Case Report: Heterogeneous endoscopic and histological presentations of gastric and gastroesophageal metastases from breast carcinoma: a three-case series from a Malaysian tertiary center

Abstract

Background Gastric metastasis from breast carcinoma is uncommon and is most often associated with invasive lobular carcinoma (ILC), although carcinoma of no special type (NST) and mixed tumors also occur. Metastatic deposits closely mimic diffuse-type gastric adenocarcinoma, and the distinction from a primary gastric tumor carries major therapeutic consequences. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status may differ between the primary tumor and its metastasis, with direct implications for systemic therapy. Case descriptions We report three women managed at a single Malaysian tertiary center. Case 1 (56 years old; metachronous interval of approximately 4 years) had an ER-positive, HER2 3+ (immunohistochemistry [IHC]) carcinoma of no special type that presented as a circumferential Siewert III gastroesophageal junction (GOJ) tumor with gastric satellites; the metastasis retained E-cadherin and was HER2 2+ with a non-amplified in situ hybridization (ISH) result, a discordance from the HER2 3+ primary. Case 2 (47 years old; synchronous) presented with a linitis plastica-like pattern and gastric outlet obstruction (GOO) from an ER-positive, HER2-negative carcinoma; the primary showed patchy E-cadherin and the metastasis showed focal E-cadherin, consistent with a mixed ductal-lobular phenotype; PR expression was lost between the primary (strong, >90%) and the metastasis (negative). Case 3 (91 years old; effectively synchronous, approximately 6-year course) had a lobular carcinoma with E-cadherin loss and a decline in PR expression (from focal weak positivity in the primary to negative in the metastasis), with a protracted course dominated by recurrent feeding-tube complications. In each case, the diagnosis rested on morphology, a breast-oriented IHC panel, and comparison with the known breast primary rather than on any single marker. Conclusion This series illustrates that gastric and GOJ metastases from breast carcinoma are morphologically and endoscopically heterogeneous and are not confined to E-cadherin-negative ILC. E-cadherin reflects tumor phenotype and cell cohesion rather than the organ of origin, and it should not be used to distinguish a breast metastasis from a primary gastric carcinoma. Because clinically relevant ER, PR, and HER2 discordance may occur, these biomarkers should be reassessed in metastatic tissue, with results interpreted proportionately to the available evidence.