Clinico-pathological and immunohistochemical profile of plasma cell rich variants of chronic cholecystitis

Xanthogranulomatous cholecystitis (XGC) is an uncommon histologic variant of chronic cholecystitis characterized by marked fibrosis with infiltration of macrophages and foamy histiocytes. Lymphoplasmacytic cholecystitis (LPC), another variant, has historically been considered specific to primary sclerosing cholangitis (PSC) and is associated with autoimmune pancreatitis. IgG4-related cholecystitis (IgG4-RC) represents gallbladder involvement in IgG4-related disease (IgG4-RD), in which autoimmune pancreatitis is the most common manifestation. Approximately 25-32% of patients with autoimmune pancreatitis demonstrate concomitant IgG4-related cholecystitis. This study aimed to evaluate the clinicopathological and immunohistochemical relationships among XGC, LPC, and IgG4-RC.

Eight hundred cases of conventional chronic cholecystitis were retrospectively reviewed. Cases of XGC, LPC, and IgG4-RC were identified using established histologic criteria, including dense lymphoplasmacytic inflammation, storiform fibrosis, obliterative phlebitis, and quantification of IgG- and IgG4-positive plasma cells.

Twenty-six cases of LPC and fifty-nine cases of XGC were identified. All LPC cases demonstrated fewer than 50 IgG- and IgG4-positive plasma cells per high-power field (HPF), with an IgG4/IgG ratio below 40%. In contrast, 11.3% (5/44) of evaluable XGC cases showed more than 50 IgG4-positive plasma cells per HPF and an IgG4/IgG ratio exceeding 40%. Among these five cases, three additionally exhibited all three characteristic histopathologic features of IgG4-RD: dense lymphoplasmacytic inflammation, storiform fibrosis, and obliterative phlebitis.

LPC appears to represent a distinct variant of chronic cholecystitis and does not share histologic or immunologic features with IgG4-related cholecystitis, aside from increased plasma cells. XGC, however, may share certain clinicoradiologic and histologic features with IgG4-RC. These overlapping features alone are insufficient to establish a diagnosis of IgG4-RD and may reflect coincidental findings, particularly in patients with multiorgan IgG4-related disease involvement.