Localized immunoglobulin light chain amyloidosis: Novel insights including prognostic factors for local progression

Abstract

In localized light chain amyloidosis (locAL), amyloidogenic light chains (aLC) are produced and deposited locally by a B‐cell clone. We present 293 patients with immunohistochemically confirmed locAL. Lung (nodular pulmonary) with 63 patients was the most involved organ. The aLC was λ in 217 cases (κ:λ ratio 1:3). A local B‐cell clone was identified in 30% of cases. Sixty‐one (21%) had a concomitant autoimmune disorder (cAD). A monoclonal component (MC) were present in 101 (34%) patients and were more frequent in subjects with cAD (51% vs 34%; P = .03). Cigarette smoking was more prevalent in lung locAL (54% vs 37%; P = .018). After a median follow‐up of 44 months, 16 patients died and 5‐ and 10‐years locAL progression‐free survival (PFS) were 62% and 44%. Interestingly, locAL‐PFS was shorter among patients with an identified clonal infiltrate at amyloid deposition site (40 vs 109 months; P = .02) and multinuclear giant cells and/or an inflammatory infiltrate resulted in longer locAL‐PFS in lung involvement (65 vs 42 months; P = .01). However, no differences in locAL PFS were observed in patients with cAD, a MC and involved organ site. Treatment was administered in 163 (54%) patients and was surgical in 135 (46%). Median locAL‐PFS after first treatment was 56 months. Responders had longer locAL‐PFS (78 vs 17 months; P < .001). Three patients with lung locAL and a MC were diagnosed as systemic AL amyloidosis at follow‐up. In summary, locAL pathogenesis seems to be heterogeneous and the clonal infiltrate leads local progression.

Management of AL amyloidosis in 2020

“…In contrast, localized deposition of LCs causes nodules to develop in the skin and in the respiratory, urinary, and gastrointestinal tracts, with local symptoms and a benign course that usually is managed with local treatment. 1 In systemic AL amyloidosis, the PC clone is usually small (median infiltrate, 10%), and presents t (11;14) and gain 1(q21) in ∼50% and 20% of clones, respectively, whereas high-risk aberrations are uncommon. 2,3 Patients whose PC clones harbor t (11;14) have a worse outcome with bortezomib and immunomodulatory drugs (IMiDs), whereas gain 1(q21) is associated with poorer results with oral melphalan.…”

First Case of Nodular Localized Primary Cutaneous Amyloidosis Treated With Bortezomib and Dexamethasone

“…4 Concomitant autoimmune disorders are commonly associated with localized cutaneous amyloidosis. 5 Of note, up to 25% of NLPCA cases are reported with co-occurring Sjogren syndrome but the nature of this association is unclear. 6 Other autoimmune diseases, including CREST syndrome and primary biliary cirrhosis may also present alongside NLPCA.…”

Case Report: Management of Primary Tracheobronchial Light Chain Amyloidosis in a Patient With Biclonal Gammopathy Using a Systemic Bortezomib-Based Regimen

“…In their analysis of 293 patients with localized AL amyloidosis (locAL), Basset et al reported lower respiratory tract involvement in 10.6% of the cases, as well as a 5-year progression free survival rate of 80%. In their study, 16 patients died during a median follow-up of 44 months, all of whom exhibited respiratory tract involvement (nine with lung involvement, four with lower airway involvement, and three with locAL in the nasopharynx) (24). Local tracheobronchial AL amyloidosis seems to be heterogeneous, with symptoms and concomitant disorders having the potential to affect prognosis.…”