Gray zone lymphoma: better treated like hodgkin lymphoma or mediastinal large B-cell lymphoma?

Abstract

Although primary mediastinal large B-cell lymphoma (PMBL) and classic Hodgkin lymphoma of the nodular sclerosis type (CHL-NS) are distinct diseases, they share several clinical characteristics and biologic features. Given that, it is not surprising that there exist mediastinal lymphomas that do not fit well into either category but have clinical and morphologic features overlapping and transitional between PMBL and CHL-NS. The term mediastinal gray zone lymphoma (MGZL) has been used for these tumors, which are included in the World Health Organization classification as "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma." Although several studies have evaluated different therapeutic strategies in PMBL and CHL-NS, there is a paucity of prospective experience treating MGZL, given its rarity and relatively recent recognition. Historically, diseases that today would be categorized as MGZL were probably called "anaplastic large-cell lymphoma Hodgkin-like," and their outcome with standard approaches was poor, with short overall survivals. In this review-following a discussion of the biology and clinical features of MGZL, and how they compare to PMBL and CHL-NS-we outline how the treatment of PMBL and CHL-NS has evolved in recent years, and how we believe MGZL should be approached therapeutically.

Fig. 1

Interrelationships among mediastinal lymphomas. Primary mediastinal large B-cell lymphoma (PMBL), classic Hodgkin lymphoma of the nodular sclerosis subtype (CHL-NS), and mediastinal gray zone lymphoma (MGZL) are all thought to be derived from a thymic B cell. In a given patient, differing histologic patterns can be seen at different times, suggesting plasticity in tumor cell phenotype and gene expression. Composite lymphomas of CHL-NS and PMBL may also be seen. Adapted from Grant et al. [3]