Endocrine pathology — MCQs

10 questions

A 37-year-old woman comes to the physician because of irregular menses and generalized fatigue for the past 4 months. Menses previously occurred at regular 25- to 29-day intervals and lasted for 5 days but now occur at 45- to 60-day intervals. She has no history of serious illness and takes no medications. She is 155 cm (5 ft 1 in) tall and weighs 89 kg (196 lb); BMI is 37 kg/m2. Her temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 146/100 mm Hg. Examination shows facial hair as well as comedones on the face and back. There are multiple ecchymotic patches on the trunk. Neurological examination shows weakness of the iliopsoas and biceps muscles bilaterally. Laboratory studies show: Hemoglobin 13.1 g/dL Leukocyte count 13,500/mm3 Platelet count 510,000/mm3 Serum Na+ 145 mEq/L K+ 3.3 mEq/L Cl- 100 mEq/L Glucose 188 mg/dL Which of the following is the most likely diagnosis?

A 45-year-old woman comes to the physician because of fatigue, irregular menses, and recurrent respiratory infections for the past 6 months. Her blood pressure is 151/82 mm Hg. Physical examination shows a round face, thinning of the skin, and multiple bruises on her arms. Further studies confirm the diagnosis of an ACTH-secreting pituitary adenoma. This patient is at greatest risk for which of the following?

A 48-year-old woman presents to her primary care physician with complaints of persistent fatigue, dizziness, and weight loss for the past 3 months. She has a history of hypothyroidism and takes thyroxine replacement. Her blood pressure is 90/60 mm Hg in a supine position and 65/40 mm Hg while sitting, temperature is 36.8°C (98.2°F), and pulse is 75/min. On physical examination, there is a mild increase in thyroid size, with a rubbery consistency. Her skin shows diffuse hyperpigmentation, more pronounced in the oral mucosa and palmar creases. Which of the following best represent the etiology of this patient’s condition?

A 37-year-old female presents to her primary care physician with constipation and abdominal pain. She notes that the pain has been present for several days and is not related to food. She also reports increased urinary frequency without incontinence, as well as increased thirst. She takes no medications, but notes taking vitamin supplements daily. Her vital signs are: BP 130/72 mmHg, HR 82 bpm, T 97.0 degrees F, and RR 12 bpm. Lab studies reveal: Na 139, K 4.1, Cl 104, HCO3 25, Cr 0.9, and Ca 12.4. Further studies show an increased ionized calcium, decreased PTH, and normal phosphate. What is the most likely cause of this patient's symptoms?

A 53-year-old man comes to the physician because of fatigue, recurrent diarrhea, and an 8-kg (17.6-lb) weight loss over the past 6 months. He has a 4-month history of recurrent blistering rashes on different parts of his body that grow and develop into pruritic, crusty lesions before resolving spontaneously. Physical examination shows scaly lesions in different phases of healing with central, bronze-colored induration around the mouth, perineum, and lower extremities. Laboratory studies show: Hemoglobin 10.1 mg/dL Mean corpuscular volume 85 μm3 Mean corpuscular hemoglobin 30.0 pg/cell Serum Glucose 236 mg/dL Abdominal ultrasonography shows a 3-cm, solid mass located in the upper abdomen. This patient's mass is most likely derived from which of the following types of cells?

A 55-year-old man presents to the emergency department because of an excruciating headache that started suddenly after he got home from work. He also reports having double vision. Specifically, in the last week he almost got into two car accidents with vehicles that "came out of nowhere" while he was trying to merge on the highway. Physical examination is notable for ptosis of the left eye, which is also inferiorly and laterally deviated. The patient is treated emergently and then started on a hormone replacement in order to avoid life-threatening post-treatment complications. The patient's current presentation was associated with a pathologic process that existed for several months prior to this event. Which of the following symptoms could this patient have experienced as part of that pre-existing pathology?

A 52-year-old woman presents to her primary care physician with symptoms of heat intolerance, unintentional weight loss, feelings of anxiety, and excessive energy that hinder her from falling asleep at night. On physical exam, the patient is found to have mildly protuberant eyes bilaterally as well as discoloration and swelling of her shins. Which of the following lab results would most likely be present in this patient?

An otherwise healthy 47-year-old woman comes to the physician for the evaluation of a 4-month history of worsening fatigue and constipation. She has also noticed that her cheeks appear fuller and her voice has become hoarse. Her temperature is 36.3°C (97.3°F) and pulse is 59/min. Examination of the neck shows a painless, mildly enlarged thyroid gland. Her skin is dry and cool and her nails appear brittle. Serum studies show antibodies against thyroid peroxidase. A biopsy of the thyroid gland is most likely to show which of the following?

A 36-year-old man is admitted to the hospital because of a 1-day history of epigastric pain and vomiting. He has had similar episodes of epigastric pain in the past. He drinks 8 oz of vodka daily. Five days after admission, the patient develops aspiration pneumonia and sepsis. Despite appropriate therapy, the patient dies. At autopsy, the pancreas appears gray, enlarged, and nodular. Microscopic examination of the pancreas shows localized deposits of calcium. This finding is most similar to an adaptive change that can occur in which of the following conditions?

Q10

A 47-year-old woman comes to the physician because of a 2-month history of a lump on her neck and a 1-week history of hoarseness. Examination shows a 3-cm, firm, non-tender nodule on the anterior neck. Further evaluation confirms a thyroid malignancy, and she undergoes thyroidectomy. Histopathologic examination of the surgical specimen shows lymphatic invasion. Genetic analysis shows an activating mutation in the RET/PTC genes. Microscopic examination of the surgical specimen is most likely to also show which of the following?

Endocrine pathology US Medical PG Practice Questions and MCQs

Question 1: A 37-year-old woman comes to the physician because of irregular menses and generalized fatigue for the past 4 months. Menses previously occurred at regular 25- to 29-day intervals and lasted for 5 days but now occur at 45- to 60-day intervals. She has no history of serious illness and takes no medications. She is 155 cm (5 ft 1 in) tall and weighs 89 kg (196 lb); BMI is 37 kg/m2. Her temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 146/100 mm Hg. Examination shows facial hair as well as comedones on the face and back. There are multiple ecchymotic patches on the trunk. Neurological examination shows weakness of the iliopsoas and biceps muscles bilaterally. Laboratory studies show: Hemoglobin 13.1 g/dL Leukocyte count 13,500/mm3 Platelet count 510,000/mm3 Serum Na+ 145 mEq/L K+ 3.3 mEq/L Cl- 100 mEq/L Glucose 188 mg/dL Which of the following is the most likely diagnosis?

A. Pheochromocytoma
B. Cushing syndrome (Correct Answer)
C. Primary hyperaldosteronism
D. Polycystic ovarian syndrome
E. Hypothyroidism

Explanation: ***Cushing syndrome*** - The constellation of **obesity**, **hypertension**, **irregular menses**, **hirsutism** (facial hair), **acne** (comedones), **easy bruising** (ecchymotic patches), **proximal muscle weakness** (iliopsoas and biceps), **leukocytosis**, **thrombocytosis**, **hypokalemia**, and **hyperglycemia** is highly characteristic of Cushing syndrome due to chronic glucocorticoid excess. - The patient's **truncal obesity** (BMI 37 kg/m2) and the metabolic derangements further support this diagnosis. *Pheochromocytoma* - While pheochromocytoma can cause **hypertension** and **tachycardia**, it typically presents with **episodic symptoms** like palpitations, sweating, and headaches. - It does not explain the other prominent features such as **hirsutism**, **menstrual irregularities**, **proximal muscle weakness**, or **easy bruising**. *Primary hyperaldosteronism* - This condition is characterized by **hypertension** and **hypokalemia**, often leading to fatigue. - However, it does not account for the patient's **hirsutism**, **menstrual irregularities**, **obesity**, **easy bruising**, **muscle weakness**, **acne**, or **hyperglycemia**. *Polycystic ovarian syndrome* - PCOS causes **irregular menses**, **hirsutism**, **acne**, and **obesity**, which are present in this patient. - However, it typically does not cause **hypertension**, **hypokalemia**, **easy bruising**, or **proximal muscle weakness**, making Cushing syndrome a more encompassing diagnosis. *Hypothyroidism* - Hypothyroidism can lead to **fatigue**, **menstrual irregularities**, and **weight gain**. - However, it typically presents with **bradycardia**, **dry skin**, **constipation**, and **cold intolerance**, not **hypertension**, **hirsutism**, **acne**, **easy bruising**, or **proximal muscle weakness**.

Question 2: A 45-year-old woman comes to the physician because of fatigue, irregular menses, and recurrent respiratory infections for the past 6 months. Her blood pressure is 151/82 mm Hg. Physical examination shows a round face, thinning of the skin, and multiple bruises on her arms. Further studies confirm the diagnosis of an ACTH-secreting pituitary adenoma. This patient is at greatest risk for which of the following?

A. Weight loss
B. Eosinophilia
C. Bitemporal hemianopsia
D. Hypoglycemia
E. Pathologic fracture (Correct Answer)

Explanation: ***Pathologic fracture*** - This patient has **Cushing's disease** due to an **ACTH-secreting pituitary adenoma**, leading to excess cortisol. - **Excess cortisol** causes **osteoporosis** by increasing bone resorption and decreasing bone formation, significantly raising the risk of **pathologic fractures**. - This is the **greatest risk** because **all patients** with chronic hypercortisolism develop bone loss, making fractures highly likely. *Weight loss* - Patients with Cushing's disease typically experience **weight gain**, particularly centrally (truncal obesity), due to **cortisol-induced fat redistribution**. - **Fatigue** is common, but weight loss is not a characteristic feature of Cushing's syndrome. *Eosinophilia* - **Hypercortisolism** (Cushing's syndrome) usually causes **eosinopenia** (decreased eosinophil count) and **lymphopenia**, not eosinophilia. - Cortisol has an anti-inflammatory and immunosuppressive effect, leading to a reduction in circulating eosinophils and lymphocytes. *Bitemporal hemianopsia* - While an **ACTH-secreting pituitary adenoma** is present, **bitemporal hemianopsia** occurs only when a pituitary tumor becomes a **macroadenoma** (>10mm) and compresses the **optic chiasm**. - Most ACTH-secreting adenomas are **microadenomas** (<10mm) that cause symptoms through **hormonal excess**, not mass effect. - The clinical picture here reflects **Cushing's syndrome** from hypercortisolism, which affects **all patients** regardless of tumor size, whereas visual field defects occur only with large tumors. *Hypoglycemia* - **Excess cortisol** **increases gluconeogenesis** and **insulin resistance**, leading to **hyperglycemia**, not hypoglycemia. - This is a common metabolic complication of Cushing's syndrome, often progressing to **steroid-induced diabetes mellitus**.

Question 3: A 48-year-old woman presents to her primary care physician with complaints of persistent fatigue, dizziness, and weight loss for the past 3 months. She has a history of hypothyroidism and takes thyroxine replacement. Her blood pressure is 90/60 mm Hg in a supine position and 65/40 mm Hg while sitting, temperature is 36.8°C (98.2°F), and pulse is 75/min. On physical examination, there is a mild increase in thyroid size, with a rubbery consistency. Her skin shows diffuse hyperpigmentation, more pronounced in the oral mucosa and palmar creases. Which of the following best represent the etiology of this patient’s condition?

A. Prolonged corticosteroid therapy
B. ↓ corticotropin-releasing hormone secretion from the hypothalamus
C. Autoimmune destruction of the adrenal gland (Correct Answer)
D. ↓ adrenocorticotropic hormone secretion from the pituitary gland
E. ↑ iron absorption and deposition in the body

Explanation: ***Autoimmune destruction of the adrenal gland*** - The patient's symptoms, including **fatigue**, **dizziness**, **weight loss**, **hypotension**, and especially **diffuse hyperpigmentation of the skin and oral mucosa**, are classic signs of **primary adrenal insufficiency (Addison's disease)**. - Given the history of **hypothyroidism** (another autoimmune disorder), **autoimmune destruction of the adrenal glands** is the most likely underlying cause. *Prolonged corticosteroid therapy* - **Prolonged corticosteroid therapy** can lead to **secondary adrenal insufficiency** by suppressing the **hypothalamic-pituitary-adrenal (HPA) axis**. - However, this would typically cause **ACTH deficiency**, leading to **pale skin** rather than hyperpigmentation, as the melanocyte-stimulating hormone (MSH) levels would also be low. *↓ corticotropin-releasing hormone secretion from the hypothalamus* - Decreased **CRH secretion** would result in **secondary adrenal insufficiency**, characterized by **low ACTH** and subsequently low cortisol. - This condition does not cause **hyperpigmentation** because MSH levels, which are co-secreted with ACTH from a common precursor (POMC), would also be low. *↓ adrenocorticotropic hormone secretion from the pituitary gland* - A reduction in **ACTH secretion** (secondary adrenal insufficiency) causes symptoms of **cortisol deficiency** but typically leads to **pallor** due to the lack of MSH stimulation. - It does not cause the **hyperpigmentation** seen in this patient, which is a hallmark of primary adrenal insufficiency where high ACTH (and MSH) levels stimulate melanocytes. *↑ iron absorption and deposition in the body* - Increased **iron absorption and deposition** is characteristic of **hemochromatosis**, which can cause fatigue and skin bronzing, but not the specific hyperpigmentation patterns (oral mucosa, palmar creases) or the significant hypotension and weight loss seen here. - Hemochromatosis primarily affects the liver, heart, and pancreas, and does not involve adrenal gland dysfunction in this manner.

Question 4: A 37-year-old female presents to her primary care physician with constipation and abdominal pain. She notes that the pain has been present for several days and is not related to food. She also reports increased urinary frequency without incontinence, as well as increased thirst. She takes no medications, but notes taking vitamin supplements daily. Her vital signs are: BP 130/72 mmHg, HR 82 bpm, T 97.0 degrees F, and RR 12 bpm. Lab studies reveal: Na 139, K 4.1, Cl 104, HCO3 25, Cr 0.9, and Ca 12.4. Further studies show an increased ionized calcium, decreased PTH, and normal phosphate. What is the most likely cause of this patient's symptoms?

A. Vitamin overdose (Correct Answer)
B. Vitamin deficiency
C. Inherited disorder
D. Plasma cell neoplasm
E. Primary endocrine dysfunction

Explanation: ***Vitamin overdose*** - The patient's symptoms of **constipation**, **abdominal pain**, **increased urinary frequency**, and **thirst** are classic signs of **hypercalcemia**. - The lab findings of **hypercalcemia (Ca 12.4)**, **increased ionized calcium**, **decreased PTH**, and increased phosphate, coupled with a history of daily vitamin supplements, strongly suggest **Vitamin D toxicity** from overdose, which leads to increased calcium absorption and bone resorption. *Vitamin deficiency* - Vitamin deficiencies typically do not cause **hypercalcemia**; in fact, severe **Vitamin D deficiency** can lead to **hypocalcemia** and **secondary hyperparathyroidism**. - Symptoms associated with common vitamin deficiencies (e.g., scurvy, rickets) are not consistent with this patient's presentation. *Inherited disorder* - While some **inherited disorders** (e.g., **Familial Hypocalciuric Hypercalcemia**) can cause hypercalcemia, the distinguishing feature is typically a **normal or mildly elevated PTH** and **low urinary calcium excretion**, which is not entirely aligned with the presented PTH and phosphate levels and the acute onset suggested by symptoms. - The patient's history of **vitamin supplement** use provides a more direct and likely explanation for acute hypercalcemia. *Plasma cell neoplasm* - **Plasma cell neoplasms** like **multiple myeloma** can cause **hypercalcemia** due to increased bone resorption from osteoclast-activating factors. - However, hypercalcemia from these conditions is often accompanied by other signs of malignancy such as **renal failure**, **anemia**, or **bone lesions**, which are not reported in this case, and the **decreased PTH** points away from malignancy-associated humorally mediated hypercalcemia. *Primary endocrine dysfunction* - **Primary hyperparathyroidism** is a common cause of **hypercalcemia**, but it is characterized by **elevated or inappropriately normal PTH levels** in the presence of hypercalcemia, which contradicts the **decreased PTH** found in this patient. - Other endocrine causes of hypercalcemia, such as **thyrotoxicosis** or **adrenal insufficiency**, present with distinct clinical features not described here.

Question 5: A 53-year-old man comes to the physician because of fatigue, recurrent diarrhea, and an 8-kg (17.6-lb) weight loss over the past 6 months. He has a 4-month history of recurrent blistering rashes on different parts of his body that grow and develop into pruritic, crusty lesions before resolving spontaneously. Physical examination shows scaly lesions in different phases of healing with central, bronze-colored induration around the mouth, perineum, and lower extremities. Laboratory studies show: Hemoglobin 10.1 mg/dL Mean corpuscular volume 85 μm3 Mean corpuscular hemoglobin 30.0 pg/cell Serum Glucose 236 mg/dL Abdominal ultrasonography shows a 3-cm, solid mass located in the upper abdomen. This patient's mass is most likely derived from which of the following types of cells?

A. Gastrointestinal enterochromaffin cells
B. Pancreatic β-cells
C. Pancreatic δ-cells
D. Pancreatic α-cells (Correct Answer)
E. Gastric G-cells

Explanation: ***Pancreatic α-cells*** - The patient's symptoms of **fatigue, recurrent diarrhea, weight loss, blistering rash (necrolytic migratory erythema)**, and **hyperglycemia** are classic features of a **glucagonoma**. - A **glucagonoma** is a tumor of the pancreatic α-cells that **secretes excessive glucagon**, leading to these characteristic signs and symptoms, supported by the presence of an **upper abdominal mass**. *Gastrointestinal enterochromaffin cells* - Tumors of gastrointestinal enterochromaffin cells (carcinoid tumors) typically produce **serotonin** and present with flushing, diarrhea, bronchospasm, and valvular heart disease, not the skin rash or hyperglycemia seen here. - While carcinoid tumors can cause diarrhea, the additional symptoms of **necrolytic migratory erythema** and **diabetes** are not characteristic. *Pancreatic β-cells* - Tumors of pancreatic β-cells (**insulinomas**) produce excessive insulin, leading to **hypoglycemia**, not the hyperglycemia observed in this patient. - Insulinomas cause symptoms like sweating, tremors, confusion, and palpitations, which are inconsistent with the patient's presentation. *Pancreatic δ-cells* - Pancreatic δ-cell tumors (**somatostatinomas**) secrete **somatostatin**, which can cause **diabetes mellitus**, steatorrhea, and gallstones. - While diabetes is present, the characteristic **necrolytic migratory erythema** and severe diarrhea are less common with somatostatinomas. *Gastric G-cells* - Tumors of gastric G-cells (**gastrinomas**) secrete **gastrin**, leading to **Zollinger-Ellison syndrome**, characterized by severe peptic ulcers, abdominal pain, and chronic diarrhea. - Gastrinomas do not typically cause **necrolytic migratory erythema** or significant hyperglycemia.

Question 6: A 55-year-old man presents to the emergency department because of an excruciating headache that started suddenly after he got home from work. He also reports having double vision. Specifically, in the last week he almost got into two car accidents with vehicles that "came out of nowhere" while he was trying to merge on the highway. Physical examination is notable for ptosis of the left eye, which is also inferiorly and laterally deviated. The patient is treated emergently and then started on a hormone replacement in order to avoid life-threatening post-treatment complications. The patient's current presentation was associated with a pathologic process that existed for several months prior to this event. Which of the following symptoms could this patient have experienced as part of that pre-existing pathology?

A. Kidney stones
B. Hyperkalemia
C. Increased hat size (Correct Answer)
D. Gastric ulcers
E. Hypoglycemia

Explanation: ***Increased hat size*** - The emergent treatment and subsequent hormone replacement for a life-threatening post-treatment complication, along with double vision and an excruciating headache, suggests a diagnosis of **pituitary apoplexy**. - Pituitary apoplexy is often due to an acute hemorrhage or infarction within a pre-existing pituitary adenoma. A large adenoma can cause symptoms like **increased hat size** due to the progressive growth of facial bones and skull, a hallmark of **acromegaly** if the adenoma secretes growth hormone. *Kidney stones* - While a pituitary adenoma secreting **ACTH** (Cushing's disease) can lead to **hypercalciuria** and kidney stones, this specific symptom is not as directly indicative of a pre-existing pathology that would explain the acute presentation and subsequent hormone replacement. - Kidney stones are not a primary or direct symptom of a pituitary adenoma in the way that acromegaly-related changes are. *Hyperkalemia* - Hyperkalemia is typically associated with conditions like **adrenal insufficiency** or **renal failure**, not directly with the pre-existing pituitary pathology leading to apoplexy. - Insufficiency of mineralocorticoids (e.g., in adrenal crisis, which can be a complication of pituitary apoplexy due to ACTH deficiency) causes **hyponatremia** and **hyperkalemia**, but this would be a consequence of the acute event and not a pre-existing symptom of the adenoma itself. *Gastric ulcers* - Although conditions like **Zollinger-Ellison syndrome** (due to a **gastrinoma**) involve ulcers, and **MEN1 syndrome** can include pituitary adenomas and gastrinomas, gastric ulcers are not a direct or common pre-existing symptom of a pituitary adenoma itself. - Additionally, **Cushing's syndrome** (which can be caused by an ACTH-secreting pituitary adenoma) can be associated with an increased risk of peptic ulcers due to high cortisol levels, but it's not a primary or specific finding. *Hypoglycemia* - Hypoglycemia can occur with **adrenal insufficiency** or **growth hormone deficiency**, both of which can be consequences of pituitary dysfunction, particularly if the adenoma destroys normal pituitary tissue or after apoplexy. - However, hypoglycemia is often an acute or late symptom of hormonal deficiencies, rather than a prominent pre-existing symptom of the growing adenoma prior to the acute event, especially compared to the chronic changes of acromegaly.

Question 7: A 52-year-old woman presents to her primary care physician with symptoms of heat intolerance, unintentional weight loss, feelings of anxiety, and excessive energy that hinder her from falling asleep at night. On physical exam, the patient is found to have mildly protuberant eyes bilaterally as well as discoloration and swelling of her shins. Which of the following lab results would most likely be present in this patient?

A. Decreased serum TSH (Correct Answer)
B. Increased anti-mitochondrial antibodies
C. Decreased free T4
D. Increased serum TSH
E. Decreased anti-TSH receptor antibodies

Explanation: ***Decreased serum TSH*** - The patient's symptoms (heat intolerance, weight loss, anxiety, insomnia, protuberant eyes, pretibial myxedema) are classic for **hyperthyroidism**, specifically **Graves' disease**. - In primary hyperthyroidism, the thyroid gland overproduces thyroid hormones (T3 and T4), which **negatively feedback** on the pituitary, leading to a decreased or **undetectable serum TSH**. *Increased anti-mitochondrial antibodies* - **Anti-mitochondrial antibodies (AMAs)** are the hallmark of **primary biliary cholangitis**, a chronic autoimmune liver disease. - This condition presents with symptoms like **fatigue, pruritus, and jaundice**, which are not observed in this patient. *Decreased free T4* - A **decreased free T4** indicates **hypothyroidism**, where the thyroid gland produces insufficient thyroid hormones. - This would present with symptoms opposite to those described, such as **cold intolerance, weight gain, fatigue, and bradycardia**. *Decreased anti-TSH receptor antibodies* - **Anti-TSH receptor antibodies (TRAb)** are characteristic of Graves' disease, and they are typically **stimulatory** (thyroid-stimulating immunoglobulins), meaning they mimic TSH and **increase** thyroid hormone production. - A decrease in these antibodies would suggest a *reduction* in the autoimmune stimulation, which is inconsistent with the patient's active hyperthyroid state. - In this patient with clear Graves' disease, these antibodies would be **elevated**, not decreased. *Increased serum TSH* - An **increased serum TSH** is indicative of **primary hypothyroidism**, where the pituitary gland attempts to stimulate an underactive thyroid. - This would lead to symptoms of **fatigue, weight gain, cold intolerance, and bradycardia**, which contradict the patient's presentation.

Question 8: An otherwise healthy 47-year-old woman comes to the physician for the evaluation of a 4-month history of worsening fatigue and constipation. She has also noticed that her cheeks appear fuller and her voice has become hoarse. Her temperature is 36.3°C (97.3°F) and pulse is 59/min. Examination of the neck shows a painless, mildly enlarged thyroid gland. Her skin is dry and cool and her nails appear brittle. Serum studies show antibodies against thyroid peroxidase. A biopsy of the thyroid gland is most likely to show which of the following?

A. Tall follicular cells, scalloped colloid, and vascular congestion
B. Lymphocytic infiltration, Hürthle cells, and germinal centers (Correct Answer)
C. Large, irregular nuclei, nuclear grooves, and Psammoma bodies
D. Spindle cells, pleomorphic giant cells, and mitotic figures
E. Multinucleated giant cells, macrophages, and degenerated follicular cells

Explanation: ***Lymphocytic infiltration, Hürthle cells, and germinal centers*** - The patient's symptoms (fatigue, constipation, fuller cheeks, hoarse voice, dry and cool skin, brittle nails, bradycardia, mildly enlarged thyroid gland) are classic for **hypothyroidism**. The presence of **anti-thyroid peroxidase antibodies** confirms an autoimmune etiology, specifically **Hashimoto's thyroiditis**. - **Hashimoto's thyroiditis** is characterized pathologically by extensive **lymphocytic infiltration** of the thyroid parenchyma, the presence of **Hürthle cells** (metaplastic follicular cells with abundant eosinophilic cytoplasm), and the formation of **germinal centers** within the thyroid gland. *Tall follicular cells, scalloped colloid, and vascular congestion* - This description is characteristic of **Graves' disease**, an autoimmune cause of **hyperthyroidism**. - The patient's symptoms and signs (e.g., bradycardia, dry skin, constipation) are consistent with **hypothyroidism**, not hyperthyroidism. *Large, irregular nuclei, nuclear grooves, and Psammoma bodies* - These are classic histological features of **papillary thyroid carcinoma**, the most common type of thyroid cancer. - While thyroid nodules can occur in Hashimoto's, the overall clinical picture points strongly to a benign autoimmune inflammatory process, not malignancy. *Spindle cells, pleomorphic giant cells, and mitotic figures* - This describes **anaplastic thyroid carcinoma**, a highly aggressive and undifferentiated thyroid malignancy. - Anaplastic carcinoma typically presents as a rapidly enlarging, painful neck mass in older individuals, which is not consistent with this patient's chronic, milder presentation. *Multinucleated giant cells, macrophages, and degenerated follicular cells* - This histological pattern is characteristic of **subacute granulomatous thyroiditis (de Quervain's thyroiditis)**. - Subacute thyroiditis typically presents with painful thyroid enlargement and often follows a viral infection, which is not suggested by the patient's symptoms or antibody findings.

Question 9: A 36-year-old man is admitted to the hospital because of a 1-day history of epigastric pain and vomiting. He has had similar episodes of epigastric pain in the past. He drinks 8 oz of vodka daily. Five days after admission, the patient develops aspiration pneumonia and sepsis. Despite appropriate therapy, the patient dies. At autopsy, the pancreas appears gray, enlarged, and nodular. Microscopic examination of the pancreas shows localized deposits of calcium. This finding is most similar to an adaptive change that can occur in which of the following conditions?

A. Primary hyperparathyroidism
B. Sarcoidosis
C. Multiple myeloma
D. Congenital CMV infection
E. Chronic kidney disease (Correct Answer)

Explanation: ***Chronic kidney disease*** - The pancreatic finding represents **dystrophic calcification** (calcium deposition in damaged tissue with normal serum calcium levels), a consequence of chronic pancreatitis. - **Chronic kidney disease** is the most similar condition because it also involves pathologic calcification as an adaptive/pathologic change, though through a different mechanism called **metastatic calcification**. - In CKD, **hyperphosphatemia** and secondary **hyperparathyroidism** elevate the serum calcium-phosphate product, leading to calcium deposition in **normal tissues** (blood vessels, kidneys, lungs, gastric mucosa). - Both conditions demonstrate **pathologic calcification as a tissue response** to metabolic derangement, making CKD the best answer among the options provided. *Primary hyperparathyroidism* - Causes **hypercalcemia** and **hypophosphatemia** due to excess PTH secretion. - Can lead to **metastatic calcification** in normal tissues, but is less commonly associated with widespread tissue calcification compared to CKD. - The mineral imbalance pattern differs from CKD (high calcium, low phosphate vs. high phosphate, variable calcium). *Sarcoidosis* - Causes **hypercalcemia** due to increased 1,25-dihydroxyvitamin D production by activated macrophages in granulomas. - Can result in **metastatic calcification**, particularly nephrocalcinosis. - However, this is less common and less extensive than the calcification seen in CKD. *Multiple myeloma* - Produces **hypercalcemia** through osteolytic bone destruction and cytokine-mediated bone resorption. - Can theoretically cause **metastatic calcification**, but this is not a typical or prominent feature of the disease. - The hypercalcemia is usually addressed before significant tissue calcification occurs. *Congenital CMV infection* - Causes **dystrophic calcification** in damaged tissues, typically **periventricular intracranial calcifications**. - While this involves the same type of calcification (dystrophic), CMV infection is not characterized by systemic or progressive calcification as an adaptive metabolic response. - The calcifications are focal sequelae of viral tissue damage, not a widespread metabolic derangement.

Question 10: A 47-year-old woman comes to the physician because of a 2-month history of a lump on her neck and a 1-week history of hoarseness. Examination shows a 3-cm, firm, non-tender nodule on the anterior neck. Further evaluation confirms a thyroid malignancy, and she undergoes thyroidectomy. Histopathologic examination of the surgical specimen shows lymphatic invasion. Genetic analysis shows an activating mutation in the RET/PTC genes. Microscopic examination of the surgical specimen is most likely to also show which of the following?

A. Pleomorphic giant cells with numerous atypical mitotic figures
B. Cuboidal cells arranged spherically around colloid lakes
C. Hyperplastic epithelium with colloid scalloping
D. Calcified spherules and large oval cells with empty-appearing nuclei (Correct Answer)
E. Sheets of polygonal cells surrounding amyloid deposition

Explanation: ***Calcified spherules and large oval cells with empty-appearing nuclei*** - The presence of an **activating mutation in RET/PTC genes**, **lymphatic invasion**, and a new neck lump with hoarseness (suggesting nerve involvement) are highly characteristic of **papillary thyroid carcinoma**. - Microscopic features of papillary thyroid carcinoma include **Psammoma bodies (calcified spherules)**, **Orphan Annie eye nuclei (large oval cells with empty-appearing nuclei)**, and nuclear grooves. *Pleomorphic giant cells with numerous atypical mitotic figures* - This description typically refers to **anaplastic thyroid carcinoma**, a highly aggressive and undifferentiated tumor. - While anaplastic carcinoma can present with rapid growth and hoarseness, it is less commonly associated with a **RET/PTC mutation** (BRAF mutations are more common) and typically has a much poorer prognosis, often presenting with a rapidly enlarging mass rather than a 2-month history suggestive of a more indolent tumor. *Cuboidal cells arranged spherically around colloid lakes* - This morphology is characteristic of **follicular thyroid carcinoma** or **follicular adenoma**. - While follicular tumors can have RET/PTC mutations in some variants, the classic features described (empty-appearing nuclei and psammoma bodies) are absent here. *Hyperplastic epithelium with colloid scalloping* - This describes the histologic features seen in **Graves' disease** or **diffuse toxic goiter**, a benign condition. - It is not indicative of malignancy, and the patient's presentation with a solitary nodule and hoarseness points to a malignant process. *Sheets of polygonal cells surrounding amyloid deposition* - This is the classic microscopic appearance of **medullary thyroid carcinoma**. - Medullary thyroid carcinoma is also associated with **RET mutations**, but these are typically **germline or somatic RET point mutations** (e.g., RET M918T), not RET/PTC rearrangements, and it arises from parafollicular C cells, producing calcitonin, not thyroid hormones.

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