Epstein-Barr Virus-associated Mixed Lymphoepithelioma-like Carcinoma and Adenocarcinoma of the Gall Bladder: An Unusual Entity

Abstract

Schmincke described lymphoepithelioma as an undifferentiated carcinoma with abundant lymphoid stroma in the nasopharynx. Tumors with a similar histomorphology in extrapharyngeal areas have been referred to as lymphoepithelioma-like carcinoma (LELC). The association of an Ebstein-Barr virus (EBV) infection with lymphoepithelioma is well established in the nasopharynx but not so well at the extrapharyngeal sites. Only four cases of LELC have been reported in the gall bladder, of which all were negative for the EBV. This paper reports the first case of an EBV-associated mixed gall bladder carcinoma exhibiting a distinct phenotype of LELC and adenocarcinoma with mucinous differentiation. The EBV was confirmed by the strong granular membranous and cytoplasmic expression of LMP-1 (latent membrane protein-1) on immunohistochemistry and nuclear EBER RNA on chromogen in-situ hybridization in the tumor. This is the first case of LELC positive for EBV in the gall bladder. LELC has a more favorable prognosis than conventional adenocarcinoma or squamous cell carcinoma, irrespective of the site. Although a higher T stage and nodal metastasis were exceptional in the present case in contrast to the previous cases, the EBV-associated lymphocytic response might limit the disease spread and confer better overall survival and prognosis in these patients. Nevertheless, more prospective studies with a larger cohort will be needed to understand the pathogenesis, biological behavior, and prognosis of this rare entity.

Is cross-species horizontal gene transfer responsible for gallbladder carcinogenesis

“…Epstein-Barr virus is commonly associated with several other types of cancer, such as nasopharyngeal carcinoma (30) , gastric cancer (31) , and lymphomas (32) . Studies have found that EBV infection is associated with development of acalculous cholecystitis and a single case of EBV virus associated mixed lymphoepithelioma-like carcinoma and adenocarcinoma is reported (33). EBV may contribute to the development of GBC by inducing chronic in ammation, promoting cell proliferation, and inhibiting apoptosis.…”

The footprint of gut microbiota in gallbladder cancer: a mechanistic review

“…A literature search identified 26 cases of acute EBV infection and AAC, 25 of which were in pediatric or adult females ( Agergaard and Larsen, 2015 ; Yesilbag et al., 2017 ; Harvey et al., 2021 ). Third, the first case of EBV-associated mixed gallbladder carcinoma was reported, which manifested a unique phenotype of lymphoepithelioma-like carcinoma and mucinous differentiated adenocarcinoma ( Jain et al., 2021 ). Although the close correlation between EBV and GBC has been widely confirmed, more mechanistic research is needed to understand the pathogenesis and biological behavior of EBV-associated GBC.…”