CD20-negative diffuse large B-cell lymphomas: biology and emerging therapeutic options

Abstract

CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare and heterogeneous group of lymphoproliferative disorders. Known variants of CD20-negative DLBCL include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease and anaplastic lymphoma kinase-positive DLBCL. Given the lack of CD20 expression, atypical cellular morphology and aggressive clinical behavior characterized by chemotherapy resistance and inferior survival rates, CD20-negative DLBCL represents a challenge from the diagnostic and therapeutic perspectives. The goals of the present review are to summarize the current knowledge on the biology of the distinct variants of CD20-negative DLBCL, provide future therapeutic directions based on the limited preclinical and clinical data available, and increase awareness concerning these rare malignancies among pathologists and clinicians.

Keywords:

• ALK-positive DLBCL
• CD20-negative
• multicentric Castleman disease
• plasmablastic lymphoma
• primary effusion lymphoma

Acknowledgements

JJ Castillo designed the review. JJ Castillo, JC Chavez, FJ Hernandez-Ilizaliturri and S Montes-Moreno gathered and analyzed the data and wrote the manuscript. S Montes-Moreno provided the pictures.

Financial & competing interests disclosure

JJ Castillo is a consultant for Otsuka Pharmaceuticals. JC Chavez, FJ Hernandez-Ilizaliturri and S Montes-Moreno have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• CD20-negative diffuse large B-cell lymphoma (DLBCL) is rare and aggressive and represents a diagnostic and therapeutic challenge.

• Known variants of CD20-negative DLBCL include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising from HHV-8-associated multicentric Castleman disease and ALK+ DLBCL.

• Plasmablastic lymphoma is strongly associated with HIV and EBV infections, presents in the oral cavity and other extralymphatic sites and has a poor prognosis with a median survival of 6–15 months.

• Primary effusion lymphoma is associated with HIV, EBV and HHV-8 infections; presents as a malignant effusion, rarely as a solid extracavitary lesion; and has a poor survival ranging between 4 and 9 months.

• Large B-cell lymphomas arising from multicentric Castleman disease is associated with HIV and HHV-8 infections and has a short survival of 1 month. Its development can be prevented by the use of rituximab.

• ALK+ DLBCL is characterized by the expression of ALK, can present with nodal and extranodal involvement, and has a poor prognosis between 10 and 20 months. It does not seem to be associated with viral infections.

• CD20-negative DLBCL patients should be treated with combination chemotherapy in academic centers. Antiretroviral therapy should be started or optimized in HIV-positive patients. Stem cell transplantation in first remission should be considered in special cases.

• Potential therapies include drugs directed against targets such as the proteasome, CD30, BET, MYC, EBV, HHV-8, PD-L1, NOTCH, IL-6 and ALK.

Notes