MORPHOMETRIC APPROACHES TO PERIFASCICULAR ATROPHY IN MUSCLE BIOPSY: DO THEY HELP TO DIAGNOSE POLYMYOSITIS?

The sizes of muscle fibres in the peripheral and central parts of fascicles were compared in biopsies from patients with polymyositis/dermatomyositis, patients with slowly progressing muscular dystrophies and normal controls. Of three quantitative parameters tested, perifascicular atrophy factor gave the best discrimination between the patient groups. This factor is obtained by subtracting the atrophy factor of the peripheral fibres from that of the central ones. In polymyositis, the values tend to be negative as a result of atrophy affecting selectively the peripheral fibres, whereas in dystrophies the values are usually close to zero or positive. For the comparison between polymyositis and muscular dystrophy, the test based on perifascicular atrophy factor has an estimated sensitivity of 83% and a specificity of 65%. This quantitative method is thus able to increase sensitivity of the diagnosis of polymyositis over that attained by the subjective evaluation, even at the cost of a sizeable false-positive rate.     

Spatial distribution of muscle necrosis in biopsies from patients with inflammatory muscle disorders

Muscle biopsies from 56 patients with polymyositis (PM), juvenile dermatomyositis (JDM) and adult dermatomyositis (ADM) were investigated using a range of quantitative histological techniques. The objective was to present data on the extent and distribution of muscle fibre degeneration in these patients and to determine whether these data were compatible with postulated mechanisms of fibre injury. Atrophy of one or more of the major fibre types was found in 45/56 biopsies but there was no evidence that particular patterns of type-specific atrophy were characteristic of any individual disease group. However, selective atrophy and/or necrosis of perifascicular fibres was much more common in JDM patients than in ADM or PM groups. In virtually all biopsies where abnormalities of the microvasculature were apparent (7/8 JDM biopsies, 4/13 ADM biopsies and 5/33 PM biopsies) the distribution of acute muscle necrosis was found to be non-random (clustered). However, a substantial proportion of biopsies in the PM group showed clustering of necrotic fibres in the absence of evidence of vascular involvement. This finding suggests that non-random targetting of muscle fibres by effector cells may occur.     

Class I MHC detection as a diagnostic tool in noninformative muscle biopsies of patients suffering from dermatomyositis (DM)

This study is to further confirm the diagnostic value of class I MHC detection in muscle biopsies of adult patients presenting with clinical features of dermatomyositis (DM) and to address its diagnostic value in the case of nonspecific biopsies. A retrospective study was performed on muscle biopsies in 22 patients presenting with clinical features of DM. Immunohistochemical detection of class I MHC was performed in all cases. On pathological features two groups of patients were recorded: group I (14 patients) with typical features of DM and group II (eight patients) with almost normal muscle biopsies (no inflammatory exudates, no perifascicular atrophy). Abnormal sarcolemmal class I MHC expression was recorded in all cases. In all muscle biopsies of group I patients, class I MHC expression was observed in almost all fibres but was stronger in perifascicular areas (eight patients) or was restricted to perifascicular atrophic fibres (six patients). In all muscle biopsies of group II patients, only some perifascicular fibres expressed class I MHC. According to Bohan and Peter criteria, patients were classified as definite DM (nine group I and three group II patients), probable DM (five group I and two group II patients) and possible DM (three group II patients). Abnormal perifascicular class I MHC expression is of diagnostic value in patients presenting with clinical features of DM especially when muscle biopsy fails to show typical features such as inflammatory infiltrates and/or perifascicular atrophy.     

Idiopathic inflammatory myopathies in childhood: a brief review of 27 cases

The most common idiopathic inflammatory myopathies in children include juvenile dermatomyositis, juvenile polymyositis, and myositis associated with another autoimmune disease (overlap myositis). Idiopathic inflammatory myopathies manifest different characteristics affecting children. Only a few investigations of childhood idiopathic inflammatory myopathies were reported, involving 27 patients. In addition, clinical findings, serum muscular enzyme levels, results of electromyography studies, muscle biopsy features, and treatment responses were studied. Seventeen female and 10 male were classified as exhibiting juvenile dermatomyositis (n = 19), juvenile polymyositis (n = 6), or overlap myositis (n = 2). Overlap myositis was associated with systemic sclerosis and systemic erythematous lupus. The mean age at onset was 6.1 years for juvenile dermatomyositis, 4.9 years for juvenile polymyositis, and 8.5 years for overlap myositis. The most common signs included proximal weakness and myalgia. The serum creatine kinase level was increased in 48.2% of patients. An electromyography study revealed myopathic features in 85% of patients. Muscle biopsies led to observations of inflammatory infiltrates with preferential perivascular involvement in the juvenile dermatomyositis group, and endomysial involvement in the juvenile polymyositis group. Fiber atrophy was predominantly perifascicular in the juvenile dermatomyositis group. Treatment with prednisone improved the findings in 81.5% of children.     

Interleukin‐1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes

The most frequent autoimmune adult inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and sarcoid myopathy. Interleukin‐1 (IL‐1) is a pleiotropic molecule, implicated in the inflammatory process, but also in tissue protection and remodelling. We evaluated the immunocytochemical expression of IL‐1α and β in frozen muscle biopsy specimens from patients with dermatomyositis (15 cases), polymyositis (five cases), inclusion body myositis (five cases) and sarcoid myopathy (five cases). Positive immunoreactivities, were observed in both inflammatory cells and muscle fibres. Specificity of the immunostaining was assessed by Western blot experiments. IL‐1 positive inflammatory cells were rare in polymyositis and inclusion body myositis, moderately abundant in dermatomyositis, and prominent in sarcoid myopathy granulomas. In sarcoid myopathy, 24.6±4.1% inflammatory cells were IL‐1α‐positive and 45.2±2.6% were IL‐1β‐positive. IL‐1 positive muscle fibres were mainly observed in dermatomyositis, usually remote from inflammatory infiltrates. Positive immunostaining for IL‐1 was observed in fibres showing ischaemic punched‐out vacuoles, that correspond to areas of myosinolysis, in atrophic perifascicular fibres, and in fibres located within healing microinfarcts. All NCAM‐positive regenerating fibres were IL‐1 positive. We conclude that: (i) IL‐1 is expressed in granulomas of sarcoid myopathy, which is in keeping with the role ascribed to IL‐1 in the formation of granulomas; (ii) IL‐1 is expressed by muscle fibres undergoing ischaemic damage; and (iii) IL‐1 expression by muscle fibres is associated with myofibrillar protein breakdown and regeneration.     

Anomalies in perifascicular muscle fibers as an differential-diagnostic criterion. I. Perifascicular atrophy in inflammatory myopathies

Thirty-four cases of inflammatory muscle disease (21% from a collective of 160 inflammatory myopathies) were suitable for morphometric measurements. A statistical analysis of our data yields a perifascicular fiber atrophy (PA) in 50% of these cases. Morphometry was able to detect also cases with significant PA which were evaluated subjectively as normal. In dermatomyositis, the finding of a PA was more frequent than in other subgroups of inflammatory myopathies. There was also an accumulation of PA in patients with a paraneoplastic polymyositis. It could not be confirmed that PA occurs more frequent in dermatomyositis of children.     

Dermatomyositis as an immunologic complication of toxoplasmosis

Summary We present immunohistochemical, light-and electron-microscopic findings on a muscle biopsy specimen from a 21-year-old woman who developed debilitating dermatomyosisits in the course of toxoplasmosis. The muscle showed perifascicular muscle cell atrophy and prominent ultrastructural changes consistent with polymyositis. These myopathic changes were interpreted as an immunologic complication of systemic toxoplasmosis and were related to immunohistochemically demonstrable immune complex deposits in the small blood vessels. Our data suggest that dermatomyositis is caused and/or related toToxoplasma infection and is an immune complexmediated systemic disease.     

Dermatomyositis‐like muscle pathology in patients with chronic graft‐versus‐host disease

Myositis is a rare complication of chronic graft‐versus‐host disease (cGVHD) following hematopoietic stem cell transplantation (HSCT). Almost all such patients have been reported to have polymyositis (PM). We describe clinical, pathologic, and molecular studies of 3 patients with cGVHD following allogeneic HSCT who developed myopathy. In each case, perifascicular atrophy, the pathognomonic histologic feature of dermatomyositis (DM), was observed. Muscle Nerve, 2009     

Matrix metalloproteinases in inflammatory myopathies: enhanced immunoreactivity near atrophic myofibers

OBJECTIVES: To further examine the role of proteolytic enzyme expression of matrix metalloproteinases (MMP) and T-cell markers in inflammatory myopathies and controls. MATERIAL AND METHODS: We studied the expression of MMP-2, MMP-7, and MMP-9 in 19 cases of inflammatory myopathies and controls using immunocytochemistry. RESULTS: Inflammatory myopathies showed distinct patterns of up-regulation of MMP. MMP-9 was strongly expressed in atrophic myofibers in all inflammatory myopathies. MMP-2 immunoreactivity was similar in its distribution, however, to a weaker intensity. In dermatomyositis the perifascicular atrophy showed pronounced MMP-9 immunoreactivity, probably reflecting denervated patterns of myofibers. Moreover, MMP-7 strongly immunolabeled invaded myofibers in polymyositis cases only. CONCLUSION: These patterns confirm, that MMP-7 up-regulation is prominent in PM, while MMP-2 immunoreactivity is only slightly elevated in inflamed muscle. In general, MMP-9 up-regulation appears to be an important additional molecular event in the multistep process of all inflammatory myopathies.     

皮肌炎肌组织中浆细胞样树突状细胞的病理学特点

目的 研究皮肌炎肌组织中浆细胞样树突状细胞(pDC)的病理学特点,探讨其病理学意义.方法 收集30例皮肌炎及25例多发性肌炎(PM)患者的肌肉活体组织标本,全部行HE染色、免疫组织化学(抗CD303分子及抗CD68分子)染色.结果 肌活体组织检查病理示,30例皮肌炎中25例可见典型束周萎缩,伴肌束膜明显增宽,5例束周萎缩不典型,但于肌束周边可见小群坏死或再生纤维;14例可见束周凿空样纤维;17例可见肌束膜内血管周围炎,6例于肌内膜可见灶性炎症细胞浸润.免疫组织化学染色示,19例在肌束膜及血管周围可见较多巨噬细胞浸润;20例可见较多pDC浸润,其中,15例此细胞仅位于宽大肌束膜内血管周围的灶性炎细胞区域,3例仅位于肌内膜灶性炎症细胞区域,2例pDC在上述2个部位均存在.25例PM患者的主要病理改变为坏死、再生纤维及炎症细胞浸润,免疫组织化学染色在血管周围灶性炎症细胞区域未发现或偶见少量散在pDC的浸润.结论 在PM患者肌组织中未发现或偶见少量散在pDC的浸润,而在皮肌炎患者肌组织内可见显著pDC的浸润,且其主要在宽大肌束膜内的血管周围分布的特点提示可能与皮肌炎束周萎缩的形成有关.

Abstract：

Objective To study the histological features of plasmacytoid dendritic cells (pDC) in muscle tissue affected by dermatomyositis (DM) and to discuss the pathological significations of pDC.Methods Muscle tissues from 30 cases of DM and 25 cases of polymyositis (PM) were collected.HE stain, immunohistochemistry studies were carried out in all muscle samples.Results Pathological features of DM included: perifascicular atrophy (25/30); punched-out fiber (14/30); perivasculitis (17/30),inflammatory infiltration in the endomysium(6/30).Using immunohistochemistry study, 19 cases from DM were infiltrated by macrophages which are CD68 positive and CD303 negative, 20 cases with DM were infiltrated by pDC which are CD303 positive.The location of pDC were: perivascular of interfascicular septae only (15/20); endomysium only (3/20) and both (2/20).Myopathic damage such as necrotic and regenerating fibers and inflammatory infiltration could be seen in PM.There was few pDC infiltration in PM.Conclusions There is few pDC in muscle tissue affected by PM and many pDC in muscle tissue affected by DM with infiltration mainly in the wide interfascicular septae.pDC may be connected to perifascicular atrophy and play a roll in the pathogenesis of DM.