Ferenczi Ádám, Kuthi Levente, Sejben Anita
Department of Pathology, University of Szeged, Szeged, Hungary.
Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest, Hungary.
Pathobiology. 2025;92(3):169-179. doi: 10.1159/000543330. Epub 2025 Jan 7.
Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare entity with worse prognosis compared to conventional gastric adenocarcinomas. Its histological characteristics are fetal gut-like architecture and tumor cells with cytoplasmic clearing, as well as positive immunohistochemical reaction to at least one of the enteroblastic markers. Hereby, we present a case of GAED with neuroendocrine marker positivity, with whole-exome sequencing (WES), and an updated literature review.
A 68-year-old woman presented at the general practitioner with abdominal pain. Abdominal ultrasound described gastric wall thickening raising suspicion of gastric cancer; thus, gastroscopy was performed, and biopsy samples were taken, which confirmed malignancy. Neoadjuvant systemic chemotherapy was initiated, and total gastrectomy was performed. Microscopically, pleomorphic polygonal cells were visible with clear cytoplasm and high-grade cellular atypia. Alcian blue and PAS stains demonstrated positivity for acidic and neutral mucins. P53 IHC was negative, indicative of null-phenotype, while Syntaxin-1 and Chromogranin showed focal positivity. SALL4 and Glypican 3 were positive; however, AFP displayed only minimal, uncertain positivity. The Ki67 labeling index was 70%. Due to the morphological and immunohistochemical characteristics, the tumor was concluded as GAED with neuroendocrine marker positivity. WES was carried out revealing 4 pathogenic, including TP53, KLHL7, RAPSN, and ACTA1, and 3 likely pathogenic mutations, encompassing PNKP, HNF1A, and ADNP.
GAED is a rare subtype of gastric adenocarcinomas, representing 0.3-5.4% of all cases, and has an unclarified etiology. Our WES results identified new pathogenic and likely pathogenic mutations. From a differential diagnostic point of view, hepatoid adenocarcinoma and the possibility of metastatic origin have to be excluded.
具有成肌细胞分化的胃腺癌（GAED）是一种罕见的实体瘤，与传统胃腺癌相比预后更差。其组织学特征为胎儿肠道样结构和具有细胞质透明的肿瘤细胞，以及对至少一种成肌细胞标志物呈阳性免疫组化反应。在此，我们报告一例具有神经内分泌标志物阳性的GAED病例，并进行了全外显子测序（WES）及最新文献综述。
一名68岁女性因腹痛就诊于全科医生处。腹部超声显示胃壁增厚，怀疑为胃癌；因此进行了胃镜检查并取活检样本，确诊为恶性肿瘤。开始进行新辅助全身化疗，随后进行了全胃切除术。显微镜下可见多形性多边形细胞，细胞质透明，细胞异型性高。阿尔辛蓝和PAS染色显示酸性和中性粘蛋白呈阳性。P53免疫组化阴性，提示无表型，而Syntaxin-1和嗜铬粒蛋白呈局灶性阳性。SALL4和磷脂酰肌醇蛋白聚糖3呈阳性；然而，甲胎蛋白仅显示微量、不确定的阳性。Ki67标记指数为70%。根据形态学和免疫组化特征，该肿瘤被诊断为具有神经内分泌标志物阳性的GAED。进行WES检测发现4个致病突变基因，包括TP53、KLHL7、RAPSN和ACTA1，以及3个可能致病的突变基因，包括PNKP、HNF1A和ADNP。
GAED是胃腺癌的一种罕见亚型，占所有病例的0.3-5.4%，病因尚不明确。我们的WES结果鉴定出了新的致病和可能致病的突变。从鉴别诊断的角度来看，必须排除肝样腺癌和转移瘤的可能性。
