Neuroendocrine liver metastasis in gastric mixed adenoneuroendocrine carcinoma with trilineage cell differentiation: a case report

Abstract

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare disease, which mostly occurs in the gastrointestinal tract and pancreas. Here we report a case of gastric MANEC with tri-lineage differentiation in which only the neuroendocrine component had metastasized to the liver. Liver and gastric masses were detected by abdominal computed tomography, and the preoperative relationship between liver and gastric masses was unknown. The histopathological analysis after operation confirmed the gastric mass to be MANEC, whereas the liver mass was actually the metastatic neuroendocrine component of the gastric MANEC. In the pathologic diagnosis, tri-lineage differentiation, including tubular adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma was observed in the gastric MANEC tissues. The mitotic and Ki-67 labeling indexes of the resected tumor tissue were high, and thus, the tumor was classified as a grade G3 neuroendocrine carcinoma, which has a poor prognosis. Multiple low-density masses were found in the right lobe of the liver 2.5 months after operation.

Keywords: Mixed adenoneuroendocrine carcinoma; differentiation; gastroenteropancreatic neuroendocrine tumor; immunohistochemistry.

Figure 1

Enhanced abdominal CT and gastroscopy of the liver and gastric masses. A: CT scan showing a large mass with intact pseudocapsule in the left lobe of the liver (left panel). Enhancement degree of the liver mass increased significantly in the arterial phase (middle panel) and decreased rapidly in the venous phase (right panel). B: CT scan showing a mass in the antrum of the stomach with mucosal enhancement in the arterial phase. C: Enlarged lymph node located above the pylorus (arrow). D: Gastroscopy showing an ulcerating malignant-looking mass in the antrum of the stomach.

Figure 2

Specimen removed from the gastric mass shows MANEC. A: Representative section of the gastric tumor shows MANEC. Hematoxylin and eosin stain showing the close juxtaposition of the adenocarcinoma and neuroendocrine carcinoma components. ×200. B: The neuroendocrine carcinoma component expresses synaptophysin, whereas the gland-forming adenocarcinoma component does not. ×200. C: The neuroendocrine carcinoma component expresses chromogranin A, whereas the gland-forming adenocarcinoma component does not. ×200. D: Representative section showing the mitotic activity of the neuroendocrine carcinoma component. ×400. E: Representative section showing the Ki-67 staining of the neuroendocrine carcinoma component. ×200. F: Representative section showing the intracellular bridges in the trabecular region (arrow). ×400. G: Representative section showing CK5 expression in a small area of the trabecular region. H: Representative section showing the expression of p63, a basal/progenitor marker, in a small area of the trabecular region.

Figure 3

Specimen removed from the liver mass shows metastasis from gastric MANEC. A. Tumor cells in the liver mass were negative for hepatocyte antigen, whereas normal hepatocytes were positive for hepatocyte antigen (arrow). ×200. B. Tumor cells in the liver mass were positive for CDX2. ×200. C. Almost all of the tumor cells in the liver mass were positive for chromogranin A. ×200. D. Almost all of the tumor cells in the liver mass were positive for synaptophysin. ×200.

Figure 4

Enhanced abdominal CT after operation. A. Enhanced abdominal CT showing no signs of recurrence 1 month after operation. B. Multiple low-density masses are found in the liver 2.5 months after operation.