Key result
Primary mediastinal large B-cell lymphoma universally harbors pathogenic variants, most commonly involving SOCS1 in ~91%.
Why the study?
Differentiating primary mediastinal large B-cell lymphoma from diffuse large B-cell lymphomas remains challenging in daily practice, but accurate identification is important because PMBL may require distinct treatment regimens.
Observational (n=49)
PMBL is characterized by frequent mutations in SOCS1, TNFAIP3, ITPKB, and GNA13, supporting the use of integrated histomolecular diagnosis.
Supports integrated histomolecular diagnosis in PMBL; leaves open effects on therapeutic decisions.
Since the description of primary mediastinal large B-cell lymphoma (PMBL) as a distinct entity from diffuse large B-cell lymphomas (DLBCL), numerous studies have made it possible to improve their definition. Despite this, this differential diagnosis can be challenging in daily practice. However, in some centers, PMBL may be treated according to a particular regimen, distinct from those used in DLBCL, emphasizing the importance of accurate identification at diagnosis. This study aimed to describe the histological and molecular characteristics of PMBL to improve the accuracy of their diagnosis. Forty-nine cases of PMBL were retrospectively retrieved. The mean age at diagnosis was 39 years (21–83), with a sex ratio of 0.88. All cases presented a fibrous background with diffuse growth of intermediate to large cells with an eosinophil (26/49, 53%) or retracted cytoplasm (23/49, 47%). “Hodgkin-like” cells were observed in 65% of cases (32/49, 65%). The phenotype was: BCL6+ (47/49, 96%), MUM1+ (40/49, 82%), CD30+ (43/49, 88%), and CD23+ (37/49, 75%). Genomic DNAs were tested by next generation sequencing of 33 cases using a custom design panel. Pathogenic variants were found in all cases. The most frequent mutations were: SOCS1 (30/33, 91%), TNFAIP3 (18/33, 54.5%), ITPKB (17/33, 51.5%), GNA13 (16/33, 48.5%), CD58 (12/33, 36.4%), B2M (12/33; 36.4%), STAT6 (11/33, 33.3%) as well as ARID1A (10/33, 30.3%), XPO1 (9/33, 27.3%), CIITA (8/33, 24%), and NFKBIE (8/33, 24%). The present study describes a PMBL cohort on morphological, immunohistochemical, and molecular levels to provide pathologists with daily routine tools. These data also reinforce interest in an integrated histomolecular diagnosis to allow a precision diagnosis as early as possible.
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Donzel et al. (2023) conducted an observational in Primary mediastinal large B-cell lymphoma (n=49). Histological and molecular characterization was evaluated on Histological and molecular characteristics (phenotype and pathogenic variants). In 49 cases of primary mediastinal large B-cell lymphoma, pathogenic variants were found in all tested cases, most frequently involving SOCS1 (91%), TNFAIP3 (54.5%), and ITPKB (51.5%).
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