Extramediastinal Lesion in Patients with Primary Mediastinal Large B-Cell Lymphoma

Introduction. Primary mediastinal large B-cell lymphoma (PMBCL) is derived from a thymic B-cell and commonly presents as a bulky lesion in anterior-superior mediastinum. Extramediastinal lesion is an extremely rare situation and requires differential diagnostics with diffuse large B-cell lymphoma (DLBCL).

Aim. To evaluate clinical features and treatment efficacy in patients with PMBCL with extramediastinal lesion.

Methods. Since 2007 to 2017 years, 157 patients were diagnosed with PMBCL (according to WHO criteria) in FSBI National Reaserch Center for Hematology Ministry of Health Russian Federation. Extramediastinal involvement was detected in 16 patients, 3 of them were at different stages of pregnancy. Median age of patients was 27 (23-69) years. Patients received different treatment protocols: m-NHL-BFM-90, R-DA-EPOCH and VACOP-B.

8/16 patients underwent molecular analysis for determination of gene overexpression JAK2, TRAF1, MAL, PDL1, PDL2 . In all 8/8 of cases, overexpression of 2 or more genes was determined, which allowed to confirm and in some cases to revise diagnosis in favor to PMBCL.

Results. The most frequently were noted involvement of kidney - 4/16 of cases, ovarian - 3/16 of cases, pancreas - 3/16 of cases and bone marrow - 3/16 of cases.Gastric involvement was revealed very rarely - 1/16 of cases, involvement of bones - 1/16 of cases, soft tissues involvement - 1/16 of cases.In 15 from 16 cases isolated extramediastinal lesion was combined with involvement of antero-superior mediastinum and only in one from 16 patients was revealed isolated thoracic soft tissues involvement (without involvement of mediastinal structures).Chemotherapy according m-NHL-BFM-90 was performed in 4/16 of patients: 1/4 of patients was dead from disease progression, 3/4 of patients achieved complete remission (CR) of disease. 11/16 of patients underwent treatment according R-DA-EPOCH, including two patients at different stages of pregnancy. CR was achieved in 6/11 of patients, 4/11 of patients achieved a partial remission (PR), subsequently last group continued chemotherapy (2/4 -Dexa-BEAM, 2/ 4 - DHAP + autologous stem cell transplantation). In one from 11 patients developed progression of PMBCL, 10/11 patients achieved CR. 1/16 patients with pregnancy performed chemotherapy according VACOP-B, and after delivery treatment was continued according to Dexa-BEAM protocol. She achieved CR. Median follow-up of patients was 25 months.

Conclusion: in 15/16 of PMBCL cases extramediastinal lesions were revealed in addition to anterior-superior mediastinum involvement. In 1 of 16 cases thoracic soft tissue involvement was not accompanied by presence of a tumor in mediastinum. This clinical feature required an additional molecular study that allowed to diagnose primary mediastinal large B-cell lymphoma. Thus, in case of mediastinal tumor and presence of extramediastinal lesions in young patients differential diagnosis between primary mediastinal large B-cell lymphoma and advanced stage diffuse large B-cell lymphoma with extramediastinal lesion should be performed.