Composite somatotroph--ACTH-immunoreactive pituitary adenoma with transformation of hyperplasia to adenoma.

The majority of pituitary adenomas are solitary and monohormonal, producing only one hormone. Double or multiple adenomas are rare. Plurihormonal adenomas may be monomorphous consisting of one cell type producing more than one hormones or plurimorphous composed of two or more distinct cell populations each producing different hormones. Primary pituitary hyperplasia is uncommon and transformation to adenoma has rarely been documented. We describe a unique case of somatotroph adenoma combined with ACTH-immunoreactive cell hyperplasia and focal transformation to adenoma. The 53-yr-old man was presented with a 2-yr history of headaches, enlargement of the hands and feet and coarsening of facial features. His blood GH was 17.5 ng/ml and he had absence of GH suppressional oral glucose tolerance testing. MRI demonstrated a mass with maximum diameter of 1.5 cm, on the left side of the pituitary, without invasion of surrounding tissues. Transsphenoidal surgery was performed. Morphology disclosed a mostly chromophobic tumor, immunoreactive for GH with ultrastructural characteristics of sparsely granulated somatotroph adenoma. The adenoma cell population was focally admixed with hyperplastic PAS positive and ACTH immunoreactive cells showing the electron microscopic features characteristic of corticotrophs. In these areas the acini were enlarged with distorted architecture of the reticulin pattern. Dissolution of the reticulin fiber network and transformation of hyperplastic ACTH-immunoreactive cells to adenoma was evident in small areas. The hyperplastic and adenomatous ACTH-immunoreactive cells were admixed with somatotroph adenoma cells. Due to lack of biochemically obvious cortisol hypersecretion, this ACTH-immunoreactive adenoma was classified as silent "corticotroph" subtype 1. This is an unusual case of composite pituitary adenoma consisting of somatotroph cells and hyperplastic ACTH-immunoreactive cells transforming to a frank adenoma.