Musculoskeletal Amyloidosis Imaging

Amyloidosis is an uncommon spectrum of heterogeneous disease patterns with local to systemic effects which may involve the cardiovascular, pulmonary, neurologic, gastrointestinal, genitourinary, musculoskeletal, and integumentary tissues. The deposition of misfolded and insoluble proteins secreted into the extracellular space defines the pathophysiology of amyloidosis. Amyloid fibrils are derived from soluble precursors, such as serum amyloid P component (SAP) and apolipoprotein E (ApoE), which aggregate into insoluble antiparallel configurations in the form of beta-pleated sheets, and are resistant to catabolic proteolysis.  Organ involvement and degree of disease is a function of amyloid protein subtype, plaque burden, and organ-specific toxic effects that leads to inflammation, swelling, end-organ dysfunction, and eventual failure. Several amyloidosis subtypes are associated with long-term dialysis dependence, plasma cell dyscrasia, malignancy, and certain hereditary conditions.  While there are around 40 identified protein subtypes of amyloidosis, the most common amyloid subtypes that involve the musculoskeletal system include the immunoglobulin light chain (AL), the beta-2 microglobulin (AB2M), and the transthyretin (ATTR) proteins--the latter having genetic and senescent variants. The diagnostic gold standard for the diagnosis of amyloidosis is tissue biopsy. Classic histologic findings include positive Congo Red staining patterns and apple-green birefringence under polarized light. The musculoskeletal tissues most commonly involved in amyloidosis include osseous, articular, ligamentous, cartilaginous, synovial tissues, and intervertebral discs. Patients experiencing symptoms of musculoskeletal amyloidosis may report fatigue, weakness, and osseous pain; other specific symptoms depend on the site of involvement. When a primary disease such as multiple myeloma exists, the signs and symptoms of secondary amyloidosis may be obfuscated.  The etiologic pattern of musculoskeletal amyloidosis is variable and can mimic other disease processes, such as rheumatoid arthritis, multiple spondyloarthropathies, myopathy, and chondrosarcoma. Furthermore, certain primary disease states convey a higher risk of developing amyloidosis. Approximately 10 to 15% of patients diagnosed with multiple myeloma will develop amyloidosis. In contrast, nearly 100% of dialysis-dependent patients will develop amyloidosis between the first to second decade following the initiation of treatment.  A separate, primary disease process combined with the nonspecific symptoms and imaging appearance of amyloidosis necessitates a careful differential consideration—especially when initial treatment for a primary diagnosis is ineffective. Underdiagnosis of amyloidosis is common and contributes to nearly 50% of patients expiring within the first two years of diagnosis. Several treatment options are available for most amyloid subtypes--however, efficacy is inversely proportional to the degree of end-organ damage. The radiologic features of amyloidosis are problematically diverse and nonspecific. Although pathologic confirmation is the most reliable diagnostic method, the need for invasive tissue sampling may be obviated in the context of specific imaging patterns and anatomic involvement. Moreover, the imaging findings of amyloidosis may precede the clinical manifestations, providing important diagnostic and prognostic information.  Advancements in radiologic imaging have improved the specificity of MRI and nuclear medicine modalities for detecting amyloidosis. Common imaging patterns seen in various amyloid subtypes include the calcification of involved tissues and infiltration into adjacent soft tissues. The most common imaging modalities used in the imaging of amyloidosis include the radiograph, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and nuclear medicine (NM) imaging techniques such as fluorodeoxyglucose positron emission tomography (FDG-PET).