Two Pituitary Neuroendocrine Tumors (PitNETs) with Very High Proliferation and TP53 Mutation — High-Grade PitNET or PitNEC?

Wolfgang Saeger,Christian Mawrin,Frank Jacobsen,Annika K Wefers,Matthias Meinhardt

doi:10.1007/s12022-021-09693-y

Abstract

We report two pituitary neuroendocrine tumors (PitNETs) with very high Ki67 labeling indices, many mitoses and TP53 mutation (nearly all tumor cell nuclei were positive for p53). One of the tumors had bone and liver metastases. One was a corticotroph cell tumor; the other was a lactotroph tumor. The classification of these tumors is the subject of this discussion. Traditionally, pituitary carcinomas are only diagnosed by demonstration of metastases according to the 2017 WHO classification. In contrast, neuroendocrine neoplasms of the gastrointestinal tract and pancreas are classified as either well differentiated NETs that are graded as G1, G2, and G3 based on proliferation as determined by Ki67 indices of ≤ 3, 3–20 and > 20%, and/or < 2, 2–20, and > 20 mitoses per 10 high-power field respectively, or as neuroendocrine carcinomas (NECs) that are poorly differentiated neoplasms with mitoses > 20/HPF and/or a Ki67 index > 20%. With the reclassificiation of PitNETs, in our opinion, the adequate term for the well-differentiated corticotroph tumor that we report is a PitNET G3, whereas the undifferentiated prolactin tumor should be classified as PitNEC. This report expands the spectrum of pituitary neuroendocrine neoplasms.

Highlights

The 2017 Consensus Conference of the International Agency for Research on Cancer developed the classification of neuroendocrine neoplasms (NENs) and distinguished well-differentiated neuroendocrine tumors (NETs) from poorly differentiated neuroendocrine carcinomas (NECs) [14]
One problem regarding the histopathology of case 1 was the negative staining for transcription factor for pituitary corticotrophs (TPIT) in the liver metastasis, whereas ACTH was positive
Two cases published in the literature can be compared with our tumors: (1) The case report of Pasquel et al (2013) [13] described a nonfunctioning pituitary neuroendocrine tumors (PitNETs) with a Ki67 index of 30 to 80%

Summary

Introduction

The 2017 Consensus Conference of the International Agency for Research on Cancer developed the classification of neuroendocrine neoplasms (NENs) and distinguished well-differentiated neuroendocrine tumors (NETs) from poorly differentiated neuroendocrine carcinomas (NECs) [14]. Ki67 indices of more than 20% are very rare, and some metastasizing pituitary carcinomas show Ki67 indices of 0–16% [19] or 0 to 22% [18]; PitNET G3 as defined by a Ki-67 index of more than 20% should be very rare. We would like to turn your attention to two pituitary tumors with an extremely high Ki67 index and evidence of TP53 mutation and discuss the problem of identifying PitNEC, Fig. 1 Case 1: ACTH-PitNET G3.

Results

Conclusion