28PAmyloid myopathy: hypertrophic subtype correlates with higher muscular amyloid deposition

Abstract

Muscle involvement is a rare complication of systemic amyloidosis resulting from monoclonal dysglobulinemia (AL amyloidosis) or from a mutation in the gene encoding the transthyretin (TTR) transport protein. We retrospectively studied 20 patients (13M- 7F; mean age: 67 years) with biopsy-proven muscular AL (16/20) and hereditary TTR amyloidosis (4/20; Ile107Val n=2; Val142Ile n=1; Ile88Leu n=1) with muscle involvement. Three patients had isolated hyperCKemia (HCK), 3 muscle hypertrophy (HPT), and 14 muscle weakness and atrophy (MYOP). CK levels ranged from N to 20xN. In AL amyloidosis, biopsy showed vascular deposits of amyloidosis in all patients, isolated in 4/16, and associated with necrotizing (11/16) and/or inflammatory (6/15) myopathy. In TTR amyloidosis, biopsy showed interstitial (4/4), vascular (1/4), and perivascular (1/4) deposits, with a myonecrotic appearance (4/4). Muscle hypertrophy was present only in patients with AL amyloidosis, and only amyloid deposits in the vessels and/or interstitium were visible. In contrast, muscle weakness was associated with signs of myonecrosis (except one) or inflammation, regardless of the type of amyloidosis. Morphometrical analysis of myofibre size and microvasculature (density, diameter) did not show difference between AL and TTR cases, or between clinical subtypes. In contrast the quantification of muscular congophilic area through home-made macro script for Fiji-ImageJ (cryosection, fluorescence, 555nm) showed that HPT subtype associated with higher amyloid deposition compared to HCK and MYOP (4.7% vs 1.2% and 0.7%, p=0.03 and p=0.003, respectively). In conclusion, amyloid myopathies presented either as muscle hypertrophy (AL) or as necrotizing ± inflammatory myopathy (AL and TTR). Morphometrical analysis indicated that hypertrophic subtype associates with higher muscular amyloid deposition compared to other subtypes.