Light chain deposition disease: pathogenesis, clinical characteristics and treatment strategies

Abstract

Light chain deposition disease (LCDD) is a rare hematologic disorder characterized by the deposition of non-amyloid monoclonal light chains in several organs. Together with renal impairment is being the primary morbidity associated with this disease. Due to its rarity, randomized clinical trials lack to explore treatment strategies and there are no approved or universally accepted standard of care treatment options. We aimed to provide a systematic summary of histological and clinical aspects of LCDD and treatment options of available literature therapies strategies. Currently, drugs used to treat multiple myeloma are recommended when LCDD patients also presented multiple myeloma. Anyway, in patients with LCDD that is not associated to multiple myeloma, haematopoietic stem cell transplantation (ASCT) and chemotherapy with thalidomide, dexamethasone, bortezomib are also recommended. In eligible patients, bortezomib-based chemotherapy followed by ASCT appears to be an effective treatment option with durable hematologic remission and organ responses. Although it appears that the patients undergoing ASCT seem to achieve deeper and durable hematologic remissions and organ responses, no statistically significant superiority can be demonstrated over non-transplant or standard chemotherapy-based approaches. As retrieved by our review, bortezomib-based therapy appears to be favorable strategy as long as no dose modification is required for renal impairment, and early hematologic responses as a recovery of renal function. Encouraging data were also demonstrated by treatment lenalidomide or melpalan based. Moreover, new myeloma treatment strategies, as monoclonal antibody Daratumumab, seem to be effective in LCDD. Instead, renal allograft is not recommended, due to high incidence of relapse.

Keywords: Autologus stem cells transplant; LCDD; Light chain deposition disease; MGRS; Monoclonal gammopathy; Plasma cells.

Fig. 1

Monoclonal immunoglobulin deposition disease: a) stained with Hematoxylin–Eosin 20x, b) PAS, c) Jones Methenamine, d) Masson Trichrome, 10x. Nodular sclerosing light are present in the glomerular mesangial regions. The nodules typically have an acellular eosinophilic center with residual cells at the periphery. The nodules are very PAS positive, less JMS positive than the nodules of diabetic glomerulosclerosis, MTS positive and Congo-red stain negative notshown here

Fig. 2

Amyloidosis in hematoxylin–eosin (a), PAS stain (b), Masson trichrome stain and Congo-Red stain (c), × 10; Red-Congo stain shows apple green birefringence at polarized microscopy (d). Amyloid deposits in the mesangial site with the formation of nodular areas and in the walls of the vessels. The amyloid deposits have a paler appearance than sclerosis of diabetic glomerulosclerosis and light chain deposition disease

Fig. 3

Myeloma cast nephropathy; hematoxylin–eosin (a), PAS stain (b) and Masson trichrome stain (c), × 10: large refractile, hyaline casts in the dilatated renal cortical tubules. The casts are dense, strongly eosinophilic, acellular and may appear multilamellar. With the trichrome stain, the casts appear polychromatic, with a mixed red-blue coloration