Monoclonal free light chains can be found in heavy chain diseases

Abstract

Heavy chain diseases (HCDs) are rare B-cell lymphoproliferative neoplasias characterized by the production of a monoclonal component consisting of a truncated monoclonal Ig heavy chain without the associated light chain. Among them, patients with gamma-HCD are so rare that no more than 150 cases can be found in the literature. In this paper, we report one additional case: an 83-year-old man with a gamma-HCD, in whom a kappa light chain component was detected in the serum by using the serum free light-chain assessment and in addition monoclonal kappa cytoplasmic expression was detected in bone marrow plasma cells by flow cytometric analysis. In the work-up of the patient, the underlying anatomopathological lymphoproliferative disease corresponded to a lymphoplasmacytic lymphoma, as it is stated in the current World Health Organization classification (2008), with both lymphadenopathic and bone marrow infiltration. As in other cases, several autoimmune manifestations (antiphospholipidic syndrome and immune thrombocytopenia) were present during the course of the disease in this patient. This case report illustrates a new case of gamma-HCD, in which serum free light-chain analysis and flow cytometry represented a valuable tool for diagnosis, a finding that could be very important for the future management of these patients.

Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias

“…Many heavy chain disease patients have lost the ability to synthesize light chains, but some patients have mutations in the heavy chain that results in the inability to bind light chain. These latter patients may therefore present with an isolated monoclonal heavy chain detected by IFE plus monoclonal free light chain as detected by a significantly abnormal FLC κ to λ ratio [25]. In a series of γ-heavy chain disease patients, the heavy/light chain assays resulted in poor recovery using IgG κ and IgG λ specific reagents, indicating that a significant amount of IgG was not quantitated.…”

Multiple myeloma and multiple plasmacytomas associated with free gamma heavy chain, free kappa light chain and IgGk paraproteins: an unusual triple gammopathy

“…However, the monoclonal free light chains in these patients were not evident by SPEP and were detected by the Freelite Õ assay only. 9,10 Prior to the availability of the Freelite Õ assay, all of the 13 reported cases of biclonal g-HCD co-existed with various IgG or IgM intact paraproteins. 9 A recent paper identified 3 of 15 patients with g-HCD who had monoclonal light chains.…”

Gamma Heavy-chain Disease

“…Prior reports have also included cases of gHCD with detection of clonal plasma cells by flow cytometry or immunohistochemistry, or with secretion of monoclonal light-chain (Bence Jones) proteins. 13,20,32,33 The finding of clonal plasmacytoid or plasmacytic cells by immunohistochemistry or by in situ hybridization therefore does not exclude the possibility of gHCD. Finally, PCR clonality studies may also be misleading.…”

“…10,12,27,31,32 gHCD is a rare disorder, with fewer than 150 cases reported in the literature to date. 12,20,31,32 The classification of the lymphoplasmacytic disorder underlying gHCD has been controversial. In general, it has been reported that most cases resemble lymphoplasmacytic lymphoma (LPL), although a wide variety of disorders have been reported in association with gHCD.…”