| Disease |
The new WHO lymphoma classification introduced the provisional category of B-cell lymphoma, unclassifiable with features that are intermediate between diffuse large cell lymphoma (DLBCL) and classical Hodkgin lymphoma (CHL) to encompass cases that do not fulfill the morphological and/or phenotypic criteria for primary mediastinal B-cell lymphoma (PMBL) or nodular sclerosis Hodgkin lymphoma (NSHL) in the mediastinum but exhibit transitional features between these two entities. (Swerdlow S, et al., 2008; Savage KJ, et al., 2003; Rosenwald A, et al., 2003).
Mediastinal gray zone lymphoma (MGZL) in a rare and new entity that shares clinical characteristics with PMBCL and NSHL. Historically, these patients were often included in series of Hodgkin-like anaplastic large cell lymphoma, which is a heterogeneous group. (Zinzani PL, et al., 1998; Grant C, et al., 2011). |
| Epidemiology | MGZL is more frequently seen in young men, with a median patient age of 30 years. (Traverse-Glehen A, et al., 2005; Rieger M, et al., 2011). |
| Clinics | The patients present a mediastinal mass larger than 10 cm, and most of 50% of them are associated with elevated LDH. A minority of patients had extranodal involvement or pleural or pericardial effusions. Also, patients had low peripheral blood absolute lymphocyte counts (ALCs) at the time of presentation. (Poppema S et al., 2005). |
| Other features | Immunophenotype The morphological and immunohistochemical features of MGZL are intermediate and transitional between PMBL and NSHL. Surface immunoglobulin is not expressed. B-cell markers such as CD20 and CD79a are typically expressed, CD30 is usually positive, and there is variable expression of CD15. PAX5, OCT2 and BOB1. (Dunleavy K, Wilson WH., 2015).
It has been demonstrated that expression of the germinal center transcription factor BCL-6 and CD68 (tumor-associated macropages) is found in close to 86% of patients tested and are biomarkers of poor survival. |
| Treatment | Their indeterminate pathobiology has led to uncertainty about what the optimal therapeutic strategy should be in MGZL. MGZLs are often found to be refractory to different chemotherapy regimens used in either DLBCL or CHL such as R-CHOP, R-CHOEP, ABVD, BEACOPP. Although patients with MGZL have been treated as aggressively as patients with B-cell lymphoma, they generally exhibit worse outcomes that patients with PMBCL. (Wilson W, et al., 2014, Song H, et al., 2016).
Lacking other options either R-CHOP or DA-EPOCH-R have been regarded as the most suitable treatments courses for patients with MGZL since those who did not receive these regimen as frontline therapy displayed disease progression.
For relapses, salvage chemotherapy followed by high-dose stem cell transplantation may be considered. Allogeneic transplantation in another option, but outcomes in patients with MGZL are inferiors to that of PMBL. |
| Prognosis | The association of a Hodgkin-like microenvironment and the poor outcomes in MGZL raise the hypothesis that a predominant HL-like morphology and/or phenotype may also be associated with a worse outcome.
Additionally, the intensity of CD15, CD68, CD209 or Bcl-6 staining on the malignant MGZL cells is associated with poor prognosis. (Wilson W, et al., 2014, Song H, et al., 2016). |
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