Unique Proteomic Features of Nodular Pulmonary Amyloidosis
KL Grogg, MC Aubry, JA Vrana, JD Theis, A Dogan. Mayo Clinic, Rochester, MN
Background: Nodular pulmonary amyloidosis is typically limited to the lung, forming single or multiple nodules. Commonly, focal aggregates of lymphocytes and plasma cells are present. Furthermore, the amyloid is usually of AL type by immunohistochemistical studies, but it is often difficult to confirm an underlying clonal lymphoplasmacytic disorder. The application of proteomic analysis to pulmonary amyloidomas provides insight into this rare condition.
Design: Mayo Clinic pathology archives were searched for cases of nodular pulmonary amyoid, and clinical/laboratory data extracted. Each case was studied with immunohistochemistry (IHC): CD3, CD20, κ and λ light chains, SAP, SAA, TTR, IgA, IgD, IgG, IgM). Liquid chromatography tandem mass spectrometry (LC MS/MS) was performed on peptides extracted from Congo Red positive, laser microdissected areas of amyloid from the FFPE tissue.
Results: 18 patients were identified, M:F 1:1, ranging in age 48-80 yrs, average 68 yrs. A subset had underlying connective tissue disease (5/14), and 3 of these presented with multiple pulmonary nodules (total patients with multifocal disease 6/18). In 13 of 18 cases, clonal plasma cells could be demonstrated by IHC. By LC MS/MS, all 18 showed a peptide profile consistent with AL type (12 AL-κ, 4 AL-λ, and 2 AL with an apparent mixture of κ and λ). In 13 of 16 cases, there was also significant codeposition of heavy chains (10 γ, 2 α, 1 δ). 3 of 12 patients had a monoclonal serum protein, which in 2 cases appeared unrelated to the pulmonary amyloid, having a heavy chain component distinct from that in the amyloidoma (one of these represented the only case of systemic amyloid in the 18 patients). Follow-up was available in 14/18, ranging 9-101 months, average 58 months. 3 patients developed recurrent pulmonary amyloidoma, 2 pulmonary recurrence plus cutaneous MALT lymphoma, and 1 had a prior history of parotid gland MALT lymphoma without amyloid.
Conclusions: Nodular pulmonary amyloidoma is a localized form of AL amyloidosis that shows unique features. AL-κ type predominates over AL-λ type, with a ratio of 3:1, in contrast to the AL-λ predominance that characterizes systemic AL amyloid. The majority of nodular pulmonary amyloid also shows codeposition of heavy chains, which has only been rarely reported in systemic amyloidosis. The association of nodular pulmonary amyloidoma with connective tissue disease and the occurrence of lymphoma at other MALT sites suggests that this represents a lymphoplasmacytic neoplasm in the spectrum of MALT lymphoma.
Monday, March 22, 2010 1:00 PM
Poster Session II # 145, Monday Afternoon