Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles

Author:

Hagel Christian,Schüller Ulrich,Flitsch Jörg,Knappe Ulrich J.,Kellner Udo,Bergmann Markus,Buslei Rolf,Buchfelder Michael,Rüdiger Thomas,Herms Jochen,Saeger WolfgangORCID

Abstract

Abstract Purpose Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5–1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown. Methods Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA). Results In accordance with the literature, combinations of GH/prolactin/TSH–FSH/LH adenoma (4/12), GH/prolactin/TSH–ACTH adenoma (3/12), and ACTH–FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern. Conclusion Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.

Funder

Fördergemeinschaft Kinderkrebs-Zentrum Hamburg

Novartis Pharma

Novo Nordisk

Pfizer Pharma DE

Ipsen Pharma DE

Universität Hamburg

Publisher

Springer Science and Business Media LLC

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

Reference16 articles.

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2. Saeger W, Lüdecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 156:203–216

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