In Situ and Invasive Adenocarcinomas of the Gallbladder Extending into or Arising from Rokitansky-Aschoff Sinuses: A Clinicopathologic Study of 49 Cases

We report 49 cases of gallbladder carcinomas that extended into or originated from Rokitansky-Aschoff sinuses (RAS), all of which were resected by laparoscopic cholecystectomy. Twenty-one tumors were in situ carcinomas that extended along RAS; six in situ carcinomas arose in adenomyomatous hyperplasia and 22 were invasive adenocarcinomas with extension into RAS. Thirty-seven patients were women and 12 men. Forty patients had cholelithiasis. The age of the patients ranged from 55 to 84 years (mean 67 years). All in situ carcinomas were incidental microscopic findings in gallbladders removed for cholelithiasis and/or cholecystitis. No patient with in situ carcinoma died as a result of the tumor, including two with in situ carcinoma that originated in adenomyomatous hyperplasia and showed microinvasion. In contrast, of 15 patients with invasive well to moderately differentiated adenocarcinoma extending into RAS and invading the muscle layer or subserosal connective tissue, 8 died 2 to 4 years after surgery. Seven patients survived 1 to 8 years after cholecystectomy. Useful clues to separate RAS with in situ carcinoma from tubular neoplastic invasive glands were the following: connection of the epithelial invaginations to the surface epithelium, recognition of normal biliary epithelium admixed with neoplastic epithelium, presence of inspissated bile in long dilated spaces, and lack of invasion to the smooth muscle bundles. In situ carcinoma spreading along RAS consisted of long tubular often dilated structures extending through the intermuscular connective tissue, whereas neoplastic glands were usually small or of medium size that invaded smooth muscle bundles or intermuscular connective tissue. Perineural invasion was seen only in invasive glands located in the subserosal connective tissue. Two cases of in situ carcinoma that arose in adenomyomatous hyperplasia and three invasive adenocarcinomas that were composed predominantly of tall columnar mucin containing cells similar to gastric foveolar cells with varying degrees of atypia and cells with biliary phenotype bear some resemblance to intraductal papillary mucinous carcinoma of the pancreas or to mucinous cystic pancreatic neoplasm. Metaplastic pyloric glands often seen in the muscle layer and subserosal connective tissue maintain their lobular pattern and should not be confused with invasive glands. Our findings indicate that distinction of in situ carcinoma spreading into RAS from tubular neoplastic glands of invasive adenocarcinomas is crucial to determine prognosis in this group of patients with gallbladder carcinoma.