Epidemiology and biomarker profile of pituitary adenohypophysial tumors

Abstract

Recent studies have reported the prevalence of pituitary tumors to be ~1/1000 population. Many are prolactin-producing tumors that are managed medically, however, the epidemiology of surgically resected pituitary adenohypophysial neuroendocrine tumors has not been reported in a large series with detailed characterization. We reviewed 1055 adenohypophysial tumors from 1169 transsphenoidal resections from the pathology files of University Health Network, Toronto, 2001-2016. Tumors were characterized by immunohistochemical localization of transcription factors (Pit-1, ERα, SF-1, Tpit), hormones (adrenocorticotropin, growth hormone, prolactin, β-thyrotropin, β-folliculotropin, β-luteotropin, α-subunit), and other biomarkers (keratins, Ki67, p27, FGFR4). Electron microscopy was used only for unusual lesions. In this cohort, 51.3% of patients were female; the average age was 51 years. Gonadotroph tumors represented 42.5%. Pit-1-lineage-tumors represented 29.9%; these were subclassified as growth-hormone-predominant (somatotroph/mammosomatotroph/mixed; 53%), prolactin-predominant (lactotroph/acidophil-stem-cell; 28%), thyrotrophs (2%), plurihormonal (14%), and not-otherwise-specified (3%). Corticotroph tumors represented 17.1%. Only 4.5% were null cell tumors and 0.5% were unusual plurihormonal tumors. In 5.5% the tumor was not characterized for technical reasons (sample size, fixation, necrosis or other artifact). All corticotroph and plurihormonal tumors were positive for keratins; others tumors showed variable negativity with highest rates in gonadotroph (37.1%) and null cell tumors (28.2%). Tumors with a Ki67 ≥ 3% comprised 60% of this cohort. Global loss of p27 was most frequent in corticotroph neoplasms, specifically those associated with elevated glucocorticoid levels. Corticotroph and lactotroph tumors were more common among females; gonadotroph tumors were more common among males. Younger patients had mainly corticotroph and Pit-1-lineage neoplasms, whereas older patients harbored mainly gonadotroph tumors. This represents one of the largest surgical series of morphologically characterized pituitary tumors reported to date and the first to include the routine use of transcription factors for tumor classification. The data provide the basis for clinicopathologic correlations that are helpful for prognostic and predictive patient management.

Clinical significance of granulation pattern in corticotroph pituitary adenomas

“…Accordingly, the groups were similar in terms of sex distribution and, as expected, female dominance existed in both groups. Although age at diagnosis was slightly increased in the SGCTs, the difference was not significant and this result was similar to a recent study (13). Early diagnosis of CD has effectively reduced the mortality rates and prevented the severe comorbidities observed in these patients (14,15).…”

“…It is reported in the literature that the majority of corticotroph tumors were densely granulated (3,(6)(7)(8)10,12). However, in a recent study, Mete et al (13) reported the frequency of SGCTs and DGCTs in their cohort as 29% and 47%, respectively and interpreted this result as an…”

“…interesting finding. However, they explained these findings with the relatively high frequency of Crooke's cell tumors (13% of corticotroph tumors), the identification of mixed densely and sparsely granulated corticotroph tumors in some patients, and the role of p27 immunohistochemistry in the prediction of corticotroph tumor functionality (13).…”

“…Some indexes such as Ki-67, p53, an loss of p27 are used for behavioral detection of pituitary tumors (12,13,21,22). We assessed the Ki-67 labeling index in corticotroph tumors with sufficient samples only.…”

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

“…Pituitary tumors (PT), a type of neuroendocrine tumors, comprise the second most common neoplasm of the central nervous system (CNS) (∼17%) 1–3 with an annual average age-adjusted incidence of 4.08 per 100,000 population 3 . Stratified by endocrine status, PT are classified as functioning (FPT) (46-64%) or nonfunctioning (NFPT) (36%–54%) subtypes, the latter also referred to as silent adenomas 1,4 . In relation to the histopathological classification the most recent recommendation by the World Health Organization (WHO) in 2017 is based on immunostaining for adenohypophyseal hormones and cell-lineage 5 .…”