Endocrine Abstracts

Introduction: Clinically non-functioning pituitary neuroendocrine tumours (NFPitNETs) include all anterior pituitary tumours that are not hormonally active. In histopathology (HP) and immunohistochemistry (IHC), most of NFPitNETs are gonadotroph (1). Immunolabeling is negative in only 10% of cases (‘null-cell’). Occasionally, NFPitNETs are positive for GH, PRL, TSH or ACTH despite absent or only minimal secretion of these hormones in vivo, which are known as silent somatotroph, lactotroph, thyrotroph or corticotroph tumours.

Materials and methods: The study included 27 patients with NFPitNETs, with a male:female ratio of 19:8 and a median age at diagnosis of 51.8 years ((±13,7). The HP-IHC features were correlated with the clinical, imaging and laboratory data. Tumour specimens were assessed for anterior pituitary hormones, pituitary-specific transcription factor 1 (PIT-1), T-box transcription factor (TPIT) and steroidogenic factor 1 (SF-1) transcription factors (TF), Ki-67 labelling index, vimentin and reticulin.

Results: All patients had macroadenomas (median 35.5 mm ±11.9 DS), the symptoms being associated with the tumoral syndrome (70.3% had headache and optic chiasm disorder). The treatment was mostly surgical, with association of radiotherapy in 33.3% of cases. Of the 16 patients with pituitary deficiency, only 2 had remission of the deficit after surgery. Most NFPitNETs were acidophilic, with alveolar and papillary growth patterns in many cases. After the IHC evaluation of anterior pituitary hormones, the 27 NFPitNETs were reclassified, according to WHO 2022 criteria. Over half of them had positive expression of LH and/or FSH, being, in fact silent gonadotropinomas. 18.5% were hormone-negative, 11.1% expressed ACTH, 7.4% expressed GH and ACTH and 7.4% expressed GH. After IHC evaluation of pituitary TF, only 4 out of 5 tumours were, in fact, ‘null-cell’. The expression of Ki-67 was <3% in all cases.

Conclusion: The clinical term ‘non-functioning’ is not a diagnosis, yet a description of a clinical scenario that has many differential diagnoses (2). More than 50% of clinically and biochemically NFPitNETs are silent gonadotropinomas, some of which have negative immunohistochemical expression of the hormones FSH and LH.

Reference

1. Chanson P, Wolf P. Clinically non-functioning pituitary adenomas. Presse Med. 2021 Dec;50(4):104086.

2. Asa SL, Mete O, Perry A, Osamura RY. Overview of the 2022 WHO Classification of Pituitary Tumors. Endocr Pathol. 2022 Mar;33(1):6–26.