Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases?

Evaluation of the malignant potential of phaeochromocytomas in the absence of metastases presents a formidable challenge to both clinicians and pathol ogists. Until now, no widely accepted clinical, histological, immunohistoch emical or molecular method has become available to discriminate malignant f rom benign phaeochromocytomas, In other endocrine tumours, estimation of pr oliferative activity by MIB-1 immunostaining has emerged as a promising app roach for the determination of metastatic potential. In this study, the uti lity of MIB-1 immunostaining as a predictive marker for the occurrence of m etastases in phaeochromocytomas was evaluated. In addition, the density of S100-positive sustentacular cells was studied, since their depletion has be en identified as a negative predictive marker in smaller series. Furthermor e, several clinicopathological parameters were evaluated, One hundred and t en patients operated on for a total of 99 benign and 37 malignant phaeochro mocytomas were studied. All malignant tumours had documented metastases. Th e histopathological diagnosis of primary tumours and metastases was reviewe d and graded for angioinvasion, capsular extension, and intra-tumoural necr osis. The proliferative index (percentage of MIB-1-positive cells) and the density of S100-positive cells were assessed. In addition, age at resection , associated familial tumour syndromes, tumour size, and tumour location we re recorded. Univariate analysis revealed statistically significant correla tions between malignancy and proliferative index (p<0.0005) and depletion o f S100-positive sustentacular cells (p<0.0005), Fifty per cent of the malig nant, but none of the benign phaeochromocytomas had a proliferative index g reater than 2.5%, Higher age at resection (p=0.03), sporadic occurrence (p< 0.0005), extra-adrenal location (p<0.0005), tumour size (p<0.0005), and nec rosis (p=0.03) were also significantly associated with malignancy. Logistic regression showed that proliferative index (p=0.0072), size (p=0.0022), an d extra-adrenal location (p=0.0012) of the primary tumour were independentl y predictive for malignancy. In conclusion, this study indicates that asses sing the proliferative activity of phaeochromocytomas by MIB-1 immunohistoc hemistry can predict the occurrence of metastases, The predictive value of S100 immunostaining, tumour size, and extra-adrenal location of the tumour was also confirmed. Copyright (C) 2000 John Wiley & Sons, Ltd.