1] Department of Pathology, Massachusetts General Hospital, Boston, MA, USA [2] Department of Pathology, University of Tokyo, Tokyo, Japan.
Mod Pathol. 2013 Dec;26(12):1620-31. doi: 10.1038/modpathol.2013.98. Epub 2013 May 31.
Very well-differentiated gastric adenocarcinoma of intestinal type is a rare variant of gastric cancer characterized by low-grade nuclear atypia, and for which the diagnostic criteria and clinical behavior are not fully established. This study presents a detailed histologic, immunohistochemical, and clinical analysis of 21 cases. Nuclear atypia was mild in all cases. Characteristic architectural features of this gastric adenocarcinoma variant were pit and glandular anastomosis, spiky glands, distended glands, discohesive cells, abortive glands, and glandular outgrowth. At least three of these features were present in all the cases. Retrospective review of preoperative biopsies in 18 patients revealed that half of the biopsies were originally reported as negative or indeterminate for malignancy. On the basis of immunohistochemical stains for intestinal (MUC2, CD10, and CDX-2) and gastric (MUC5AC and MUC6) markers, 11 (52%) cases had an intestinal immunophenotype and 10 (48%) cases had a mixed immunophenotype. Foci of discohesive neoplastic cells, indicating dedifferentiation toward a poorly cohesive carcinoma, were observed exclusively in neoplasms of mixed immunophenotype (n=5). All patients with follow-up but one were alive without disease at a mean of 19 months (range 1-60 months). One individual with a pT4 tumor with associated poorly cohesive carcinoma died of disease. In summary, very well-differentiated gastric adenocarcinomas are diagnostically challenging. Architectural features are critical to making the diagnosis. Cases with pure intestinal immunophenotype have not been associated with transformation into poorly cohesive carcinoma, and appear to behave as biologically low grade. Those with mixed immunophenotype appear more likely to dedifferentiate and behave more aggressively.
高度分化的肠型胃腺癌是一种罕见的胃癌变体，其特征为低级别核异型性，其诊断标准和临床行为尚未完全确定。本研究对 21 例病例进行了详细的组织学、免疫组织化学和临床分析。所有病例的核异型性均较轻。这种胃腺癌变体的特征性结构特征是 pit 和腺体吻合、刺状腺体、膨胀腺体、离散细胞、发育不良腺体和腺体外生。所有病例均至少存在其中三种特征。对 18 例患者的术前活检进行回顾性复查显示，一半的活检最初报告为恶性阴性或不确定。基于肠（MUC2、CD10 和 CDX-2）和胃（MUC5AC 和 MUC6）标志物的免疫组化染色，11 例（52%）具有肠免疫表型，10 例（48%）具有混合免疫表型。仅在混合免疫表型的肿瘤中观察到离散的肿瘤细胞灶，表明向低黏附性癌的去分化（n=5）。所有有随访的患者均存活且无疾病，平均随访时间为 19 个月（范围 1-60 个月）。1 例伴有低黏附性癌的 pT4 肿瘤患者死亡。总之，高度分化的胃腺癌诊断具有挑战性。结构特征对于做出诊断至关重要。具有纯肠免疫表型的病例尚未与低黏附性癌转化相关，并且似乎表现为生物学低度恶性。具有混合免疫表型的病例似乎更有可能去分化并表现出更具侵袭性。
