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Surgical Pathology Criteria
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Carcinoid / Well Differentiated Endocrine Neoplasm of the Ileum, Distal Jejunum and Cecum

WHO 2010 has changed back to usage of the term Neuroendocrine rather than Endocrine

See: Ileum Neuroendocrine Tumor (Carcinoid)

Differential Diagnosis

  • Conventional GI adenocarcinoma
  • Site of origin of metastatic well differentiated endocrine carcinoma
Ileal Carcinoid / Well Differentiated Neuroendocrine Cell Neoplasm Ileal or Other GI Adenocarcinoma
Bland cytologic features Atypical cytology
Chromogranin or synaptophysin positive Chromogranin and synaptophysin negative
No desmoplastic response Desmoplastic response frequent
Rare mitotic figures Mitotic figures frequently numerous
Cohesive nests and cords Frequent single cell infiltration
No surface adenoma or in situ lesion May have surface adenoma or in situ component
No intracytoplasmic mucin May have intracytoplasmic mucin and/or signet ring cells

 

Determination of common sites of origin for metastatic well differentiated endocrine neoplasms
  TTF1 CDX2 PDX1 ISL1 PAX8
Lung 40-50% Negative Negative Negative Negative
Pancreas Negative 0-18% 28% 68% 50-67%
Stomach Negative 0-17% 60% Negative 20%
Duodenum Negative 0-17% 60% Negative 100%
Ileum Negative >90% Negative Negative Negative
Appendix Negative >90% 55% Negative 21%
Rectum Negative 0-55% 17% Negative 85%
Detection of specific islet hormones may be useful; PAX8 data has been questioned (see Pancreas).

 

Determination of common sites of origin for metastatic well differentiated endocrine neoplasms-keratins
  CK7 CK20
Lung Variable Negative
Pancreas Variable Variable
Stomach Variable Negative
Duodenum Negative Variable
Ileum Negative Variable
Appendix Negative Variable
Rectum Variable Variable
CK7/20 staining is only helpful in instances of positivity where a negative result is expected

Clinical

  • Five year survival
    • No liver metastases at presentation 65%
    • 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

Grading and Staging

  • Histopathologic features are predictive of behavior
    • Benign
      • Non-functioning
      • Well differentiated
      • ≤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
        • Vascular invasion
    • Low grade malignant
      • Non-functioning and well differentiated, with
        • Invasion of muscularis propria or beyond and/or
        • Metastasis and/or
        • >2 cm in greatest dimension (not uniformly accepted)
      • OR, functioning and well differentiated
        • Any size and extent
    • Poorly differentiated neuroendocrine carcinoma is covered separately
  • AJCC TNM 7th edition now includes carcinoids of the ileum

Classification/Lists

Gastrointestinal Endocrine Cell Proliferations and Neoplasms

Bibliography

  • Riddell RH, Petras RE, Williams GT, Sobin LH. Tumors of the Intestines, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 32, 2003.
  • Hamilton SR, Aaltonen LA eds. Pathology and genetics of tumours of the digestive system. World Health Organization classification of tumours, Vol. 2. Lyon: IARC Press 2000.
  • Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997 Feb 15;79(4):813-29.
  • Williams GT. Endocrine tumours of the gastrointestinal tract-selected topics. Histopathology. 2007 Jan;50(1):30-41.
  • Burke AP, Thomas RM, Elsayed AM, Sobin LH. Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases. Cancer. 1997 Mar 15;79(6):1086-93.
  • Nies C, Zielke A, Hasse C, Rüschoff J, Rothmund M. Carcinoid tumors of Meckel's diverticula. Report of two cases and review of the literature. Dis Colon Rectum. 1992 Jun;35(6):589-96. Review.
  • Yantiss RK, Odze RD, Farraye FA, Rosenberg AE. Solitary versus multiple carcinoid tumors of the ileum: a clinical and pathologic review of 68 cases. Am J Surg Pathol. 2003 Jun;27(6):811-7.
  • 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.
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