Lewis Jason T, Talwalkar Jayant A, Rosen Charles B, Smyrk Thomas C, Abraham Susan C
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Am J Surg Pathol. 2007 Jun;31(6):907-13. doi: 10.1097/01.pas.0000213435.99492.8a.
Primary sclerosing cholangitis (PSC) carries an increased risk (10% to 20%) of hepatobiliary malignancy, especially cholangiocarcinoma (CC). Dysplasia, adenomas, and carcinomas of the gallbladder have been described in PSC but are less common than bile duct carcinomas. However, the prevalence and risk factors for gallbladder neoplasia among patients with PSC undergoing orthotopic liver transplantation (OLT) have not been well studied. We evaluated 72 gallbladders from 100 consecutive liver explants for PSC, including 66 cholecystectomies performed at the time of OLT and 6 performed before OLT. All specimens were totally embedded for histologic examination. We evaluated the following histologic features: presence of diffuse lymphoplasmacytic chronic cholecystitis, pyloric metaplasia, intestinal metaplasia, dysplasia (low-grade or high-grade), and adenocarcinoma. Gallbladder dysplasia and adenocarcinoma were correlated with several clinicopathologic parameters using Fisher exact test and t test, including: (1) sex, (2) age, (3) PSC duration, (4) inflammatory bowel disease (IBD) at time of OLT, and (5) concomitant bile duct dysplasia or carcinoma. Lymphoplasmacytic chronic cholecystitis was present in 35 (49%), pyloric metaplasia in 69 (96%), intestinal metaplasia in 36 (50%), dysplasia in 27 (37%; low-grade in 12 and high-grade in 15), and adenocarcinoma in 10 (14%; 2 with lamina propria invasion and 8 with invasion into muscularis or adventitia). Gallbladder carcinoma was associated with intrahepatic bile duct dysplasia (P=0.001), CC (P=0.023), and IBD (P=0.03). Gallbladder dysplasia was associated with hilar/intrahepatic bile duct dysplasia (P=0.0006), CC (P=0.028), IBD (P=0.0014), and older age at OLT (P=0.007). Neither gallbladder carcinoma nor dysplasia had a significant association with sex or PSC duration. These results indicate that complete histologic evaluation of gallbladders in patients undergoing transplantation for PSC yields high frequencies of inflammatory, metaplastic, and neoplastic changes. The strong correlation between gallbladder dysplasia/adenocarcinoma and bile duct dysplasia/CC supports the concept of a neoplastic "field effect" along the intrahepatic and extrahepatic biliary tract in PSC.
原发性硬化性胆管炎（PSC）发生肝胆恶性肿瘤的风险增加（10%至20%），尤其是胆管癌（CC）。PSC患者中已发现胆囊发育异常、腺瘤和癌，但不如胆管癌常见。然而，接受原位肝移植（OLT）的PSC患者中胆囊肿瘤的患病率及危险因素尚未得到充分研究。我们评估了连续100例因PSC进行肝移植切除的肝脏中72个胆囊，包括OLT时进行的66例胆囊切除术和OLT前进行的6例。所有标本均全部包埋以进行组织学检查。我们评估了以下组织学特征：弥漫性淋巴细胞浆细胞性慢性胆囊炎、幽门化生、肠化生、发育异常（低级别或高级别）和腺癌。使用Fisher精确检验和t检验将胆囊发育异常和腺癌与几个临床病理参数相关联，这些参数包括：（1）性别，（2）年龄，（3）PSC病程，（4）OLT时的炎症性肠病（IBD），以及（5）伴发的胆管发育异常或癌。35个（49%）存在淋巴细胞浆细胞性慢性胆囊炎，69个（96%）存在幽门化生，36个（50%）存在肠化生，27个（37%；低级别12个，高级别15个）存在发育异常，10个（14%；2个侵犯固有层，8个侵犯肌层或外膜）存在腺癌。胆囊癌与肝内胆管发育异常（P=0.001）、胆管癌（P=0.023）和IBD（P=0.03）相关。胆囊发育异常与肝门/肝内胆管发育异常（P=0.0006）、胆管癌（P=0.028）、IBD（P=0.0014）以及OLT时年龄较大（P=0.007）相关。胆囊癌和发育异常与性别或PSC病程均无显著关联。这些结果表明，对因PSC接受移植患者的胆囊进行完整的组织学评估可发现炎症、化生和肿瘤性改变的高发生率。胆囊发育异常/腺癌与胆管发育异常/胆管癌之间的强相关性支持了PSC患者肝内和肝外胆道存在肿瘤性“场效应”的概念。
