Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Abstract

The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014

“… Tumor specimen or biopsy: the histopathological report shall provide the WHO classification and TNM staging [ 5 – 8 ]. Inmunohistochemical staining should always include Ki-67 (% of positive cells assessed in 2,000 tumor cells in areas of highest nuclear labeling) and general neuroendocrine markers (chromogranin A, synaptophysin and neuron-specific enolase) [ 9 ]. Specific markers are not mandatory and should only be performed if clinically indicated (insulin, glucagon, etc).…”

Follow-Up Recommendations after Curative Resection of Well-Differentiated Neuroendocrine Tumours: Review of Current Evidence and Clinical Practice

“…The use of staining with peptide hormones, such as insulin, glucagon, or other specific peptides is of use in selected cases only, when such diagnoses as insulinoma, glucagonoma, etc. are suspected [52].…”

SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2018)

“…The diagnosis of NENs may require clinical, biochemical, pathological, radiological, nuclear medicine or endoscopic procedures, depending upon primary tumor site, tumor stage and clinical presentation including hormonal syndromes [ 3 ]. Besides a comprehensive medical history, physical examination and laboratory tests (including hematological, liver and renal function parameters), the following procedures are recommended for an adequate diagnosis of NENs: Chromogranin A (well-differentiated NETs) (III,B) or neuron-specific enolase (NSE) [poorly differentiated neuroendocrine carcinomas (NECs)] (I, C).…”

“…The diagnosis of NENs may require clinical, biochemical, pathological, radiological, nuclear medicine or endoscopic procedures, depending upon primary tumor site, tumor stage and clinical presentation including hormonal syndromes [3]. Besides a comprehensive medical history, physical examination and laboratory tests (including hematological, liver and renal function parameters), the following procedures are recommended for an adequate diagnosis of NENs:Chromogranin A (well-differentiated NETs) (III,B) or neuron-specific enolase (NSE) [poorly differentiated neuroendocrine carcinomas (NECs)] (I, C).Urinary 5-hydroxyindoleacetic acid (5-HIAA) (carcinoid syndrome); gastrin ± secretin test (gastrinomas); insulin/glucose ratio, proinsulin, C peptide (insulinomas), glucagon, VIP and others depending upon clinical symptoms (IV, C).Histopathological report should include the WHO classification and TNM staging, as well as immunohistochemistry staining including ki67 and general neuroendocrine markers (chromogranin A, synaptophysin and NSE).…”

“…About 20–25% of NENs are functioning tumors, that is, they are associated with a clinical syndrome due to excessive hormone production (carcinoid syndrome, Zollinger–Ellison syndrome, etc.). This proportion is decreasing with time due to earlier diagnosis and improved symptomatic and antineoplastic therapy [ 3 ]. They are generally diagnosed in the fifth decade of life, and about 5% of them are associated with hereditary predisposition syndromes.…”