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Appendiceal Carcinoid / Well Differentiated Endocrine Neoplasm

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

See: Appendiceal Neuroendocrine Tumor (Carcinoid)

Differential Diagnosis

  • Conventional GI adenocarcinoma
  • Goblet cell carcinoid vs. appendiceal carcinoid
  • Site of origin of metastatic well differentiated endocrine carcinoma
Appendiceal Carcinoid / Well Differentiated Neuroendocrine Cell Neoplasm Appendiceal 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

 

Appendiceal Carcinoid / Well Differentiated Neuroendocrine Cell Neoplasm Goblet Cell Carcinoid and/or Carcinoma ex-GCC
Chromogranin or synaptophysin positive Chromogranin and synaptophysin stain rare to scattered cells only
No intracytoplasmic mucin (lumenal mucin may be present in tubular carcinoid) Intracytoplasmic mucin in goblets
CK7 negative, CK20 variable CK7 variable, CK20 100%
Rare mitotic figures at most Mitotic figures may be numerous in carcinoma ex-GCC
Cohesive nests and cords Single cell infiltration or sheet like growth in carcinoma ex-GCC
No desmoplasia Desmoplasia may be present in carcinoma ex-GCC

 

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
    • Confined to appendix 94%
    • Local invasion or metastases to lymph nodes 85%
    • Organ metastases 34%
  • Carcinoid syndrome is usually present only if the liver is involved by metastases
  • 4% of patients also have a small intestinal carcinoid
  • Indications for hemicolectomy for carcinoid (if noted at time of appendectomy)
    • >2 cm in greatest dimension
    • Involvement of mesoappendix
    • Transection
    • Lymph node involvement
  • Recommendations for re-opening the patient for right colectomy if tumor noted after closure
    • If <1 cm and margins clear, no further surgery
    • If 1-2 cm consider right colectomy if:
      • Deep mesoappendiceal invasion (>3 mm)
      • Margins not clearly negative
      • Vascular invasion
    • If >2 cm, recommend right colectomy
    • Metastatic workup should be performed before above decisions made.

Grading and Staging

  • Histopathologic features are predictive of behavior (based on WHO,  Odze and AFIP, each are a bit different)
    • Benign
      • Non-functioning
      • Well differentiated
      • ≤2 cm in greatest dimension
      • Confined to appendiceal wall
        • No involvement of mesoappendix
      • No vascular invasion
    • Uncertain malignant behavior
      • As for benign, but with:
        • >2 cm in greatest dimension and/or
        • Vascular invasion
    • Low grade malignant
      • Non-functioning and well differentiated, with:
        • Invasion of mesoappendix and/or
        • Metastasis
      • OR, functioning and well differentiated
        • Any size and extent
    • Poorly differentiated endocrine carcinoma is covered separately
  • Staging
    • AJCC TNM 7th edition now includes carcinoids of the appendix

 

Classification/Lists

Gastrointestinal Endocrine Cell Proliferations and Neoplasms

Appendiceal Epithelial Neoplasms and Proliferations

Clinical / Descriptive Terms

Bibliography

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  • 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.
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  • Moertel CG, Dockerty MB, Judd ES. Carcinoid tumors of the vermiform appendix. Cancer. 1968 Feb;21(2):270-8.
  • Williams GT. Endocrine tumours of the gastrointestinal tract-selected topics. Histopathology. 2007 Jan;50(1):30-41.
  • Carr NJ, Sobin LH. Neuroendocrine tumors of the appendix. Semin Diagn Pathol. 2004 May;21(2):108-19.
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  • Warkel RL, Cooper PH, Helwig EB. Adenocarcinoid, a mucin-producing carcinoid tumor of the appendix: a study of 39 cases. Cancer. 1978 Dec;42(6):2781-93.
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  • Burke AP, Sobin LH, Federspiel BH, Shekitka KM, Helwig EB. Goblet cell carcinoids and related tumors of the vermiform appendix. Am J Clin Pathol. 1990 Jul;94(1):27-35.
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  • 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.
  • La Rosa S, Finzi G, Puppa G, Capella C. Lipid-rich variant of appendiceal well-differentiated endocrine tumor (carcinoid). Am J Clin Pathol. 2010 May;133(5):809-14.
  • Chetty R, Serra S. Lipid-rich and clear cell neuroendocrine tumors ("carcinoids") of the appendix: potential confusion with goblet cell carcinoid. Am J Surg Pathol. 2010 Mar;34(3):401-4.
  • Plöckinger U, Couvelard A, Falconi M, Sundin A, Salazar R, Christ E, de Herder WW, Gross D, Knapp WH, Knigge UP, Kulke MH, Pape UF; Frascati Consensus Conference participants. Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated tumour/carcinoma of the appendix and goblet cell carcinoma. Neuroendocrinology. 2008;87(1):20-30.
  • Deschamps L, Couvelard A. Endocrine tumors of the appendix: a pathologic review. Arch Pathol Lab Med. 2010 Jun;134(6):871-5.
  • Long KB, Srivastava A, Hirsch MS, Hornick JL. PAX8 Expression in well-differentiated pancreatic endocrine tumors: correlation with clinicopathologic features and comparison with gastrointestinal and pulmonary carcinoid tumors. Am J Surg Pathol. 2010 May;34(5):723-9.
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