Biology and Microenvironment
Carlijn Veldman1,2, Stefano Rosati1, Anke van den Berg1, Lydia Visser1, Wouter Plattel2, Arjan Diepstra1
1University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology,2University of Groningen, University Medical Center Groningen, Department of Hematology, Groningen, the Netherlands
Introduction: Thymus and activation regulated chemokine (TARC or CCL17) is produced in high amounts by Hodgkin and Reed-Sternberg (HRS) cells and is largely responsible for the attraction of CD4+ T cells into the tumor micro-environment of classical Hodgkin lymphoma (cHL). In recent years, TARC has gained attention as a clinically useful biomarker as it has shown to be a sensitive tumor cell marker in serum. TARC can also be detected in diagnostic cHL tissue by immunohistochemistry (IHC). We here aim to define a role for TARC IHC in the diagnostic and research setting of cHL.
Methods: TARC IHC was introduced as a routine staining in June 2014 at the department of Pathology of the University Medical Center Groningen, a tertiary referral center in the Netherlands. Briefly, after heat induce antigen retrieval (Ultra CC1), slides were incubated with a polyclonal goat-anti-human TARC antibody (1:800, R&D Systems, Minneapolis, MN) in an automated stainer (Ventana Benchmark). The staining was used for all new cHL cases for correlation with serum levels and in selected cases of reactive lymphadenopathies and non-Hodgkin lymphomas in which HRS-like cells were present. In 2017, all cases that had been stained for TARC until December 2016 were retrospectively selected.
Results: A total of 98 cases were retrieved and reviewed. Of 56 cHL cases, 54 (96%) showed medium to strong TARC expression in the HRS cells. In only 2 of these cases a minority of tumor cells was stained positive. In general, TARC staining was almost exclusively seen in tumor cells and only very occasionally in dendritic cells. In the vast majority of these cHL cases TARC was much more specific in pinpointing HRS cells than CD30. A weak TARC staining in a minority of the tumor cells was seen in 3/3 primary mediastinal B cell lymphomas, 4/4 grey zone lymphomas, 2/7 (partially anaplastic) diffuse large B-cell lymphomas, 1/8 T-cell and histiocyte rich diffuse large B-cell lymphoma, and 1/7 T-cell lymphomas. All 5 nodular lymphocyte predominant Hodgkin lymphoma cases were negative, as well as 8 reactive/infectious lymphadenopathies (of which 2 were EBV positive).
Conclusions: TARC IHC is highly suitable for detecting HRS cells both in a research and a diagnostic setting. In combination with morphology and other IHC markers, TARC helps to differentiate between cHL and alternative diagnoses like nodular lymphocyte predominant Hodgkin lymphoma, benign lymphadenopathy and T-cell lymphoma.