Background Neuroimaging Gross Pathology Histopathology & Immunohistochemistry

BACKGROUND AND CLINICAL INFORMATION: Head

Summary: IBM is the most common myositis in patients over 50 years of age witn insidious onset of weakness that progress slowly over years. They are not responsive to steroid therapy. Histologically, the characteristic features include rimmed vacuoles and atrophic muscle bundles. There is often mild or minimal amount of inflammatory cell infiltration (predominantly T-cells), abnormal filaments and membranous whorls under electron microscope. Amyloid deposition may also be seen within affected muscle fibers. They are not responsive to steroid.l

History: First described in 1967 by Chou and named inclusion body myositis in 1971 by Yunis and Samaha.

Incidence: as common as polymyositis, at least in North America.

Age and sex: Average of onset is after 50 years of age. It is the most common myositis in patients over 50 years old. Male: female ratio is 2:1 (in contrast to polymyositis and dermatomyositis).

Muscle involved: both proximal and distal muscle.

Clinical: Typically, there is insidious onset of weakness which progresses slowly over several years. Atrophy of affected muscles is often out of proportion to the degree of weakness. IBM is usually not responsive to steroid or immunosuppression. Dysphagia occurs in about 25% of patients. Cardiovascular abnormalities is seen in about 20% of patients. IBM may be associated with other diseases. EMG studies show a mixed pattern and may suggest a neurogenic mechanism.

Since rimmed vacuoles are seen only in 2% of the fibers in some cases, a negative biopsy does not rule out IBM, especially, when the patients has a myositis like picture and is not responsive to steroid. A repeated biopsy should be recommended.
They are not responsive to steroid therapy.

Associated disorders: IBM is not related to increased incidency of malignancy. IBM may develop in the setting of another disease, most often an autoimmune disorder.

Genetics: It has been suggested that two distinct groups may be identified, sporadic-IBM (s-IBM) and familial or hereditary-IBM (h-IBM), and that s-IBM should be denoted as a myositis and h-IBM as myopathy.

Pathogenesis: the formation of vacuoles is hypothesized to be resulted from nuclear breakdown. There is evidence to suggest that the filaments are similar to PHF in Alzheimer's disease. The demonstration of Beta-APP containing amyloid and prion disease is also interesting.

NEUROIMAGING: Head

GROSS PATHOLOGY: Head

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Diagnostic criteria: [Greenfield 6th edt. pg. 543]

Each low power field should contain:

one or more fibers with rimmed vacuoles
one or more groups of atrophic fibers, and
a mononuclear infiltrate in the endomysium.

See also Greenfield 6th edt. pg. 544 for a clinico-pathologic approach for the diagnosis of IBM.

General:

IBM frequently gives a taste of neurogenic atrophy. Angular atrophic fibers are grouped, though tending to be more diverse in size than atrophic denervated fibers, which often appear as distinct populations. Hypertrophied fibers are found.
Nuclear clumps that are frequently seen in denervated atrophy are also seen in IBM.

Inflammation: the amount of inflammation in IBM varies. Sometimes, the amount of inflammation may be minimal. Aside from familial cases, inflammation is usually present and is primarily endomysial but not in septa. Some non-necrotic fibers are usually seen undergoing partial invasion by T8 lymphocytes and macrophages. There is only a small amount or no B-cells.

Histochemistry: Ragged red fibers and cytochrome C oxidase negative muscle fibers are present more frequently in IBM than can be accounted for by age. Mitochondrial mutations have also been documented in IBM [Moslemi AR et al., 1997].

Rimmed vacuoles:

Although rimmed vacuoles are required for the diagnosis of IBM other diseases that have rimmed vacuoles include chloroquine myopathy, acid maltase deficiency, and rare cases of juvenile Batten's disease. Intralysosomal membranous granules occur in these entities and may give rise to rimmed vacuoles.
On cryostat sections, rimmed vacuoles are popcorn like clear vacuoles with a densely blue rim in HE frozen sections. They are are best demonstrated in modified Gomori’s trichrome. The vacuoles are often assoctiated with cytoplasmic and occasionally intranuclear eosinophilic inclusions. On paraffin sections the granules are dissolved so that only rather anonymous vacuoles remain.
Extent of involvement: although over 70% of fibers are involved in some cases, fibers with rimmed vacuoles may be difficult to be found in some cases.

Immunohistochemistry:

Rimmed vacuoles contain amyloid Ab, ApoE, and ubiquitin. Amyloid is most frequently found adjacent to the vacuole, less often perinuclear, and rarely intranuclear. But amyloid is not very helpful in establishing the diagnosis.
Epitopes of Beta-amyloid precursor protein (Beta-APP) had been demonstrated in vacuolated fibers, most, but not all of these are Congo red positive.
Class I MHC: Immunoreactivity is essentially limited to fibers that are partially invaded by lymphocytes, unlike polymyositis, where all fibers become positive.
Ubiquitin has also been demonstrated in IBM fibers.

On semithin sections there are round osmiophillic granules of various sizes that often occur in clusters in subsarcolemmal locations.

EM: there are abnormal cytoplasmic, and less frequently nuclear, collections of abnormal filaments characterized by circular hollow profiles on cross section (on well oriented sections) and a rippled, and with periodic transverse striations, appearance on longitudinal sections. The cytoplasmic filaments (15-19 nm) tend to be larger than intranuclear filaments (12-15 nm). The filaments may be surrounded by membranous whorls. Prion protein was demonstrated to be present in IBM fibers by EM.

DIFFERENTIAL DIAGNOSIS: Head

REFERENCES: Head