Gastric Adenocarcinoma With Enteroblastic Differentiation: A Clear Cell Conundrum

Gastric Adenocarcinoma with Enteroblastic Differentiation (GAED) is an aggressive and rare subtype of Gastric Carcinoma (GC). The authors report a case of 65-year-old male presented with complaints of upper Gastrointestinal tract (GI) bleeding for two months. Endoscopy revealed an ulceroproliferative growth in the incisura and distal body of stomach. Small biopsy was suggestive of adenocarcinoma. Patient underwent D1 subtotal gastrectomy. Gross specimen had an ulcerative growth in the lesser curvature. Histopathology showed malignant neoplasm consisting of tubules lined by cuboidal to columnar cells with clear cytoplasm resembling primitive foetal gut epithelium. Periodic Acid-Schiff (PAS) staining highlighted the glycogen rich clear cytoplasm. Oncofoetal Immunohistochemical (IHC) markers such as Glypican-3 (GPC3) and Spalt-like transcription factor (SALL-4) were positive supporting enteroblastic differentiation. Tumour penetrated the subserosal tissue and showed lymph node metastasis. Compared to conventional GCs, GAED has aggressive behavior and poor prognosis with tumour showing early deep tumour invasion, lymph node and distant metastasis. Serum tumour marker such as Alpha-fetoprotein (AFP) can be elevated aiding in diagnosis and follow up. Further prognostic markers such as Human Epidermal Growth Factor Receptor 2 (HER2/neu) was done and was negative and tumour protein p53 (p53) showed mutant type staining underscoring GAEDs aggressive nature. Recognition of this histologic subtype is crucial, to differentiate it from other AFP producing and clear cell tumours such as hepatoid gastric adenocarcinoma, metastatic clear cell renal cell carcinoma, yolk sac tumour-like adenocarcinoma, well differentiated tubular or papillary adenocarcinoma with clear cell features, and in case of patient presenting with early liver metastasis from primary hepatocellular carcinoma. The present case highlighted the importance of considering GAED as a differential on encountering clear cells in a gastric cancer which also resembled foetal intestinal epithelium. Histochemical staining such as PAS and IHC staining like AFP for antigen markers like, GPC3, SALL-4, Hepatocyte Paraffin 1 (HepPar1) and sometimes cytokeratin can help with the diagnosis and to exclude other clear cell tumours. HER2/neu was negative and p53 IHC showed mutant-type expression. Early diagnosis of this rare aggressive subtype is essential to guide further follow up, improving patient outcome and further understanding of its clinicopathologic spectrum.