General Pathology Practice Questions

Q: RET gene mutation is associated with which malignancy?

Medullary carcinoma thyroid. The **RET proto-oncogene**, located on chromosome 10q11.2, encodes a receptor tyrosine kinase essential for the development of neural crest-derived cells. **Why Medullary Carcinoma Thyroid (MCT) is correct:** MCT arises from the parafollicular C-cells of the thyroid [1]. Gain-of-function mutations in the *RET* gene are the hallmark of this malignancy. It is seen in: * **Sporadic MCT (75%):** Somatic *RET* mutations are found in about 50% of cases. * **Familial MCT (25%):** Germline *RET* mutations are present in nearly 100% of cases, occurring as part of **Multiple Endocrine Neoplasia (MEN) syndromes 2A and 2B**, or Familial MCT [2]. **Analysis of Incorrect Options:** * **Pheochromocytoma:** While *RET* mutations are associated with pheochromocytoma (as part of MEN 2A/2B), it is not the primary malignancy defined by this gene in isolation [2]. MCT is the most consistent feature across all *RET*-associated syndromes. * **Lymphoma:** Associated with genes like *c-MYC* (Burkitt), *BCL-2* (Follicular), or *BCL-6*. * **Renal Cell Carcinoma:** Primarily associated with the *VHL* gene (Clear cell variant) or *MET* proto-oncogene (Papillary variant) [2]. **High-Yield Clinical Pearls for NEET-PG:** 1. **MEN 2A:** MCT + Pheochromocytoma + Parathyroid Hyperplasia [2]. 2. **MEN 2B:** MCT + Pheochromocytoma + Mucosal Neuromas + Marfanoid habitus [2]. 3. **Prophylactic Thyroidectomy:** In children with known germline *RET* mutations, the thyroid is removed early because MCT penetrance is nearly 100%. 4. **Hirschsprung Disease:** Loss-of-function mutations in *RET* are associated with this congenital condition (failure of neural crest migration). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1137.

Q: In Marfan's syndrome, the defect is in which of the following?

Fibrillin I. **Explanation:** **Marfan’s Syndrome** is an autosomal dominant disorder of connective tissue caused by a mutation in the **FBN1 gene** located on chromosome **15q21**. 1. **Why Fibrillin-I is correct:** The FBN1 gene encodes **Fibrillin-I**, a glycoprotein that serves as a major structural component of microfibrils. These microfibrils act as a scaffold for the deposition of elastin. Furthermore, Fibrillin-I normally sequesters **TGF-β** (Transforming Growth Factor beta) [1]. A defect leads to excessive TGF-β signaling, which causes abnormal vascular remodeling and bone overgrowth, explaining the skeletal and cardiovascular manifestations [1]. 2. **Why other options are incorrect:** * **Fibrillin-II:** Mutations in the FBN2 gene (chromosome 5) lead to **Congenital Contractural Arachnodactyly (Beals Syndrome)**, characterized by "crumpled" ears and joint contractures, but without the life-threatening aortic complications of Marfan’s. * **Collagen:** Defects in collagen synthesis or structure are characteristic of **Ehlers-Danlos Syndrome (EDS)** and **Osteogenesis Imperfecta**, not Marfan’s. * **Elastin:** While elastin is associated with fibrillin, primary mutations in the elastin gene (ELN) are linked to **Williams Syndrome** and supravalvular aortic stenosis. **High-Yield Clinical Pearls for NEET-PG:** * **Cardiovascular:** Most common cause of death is **Aortic Dissection** (due to cystic medial necrosis). Mitral Valve Prolapse (MVP) is also common. * **Ocular:** **Ectopia lentis** (dislocation of the lens) typically occurs **upward and outward** (Superior-temporal). * **Skeletal:** Arachnodactyly (long fingers), pectus excavatum, and high-arched palate [1]. * **Diagnosis:** Based on the **Ghent Criteria**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154.

Q: Gastrin is a biochemical marker for which of the following tumours?

Pancreatic neuroendocrine tumour. **Explanation:** **Gastrin** is a peptide hormone primarily produced by the G-cells of the gastric antrum. In a pathological context, it serves as a specific biochemical marker for **Gastrinomas** [1], which are a type of **Pancreatic Neuroendocrine Tumour (PanNET)**. These tumours (often located in the "Gastrinoma Triangle") secrete excessive gastrin, leading to **Zollinger-Ellison Syndrome (ZES)**, characterized by refractory peptic ulcers and severe diarrhea [1]. **Analysis of Options:** * **Medullary Carcinoma of Thyroid (MCT):** The classic biochemical marker is **Calcitonin**. Carceaembryonic Antigen (CEA) is also used for monitoring. * **Pheochromocytoma:** This tumour of the adrenal medulla secretes catecholamines. The diagnostic markers are urinary and plasma **Metanephrines** and Vanillylmandelic acid (VMA). * **Gastrointestinal Stromal Tumor (GIST):** This is a mesenchymal tumour, not a neuroendocrine one. Its hallmark is the expression of **CD117 (c-KIT)** and **DOG1** on immunohistochemistry. **High-Yield Clinical Pearls for NEET-PG:** * **Zollinger-Ellison Syndrome:** Suspect this when ulcers are multiple, distal to the duodenum, or recur after treatment [1]. * **MEN1 Syndrome:** Gastrinomas are the most common functional pancreatic neuroendocrine tumours associated with Multiple Endocrine Neoplasia Type 1 (The 3 P’s: Pituitary, Parathyroid, Pancreas) [1]. * **Diagnostic Test:** The **Secretin Stimulation Test** is the provocative test of choice; secretin causes a paradoxical *increase* in serum gastrin levels in gastrinoma patients. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1124-1125.

Q: What is the characteristic shape of Birbeck granules?

Tennis racket. **Explanation:** **Birbeck granules** are the pathognomonic ultrastructural hallmark of **Langerhans Cell Histiocytosis (LCH)**. These are rod-shaped, pentalaminar cytoplasmic organelles with a central striated line and a bulbous end, giving them a classic **tennis racket** appearance under electron microscopy [1]. They are formed by the invagination of the cell membrane and are associated with the protein **Langerin (CD207)**, which is involved in antigen processing [1]. **Analysis of Options:** * **Option D (Tennis racket):** This is the correct description. The "handle" of the racket is the rod-like portion, and the "head" is the dilated vesicular end [1]. * **Option A (Hockeystick):** This is a distractor. While some granules might appear slightly curved, "tennis racket" is the standard medical descriptor. * **Option B (Bat):** Incorrect. This does not describe the specific pentalaminar structure seen on EM. * **Option C (Ball):** Incorrect. Birbeck granules are elongated rods, not spherical structures. **High-Yield Clinical Pearls for NEET-PG:** * **Cell of Origin:** Langerhans cells (dendritic cells of the skin/monocyte-macrophage lineage). * **Immunohistochemistry (IHC) Markers:** LCH cells are characteristically positive for **S-100**, **CD1a**, and **Langerin (CD207)** [1]. CD207 is the most specific marker. * **Clinical Presentation:** Can range from a solitary bone lesion (Eosinophilic Granuloma) to multisystem involvement (Letterer-Siwe disease). * **Radiology:** Often presents as "punched-out" lytic lesions in the skull. **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, p. 630.

Question 1

RET gene mutation is associated with which malignancy?

Accepted Answer

Medullary carcinoma thyroid

Answer

Pheochromocytoma

Answer

Lymphoma

Answer

Renal cell carcinoma

Question 2

Internucleosomal cleavage of DNA is characteristic of which of the following?

Accepted Answer

Apoptosis

Answer

Reversible cell injury

Answer

Irreversible cell injury

Answer

Necrosis

Question 3

Progressive cellular damage, including to DNA, can lead to which of the following outcomes?

Accepted Answer

Necrosis or Apoptosis

Answer

Atrophy

Answer

Metaplasia

Answer

Calcification

Question 4

Acute graft-versus-host disease (GVHD) reaction occurs in all of the following organs except:

Accepted Answer

Adrenals

Answer

Liver

Answer

Gut

Answer

Skin

Question 5

What is the inheritance pattern of familial retinoblastoma?

Accepted Answer

X-linked dominant

Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked recessive

Question 6

In Marfan's syndrome, the defect is in which of the following?

Accepted Answer

Fibrillin I

Answer

Fibrillin II

Answer

Collagen

Answer

Elastin

Question 7

What is the term for a cell's capacity to differentiate into diverse lineages?

Accepted Answer

Transdifferentiation

Answer

Dedifferentiation

Answer

Metaplasia

Answer

Developmental plasticity

Question 8

What accumulates in tissues in hemochromatosis?

Accepted Answer

Iron

Answer

Copper

Answer

Ceruloplasmin

Answer

Lipofuschin

Question 9

Gastrin is a biochemical marker for which of the following tumours?

Accepted Answer

Pancreatic neuroendocrine tumour

Answer

Medullary carcinoma of thyroid

Answer

Pheochromocytoma

Answer

Gastrointestinal stromal tumor

Question 10

What is the characteristic shape of Birbeck granules?

Accepted Answer

Tennis racket

Answer

Hockeystick

Answer

Bat

Answer

Ball

General Pathology — MCQs

General Pathology — MCQs

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