Dopamine-Secreting Pheochromocytoma and Paraganglioma

Abstract

Predominantly or exclusively dopamine-secreting pheochromocytoma and paraganglioma are very rare. We report a 64-year-old woman with an adrenal incidentaloma. She was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 μg/day), normal epinephrine (24.3 μg/day), and markedly elevated dopamine (148 212.4 μg/day). ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy revealed tumor uptake. After α-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all 3 catecholamine-synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine β-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis were evident 1 year after the surgery. We conducted a literature search in the PubMed database. A total of 33 cases were collected. Our case had the second-highest 24-hour urinary dopamine excretion and was the first in which immunostaining for catecholamine synthase and electron microscopy were performed together. Histological findings in our case give a possible hypothesis that the mechanism underlying a dopamine-secreting pheochromocytoma is associated with immature catecholamine vesicles in which dopamine β-hydroxylase is localized, thus resulting in inhibited conversion from dopamine to norepinephrine. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of α-blockade is needed, and the association between the prognosis and genetic mutation, with an extensive literature review.

Keywords: dopamine; dopamine-secreting; electron microscopy; immunohistochemistry; paraganglioma; pheochromocytoma.

Figure 1.

Diagnostic imaging: CT, MRI, ¹²³I-MIBG scintigraphy, and FDG-PET. A, CT scan shows left abdominal mass (5.6 × 5.1 × 10.6 cm). B, C, and D, MRI shows diffusely heterogenous with mixed high and low intensity on both T1- and T2-weighted. There is a large cystic lesion within the tumor that showed high signal with the same intensity as water on T2-weighted and a thinning normal adrenal gland (red arrow) on the ventral side of the tumor. E, ¹²³I-MIBG scintigraphy and F, FDG-PET indicate marked uptake into the tumor but no metastatic lesions.

Figure 2.

Microscopic findings. The hematoxylin and eosin–stained tumor cells were small, with spindle-shaped to round nuclei, a granular cytoplasm, a high N/C ratio, and high density. A small portion was arranged in a pseudo-rosette pattern (a). CgA was positive with heterogeneity (b). Compared with positive controls of normal adrenal medulla, TH was mostly negative (c), DBH was positive with heterogeneity (d), PNMT was mostly negative (e). SDHB was diffusely positive (f). EM showed that the tumor tissue contained small secretory granules with diameters of about 100 nm (g, h, red arrows). Abbreviations: CgA, chromogranin A; DBH, dopamine β-hydroxylase; EM, electron microscopy; N/C, nucleo-cytoplasmic, PCC, pheochromocytoma; PNMT, phenylethanolamine-N-methyltransferase; SDHB, succinate dehydrogenase subunit B; TH, tyrosine hydroxylase.