Molecular Pathology Practice Questions

Q: In the alveolar variant of rhabdomyosarcoma, the resultant fusion protein is believed to function as what?

Chimeric transcription factor. **Explanation:** The correct answer is **B. Chimeric transcription factor.** **Understanding the Mechanism:** Alveolar Rhabdomyosarcoma (ARMS) is characterized by specific chromosomal translocations, most commonly **t(2;13)(q35;q14)** and less frequently **t(1;13)(p36;q14)**. These translocations result in the fusion of the **PAX3** (or PAX7) gene with the **FOXO1** (formerly FKHR) gene. * **PAX3/7** are genes involved in muscle differentiation (transcription factors). * **FOXO1** is a transcription factor involved in cell cycle regulation. The resulting **PAX3-FOXO1** fusion protein is a **chimeric transcription factor**. It possesses the DNA-binding domain of PAX and the transactivation domain of FOXO1, making it a much more potent activator of myogenic genes than wild-type PAX3. This leads to dysregulated gene expression, promoting cell proliferation and inhibiting apoptosis. **Analysis of Incorrect Options:** * **A & D (Growth Factor/Receptor):** While many cancers (like GIST or HER2+ breast cancer) involve growth factors or their receptors, ARMS is driven by nuclear genetic rearrangement, not extracellular signaling molecules. * **C (Constitutively active kinase):** This mechanism is classic for **Chronic Myeloid Leukemia (BCR-ABL)**, where the fusion protein acts as a tyrosine kinase. In ARMS, the fusion protein acts directly on DNA in the nucleus. **High-Yield Clinical Pearls for NEET-PG:** * **Embryonal RMS:** Most common type; associated with **loss of heterozygosity (LOH) at 11p15.5** (IGF-2 gene). * **Alveolar RMS:** More aggressive; characterized by **t(2;13)** fusion. * **Histology:** ARMS shows small round blue cells arranged in clusters separated by fibrous septa, resembling pulmonary alveoli. * **IHC Markers:** Desmin, Myogenin (Myf4), and MyoD1 are positive. Myogenin expression is typically more diffuse in the Alveolar variant compared to the Embryonal variant.

Q: The SYT-SSX1 gene fusion is associated with which of the following neoplasms?

Synovial sarcoma. **Explanation:** The correct answer is **Synovial sarcoma**. This neoplasm is characterized by a highly specific reciprocal translocation, **t(X;18)(p11;q11)** [1]. This translocation results in the fusion of the **SS18** (formerly *SYT*) gene on chromosome 18 with one of the **SSX** genes (usually *SSX1*, *SSX2*, or rarely *SSX4*) on the X chromosome [1]. The resulting **SYT-SSX** fusion protein acts as an aberrant transcriptional regulator that disrupts chromatin remodeling (SWI/SNF complex), leading to oncogenesis. **Analysis of Incorrect Options:** * **Liposarcoma:** Most commonly associated with **t(12;16)** resulting in the **FUS-CHOP** fusion (Myxoid/Round cell subtype) or **MDM2** amplification (Well-differentiated/Dedifferentiated subtype). * **Rhabdomyosarcoma:** Alveolar rhabdomyosarcoma is characterized by **t(2;13)** or **t(1;13)**, involving the **PAX3-FOXO1** or **PAX7-FOXO1** gene fusions. * **Ewing sarcoma:** Classically associated with **t(11;22)(q24;q12)**, leading to the **EWS-FLI1** gene fusion. **High-Yield NEET-PG Pearls:** * **Synovial Sarcoma:** Despite the name, it does *not* arise from synovial cells; it originates from mesenchymal stem cells near joints [1]. * **Morphology:** Can be **biphasic** (epithelial glands + spindle cells) or **monophasic** (spindle cells only) [1]. * **Immunohistochemistry (IHC):** Positive for **TLE1**, Cytokeratin, and EMA. * **Prognostic Correlation:** The **SYT-SSX1** variant is more common in biphasic tumors and is generally associated with a poorer prognosis compared to the *SYT-SSX2* variant. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1225-1226.

Question 1

What is the first manifestation in cell injury?

Accepted Answer

Cell swelling

Answer

Pyknosis

Answer

Nuclear fragmentation

Answer

Nuclear lysis

Question 2

Which of the following cellular components is capable of recognizing dead material?

Accepted Answer

Inflammasome

Answer

NET (Neutrophil Extracellular Traps)

Answer

Necrosis

Answer

Toll-like receptor

Question 3

Why do fetal cells continue to divide while terminally differentiated adult cells do not?

Accepted Answer

Adult cells have many cyclin inhibitors that prevent entry into the S phase.

Answer

Phosphatase is absent in fetal cells.

Answer

Proteinase is absent in the fetus.

Answer

CD kinases are absent in fetal cells.

Question 4

In the alveolar variant of rhabdomyosarcoma, the resultant fusion protein is believed to function as what?

Accepted Answer

Chimeric transcription factor

Answer

Activated growth factor receptor

Answer

Constitutively active kinase

Answer

Novel growth factor

Question 5

The SYT-SSX1 gene fusion is associated with which of the following neoplasms?

Accepted Answer

Synovial sarcoma

Answer

Liposarcoma

Answer

Rhabdomyosarcoma

Answer

Ewing sarcoma

Question 6

What is the function of peroxisomes?

Accepted Answer

Generating hydrogen peroxide (H2O2)

Answer

Protein synthesis

Answer

Carbohydrate metabolism

Answer

DNA replication

Question 7

What genetic mutation leads to Duchenne Muscular Dystrophy?

Accepted Answer

Duchenne Muscular Dystrophy

Answer

Myasthenia gravis

Answer

Motor neuron disease

Answer

Poliomyelitis

Question 8

Xeroderma pigmentosum is characterized by

Accepted Answer

Inability to repair sunlight induced damage to DNA

Answer

Autosomal dominant inheritance

Answer

Irregular accumulation of melanin in the basal cell layer

Answer

Acanthosis of epithelium with elongation of rete ridges

Question 9

What is the immunohistochemical marker used to label basal cells in suspected prostate carcinoma?

Accepted Answer

Alpha-Methylacyl-coenzyme Racemase

Answer

Alpha Fetoprotein

Answer

Annexin

Answer

AgNOR

Question 10

A 1-year-old girl with an inborn error of metabolism resulting in a lysosomal storage disease receives a hematopoietic stem cell transplant intended to replace her macrophage population. The gene of interest has a 'marker' small nucleotide polymorphism within a non-coding intron of the affected gene in which an A (patient gene) is substituted for a G (donor gene). She does quite well for the first 3 weeks. She tests positive for the missing enzyme, her previously abnormally enlarged organs begin to diminish in size, and assay of peripheral blood lymphocytes reveals increasing numbers of cells with the G polymorphism. However, the attending physicians are now concerned because repeated genetic testing reveals a progressive increase in lymphocytes with the A nucleotide polymorphism. Which of the following is the best explanation for this finding?

Accepted Answer

Rejection of the stem cell transplant

Answer

Generalized immune complex formation

Answer

Graft-versus-host disease

Answer

Immune paralysis

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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