Challenges in the Diagnosis of Pituitary Neuroendocrine Tumors.

Detailed analysis of cytodifferentiation and hormone production has classified pituitary neuroendocrine tumors (PitNETs) in a formal system that reflects the lineage differentiation of nontumorous adenohypophysial cells as well as subtypes of tumors that have predictive value. In addition, tumors composed of cells that lack terminal differentiation are well characterized. To comply with the proposal to create an overarching classification of neuroendocrine neoplasia, these tumors are now called PitNETs rather than adenomas. The next important step will be to relinquish the term "pituitary carcinoma" for metastatic PitNETs that remain well differentiated, and to alter the terminology used for tumors that are not terminally differentiated to reflect only their immature lineage. The existence of mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) similar to those at other body sites is proven by mixed craniopharyngiomas with PitNETs. As with other NETs, these neoplasms should be reported with synoptic data that guide completeness of reporting. A formal system of grading should be created, but not only based on proliferation, as these tumors have shown the prognostic value of cytodifferentiation. A formal system of staging should also be devised to complement grade in the thorough and accurate diagnosis of tumors that arise from adenohypophysial cells.