Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder (Neoplastic Polyps, Adenomas, and Papillary Neoplasms That Are ≥1.0 cm)

Abstract

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 preinvasive 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 intraepithelial 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 intr...

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases

“…We also excluded intraductal tubulopapillary neoplasm-like tumors of the gallbladder that are increasingly being recognized as a distinct subset of tumoral intraepithelial neoplasms of the gallbladder. 20,21 Defined by these criteria, our study of 20 biliary intraductal tubulopapillary neoplasms does indeed outline that intraductal tubulopapillary neoplasms represent a discrete entity from both intraductal papillary neoplasms of the bile duct and ordinary cholangiocarcinoma with distinct morphology, immunohistochemical expression profile, molecular carcinogenesis, and tumor biology.…”

“…2,20 The amount of invasive carcinoma relative to non-invasive component was estimated according to the available material (less than 10%: microinvasion; 10-50% as substantial, and extensive, if 450%).…”

“…MUC6 was expressed at lower frequencies (30% of noninvasive tumors and 54% of invasive carcinomas), and the non-invasive components labeled diffusely in 6/20 (30%) cases, as it may be seen in complexpyloric type of intracholecystic papillary tubular neoplasms. 20 None of the cases expressed MUC2, the intestinal (goblet) type mucin, and MUC5AC (exclusion criteria). Focal nuclear expression of CDX2 was observed in two intraductal tumors (11%).…”

“…19 In detail, the neoplasms showed a pancreatobiliary epithelial phenotype (expression of MUC1 and MUC6, the absence of MUC2 and MUC5AC) had intact SMAD4 and TP53 function and were associated with a favorable prognosis. Tumors similar to pancreatic intraductal tubulopapillary neoplasms also occur in the gallbladder and have recently been analyzed as a subset under the heading of intracholecystic papillary tubular neoplasm; 20 however, those with more tubular nonmucinous configuration may be a distinct entity. 21 As data on the histological spectrum of biliary intraductal tubulopapillary neoplasms, their clinical behavior and the molecular carcinogenesis are still limited due to the small number of reported cases, we conducted a study in a large international intraductal tubulopapillary neoplasm cohort including patients from Europe, United States, Japan, and Korea.…”

Hemobilia due to intracholecystic papillary neoplasm

“…The pancreatobiliary subtype typically shows CK7 and MUC1 expression, while the gastric subtype usually expresses MUC5AC y MUC6, the intestinal expresses MUC2, CDX2 and CK20, and the oncocytic MUC1. Immunohistochemical staining MUC1 has been described as a marker of poor prognosis in ICPN (3).…”