Composite Pheochromocytomas: More Common Than Expected and Associated With Distinct Clinical Profile

Composite pheochromocytomas, defined by the coexistence of pheochromocytoma and neural crest-derived elements and their clinical course remain poorly defined. The aim of this study was to assess the clinical characteristics and outcomes of composite pheochromocytomas compared with typical pheochromocytomas.

We retrospectively analyzed 190 patients with pheochromocytoma. Clinical outcomes were compared between composite and typical pheochromocytomas.

The study included 190 patients: 28 (14.9%) had composite tumors and 160 had typical pheochromocytoma; 2 additional patients with mixed corticomedullary tumors (MCMTs) were analyzed separately. Patients with composite tumors were older (median 67 vs 56 years, P = .015) compared with patients with typical pheochromocytoma. In multivariable analysis, the composite phenotype was associated with preoperative systolic hypertension (odds ratio (OR)-2.47, 95% confidence interval [CI] 1.00-6.06, P = .049) and postoperative elevation of blood pressure, both systolic (OR-3.24, 95%CI 1.30-8.11, P = .012) and diastolic (OR-4.66, 95%CI 1.79-12.11, P = .002). On unenhanced computed tomography, attenuation of composite pheochromocytomas was lower (median 30 vs 35 Hounsfield units, P = .01), and these were less often detected as adrenal incidentalomas. Laparoscopic adrenalectomy was performed less frequently in composite pheochromocytomas (67.9% vs 87.5%, P = .02). Composite pheochromocytomas had a higher risk of Ki-67 expression in the 3% to 5% range (OR-28.68, 95%CI 1.49-552.79, P = .026). Tumor size, recurrence and metastasis rates, and mortality were comparable to typical pheochromocytoma.

Composite pheochromocytomas were associated with older age, lower computed tomography attenuation, distinct perioperative features, and a higher burden of hypertension. These findings suggest that this subgroup may require closer postoperative monitoring. Although Ki-67 was higher in composite pheochromocytomas, its prognostic significance remains uncertain.