PMC4963962_01
(A) A computed tomography scan demonstrating a large ulcerofungating hypodense mass in the anterior gastric wall (arrow) and enlargement of multiple perigastric lymph nodes (arrowhead). Macroscopic findings (B) and cross-section of gastric cancer (C). (D) Mapping of the gastric mixed adenoneuroendocrine carcinoma with trilineage histologic differentiation composed of adenocarcinoma (pink color), large cell neuroendocrine carcinoma, and squamous cell carcinoma (green color).
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Computed tomography demonstrated a large hypodense ulcerofungating mass in the gastric anterior wall along with multiple perigastric lymphadenopathies (Fig. 1A). Gross examination of the resected stomach showed a smooth serosal surface and a large ulcerofungating mass measuring 8.5 x 7.0 cm, consistent with Borrmann type 2, in the lower anterior wall (Fig. 1B). On sectioning, the tumor had a heterogeneous appearance with a mixture of white and yellow lesions with infiltrative boundaries, invading to the serosal layer (Fig. 1C). The adenocarcinoma component was in the upper portion of the tumor, whereas the NEC component presented in the deep portion, with a small proportion in the upper portion, up to the mucosal layer (Fig. 1D).
Representative microscopic findings of mixed adenoneuroendocrine carcinoma with trilineage histologic differentiation. (A) Moderately differentiated adenocarcinoma admixed with large cell neuroendocrine carcinoma (NEC). (B) The NEC component demonstrates positive staining for chromogranin A, whereas the adenocarcinoma component shows negativity. (C) Squamous cell carcinoma (SqCC) component admixed with the NEC component, and (D) the NEC component presented positivity for chromogranin A, but not the SqCC component. (E) The cells with squamous cell differentiation are identified by expression of p63. (F) Metastasis of only the adenocarcinoma component to the gastric regional lymph nodes.
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In particular, the collision between the adenocarcinoma and NEC components was found in the ulcerated tumor area (Fig. 2A). Additionally, transition from NEC to SqCC was found in some areas (Fig. 2C). As expected, immunohistochemical staining for synaptophysin and chromogranin A were positive in the NEC component but negative in the adenocarcinoma and SqCC components (Fig. 2B, D). The SqCC component but not the NEC or adenocarcinoma component revealed strong nuclear expression for p63 (Fig. 2E). The tumor penetrated the serosa, and 14 of the 48 regional lymph nodes showed metastasis, which, interestingly, was composed of only the adenocarcinoma component (Fig. 2F), but distant metastasis was not detected.
Photomicrographs of immunohistochemistry (IHC) for c-erbB2 in mixed adenoneuroendocrine carcinoma with trilineage histologic differentiation. IHC for c-erbB2 shows strong positivity in the adenocarcinoma component (A), and in the metastatic regional lymph nodes (B), whereas IHC for c-erbB2 is negative in neuroendocrine carcinoma (C) and squamous cell carcinoma component (D).
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Interestingly, for c-erbB2, the NEC component revealed negativity, whereas the adenocarcinoma component showed complete membranous staining of strong intensity in primary gastric cancer and in its corresponding metastatic regional lymph nodes (Fig. 3).