Atypical pituitary adenomas: A new entity in the WHO classification of 2004

Objectives: In the WHO classification for pituitary tumors of 2004, a new adenoma entity, the atypical adenoma, was defined as an invasive tumor with elevated mitotic index, a MiB-1 labelling index greater than 3%, and a significant immunostaining for p53 protein. It is distinguished from pituitary carcinoma only by the lack of metastases or extensive brain invasion. Atypical adenomas account for 3.8% (32/845) of surgically removed adenomas (2000–2006). The morphological and clinical data of these 32 tumors will be presented.

Methods: Paraffin section were immunostained for GH, prolactin, ACTH, TSH, ß-FSH, ß-LH, a-subunit, Ki-67 (MiB-1) and p53 protein. Histological findings were compared with clinical data.

Results: Three atypical adenoma types correlated to acromegaly: Two tumors were densely granulated GH cell adenomas, five represented sparsely granulated GH cell adenomas, and one adenoma was a mixed GH-prolactin cell adenoma. Four adenomas were classified as sparsely granulated prolactin cell adenomas with hyperprolactinemia. Three densely granulated ACTH cell adenomas in Cushing disease are included. Four could be classified as sparsely granulated ACTH cell adenomas, three of them were inactive, one had induced Cushing disease. One tumor was an inactive TSH cell adenoma with concommitant hyperprolactinemia. One plurihormonal adenoma without hyperfunction was identified. Typical inactive adenomas were four gonadotroph adenomas, five null cell adenomas, and two null cell adenomas of oncocytic variant. Ages ranged from 16 to 78 years. 53.5% were males. Tumor sizes ranged from 3.5mm to 50mm. Six tumors of 19 cases with sufficient clinical data were recurrent adenomas. Invasion affected the cavernous sinus, clivus, sellar bone, sphenoid sinus or the suprasellar tissues.

Conclusions: According to the histological, clinical and hormonal classification all adenoma types can be atypical. They are characterized by an increased tumor growth, invasion, and higher rate of recurrences. Their potential transformation into carcinomas should be critically studied.