Endocrine Pathology Practice Questions

Q: A 42-year-old woman presents with a diffuse swelling in front of her neck. Thyroid function tests are within normal limits. A fine-needle biopsy reveals malignant cells. On examination of the excised tumor, the tumor cells are positive for calcitonin on immunohistochemistry. What is the appropriate pathologic diagnosis?

Medullary carcinoma. ### Explanation **Correct Answer: C. Medullary Carcinoma** The definitive diagnostic clue in this case is the **immunohistochemical (IHC) positivity for calcitonin**. Medullary Thyroid Carcinoma (MTC) originates from the **Parafollicular C-cells** (derived from the neural crest), which are responsible for secreting calcitonin. Unlike other thyroid cancers, MTC is not derived from follicular cells; therefore, patients are typically euthyroid (normal T3, T4, TSH). **Why other options are incorrect:** * **Papillary Carcinoma (D):** The most common thyroid malignancy. It is characterized by nuclear features (Orphan Annie eyes, Psammoma bodies) and is IHC positive for **Thyroglobulin**, not calcitonin. * **Follicular Carcinoma (B):** Derived from follicular cells and spreads hematogenously. Like papillary carcinoma, it is IHC positive for **Thyroglobulin**. * **Anaplastic Carcinoma (A):** A highly aggressive, undifferentiated tumor usually seen in the elderly. It typically presents as a rapidly enlarging mass with compressive symptoms and lacks specific markers like calcitonin. **High-Yield Clinical Pearls for NEET-PG:** * **Biomarkers:** Calcitonin is used for both diagnosis and monitoring recurrence. Carcinoembryonic Antigen (CEA) is also often elevated. * **Genetics:** Approximately 25% of MTC cases are familial (associated with **MEN 2A and 2B** syndromes) due to **RET proto-oncogene** mutations. 75% are sporadic. * **Pathology:** Characterized by deposits of **Amyloid** (formed by pro-calcitonin) which stains with **Congo Red** (showing apple-green birefringence). * **Surgery:** The treatment of choice is **Total Thyroidectomy with Central Compartment Neck Dissection**, as MTC does not concentrate radioiodine (I-131).

Q: Which of the following is NOT a true statement about papillary carcinoma?

Hematogenous spread is common.. **Explanation:** Papillary Thyroid Carcinoma (PTC) is the most common type of thyroid malignancy. The hallmark of PTC is its tendency for **lymphatic spread** rather than hematogenous spread. 1. **Why Option C is the correct (False) statement:** Unlike Follicular Thyroid Carcinoma, which characteristically spreads via the bloodstream (hematogenous), Papillary Carcinoma primarily spreads through the lymphatics to the cervical lymph nodes. While hematogenous spread can occur, it is **uncommon** (occurring in <5-10% of cases). Therefore, stating it is "common" is incorrect. 2. **Analysis of other options:** * **Option A (Radiation):** Exposure to ionizing radiation (especially during childhood) is the most well-established environmental risk factor for PTC. * **Option B (Multifocal):** PTC is frequently multifocal (involving multiple sites within the gland) and bilateral in up to 20-80% of cases, which often influences the decision for total thyroidectomy. * **Option D (Distant metastasis):** Although rare compared to lymphatic spread, distant metastasis can occur, most commonly involving the **lungs** (often presenting as a miliary pattern) and occasionally the bones. **NEET-PG High-Yield Pearls:** * **Most common** thyroid cancer overall and most common after radiation exposure. * **Microscopic Hallmarks:** Psammoma bodies (calcified laminations), Orphan Annie eye nuclei (clear nuclei), and nuclear grooves. * **Prognosis:** Generally excellent; the **AMES** (Age, Metastasis, Extent, Size) and **MACIS** scores are used for staging. * **BRAF Mutation:** The most common genetic mutation associated with PTC.

Q: A 27-year-old female presented with a long-standing 2 cm x 2 cm nodule in the right lobe of her thyroid, for which she underwent a right hemithyroidectomy. What is the most likely histopathological finding given these clinical details?

Papillary carcinoma. **Explanation:** The correct answer is **Papillary Thyroid Carcinoma (PTC)**. In the context of NEET-PG, any solitary thyroid nodule in a young female (20–40 years) is considered a "red flag." Statistically, PTC is the most common thyroid malignancy (85% of cases) and frequently presents as a painless, slow-growing solitary nodule in an otherwise euthyroid patient [2]. **Why the other options are less likely:** * **Adenomatous Goiter:** This typically presents as a multinodular enlargement of the thyroid (Multinodular Goiter) rather than a discrete, long-standing solitary nodule [1]. * **Follicular Adenoma:** While it presents as a solitary nodule, it is less common than PTC [2]. Furthermore, the "most likely" examiner expectation for a solitary nodule in a young female is malignancy, specifically PTC. * **Graves Disease:** This is a functional disorder presenting with diffuse thyroid enlargement (goiter) and clinical features of hyperthyroidism (tachycardia, tremors, exophthalmos), not a localized 2 cm nodule. **High-Yield Clinical Pearls for NEET-PG:** * **Diagnosis:** Fine Needle Aspiration Cytology (FNAC) is the investigation of choice for thyroid nodules [1]. * **Hallmark Histology of PTC:** Look for **Orphan Annie eye nuclei** (optically clear), **Psammoma bodies** (laminated calcifications), and **Nuclear grooves/pseudoinclusions** [1]. * **Prognosis:** PTC has an excellent prognosis despite a tendency for early lymphatic spread to cervical lymph nodes [2]. * **Risk Factor:** Prior exposure to ionizing radiation is a significant risk factor for developing PTC. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1095-1100. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 428-430.

Q: What is the most common cause of primary hyperparathyroidism?

Single adenoma. **Explanation:** Primary hyperparathyroidism (PHPT) is characterized by the autonomous overproduction of parathyroid hormone (PTH), leading to hypercalcemia. **1. Why "Single Adenoma" is correct:** A **solitary parathyroid adenoma** is the most frequent cause, accounting for approximately **85% to 95%** of all cases of PHPT. Pathologically, these are usually well-circumscribed, solitary nodules (often involving the inferior parathyroid glands) composed of chief cells, with a characteristic rim of compressed normal parathyroid tissue. **2. Why the other options are incorrect:** * **Multiple gland hyperplasia:** This accounts for about **10% to 15%** of cases. It typically involves all four glands and is frequently associated with familial syndromes like MEN1 or MEN2A [1]. * **Multiple adenomas:** These are rare (approx. **1%**) and involve two or more glands while others remain normal. * **Single gland hyperplasia:** This is not a standard pathological entity; hyperplasia by definition involves a proliferation of cells that typically affects multiple glands in the parathyroid context. * **Parathyroid Carcinoma:** (Not listed, but important) This is the rarest cause, occurring in <1% of cases. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Presentation:** Classically described as "Bones, Stones, Abdominal Groans, and Psychic Moans" (osteitis fibrosa cystica, nephrolithiasis, peptic ulcers, and depression). * **Biochemical Hallmark:** Elevated Serum Calcium + Elevated (or inappropriately normal) PTH + Low Serum Phosphate. * **Most common genetic mutation:** *MEN1* gene (sporadic or syndromic) and *CCND1* (Cyclin D1) inversions [1]. * **Sestamibi Scan:** The investigation of choice for localizing an adenoma before surgery. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1104-1105.

Q: Compared to follicular carcinoma, papillary carcinoma of the thyroid is associated with which of the following?

Radiation exposure. **Explanation:** The correct answer is **Radiation exposure**. Papillary Thyroid Carcinoma (PTC) is the most common thyroid malignancy and has a strong, well-documented association with prior exposure to ionizing radiation (e.g., childhood neck irradiation or nuclear accidents). In contrast, Follicular Thyroid Carcinoma (FTC) is more closely linked to dietary factors. **Analysis of Options:** * **Radiation Exposure (Correct):** Ionizing radiation is a major risk factor for PTC, often involving mutations in the *RET/PTC* rearrangement or *BRAF* gene. * **More Male Preponderance (Incorrect):** Both PTC and FTC are significantly more common in females (approx. 3:1 ratio). There is no male preponderance for PTC. * **Iodine Deficiency (Incorrect):** This is a classic risk factor for **Follicular Carcinoma** and Anaplastic Carcinoma. In contrast, iodine-rich areas often see a higher relative incidence of Papillary Carcinoma. * **Increased Mortality (Incorrect):** PTC has an excellent prognosis with a 10-year survival rate exceeding 90-95%. FTC is generally more aggressive than PTC due to its tendency for early hematogenous spread (to bone and lungs), whereas PTC primarily spreads via lymphatics. **High-Yield Clinical Pearls for NEET-PG:** * **Psammoma Bodies:** Laminated calcifications pathognomonic for PTC (found in 50% of cases). * **Orphan Annie Eye Nuclei:** Characteristic clear/ground-glass nuclei seen in PTC. * **Spread:** PTC spreads **Lymphatically** (most common site: Level VI nodes); FTC spreads **Hematogenously**. * **Diagnosis:** PTC can be diagnosed via FNAC (nuclear features); FTC **cannot** be diagnosed by FNAC (requires histological proof of capsular or vascular invasion).

Q: A 45-year-old female patient presented with features of hypothyroidism. Based on the provided histological features, what is your diagnosis?

Hashimoto thyroiditis. ***Hashimoto thyroiditis*** - Classic histological features include **lymphocytic infiltration** with **germinal center formation** and **Hürthle cell metaplasia**, consistent with hypothyroidism in a middle-aged female. - Shows **follicular atrophy** and **fibrosis**, leading to gradual thyroid dysfunction and is the most common cause of hypothyroidism in iodine-sufficient areas. *Granulomatous thyroiditis* - Characterized by **epithelioid granulomas** and **giant cells** histologically, not lymphocytic infiltration with germinal centers. - Typically presents with **painful thyroid enlargement** and **transient hyperthyroidism** followed by hypothyroidism, rather than primary hypothyroidism. *Papillary carcinoma of the thyroid* - Shows **papillary architecture** with **psammoma bodies** and **nuclear features** like overlapping, grooves, and pseudoinclusions. - Usually presents as a **thyroid nodule** rather than diffuse hypothyroidism, and patients are typically **euthyroid**. *Riedel's thyroiditis* - Characterized by **dense fibrous tissue** replacing thyroid parenchyma with **woody hardness** on palpation. - Shows **storiform fibrosis** without significant lymphocytic infiltration or germinal centers, and often involves surrounding structures.

Q: All are seen in MEN IIA syndrome except?

Caused by loss of function mutation in RET protooncogene.. **Explanation:** **MEN IIA (Sipple Syndrome)** is an autosomal dominant disorder characterized by a triad of Medullary Thyroid Carcinoma (MTC), Pheochromocytoma, and Parathyroid Hyperplasia [1]. **1. Why Option C is the correct answer (The False Statement):** MEN IIA is caused by a **gain-of-function** (activating) mutation in the **RET proto-oncogene** on chromosome 10 [1]. In contrast, "loss-of-function" mutations in the RET gene are associated with **Hirschsprung disease**. This is a high-yield distinction for NEET-PG. **2. Analysis of Incorrect Options (True Statements):** * **Option A:** MTC is the most consistent feature of MEN IIA, occurring in **100%** of patients [1]. It is often multifocal and preceded by C-cell hyperplasia. * **Option B:** Pheochromocytomas occur in approximately **40-50%** of patients [1]. They are frequently bilateral and extra-adrenal. * **Option C:** Primary hyperparathyroidism (due to hyperplasia) is seen in **10-20%** of cases. Because it occurs in the minority of patients compared to MTC and Pheochromocytoma, it is considered the **most variable** clinical feature. **Clinical Pearls for NEET-PG:** * **MEN IIA Components:** MTC + Pheochromocytoma + Parathyroid Hyperplasia [1]. * **MEN IIB Components:** MTC + Pheochromocytoma + Mucosal Neuromas/Marfanoid habitus (No parathyroid involvement) [1]. * **Prophylactic Thyroidectomy:** Recommended in children carrying the RET mutation because MTC is inevitable. * **Screening:** Always rule out Pheochromocytoma (via urinary metanephrines) before performing surgery for MTC to prevent a hypertensive crisis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1137.

Question 1

A 42-year-old woman presents with a diffuse swelling in front of her neck. Thyroid function tests are within normal limits. A fine-needle biopsy reveals malignant cells. On examination of the excised tumor, the tumor cells are positive for calcitonin on immunohistochemistry. What is the appropriate pathologic diagnosis?

Accepted Answer

Medullary carcinoma

Answer

Anaplastic carcinoma

Answer

Follicular carcinoma

Answer

Papillary carcinoma

Question 2

Which of the following is NOT a true statement about papillary carcinoma?

Accepted Answer

Hematogenous spread is common.

Answer

Radiation is a risk factor.

Answer

It can be multifocal.

Answer

Distant metastasis is seen.

Question 3

A 27-year-old female presented with a long-standing 2 cm x 2 cm nodule in the right lobe of her thyroid, for which she underwent a right hemithyroidectomy. What is the most likely histopathological finding given these clinical details?

Accepted Answer

Papillary carcinoma

Answer

Adenomatous goiter

Answer

Follicular adenoma

Answer

Graves disease

Question 4

What is the pathognomic feature of hyperparathyroidism?

Accepted Answer

Subperiosteal resorption of phalanges

Answer

Osteopenia

Answer

Loss of lamina dura

Answer

Brown's tumor

Question 5

A 25-year-old man presents with 3 months of polyuria and increased thirst. The patient suffered trauma to the base of the skull in a motorcycle accident 4 months ago. A 24-hour urine collection shows polyuria but no evidence of hematuria, glucosuria, or proteinuria. The pathogenesis of polyuria in this patient is most likely caused by a lesion in which of the following areas of the brain?

Accepted Answer

Neurohypophysis

Answer

Adenohypophysis

Answer

Brain stem

Answer

Mammillothalamic tract

Question 6

What is the most common cause of primary hyperparathyroidism?

Accepted Answer

Single adenoma

Answer

Multiple adenomas

Answer

Single gland hyperplasia

Answer

Multiple gland hyperplasia

Question 7

Compared to follicular carcinoma, papillary carcinoma of the thyroid is associated with which of the following?

Accepted Answer

Radiation exposure

Answer

More male preponderance

Answer

Iodine deficiency

Answer

Increased mortality

Question 8

A 45-year-old female patient presented with features of hypothyroidism. Based on the provided histological features, what is your diagnosis?

Accepted Answer

Hashimoto thyroiditis

Answer

Granulomatous thyroiditis

Answer

Papillary carcinoma of the thyroid

Answer

Riedel's thyroiditis

Question 9

All are seen in MEN IIA syndrome except?

Accepted Answer

Caused by loss of function mutation in RET protooncogene.

Answer

Medullary carcinoma of thyroid is seen in 100% of the patients.

Answer

40-50% patients have phaeochromocytomas.

Answer

Primary hyperparathyroidism is the most variable feature of MEN IIA syndrome.

Question 10

Pancreatitis, pituitary tumor, and pheochromocytoma may be associated with which of the following types of thyroid cancer?

Accepted Answer

Medullary carcinoma of the thyroid

Answer

Anaplastic carcinoma of the thyroid

Answer

Papillary carcinoma of the thyroid

Answer

Follicular carcinoma of the thyroid

Endocrine Pathology — MCQs

Endocrine Pathology — MCQs

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