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

Abstract

E. Manojlovic-Gacic, J. Bollerslev, O. Casar-Borota (2020) Neuropathology and Applied Neurobiology 46, 89-110 Invited Review: Pathology of pituitary neuroendocrine tumours: present status, modern diagnostic approach, controversies and future perspectives from a neuropathological and clinical standpoint Neuroendocrine tumours of the adenohypophysis have traditionally been designated as pituitary adenomas to underline their usually indolent growth and lack of metastatic potential. However, they may demonstrate a huge spectrum of growth patterns and endocrine disturbances, some of them significantly affecting health and quality of life. To predict tumour growth, risk of postoperative recurrence and response to medical therapy in patients with pituitary neuroendocrine tumours is challenging. A thorough histopathological and immunohistochemical diagnostic work-up is an obligatory part of a multidisciplinary effort to precisely define the tumour type and assess prognostic and predictive factors on an individual basis. In this review, we have summarized the current status in the pathology of pitu-itary neuroendocrine tumours based on the selection of references from the PubMed database. We have presented possible diagnostic approaches according to the current pituitary cell lineage-based classification. The importance of recognizing histological subtypes with potentially aggressive behaviour and identification of prognostic and predictive tissue biomarkers have been highlighted. Controversies related to particular subtypes of pituitary tumours and a still limited prognostic impact of the current classification indicate the need for further refinement. Multidisciplinary approach including clinical, pathological and molecular genetic characterization will be essential for improved personalized therapy and the search for novel therapeutic targets in patients with pituitary neuroendocrine tumours.

Cushing’s disease and aggressive pituitary tumours : Aspects on epidemiology, treatment, and long-term follow-up

“…Although grading of symptoms was not possible in our study, the results imply persisting mental health issues despite achieved biochemical remission. The findings in study IV support two previous cross-sectional studies in which increased prevalence of psychopathology and cognitive impairment was found after remission for 11 (range 1-32), and 13 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) years, respectively (90,91).…”

“…Most clinically non-functioning adenomas stain positive for gonadotropins, and on rare occasions for prolactin, ACTH or growth hormone, and are referred to as "silent" gonadotrophs, lactotrophs, corticotrophs and somatotrophs respectively. Less than 3% are immunonegative for all hormones/transcription factors and are termed null cell adenomas (5,6). Evaluation of proliferation markers, somatostatin receptors and granulation patterns may have prognostic and/or predictive implications.…”

“…In a study by Dorn et al (89), including 33 patients with Cushing's syndrome, significant psychopathology was present in two thirds at diagnosis, and decreased to 24% 12 months after remission. However, compared to controls, cross-sectional studies have shown increased psychopathology and cognitive impairment after longterm remission for 11 (range 1-32), and 13 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) years respectively (90,91).…”

DNA Methylation-based Signatures Classify Sporadic Pituitary Tumors According to Clinicopathological Features

“…These results are concordant with a report that silent ACTH and gonadotroph tumors share cytopathological features and clinical behavior 29 . Taking into account that cell-specific methylation patterns are preserved during development and tumorigenesis, it is also possible that null cell, a subset of gonadotrophs and of corticotroph adenomas share a common precursor 30,31 10,32,33 (Figure 1B). In addition, a study showed that a subset of functioning corticotroph adenoma displayed a more intermediate methylation profile between FPT and NFPT 10,32,33 .…”

“…Taking into account that cell-specific methylation patterns are preserved during development and tumorigenesis, it is also possible that null cell, a subset of gonadotrophs and of corticotroph adenomas share a common precursor 30,31 10,32,33 (Figure 1B). In addition, a study showed that a subset of functioning corticotroph adenoma displayed a more intermediate methylation profile between FPT and NFPT 10,32,33 . Specific gene mutations such as GATA3 and USP8 accounted for the differences among these corticotroph adenomas variants 10,28 .…”