Erythema migrans: a reassessment of diagnostic criteria for early cutaneous manifestations of borreliosis with particular emphasis on clonality investigations

Abstract

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. (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. 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. 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. 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.