Pheochromocytomas and paragangliomas, which exclusively produce dopamine, are very rare. Herein, we report for the first time a Japanese case of an exclusively dopamine-producing paraganglioma accompanied by detailed immunohistochemical analyses. A 70-year-old Japanese woman was referred to our hospital for functional examination of her left retroperitoneal mass. Her adrenal functions were normal, except for excessive dopamine secretion. After the tumorectomy, her dopamine level normalized. The histopathological diagnosis of the tumor was paraganglioma; this was confirmed by positive immunostaining of chromogranin A (CgA), tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), and succinate dehydrogenase gene subunit B (SDHB). However, the immunostaining of CgA in the tumor cells showed peculiar dot-like staining located corresponding to Golgi complex in the perinuclear area, rather than the diffuse cytoplasmic staining usually observed in epinephrine- or norepinephrine-producing functional pheochromocytomas and paragangliomas. The immunohistochemical results suggested that the tumor cells had sparse neuroendocrine granules in the cytoplasm, resulting in inhibition of catecholamine synthesis from dopamine to norepinephrine in neurosecretory granules. This may be the mechanism responsible for exclusive dopamine secretion in the present case.

BackgroundSunitinib, an oral multitarget tyrosine kinase inhibitor and standard first-line treatment for metastatic renal cell carcinoma (mRCC), is generally administered on a 6-week schedule (4 weeks on/2 weeks off). However, drug toxicity often leads to temporary treatment interruption, resulting in reduced treatment efficacy. In this report, we investigated whether sunitinib administration of at a dose of 25 mg/day in a 2-weeks-on/1-week-off cycle would reduce the incidence of drug-related side effects while maintaining drug efficacy.FindingsA total of six patients with mRCC were orally administered sunitinib at a dose of 25 mg/day in a 2-weeks-on/1-week-off regimen until intolerable toxicities occurred. All enrolled patients were assessed for toxicity and response. The median treatment period was 24 months (range, 9–40 months). Objective responses were as follows: disease stabilization of >6 months was achieved in all patients. The most important toxicities were neutropenia, fatigue, and proteinuria, but all were controlled.ConclusionsOral sunitinib at 25 mg/day in a 2-weeks-on/1-week-off regimen to Japanese patients can avoid drug-related toxicities while achieving the same dose intensity as a 6-week schedule. Because these data were derived from a small number of patients, future prospective studies of modified sunitinib administration schedules are warranted.

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