Clinicopathologic analysis of hyalinizing cholecystitis and associated carcinomas

 The authors described a clinicopathologically distinct subtype of cholecystitis, the extensively calcific version of which has been presented in the clinical literature as “porcelain” gallbladder. This cholecystitis, referred to herein as hyalinizing cholecystitis (HC), is characterized by dense, paucicellular hyaline fibrosis transforming the gallbladder wall into a relatively thin and uniform band. The process diffusely effaces most of the normal structures of the gallbladder, and some cases show calcifications. To determine the clinicopathologic associations of HC, the authors systematically analyzed 4,231 cholecystectomies (606 of which had carcinoma) histopathologically and conducted a targeted search in their databases. The authors identified 96 cases of HC (1.6 percent of cholecystectomies). Patients with HC were a decade older than “ordinary” cholecystitis patients (56 versus 47; P<.001), suggesting that HC may be a long-term complication of chronic injury in some patients. Calcifications of variable amounts and degrees were identified in two-thirds of the cases. Furthermore, 10 cases showed diffuse marked calcifications and were considered separately as complete porcelain gallbladder. Thirty-eight HC cases had carcinoma with a calculated frequency of 15 percent and an odds ratio of cancer risk of 4.6. Only 42 percent of the invasive cases were associated with calcifications; none of the 10 diffusely calcific cases had carcinoma. HC-related carcinomas were challenging diagnostically. They did not form distinct masses or significant thickening (mean thickness, 2.6 mm versus 4.0 mm in ordinary adenocarcinomas; P<.002). Microscopically, they had widely scattered and bland-appearing glands embedded in the thin band of hyaline stroma of HC, commonly showing a disappearing lining, leaving behind the granular, necrotic intraluminal debris (regression) with or without calcifications, which could be the only sign of cancer in some sections. The morphologic features that allowed these glands to be recognized as malignant included their longitudinal axis parallel to the surface, irregular contours, clear cytoplasm with distinct borders, nuclear irregularities, and washed-off chromatin. Surface epithelium, if preserved (and it was not in most cases), typically showed carcinoma in situ of denuding or micropapillary types. HC-associated carcinomas, with a median survival of seven months, appeared to have a clinical course at least as aggressive as that of regular carcinomas (median survival, 12 months; P=.02). The authors concluded that HC is a distinct clinicopathologic entity that is often associated with carcinoma, and the carcinomas arising from this group are often very subtle and prone to misdiagnosis microscopically. As HC is typically devoid of epithelium, any glandular elements on the wall of HC should be regarded as suspect for carcinoma. This study also confirms recent findings in the radiology literature that it is not the complete (diffusely calcific) porce- lain gallbladder that is associated with cancer. Instead, a distinct, histopathologically defined form of cholecystitis—HC with minimal or no calcifications (incomplete porcelain gallbladder)—is associated with invasive carcinoma. Therefore, imaging protocols should focus on the correlates of HC rather than fixating on calcifications. Additional studies into the pathogenesis of this process and its mechanisms of progression to carcinoma are warranted