SUN-284 - Neuroendocrine Metastatic Prostate Cancer Masquerading as Pelvic Paraganglioma Associated with MDH2 Mutation of Uncertain Significance

Paragangliomas (PGL) and neuroendocrine prostate carcinoma (NEPC) may exhibit overlapping clinical, biochemical, and imaging features despite distinct cellular origins. We report a case of metastatic prostate carcinoma initially mischaracterized as paraganglioma, highlighting a diagnostic pitfall.
A 78-year-old man was referred after CT revealed two enhancing hemipelvic masses (up to 5.6 cm), suspicious for extra-adrenal paraganglioma. He reported episodic diaphoresis, hot flashes, and lightheadedness. Biochemical evaluation showed plasma epinephrine of 79 pg/mL ( < 58), norepinephrine of 1418 pg/mL ( < 564), dopamine of 107 pg/mL ( < 16), and total catecholamines of 1604 pg/mL ( < 632). Ga-68 DOTATATE PET/CT demonstrated somatostatin receptor–avid pelvic masses (SUVmax 3.3 and 4.7) and diffuse prostate uptake (SUVmax 8.6), initially considered nonspecific and possibly prostatitis.
The patient underwent resection of the presumed paraganglioma. Histopathology instead demonstrated metastatic prostatic adenocarcinoma with neuroendocrine differentiation, with tumor cells positive for synaptophysin, cytokeratins, PSA, and NKX3.1, and negative for GATA3 and S100. Notably, PSA obtained preoperatively was markedly elevated at 689.7 ng/mL. Postoperatively, symptoms persisted, along with mild elevation in plasma metanephrine, normetanephrine, and total metanephrines measuring 54 pg/mL, 239 pg/mL, and 293 pg/mL, respectively. PSA decreased to 5 ng/mL. Subsequent pelvic MRI further characterized the prostatic primary tumor. A diagnosis of stage IV metastatic prostate adenocarcinoma with neuroendocrine differentiation was established, and treatment with carboplatin–etoposide and androgen deprivation therapy was offered.

This case illustrates a diagnostic pitfall in which metastatic prostate neuroendocrine carcinoma mimicked paraganglioma based on symptoms, biochemical findings, and somatostatin receptor imaging. The markedly elevated preoperative PSA and diffuse prostate uptake were key but initially underrecognized clues to prostatic origin. Definitive diagnosis required immunohistochemical confirmation of epithelial prostate lineage and absence of GATA3 and S100. NEPC typically secretes neuropeptides such as serotonin, chromogranin A, neuron-specific enolase, bombesin, and neurotensin rather than catecholamines. The mechanism of persistent metanephrine elevation remains unclear, with considerations including physiologic sympathetic activation, false-positive biochemical testing, or atypical metabolic reprogramming. Genetic studies in our patient, showed an MDH2 variant of uncertain significance. This raises the possibility of shared pseudohypoxia-related pathways described in paraganglioma syndromes, though its role in NEPC remains unclear. When clinical features are discordant, tissue diagnosis remains essential.

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