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

Burkitt lymphoma (BL) is an aggressive B-cell lym-phoma that, in some instances, may show a granuloma-tous reaction associated with a favourable prognosis andoccasional 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 oftumour cells with the typical morphology, molecularcytogenetics and immunophenotype of BL surroundedby a florid epithelioid granulomatous reaction. Allfour cases were Epstein–Barr virus (EBV)-positive withtype I latency. Investigation of the TME showedsimilar features in all four cases. The analysisrevealed a proinflammatory response triggered byTh1 lymphocytes and M1 polarised macrophagesencircling the neoplastic cells with a peculiar topo-graphic distribution.Conclusions: Our data provide an in-vivo picture of therole that specific immune cell subsets might play duringthe early phase of BL, which may be capable of main-taining the tumour in a self-limited state or inducing itsregression. These novel results may provide insightsinto new potential therapeutic avenues in EBV-positiveBL patients in the era of cellular immunotherapy