Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach?

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that is putatively derived from a thymic B cell. Accounting for up to 10% of cases of DLBCL, this subtype predominantly affects women in the third and fourth decades of life. Its clinical and molecular characteristics are distinct from other subtypes of DLBCL and, in fact, closely resemble those of nodular sclerosing Hodgkin lymphoma (NSHL). Recently, mediastinal lymphomas with features intermediate between PMBL and NSHL, called mediastinal gray-zone lymphomas, have been described. The optimal management of PMBL is controversial, and most standard approaches include a combination of immunochemotherapy and mediastinal radiation. Recently, the recognition that mediastinal radiation is associated with significant long-term toxicities has led to the development of novel approaches for PMBL that have shown excellent efficacy and challenge the need for routine mediastinal radiation.

Figure 1

Primary mediastinal B-cell lymphoma. Hematoxylin and eosin is shown and CD20 and MUM1 staining are positive. MIB-1 scoring is high. (Figure courtesy of Stefania Pittaluga.)

Figure 2

Spectrum of mediastinal B-cell lymphomas. (A) Both PMBL and Hodgkin lymphoma (HL) are putatively derived from a thymic B cell. The events that transform a thymic B cell into PMBL or HL are poorly understood, but there appears to be plasticity in these events, as HL can recur as PMBL and vice versa. (B) Although NSHL is CD15- and CD30-positive and PMBL is CD20-positive, there are mediastinal lymphomas between these 2 entities with histologic and immunohistochemical features intermediate and transitional between NSHL and PMBL. These diseases are MGZLs.

Figure 3

Relationship of PMBL to Hodgkin lymphoma. Relative gene expression is shown in primary PMBLs (average of all biopsy samples), the PMBL cell line K1106, 3 Hodgkin lymphoma cell lines, and 6 GCB DLBCL cell lines. Red represents high gene expression and green low expression. PMBL signature genes that are also expressed at high levels in Hodgkin lymphoma cell lines compared with GCB DLBCL cell lines. (Figure courtesy of Louis Staudt.)

Figure 4

FDG-PET imaging after completion of therapy in PMBL. These are sequential FDG-PET scans of a patient with PMBL who received 6 cycles of DA-EPOCH-R. (A) Three weeks after the completion of therapy, there was an FDG-PET avid lesion in the anterior mediastinum with an standardized value of 6. (B) The patient was followed, and approximately 6 weeks later had another FDG-PET (B). The lesion now had a standardized value of 2. A subsequent FDG-PET scan 6 weeks later was entirely normal, and the patient remains in complete remission several years later.