title: Cellular proliferation and nuclear ploidy assessments augment established prognostic factors in predicting malignancy in testicular Leydig cell tumours.
abstract: OBJECTIVE
  Testicular Leydig cell tumours are rare. Although most behave benignly approximately 10% are malignant. Clinicopathological features have been described which have some value in predicting malignant behaviour, although as with other endocrine tumours uncertainties remain in many individual cases. Our aim was to determine the clinicopathological features of 20 testicular Leydig cell tumours. We wished to investigate whether, in addition to established clinicopathological features, the MIB1 index and/or flow cytometric analysis of nuclear DNA content are of value in predicting malignancy. We also wished to investigate the frequency of p53 protein accumulation in these neoplasms.
  
  
  RESULTS
  Twenty testicular Leydig cell tumours were studied and the clinical case notes examined. Histological sections were assessed by pathologists involved in the study. Pathological features evaluated included: 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 flow cytometric analysis of nuclear DNA content was also performed. Three tumours behaved in a malignant fashion with the development of metastases. Another had morphological features of malignancy but the patient died a short time after diagnosis from unrelated causes. These four neoplasms were larger than benign tumours, often contained areas of necrosis and sometimes exhibited vascular invasion. They generally exhibited greater nuclear pleomorphism and a higher mitotic rate than benign tumours. Three of the four malignant tumours had a high MIB1 index (20-50%) and the fourth exhibited DNA aneuploidy by flow cytometry. Two malignant tumours showed increased expression of p53 protein, with approximately 50% of nuclei staining with DO-7. All benign tumours had a low MIB1 index (0-2%) and a diploid DNA profile, except for one case where there was DNA aneuploidy. There was little or no staining of benign tumours with DO-7.
  
  
  CONCLUSIONS
  The study confirms that large size, marked nuclear pleomorphism, high mitotic rate, necrosis and vascular invasion are important factors in predicting malignant behaviour in testicular Leydig cell tumours. Additional prognostic value may be derived from the MIB1 index and flow cytometry. Accumulation of p53 protein, through mutational or other events, may be important in malignant progression in these tumours.
authors.affiliation: Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland.
authors.forename: W G
authors.initials: WG
authors.lastname: McCluggage
authors.forename: J H
authors.initials: JH
authors.lastname: Shanks
authors.forename: K
authors.initials: K
authors.lastname: Arthur
authors.forename: S S
authors.initials: SS
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000378:metabolism; D002455:Cell Division; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007984:Leydig Cell Tumor / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011003:Ploidies; D011379:Prognosis; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; D009687:Nuclear Proteins