A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 56-year-old man presents to his physician’s office with a sudden increase in urinary frequency. During the past month, he has observed that he needs more frequent bathroom breaks. This is quite unusual as he hasn’t been consuming extra fluids. He reports feeling generally unwell over the past 2 months. He has lost over 7 kg (15.4 lb) of weight and has also been feeling progressively fatigued by the end of the day. He also has a persistent cough and on a couple of occasions, he noticed blood streaks on his napkin. In addition to all of this, he has been feeling weak with frequent muscle cramps during the day. He has never been diagnosed with any medical condition in the past. He doesn’t drink but has smoked 2 packs of cigarettes daily for the last 25 years. Prior to his appointment, he took a couple of tests. The results are given below:
Hemoglobin (Hb) 13.1 g/dL
Serum creatinine 0.8 mg/dL
Serum urea 13 mg/dL
Serum sodium 129 mEq/L
Serum potassium 3.2 mEq/L
His chest X-ray shows a central nodule with some hilar thickening. The physician recommends a biopsy of the nodule. Which of the following histological patterns is the nodule most likely to exhibit?
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A
Glandular cells, positive for mucinIncorrect. Mucin-positive glandular cells describe adenocarcinoma, peripheral and not strongly tied to paraneoplastic SIADH/ectopic ACTH.
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B
Squamous cells with keratin pearlsIncorrect. Keratin pearls describe squamous cell carcinoma, which causes hypercalcemia (PTHrP), not hyponatremia/hypokalemia from ectopic ADH and ACTH.
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C
Pleomorphic giant cellsIncorrect. Pleomorphic giant cells describe large cell carcinoma, not associated with this paraneoplastic profile.
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D
Kulchitsky cells with hyperchromatic nucleiCorrect. small cell lung carcinoma arises from Kulchitsky neuroendocrine cells and produces ectopic ADH (SIADH) and ectopic ACTH causing this electrolyte picture.
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E
Anaplastic cells with abundant clear cytoplasm and prominent vasculatureIncorrect. Clear-cell histology with prominent vasculature describes renal cell carcinoma, which arises in the kidney rather than the lung and would not produce a central pulmonary nodule.
↑ Tap an answer to reveal the reasoning
Answer: D. A heavy smoker (50 pack-years) with weight loss, fatigue, hemoptysis, muscle cramps, AND laboratory findings of HYPONATREMIA (Na 129) plus HYPOKALEMIA (K 3.2) has a paraneoplastic syndrome from a central lung mass. The combination of polyuria/urinary frequency and hyponatremia points to SIADH (syndrome of inappropriate ADH secretion), where ectopic ADH from the tumor causes water retention and dilutional hyponatremia. The hypokalemia and muscle cramps suggest additional ectopic Cushing syndrome — ectopic ACTH production from the tumor causes hypokalemic metabolic alkalosis.
The lung cancer that classically produces BOTH ectopic ADH (SIADH) and ectopic ACTH is SMALL CELL LUNG CARCINOMA (SCLC). SCLC is strongly tobacco-related, arises centrally, and is a neuroendocrine tumor derived from KULCHITSKY cells (neuroendocrine cells of the bronchial epithelium). Histologically, small cell carcinoma shows sheets of small, round to oval cells with scant cytoplasm, finely stippled ("salt and pepper") chromatin, hyperchromatic nuclei, and inconspicuous nucleoli. It is positive for neuroendocrine markers (chromogranin, synaptophysin).
The other histologies:
- Mucin-positive glandular cells = adenocarcinoma (most common in non-smokers, peripheral).
- Squamous cells with keratin pearls = squamous cell carcinoma (central, hypercalcemia from PTHrP).
- Pleomorphic giant cells = large cell carcinoma.
**Why each option:**
**A.** Mucin-positive glandular cells describe adenocarcinoma, peripheral and not strongly tied to paraneoplastic SIADH/ectopic ACTH.
**B.** Keratin pearls describe squamous cell carcinoma, which causes hypercalcemia (PTHrP), not hyponatremia/hypokalemia from ectopic ADH and ACTH.
**C.** Pleomorphic giant cells describe large cell carcinoma, not associated with this paraneoplastic profile.
**D.** Correct — small cell lung carcinoma arises from Kulchitsky neuroendocrine cells and produces ectopic ADH (SIADH) and ectopic ACTH causing this electrolyte picture.