Inflammatory neuromuscular disorders associated with chronic lymphoid leukemia: Evidence for clonal B cells within muscle and nerve

Abstract

It is frequently difficult to determine whether a neuromuscular disorder (NMD) related to a lymphoproliferative disease is neoplastic, paraneoplastic, or incidental. This may explain why neuromuscular complications of chronic lymphoid leukemia (CLL), a frequent disorder, have been rarely reported. We describe 7 patients with CLL and neuromuscular involvement in whom phenotypic and genotypic characterization of infiltrating lymphoid cells was carried out by immunocytochemistry and PCR-amplification of immunoglobulin heavy chain locus. One patient had massive neoplastic infiltration of muscle, and six presented with inflammatory-like NMDs (dermatomyositis: 2, polymyositis: 1, vasculitic mononeuropathy: 2; inflammatory demyelinating neuropathy: 1). Immunocytochemistry on nerve and muscle frozen sections showed a monotypic lymphoid cell population in 3 cases and failed in 4 cases. The PCR analysis of immunoglobulin heavy chain gene (FR3-FR4) rearrangement detected clonal B-cells in all biopsy specimens. There are arguments suggesting that incidental or paraneoplastic inflammatory NMDs may progress to neoplastic infiltration in CLL patients, as a result of the traffic of tumor B-cells from circulation to nerve and muscle tissues. This may question the traditional distinction between inflammatory and neoplastic NMDs in patients with lymphoid cell proliferations.