Double-hit and double-expressor primary central nervous system lymphoma: Experience from North India of an infrequent but aggressive variant

Abstract

Background: High-grade non-Hodgkin B-cell lymphoma is an aggressive mature B-cell lymphoma that depicts poor treatment response and worse prognosis. The presence of MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements qualifies for triple-hit and double-hit lymphomas (THL/DHL), respectively. We attempted to explore the incidence, distribution, and clinical characteristics of the primary high-grade B-cell lymphoma of the central nervous system (CNS) in our cohort from North India. Methods: All the histologically confirmed cases of primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) over a period of 8 years were included. Cases showing MYC and BCL2 and/or BCL6 expression on immunohistochemistry (IHC) (double- or triple-expressor) were further analyzed by fluorescence in situ hybridization for MYC, BCL2 and /or BCL6 rearrangements. The results were correlated with other clinical and pathological parameters, and outcome. Results: Of total 117 cases of PCNS-DLBCL, there were seven (5.9%) cases of double/triple-expressor lymphomas (DEL/TEL) (six double- and one triple-expressor) with median age of 51 years (age range: 31–77 years) and slight female predilection. All were located supratentorially and were of non-geminal center B-cell phenotype. Only triple-expressor case (MYC+/BCL2+/BCL6+) demonstrated concurrent rearrangements for MYC and BCL6 genes indicating DHL (n = 1, 0.85%), while none of the double-expressors (n = 6) showed MYC, BCL2, or BCL6 rearrangements. The mean overall survival of the DEL/TEL was 48.2 days. Conclusion: DEL/TEL and DHL are uncommon in CNS; mostly located supratentorially and are associated with poor outcome. MYC, BCL2, and BCL6 IHC can be used as an effective screening strategy for ruling out double/ triple-expressor PCNS-DLBCLs.

Double-hit primary central nervous system lymphoma with histogenetically proven bone marrow infiltration: A case report and a review of the literature

“…Previous reports of patients treated with HD-MTX alone or with HD-MTX and rituximab have limited overall survival to approximately 3 months [9,15], while one patient treated with three cycles of HD-MTX and high-dose cytarabine followed by three doses of singleagent rituximab was alive for 3 years [9]. Further studies are needed to assess whether the current intensive immunochemotherapy is as effective in patients with DH-PCNSL as in patients with PCNSL without genetic rearrangements.…”

“…Since PCNSL predominantly shows a non-GCB immunophenotype [14], further investigation is needed to explore whether there is a speci c background for the fact that all the patients with DH-PCNSL reported to date, including our case, were of the non-GCB type, in contrast to systemic DHL. Despite a few reports describing the detailed clinical course of DH-PCNSL, their outcomes are mostly unfavorable [9,15].…”

“…PCNSL occasionally metastasizes outside the CNS [20,21], but rarely shows BM in ltration early in the clinical course [22][23][24]. The results of systemic surveillance in patients with DH-PCNSL have not been well described [7,10,11,15,25]. The International PCNSL Collaborative Group recommends BMB and CT scans for patients with PCNSL to rule out the presence of extra-CNS lesions.…”

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

“…There are many target receptors in PCNSL apart from B-cell antigen receptor and Toll-like receptor signaling, such as programmed cell death-1 (PD-1)/PD-1 Ligand and immune activation shown by presence of tumor infiltrating lymphocytes. So, targeting one pathway may not be sufficient to treat such a debilitating disease[ 15 , 16 ]. CSF analysis may not provide information about the tumor microenvironment.…”