Endocrine Pathology Practice Questions

Q: Persistent multinodular goiter may cause which of the following complications?

Follicular Carcinoma. **Explanation:** The correct answer is **Follicular Carcinoma (Option A)**. **Underlying Concept:** Long-standing or persistent Multinodular Goiter (MNG) is a known risk factor for the development of Follicular Thyroid Carcinoma (FTC). This association is primarily linked to areas of **endemic iodine deficiency**, where chronic stimulation by Thyroid Stimulating Hormone (TSH) leads to follicular hyperplasia. Over time, this persistent proliferative stress can result in malignant transformation into follicular carcinoma. While most MNGs are benign, any dominant or rapidly growing nodule within a long-standing goiter must be evaluated for malignancy. **Analysis of Incorrect Options:** * **B. Papillary Carcinoma:** This is the most common thyroid malignancy overall. Its primary risk factor is **ionizing radiation** exposure, not long-standing MNG. It is more common in iodine-sufficient areas. * **C. Medullary Carcinoma:** This arises from the **parafollicular C-cells** (neuroendocrine origin) and is often associated with genetic mutations (RET proto-oncogene) or MEN 2 syndromes. It has no etiologic link to MNG. * **D. Colloid Carcinoma:** This is not a standard primary thyroid malignancy; "colloid" typically refers to the benign storage material found within thyroid follicles in a goiter. **High-Yield Clinical Pearls for NEET-PG:** * **Iodine Status:** FTC is more common in iodine-deficient areas; Papillary carcinoma is more common in iodine-rich areas. * **Diagnosis:** FTC cannot be diagnosed by FNAC alone because FNAC cannot distinguish between a follicular adenoma and carcinoma. Diagnosis requires histological evidence of **capsular or vascular invasion**. * **Spread:** FTC typically spreads **hematogenously** (to lungs and bone), whereas Papillary carcinoma spreads via **lymphatics**. * **Anaplastic Carcinoma:** Long-standing MNG is also a significant risk factor for Anaplastic carcinoma in elderly patients.

Q: Multiple Endocrine Neoplasia (MEN) types II and III are associated with which gene mutation?

Ret. **Explanation:** The correct answer is **D. Ret**. **1. Why Ret is correct:** The **RET proto-oncogene**, located on chromosome **10q11.2**, encodes a receptor tyrosine kinase involved in cell growth and differentiation. Germline **gain-of-function mutations** in the RET gene are the hallmark of **MEN 2A (Type II)** and **MEN 2B (Type III)** [1]. * **MEN 2A:** Characterized by Medullary Thyroid Carcinoma (MTC), Pheochromocytoma, and Parathyroid hyperplasia [1]. * **MEN 2B:** Characterized by MTC, Pheochromocytoma, Mucosal neuromas, and Marfanoid habitus [1]. * *Note:* In contrast, MEN Type I is caused by a mutation in the *MEN1* gene (Menin protein) on chromosome 11. **2. Why other options are incorrect:** * **A. C-myc:** An oncogene (transcription factor) associated with **Burkitt Lymphoma** (t[8;14]). * **B. Erb-B2 (HER2/neu):** A growth factor receptor overexpressed in certain **Breast and Gastric cancers**. * **C. L-myc:** An oncogene primarily associated with **Small Cell Carcinoma of the Lung**. **High-Yield Clinical Pearls for NEET-PG:** * **Screening:** Prophylactic thyroidectomy is recommended for children carrying the RET mutation because Medullary Thyroid Carcinoma (MTC) occurs in nearly 100% of these patients. * **Hirschsprung Disease:** While *gain-of-function* RET mutations cause MEN 2, *loss-of-function* RET mutations are associated with Hirschsprung disease. * **MTC Marker:** Calcitonin is the tumor marker used for diagnosis and monitoring of MTC in MEN 2 patients. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1137.

Q: A 40-year-old male presented with a thyroid swelling and dysphagia. He gave history of on and off watery diarrhea. Biopsy of the lesion is shown. What is your diagnosis?

Medullary carcinoma of the thyroid. ***Medullary carcinoma of the thyroid*** - The combination of **thyroid swelling** with **watery diarrhea** strongly suggests medullary carcinoma, which arises from **C-cells** and secretes **calcitonin**. - Histologically shows **amyloid deposits in the stroma** and is associated with **MEN syndromes**, explaining the diarrheal symptoms due to excess calcitonin. *Follicular carcinoma of the thyroid* - Arises from **follicular epithelial cells** and typically presents as a **solitary thyroid nodule** without systemic symptoms like diarrhea. - Histologically shows **follicular architecture** with **capsular** or **vascular invasion**, lacking the amyloid deposits seen in medullary carcinoma. *Papillary carcinoma of the thyroid* - Most common thyroid malignancy arising from **follicular epithelial cells**, usually presenting as a painless thyroid mass without diarrhea. - Characterized by **papillary architecture**, **psammoma bodies**, and **Orphan Annie eye nuclei**, distinct from the neuroendocrine features of medullary carcinoma. *Anaplastic carcinoma of the thyroid* - Highly aggressive tumor presenting as a **rapidly enlarging thyroid mass** with severe **compressive symptoms** in elderly patients. - Histologically shows **undifferentiated cells** with **high mitotic activity** and **necrosis**, lacking the organized structure and amyloid deposits of medullary carcinoma.

Q: What is the ultrastructural finding in a case of paraganglioma?

Dense core granules. **Explanation:** **Paragangliomas** (and their adrenal counterpart, Pheochromocytoma) are neuroendocrine tumors derived from the extra-adrenal chromaffin cells of the autonomic nervous system. **Why "Dense core granules" is correct:** Under electron microscopy (ultrastructure), these cells characteristically contain numerous membrane-bound, electron-dense neurosecretory granules [1]. These are known as **"Zellballen"** granules or dense-core granules. They represent the storage sites for catecholamines (epinephrine and norepinephrine) and are a hallmark of neuroendocrine differentiation [1]. **Why the other options are incorrect:** * **A. Deposition of glycogen:** This is a characteristic feature of "Clear Cell" tumors, such as Clear Cell Renal Cell Carcinoma (RCC) or Ewing Sarcoma, but not neuroendocrine tumors. * **B & C. Enlarged/Shrunken mitochondria:** While mitochondrial abnormalities occur in various pathologies (e.g., Oncocytomas show an abundance of mitochondria), they are not the diagnostic ultrastructural feature for paragangliomas. **High-Yield Clinical Pearls for NEET-PG:** * **Histology:** Shows a characteristic **"Zellballen" pattern** (nests of cells surrounded by a delicate vascular stroma). * **Immunohistochemistry (IHC):** The chief cells are positive for **Chromogranin** and **Synaptophysin**, while the peripheral sustentacular cells are positive for **S-100**. * **Rule of 10s:** Historically associated with Pheochromocytoma (10% bilateral, 10% malignant, 10% extra-adrenal), though genetic understanding is evolving. * **Genetic Association:** Often linked to mutations in the **SDH (Succinate Dehydrogenase)** gene complex. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 484-485.

Question 1

Which of the following statements about pheochromocytoma is incorrect?

Accepted Answer

90% of non-familial cases are bilateral.

Answer

Extra-adrenal tumors typically exhibit a zellballen pattern.

Answer

It follows the 'rule of 10s'.

Answer

10% of pheochromocytomas are extra-adrenal.

Question 2

Persistent multinodular goiter may cause which of the following complications?

Accepted Answer

Follicular Carcinoma

Answer

Papillary Carcinoma

Answer

Medullary Carcinoma

Answer

Colloid Carcinoma

Question 3

Which is the most well-differentiated thyroid tumor?

Accepted Answer

Papillary carcinoma

Answer

Medullary carcinoma

Answer

Follicular carcinoma

Answer

Anaplastic carcinoma

Question 4

Medullary thyroid carcinoma occurs due to the mutation of which oncogene or gene?

Accepted Answer

RET oncogene

Answer

P53 gene

Answer

RAS (H-RAS, K-RAS, N-RAS)

Answer

BRCA-1

Question 5

All of the following are features of De Quervain thyroiditis except?

Accepted Answer

Bacterial infection is a trigger in most patients.

Answer

In the early phase, follicles are disrupted and replaced by neutrophils forming microabscesses.

Answer

Inflammatory infiltrate is composed of lymphocytes, plasma cells, and macrophages with granuloma formation.

Answer

It is the most common cause of painful thyroid.

Question 6

A 32-year-old woman develops an Addisonian crisis (acute adrenal insufficiency) 3 months after suffering massive hemorrhage during the delivery of her baby. A CT scan of the abdomen shows small adrenal glands. Which of the following mechanisms of disease best accounts for adrenal atrophy in this patient?

Accepted Answer

Lack of trophic signals

Answer

Chronic inflammation

Answer

Chronic ischemia

Answer

Hemorrhagic necrosis

Question 7

Multiple Endocrine Neoplasia (MEN) types II and III are associated with which gene mutation?

Accepted Answer

Ret

Answer

C-myc

Answer

Erb-B2

Answer

L-myc

Question 8

A 40-year-old male presented with a thyroid swelling and dysphagia. He gave history of on and off watery diarrhea. Biopsy of the lesion is shown. What is your diagnosis?

Accepted Answer

Medullary carcinoma of the thyroid

Answer

Follicular carcinoma of the thyroid

Answer

Papillary carcinoma of the thyroid

Answer

Anaplastic carcinoma of the thyroid

Question 9

Which of the following is seen on electron microscopy of medullary thyroid carcinoma specimens?

Accepted Answer

Presence of electron-dense granules in the cytoplasm

Answer

Presence of electron-dense granules in the nucleus

Answer

Presence of electron-dense granules in the mitochondria

Answer

Presence of electron-dense granules in the endoplasmic reticulum

Question 10

What is the ultrastructural finding in a case of paraganglioma?

Accepted Answer

Dense core granules

Answer

Deposition of glycogen

Answer

Enlarged mitochondria

Answer

Shrunken mitochondria

Endocrine Pathology — MCQs

Endocrine Pathology — MCQs

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