Dual Paraneoplastic Endocrine Syndromes Heralding Onset of Extrapulmonary Small Cell Carcinoma: A Case Report and Narrative Review

OBJECTIVE: Extrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance. METHODS: Clinical, laboratory, imaging, and pathology data are presented. RESULTS: A 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube. Laboratory results included calcium 13.8 mg/dL (8.5–10.5 mg/dL), albumin 3.6 g/dL (3.5–5 mg/dL), and potassium 2.8 mmol/L (3.5–5.2 mmol/L). Hypercalcemia investigation revealed intact PTH 19 pg/mL (16–87 pg/mL), 25-OH vitamin D 15.7 ng/mL (>30 ng/mL), and PTH-related peptide (PTHrP) 63.4 pmol/L (<2.3 pmol/L). Workup for hypokalemia yielded aldosterone 5.3 ng/dL (<31 ng/dL), renin 0.6 ng/mL/h (0.5–4 ng/mL/h), and 6:00 a.m. cortisol 82 µg/dL (6.7–22.6 µg/dL) with ACTH 147 pg/mL (no ref. range). High-dose Dexamethasone suppression testing suggested ACTH-dependent ectopic hypercortisolism. Contrast-enhanced CT findings included masses in the liver and right renal pelvis, a heterogeneous enlarged mass in the region of the prostate invading the bladder, bilateral adrenal thickening, and lytic lesions in the pelvis and spine. Liver biopsy identified epithelioid malignancy with Ki proliferation index 98% and immunohistochemical staining positive for synaptophysin and neuron-specific enolase, compatible with high-grade small cell carcinoma. Staining for ACTH was negative; no stain for CRH was available. Two weeks after chemotherapy, 6:00 a.m. cortisol normalized and CT scans showed universal improvement. CONCLUSION: Extensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes.