Molecular Pathology Practice Questions

Q: The MYD88 L265P mutation is characteristically seen in which of the following hematological malignancies?

Waldenstrom Macroglobulinemia. ### Explanation **Correct Answer: B. Waldenstrom Macroglobulinemia** **Mechanism:** The **MYD88 L265P** mutation is a gain-of-function mutation found in over **90-95%** of patients with Waldenstrom Macroglobulinemia (WM). MYD88 is an adapter protein in the Toll-like receptor (TLR) and Interleukin-1 receptor signaling pathways. The L265P mutation (substitution of proline for leucine at position 265) leads to constitutive activation of the **NF-̀B pathway**, promoting the survival and proliferation of malignant lymphoplasmacytic cells. **Analysis of Incorrect Options:** * **A. Hairy Cell Leukemia:** The hallmark genetic driver here is the **BRAF V600E** mutation (seen in >95% of cases). * **C. Multiple Myeloma:** Characterized by complex cytogenetics, most commonly involving **IGH translocations** [e.g., t(11;14), t(4;14)] or 13q deletions, rather than MYD88 mutations. * **D. Acute Myeloid Leukemia (AML):** Associated with mutations in **FLT3, NPM1, or DNMT3A**, and various chromosomal translocations [e.g., t(8;21), t(15;17)]. **High-Yield Clinical Pearls for NEET-PG:** * **Waldenstrom Macroglobulinemia (WM):** Defined as Lymphoplasmacytic Lymphoma (LPL) with bone marrow involvement and an **IgM monoclonal gammopathy** [1]. * **Clinical Triad:** Hyperviscosity syndrome (visual disturbances, neurological symptoms), hepatosplenomegaly, and lymphadenopathy [1]. * **Diagnostic Clue:** Absence of lytic bone lesions (unlike Multiple Myeloma) and presence of **Dutcher bodies** (intranuclear inclusions of immunoglobulins). * **Therapeutic Target:** The presence of MYD88 mutation makes these patients highly responsive to **Ibrutinib** (a BTK inhibitor). **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. 609-610.

Q: Which of the following mutations is seen in Cowden syndrome?

PTEN mutation. **Explanation:** **Cowden Syndrome** is an autosomal dominant disorder characterized by multiple hamartomas and an increased risk of various malignancies. It is caused by a germline mutation in the **PTEN (Phosphatase and Tensin homolog)** gene located on chromosome 10q23. **PTEN** is a critical tumor suppressor gene that encodes a lipid phosphatase. It acts as a negative regulator of the **PI3K/AKT/mTOR signaling pathway**. When PTEN is mutated or lost, the pathway becomes constitutively active, leading to uncontrolled cell proliferation and survival. Clinically, Cowden syndrome presents with trichilemmomas (skin tumors), oral papillomas, and a high risk of breast, thyroid (follicular), and endometrial carcinomas. **Analysis of Incorrect Options:** * **A. STK 11 mutation:** Associated with **Peutz-Jeghers Syndrome**, characterized by hamartomatous GI polyps and perioral hyperpigmentation. * **B. SMAD 4 mutation:** Associated with **Juvenile Polyposis Syndrome** (along with BMPR1A mutations), which predisposes to gastric and colonic adenocarcinomas. * **D. PTCH mutation:** Associated with **Gorlin Syndrome** (Nevoid Basal Cell Carcinoma Syndrome) [1][2], characterized by multiple basal cell carcinomas, odontogenic keratocysts, and bifid ribs [1][2]. **High-Yield Clinical Pearls for NEET-PG:** * **PTEN** is the most frequently mutated gene in **Endometrial Carcinoma** (Endometrioid type). * Cowden syndrome is part of the **PTEN Hamartoma Tumor Syndrome (PHTS)** spectrum, which also includes Bannayan-Riley-Ruvalcaba syndrome. * **Lhermitte-Duclos disease** (dysplastic gangliocytoma of the cerebellum) is a pathognomonic CNS feature of Cowden syndrome. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 306-307. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Skin, pp. 1157-1158.

Question 1

Apoptosis is inhibited by:

Accepted Answer

Bcl2

Answer

p53

Answer

NMYC

Answer

ras

Question 2

Which type of necrosis is most commonly associated with pyogenic infection and brain infarction?

Accepted Answer

Liquefaction necrosis

Answer

Coagulative necrosis

Answer

Caseous necrosis

Answer

Fat necrosis

Question 3

The MYD88 L265P mutation is characteristically seen in which of the following hematological malignancies?

Accepted Answer

Waldenstrom Macroglobulinemia

Answer

Hairy cell leukemia

Answer

Multiple Myeloma

Answer

Acute Myeloid Leukemia (AML)

Question 4

Which of the following mutations is seen in Cowden syndrome?

Accepted Answer

PTEN mutation

Answer

STK 11 mutation

Answer

SMAD 4 mutation

Answer

PTCH mutation

Question 5

BRCA-1 gene is located on which chromosome?

Accepted Answer

Chromosome 17

Answer

Chromosome 13

Answer

Chromosome 11

Answer

Chromosome 22

Question 6

Increase in the number of goblet cells in the non-respiratory terminal bronchiole is an example of?

Accepted Answer

Metaplasia

Answer

Anaplasia

Answer

Dysplasia

Answer

Hyperplasia

Question 7

During which phase of the cell cycle is DNA synthesis observed?

Accepted Answer

Synthetic phase

Answer

Resting phase

Answer

Mitotic phase

Answer

Premitotic phase

Question 8

Which of the following is a DNA repair defect?

Accepted Answer

Xeroderma pigmentosum

Answer

Retinoblastoma

Answer

Neurofibromatosis

Answer

MEN-I

Question 9

What is the earliest cellular change observed in cell death?

Accepted Answer

Cell swelling

Answer

Karyolysis

Answer

Loss of plasma membrane

Answer

Karyorrhexis

Question 10

On which chromosome is the Her2/neu gene located?

Accepted Answer

17

Answer

13

Answer

14

Answer

15

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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