A novel type of pituitary adenoma: morphological features and clinical correlations.

Twenty patients with a novel, frequently aggressive type of pituitary adenoma, termed silent subtype 3 adenoma on the basis of fine structural criteria, are reported. The surgically removed tumors were studied by morphological techniques, and the findings were correlated with clinical and biochemical data. All tumors were macroadenomas, often with parasellar extension. The histologically diffuse tumors frequently exhibited focal immunopositivity for one or more adenohypophysial hormones, although the majority of adenoma cells were negative. The tumors had characteristic electron microscopic features, assuring specific diagnosis and delineating this tumor type as a distinct ultrastructural entity. The tumors were removed from 9 women and 11 men (median ages, 27 and 41 yr, respectively). In all women, mild to moderate hyperprolactinemia and its sequelae were present from the early phase of the disease, leading to the erroneous diagnosis of prolactinoma. Bromocriptine therapy (3 patients) reduced serum PRL levels to normal, but failed to halt tumor growth. In men, most adenomas were nonfunctioning; 4 men had mild to moderate hyperprolactinemia. Three men had elevated serum GH levels and acromegaly, suggestive of multidirectional differentiation. Although the putative cell type giving rise to silent subtype 3 adenomas is not known, the tumor should be recognized to avoid erroneous diagnosis and inappropriate treatment.