Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder (Neoplastic Polyps, Adenomas, and Papillary Neoplasms That Are ≥ 1.0 cm) Clinicopathologic and Immunohistochemical Analysis of 123 Cases
Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder (Neoplastic Polyps, Adenomas, and Papillary Neoplasms That Are ≥ 1.0 cm) Clinicopathologic and Immunohistochemical Analysis of 123 Cases
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DOI：
10.1097/pas.0b013e318262787c
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发表时间：
2012-09-01
影响因子：
5.6
通讯作者：
Terry, Paul
中科院分区：
文献类型：
--
作者：
Adsay, Volkan;Jang, Kee-Taek;Terry, Paul
关于胆囊上皮内肿瘤（肿瘤性息肉）临床病理特征的文献相当有限，部分原因是定义和术语的变化。大多数报告的腺瘤（幽门腺型和其他）是显微镜下的，因此被认为是临床上无关紧要的，而乳头状原位癌在很大程度上被认为是一种侵袭性腺癌，标题为“乳头状腺癌”。“在这项研究中，分析了123例具有明确定义的外生性浸润前肿瘤的GB病例，测量>= 1 cm。患者主要为女性（F/M= 2：1），平均年龄为61岁，中位肿瘤大小为2.2 cm。一半的患者表现为疼痛，另一半的肿瘤是偶然发现的。22%的病例中存在其他肿瘤，大多数为胃肠道恶性肿瘤。只有20%的病例发现胆结石。放射学上，几乎一半被诊断为“癌症”，大约一半为息肉样肿瘤，10%的病变被遗漏。病理结果：（1）乳头状占43%，管状乳头状占31%，管状占26%。(2)根据形态学上的主要模式（> 75%的病变），并结合特异性免疫组织化学细胞谱系标记物，对每个病例分配最终谱系类型。50%的胆管癌细胞为主要细胞系MUC 1（+）占66%，胃小凹占16%，（均为MUC 5AC（+）），胃幽门20%（92% MUC 6（+）），肠内8%（100%CK20（+）; 75%CDX2（+）; 50%MUC2（+）），6%为嗜酸性细胞（17%HepPar（+）和17%MUC6（+））;然而，90%的病例具有一定量的继发或不可分类的模式和杂交免疫表型。(3)在符合“幽门腺腺瘤”的病例中，21/24（88%）至少有局灶性高度异型增生，18%有相关的浸润性癌。相反，47例“乳头状腺癌”型病例中有8例显示一些低度异型增生灶，15/47例（32%）没有可识别的浸润。(4)总的来说，55%的病例有相关的浸润性癌（胰胆管型，58;其他，10）。与浸润显著相关的因素是高度异型增生的程度、细胞类型（胆管或小凹）和乳头形成。在系统分析的浸润性癌中，6.4%（39/606）检测到肿瘤上皮内瘤变。(5)3年精确生存率为90%的情况下，没有入侵和60%的那些与入侵。相反，与胰胆型GB癌相比，与浸润相关的患者的临床结局要好得多（3年生存率为27%），即使在分期匹配的比较中，这种生存优势仍然存在。在长期随访中，甚至在少数非侵入性病例（4/55;中位数73.5个月）中也发生了死亡，强调了长期随访的重要性。总之，GB中的肿瘤浸润前肿瘤（>= 1 cm）类似于其胰腺和胆道对应物（胆管内乳头状肿瘤、胰腺管内乳头状粘液性肿瘤和管内管状乳头状肿瘤）。它们表现出不同的细胞谱系，一系列的异型增生，以及乳头状或管状生长模式的混合物，通常有明显的重叠，将其分类为1个统一的平行类别，胆囊内乳头状管状肿瘤，胆囊内乳头状管状肿瘤是相对惰性的肿瘤，与胰胆型GB癌相比，预后明显更好。相反，即使是看似无害的例子，如那些被称为“幽门腺腺瘤”可以进展为癌，并与入侵和致命的结果。
The literature on the clinicopathologic characteristics of tumoral intraepithelial neoplasms (neoplastic polyps) of the gallbladder (GB) is fairly limited, due in part to the variability in definition and terminology. Most reported adenomas (pyloric gland type and others) were microscopic and thus regarded as clinically inconsequential, whereas papillary in situ carcinomas have been largely considered a type of invasive adenocarcinoma under the heading of "papillary adenocarcinomas." In this study, 123 GB cases that have a well-defined exophytic pre-invasive neoplasm measuring >= 1 cm were analyzed. The patients were predominantly female (F/M= 2:1) with a mean age of 61 y and a median tumor size of 2.2 cm. Half of the patients presented with pain, and in the other half the neoplasm was detected incidentally. Other neoplasms, most being gastrointestinal tract malignancies, were present in 22% of cases. Gallstones were identified in only 20% of cases. Radiologically, almost half were diagnosed as "cancer," roughly half with polypoid tumor, and in 10% the lesion was missed. Pathologic findings: (1) The predominant configuration was papillary in 43%, tubulopapillary in 31%, tubular in 26%. (2) Each case was assigned a final lineage type on the basis of the predominant pattern (> 75% of the lesion) on morphology, and supported with specific immunohistochemical cell lineage markers. The predominant cell lineage could be identified as biliary in 50% (66% of which were MUC1(+)), gastric foveolar in 16% (all were MUC5AC(+)), gastric pyloric in 20% (92% MUC6(+)), intestinal in 8% (100% CK20(+); 75% CDX2(+); 50%, MUC2(+)), and oncocytic in 6% (17% HepPar(+) and 17% MUC6(+)); however, 90% of cases had some amount of secondary or unclassifiable pattern and hybrid immunophenotypes. (3) Of the cases that would have qualified as " pyloric gland adenoma," 21/24 (88%) had at least focal high- grade dysplasia and 18% had associated invasive carcinoma. Conversely, 8 of 47 " papillary adenocarcinoma"-type cases displayed some foci of low-grade dysplasia, and 15/47 (32%) had no identifiable invasion. (4) Overall, 55% of the cases had an associated invasive carcinoma (pancreatobiliary type, 58; others, 10). Factors associated significantly with invasion were the extent of high-grade dysplasia, cell type (biliary or foveolar), and papilla formation. Among systematically analyzed invasive carcinomas, tumoral intra-epithelial neoplasia was detected in 6.4% (39/606). (5) The 3-year actuarial survival was 90% for cases without invasion and 60% for those associated with invasion. In contrast, those associated with invasion had a far better clinical outcome compared with pancreatobiliary-type GB carcinomas (3-yr survival, 27%), and this survival advantage persisted even with stage-matched comparison. Death occurred in long-term follow-up even in a few noninvasive cases (4/55; median 73.5 mo) emphasizing the importance of long-term follow-up. In conclusion, tumoral preinvasive neoplasms (>= 1 cm) in the GB are analogous to their pancreatic and biliary counterparts (biliary intraductal papillary neoplasms, pancreatic intraductal papillary mucinous neoplasms, and intraductal tubulopapillary neoplasms). They show variable cellular lineages, a spectrum of dysplasia, and a mixture of papillary or tubular growth patterns, often with significant overlap, warranting their classification under 1 unified parallel category, intracholecystic papillary-tubular neoplasm.Intracholecystic papillary-tubular neoplasms are relatively indolent neoplasia with significantly better prognosis compared with pancreatobiliary-type GB carcinomas. In contrast, even seemingly innocuous examples such as those referred to as "pyloric gland adenomas" can progress to carcinoma and be associated with invasion and fatal outcome.