8_well_differentiated_neuroendocrine

96

Digestive System Tumours

Well‐Differentiated Neuroendocrine Tumours of the Gastrointestinal Tract Rules for Classification This classification system applies to well‐differentiated neuroendocrine tumours (carcinoid tumours and atypical carcinoid tumours) of the gastro­ intestinal tract, including the pancreas. Neuroendocrine tumours of the lung should be classified according to criteria for carcinoma of the lung.

Merkel cell carcinoma of the skin has a separate classification.

High‐grade (Grade 3) neuroendocrine carcinomas are excluded and should be c­ lassified according to criteria for classifying carcinomas at the respective site.

Histopathological Grading The following grading scheme has been proposed for all gastrointestinal neuroendocrine tumours: Grade

Mitotic count (per 10 HPF)a

Ki‐67 index (%)b

G1

<2

≤2

G2

2–20

3–20

G3

>20

>20

Notes a 10 HPF (high power fields) = 2 mm2; at least 40 fields (at 40× magnification) evaluated in areas of highest mitotic density. b MIB1 antibody; % of 500–2000 tumour cells in areas of highest nuclear labelling.

Well‐Differentiated Neuroendocrine Tumours (G1 and G2) – Gastric, Jejunum/Ileum, Appendix, Colonic, and Rectal Regional lymph nodes The regional lymph nodes correspond to those listed under the appropriate sites for carcinoma.

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TNM Clinical Classification Stomach

T – Primary Tumour TX T0

Primary tumour cannot be assessed No evidence of primary tumour

T1 Tumour invades lamina propria or submucosa and 1 cm or less in greatest dimension T2 Tumour invades muscularis propria or is more than 1 cm in greatest dimension T3 Tumour invades subserosa T4 Tumour perforates visceral peritoneum (serosa) or invades other organs or adjacent structures Note For any T, add (m) for multiple tumours.

N – Regional Lymph Nodes Digestive System

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis

M – Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Hepatic metastasis(is) only M1b Extrahepatic metastasis(is) only M1c Hepatic and extrahepatic metastases

Stage Stage I Stage II Stage III Stage IV

T1 T2, T3 T4 Any T Any T

N0 N0 N0 N1 Any N

M0 M0 M0 M0 M1

98

Digestive System Tumours

TNM Clinical Classification Duodenal/Ampullary Tumours

T – Primary Tumour TX T0

Primary tumour cannot be assessed No evidence of primary tumour

T1 Duodenal: Tumour invades mucosa or submucosa and 1 cm or less in greatest dimension

Ampullary: Tumour 1 cm or less in greatest dimension and confined within the sphincter of Oddi T2 Duodenal: Tumour invades muscularis propria or is more than 1 cm in greatest dimension

Ampullary: Tumour invades through sphincter into duodenal sub­ mucosa or muscularis propria, or more than 1 cm in greatest dimension T3 Tumour invades the pancreas or peripancreatic adipose tissue T4 Tumour perforates visceral peritoneum (serosa) or invades other organs Note For any T, add (m) for multiple tumours.

N – Regional Lymph Nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis

M – Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Hepatic metastasis(is) only M1b Extrahepatic metastasis(is) only M1c Hepatic and extrahepatic metastases

Stage Stage I Stage II Stage III Stage IV

T1 T2, T3 T4 Any T Any T

N0 N0 N0 N1 Any N

M0 M0 M0 M0 M1

Well‐Differentiated Neuroendocrine Tumours of the Gastrointestinal Tract

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TNM Clinical Classification Jejunum/Ileum

T – Primary Tumour TX T0

Primary tumour cannot be assessed No evidence of primary tumour

T1 Tumour invades lamina propria or submucosa and 1 cm or less in greatest dimension T2 Tumour invades muscularis propria or is greater than 1 cm in greatest dimension T3 Tumour invades through the muscularis propria into subserosal tissue without penetration of overlying serosa (jejunal or ileal) T4 Tumour perforates visceral peritoneum (serosa) or invades other organs or adjacent structures

N – Regional Lymph Nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Less than 12 regional lymph node metastasis without mesenteric mass(es) greater than 2 cm in sizes N2 12 or more regional nodes and/or mesenteric mass(es) greater than 2 cm in maximum dimension

M – Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Hepatic metastasis(is) only M1b Extrahepatic metastasis(is) only M1c Hepatic and extrahepatic metastase

Stage Stage I Stage II Stage III Stage IV

T1 T2,T3 T4 Any T Any T

N0 N0 Any N N1, N2 Any N

M0 M0 M0 M0 M1

Digestive System

Note For any T, add (m) for multiple tumours.

100

Digestive System Tumours

TNM Clinical Classification Appendix

T – Primary Tumoura TX T0

Primary tumour cannot be assessed No evidence of primary tumour

T1 Tumour 2 cm or less in greatest dimension T2 Tumour more than 2 cm but not more than 4 cm in greatest dimension T3 Tumour more than 4 cm or with subserosal invasion or involvement of the mesoappendix T4 Tumour perforates peritoneum or invades other adjacent organs or structures, other than direct mural extension to adjacent subserosa, e.g., abdominal wall and skeletal muscleb Notes a High‐grade neuroendocrine carcinomas, mixed adenoneuroendocrine carcinomas and goblet cell carcinoid, are excluded and should be classified according to criteria for classifying carcinomas. b Tumour that is adherent to other organs or structures, macroscopically, is classified T4. However, if no tumour is present in the adhesion, microscopically, the classifica­ tion should be classified pT1–3.

N – Regional Lymph Nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis

M – Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Hepatic metastasis(is) only M1b Extrahepatic metastasis(is) only M1c Hepatic and extrahepatic metastases

pTNM Pathological Classification The pT and pN categories correspond to the T and N categories. For pM see page 8. pN0 Histological examination of a regional lymphadenectomy specimen will ordinarily include 12 or more lymph nodes. If the lymph nodes are negative, but the number ordinarily examined is not met, classify as pN0.

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Stage Stage I Stage II Stage III Stage IV

T1 T2, T3 T4 Any T Any T

N0 N0 N0 N1 Any N

M0 M0 M0 M0 M1

TNM Clinical Classification Colon and Rectum

T – Primary Tumour Primary tumour cannot be assessed No evidence of primary tumour

T1 Tumour invades lamina propria or submucosa or is no greater than 2 cm in size T1a Tumour less than 1 cm in size T1b Tumour 1 or 2 cm in size T2 Tumour invades muscularis propria or is greater than 2 cm in size T3 Tumour invades subserosa, or non‐peritonealized pericolic or perirectal tissues T4 Tumour perforates the visceral peritoneum or invades other organs Note For any T, add (m) for multiple tumours.

N – Regional Lymph Nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis

M – Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Hepatic metastasis(is) only M1b Extrahepatic metastasis(is) only M1c Hepatic and extrahepatic metastases

pTNM Pathological Classification The pT and pN categories correspond to the T and N categories. For pM see page 8.

Digestive System

TX T0

102

Digestive System Tumours

Stage Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB Stage IV

T1 T2 T3 T4 Any T Any T

N0 N0 N0 N0 N1 Any N

M0 M0 M0 M0 M0 M1

Well‐Differentiated Neuroendocrine Tumours – Pancreas (G1 and G2) Rules for Classification This classification system applies to well‐differentiated neuroendocrine tumours (carcinoid tumours and atypical carcinoid tumours) of the pancreas.

High‐grade neuroendocrine carcinomas are excluded and should be classified according to criteria for classifying carcinomas of the pancreas.

Regional lymph nodes The regional lymph nodes correspond to those listed under the appropriate sites for carcinoma.

TNM Clinical Classification Pancreas

T – Primary Tumoura TX T0

Primary tumour cannot be assessed No evidence of primary tumour

T1 Tumour limited to pancreas,b 2 cm or less in greatest dimension T2 Tumour limited to pancreasb more than 2 cm but less than 4 cm in greatest dimension T3 Tumour limited to pancreas,b more than 4 cm in greatest dimension or tumour invading duodenum or bile duct.

T4 Tumour perforates visceral peritoneum (serosa) or invades other organs or adjacent structures Notes a For any T, add (m) for multiple tumours. b Invasion of adjacent peripancreatic adipose tissue is accepted but invasion of adja­ cent organs is excluded.

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N – Regional Lymph Nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis

M – Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Hepatic metastasis(is) only M1b Extrahepatic metastasis(is) only M1c Hepatic and extrahepatic metastases

Stage I Stage II Stage III Stage IV

T1 T2, T3 T4 Any T Any T

N0 N0 N0 N1 Any N

M0 M0 M0 M0 M1

Digestive System

Stage