title: Erythema migrans: a reassessment of diagnostic criteria for early cutaneous manifestations of borreliosis with particular emphasis on clonality investigations.
abstract: BACKGROUND
  Controversy exists about the relationship of borrelia infection with B-cell lymphomas because B-cell clonality has been identified in infiltrates that contained borrelia-specific DNA. Systematic clinicopathological, immunophenotypical and molecular pathological studies of early borreliosis are lacking.
  
  
  OBJECTIVE
  (i) To clarify whether clonal B-cell populations are present already in early borreliosis of the skin (erythema migrans); (ii) to re-evaluate clinicopathological, immunophenotypical and molecular pathological criteria for diagnosis of erythema migrans.
  
  
  METHODS
  Study of 34 patients with erythema migrans confirmed by polymerase chain reaction (PCR). Infiltrates were analysed by histopathological and immunohistochemical methods and multiplex PCR for clonal IgH rearrangements.
  
  
  RESULTS
  Erythema migrans shows a broad spectrum of changes including sparse infiltrates of T lymphocytes, dense interstitial granulomatous infiltrates (CD68+), and pseudolymphomatous patterns with germinal centre formation. There were accompanying epidermal changes in 59% of patients, and plasma cells were an inconsistent finding. B cells were few when infiltrates were sparse, but increased disproportionately when infiltrates were dense. IgH rearrangement studies revealed one pseudo-oligoclonal, three pseudoclonal and three clonal infiltrates. Pseudoclonality was encountered when infiltrates contained only few B lymphocytes.
  
  
  CONCLUSIONS
  Infiltrates in erythema migrans are dominated by T cells followed by CD68+ histiocytes and B lymphocytes. Plasma cells are an inconsistent finding. Pseudoclonality of IgH rearrangement is a result of infiltrates being sparse in B lymphocytes and represents a pitfall in molecular pathological diagnosis that can only be avoided by duplicate or triplicate tests. Incidental B-cell clonality may be encountered in patients with unequivocal erythema migrans and should not be interpreted as a malignant lymphomatous process induced by borrelia.
authors.affiliation: Dermatologikum Hamburg, Stephansplatz 5, 20354 Hamburg, Germany. boer@dermatologikum.de
authors.forename: A
authors.initials: A
authors.lastname: Böer
authors.forename: M
authors.initials: M
authors.lastname: Bresch
authors.forename: J
authors.initials: J
authors.lastname: Dayrit
authors.forename: T M
authors.initials: TM
authors.lastname: Falk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology*; D001899:Borrelia Infections / Q000473:pathology*; D002648:Child; D015787:Erythema Chronicum Migrans / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged