title: Clonal relationship of classical hodgkin lymphoma and its recurrences.
abstract: OBJECTIVE
  We investigated whether the first and all subsequent manifestations of Hodgkin lymphoma (HL) in a patient are clonally related.
  
  
  METHODS
  We identified a collective of 20 patients with sometimes multiple HL recurrences. Relapses were classified as early, that is, within twelve months (eight events in seven patients) or as late, that is, later than one year after the previous neoplasm (24 events in 17 patients). Hodgkin and Reed-Sternberg cells were microdissected after CD30 staining using laser capture technique. Immunoglobulin heavy chain (IgH) gene fragment lengths were analyzed after DNA preamplification, applying consensus FR3 and J primers by ABI 310 Genetic Analyzer. Sequencing of the amplified IgH products was carried out by ABI 3130 and 3730XL Genetic Analyzer. Epstein-Barr virus (EBV) association was assessed by EBV early RNA and LMP1.
  
  
  RESULTS
  Three cases with early relapses after a first HL diagnosis were clonally related to the initial tumor, whereas three of four patients with early relapses after a first or second relapse were not, which was accompanied by change of EBV association in one case. Six patients presenting with late relapses were clonally unrelated, which was accompanied by change of phenotype in two cases and change of EBV association in one case. Two samples from recurrent tumors of the same patient could be successfully sequenced. These two late relapses were clonally unrelated by IgH fragment length and sequencing analysis.
  
  
  CONCLUSIONS
  Recurrent HL, especially those accompanied by an EBV-association switch or after a relapse, can represent an unrelated novel neoplasm. Our finding might play a role in clinical decision making.
authors: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors: Ellen C
authors: EC
authors: Obermann
authors: Nadine
authors: N
authors: Mueller
authors: Alexander
authors: A
authors: Rufle
authors: Thomas
authors: T
authors: Menter
authors: Esther
authors: E
authors: Mueller-Garamvoelgyi
authors: Gieri
authors: G
authors: Cathomas
authors: Stephan
authors: S
authors: Dirnhofer
authors: Alexandar
authors: A
authors: Tzankov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017730:Ki-1 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D012008:Recurrence; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D007143:Immunoglobulin Heavy Chains; D017730:Ki-1 Antigen; D012367:RNA, Viral; D014763:Viral Matrix Proteins