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.
Granular cell tumor (GCT) is an uncommon soft tissue neoplasm which has an unclear histogenesis. The aim of this study was to analyze its immunophenotype and hypothesize on the histogenesis of GCT. A database of 2,250 soft tissue tumors was examined to identify and characterize the particularities of GCTs. A large panel of antibodies was used. Of the 2,250 tumors, only 15 were GCTs (0.66 %); these were diagnosed in patients whose average age was 37 years. Among them, 5 had malignant potential, the remaining 10 were benign. One of these benign tumors was associated with a metachronous chondrosarcoma with metastases in the lungs. No recurrences were reported in these cases. The benign tumors displayed positivity for S-100, neuron-specific enolase (NSE), CD56, epithelial membrane antigen (EMA), and inhibin. In the atypical GCTs, NSE, S-100 protein, c-KIT, RET and EMA were positive, while inhibin and CD56 were negative; rare osteoclastic-like histiocytes, marked by CD68, were seen. All cases were negative for CD31, CD34, smooth muscle actin, desmin, maspin, and calretinin. Ovoid bodies expressed CD105, synaptophysin, and HER-2. All the cases were microsatellite-stable tumors. The immunoprofile suggests that the GCT seems to have an endomesenchymal origin. The c-KIT and RET positivity, associated with microsatellite stability, and the immunoprofile of the ovoid bodies have never reported before in GCTs.
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