PITUITARY CARCINOMA - A CLINICOPATHOLOGICAL STUDY OF 15 CASES

BACKGROUND. Pituitary carcinomas are rare adenohypophysial neoplasms, the definition, diagnosis, therapy, and prognosis of which are controv ersial, METHODS, Pituitary carcinomas were defined as primary adenohyp ophysial neoplasms with documented craniospinal and/or systemic metast ases. The authors report a clinicopathologic study of 15 examples exam ined by light microscopy, immunohistochemistry, and image analysis. Bo th proliferative activity and p53 tumor suppressor gene expression wer e studied. RESULTS, The study group consisted of 15 patients, includin g 8 males and 7 females ranging in age from 34-71 years (mean, 56 year s). Of these patients, seven had adrenocorticotropic hormone (ACTH)-pr oducing tumors (four in the context of Nelson's syndrome), seven had p rolactin-producing tumors, and one had a nonfunctioning tumor. No evid ence of diabetes insipidus was seen in any case, Fourteen tumors were initially considered macroadenomas. Of the ten cases for whom tumor ex tent was known, all had invasive tumors. The interval from the initial diagnosis of adenoma to that of carcinoma ranged from 0.3 to 18.0 yea rs (mean, 6.6 years; median, 5.0 years): the longest mean interval (15 .3 years) occurred for patients with Nelson's syndrome. The latency wa s twice as long for ACTH-producing tumors as for prolactin (PRL) cell tumors (9.5 vs. 4.7 years). AU carcinomas showed a greater tendency to ward systemic metastasis than craniospinal metastasis; the rate of sys temic metastasis was 71% for PRL cell tumors and 57% for ACTH-producin g tumors. Thirteen percent of tumors showed both patterns of metastasi s. Fully 50% of primary tumors and the majority of metastases showed n uclear pleomorphism and/or hyperchromasia. The mean mitotic, MIB-1, an d proliferating cell nuclear antigen indices for primary tumors and me tastases were as follows: 2/10 high-power field (hpf), 2.6% and 11%, r espectively; 6/10 hpf, 7.8% and 16%, respectively. Staining for p53 pr otein was noted in 57% of primary tumors and 88% of metastatic tumors; a relative increase in p53 expression in metastases was noted in 83%. AU but one of the primary and metastatic tumors were aneuploid, The m ost common treatments were radiation therapy and, for PRL cell carcino mas, dopamine agonist administration. Both treatments provided only pa lliation. Eighty percent of the patients died of metastatic disease 7 days to 8 years after the diagnosis of carcinoma; of these, 66% died w ithin 1 year. At last follow-up, 20% of patients were alive with metas tases 9-18 months after diagnosis, CONCLUSIONS, Nearly all pituitary c arcinomas present as functioning, microscopically atypical or mitotica lly active, invasive macroadenomas. By definition, after an interval r elated to their immunotype, all metastasize. The tumors show a greater tendency toward systemic metastasis than craniospinal metastasis and are associated with poor prognosis. Radiation and dopamine agonist the rapy generally provide only palliation. Proliferation indices and p53 expression tend to be higher in metastases than in primary tumors. The current definition of pituitary carcinoma requires tile demonstration of metastasis; however, high mitotic and MIB-1 labeling indices as we ll as p53 immunoreactivity suggest the diagnosis and appear to be of p rognostic significance. A redefinition of aggressive pituitary tumors is proposed - one that facilitates the recognition of rumors prone to metastasis. (C) 1997 American Cancer Society.