The 2017 World Health Organization (WHO) introduced a new category of high-grade, well-differentiated neuroendocrine neoplasms (NENs) that called neuroendocrine tumors (NETs) G3 in pancreatic NENs classification and, then, in 2019, for all gastro-entero-pancreatic (GEP) tract NENs.
The new classification made it possible to separate NETs G3 from high-grade, poorly-differentiated, NENs that are called neuroendocrine carcinomas (NECs).
However, in clinical practice, we observed that several clinical, pathological and radiological differences are arising among NET G3 patients, suggesting that a multiparametric definition of NET G3 is needed.
Histological diagnosis of well-differentiated neuroendocrine tumor G3 performed or reviewed by a NEN-dedicated pathologist. In case of "late-NET G3" (see Patients and Methods), a NEN-dedicated pathologist will perform a pathologic review of the previous NET G1/2, too, unless a NEN-dedicated pathologist has already done and except for diagnoses performed in a NEN-referral Center.
Age > 18 years
Signed written informed consent
Available tumor tissue (formalin-fixed paraffin-embedded, FFPE) (preferably within 6 months). If the tumor contained in FFPE tissue block cannot be provided in total, sections from this block should be provided that are freshly cut. Preferably, 25 slides should be provided (minimum of 15 slides). If tumor tissue is not available, patients should be willing to undergone to a new biopsy.
Diagnosis of well-differentiated NET G1/2 or poorly-differentiated NEC
Diagnosis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) in which a NET G3 as neuroendocrine component
Cytological diagnosis of NET G3 or not availability of tumor tissue for pathological analysis
Concurrent neoplastic disease (e.g. advanced breast or prostatic cancer in hormonal treatment, hematologic diseases)
NET G3 patients managed at IEO. Histological diagnosis of well-differentiated neuroendocrine tumor G3 performed or reviewed by a NEN-dedicated pathologist. In case of "late-NET G3" a NEN-dedicated pathologist will perform a pathologic review of the previous NET G1/2, too, unless a NEN-dedicated pathologist has already done and except for diagnoses performed in a NEN-referral Center.
Cohort
Prospective
Not listed
Immunohistochemical characteristics analysis
Analysis of the morphology Analysis of proliferation index Ki-67 Analysis of Ki-67 expression (as hotspot or a diffuse expression on the sample) Analysis of Synaptophysin, and chromogranin expression
Review of the functional imaging
Analysis of homogeneity or inhomogeneity of radiotracer distribution Analysis of the concordance/discordance between functional imaging. For "late-NET G3", the specialist in nuclear medicine will review both functional imaging (before and after NET G3 diagnosis)
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