PB2055 HIGH PREVALENCE OF NON‐GERMINAL CENTER B‐CELL PHENOTYPE WITH MYC OVEREXPRESSION IN JAPANESE PATIENTS WITH INTRAVASCULAR LARGE B‐CELL LYMPHOMA
Authors: Takahashi H. , Nakanishi Y. , Miura K. , Hamada T. , Nakagawa M. , Nishimaki H. , Iizuka K. , Uchino Y. , Iriyama N. , Koike T. , Kurihara K. , Nakayama T. , Sugitani M. , Hatta Y. , Masuda S. , Takei M. 
Published: June 2019

Background:

Intravascular large B‐cell lymphoma (IVLBCL) is a rare subtype of B‐cell non‐Hodgkin lymphoma characterized by its unique disease progression within the lumen of multi vessels, nonspecific symptoms such as fever of unknown origin, and poor prognosis. Although recent studies have demonstrated some advances in understanding the pathogenesis of IVLBCL, clinicopathological features of the disease are still to be investigated especially in hemophagocytic syndrome (HPS)‐associated variant, formerly known as “Asian variant”.

Aims:

This study is conducted to identify the clinicopathological characteristics of IVLBCL, including HPS‐associated variant in the Japanese cohort.

Methods

This is a retrospective analysis of patients with de novo IVLBCL who were diagnosed in Nihon University Itabashi Hospital between 2004 and 2018. The diagnosis of IVLBCL required; no masses were found in lymph nodes nor extranodal sites; lymphoma cells were limited in the blood vessels in subcutaneous or solid organs, or bone marrow; and lymphoma cells were pathologically originated from mature, CD20‐positive B‐cells. HLH‐2004 criteria were used to determine whether patients were complicated with HPS. Immunohistochemistry analysis was performed using antibodies against MYC, BCL2, CD10, BCL‐6, MUM1, and CD5 according to the standard procedure. Cell‐of‐origin (COO) subtype was classified into germinal center B‐cell – like (GCB) or non‐GC type according to the Hans algorithm. As for MYC immunostaining, positivity of <40%, ≥40%–69%, and ≥70% were defined negative (MYC−), positive (MYC+), and strongly positive (MYC + +), respectively. If the sample demonstrated concurrent positivity for MYC (≥40%) and BCL2 (≥50%), it was categorized into the double expressor lymphoma (DEL). Epstein‐Barr virus early RNA (EBER) in situ hybridization was also performed.

Results:

A total of 17 patients with a median 66‐years (range 43‐81) of age were analyzed. Of these patients, 10 (59%) were considered to be an HPS‐associated variant. All patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapies with or without CNS prophylaxis, resulting in 71% of complete remission (CR) rate and 26 months of median progression‐free survival (PFS). During the observation period, the central nervous system (CNS) relapse was found in 5 patients (29%). COO subtype was non‐GC type in all patients (100%). The numbers of patients with MYC−, MYC+, and MYC + + were 3 (18%), 7 (41%), 7 (41%), respectively. Nine patients (53%) were categorized into DEL. CD5 was positive in 5 patients (29%). EBER was negative in all patients (100%). These clinical or pathological findings were not significantly different between patients with and without HPS. Whereas the clinical outcome of 3 patients with MYC− was comparably favorable (all 3 patients achieved CR and had at least 6–16 months remission duration without CNS relapse), none of MYC positivity, CD5 positivity, nor DEL status was significantly associated with clinical outcomes such as CR rate, PFS duration, or CNS relapse rate.

Summary/Conclusion:

Our finding confirmed a high prevalence of non‐GC phenotype with MYC overexpression in IVLBCL both with and without HPS. These pathological characteristics may partially account for the clinical aggressiveness of the disease.