title: Hodgkin lymphoma as a novel presentation of familial DICER1 syndrome.
abstract: DICER1 germline mutations are associated with an inherited cancer syndrome, most commonly presenting with pleuropulmonary blastoma (PPB), ovarian sex cord tumors, thyroid cysts/goitre, and cystic nephroma. We describe the occurrence of a Hodgkin lymphoma (HL) of the T cell phenotype in a family with DICER1 syndrome. The patient presented with PPB Type I and HL. Immunohistochemical staining of the Hodgkin and Reed-Sternberg cells revealed CD30, TGP, CD2, CD3, CD15, and IRF4 positivity and weekly positivity of PAX5. T cell receptor repertoire analysis suggested HL of T cell origin, which is in contrast to common B cell-derived HL. The mother had been diagnosed with thyroid cysts, one sister had died from a primitive neuroectodermal tumor, and a brother had died from PPB Type III. Two mutational events were revealed in all affected family members; a single bp deletion, c.5299delC, leading to a frameshift and premature stop in exon 24 and a heterozygous variant (c.4616C>T; p.Thr1539Met) located in exon 23 of the DICER1 gene. This variant is predicted to be benign by in silico analysis.
  
  
  CONCLUSIONS
  Future studies looking for DICER1 mutations in HL cases of the T cell phenotype will be important to confirm its association with constitutional DICER1 syndrome.
  
  
  BACKGROUND
  • DICER1 germline mutations are associated with an inherited cancer syndrome, most commonly pleuropulmonary blastoma, ovarian sex cord tumors, thyroid cysts/goitre, and cystic nephroma. • Hodgkin lymphoma is one of the most frequent types of malignant lymphomas and typically arises sporadically. T cell-derived Hodgkin lymphomas are exceptionally rare. What is New: • DICER1 syndrome may have an even broader phenotypic spectrum and seems to be associated with rare forms of T cell Hodgkin lymphoma.
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Duesseldorf, Germany. Michaela.Kuhlen@med.uni-duesseldorf.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kuhlen
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Duesseldorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hönscheid
authors.affiliation: Department of Pathology, Medical University of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Schemme
authors.affiliation: Department of Pathology, Medical University of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Merz
authors.affiliation: Department of Pediatrics, Martin-Luther University Medical Center, Halle, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Mauz-Körholz
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Duesseldorf, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.affiliation: Pediatric Hematology and Oncology, Children's Hospital Medical Centre, University of Bonn, Bonn, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Troeger
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D010375:Pedigree; D018202:Pulmonary Blastoma / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics*
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER1 syndrome; Hodgkin lymphoma; T cell type