title: Detection of subclinical systemic disease in primary CNS lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes.
abstract: OBJECTIVE
  To search for subclinical systemic disease in bone marrow and peripheral blood in patients with primary CNS lymphoma (PCNSL) to elucidate whether extracerebral relapse may represent a sequel of initial occult systemic disease rather than true extracerebral spread.
  
  
  METHODS
  Bone marrow and peripheral-blood specimens of 24 PCNSL patients were examined using polymerase chain reaction (PCR) for analysis of clonally rearranged immunoglobulin heavy-chain (IgH) genes.
  
  
  RESULTS
  Identical dominant PCR products were found in bone marrow aspirates, blood samples, and tumor biopsy specimens of two patients, indicating that the same tumor cell population is present in the CNS and in extracerebral sites. Follow-up IgH PCR performed in one of these patients in complete remission 24 months after diagnosis yielded a persistent monoclonal product in the blood. An oligoclonal IgH rearrangement pattern was found in the tumor specimen of two other patients, whereas bone marrow and blood samples demonstrated the same dominant PCR products. Follow-up PCR showed a persistent monoclonal amplificate in blood in one of these patients 27 months after diagnosis.
  
  
  CONCLUSIONS
  It could be demonstrated for the first time that subclinical systemic disease can be present in PCNSL patients at initial diagnosis. Our findings may have an impact on the understanding of PCNSL pathogenesis and the extent of staging and treatment.
authors.affiliation: Department of Hematology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. kristoph.jahnke@charite.de
authors.forename: Kristoph
authors.initials: K
authors.lastname: Jahnke
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korfel
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Philipp
authors.initials: P
authors.lastname: Kiewe
authors.forename: Hermann Ayke
authors.initials: HA
authors.lastname: Klasen
authors.forename: Hans-Henning
authors.initials: HH
authors.lastname: Müller
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000737:chemistry; D019046:Bone Marrow Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D016133:Polymerase Chain Reaction; D012008:Recurrence
chemical_list: D007143:Immunoglobulin Heavy Chains