title: Development of classical Hodgkin's lymphoma in an adult with biallelic STXBP2 mutations.
abstract: 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.
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska Institutet, and Hematology Center Karolinska, Karolinska University Hospital Huddinge, Stockholm, Sweden. Maciej.Machaczka@ki.se
authors.forename: Maciej
authors.initials: M
authors.lastname: Machaczka
authors.forename: Monika
authors.initials: M
authors.lastname: Klimkowska
authors.forename: Samuel C C
authors.initials: SC
authors.lastname: Chiang
authors.forename: Marie
authors.initials: M
authors.lastname: Meeths
authors.forename: Martha-Lena
authors.initials: ML
authors.lastname: Müller
authors.forename: Britt
authors.initials: B
authors.lastname: Gustafsson
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
mesh_terms: D000293:Adolescent; D000483:Alleles; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral; D005260:Female; D015870:Gene Expression; D006689:Hodgkin Disease / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D064847:Multimodal Imaging; D051938:Munc18 Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology
chemical_list: D051938:Munc18 Proteins; C497940:STXBP2 protein, human