EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 2)

Abstract

Epstein-Barr virus (EBV) is a common pathogen infecting people primarily early in life. The virus has the ability to persist throughout a person's life, usually in B lymphocytes. Conditions of immunodeficiency as well as the introduction of immunosuppressive therapies and the advent of transplant technologies has brought immunodeficiency-associated lymphoproliferative disorders into view, which are often driven by EBV. The group of EBV-associated lymphoproliferative disorders includes different entities, with distinct biological features, ranging from indolent disorders, which may even spontaneously regress, to aggressive lymphomas requiring prompt and adequate treatment. These disorders are often diagnostically challenging due to their overlapping morphology and immunophenotype. Both nodal and extra-nodal sites, including the gastrointestinal tract, may be involved. This review, divided in three parts, summarizes the clinical, pathological, molecular features and treatment strategies of EBV-related lymphoproliferative disorders occurring in the gastrointestinal tract and critically analyzes the major issues in the differential diagnosis. In this part of the review, we discuss plasmablastic lymphoma, extra-cavitary primary effusion lymphoma and Burkitt lymphoma.

Keywords: Burkitt lymphoma; Epstein–Barr virus; plasmablastic lymphoma; primary effusion lymphoma.

Figure 1

(A) PBL of the colon: high power view showing a diffuse proliferation of large-sized cells with evident nucleoli (Giemsa staining, magnification 400×; original image from Prof Ascani); (B) PBL of the colon: diffuse EMA expression of the neoplastic cells (immunostaining, Ventana immunostainer, magnification 400×; original image from Prof Ascani).

Figure 2

(A) PBL of the colon: MUM18 expression of the neoplastic proliferation (immunostaining, Ventana immunostainer, magnification 100×; original image from Prof Ascani); (B) PBL of the colon: diffuse EBV positivity of the neoplastic cells (EBER-ISH, magnification 200×; original image from Prof Ascani).

Figure 3

PBL of the colon: the lack of B-cell marker expression is a feature common among neoplasms with plasma cell differentiation such as PBL and PEL (CD20 immunostaining, Ventana immunostainer, magnification 400×; original image from Prof Ascani).

Figure 4

EC-PEL of the ileum: low power view of the neoplastic proliferation involving the bowel wall (Giemsa staining, magnification 100×; original image from Prof Ascani).

Figure 5

EC-PEL of the ileum: high power highlighting the morphological details of large neoplastic cells with prominent nucleoli (Giemsa staining, magnification 400×; original image from Prof Ascani).

Figure 6

EC-PEL of the ileum: in this case, the neoplastic proliferation lacks B-cell marker expression; this is often a common feature of neoplasms with plasma cell differentiation such as PBL and PEL (CD20 immunostaining, Ventana immunostainer, magnification 200×; original image from Prof Ascani).

Figure 7

EC-PEL of the ileum: Diffuse and intense expression of MUM18; similar to PBL, EC-PEL expresses markers of plasma cell differentiation (immunostaining, Ventana immunostainer, magnification 400×; original image from Prof Ascani).

Figure 8

(A) EC-PEL of the ileum: strong and diffuse HHV8 positivity of the neoplastic cells; HHV8 expression is a diagnostic feature for EC-PEL (immunostaining, Ventana immunostainer, magnification 200×; original image from Prof Ascani); (B) EC-PEL of the ileum: diffuse EBV positivity of the neoplastic proliferation (EBER-ISH, magnification 40×; original image from Prof Ascani).

Figure 9

EC-PEL of the ileum: MYC protein expression is frequently found in EC-PEL despite the lack of MYC gene alterations (immunostaining, Ventana immunostainer, magnification 400×; original image from Prof Ascani).

Figure 10

(A) BL of the duodenum: lymphoid infiltrate within the duodenal mucosa (Hematoxylin and eosin, magnification 200×; original image from Prof Ascani); (B) BL: diffuse CD20 positivity confirming the B-cell phenotype of the lymphoid cells (immunostaining, Ventana immunostainer, magnification 100×; original image from Prof Ascani).

Figure 11

(A) BL of the duodenum: diffuse EBV expression by in situ hybridization (EBER-ISH, magnification 200×; original image from Prof Ascani); (B) BL of the duodenum: diffuse MYC protein overexpression of the lymphoid cells (immunostaining, Ventana immunostainer, magnification 200× original image from Prof Ascani).