Hereditary Inclusion Body Myopathies
Background Neuroimaging Gross Pathology Histopathology & Immunohistochemistry Differential Diagnosis Reference
BACKGROUND AND CLINICAL INFORMATION:
Summary: Hereditary inclusion body
myopathies are a heterogeneous group of disease that could be transmitted in an
autosomal dominant or recessive fashion. Clinically, they affect primarily limb
muscles and adolescenece or early adulthood onset. Some subtypes have late onset
in the 5th decades. Histologically, their histological features are
almost identical to that of inclusion body myositis except that there is no
inflammation. The salient diagnostic feature is 15 to 21 nm tubular filamentous
limb muscle weakness (ophthalmoplegia or facial weakness are possible)
adolescence or early adulthood (early and late onset may occur)
At least 2
affected members in the same family (typically phenotype in a known ethnic
rimmed vacuoles and 15 to 21 nm tubular filamentous inclusions.
Behavior: Heterogeneous among
different subtypes but most commonly they are slowly progressibe.
Age: Except for some subtypes,
most of them have onset in adolescence or early adulthood. Childhood onset and
late onset (5th decade) can be seen in some subtypes.
Location: The limb mucles are most
commonly affected. Some of the subtypes may be present as quadriceps-sparing
myopathy or affecting the oculopharyngodistal myopathy.
HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY:
General: Other than no
inflammation, the histology is very similar if not identical to inclusion body
myositis. Typically, there are vacuolated fibers, endomysial fibrosis, and a
variable degree of neurogenic atrophy.
Vacuoles: Rimmed vacuoles are
typically seen in frozen sections and they range from 2-25 mm. Both type I and type
II fibers are affected. On paraffin sections, the content of the vacuoles
dissolves away and only empty vacuoles are present. The vacuoles are often found
in subsarcolemmal locations and sometimes the center of the fibers. The number
of vacuolated fibers varies from a few to up to 70% of the fibers. Small
refractive eosinophilic bodies are often seen in the cytoplasm near the
Immunohistochemistry: The content of the
vacuoles are reactive for an antibody (SM-31) that recognize phosphorylated high
molecular weight neurofilament proteins and interestingly these antibodies also
cross react with hyperphosphorylated tau. Similar to the rimmed vacuoles in
inclusion body myositis, accumulation of cellular prion protein and several
proteins that are characteristically seen in Alzheimer’s disease brain such as
have also been documented.
Filamentous inclusions: Cytoplasmic, and sometime myonuclear, collections of
15 to 21 nm tubular filaments. These filaments are randomly dispersed, but
sometimes run parallel to one another and they are believed to be made of paired
helical filaments. The filamentous inclusions are typically present near the
vacuoles. Diagnostic criteria: A minmum of 3 vacuolated fibers must be examined.
Others: Concentric “myeloid
bodies”, cytoplasmic debris, cytoplasmic inclusion bodies, and occasional
Inclusion body myositis: They have adult onset and inflammation.REFERENCES: Head
Z, Eisenberg I, Mitrani-Rosenbaum S. Genetics
of inclusion body myopathies. Curr Opin Rheumatol.