Endocrine Pathology — MCQs

Endocrine Pathology Indian Medical PG Practice Questions and MCQs

Question 241: A 45-year-old male presents with a neck mass. Fine needle aspiration shows pleomorphic cells with grooved nuclei (coffee bean appearance), nuclear pseudoinclusions, and psammoma bodies. What is the most likely diagnosis?

A. Medullary thyroid carcinoma
B. Follicular thyroid carcinoma
C. Papillary thyroid carcinoma (Correct Answer)
D. Anaplastic thyroid carcinoma

Explanation: ***Papillary Thyroid Carcinoma*** - The classic cytological findings described—**nuclear grooves** (coffee bean appearance), **nuclear pseudoinclusions** (referring to the hypochromatic "Orphan Annie Eye" nuclei), and **psammoma bodies**—are virtually diagnostic of **Papillary Thyroid Carcinoma (PTC)** [1], [2]. - Psammoma bodies are laminar calcifications often found in the core of vascular stalks of papillary structures in PTC, resulting from the degeneration of papillary fronds. *Follicular Thyroid Carcinoma* - Follicular carcinoma is characterized by a follicular architecture without the distinctive **nuclear features** (grooves, pseudoinclusions) or psammoma bodies seen in PTC [4]. - Definitive diagnosis requires surgical pathology to demonstrate **vascular or capsular invasion**, as FNA/cytology cannot reliably differentiate it from a benign follicular adenoma [4]. *Medullary Thyroid Carcinoma* - This tumor arises from parafollicular C cells (C cells) and characteristically features extracellular deposits of **amyloid**, which is typically derived from calcitonin [3]. - Cytologically, the cells are often plasmacytoid or spindle-shaped and lack the specific nuclear changes and psammoma bodies found in PTC. *Anaplastic Thyroid Carcinoma* - Anaplastic carcinoma is an aggressive, high-grade malignancy presenting with marked cellular pleomorphism, spindle cells, and/or bizarre **multinucleated giant cells**. - It typically presents as a rapidly enlarging neck mass in older adults and does **not display the characteristic features** (grooves, pseudoinclusions, psammoma bodies) of PTC [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1099. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 429-430. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 428-429. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1100-1101.

Question 242: A patient presents with a mass in the front of the neck, along with odynophagia and dyspnea. Histopathology reveals tumor cells positive for TTF-1, synaptophysin, and chromogranin, and there is evidence of amyloid deposition. What is the most likely diagnosis?

A. Follicular thyroid carcinoma
B. Medullary thyroid carcinoma (Correct Answer)
C. Papillary thyroid carcinoma
D. Anaplastic thyroid carcinoma

Explanation: ***Medullary thyroid carcinoma*** - The tumor cells are positive for **Synaptophysin** and **Chromogranin**, confirming their **neuroendocrine origin** from the parafollicular C cells [1][2]. - The characteristic finding of **amyloid deposition** is due to the precipitation of stored pro-hormone (primarily **calcitonin**) produced by these C cells, which is highly diagnostic for MTC [2]. *Papillary thyroid carcinoma* - While positive for TTF-1, it is characterized by distinctive nuclear features such as **Orphan Annie eye nuclei** and **nuclear grooves**. - It does **not** exhibit neuroendocrine differentiation (Synaptophysin/Chromogranin negative) or **amyloid deposition**. *Follicular thyroid carcinoma* - This tumor consists of follicular cells and is diagnosed by the demonstration of **capsular** or **vascular invasion**. - It is **negative** for neuroendocrine markers and **lacks** the pathognomonic **calcitonin-derived amyloid**. *Anaplastic thyroid carcinoma* - This is highly malignant and rapidly growing, often presenting with severe compression symptoms, but is histologically characterized by undifferentiated **spindle and giant cells**. - It is typically **negative** for specific neuroendocrine markers and TTF-1 expression is often lost; **amyloid deposits are not a feature**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 430-431.

Question 243: Osteitis fibrosa cystica is a feature of

A. milk-alkali syndrome
B. rickets
C. hyperthyroidism
D. hyperparathyroidism (Correct Answer)

Explanation: ***Correct: Hyperparathyroidism*** - **Osteitis fibrosa cystica** is a classic bone manifestation of **severe primary hyperparathyroidism**, resulting from excessive **parathyroid hormone (PTH)** [1]. - **PTH** causes increased bone resorption, leading to fibrous tissue replacement, cystic changes, and **brown tumors** (osteoclast-rich lesions with hemosiderin deposition) [1], [2]. - This represents advanced skeletal disease in hyperparathyroidism, though now rare due to early detection [1]. *Incorrect: Milk-alkali syndrome* - This syndrome is characterized by **hypercalcemia**, **metabolic alkalosis**, and **renal insufficiency** due to excessive intake of calcium and absorbable alkali. - It does not cause osteitis fibrosa cystica, which is a specific bone lesion requiring prolonged elevated **PTH**. *Incorrect: Rickets* - **Rickets** is a disorder primarily affecting children, characterized by defective bone mineralization leading to soft and weakened bones. - It is caused by **vitamin D deficiency** or resistance and manifests as bone deformities (bowing, rachitic rosary), not cystic bone lesions. *Incorrect: Hyperthyroidism* - **Hyperthyroidism** can lead to generalized **osteopenia** or **osteoporosis** due to increased bone turnover, but it does not cause osteitis fibrosa cystica. - The bone changes in hyperthyroidism are diffuse and distinct from the focal cystic lesions seen in excessive **PTH** activity. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1105-1106. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1194.

Question 244: The following is a histopathological image of thyroid pathology. What is the diagnosis?

A. Papillary carcinoma of thyroid
B. Medullary carcinoma of thyroid (Correct Answer)
C. Follicular carcinoma of thyroid
D. Anaplastic carcinoma of thyroid

Explanation: ***Medullary carcinoma of thyroid*** - This image shows sheets and nests of **polygonal to spindle-shaped cells**, which are characteristic of medullary thyroid carcinoma, especially when mixed with an **amyloid stroma** (seen as amorphous eosinophilic material) [2]. - The presence of **neuroendocrine features** and the production of **calcitonin** are hallmarks of these C-cell tumors [1], [2]. *Papillary carcinoma of thyroid* - Characterized by **papillary architecture**, **ground-glass (Orphan Annie eye) nuclei**, nuclear grooves, and intranuclear cytoplasmic inclusions. - These features are not prominently seen in the provided image. *Follicular carcinoma of thyroid* - Defined by an invasive growth pattern of **well-differentiated follicular cells** forming follicles, with either capsular or vascular invasion [2]. - The image does not show classic follicular architectural patterns or clear evidence of invasion in the absence of a capsule. *Anaplastic carcinoma of thyroid* - This is a highly aggressive and undifferentiated tumor with **marked pleomorphism**, bizarre giant cells, and high mitotic activity [2]. - While there is some pleomorphism, the overall pattern and cellular morphology in the image are more consistent with medullary carcinoma than the extreme anaplasia. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 428-431.

Question 245: A thyroid FNA shows 'bubble gum' colloid. Which nuclear feature would best support papillary thyroid carcinoma?

A. Nuclear grooves
B. Ground glass nuclei (Correct Answer)
C. Prominent nucleoli
D. Salt and pepper chromatin

Explanation: ***Ground glass nuclei*** - **Ground glass nuclei**, also known as **Orphan Annie eye nuclei** [1][2], are the most **characteristic and recognized nuclear feature** of **papillary thyroid carcinoma (PTC)** on FNA cytology. [1] - This appearance results from **fine, evenly dispersed chromatin** that gives the nucleus a clear, empty, or translucent appearance with a prominent nuclear membrane. [1] - Among the given options, this is the **single best feature** that would support a PTC diagnosis when 'bubble gum' colloid is present. *Nuclear grooves* - **Nuclear grooves** are a common and highly supportive feature of PTC, particularly when **prominent and numerous**. - However, as a **single finding**, they are less definitive than ground glass nuclei, as grooves can occasionally be seen in benign conditions (though usually less prominent). - In combination with other features, nuclear grooves are highly specific for PTC. *Prominent nucleoli* - **Prominent nucleoli** are more frequently associated with **follicular neoplasms**, **medullary thyroid carcinoma**, or anaplastic thyroid carcinoma. - Classical PTC typically has **inconspicuous nucleoli**, so prominent nucleoli would suggest an alternative diagnosis or a tall cell variant of PTC. *Salt and pepper chromatin* - **Salt and pepper chromatin** (finely stippled chromatin) is a classic cytological feature of **medullary thyroid carcinoma** (MTC). - This chromatin pattern reflects neuroendocrine differentiation and is distinct from the nuclear characteristics of PTC. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1098-1100. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 429-430.

Question 246: Malignancy in a multinodular goiter is most often:-

A. Papillary carcinoma (Correct Answer)
B. Anaplastic carcinoma
C. Follicular carcinoma
D. Medullary carcinoma

Explanation: ***Papillary carcinoma*** - **Papillary carcinoma** is the most common type of thyroid cancer, accounting for about 80-85% of all thyroid malignancies [1], [2]. - It often arises in the setting of multifocal disease or within a **multinodular goiter**, particularly when a dominant nodule undergoes malignant transformation [2]. *Anaplastic carcinoma* - **Anaplastic carcinoma** is a very aggressive and rare form of thyroid cancer, typically presenting as a rapidly growing neck mass in elderly patients [2]. - While it can occur in a multinodular goiter, it is far less common than papillary carcinoma and carries a much poorer prognosis [2]. *Follicular carcinoma* - **Follicular carcinoma** is the second most common type of thyroid cancer (10-15%) and is often difficult to distinguish from benign follicular adenomas without surgical excision [2]. - While it can be found in a multinodular goiter, **papillary carcinoma** is still statistically more frequent in this context [1]. *Medullary carcinoma* - **Medullary carcinoma** originates from the parafollicular C cells of the thyroid and accounts for about 1-2% of all thyroid cancers [2]. - It is often associated with inherited syndromes like **Multiple Endocrine Neoplasia type 2 (MEN2)** and is distinct from tumors arising from follicular cells within a multinodular goiter [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1098-1099. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 429-430.

Question 247: Nesidioblastoma is due to hyperplasia of?

A. Alpha cell
B. D cells
C. Acinus
D. Beta cell (Correct Answer)

Explanation: ***Beta cell*** - Nesidioblastoma is a rare pancreatic disorder characterized by the **hyperplasia of pancreatic islet beta cells**. - This over-proliferation of **insulin-producing beta cells** leads to excessive insulin secretion and recurrent hypoglycemia [2]. *Alpha cell* - Hyperplasia of **alpha cells** would primarily lead to an overproduction of **glucagon**, potentially causing hyperglycemia [1], [2]. - Nesidioblastoma is specifically linked to hypoglycemia due to excessive insulin. *D cells* - **D cells** (delta cells) in the pancreas produce **somatostatin**, which inhibits the secretion of insulin and glucagon [2]. - Hyperplasia of D cells would more likely dampen both insulin and glucagon effects rather than cause insulin-driven hypoglycemia. *Acinus* - The **acinus** refers to the exocrine portion of the pancreas, responsible for producing digestive enzymes [1]. - Nesidioblastoma originates from the **endocrine islet cells**, not the exocrine acinar cells. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 433-434. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1109, 1125.

Question 248: Which of the following occurs in long standing goitre:

A. Medullary Ca
B. Papillary Ca
C. Anaplastic Ca
D. Follicular Ca (Correct Answer)

Explanation: ***Follicular Ca*** - **Follicular carcinoma** is the second most common type of thyroid cancer and is **classically associated with long-standing endemic goiters**, especially in areas of **iodine deficiency** [1]. - The risk of malignant transformation in a long-standing multinodular goiter to follicular carcinoma increases over time due to chronic TSH stimulation and accumulation of genetic alterations. - This is the **most characteristic malignancy** developing in the setting of a long-standing benign goiter [1]. *Medullary Ca* - **Medullary thyroid carcinoma** originates from the parafollicular **C cells** of the thyroid, not from follicular epithelium [3]. - It is **not associated with chronic goiter formation** and occurs sporadically or as part of **Multiple Endocrine Neoplasia type 2 (MEN2)** syndromes [3]. *Papillary Ca* - **Papillary carcinoma** is the most common type of thyroid cancer overall and is primarily associated with **radiation exposure**, not iodine deficiency or long-standing goiters [1]. - While it can arise in a nodular thyroid, it is not the typical malignant transformation seen in chronic endemic goiter [4]. *Anaplastic Ca* - **Anaplastic carcinoma** is a highly aggressive undifferentiated thyroid cancer that can arise from **transformation of pre-existing differentiated thyroid cancers** (papillary or follicular carcinoma) within a long-standing goiter [2]. - However, it represents **dedifferentiation of existing malignancy** rather than direct malignant transformation of benign goiter tissue. - It typically presents as a rapidly growing neck mass in **elderly patients** with very poor prognosis and is much less common than follicular carcinoma in the setting of endemic goiter [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1098-1099. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1101-1102. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1099-1100.

Question 249: Marker for pancreatic non-functional neuro-endocrine tumor is

A. CEA
B. PSA
C. CD100
D. Chromogranin-A (Correct Answer)

Explanation: ***Chromogranin-A*** - **Chromogranin-A** is a glycoprotein found in the neurosecretory granules of various neuroendocrine cells, making it a reliable **general neuroendocrine tumor marker** [1]. - Elevated levels are particularly useful for detecting and monitoring **pancreatic non-functional neuroendocrine tumors**, which often lack specific hormonal symptoms. *CEA* - **Carcinoembryonic antigen (CEA)** is primarily used as a tumor marker for **colorectal cancer**, and less commonly for other adenocarcinomas like pancreatic adenocarcinoma. - It is generally **not a specific marker** for neuroendocrine tumors. *PSA* - **Prostate-specific antigen (PSA)** is a specific marker for **prostate cancer**, used for screening, diagnosis, and monitoring of this particular malignancy. - It has **no relevance** in the diagnosis or monitoring of pancreatic neuroendocrine tumors. *CD100* - **CD100** (also known as semaphorin-4D) is a membrane glycoprotein involved in immune cell regulation and has been implicated in certain cancers, such as those of **hematopoietic origin**. - It is **not used as a marker** for pancreatic non-functional neuroendocrine tumors. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 780-781.

Question 250: A patient presents with neck swelling causing compression of the trachea and esophagus. Histopathological assessment reveals cell nests and pink extracellular amyloid stroma. What is the cell of origin of the tumor associated with these findings?

A. Parafollicular C cells (Correct Answer)
B. Hurthle cells
C. Follicular cells
D. Chief cells

Explanation: ***Parafollicular C cells*** - The presence of **cell nests** and **pink extracellular amyloid stroma** are classic histopathological findings for **medullary thyroid carcinoma (MTC)**, which originates from the parafollicular C cells [2], [3]. - Parafollicular C cells are responsible for producing **calcitonin**, and the amyloid in these tumors is derived from calcitonin [3]. - MTC accounts for 5-10% of thyroid cancers and can be sporadic or familial (associated with MEN 2A and 2B syndromes) [1], [4]. *Chief cells* - Chief cells are **parathyroid gland cells** that produce parathyroid hormone (PTH), not thyroid tumor cells. - While parathyroid adenomas can cause neck masses, they do not produce the characteristic amyloid stroma seen in medullary carcinoma. *Hürthle cells* - Hürthle cells (also known as Askanazy cells or oncocytes) are a type of **follicular cell** characterized by abundant **eosinophilic, granular cytoplasm** due to numerous mitochondria. - While they can form tumors (**Hürthle cell adenoma or carcinoma**), these tumors do not typically feature cell nests or amyloid stroma. *Follicular cells* - Follicular cells are the most common cell type in the thyroid and are the origin of most thyroid cancers, including **papillary** and **follicular carcinomas** [4]. - These tumors generally do not present with the characteristic **amyloid stroma** and cell nests described in the question. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 430-431. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 428-429. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 429-430.

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