Clinicopathologic Correlates of PIT1 and SF1-Multilineage Pituitary Neuroendocrine Tumors and the Diagnostic Utility of NKX2.2 Immunohistochemistry in Pituitary Pathology

Context.-PIT1 and SF1-multilineage pituitary neuroendocrine tumors (PitNETs) have been defined since the classification of adenohypophysial tumors based on the PIT1, SF1, and TPIT transcription factors. Objective.-To describe the clinicopathologic features of PIT1 and SF1-multilineage PitNETs and to contribute to the pituitary pathology practice by questioning the expression of NKX2.2 in PitNETs. Design.-We reviewed 345 PitNETs and described the clinicopathologic features of 8 PIT1 and SF1-multilineage tumors. NKX2.2 positivity and staining pattern were compared to those of 45 PitNETs from the control group. Results.-PIT1 and SF1-multilineage PitNET patients had a mean age of 41.13 (range, 14-58 years) and a mean tumor diameter of 14.0 mm (range, 8-20 mm). The most common clinical presentation was acromegaly (6 of 8), and postoperative remission was achieved in all patients. On histomorphologic examination, a pseudo- papillary pattern was seen in 5 of the tumors, either focally or diffusely. In addition to PIT1 and SF1, there was a diffuse staining with growth hormone and a predominantly perinuclear staining with cytokeratin 18. With NKX2.2, all multilineage tumors were positive, of which 5 were diffuse and 3 were focal. In the control group, 8 tumors (8 of 45) were positive, of which only 1 was diffuse and 7 were focal. Conclusions.-In conclusion, NKX2.2 is a transcription factor that can be used as an additional tool in pituitary pathology, and PIT1 and SF1-multilineage PitNETs are specific tumors that usually present with acromegaly, show signs of a nonaggressive clinical course, have a pseudopapillary histomorphology, and express NKX2.2.