Pathology of pituitary adenoma

Abstract According to the WHO classification 2017 of pituitary tumors, adenomas are classified not only by structure and immunostaining for pituitary hormones but also by expression of the pituitary transcription factors Pit-1, T-pit, and SF-1. By these factors, three cell lineages can be identified: Pit-1 for the GH, prolactin, and TSH cell lineage, T-pit for the ACTH cell lineage, and SF-1 for the gonadotrophic cell lineage. By this principle, all GH- and/or prolactin-producing and all TSH-producing adenomas must be positive for Pit-1, all corticotropic adenomas for T-pit, and all gonadotrophic for SF-1. In adenomas without expression of pituitary hormones, immunostainings for the transcription factors have to be examined. If these are also negative, the criteria for an endocrine inactive null cell adenoma are fulfilled. If one transcription factor is positive, the corresponding cell lineage indicates a potential hormonal activity of the adenoma. So Pit-1-expressing hormone-negative adenomas can account for acromegaly, hyperprolactinemia, or TSH hyperfunction. T-pit-positive hormone-negative adenomas can account for Cushing's disease, and SF-1-positive hormone-negative tumors for gonadotrophic adenomas. The term atypical adenoma should not be used since the WHO classification of 2017. Now, criteria exist for the identification of aggressive adenomas with a potential worse prognosis. Some adenoma subtypes (sparsely granulated GH adenomas, densely granulated prolactin adenomas, sparsely granulated prolactin macroadenomas in men, Crooke cell adenomas, inactive ACTH adenomas, undifferentiated plurihormonal Pit-1-positive adenomas, and acidophil stem cell adenomas) are described as aggressive “per se” without necessity of increased morphological signs of proliferations. All other adenoma subtypes could also be designated as aggressive if they show signs of increased proliferation (mitoses, Ki-67 index > 3%–5%, and clinically rapid tumor growth) and invasion.