How to Classify Pituitary Neuroendocrine Tumors (PitNET)s in 2020

Abstract

Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, “aggressive” and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as “high risk” tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.

Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours

“…Therefore, the higher expression of E2F, MYC, and miR-17-5p in invasive and proliferative tumours (grade 3) than in grade 1 (non-invasive tumours) confirms that both invasiveness and proliferation must be taken into account in PitNET classification [20]. In addition, the high expression of these genes and miRNA, implicated in the cancer, confirms that an invasive and proliferative tumour is not a benign adenoma as a non-invasive tumour, with or without proliferation [20].…”

“…However, many researchers have raised doubts about their usefulness [12,[23][24][25]. Indeed, some years ago, Trouillas et al [19,20] suggested a classification of the behaviour of pituitary tumours taking into account not only markers of proliferation, but also the IHC type, the invasiveness of the tumours, and their ability to relapse. To the best of our knowledge, E2F1 and MYC have never been studied as possible biomarkers of PitNETs.…”

“…Diagnostics 2020, 10, 227 3 of 13 According to the clinicopathological classification proposed by Trouillas et al [19,20], we defined three grades: 1. non-invasive tumours, regardless of the Ki-67 index (value from 0.081 to 11.631; 6 tumours with ki-67 ≥ 2.59), 2. invasive and non-proliferative tumours with Ki-67 index < 2.59, and 3. invasive and proliferative tumours with Ki-67 index ≥ 2.59. Grade 1 corresponds to grades 1a and 1b of the Trouillas' classification; grades 2 and 3 are similar to grade 2a and grade 2b respectively [19].…”

The DLK1/MEG3 Locus is Related to the Differentiation of Pituitary Neuroendocrine Tumors

“…The 2017 WHO classi cation classi es PitNETs into seven morphofunctional types and three lineages. The French ve-tiered classi cation emphasizes tumor proliferation and invasion, which provide prognostic value for the clinical treatment of PitNETs [5]. Mario et al found gonadotroph signatures in some corticotroph and somatotroph PitNETs by integrated pangenomic analyses [4].…”

Classification of neuroendocrine neoplasms: lights and shadows

“…Taken together, these considerations prompted a multidisciplinary group of experts in pituitary pathology to propose the new terminology "pituitary neuroendocrine tumor (PitNET)" instead of "pituitary adenoma" (Table 1) [23]. Thus, all anterior pituitary tumors are considered as lesions showing a potential clinical impact that can be additionally evaluated and better defined in terms of prognosis using a multiparametric approach including the Ki67 proliferative index and radiology appearance (Table 2) [24,25]. Although this new approach appears appropriate and clinically useful since it reflects the real biology of these tumors, it is still matter of debate [26][27][28].…”