Development of classical Hodgkin’s lymphoma in an adult with biallelic STXBP2 mutations
Maciej Machaczka,
Monika Klimkowska,
Samuel C.C. Chiang,
Marie Meeths,
Martha-Lena Müller,
Britt Gustafsson,
Jan-Inge Henter,
Yenan T. Bryceson
Affiliations
Maciej Machaczka
Division of Hematology, Department of Medicine, Karolinska Institutet, and Hematology Center Karolinska, Karolinska University Hospital Huddinge, Stockholm, Sweden
Monika Klimkowska
Department of Clinical Pathology and Cytology, Karolinska University Hospital Huddinge, Stockholm, Sweden
Samuel C.C. Chiang
Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Marie Meeths
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
Martha-Lena Müller
Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Britt Gustafsson
Department for Clinical Science Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Jan-Inge Henter
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
Yenan T. Bryceson
Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;Broegelmann Research Laboratory, The Gades Institute, University of Bergen, Bergen, Norway
Experimental model systems have delineated an important role for cytotoxic lymphocytes in the immunosurveillance of cancer. In humans, perforin-deficiency has been associated with occurrence of hematologic malignancies. Here, we describe an Epstein-Barr virus-positive classical Hodgkin’s lymphoma in a patient harboring biallelic mutations in STXBP2, a gene required for exocytosis of perforin-containing lytic granules and associated with familial hemophagocytic lymphohistocytosis. Cytotoxic T lymphocytes were found infiltrating the tumor, and a high frequency of Epstein-Barr virus-specific cytotoxic T lymphocytes were detected in peripheral blood. However, lytic granule exocytosis and cytotoxicity by cytotoxic T lymphocytes, as well as natural killer cells, were severely impaired in the patient. Thus, the data suggest a link between defective lymphocyte exocytosis and development of lymphoma in STXBP2-deficient patients. Therefore, with regards to treatment of familial hemophagocytic lymphohistocytosis patients with mutations in genes required for lymphocyte exocytosis, it is important to consider both the risks of hemophagocytic lymphohistocytosis and malignancy.
