Myxomatous Degeneration: Definition and Clinical Significance
Myxomatous (or myxoid) degeneration is a pathological process characterized by the accumulation of mucopolysaccharides (mucin) within connective tissue, resulting in a gelatinous, myxoid matrix that replaces normal tissue architecture.
Pathological Features
Myxomatous degeneration involves:
- Accumulation of extracellular mucoid material within the affected tissue, creating a characteristic gelatinous appearance on gross examination 1
- Replacement of normal collagen architecture with abundant mucopolysaccharide-rich matrix 1
- Disruption of normal tissue structure while maintaining the general tissue framework 2
Common Clinical Manifestations
Cardiac Involvement
Mitral valve myxomatous degeneration is the most clinically significant manifestation:
- Represents a degenerative condition common with advancing age, distinct from rheumatic heart disease 2
- Causes mitral valve prolapse defined as ≥2 mm billowing of leaflet tissue into the left atrium during systole, visible from at least two echocardiographic views including parasternal long-axis 2
- In adults, myxomatous degeneration is the most common etiology of chordal rupture, followed by endocarditis, then rheumatic heart disease 2
- The free edges of leaflets generally remain in apposition below the mitral valve annulus plane, and may or may not cause mitral regurgitation 2
Musculoskeletal Involvement
Meniscal myxoid degeneration:
- Minimal myxoid degeneration in the center of the meniscus is considered normal given its high frequency 3
- Classic myxoid degeneration divides into Type A (parameniscal cystic degeneration) and Type B (intrameniscal myxoid degeneration) 3
- Intrameniscal myxoid degeneration represents a nonspecific reaction to injury 3
Anterior cruciate ligament (ACL) mucoid degeneration:
- Produces knee pain and limited motion, particularly painful deep flexion 4
- MRI reveals characteristic findings with possible associated cyst formation 4
- Responds well to partial arthroscopic debridement without development of instability 4
Renal Neoplasms
ALK-rearranged renal cell carcinoma:
- An extensive mucinous/myxoid background, including intracytoplasmic mucin, is a frequent and important finding 2
- Should be considered in any renal cell carcinoma with heterogeneous, difficult-to-classify morphology with mucinous/myxoid background before labeling as "unclassified RCC" 2
Other Tissue Involvement
Pulmonary fibrosis:
- Fibroblast foci in usual interstitial pneumonia are composed of bland fibroblasts arranged parallel to the airspace within a myxoid matrix, with a reactive cap of cuboidal epithelial cells 2
Bladder carcinoma:
- Urothelial carcinoma with chordoid features shows cellular cording within abundant myxoid matrix, which may be prominent and has been described as "urothelial carcinoma with prominent myxoid stroma" 2
Diagnostic Approach
When myxoid degeneration is suspected:
- Imaging characteristics: MRI typically shows high signal intensity on T2-weighted sequences due to high water content 4
- Histopathological confirmation: Demonstrates abundant extracellular mucoid material replacing normal tissue architecture 1
- Differentiation from neoplastic myxoid tumors: Myxoid degeneration lacks the cellular atypia and specific molecular alterations seen in myxoid sarcomas 1
Clinical Pitfalls
- Do not confuse myxomatous mitral valve prolapse with rheumatic heart disease: Rheumatic disease shows excessive leaflet tip motion with chordal rupture, while myxomatous degeneration shows billowing of leaflet bodies 2
- Minimal myxoid change in menisci is normal: Only extensive or symptomatic myxoid degeneration requires intervention 3
- In children, chordal rupture is predominantly rheumatic (7-17% of cases), not myxomatous, except in rare cases of severe connective tissue disorders 2
- Myxoid background in renal tumors warrants ALK testing before classifying as unclassified RCC 2