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. Author manuscript; available in PMC: 2021 Feb 1.
Published in final edited form as: Hum Pathol. 2019 Dec 17;96:8–33. doi: 10.1016/j.humpath.2019.12.002

Table 3.

Required and Recommended Reporting Elements for Biopsies and Resections of Neuroendocrine Epithelial Neoplasms

Required Data Element: Associated Required or Recommended
Immunohistochemistry
Diagnosis: well-differentiated neuroendocrine tumor (typical or atypical carcinoid tumor for lung) or poorly differentiated neuroendocrine carcinoma (small cell or large cell-type)

  • Chromogranin A and synaptophysin (or INSM1) to establish neuroendocrine nature (required)

  • Broad-spectrum epithelial marker to confirm epithelial nature (highly recommended in primary and regional disease and required in distant metastasis)

  • p53 and Rb are recommended in the distinction of well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma; other immunostains may be useful in this differential
Ki-67 proliferation index (proliferation index >20% is implied for poorly differentiated neuroendocrine carcinoma and performance is not mandatory)

  • Ki-67 on at least one block of tumor (required)

  • Ki-67 on additional blocks (e.g., matched primary and metastasis) (recommended)
Mitotic count per 2 mm2 (assessed in at least 10mm2 [50 HPF for microscopes with a field number of 20] and expressed as mitotic figures per 2 mm2; in biopsies with fewer HPF it is reasonable to express the total number of mitotic figures per the total number of HPFs; for poorly differentiated neuroendocrine carcinoma a “G3 range”-mitotic count is implied and performance is not mandatory)
Grade: G1, G2, or G3 (G3 is implied for poorly differentiated neuroendocrine carcinoma and need not be explicitly stated)
Data elements in CAP Cancer Protocol: for resection specimens
Recommended Data Element:
Comment on site of origin (for metastasis of occult origin)

  • Panel in a well-differentiated neuroendocrine tumor to include widely available markers of midgut (CDX2), pancreatic (polyclonal PAX8 and/or PR), lung (TTF-1), and rectal (SATB2) origin; if available, islet 1 and OTP are the best pancreatic and lung NET markers and serotonin may be useful to supplement the sensitivity of CDX2 for midgut

  • Panel in a poorly differentiated neuroendocrine carcinoma to include TTF-1 for visceral origin and CK20 for cutaneous origin; neurofilament, CM2B4, and strong SATB2-positivity may also be helpful to support a cutaneous origin