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IRF8 as a Novel Marker to Differentiate Between CD30-Positive Large Cell Lymphomas
Daniel C McQuaid1, Samuel G Katz1, Mina L Xu1
1Department of Pathology, Yale New-Haven Hospital, Yale School of Medicine, New Haven, CT, USA.
Insights
Interferon regulatory factor 8 (IRF8) is a promising biomarker for differentiating lymphomas. IRF8 is positive in Hodgkin lymphoma but negative in anaplastic large cell lymphoma (ALCL), aiding diagnosis.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Lymphomas, including Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL), can present diagnostic challenges due to overlapping immunophenotypes.
- Accurate differentiation is crucial as these neoplasms require distinct treatment strategies.
Purpose of the Study:
- To evaluate the utility of Interferon regulatory factor 8 (IRF8) as a biomarker for distinguishing between classic Hodgkin lymphoma (CHL) and ALK-negative anaplastic large cell lymphoma (ALCL).
- To assess the role of IRF8 in conjunction with Paired box 5 (PAX5) in lymphoma subtyping.
Main Methods:
- A retrospective study involving immunostaining for IRF8 and PAX5 on tissue microarrays of 74 CHL, 7 nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) cases, and 19 ALCL cases (15 ALK-negative, 4 ALK-positive).
Main Results:
- IRF8 was positive in 100% of NLPHL and 85% of CHL cases, but negative in 0% of ALCL cases.
- PAX5 expression varied, with some CHL cases being PAX5 negative/IRF8 positive, and others PAX5 positive/IRF8 negative, highlighting diagnostic complexities.
- IRF8 staining demonstrated distinct patterns between CHL and ALCL.
Conclusions:
- IRF8 is a valuable marker that aids in differentiating CHL from ALCL, particularly in cases with overlapping immunophenotypes.
- The combination of IRF8 and PAX5 can improve diagnostic accuracy in challenging lymphoma cases.
- IRF8's distinct expression profile offers a new avenue for precise lymphoma classification and treatment guidance.
Objectives:
Interferon regulatory factor 8 (IRF8) is a new biomarker shown to be positive in monocytic leukemias as well as in B cells. As a transcription factor, it plays a critical role in pre-B-cell differentiation and induction of tolerance pathways, among other functions. Given the frequent diagnostic dilemma in CD30-positive large cell lymphomas that could resemble both Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL), we sought to determine whether IRF8 can be useful in distinguishing between these neoplasms that require different treatment strategies.
Methods:
In this retrospective study, 74 cases of classic Hodgkin lymphoma (CHL) and 7 cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) on a tissue microarray (TMA), as well as 15 individual cases of ALK-negative ALCL and 4 cases of ALK-positive ALCL, were stained for IRF8. Paired box 5 (PAX5) immunostaining of the TMA was also performed and compared alongside since that marker is occasionally the only marker to help clinically differentiate between T- and B-cell lymphomas with anaplastic/Hodgkin-like cytology.
Results:
None (0%) of the ALCLs were positive for IRF8 while all (100%) of the NLPHLs and 85% of the CHLs were positive for IRF8. Six (8%) cases of CHL were PAX5 negative but IRF8 positive. Conversely, seven (10%) cases of CHL were PAX5 positive but IRF8 negative. Four (6%) cases of CHL were negative for both PAX5 and IRF8.
Conclusions:
There is significant morphologic and immunophenotypic (CD30 positive and CD45 and CD20 negative) overlap between CHL and ALCL. Since many ALCLs show downregulation of lineage-specific T-cell markers or are "null cell" type, only PAX5 has been a reliable marker to differentiate between borderline cases. This is further confounded by positivity of PAX5 in some ALCLs due to amplification of PAX5. On the basis of recent discoveries of IRF8 function as well as performance as an immunostain, we tested this marker in human lymphoma samples and found that it aids in the discrimination between these tumors.
