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

Abstract

Aims 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. Methods and results 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. Conclusions 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.

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

“…While increased numbers of effector T cells, B cells and NK cells have been related to better survival [119], higher numbers of Tregs, inhibitory DC subsets and M2-polarized TAMs known to support an immune-suppressive TME are associated with shorter disease-free survival [128,149,301]. Of note, BLs with a proinflammatory TME characterized by higher levels of M1-polarized TAMs and associated granulomatous reaction have a favorable prognosis and an occasionally spontaneous regression [302]. However, not only the frequencies of the different immune cell subsets but also their functional status are of clinical relevance.…”

B Lymphoproliferative Neoplasms of Uncertain Biological Significance: Report from the IV Workshop of the Italian Group of Hematopathology and Review of the Literature

“…Moving outside the germinal center, more specifically in the context of MBC hyperplasia, we notice a possible role of MBC in controlling the neoplastic disease [15,19,20]. In fact, in case #6, all the subsequent biopsies displayed RS cells closely associated with clusters of MBCs, and two previous studies have documented this aspect in overt cHL [19,20].…”

“…Another niche where early lesions have been described beside the germinal center is monocytoid B-cell hyperplasia [14,15]. Monocytoid B cells (MBCs) were described for the first time by Karl Lennert as immature sinus histiocytosis, representing cells closely related to marginal zone hyperplasia [16].…”

“…Reactive MBCs are frequently associated with follicular hyperplasia and epithelioid macrophages [18] and have been recognized occurring in association with lymphoproliferative diseases, like classic Hodgkin lymphomas (cHL) [19,20]. More recently, clusters of Burkitt cells have been reported with MBC hyperplasia in both immunocompromised and immunocompetent patients [14,15]. In immunocompromised patients, it has been proven that these early lesions carry the risk of progression into an overt Burkitt lymphoma with a worse outcome [14,15].…”

“…More recently, clusters of Burkitt cells have been reported with MBC hyperplasia in both immunocompromised and immunocompetent patients [14,15]. In immunocompromised patients, it has been proven that these early lesions carry the risk of progression into an overt Burkitt lymphoma with a worse outcome [14,15].…”