Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are composed of cells with a neuroendocrine phenotype. The old and the new WHO classifications distinguish between well-differentiated and poorly differentiated neoplasms. All well-differentiated neoplasms, regardless of whether they behave benignly or develop metastases, will be called neuroendocrine tumours (NETs), and graded G1 (Ki67 !2%) or G2 (Ki67 2-20%). All poorly differentiated neoplasms will be termed neuroendocrine carcinomas (NECs) and graded G3 (Ki67 O20%). To stratify the GEP-NETs and GEP-NECs regarding their prognosis, they are now further classified according to TNM-stage systems that were recently proposed by the European Neuroendocrine Tumour Society (ENETS) and the AJCC/UICC. In the light of these criteria the pathology and biology of the various NETs and NECs of the gastrointestinal tract (including the oesophagus) and the pancreas are reviewed.

Gastroenteropancreatic Neuroendocrine Tumours – An Institutional Experience

“…The poorly differentiated ones were grouped as Grade 3 tumors and further subtyped into small cell and large cell type. They are also designated as high-grade neuroendocrine carcinomas [3] [10].…”

“…The size and extent of tumor, histological pattern, type of cell, cytological atypia, necrosis, presence or absence of angioinvasion and metastasis at presentation have been the core factors studied to predict the clinical behavior of these NETs [10]. However, in the recent2010 WHO classification the proliferative activity of the tumors determined by the mitotic rate and Ki-67 labeling index has been used as the key criteria to grade the tumors as Grade I-III (Table 2).…”

ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin

“…10,11 Accordingly, it is not surprising that ISL1 is lacking or only weakly expressed in poorly differentiated pancreatic neuroendocrine carcinomas. Interestingly, ISL1 expression was preserved in a subset of pancreatic neuroendocrine neoplasms, which were assigned grade 3 because of their high proliferation index (Ki67420%), [18][19][20] but still retained the typical histological pattern of NETs, thus clearly deviating in their histological differentiation from poorly differentiated neuroendocrine neoplasms of small or large cell type. This observation supports our interpretation of a differentiation-associated expression of ISL1 in pancreatic neuroendocrine neoplasms and may also serve as a further argument that some pancreatic grade 3 neuroendocrine neoplasms, although overlapping in their proliferative activity with poorly differentiated neuroendocrine carcinomas, still remain distinct from the latter neoplasms.…”

“…Neuroendocrine neoplasms were diagnosed and classified according to the current World Health Organization (WHO) classification of NETs of the digestive tract. 18,19 All tumors showed diffuse immunohistochemical expression of synaptophysin (antibody clone SY38, 1:50, Dako) with or without expression of chromogranin A (clone LK2H10, 1:500, Beckman-Coulter GmbH). In cases of Merkel cell carcinoma, neuroendocrine carcinomas of the head and neck region, small cell lung neuroendocrine carcinomas, pulmonary carcinoids, neuroblastomas, paragangliomas/pheochromocytomas, olfactory neuroblastomas, medullary thyroid carcinomas, and basaloid squamous cell carcinoma of head and neck the diagnosis was established where needed by using appropriate markers such as CK20, S100, calcitonin, CK5 and p63, respectively.…”

“…The pancreatic neuroendocrine neoplasms were graded using the three-tiered grading system of the WHO that is based on the quantification of the nuclear labeling with Ki67 (MiB-1, 1:100, Dako). [18][19][20] Welldifferentiated pancreatic neuroendocrine neoplasms G1 and G2 were called pancreatic NETs. Pancreatic neuroendocrine carcinomas were defined by their poor histological differentiation, with either small cell or large cell features.…”