Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: report of two cases

Abstract

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumor. To date, only seven cases have been reported in the cecum, and less than 40 in the stomach. Our first case was diagnosed in a 74-years-old female as a polypoid lesion of the cecum with direct invasion in the transverse colon, without lymph node metastases. The second case was diagnosed in the stomach of a 46-years-old male as a polypoid tumor of the antral region that invaded the pancreas and presented metastases in 22 regional lymph nodes. The metastatic tissue was represented by the glandular component. In both cases, the tumor consisted of a moderately-differentiated tubular adenocarcinoma (with mucinous component in Case 1) intermingled with neuroendocrine carcinoma. Ki67 index was lower than 20% in Case 1, respectively higher than 20% in Case 2. The neuroendocrine component was marked by synaptophysin and neuron specific enolase, being negative for Keratins 7/20. The neuroendocrine component represented 60% in Case 1, and 40% in Case 2, respectively. The glandular components were marked by carcinoembryonic antigen, maspin and keratin 20/7 (Case 1/2). Both cases were proved to be microsatellite stable. Independently by the localization and tumor stage, MANECs appear to be highly malignant tumors, with high risk for distant metastases. The aggressiveness seems to depend on the endocrine component, independent of its proportion. The neuroendocrine component could be a dedifferentiated adenocarcinoma with a neuroendocrine phenotype.

Keywords: Carcinoembryonic antigen; Cecum; Colorectal; Composite tumor; Keratin 20; Keratin 7; Maspin; Mixed adenoneuroendocrine carcinoma; Mixed tumor; Stomach.

Figure 1

Cecum mixed adenoneuroendocrine carcinoma consists of proliferation of two components. First component is represented by glandular structures with mucinous foci (A-B) and displays positivity for keratin 20 (C) without immunoreactivity for synaptophysin (D), with a high Ki67 index (E) and cytoplasmic expression of maspin (F); The second component is represented by solid tumor islands (G) that are negative for keratin 20 (H) and are immunoreactive for synaptophysin (I), with a lower Ki67 index (J) and slightly cytoplasmic expression of maspin (K).

Figure 2

Gastric mixed adenoneuroendocrine carcinoma consists of mixed proliferation of glandular with specific immunoexpression. Solid tumor areas (A); The glandular structures are reactive for keratin AE1/AE3 (B) and solid structures express synaptophysin (C); A high Ki67 index can be seen in both tumor components (D); The nuclear expression of maspin in the glandular component (E) reflects the tumor aggressiveness that is confirmed by predominance of this component in lymph node metastases (F).