Comparison of Muscle Biopsy Features with Myositis Autoantibodies in Inflammatory Myopathies: A Pilot Experience

Abstract

Background: Idiopathic inflammatory myopathies (IIM), also called autoimmune myositis, are heterogeneous. These include dermatomyositis (DM), inclusion body myositis, immune mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASS), and overlap polymyositis. Classification of IIM has evolved from clinical to clinico-pathologic to the recent clinico-sero-pathologic with the discovery of myositis-specific antibodies (MSA) and myositis-associated antibodies. The various antibodies have shown association with specific phenotypes.

Objective: To analyze muscle biopsy features with respect to each MSA and MAA to understand the frequency of findings in each entity.

Materials and methods: Biopsy-proven cases of IIM where myositis profile was available were included in the study after obtaining Institutional Ethics Committee (IEC) approval. In addition to the stains and enzyme histochemistry, immunohistochemistry with MHC class I and II and MxA was performed. Features like perifascicular atrophy, perifascicular necrosis, scattered necrosis, inflammation, etc. were analyzed. Myositis profile was performed by line-blot technique using a 16-antigen panel. Cases were divided into different autoantibody subgroups. Various clinical, demographic, and muscle biopsy features were studied with respect to each MSA and MAA.

Results: There were a total of 64 cases. Mi2 (N = 18) was the most common autoantibody. Some of the salient observations included PFA with perivascular inflammation in Mi2; pediatric cases and microinfarcts in NXP2; no PFA or inflammation in MDA5; perifascicular necrosis in JO1; extensive necrosis with sparse inflammation in SRP; more inflammation in overlap myositis; MxA positivity in DM; and absent in ASS.

Conclusion: This is a pilot study documenting differences in biopsy phenotype with each MSA and MAA which is comparable to the literature. These findings can be used to characterize IIM in seronegative biopsies.

Keywords: Inflammatory myopathy; muscle biopsy; myositis antibodies.

Figure 1

Showing dermatomyositis cases of various autoantibody positivity: Anti-Mi2 cases (a-d) showing perifascicular atrophy in all along with perivascular inflammation in A to C (arrow); the infiltrate is extending into the endomysium surrounding the non-necrotic fibers in B (arrow head) (a, b = H and E x 40; c, d = H and E x 100). Anti-NXP2 cases (e-h) showing perifascicular atrophy (e) and extensive necrosis forming microinfarcts (e, f); IHC with MHC class I shows sarcolemmal positivity (g) as opposed to control showing only positivity in vessels (h) (e = H and E x 40; f = H and E x 100; g, h = DAB x 400). Anti-TIF 1γ case (i and j) showing nonspecific atrophy of type II fibers (i = H and E x 400; j = ATPase at pH 9.4 x 400). Anti-MDA5 case (k and l) showing only scattered regenerating fibers; there is no PFA, necrosis or inflammation (k = H and E x 100; l = H and E x 400)

Figure 2

Showing different patterns of MxA staining on IHC: Perifascicular (a), focal (b), diffuse (c) and negative (d) staining (a = DAB x 100; b-d = DAB x 400)

Figure 3

Showing other autoimmune myositis cases other than dermatomyositis: ASS cases (a-d) showing necrotic fibers (arrow) concentrated in the perifascicular area (a = H and E x 400; b = SDH x 400); IHC with MHC class II shows sarcolemmal positivity showing a gradient in staining from periphery of the fascicle toward the center (c = DAB x 400) as opposed to control showing positivity in vessels (d = DAB x 400). Anti-SRP positive IMNM (e-h) cases showing randomly scattered single necrotic fibers (arrow) throughout the fascicle with conspicuously absent inflammation (inset shows a perimysial arteriole which is devoid of perivascular inflammation); basophilic regenerating fibers (asterix) are seen around the necrotic fibers (g); the necrotic fibers have a moth-eaten appearance on SDH (arrow head) (H) (e-g = H and E x 400; h = SDH x 400). Ro-52 positive overlap myositis cases (i and j) showing dense perimysial inflammation (arrow) along with scattered regenerating fibers (white asterix) (i = H and E x 400), and perimysial perivascular inflammation (arrow) which is seen extending into the endomysium surrounding non-necrotic fibers (black asterix) (j = H and E x 400)

Figure 4

A case with fascicular necrosis (circle) with minimal inflammation (a-d) (a,c= H and E x 40; b,d = H and E x 100). Subsequent IHC with MX1 (e and f)was positive (e = DAB x 40; f = DAB x 400) and the case was revised as dermatomyositis