Molecular Characterization of Primary Mediastinal Large B-Cell Lymphomas
by
,
Marie Donzel
1,2,3,*, 
Florian Pesce
4,
Alexis Trecourt
1,2,
Razika Groussel
5,
Emmanuel Bachy
2,3,6,
Hervé Ghesquières
2,3,6,
Juliette Fontaine
1,
Nazim Benzerdjeb
1,2,
Claire Mauduit
1,3,7 and
Alexandra Traverse-Glehen
1,2,3 1
Hospices Civils de Lyon, Institut de Pathologie Multisite, Hôpital Lyon Sud, 69310 Lyon, France
2
UFR Claude Bernard Lyon 1, 69100 Villeurbanne, France
3
Centre International de Recherche en Infectiologie (CIRI), UFR Lyon-1, Institut National de la Santé et de la Recherche Médicale (INSERM) U1111, Centre National de la Recherche Scientifique (CNRS), UMR5308, Ecole Normale Supérieure de Lyon, 69342 Lyon, France
4
Institut Paoli-Calmettes, 13009 Marseille, France
5
Centre Hospitalier de Roanne, 42300 Roanne, France
6
Hospices Civils de Lyon, Service d’Hématologie, Hôpital Lyon Sud, 69310 Lyon, France
7
Institut National de la Santé et de la Recherche Médicale, Centre Méditerranéen de Médecine Moléculaire (C3M), Unité 1065, Equipe 10, 06000 Nice, France
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(19), 4866; https://doi.org/10.3390/cancers15194866
Submission received: 8 September 2023
/
Accepted: 3 October 2023
/
Published: 6 October 2023
Simple Summary
The present study describes a primary mediastinal large B-cell lymphoma (PMBL) cohort on the morphological, immunohistochemical, and molecular levels, allowing to go deeper in the molecular characterization of PMBL. The mean age at diagnosis was 39 years (21–83), with a sex ratio of 0.88, and a predominance Ann Arbor stage II (67%). Most patients presented a non-germinal center phenotype (non-GC-B) using the Hans algorithm (88%). CD30 was expressed in 88% of cases; with a partial and heterogeneous (67%) or intense and diffuse (20%) expression. CD23 was expressed in 75% of cases with a focal (8%), partial (45%), or diffuse (22%) expression. CIITA breaks were observed in 35% of cases. None of the cases displayed BCL2 rearrangement. The most frequent mutations were: SOCS1 (91%), TNFAIP3 (54.5%), ITPKB (51.5%), GNA13 (48.5%), CD58 (36.4%), B2M (36.4%), STAT6 (33.3%), ARID1A (30.3%), XPO1 (27.3%), CIITA (24%), and NFKBIE (24%). These data also provide pathologists with daily routine tools and reinforce the interest in an integrated histomolecular diagnosis to allow precision diagnosis as early as possible and to adapt the therapeutic strategy.
Abstract
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.
