Which histologic findings are characteristic of sporadic inclusion body myositis (s-IBM)?

Updated: Jun 08, 2018
  • Author: Michael P Collins, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Muscle biopsy sample shows myopathic changes with varying degrees of inflammation, predominantly within the endomysium.

The inflammatory infiltrates consist mainly of T cells and macrophages, which focally surround and invade nonnecrotic MFs.

Modified Gomori trichrome stained section showing Modified Gomori trichrome stained section showing (1) 2 muscle fibers (MFs) containing intracytoplasmic vacuoles (open arrows) and (2) mononuclear inflammatory infiltrates invading a nonnecrotic MF (solid arrow). Copyright, Isabel P Collins, MD, 2000, with permission.

Fiber size variability is increased with atrophic fibers consisting of both small rounded and angular MFs. Hypertrophied fibers are seen as well.

Scattered fiber necrosis and regeneration are typically seen.

The presence of rimmed vacuoles is a characteristic feature of s-IBM. The vacuoles occur singly or in multiples and are either subsarcolemmal or centrally located. These also may be seen in other conditions, such as inherited distal myopathies and oculopharyngeal muscular dystrophy. (see Table 1 in Other Problems to be Considered).

In a retrospective study, the morphology and distribution of p62 aggregates in s-IBM were characteristic, and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for s-IBM, with a sensitivity of 93% and a specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for s-IBM; characteristic p62 aggregates were specific (91%), but they lacked sensitivity (44%). [91]

Ragged red fibers and cytochrome C-oxidase (COX) negative fibers are frequently observed to a greater degree than is expected with age.

Sections stained with Congo red and examined under polarized light demonstrate amyloid as apple green birefringent deposits within MFs.

Congo red-stained section showing apple green bire Congo red-stained section showing apple green birefringent amyloid deposits within muscle fibers (MFs) (arrow). The MF on the right side of the section is focally surrounded and invaded by inflammatory cells. Courtesy of Jerry R Mendell, MD.

If amyloid deposits are not seen with this method, fluorescent technique should be used as an alternative means to detect amyloid. The amyloid deposits tend to occur adjacent to vacuoles and are wispy or plaquelike in appearance. Examination under high power (X40 objective) is often required. [92]

MHC-1 upregulation is reported in as much as 100% of biopsy specimens and, though nonspecific, it may be helpful in distinguishing s-IBM from noninflammatory conditions.

Table 1. Clinical Differential Diagnosis of s-IBM (Open Table in a new window)

Disease

Points of Differentiation

h-IBM

Clinically and genetically heterogeneous group of diseases; positive family history; muscle biopsy features similar to s-IBM, but no inflammation

Polymyositis (PM)*

Weakness usually symmetric and proximally predominant; occasional cardiac and pulmonary involvement; similar to s-IBM, biopsy shows endomysial inflammation with invasion of non-necrotic fibers by CD8+ cells, but unlike s-IBM, rimmed vacuoles and ragged red fibers are infrequent and amyloid deposits and tubulofilaments not seen (see Histologic Findings)

Dermatomyositis (DM)

Weakness usually symmetric and proximally predominant; occasional cardiac and pulmonary involvement; characteristic skin lesions; characteristic biopsy findings (eg, perifascular atrophy, muscle infarcts, microvascular MAC deposits in the endomysium, focal capillary depletion, and conspicuous alterations in endothelial cells of endomysial microvasculature)

Oculopharyngeal muscular dystrophy (OPMD)

Predominant involvement of oculopharyngeal musculature (no extraocular muscle involvement in s-IBM); biopsy shows vacuoles, myopathic changes, and infrequent tubulofilaments (similar to s-IBM) but no inflammation; biopsy also shows pathognomonic intranuclear filamentous inclusions having smaller diameters than s-IBM tubulofilaments in 2-9% of nuclei; genetic testing is available for OPMD (PABPN1 gene); rare, genetically distinct oculopharyngodistal variant in Japan

Late-onset distal myopathies

Clinically and genetically heterogeneous group of diseases; positive family history unless sporadic case; biopsy may show rimmed vacuoles and tubulofilamentous inclusions in Welander, distal myopathy, Nonaka distal myopathy, and tibial muscular dystrophy, all of which can be classified as h-IBM. Gene testing is available for Nonaka distal myopathy (GNE) and tibial muscular dystrophy (titin).

Overlap myositis

PM- or DM-like clinical and myopathological presentation but with additional systemic and serologic features diagnostic of an underlying connective tissue disease (eg, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, or mixed connective tissue disease)

Myasthenia gravis

Unlike s-IBM, extraocular muscles are routinely involved; weakness is usually symmetric and tends to fluctuate, increasing with repeated or sustained exertion; spontaneous remissions can occur; motor unit action potentials (MUAPs) are unstable (increased jitter), whereas jitter is typically normal in s-IBM; repetitive nerve stimulation often shows abnormal decrement (rare in s-IBM); antibodies to acetylcholine receptors or muscle-specific kinase (MuSK) absent in s-IBM

Motor neuron disease

Upper motor neuron signs such as hyperreflexia and extensor plantar responses are not present in s-IBM; EMG in s-IBM may show neurogenic changes (ie, enlarged MUAPs), but these changes are relatively minor compared with predominance of smaller MUAPs, suggesting myopathy; fasciculation potentials are characteristic of motor neuron disease but rarely reported in s-IBM; recruitment is decreased in motor neuron disease and "early" in s-IBM; muscle biopsy in motor neuron disease shows denervation atrophy.

Acid maltase deficiency

Weakness is typically proximal-predominant (torso included); respiratory failure seen in about one third of adults; EMG is myopathic, similar to that of s-IBM, but in acid maltase deficiency, insertional activity is prominently increased, with profuse complex repetitive and myotonic discharges, whereas myotonic discharges are not seen in s-IBM and complex repetitive discharges are uncommon; muscle biopsy shows lysosomal (acid phosphatase-positive), glycogen-laden (PAS-positive) vacuoles, foci of acid phosphatase reactivity in nonvacuolated fibers, and glycogen accumulation by electron microscopy.

Chronic inflammatory demyelinating polyradiculoneuropathy

Weakness is usually both proximal and distal and mildly asymmetric, similar to s-IBM, but more often distally accentuated and lacking in the characteristic quadriceps/deep finger flexor emphasis of s-IBM; almost all patients have sensory signs and symptoms; examination shows diffuse hypo/areflexia; nerve conductions are abnormal, consistent with demyelination; EMG shows chronic reinnervational and no myopathic changes; serum creatine kinase (CK) is typically normal.

*Patients whose polymyositis does not respond to treatment and who have a clinical picture suggestive of s-IBM should be reevaluated. A repeat biopsy should be considered, as they may have s-IBM. Failure to confirm the diagnosis on initial biopsy may have been due to sampling error or insufficient processing.


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