Markedly Melanin-Pigmented Paraganglioma Associated With Decreased Dopa-Decarboxylase Expression

A 49-year-old woman undergoing evaluation for sigmoid colon cancer was incidentally found to have a 56-mm retroperitoneal tumor. Although asymptomatic, her blood dopamine level was elevated to 783 pg/mL (reference range, ≤20 pg/mL [SI: ≤79.55 pmol/L]). Magnetic resonance imaging revealed high intensity on T2-weighted and diffuse high intensity on fat-suppressed T1-weighted images, suggestive of a melanin-producing paraganglioma (PGL). The surgically resected tumor appeared black macroscopically, and histological examination showed brown melanin granules on hematoxylin and eosin staining, consistent with pigmented PGL. This rare tumor's pathogenesis remains poorly understood. Catecholamines and melanin both originate from tyrosine via L-DOPA. Normally, in the adrenal medulla and ganglia, L-DOPA is converted to dopamine by dopa decarboxylase (DDC). However, decreased DDC activity can lead to elevated L-DOPA levels, which may contribute to melanin synthesis and pigmentation. Since L-DOPA secreted into the blood is rapidly converted to dopamine by vascular endothelial DDC, blood dopamine can rise even without a dopamine-producing tumor. In this case, DDC immunostaining was negative, suggesting an L-DOPA-producing tumor. Based on these findings, we hypothesize that all pigmented PGLs may represent L-DOPA-producing tumors.