WHO The World Health Organization (WHO) classification scheme places<unk> s into three main categories, which emphasize the<unk>  grade rather than the anatomical origin: * well-differentiated<unk> rs, further subdivided into<unk> s with benign and those with uncertain behavior * well-differentiated (low grade)<unk>  carcinomas with low-grade malignant behavior * poorly differentiated (high grade)<unk>  carcinomas, which are the large cell<unk>  and small cell carcinomas. Additionally, the WHO scheme recognizes mixed<unk> s with both<unk>  and epithelial carcinoma features, such as goblet cell cancer, a rare gastrointestinal tract<unk> . Placing a given<unk>  into one of these categories depends on well-defined histological features: size, lymphovascular invasion, mitotic count, Ki-67 labelling index, invasion of adjacent organs, presence of metastases and whether they produce hormones. Anatomic distribution Traditionally,<unk> s have been classified by their anatomic site of origin.<unk> s can arise in many different areas of the body, and are most often located in the intestine, pancreas or the lungs. The various kinds of cells that can give rise to<unk> s are present in endocrine glands and are also diffusely distributed throughout the body, most commonly Kulchitsky cells or similar enterochromaffin-like cells, that are relatively more common in the gastrointestinal and pulmonary systems.<unk> s include certain<unk> s of the gastrointestinal tract and of the pancreatic islet cells, certain thymus and lung<unk> s, and medullary carcinoma of the parafollicular cells of the thyroid.<unk> s with similar cellular characteristics in the pituitary, parathyroid, and adrenomedullary glands are sometimes included or excluded. Within the broad category of<unk> s there are many different<unk>  types, representing only a small proportion of the<unk> s or cancers in most of these tissues: * Pituitary gland:<unk>  of the anterior pituitary * Thyroid gland:<unk>  thyroid<unk> s, particularly medullary carcinoma * Parathyroid<unk> s * Thymus and mediastinal carcinoid<unk> s * Pulmonary<unk> s * bronchus * pulmonary carcinoid<unk> s: typical carcinoid (TC; low-grade); atypical carcinoid (AC; intermediate-grade) * small-cell lung cancer (SCLC) * large cell<unk>  carcinoma of the lung (LCNEC) * Extrapulmonary small cell carcinomas (ESCC or EPSCC) * Gastroenteropancreatic<unk> s (GEP-NET) * Foregut GEP-NET (foregut<unk> s can conceptually encompasses not only<unk> s of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus) * Pancreatic endocrine<unk> s (if considered separately from foregut GEP-NET) * Midgut GEP-NET (from distal half of 2nd part of the duodenum to the proximal two-thirds of the transverse colon) * appendix, including well differentiated<unk> s (benign); well differentiated<unk> s (uncertain malignant potential); well differentiated<unk>  carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and mucous adenocarcinoid) * Hindgut GEP-NET * Liver and gallbladder * Adrenal<unk> s, particularly adrenomedullary<unk> s * Pheochromocytoma * Peripheral nervous system<unk> s, such as: * Schwannoma * paraganglioma * neuroblastoma * Breast * Genitourinary tract * urinary tract carcinoid<unk>  and<unk>  carcinoma * ovary *<unk>  of the cervix * Prostate<unk>  with<unk>  differentiation * testes * Merkel cell carcinoma of skin (trabecular cancer) * Inherited conditions: * multiple endocrine neoplasia type 1 (MEN1) * multiple endocrine neoplasia type 2 (MEN2) * von Hippel-Lindau (VHL) disease * neurofibromatosis type 1 * tuberous sclerosis * Carney complex Grading<unk>  lesions are graded histologically according to markers of cellular proliferation, rather than cellular polymorphism. The following grading scheme is currently recommended for all gastroenteropancreatic<unk>  neoplasms by the World Health Organization: Mitoses in a<unk> . G Mitotic count (per 10 HPF) Ki-67 index (%) GX Grade cannot be assessed G1 20 > 20% If mitotic count and Ki-67 are discordant, the figure which gives the highest grade is used. G1 and G2<unk>  neoplasms are called<unk> s <unk> s) – formerly called carcinoid<unk> rs. G3 neoplasms are called<unk>  carcinomas (NECs). It has been proposed that the current G3 category be further separated into histologically well-differentiated and poorly-differentiated neoplasms to better reflect prognosis. Staging Lymph node metastasis of a<unk> . Currently there is no one staging system for all<unk>  neoplasms. Well-differentiated lesions generally have their own staging system based on anatomical location, whereas poorly differentiated and mixed lesions are staged as carcinomas of that location. For example, gastric NEC and mixed adenoneuroendocrine cancers are staged as primary carcinoma of the stomach. TNM staging of gastroenteropancreatic Grade 1 and Grade 2<unk> s are as follows: Stomach Primary<unk>  (T) T Category<unk>  Criteria TX Primary<unk> r cannot be assessed T0 No evidence of primary<unk> r T1 Invades the lamina propria or submucosa, and less than or equal to 1 cm in size T2 Invades the muscularis propria, or greater than 1 cm in size T3 Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa T4 Invades visceral peritoneum (serosal) or other organs or adjacent structures Regional Lymph Node (N) N Category N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) M Category M Criteria M0 No distant metastasis M1 Distant metastasis M1a Metastasis confined to liver M1b Metastasis in at least one extra-hepatic site M1c Both hepatic and extra-hepatic metastases AJCC Prognostic Stage Groups Stage Criteria I T1, N0, M0 II T2 or T3, N0, M0 III Any T, N1, M0; T4, N0, M0 IV Any T, any N, M1 Duodenum / Ampulla of Vater Primary<unk>  (T) T Category<unk>  Criteria TX Primary<unk> r cannot be assessed T1 Invades the mucosa or submucosa only, and less than or equal to 1 cm in size (duodenal<unk> s)Confined within the sphincter of Oddi, and less than or equal to 1 cm in size (ampullary<unk> s) T2 Invades the muscularis propria, or is > 1 cm (duodenal)Invades through sphincter into duodenal submucosa or muscularis propria, or is > 1 cm (ampullary) T3 Invades the pancreas or peripancreatic adipose tissue T4 Invades visceral peritoneum (serosal) or other organs Regional Lymph Node (N) N Category N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) M Category M Criteria M0 No distant metastasis M1 Distant metastasis M1a Metastasis confined to liver M1b Metastasis in at least one extra-hepatic site M1c Both hepatic and extra-hepatic metastases AJCC Prognostic Stage Groups Stage Criteria I T1, N0, M0 II T2 or T3, N0, M0 III T4, N0, M0; Any T, N1, M0 IV Any T, any N, M1 Jejunum and Ileum Primary<unk>  (T) T Category<unk>  Criteria TX Primary<unk> r cannot be assessed T0 No evidence of primary<unk> r T1 Invades the lamina propria or submucosa, and less than or equal to 1 cm in size T2 Invades the muscularis propria, or greater than 1 cm in size T3 Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa T4 Invades visceral peritoneum (serosal) or other organs or adjacent structures Regional Lymph Node (N) N Category N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis less than 12 nodes N2 Large mesenteric masses (> 2 cm) and / or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels Distant Metastasis (M) M Category M Criteria M0 No distant metastasis M1 Distant metastasis M1a Metastasis confined to liver M1b Metastasis in at least one extra-hepatic site M1c Both hepatic and extra-hepatic metastases AJCC Prognostic Stage Groups Stage Criteria I T1, N0, M0 II T2 or T3, N0, M0 III Any T, N1 or N2, M0; T4, N0, M0; IV Any T, any N, M1 Appendix Primary<unk>  (T) T Category<unk>  Criteria TX Primary<unk> r cannot be assessed T0 No evidence of primary<unk> r T1 2 cm or less in greatest dimension T2<unk>  more than 2 cm but less than or equal to 4 cm T3<unk>  more than 4 cm or with subserosal invasion or involvement of the mesoappendix T4 Perforates the peritoneum or directly invades other organs or structures (excluding direct mural extension to adjacent subserosa of adjacent bowel) Regional Lymph Node (N) N Category N Criteria NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) M Category M Criteria M0 No distant metastasis M1 Distant metastasis M1a Metastasis confined to liver M1b Metastasis in at least one extra-hepatic site M1c Both hepatic and extra-hepatic metastases AJCC Prognostic Stage Groups Stage Criteria I T1, N0, M0 II T2 or T3, N0, M0 III Any T, N1, M0; T4, N1, M0 IV Any T, any N, M1 Colon and Rectum Primary<unk>  (T) T Category<unk>  Criteria TX Primary<unk> r cannot be assessed T0 No evidence of primary<unk> r T1 Invades the lamina propria or submucosa, and less than or equal to 2 cm T1a Less than 1 cm in greatest dimension T1b 1–2 cm in greatest dimension T2 Invades the muscularis propria, or greater than 2 cm in size with
Neuroendocrine tumor
Pituitary adenoma
Metastatic insulinoma
Insulinoma
Glucagonoma
Granular cell tumor
Endocrine gland neoplasm
Glial tumor