Korean J Gastroenterol.  2021 Sep;78(3):188-194. 10.4166/kjg.2021.045.

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

Affiliations
  • 1Departments of Pathology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
  • 2Departments of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India

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.

Keyword

Gallbladder neoplasm; Lymphoepithelioma-like carcinoma; Epstein-Barr virus; Adenocarcinoma

Figure

  • Fig. 1 (A) Axial arterial and (B) venous phase and (C) coronal venous phase contrast-enhanced CT images show heterogeneously and intensely enhancing mass involving the body of gall bladder (asterisk) with contiguous infiltration into segment 5 of the liver (arrows). Gross photograph shows (D) a gray white growth in the posterior wall of the gall bladder infiltrating the adjacent liver parenchyma. (E) On cut, gall bladder lumen showing a polypoidal growth measuring 4.5×4×3 cm with mucinous areas.

  • Fig. 2 (A) Section shows two phenotypically distinct components with LELC on the right side and an adenocarcinoma on the left (H&E, ×40). (B) LELC on the left side with adenocarcinoma showing glands and mucinous areas in the right half (H&E, ×40). (C) Higher magnification shows tumor arranged in anastomosing papillae and back-to-back arranged glandular pattern (H&E, ×200). (D) Areas of adenocarcinoma comprised of conspicuous extracellular mucin pools with floating tumor cells within them (H&E, ×40).

  • Fig. 3 Microphotographs show (A) an expansile, well-circumscribed tumor arranged in diffuse sheets and infiltrating the liver with broad pushing borders and dense peritumoral lymphoid infiltrate (H&E, ×40). (B) Higher magnification showing the two distinct components comprised a dilated mucin-filled tumor gland on the left with lymphoepithelioma-like carcinoma (LELC) on the right side (H&E, ×100). (C) LELC component comprised of cells arranged in syncytial sheets having prominent intratumoral and peritumoral lymphocytic infiltrate with the formation of many lymphoid follicles. Few dysplastic glands lined by columnar to cuboidal cells with marked nuclear stratification, hyperchromasia, and conspicuous nucleoli are seen at the junction of two components (H&E, ×200). (D) Higher magnification of LELC areas shows tumor cells present in the syncytial sheets. These have moderate eosinophilic cytoplasm indistinct cell boundaries, large vesicular round to oval-shaped nuclei with single large prominent nucleoli (H&E, ×400).

  • Fig. 4 (A) Tumor cells in the LELC areas show retained nuclear expression of MLH1. MSH2, MSH6, and PMS2 also showed similar findings in both the components (MLH1; IHC, ×100). (B) LELC cells showing strong membranous staining with cytokeratin 7 (CK7; IHC, ×100). (C, D) Photomicrographs show a sprinkling of CD20 and CD3 positive lymphocytes in the peritumoral infiltrate (CD20; IHC, ×20, CD3; IHC, ×20).

  • Fig. 5 (A) Strong granular membranous and cytoplasmic expression of latent membrane protein-1 (LMP-1) in the lymphoepithelioma-like carcinoma (LELC) component. Note the negative expression in the surrounding infiltrating lymphocytes and benign bile duct (LMP1; IHC, ×200). (B) Components of adenocarcinoma and LELC both showing strong cytoplasmic and membranous expression of latent membrane protein-1 (LMP1; IHC, ×40). (C) Positive nuclear expression of EBV encoded RNA on chromogenic in situ hybridization (EBER CISH, ×200).


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