Advances in Hodgkin lymphoma: A Theme Issue in Honor of Prof. Dr. Harald Stein

Dear Colleagues,

We are preparing a Special Issue in honor of Prof. Harald Stein because of his important contribution to the modern classification of lymphomas.

When Harald Stein was employed in Karl Lennert’s Institute in 1968, he was exposed to Lennert’s classification. Stein could not understand the doctrine of the classification that large cell neoplasms of lymph nodes are derived from reticulum cells. This doctrine was based on morphology alone. Nobody at the time knew what reticulum cells were, and the reproducibility of the diagnosis was low. Therefore, Stein decided to search for molecular markers. In 1970, Stein read the Nature publication by Martin Raff in which Raff reported that B cells carry IgM on their surface. Stein then analyzed reticulum sarcomas for IgM with the radial immunodiffusion technique. The majority of these tumors were IgM positive, and thus, proved to be B-cell lymphomas (Stein et al. Lancet 2002). However, it took Stein 9 years to solve the classification of IgM-negative large cell tumors. Stein and his team of Johannes Gerdes and Hilmar Lemke succeeded in 1981 when they discovered—by using the L428 cell line—the Ki-1 molecule; in 1986, this was included in the CD classification as CD30. The  IgM-negative large cell tumors proved to be Ki-1/CD30 positive and were first called Ki-1 lymphomas; they were finally designated, on Stein’s proposal, as anaplastic large cell lymphomas (ALCL). For the worldwide application of CD30 for diagnostic purposes, Stein generated with another team the monoclonal antibody Ber-H2 which functions on FFPE tissue sections (1989). The usage of Ber-H2 (Ber for Berlin) confirmed the constant expression of CD30 by HRS cells of classical Hodgkin lymphoma (CHL) and its constant absence in lymphocyte-predominant Hodgkin lymphoma (NLPHL).  The application of the Ber-H2 antibody was further revealed by the large European Task Force on Lymphoma project to be a new subtype of CHL: nodular lymphocyte-rich classical Hodgkin lymphoma (NLRCHL), which was frequently misdiagnosed as NLPHL. Stein also discovered with Johannes Gerdes and Hilmar Lemke the Ki-67 molecule as a marker for cell proliferation, which was published in 1983.

In cooperation with David Mason, Stein generated monoclonal antibodies specific for B cells (clustered as CD22) and follicular dendritic cells (clustered das CD21).

In 1991, Stein and Peter Isaacson founded the “International Lymphoma Study Group (ILSG)” by bringing together 19 internationally known experts in hematopathology with the aim of establishing a biologically correct lymphoma classification valid on both sides of the Atlantic. In 1994, the ILSG proposed the REAL classification of lymphomas, which was subsequently taken over by the WHO classification. Stein worked as a co-editor for the WHO’s lymphoma projects until 2017.

Prof. Dr. Antonino Carbone
Prof. Dr. ‪Brunangelo ‪Falini
Prof. Dr. Lorenzo Leoncini
Guest Editors

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• Hodgkin lymphoma