A 35-year-old Caucasian woman presents with symptomatic aortic and mitral valve stenosis. She has no history of congenital heart disease, is noted to have short stature, and has a history of vision problems. She undergoes aortic and mitral valve replacement. Hematoxylin and eosin-stained sections of her mitral valve is shown in Figure 1.
The correct answer is ...
Valve disease associated with mucopolysaccharidosis.
Mucopolysaccharidosis is a lysosomal storage disease,wherein glycosaminoglycans are not properly degraded, and thus deposit and accumulate within bodily tissues including those of the heart valves. Valve disease associated with mucopolysaccharidosis is just one of several systemic manifestations. There are several subtypes of mucopolysaccharidosis depending on the enzyme affected and the particular glycosaminoglycan involved, and the disease spectrum can range from severe to attenuated. In this patient, a mutation in the alpha-L-iduronidase gene, IDUA, caused low enzyme levels associated with elevated urine and blood spot dermatan and heparan sulfate. These findings were consistent with mucopolysaccharidosis type I, Sheie type. As seen in Figure 1, sections of mitral valve show collections of vacuolated histiocytes present both within the fibrous and spongy layers of the mitral valve. Electron microscopy was performed and showed the histiocytes to contain floculent material, in keeping with a lysosomal storage disease. This case highlights the crucial role pathologists play in rendering unsuspected tissue diagnoses that directly impact a patient’s further clinical management. There are several known effective enzyme replacement therapies for mucopolysaccharidosis that may improve patient outcomes and slow disease progression.
Myxomatous degeneration is histologically characterized by expansion of the spongiosa layer of the valve; a consequence of constitutively activated valvular interstitial cells. Discrete vacuolated cells are not a feature. These histologic and gross features are commonly seen in association with valve prolapse.
Chronic rheumatic mitral valve disease falls within the category of post-inflammatory valve disease, and is caused by valvular scarring occurring secondary to an autoimmune reaction following group A streptococci infection, which usually presents as valvular stenosis many years after initial infection. The latent period between infection and symptomology is usually 20 to 40 years. Grossly, the valve tissue is diffusely white, thickened and scarred, with commisural and cordal fusion frequently encountered. Again, vacuolated cells are not a feature. Histologically, fibrosis, neovascularization, and mild chronic inflammation is seen. Calcification may also be appreciated.
Mitral annular calcification is a type of degenerative valve disease, which is most commonly seen in patients over 65 years of age. Gross findings, usually best appreciated at autopsy, demonstrate a calcified annulus with variable valvular leaflet thickening. Histology would show annular calcification, with some degree of leaflet thickening. Scattered vacuolated cells would also not be seen in this instance.
Sarah Thomas, M.D., M.S.
Fellow, Cardiovascular Pathology
Joseph Maleszewski, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Professor of Medicine
Mayo Clinic College of Medicine and Science