Answer: Gastric poorly differentiated adenocarcinoma with signet ring cell features

Histology: Sections show gastric cardiac and esophageal squamous mucosa partially undermined by a poorly differentiated adenocarcinoma, predomemantly composed of signet ring cells. Focal gland formation (intestinal type) is noted that is best seen in the esophageal fragment. Immunohistochemistry for Her2/Neu (Herceptest) demonstrates strong basolateral membranous staining in the glandular component while very focal weak incomplete membranous staining of the signet ring cells. This staining pattern is interpreted as positive (3+). Fluorescent in situ hybridization was also performed and demonstrated amplification of the her2/Neu gene (Her2:CEP17 ratio: 7.5). The morphologic findings and the Her2 staining pattern is consistent with a gastric primary.

Discussion: Her2 expression in gastric tumor is different from Her2 expression in breast cancer. In gastric/esophageal adenocarcinoma (primarily intestinal type) Her2 positivity is less homogeneous and therefore the scoring criteria have been changed. In a small biopsy a cluster of at least 5 tumor cells with strong basolateral membranous staining is considered positive irrespective of percentage. In surgical specimen, strong complete basolateral or lateral reactivity is required in >10% of tumor cells. Furthermore, the correlation between protein overexpression and gene amplification appears to be less stringent and therefore testing with both methods is recommended.