a neoplastic process rather than a reactive one. **Clinical Pearls for NEET-PG:** 1. **Papillary Thyroid Carcinoma:** BRAF V600E is the most common mutation (approx. 45%) and is often associated with a poorer prognosis. 2. **Colon Cancer:** BRAF mutations are seen in about 10% of cases, typically associated with the **microsatellite instability (MSI)** pathway and serrated polyps. 3. **Targeted Therapy:** The presence of BRAF mutations allows for the use of **BRAF inhibitors** (e.g., Vemurafenib), which have revolutionized the treatment of metastatic melanoma and refractory HCL [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Skin, pp. 1150-1151. [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. 629-630.

Q: Which of the following tumours produces a marked elevation of Alpha fetoprotein?

Alpha fetoprotein. **Explanation:** **Alpha-fetoprotein (AFP)** is a glycoprotein normally synthesized by the fetal liver and yolk sac. In adult pathology, it serves as a highly specific tumor marker for two primary conditions: **Hepatocellular Carcinoma (HCC)** and **Yolk Sac Tumors** (Endodermal Sinus Tumors) [1]. A marked elevation (often >500 ng/mL) is diagnostic of these malignancies in the appropriate clinical context [1]. **Analysis of Options:** * **Placental Alkaline Phosphatase (PLAP):** This is a characteristic marker for **Seminoma** (in males) and **Dysgerminoma** (in females). While useful for diagnosis, it does not correlate with AFP production. * **Human Placental Lactogen (hPL):** This is primarily produced by syncytiotrophoblasts. It is a marker for **Placental Site Trophoblastic Tumors (PSTT)**, not yolk sac-derived tumors. * **CA 125:** This is the classic marker for **Serous Cystadenocarcinoma of the ovary**. It is used for monitoring treatment response rather than primary diagnosis, as it can be elevated in various inflammatory peritoneal conditions. **High-Yield Clinical Pearls for NEET-PG:** * **Yolk Sac Tumor:** Look for **Schiller-Duval bodies** (glomeruloid structures) on histology; AFP is the definitive marker. * **Hepatocellular Carcinoma:** AFP levels correlate with tumor size; however, 20% of HCC cases may be AFP-negative [1]. * **Neural Tube Defects:** AFP is also elevated in maternal serum during pregnancy if the fetus has anencephaly or spina bifida. * **Triple Marker Test:** AFP is *decreased* in Down Syndrome (Trisomy 21). **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 398-400.

Q: A 74-year-old woman has metastatic bone disease on x-ray. Which of the following mediators is least likely to be involved?

ectopic parathyroid hormone (PTH). The primary mechanism behind metastatic bone disease (bone resorption) is the activation of **osteoclasts**. In malignancy, this occurs via local or systemic release of cytokines that stimulate the RANK/RANKL pathway [1]. **Why Ectopic PTH is the Correct Answer:** True **ectopic production of PTH** (the intact hormone) by non-parathyroid tumors is an **extremely rare** clinical entity. While many tumors cause hypercalcemia, they do so by secreting **Parathyroid Hormone-related Protein (PTHrP)**, not native PTH [2]. PTHrP mimics PTH action at the receptor level but is a distinct molecule [2]. Therefore, in the context of metastatic bone disease, ectopic PTH is the least likely mediator. **Analysis of Incorrect Options:** * **IL-1, IL-6, and TNF:** These are potent inflammatory cytokines often referred to as "Osteoclast Activating Factors" (OAFs) [1]. * **IL-1 (Osteoclast Activating Factor):** Directly stimulates osteoclast precursors [1]. * **IL-6:** Frequently secreted by myeloma cells and breast cancer metastases; it induces RANKL expression. * **TNF (Tumor Necrosis Factor):** Synergizes with RANKL to enhance bone resorption and is a key mediator in local bone destruction [1]. **NEET-PG High-Yield Pearls:** 1. **Humoral Hypercalcemia of Malignancy (HHM):** Most commonly caused by **PTHrP** (seen in Squamous cell CA of lung, renal cell CA) [1]. 2. **Local Osteolytic Hypercalcemia:** Driven by **IL-1, TNF-alpha, and IL-6** (seen in Multiple Myeloma and Breast Cancer). 3. **Lab Findings in HHM:** High Calcium, **Low PTH** (suppressed by high Ca2+), and High PTHrP [2]. 4. **1,25-dihydroxyvitamin D:** The mediator of hypercalcemia in **Lymphomas** (due to increased 1-alpha-hydroxylase activity).

Question 1

BRAF acts as a main proto-oncogene in which of the following conditions?

Accepted Answer

All of the above

Answer

Hairy cell leukemia

Answer

Langerhans cell histiocytosis

Answer

Melanoma

Question 2

A child is born with a single functional copy of a tumor suppressor gene. At the age of 5 years, the remaining normal allele is lost through mutation, resulting in the loss of control over the transition from G1 to the S phase of the cell cycle. Which of the following neoplasms is most likely to arise by this mechanism?

Accepted Answer

Retinoblastoma

Answer

Breast carcinoma

Answer

Adenocarcinoma of colon

Answer

Cerebral astrocytoma

Question 3

Carcinomas of all of the following sites metastasize to the vertebral column except?

Accepted Answer

Esophagus

Answer

Breast

Answer

Bronchus

Answer

Prostate

Question 4

BRCA 1 gene is located on which chromosome arm?

Accepted Answer

17q

Answer

11q

Answer

13q

Answer

19q

Question 5

Which of the following tumours produces a marked elevation of Alpha fetoprotein?

Accepted Answer

Alpha fetoprotein

Answer

Placental alkaline phosphatase

Answer

Human placental lactogen

Answer

CA 125

Question 6

Verrucous carcinoma is an:

Accepted Answer

Extremely well differentiated squamous cell carcinoma

Answer

Poorly differentiated squamous cell carcinoma

Answer

Example of condyloma

Answer

An example of adenocarcinoma

Question 7

Which of the following malignancies is not associated with Trousseau's syndrome?

Accepted Answer

Liposarcoma

Answer

Carcinoma of the pancreas

Answer

Carcinoma of the lung

Answer

Carcinoma of the stomach

Question 8

A 74-year-old woman has metastatic bone disease on x-ray. Which of the following mediators is least likely to be involved?

Accepted Answer

ectopic parathyroid hormone (PTH)

Answer

interleukin-6 (IL-6)

Answer

tumor necrosis factor (TNF)

Answer

interleukin-1 (IL-1)

Question 9

Cancer cell survival is enhanced by which of the following mechanisms?

Accepted Answer

Suppression of p53 protein

Answer

Overexpression of the p53 gene

Answer

Bcl-2

Answer

Bax

Question 10

Which of the following is an antibody against tumor cells?

Accepted Answer

MHC-I

Answer

MHC-II

Answer

Anti-viral

Answer

Differentiated antigen

Neoplasia — MCQs

Neoplasia — MCQs

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