Burkitt lymphoma with a granulomatous reaction: an M1/Th1-polarised microenvironment is associated with controlled growth and spontaneous regression.

in Histopathology by Massimo Granai, Stefano Lazzi, Virginia Mancini, Ayse Akarca, Raffaella Santi, Federica Vergoni, Ester Sorrentino, Raffaella Guazzo, Lucia Mundo, Gabriele Cevenini, Claudio Tripodo, Gioia Di Stefano, Benedetta Puccini, Maurilio Ponzoni, Elena Sabattini, Claudio Agostinelli, Nuray Bassüllü, Tülay Tecimer, Ahu Senem Demiroz, Leah Mnango, Stephan Dirnhofer, Leticia Quintanilla-Martinez, Teresa Marafioti, Falko Fend, Lorenzo Leoncini

TLDR

  • The study looked at four cases of Burkitt lymphoma (BL) and found that the tumor cells were surrounded by a florid epithelioid granulomatous reaction. The study also found that specific immune cells were involved in a proinflammatory response that helped regulate the tumor. The findings suggest that these immune cells may be able to help keep the tumor in a self-limited state or induce its regression. The study provides insights into new potential treatments for EBV-positive BL patients in the era of cellular immunotherapy.

Abstract

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.

Overview

  • The study aims to define the tumour microenvironment (TME) in four cases of Burkitt lymphoma (BL) with a favorable prognosis and occasional spontaneous regression. The study investigates the role of specific immune cell subsets in the early phase of BL and provides insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.

Comparative Analysis & Findings

  • The study found that all four cases showed aggregates of tumor cells with the typical morphology, molecular cytogenetics, and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were EBV-positive with type I latency. Investigation of the TME revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarized macrophages encircling the neoplastic cells with a peculiar topographic distribution.

Implications and Future Directions

  • The study's findings suggest that specific immune cell subsets may play a role in maintaining the tumor in a self-limited state or inducing its regression. The study provides insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy. Future research should focus on identifying the specific immune cell subsets involved in the proinflammatory response and their role in regulating BL progression.
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