CK7/20 staining is only helpful in instances of positivity where a negative result is expected
Five year survival
No liver metastases at presentation 70%
Liver metastases at presentation 35%
Deaths due to disease continue to occur beyond 5 years
Carcinoid syndrome is usually present only if the liver is involved by metastases
15% of patients also have a non-endocrine neoplasm, usually gastrointestinal adenocarcinoma
Less frequently associated with MEN-1 than are gastric and duodenal endocrine neoplasms
Patients with multiple jejuno-ileal carcinoids have a decreased survival
Histopathologic features are predictive of behavior
≤1 cm in greatest dimension
Confined to mucosa and submucosa
No involvement of muscularis propria
No vascular invasion
Uncertain malignant behavior
As for benign, but with:
>1 but ≤2 cm in greatest dimension and/or
Low grade malignant
Non-functioning and well differentiated, with
Invasion of muscularis propria or beyond and/or
>2 cm in greatest dimension (not uniformly accepted)
OR, functioning and well differentiated
Any size and extent
Grading and Staging
WHO 2010 recommends the following grading scheme
Proposed grading scale based on proliferation
Mitotic count per 10 hpf
% of cells Ki67+
Mitotic counts based on 50 hpf
Ki67 % based on 500-2000 cells
If discrepant, use higher grade
Scale proposed by European Neuroendocrine Society (ENETS)
Carcinoids / neuroendocrine tumors may be G1 or G2
G3 is definitional for high grade neuroendocrine carcinoma
Progression from G1/2 to G3 is quite rare
G3 appears to be a separate process
Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007 Oct;451(4):757-62.
Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B; and all other Frascati Consensus Conference participants; European Neuroendocrine Tumor Society (ENETS). TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006 Oct;449(4):395-401.
Other features described above should also be reported
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Williams GT. Endocrine tumours of the gastrointestinal tract-selected topics. Histopathology. 2007 Jan;50(1):30-41.
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Anthony PP, Drury RA. Elastic vascular sclerosis of mesenteric blood vessels in argentaffin carcinoma. J Clin Pathol. 1970 Mar;23(2):110-8.
Lin X, Saad RS, Luckasevic TM, Silverman JF, Liu Y. Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. Appl Immunohistochem Mol Morphol. 2007 Dec;15(4):407-14.
Schmitt AM, Riniker F, Anlauf M, Schmid S, Soltermann A, Moch H, Heitz PU, Klöppel G, Komminoth P, Perren A. Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases. Am J Surg Pathol. 2008 Mar;32(3):420-5.
Moskaluk CA, Zhang H, Powell SM, Cerilli LA, Hampton GM, Frierson HF Jr. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003 Sep;16(9):913-9.
Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009 Apr;33(4):626-32.