Appendiceal Carcinoid / Well Differentiated Neuroendocrine Neoplasm / Tumor
Definition
- Low grade neoplasm of the appendix demonstrating neuroendocrine differentiation
Note
- WHO 2010 has changed back to neuroendocrine cell from endocrine cell for these lesions
- Endocrine neoplasm/tumor are equivalent terms to those used below
- Carcinoid and low grade or well differentiated neuroendocrine neoplasm/tumor/carcinoma are equivalent terms
- Goblet cell carcinoid is covered separately
- High grade / poorly differentiated neuroendocrine carcinoma is covered separately
Diagnostic Criteria
- Most cells show evidence of neuroendocrine differentiation
- Synaptophysin stain positive in nearly all cases
- Chromogranin positive in most
- Argyrophil stain positive in nearly all cases
- Argentaffin positive in most
- Neuron specific enolase, PGP9.5 and CD56 are sensitive but not specific
- Most well differentiated neoplasms exhibit characteristic cytologic and architectural features
- Round regular nuclei
- Stippled (salt and pepper) chromatin
- Moderate to abundant cytoplasm
- Rarely may contain lipid vacuoles
- Various growth patterns
- Insular growth pattern
- Round nests of cells
- May palisade
- Trabecular
- Rows and strands of cells
- Cells are “stacked” with their long axis perpendicular to the long axis of the row
- Tubular (see below)
- Lined by single layer of uniform cells
- True glands with intracytoplasmic mucin not seen
- May form rosettes
- Usually involves only base of crypts and below, leaving mucosa largely intact
- Carcinoids can be subdivided by pattern and secretory products
- Enterochromaffin (EC) cell serotonin producing carcinoid is the most common type in the appendix
- Predominantly insular
- S100 positive sustentacular cells around nests
- (Differs from ileal carcinoids)
- Produce serotonin and substance P
- Synaptophysin and chromogranin A positive
- Argentaffin and argyrophil positive
- Frequent invasion
- Muscularis propria and serosa
- Usually permeates muscle without desmoplastic response
- Lymphatics and perineural space involvement frequent
- L cell glucagon-like peptide and pancreatic polypeptide (PP/PYY) producing carcinoid is uncommon in the appendix
- Predominantly tubular and/or trabecular
- Produce GLP-1, GLP-2, glycentin, oxyntomodulin, PP/PYY
- Synaptophysin positive, usually chromogranin A negative,
- Chromogranin B positive (not detected by most common anti-chromogranin antibodies)
- Argyrophil positive, usually argentaffin negative,
- Usually <3 mm and non-invasive
- Tubular carcinoid is uncommon in the appendix
- Predominantly tubular pattern
- May contain inspissated mucin
- Short trabeculae may be present
- No other above described pattern present
- Solid nests not seen
- No sustentacular cells
- True glands with intracytoplasmic mucin not seen
- No desmoplastic response
- May produce chromogranin, glucagon, serotonin
- May stain for IgA
- Argentaffin positive in scattered cells in 75% of cases
- Benign
- One report of lipid-rich clear cell carcinoids
- Mixture of cells with microvesicular and clear cytoplasm
- All reported cases were incidental with benign behavior
- One small series of combined GCC and classical carcinoid reported (Chetty 2010)
- This may represent a collision tumor as incidental classical carcinoids are not rare
Robert V Rouse MD
Teri A Longacre MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting / updates: 7/27/10, 8/21/10, 12/28/11
