Neuroendocrine markers and sustentacular cell count in benign and malignant pheochromocytomas - a comparative study

Pheochromocytomas are rare tumours with uncertain clinical behaviour. Histological separation between benign and malignant pheochromocytomas is usually difficult. The utilization of PASS criteria (Pheochromocytoma of the Adrenal Gland Scaled Score) has not provided a solid basis for separating benign from malignant tumours. The aim of this study was to investigate immunohistochemical markers (chromogranin, synaptophysin, S-100 and Ki-67) to find out if they could provide useful diagnostic and/or prognostic data in a series of 62 pheochromocytomas (5 cases followed an aggressive clinical course). Chromogranin and synaptophysin immunoreactivity proved to be diagnostically useful, allowing, together with the absence of immunoreactivity for inhibin and melan A, an unequivocal diagnosis of pheochromocytoma. The pattern of staining did not provide, however, significant prognostic information. The mean count of sustentacular S-100 positive cells was lower in malignant than in benign pheochromocytomas but the frequent architectural variability and the haemorrhagic and cystic changes make it very difficult to achieve a precise and reproducible count in the majority of tumours. Without questioning that the occurrence of metastases and/or recurrent disease still remains the only unquestionable criterion for diagnosing a malignant pheochromocytoma, we think that the combined use of the PASS score and Ki-67 index provides useful information for diagnosing malignancy.