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Editorials
Plasmablastic lymphoma: one or more tumors?
Stefano A. Pileri,1 Saveria Mazzara1 and Enrico Derenzini2
1Division of Hematopathology, European Institute of Oncology IRCCS and 2Division of Hemato-oncology, European Institute of Oncology IRCCS, Milan, Italy
E-mail: STEFANO A. PILERI - stefano.pileri@ieo.it
doi:10.3324/haematol.2021.278841
In this issue of Haematologica, Ramis-Zaldivar et al. report on a series of cases of plasmablastic lymphoma (PBL), studied by a high-resolution approach to unravel the genomic landscape of the tumor, which has remained so far largely unexplored.1 According to the revised fourth edition of the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues, PBL is a rare and very aggressive disease entity with diffuse proliferation of large neoplas- tic cells, most of which resemble B immunoblasts or plasmablasts that have a CD20-negative plasmacytic phenotype and frequently carry MYC rearrangements.2 PBL was originally described in the oral cavity and fre- quently occurs in association with human immunodefi- ciency virus (HIV) infection, but it may also develop at other sites, predominantly extranodal, and in association with other causes of immunodeficiency.2 In the majority of cases, neoplastic cells are infected by Epstein-Barr virus (EBV).2 The differential diagnosis may include other varieties of diffuse large B-cell lymphoma, Burkitt lymphoma, plasmablastic plasma cell myeloma, and anaplastic large cell lymphoma. There is no standard of care at the time being and immunotherapy with anti- CD20 antibodies is unfeasible because of the lack of the target. DA-EPOCH chemotherapy has been recom-
mended, possibly in conjunction with combined anti- retroviral therapy in HIV-positive patients.3 However, studies of patients with PBL treated with chemotherapy regimens more intensive than CHOP did not identify a survival benefit and anyway the median overall survival with DA-EPOCH treatment is disappointing, being reported as 15months in HIV-positive patients, and likely worse in HIV-negative patients.4 The usage of other therapies, such as chimeric antigen receptor T-cell therapy, remains anecdotal,5 the optimal treatment of PBL being still an open issue.
Ramis-Zaldivar et al. applied a highly refined approach to 34 cases of PBL; their investigations included muta- tional and copy number analyses, targeted gene expres- sion profiling, fluorescence in situ hybridization, and immunohistochemistry.1 Such an array of techniques is the ideal way to explore the pathobiology of each neo- plasm, if one aims to understand the possible range of mechanisms which sustain it, and discover novel poten- tial therapeutic targets.
Their study highlights the molecular heterogeneity of PBL, which is in keeping with the scenario arising in the field of malignant lymphomas in general. For a long time, lymphomas have been considered monoclonal/ monolithic conditions. It is now becoming increasingly
Figure 1. Array of potential targeted therapies based on specific molecular abnormalities detected in plasmablastic lymphomas.
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haematologica | 2021; 106(10)