Gall bladder and extrahepatic bile duct lymphomas: clinicopathological observations and biological implications

Abstract

Lymphomas of the gall bladder and extrahepatic bile ducts are exceedingly rare. We present the clinicopathological features of 19 cases from our files; 14 patients had primary lymphoma (13 involving gall bladder and 1 involving common hepatic duct), while 5 had systemic lymphoma on further work-up. Most patients presented with symptoms mimicking cholecystitis. The most common primary lymphoma types were diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. Two cases had features of lymphomatous polyposis, one a case of follicular lymphoma and the second a case of mantle cell lymphoma, with disease limited to the mantle zones, so-called in situ mantle cell lymphoma. Other rare lymphoma subtypes not described earlier in this site included the extracavitary variant of primary effusion lymphoma and plasmablastic lymphoma. Patients with diffuse large B-cell lymphoma and extranodal marginal zone lymphoma were older (mean age 75.8 y) than those with other subtypes (mean age 47 y) and more likely to have gallstones (60% vs. 12.5%). A comprehensive literature review revealed 36 primary gall bladder and 16 primary extrahepatic bile duct lymphomas. When compared with primary gall bladder lymphomas, those involving the extrahepatic bile ducts present at a younger age (47 y vs. 63 y) usually with obstructive jaundice, and are less often associated with gallstones (17% vs. 50%) or regional lymph node involvement (6% vs. 31%). In conclusion, primary lymphomas of the gall bladder and extrahepatic bile ducts show a broad spectrum of disease types, but in many respects mirror the spectrum of primary lymphomas of the gastrointestinal tract.

Fig. 1. Extranodal marginal zone lymphoma

A. The gall bladder mucosa is involved by a dense lymphoid infiltrate. B. Many cells exhibit plasmacytoid differentiation whereas others have a rim of pale cytoplasm and a monocytoid appearance.

Fig. 2. Mantle cell lymphoma with features of lymphomatous polyposis

A. A polypoid infiltrate is present within the gall bladder mucosa. B. Cyclin D1 immunostain highlights the neoplastic cells, which are largely confined to the mantle zones surrounding negative reactive germinal centers.

Fig. 3. Extracavitary variant of primary effusion lymphoma

A. The cells are large and pleomorphic with ample cytoplasm and prominent central eosinophilic nucleoli. B. In-situ hybridization for EBV (EBER probe) and C. HHV-8 immunostain shows positivity in nuclei of neoplastic cells.

Fig. 4. Plasmablastic lymphoma

A. There is a monomorphic infiltrate of cells with enlarged nuclei, prominent nucleoli and moderate amount of eosinophilic cytoplasm. B. Neoplastic cells are strongly and diffusely positive for MUM-1/IRF-4.