Amyloidoisis: Bone Marrow (BM), Flow Cytometry (FC), and Mass Spectrometry (MS) Evaluation of 92 Patients.
Matthew T Howard, Janice M Hodnefield, Angela Dispenzieri, James D Hoyer, William G Morice, Ahmet Dogan, Curtis A Hanson. Mayo Clinic, Rochester, MN
Background: BM aspirate and biopsy are standard in in evaulating a patient with amyloidosis. We reviewed the BMs of 91 patients with amyloidosis to better characterize the laboratory and morphologic features of this disease.
Design: Patients with amyloidosis subtyped using liquid chromatography tandem MS were identified. Amyloid diagnoses were not exclusive to the BM. BM aspirates, biopsies and six-color FC data were reviewed.
Results: 92 patients with amyloidosis were identified; median age=63 and M:F=1.9:1. The diagnostic biopsy site included BM biopsies, fat aspirates, and non-BM tissue biopsies. Amyloid subtyping by MS identified: 58(63%) lambda light chain, 19(21%) kappa light chain, 13(14%) transthyretin (TTR), 1(1%) IgM heavy chain, and 1(1%) AA. Plasma cells (PC) % in the BM ranged from 0% to 94% with 26(29%) >10% PCs. All primary amyloid patients showed monotypic PCs by FC. 8 patients had >30% PCs; 6 of these had lytic bone lesions. PCs ranged from 1% to 22% in 14 patients with TTR or AA subtypes; 3(23%) TTR patients had monotypic PCs in the BM aspirate; 2 of the 3 had >5% PCs.
BM biopsy demonstrated amyloid in the vasculature (n=59), periosteal soft tissue (n=42) and BM interstitium (n=19) with no difference between amyloid subtypes. Amyloid was identified by H&E stain alone in 41(45%) patients; by Congo red: 70(77%). The remaining 22 patients were diagnosed in non-BM tissue. PC distribution was inconspicuous in 81(88%) BMs; 5 BMs had PCs in large aggregates, and 5 had PCs as part of a low grade B-cell lymphoma (LGBCL) with BM involvement. 1 patient had PCs surrounding interstitial amyloid; a spatial relationship between amyloid and PCs was not identified in other cases.
Conclusions: Our results show that most patients with primary amyloidosis have demonstrable BM involvement with amyloid. % PCs can vary, but most have low numbers; 28% of patients in our study had >10% PCs. Amyloid may also be associated with LGBCL with plasmacytic differentiation. The vasculature is the most frequently recognized area of amyloid deposition. Recognizing BM amyloid requires Congo red staining as amyloid deposits will be missed by H&E staining alone in the majority of specimens, emphasizing the need for clinical recognition of signs of possible amyloidosis. TTR amyloid can be identified in patients who also have detectable monotypic PCs, thus mandating MS subtyping whenever amyloidosis is diagnosed; a diagnosis of primary amyloidosis cannot be assumed in patients who have both amyloid and either MGUS or myeloma.
Tuesday, March 1, 2011 9:15 AM
Platform Session: Section B, Tuesday Morning