Dataset Information

Gene Expression Profiling of Mediastinal Gray Zone Lymphoma and Its Relationship to Primary Mediastinal B-cell Lymphoma and Classical Hodgkin Lymphoma.

ABSTRACT: Mediastinal gray zone lymphoma (MGZL) has immunopathologic features between classical Hodgkin lymphoma (cHL) and primary mediastinal thymic B-cell lymphoma (PMBL), leading to uncertainty regarding its biological relationship to these entities. We performed gene expression profiling from patients with MGZL (20), cHL (18), and PMBL (17) and show MGZL clusters between cHL and PMBL. Expression signatures reveal germinal B-cell and IFN regulatory factor 4 (IRF4) signatures were relatively low in MGZL and cHL compared with PMBL, indicating downregulation of the B-cell program in MGZL, a hallmark of cHL. T-cell and macrophage signatures were higher in MGZL and cHL compared with PMBL, consistent with infiltrating immune cells, which are found in cHL. The NFκB signature was higher in MGZL than PMBL, and like cHL, MGZL and PMBL express NFκB inducing kinase (NIK), indicating noncanonical signaling. These findings indicate that while MGZL has distinctive clustering, it is biologically closer to cHL.

SUBMITTER: Pittaluga S

PROVIDER: S-EPMC7478163 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Gene Expression Profiling of Mediastinal Gray Zone Lymphoma and Its Relationship to Primary Mediastinal B-cell Lymphoma and Classical Hodgkin Lymphoma.

Pittaluga Stefania S Nicolae Alina A Wright George W GW Melani Christopher C Roschewski Mark M Steinberg Seth S Huang DaWei D Staudt Louis M LM Jaffe Elaine S ES Wilson Wyndham H WH

Blood cancer discovery 20200330 2

Mediastinal gray zone lymphoma (MGZL) has immunopathologic features between classical Hodgkin lymphoma (cHL) and primary mediastinal thymic B-cell lymphoma (PMBL), leading to uncertainty regarding its biological relationship to these entities. We performed gene expression profiling from patients with MGZL (20), cHL (18), and PMBL (17) and show MGZL clusters between cHL and PMBL. Expression signatures reveal germinal B-cell and IFN regulatory factor 4 (IRF4) signatures were relatively low in MGZL ...[more]

PMID: 32914098

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Project description:BACKGROUND:Interpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions. METHODS:Search for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above. RESULTS:Most clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL. CONCLUSIONS:P63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.

Dataset Information

Gene Expression Profiling of Mediastinal Gray Zone Lymphoma and Its Relationship to Primary Mediastinal B-cell Lymphoma and Classical Hodgkin Lymphoma.

Publications

Gene Expression Profiling of Mediastinal Gray Zone Lymphoma and Its Relationship to Primary Mediastinal B-cell Lymphoma and Classical Hodgkin Lymphoma.

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