Treatment-related neuroendocrine prostatic carcinoma masquerading as a pheochromocytoma: an unusual presentation

Prostatic adenocarcinoma metastases to adrenal gland are rare and can be difficult to distinguish from primary adrenal neoplasms, particularly pheochromocytoma, especially in the post- treatment setting where neuroendocrine transformation is possible. We report a case of a 76-year-old man with a history of Grade Group 1 prostatic acinar adenocarcinoma, who presented with biochemical recurrence. A 68 Ga-prostate specific membrane antigen-positron emission tomography computed tomography (PSMA-PET CT) scan revealed a mass in the right adrenal gland. Histology of the adrenalectomy specimen demonstrated a mass arising in the adrenal medulla with lobulated architecture containing non-acinar sheets of monotonous cells with speckled chromatin, suggestive of a low-grade neuroendocrine neoplasm. Notably, there was no necrosis, no significantly increased mitotic figures, and no single cell apoptoses seen. The immunohistochemical profile showed that the neoplastic cells were positive for synaptophysin, chromogranin, CAM5.2, MNF116 and NKX3.1, and negative for GATA3 and SF1. A PSMA immunostain demonstrated strong membranous staining in the neoplastic cells, in contrast to the nonspecific, peri-nuclear dot-like pattern observed in three representative pheochromocytomas. Ki-67 showed a single hotspot proliferation index of 9%. p53 showed a null mutant pattern and RB expression was lost. Altogether, the findings were consistent with metastatic treatment-related neuroendocrine prostatic carcinoma. This case highlights the morphologic difficulty in distinguishing treatment-related prostatic neuroendocrine carcinoma from pheochromocytoma and demonstrates how distinct immunohistochemical staining patterns can be a useful tool for differentiation.