Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231-2410, USA.
Am J Surg Pathol. 2012 Jul;36(7):1030-5. doi: 10.1097/PAS.0b013e31825033e7.
Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been reported as a new, rare variant of gastric adenocarcinoma. Only 12 cases in Japanese patients have been described to date, but they demonstrate distinct clinicopathologic features. To further characterize these lesions, we have collected 10 additional cases. Patients ranged in age from 44 to 79 years (mean, 64.2 y) with a relatively equal sex distribution (6 women and 4 men). Stratified by race, 4 patients were Hispanic, 2 were White, 2 were African American, 1 was Asian (Chinese), and the race was unknown for 1 patient. All patients presented with gastroesophageal reflux that prompted an endoscopic examination. The majority of GA-CCDs were identified in the fundus (7 of 10, 70%) and the remaining in the cardia (n=3). Grossly, they were solitary and polypoid, ranging in size from 0.2 to 0.8 cm (mean, 0.4 cm). Histologically, all cases were centered in the deep mucosa, with focal involvement of surface foveolar epithelium in 3 (30%) cases but not the submucosa. The tumors consisted of clustered glands and irregular branching cords of oxyntic epithelium. Thin wisps of radiating smooth muscle separated the epithelium, but desmoplasia was distinctly absent in all cases. The oxyntic mucosa was 1 to 2 cells thick and composed of a mixture of mucous neck, parietal, and chief cells. In 7 of 10 (70%) cases, chief cells were the predominant cell type, whereas the remaining 3 cases consisted primarily of mucous neck cells. The nuclei were mildly enlarged with slight nuclear pleomorphism, but no mitotic figures were identified. In addition, necrosis, lymphovascular invasion, and perineural invasion were absent. Immunohistochemically, GA-CCDs were diffusely positive for MUC6 (10 of 10, 100%) and negative for MUC5AC (0%) and MUC2 (0%). Ki-67 immunolabeling demonstrated variable expression, with the highest areas ranging from 0.2% to 10%. Clinical follow-up was available for 9 of 10 (90%) patients and ranged from 6 to 39 months. One patient had persistence of lesion at 6 months because of incomplete removal, whereas the other 8 were disease free. In summary, GA-CCDs are solitary, mucosal lesions of the gastric cardia/fundus that arise in patients from multiple ethnic backgrounds. Considering that patients within this study and those reported previously have had neither true recurrence nor progression of disease, these lesions are best regarded as benign. Consequently, the term GA-CCD is contradictory and we prefer the descriptive term "oxyntic gland polyp/adenoma" until further studies can clarify the pathogenesis of these lesions and their natural history.
胃腺主细胞分化型腺癌（GA-CCD）已被报道为一种新的、罕见的胃腺癌变体。迄今为止，仅在日本患者中描述了 12 例，但它们表现出明显的临床病理特征。为了进一步描述这些病变，我们收集了另外 10 例。患者年龄在 44 岁至 79 岁之间（平均年龄 64.2 岁），性别分布相对均衡（女性 6 例，男性 4 例）。按种族分层，4 例为西班牙裔，2 例为白人，2 例为非裔美国人，1 例为亚洲人（中国人），1 例种族不详。所有患者均因胃食管反流病就诊行内镜检查。大多数 GA-CCDs 位于胃底（10 例中的 7 例，70%），其余位于贲门（n=3）。大体上，它们是单发的息肉样，大小 0.2 至 0.8cm（平均 0.4cm）。组织学上，所有病例均位于深部黏膜，3 例（30%）病例表面有小凹上皮局灶受累，但不累及黏膜下层。肿瘤由簇状腺体和不规则分支的泌酸腺管组成。薄的放射状平滑肌丝将上皮细胞分开，但所有病例均明显无纤维组织增生。泌酸黏膜厚 1 至 2 个细胞，由黏液颈、壁细胞和主细胞混合组成。在 10 例中的 7 例（70%）中，主细胞是主要的细胞类型，而其余 3 例主要由黏液颈细胞组成。细胞核轻度增大，核异型性轻微，但未见有丝分裂象。此外，未见坏死、脉管浸润和神经周围浸润。免疫组织化学染色显示，GA-CCDs 弥漫性表达 MUC6（10 例中的 10 例，100%），不表达 MUC5AC（0%）和 MUC2（0%）。Ki-67 免疫标记显示不同程度的表达，最高区域范围为 0.2%至 10%。本研究中 9 例（90%）患者有临床随访，随访时间 6 至 39 个月。1 例因不完全切除，6 个月时仍有病变残留，而其余 8 例无疾病。总之，GA-CCDs 是胃底/胃贲门的单发黏膜病变，发生于多种族背景的患者。鉴于本研究中的患者和以前报道的患者既没有真正的复发，也没有疾病进展，这些病变最好被视为良性。因此，术语“GA-CCD”是矛盾的，我们更倾向于使用描述性术语“泌酸腺息肉/腺瘤”，直到进一步的研究能够阐明这些病变的发病机制及其自然病史。
