Neuroendocrine neoplasms of the appendix, colon and rectum

Abstract

Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most recent WHO classification as neuroendocrine tumors (NET), neuroendocrine carcinomas (NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNENs). NECs and MiNENs are aggressive neoplasms requiring multimodal treatment strategies. By contrast, NETs are, in most cases, indolent lesions occurring as incidental findings in the appendix or as polyps in the rectum. While most appendiceal and rectal NETs are considered relatively non-aggressive neoplasms, a few cases, may show a more aggressive clinical course. Unfortunately, clinical/pathological characteristics to select patients at high risk of recurrence/metastases are poorly consolidated. Diagnosis is generally easy and supported by the combination of morphology and immunohistochemistry. Differential diagnostic problems are for NECs/MiNENs with poorly differentiated adenocarcinomas, when immunohistochemical neuroendocrine markers are not obviously positive, whereas for NETs they are represented by the rare appendiceal tubular and clear cell variants (which may be confused with non-neuroendocrine cancers) and rectal L-cell tumors which may be chromogranin negative and prostatic marker positive.

Keywords: appendix; colon; neuroendocrine; rectum; tumor.

Figure 1.

Neuroendocrine tumor of the appendix associated with acute appendicitis (a), with invasion of the mesoappendix (b), infiltrative growth, highlighted by chromogranin A immunohistochemical staining (c), but with low mitotic and proliferative index (Ki-67 staining) coding for G1 tumor grade (d).

Figure 2.

Neuroendocrine tumor of the appendix, clear cell variant, with clear granular cells (a) negative for PAS staining (b) and with diffuse granular positivity for chromogranin A (c) and nuclear positivity for CDX-2 (d).

Figure 3.

Poorly differentiated neuroendocrine carcinoma of the colon (a). Mixed neuroendocrine-non neuroendocrine neoplasm (MiNEN) (b) with poorly differentiated neuroendocrine component (yellow asterisk) and adenomatous component (green asterisk). Mixed neuroendocrine-non neuroendocrine neoplasm (MiNEN) with poorly differentiated neuroendocrine component (yellow asterisk) and adenocarcinoma with evident mucin production (black asterisk) (c). Synatophysin of MiNEN (d) showing diffuse expression in the neuroendocrine component (yellow asterisk) and no expression in the adenocarcinomatous areas (black asterisk).

Figure 4.

Rectal well differentiated neuroendocrine tumor L-cell type (a). Ribbon-like and festooned architecture of cytologically bland cells (b). L-cell rectal NET with pseudo-glandular architecture and overlying mucosa (c). Lympho-vascular invasion is an important prognostic factor (d).