The WHO Classification of Tumors of the Digestive System, 4th edition, 2010, revised the nomenclature and classification of neuroendocrine tumors. Our country is also very inconsistent in the pathological diagnosis name, classification and grading of GEP-NEN. We suggest you to pay attention to it.
Definition of neuroendocrine tumors
Neuroendocrine tumors are defined as highly differentiated (well-differentiated) neuroendocrine neoplasms with tumor cell morphology similar to normal intestinal endocrine cells and tumor cell arrangement with organoid features, such as nest-like, trabecular or cerebral gyrus-like. They express common neuroendocrine differentiation markers (usually diffuse and high expression of chromogranin A and synaptophysin) and may have corresponding hormonal expression depending on the site of pathogenesis (usually high expression without diffuse expression).
Light microscopy shows mild to moderate nuclear anisotropy and a low nuclear division number (<20/10 HPF); G1 and G2 are identified according to histology and proliferation indices. this definition covers the "carcinoid tumor" in the 2000 WHO staging.
Definition of neuroendocrine carcinoma
Neuroendocrine carcinoma is defined as a group of poorly differentiated (poorly differentiated), highly malignant tumors that exhibit small cell or large to medium cell morphology with a lamellar or mixed irregular arrangement of tumor cells, and sometimes may exhibit organoid features similar to neuroendocrine tumors. Diffuse expression of common neuroendocrine differentiation markers (diffuse expression of synaptophysin; weak or focal expression of chromogranin A).
The definition includes the previous versions of small cell carcinoma, large cell (neuroendocrine) carcinoma, and neuroendocrine carcinoma. neuroendocrine carcinoma, and poorly differentiated neuroendocrine carcinoma.
Definition of mixed adenoneuroendocrine carcinoma (MANEC)
Mixed adenoneuroendocrine carcinoma is defined as a carcinoma that includes both adenoid epithelium and neuroendocrine expressing cells in the tumor tissue, and is required because both components have malignant potential. Squamous cell carcinoma is rare. Each component must be at least 30% or more to meet this definition. Scattered neuroendocrine staining in adenocarcinoma does not meet this definition.
WHO neuroendocrine tumor grading and classification
The updated classification criteria combine information on tumor cell differentiation and grade to classify neuroendocrine tumors, removing the entries for tumor size, peripheral nerve vascular invasion, and visual invasion of peripheral organs from the previous version. The term “differentiation” represents the similarity of cell morphology in neoplastic and non-neoplastic tissues, while “grade” indicates the biological behavior of the tumor.
Studies on neuroendocrine tumors of foregut origin (stomach and pancreas) have shown that proliferative capacity is an important prognostic correlate, and the updated WHO grading system has adopted the grading method recommended by ENETS, including the nuclear division number and Ki-67 index of tumor cells (Table 1).
Table 1 WHO grading method
Nuclear division number Ki-67 index
G1 <2/10HPF ≤2%
G2 2-20/10HPF and/or 3-20%
G3 >20/10HPF >20%
1.Nuclear division number should be counted at least 50 high power field (1HPF=2mm2), apply MIB antibody to detect and calculate Ki-67 index, need to count 500-2000 cells in the area of strongest nuclear staining.
2, If the nuclear division number and Ki-67 index are different, it is recommended to use a higher fraction. The source of evidence for the relevant studies is related to NET of the stomach, duodenum and pancreas, but no evidence of NET of the small intestine.
This version adjusts the nomenclature of each classification at the same time, removing the terms such as highly differentiated or hypofractionated in the previous version, and classifying them by unifying the nomenclature as neuroendocrine tumors or neuroendocrine carcinomas with different scores.
WHO reporting of neuroendocrine tumors
The minimum elements to be reported when reporting neuroendocrine tumors include: site of tumor occurrence, size, and distance from the incisional margin (for resected specimens). Light microscopy requires reporting the number of nuclear divisions per 10 high-powered views, the number of high-powered views examined, and the Ki-67 index. A diagnosis of neuroendocrine tumor or carcinoma only without differentiation and grading will not be used for clinical prognosis determination and guiding subsequent treatment. The diagnosis of endocrine function requires specific clinical information from the clinician.
Diagnosis of neuroendocrine tumors requires including.
1. lesion classification (NET or NEC);
2. staging (G1, G2 or G3);
3. The corresponding TNM staging (surgical resection of the specimen);
4, cell type and functional status according to clinical information. The use of “hormone name” plus “tumor” (e.g., growth-dependent hormone tumor, gastrinoma) is only applicable when the patient presents with clinical symptoms related to hormone secretion. When only immunohistochemical evidence is available, it is not recommended for neuroendocrine tumors similar to gastrin-secreting neuroendocrine tumors or growth-inhibiting neuroendocrine tumors, but can be added after the diagnostic classification of neuroendocrine tumors, such as neuroendocrine tumors with immunohistochemistry showing gastrin secretion.