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Genomics of primary mediastinal B-cell lymphoma
Source: Childhood Cancer Genomics (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 30, 2025 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary. Independent clinical review is pending.
Context: Non-Hodgkin Lymphoma / Mature B-cell Lymphoma / Primary mediastinal B-cell lymphoma
Primary mediastinal B-cell lymphoma was previously considered a subtype of diffuse large B-cell lymphoma, but is now a separate entity in the World Health Organization (WHO) classification.[14] These tumors arise in the mediastinum from thymic B cells and show a diffuse large cell proliferation with sclerosis that compartmentalizes neoplastic cells.
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Primary mediastinal B-cell lymphoma can be very difficult to distinguish morphologically from the following types of lymphoma:
Diffuse large B-cell lymphoma: Cell surface markers in primary mediastinal B-cell lymphoma are similar to the ones seen in diffuse large B-cell lymphoma (i.e., CD19, CD20, CD22, CD79a, and PAX-5). However, primary mediastinal B-cell lymphoma may display cytoplasmic immunoglobulins, and CD30 expression is commonly present.[34]
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Hodgkin lymphoma: Primary mediastinal B-cell lymphoma may be difficult to distinguish from Hodgkin lymphoma clinically and morphologically, especially with small mediastinal biopsies because of extensive sclerosis and necrosis.
Primary mediastinal B-cell lymphoma has distinctive gene expression and variant profiles compared with diffuse large B-cell lymphoma. However, its gene expression and variant profiles have features similar to those seen in Hodgkin lymphoma.[35-37] Primary mediastinal B-cell lymphoma is also associated with a distinctive constellation of chromosomal aberrations compared with other NHL subtypes. Because primary mediastinal B-cell lymphoma is primarily a cancer of adolescents and young adults, the genomic findings are presented without regard to age.
Multiple genomic alterations contribute to immune evasion in primary mediastinal B-cell lymphoma:
Multiple genomic alterations contribute to immune evasion in primary mediastinal B-cell lymphoma:
Structural rearrangements and copy number gains at chromosome 9p24 are common in primary mediastinal B-cell lymphoma. This region encodes the immune checkpoint genes CD274 (PDL1) and PDCD1LG2. The genomic alterations lead to increased expression of these checkpoint proteins.[37-41] Structural rearrangements are also observed in other genes involved in immune evasion (CTIIA, DOCK8, and CD83).[42]
Multiple genomic alterations contribute to immune evasion in primary mediastinal B-cell lymphoma:
Genomic alterations in CIITA, which is the master transcriptional regulator of major histocompatibility complex (MHC) class II expression, are common in primary mediastinal B-cell lymphoma. These alterations lead to loss of MHC class II expression.[37,41,43]
Multiple genomic alterations contribute to immune evasion in primary mediastinal B-cell lymphoma:
Approximately 50% of primary mediastinal B-cell lymphoma cases show variants or focal copy number losses in B2M, the gene that encodes beta-2-microglobulin (the invariant chain of the MHC class I). These alterations lead to reduced expression of MHC class I.[37,41]
Genomic alterations involving genes of the JAK-STAT pathway are observed in most cases of primary mediastinal B-cell lymphoma.[44]
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Genomic alterations involving genes of the JAK-STAT pathway are observed in most cases of primary mediastinal B-cell lymphoma.[44]
STAT6 is altered in approximately 40% of primary mediastinal B-cell lymphoma cases.[37,41]
Genomic alterations involving genes of the JAK-STAT pathway are observed in most cases of primary mediastinal B-cell lymphoma.[44]
The chromosome 9p region that shows gains and amplification in primary mediastinal B-cell lymphoma encodes JAK2, which activates the STAT pathway.[45,46]
Genomic alterations involving genes of the JAK-STAT pathway are observed in most cases of primary mediastinal B-cell lymphoma.[44]
SOCS1, a negative regulator of JAK-STAT signaling, is inactivated in approximately 50% to 60% of primary mediastinal B-cell lymphoma cases by either variant or gene deletion.[37,41,47,48]
Genomic alterations involving genes of the JAK-STAT pathway are observed in most cases of primary mediastinal B-cell lymphoma.[44]
The IL4R gene shows activating variants in approximately 20% to 30% of primary mediastinal B-cell lymphoma cases. IL4R activation leads to increased JAK-STAT pathway activity.[37,41,44]
Genomic alterations leading to NF-ĸB activation are also common in primary mediastinal B-cell lymphoma. These include copy number gains and amplifications at 2p16.1, a region that encodes BCL11A and REL.[37,41,45,46] Genes encoding negative regulators of NF-kB signaling (e.g., TNFAIP3 and NFKBIE) show inactivating variants in primary mediastinal B-cell lymphoma.[37,41]
Other genes that are altered in primary mediastinal B-cell lymphoma include ZNF217, XPO1, and EZH2.[37,41]
For information about the treatment of childhood primary mediastinal B-cell lymphoma, see Childhood Non-Hodgkin Lymphoma Treatment.
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Publication references
Read the original reference and check its publication notices.
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Preserved source evidence · Independent clinical review pending · Not medical advice