CELLULAR PROLIFERATION AND NUCLEAR PLOIDY ASSESSMENTS AUGMENT ESTABLISHED PROGNOSTIC FACTORS IN PREDICTING MALIGNANCY IN TESTICULAR LEYDIG-CELL TUMORS

Aims: Testicular Leydig cell tumours are rare. Although most behave be nignly approximate to 10% are malignant. Clinicopathological features have been described which have some value in predicting malignant beha viour, although as with other endocrine tumours uncertainties remain i n many individual cases. Our aim was to determine the clinicopathologi cal features of 20 testicular Leydig cell tumours. We wished to invest igate whether, in addition to established clinicopathological features , the MIB1 index and/or now cytometric analysts of nuclear DNA content are of value in predicting malignancy. We also wished to investigate the frequency of p53 protein accumulation in these neoplasms. Methods and results: Twenty testicular Leydig cell tumours were studied and th e clinical case notes examined. Histological sections were assessed by pathologists involved in the study. Pathological features evaluated i ncluded: tumour size, extratesticular extension, nuclear pleomorphism, mitotic activity, necrosis and vascular invasion. Immunohistochemical staining was performed with the anti-p53 monoclonal antibody DO-7 and the cell proliferation marker MIB1. A now cytometric analysis of nucl ear DNA content was also performed. Three tumours behaved in a maligna nt fashion with the development of metastases. Another had morphologic al features of malignancy but the patient died a short time after diag nosis from unrelated causes, These four neoplasms were larger than ben ign tumours, often contained areas of necrosis and sometimes exhibited vascular invasion. They generally exhibited greater nuclear pleomorph ism and a higher mitotic rate than benign tumours. Three of the four m alignant tumours had a high MIB1 index (20-50%) and the fourth exhibit ed DNA aneuploidy by now cytometry. Two malignant tumours showed incre ased expression of p53 protein, with approximate to 50% of nuclei stai ning with DO-7. All benign tumours had a low MIB1 index (0-2%) and a d iploid DNA profile, except for one case where there was DNA aneuploidy . There was little or no staining of benign tumours with DO-7. Conclus ions: The study confirms that large size, marked nuclear pleomorphism, high mitotic rate, necrosis and vascular invasion are important facto rs in predicting malignant behaviour in testicular Leydig cell tumours . Additional prognostic value may be derived from the MIB1 index and n ow cytometry. Accumulation of p53 protein, through mutational or other events, may be important in malignant progression in these tumours.