Histopathological classification of non-functioning pituitary neuroendocrine tumors

Abstract

Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify “high-risk adenomas.” A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.

Invited Review: Pathology of pituitary neuroendocrine tumours: present status, modern diagnostic approach, controversies and future perspectives from a neuropathological and clinical standpoint

“…It should be expected that a complementary use of immunohistochemistry for anterior pituitary hormones and pituitary specific transcription factors, in combination with additional organ‐specific neuroendocrine markers and imaging work‐up in order to search for NETs in other organs, will result in such a low frequency of ‘null cell adenomas’ that their existence needs to be seriously questioned. As previously speculated, this tumour category might potentially only reflect the methodological problems in the diagnostics of PitNETs .…”

Clinicopathological analysis of 250�cases of pituitary adenoma under the new WHO classification

“…For 35-45% of PAs, the surrounding structure is involved (2). The classification system collectively refers to sparsely granulated somatotroph adenoma, lactotroph adenoma in men, Crooke's cell adenoma, silent corticotroph adenoma, and plurihormonal POU class 1 homeobox 1-positive adenoma as 'invasive adenoma' or 'high-risk adenoma' (12). This type of adenoma grows rapidly, tends to recur or progress and is resistant to surgery and radiotherapy.…”

“…non-functioning or hormonally silent tumours, resulting in pituitary insufficiency and/or other symptoms associated with the intrasellar tumour mass (2). However, ~80% of clinically non-functioning or silent pituitary tumours are of the gonadotroph subtype, expressing follicle stimulating hormone (FSH) and/or luteinising hormone (LH), corticotroph tumours are the second most prevalent and the other hormonal subtypes are rarely reported (12). Hormonally inactive sellar tumours, negative for both anterior pituitary hormones and pituitary-specific TFs, are designated null cell adenomas (2).…”

Lower 68Ga‐DOTATOC uptake in nonfunctioning pituitary neuroendocrine tumours compared to normal pituitary gland—A proof‐of‐concept study

“…According to the 2017 WHO classification, NF‐PitNETs are divided into eight subtypes based on the immunohistochemical expression of adenohypophyseal hormones and pituitary‐specific transcription factors . The most common NF‐PitNET subtypes are gonadotroph and corticotroph tumours, comprising about 80% and 15% of all NF‐PitNETs, respectively . Other subtypes account for only a few per cent.…”

“…3 The most common NF-PitNET subtypes are gonadotroph and corticotroph tumours, comprising about 80% and 15% of all NF-PitNETs, respectively. 6,7 Other subtypes account for only a few per cent.…”