Absent p53 immunohistochemical staining in a pituitary carcinoma

Background: Carcinomatous transformation of pituitary adenomas is uncommon, and is generally accompanied by nuclear accumulation of p53 protein. Pitui tary carcinoma lacking accumulation of p53 protein is very rare, only two s uch cases being previously reported. Methods: A patient presented with visu al disturbance and cranial nerve palsies and was found to have a suprasella r mass. He underwent both transphenoidal and transfrontal excision of a non functioning pituitary adenoma which recurred several times. The third recur rence was accompanied by multiple dural-based metastases. Despite aggressiv e surgical management, he continued to develop additional intracranial lesi ons and died two years after the discovery of metastatic disease. Specimens from 1984, 1995, 1997 and 1998 were available for histological and immunoc ytochemical analysis. Antibodies recognizing the pituitary hormones (ACTH, PRL, GH, FSH, LH and TSH), as well as cytokeratin, epithelial membrane anti gen (EMA), glial fibrillary acidic protein (GFAP) and chromogranin A were a pplied to investigate the lineage of the neoplasm. Antisera specific for Ki -67 (MIB-1) and p53 protein were also applied to further delineate the biol ogy of the tumour. Results: Although cytokeratin and chromogranin A were de tected in neoplastic cells, no expression of pituitary hormones was demonst rable, indicative of a nonfunctioning, null-cell pituitary adenoma. Nuclear pleomorphism and mitotic activity increased with subsequent resections. Ab normal accumulation of p53 protein was not observed, neither in early resec tions nor in the metastatic deposits. Conclusions: Failure to demonstrate p 53 protein accumulation does not ensure a favourable outcome for pituitary adenoma. Accordingly, pituitary carcinoma may occur in the absence of p53 a ccumulation. The factors which underlie aggressive behaviour of pituitary n eoplasms are uncertain but are under investigation.