Follicular Lymphoma Transformation to EBV+ Hodgkin-Like Lymphoma, Oh those EBV+ Hodgkin-Like Lymphomas

Lessons From the Friday Unknowns

Histologic sections show an enlarged lymph node almost completely replaced by lymphoma with an entirely follicular pattern.

The follicles are composed of a mixture of centrocytes and centroblasts supporting grade 3A. Occasional large centroblasts are multilobated with Reed-Sternberg-like features.

The cells in the follicular lymphoma are positive for CD10, CD20, CD23, CD45, Pax-5, BCL–2 and BCL–6, and are negative for CD3, CD15, CD21, CD30, CD43, MUM1/IRF4 & ALK. The antibody specific for Ki-67 shows a proliferation rate of approximately 40–50% within these follicles. In situ hybridization analysis for Epstein–Barr virus encoded RNA (EBER) is negative.

In addition, there is a very small focus (5%) composed of necrosis and surrounded by Reed-Sternberg–like and Hodgkin–-like cells in a background of small lymphocytes, histiocytes, and occasional neutrophils.

In the small focus with Reed-Sternberg–like and Hodgkin-like cells, these large cells are positive for CD20 (strong), CD30, Pax-5, MUM1/IRF4 and Ki-67, and are negative for CD15.

In situ hybridization analysis is positive for EBER in the Reed-Sternberg-like and Hodgkin-like cells.

EBER positivity in the small focus with Reed-Sternberg–like and Hodgkin-like cells

Follicular lymphoma transformation into higher grade hematopoietic neoplasms (including transformation into Langerhans cell sarcoma, see suggested articles below), is well-established in literature.

In summary, the small EBER-positive Hodgkin-like area in this specimen likely represents an unusual form of follicular lymphoma transformation to higher grade B-cell lymphoma, likely driven by EBV infection.

Link to digital slides: https://bit.ly/2QsRzkS | Slides labeled case 5

Further read: https://bit.ly/2QxFwTo