Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations

Abstract

This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

Mutational profile of primary breast diffuse large B-cell lymphoma

“…We could not classified 16.6% of them. This results are similar to others series of PB-DLBCL [ 10 , 15 , 17 – 19 ]. The proliferation index, determined by Ki-67 expression, is strikingly high in these samples, higher than or equal to 80% in 16/18 samples.…”

“…In the last twenty years multiple PBL retrospective clinical studies were published including one randomized clinical trial [ 1 – 10 , 15 – 16 ]. However, only two molecular studies, both in oriental population (China and Japan), has been reported [ 10 , 17 ]. The clinical profile of the patients in this series presented a great deal of similarities with previously published ones (clinical presentation, burden of disease, age and response to treatment), with an average age of 66 years [ 1 – 10 ].…”

“…Studies in others extra-nodal lymphomas, such as central nervous system and testis lymphomas, also showed MYD88, CD79B and PIM1 as the most frequently mutated genes, and points out a common molecular profile for extra-nodal DLBCL [ 24 – 26 ]. Recently, a study described the mutational frequency of MYD88 and CD79B in seven PB-DLBCL cases [ 17 ]. In this study 5 patients presented mutations in MYD88 (L265P mutation in 4 cases and 1 case the L265S mutation) and 4 patients presented mutations in CD79B (Y196N, Y196H and Y196D).…”

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

“…Both clinical retrospectives and population-based studies report >90% prevalence of stage IE/IIE disease, and 5-year OS of 75–80% [106–108]. Clinicopathologic series consistently show predominance of the non-GCB phenotype (60–90%) [109, 107], as well as high prevalence of MYD88 (58–70%) and CD79B (36–40%) mutations [110, 111]. Interestingly, these features resemble testicular lymphoma, and breast lymphomas have recently been also recognized to have a notable predilection for CNS recurrence [107, 108].…”

“…Similarly, in a series of 6 Chinese patients with DLBCL of the female genital tract, 4 (including 3 uterine/cervical) relapsed in the CNS [113]. Five of the 7 studied uterine lymphomas had the non-GCB phenotype and 4 had the MYD88 L265P mutation [110]. Although confirmatory research is needed, DLBCL of the uterus may be genetically and clinically similar to breast and testicular lymphoma, including the risk of CNS recurrence.…”