Idiopathic Inflammatory Myopathy-Associated Cancer: A Review of Risk Factors and Screening Recommendations

Authors

  • Eugene Krustev, MD University of Calgary, Calgary, AB, Canada; Johns Hopkins School of Medicine, Baltimore, MD, USA

DOI:

https://doi.org/10.58931/crt.2025.2264

Abstract

Idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune diseases that are characterized by autoimmune myositis. However, systemic extramuscular manifestations are frequently observed. IIMs have been associated with cancer, and given the increased frequency of co-incident cancers in IIM, malignancy screening in newly diagnosed IIM patients is an important consideration. That being said, cancer risk varies across IIM subtypes, antibody specificities, and with clinicodemographic factors. As such, cancer screening should be tailored using a risk stratification approach. This review discusses the evidence regarding cancer risk in IIM, as well as recently-published guidelines for cancer screening in IIM.

Author Biography

Eugene Krustev, MD, University of Calgary, Calgary, AB, Canada; Johns Hopkins School of Medicine, Baltimore, MD, USA

Dr. Eugene Krustev is a myositis fellow at Johns Hopkins University in Baltimore, Maryland, USA. Eugene completed his Bachelor’s and Master of Science degrees at Dalhousie University in Halifax, Nova Scotia, and his medical training at Memorial University of Newfoundland. He subsequently completed his internal medicine residency and rheumatology fellowship at
the University of Calgary.

References

Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, et al. Idiopathic inflammatory myopathies. Nat Rev Dis Primers. 2021;7(1):86. doi:10.1038/s41572-021-00321-x DOI: https://doi.org/10.1038/s41572-021-00321-x

Oldroyd AGS, Allard AB, Callen JP, Chinoy H, Chung L, Fiorentino D, et al. A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies. Rheumatology (Oxford). 2021;60(6):2615–2628. doi:10.1093/rheumatology/keab166 DOI: https://doi.org/10.1093/rheumatology/keab166

Stertz G. Polymyositis. . Berl Klin Wochenschr. 1916;53(489).

Oldroyd AGS, Callen JP, Chinoy H, Chung L, Fiorentino D, Gordon P, et al. International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical Studies Group (IMACS) initiative. Nat Rev Rheumatol. 2023;19(12):805–817. doi:10.1038/s41584-023-01045-w DOI: https://doi.org/10.1038/s41584-023-01045-w

Opinc AH, Makowska JS. Update on malignancy in myositis-well-established association with unmet needs. Biomolecules. 2022;12(1). doi:10.3390/biom12010111 DOI: https://doi.org/10.3390/biom12010111

Pinal-Fernandez I, Ferrer-Fabregas B, Trallero-Araguas E, Balada E, Martínez MA, Milisenda JC, et al. Tumour TIF1 mutations and loss of heterozygosity related to cancer-associated myositis. Rheumatology (Oxford). 2018;57(2):388–396. doi:10.1093/rheumatology/kex413 DOI: https://doi.org/10.1093/rheumatology/kex413

Selva-O’Callaghan A, Ros J, Gil-Vila A, Vila-Pijoan G, Trallero-Araguás E, Pinal-Fernandez I. Malignancy and myositis, from molecular mimicry to tumor infiltrating lymphocytes. Neuromuscul Disord. 2019;29(11):819–825. doi:10.1016/j.nmd.2019.09.014 DOI: https://doi.org/10.1016/j.nmd.2019.09.014

Mecoli CA, Igusa T, Chen M, Wang X, Albayda J, Paik JJ, et al. Subsets of idiopathic inflammatory myositis enriched for contemporaneous cancer relative to the general population. Arthritis Rheumatol. 2023;75(4):620–629. doi:10.1002/art.42311 DOI: https://doi.org/10.1002/art.42311

Chinoy H, Fertig N, Oddis CV, Ollier WE, Cooper RG. The diagnostic utility of myositis autoantibody testing for predicting the risk of cancer-associated myositis. Ann Rheum Dis. 2007;66(10):1345–1349. doi:10.1136/ard.2006.068502 DOI: https://doi.org/10.1136/ard.2006.068502

Ichimura Y, Matsushita T, Hamaguchi Y, Kaji K, Hasegawa M, Tanino Y, et al. Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy. Ann Rheum Dis. 2012;71(5):710–713. doi:10.1136/annrheumdis-2011-200697 DOI: https://doi.org/10.1136/annrheumdis-2011-200697

Fiorentino DF, Chung LS, Christopher-Stine L, Zaba L, Li S, Mammen AL, et al. Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ. Arthritis Rheum. 2013;65(11):2954–2962. doi:10.1002/art.38093 DOI: https://doi.org/10.1002/art.38093

Zhong L, Yu Z, Song H. Association of anti-nuclear matrix protein 2 antibody with complications in patients with idiopathic inflammatory myopathies: a meta-analysis of 20 cohorts. Clin Immunol. 2019;198:11–18. doi:10.1016/j.clim.2018.11.008 DOI: https://doi.org/10.1016/j.clim.2018.11.008

Labrador-Horrillo M, Martinez MA, Selva-O’Callaghan A, Trallero-Araguas E, Balada E, Vilardell-Tarres M, et al. Anti-MDA5 antibodies in a large Mediterranean population of adults with dermatomyositis. J Immunol Res. 2014;2014:290797. doi:10.1155/2014/290797 DOI: https://doi.org/10.1155/2014/290797

Ungprasert P, Leeaphorn N, Hosiriluck N, Chaiwatcharayut W, Ammannagari N, Raddatz DA. Clinical features of inflammatory myopathies and their association with malignancy: a systematic review in asian population. ISRN Rheumatol. 2013;2013:509354. doi:10.1155/2013/509354 DOI: https://doi.org/10.1155/2013/509354

Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet. 2001;357(9250):96-100. doi:10.1016/S0140-6736(00)03540-6 DOI: https://doi.org/10.1016/S0140-6736(00)03540-6

Azuma K, Yamada H, Ohkubo M, Yamasaki Y, Yamasaki M, Mizushima M, et al. Incidence and predictive factors for malignancies in 136 Japanese patients with dermatomyositis, polymyositis and clinically amyopathic dermatomyositis. Mod Rheumatol. 2011;21(2):178–183. doi:10.1007/s10165-010-0362-y DOI: https://doi.org/10.3109/s10165-010-0362-y

Allenbach Y, Mammen AL, Benveniste O, Stenzel W. 224th ENMC International Workshop:: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016. Neuromuscul Disord. 2018;28(1):87–99. doi:10.1016/j.nmd.2017.09.016 DOI: https://doi.org/10.1016/j.nmd.2017.09.016

Allenbach Y, Keraen J, Bouvier AM, Jooste V, Champtiaux N, Hervier B, et al. High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody. Brain. 2016;139(Pt 8):2131–2135. doi:10.1093/brain/aww054 DOI: https://doi.org/10.1093/brain/aww054

Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017;56(5):787–794. doi:10.1093/rheumatology/kew470 DOI: https://doi.org/10.1093/rheumatology/kew470

Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63(3):713–721. doi:10.1002/art.30156 DOI: https://doi.org/10.1002/art.30156

Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;62(9):2757–2766. doi:10.1002/art.27572 DOI: https://doi.org/10.1002/art.27572

Troyanov Y, Targoff IN, Tremblay JL, Goulet JR, Raymond Y, Senécal JL. Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients. Medicine (Baltimore). 2005;84(4):231–249. doi:10.1097/01.md.0000173991.74008.b0 DOI: https://doi.org/10.1097/01.md.0000173991.74008.b0

Casal-Dominguez M, Pinal-Fernandez I, Derfoul A,Graf R, Michelle H, Albayda J, et al. The phenotype of myositis patients with anti-Ku autoantibodies. Semin Arthritis Rheum. 2021;51(4):728-734. doi:10.1016/j.semarthrit.2021.04.012 DOI: https://doi.org/10.1016/j.semarthrit.2021.04.012

Franco-Leyva T, Mariscal A, Baucells A, Ortiz E, Fuste V, Tandaipan J-L, et al. Immune-mediated necrotizing myopathy with Anti-Ku antibodies and simultaneous papillary thyroid tumour: a case report. Ann Case Report. 2023;8:1149. https://doi.org/10.29011/2574- 7754.101149

Belizna C, Henrion D, Beucher A, Lavigne C, Ghaali A, Lévesque H. Anti-Ku antibodies: clinical, genetic and diagnostic insights. Autoimmun Rev. 2010;9(10):691-694. doi:10.1016/j.autrev.2010.05.020 DOI: https://doi.org/10.1016/j.autrev.2010.05.020

De Lorenzo R, Pinal-Fernandez I, Huang W, Albayda J, Tiniakou E, Johnson C, et al. Muscular and extramuscular clinical features of patients with anti-PM/Scl autoantibodies. Neurology. 2018;90(23):e2068-e2076. doi:10.1212/WNL.0000000000005638 DOI: https://doi.org/10.1212/WNL.0000000000005638

Marie I, Lahaxe L, Benveniste O, Delavigne K, Adoue D, Mouthon L, et al. Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody. Br J Dermatol. 2010;162(2):337-344. doi:10.1111/j.1365-2133.2009.09484.x DOI: https://doi.org/10.1111/j.1365-2133.2009.09484.x

Casal-Dominguez M, Pinal-Fernandez I, Corse AM, Paik J, Albayda J, Casciola-Rosen L, et al. Muscular and extramuscular features of myositis patients with anti-U1-RNP autoantibodies. Neurology. 2019;92(13):e1416-e1426. doi:10.1212/WNL.0000000000007188 DOI: https://doi.org/10.1212/WNL.0000000000007188

Shah AA, Rosen A, Hummers L, Wigley F, Casciola-Rosen L. Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum. 2010;62(9):2787-2795. doi:10.1002/art.27549 DOI: https://doi.org/10.1002/art.27549

Shah AA, Xu G, Rosen A, Hummers LK, Wigley FM, Elledge SJ, et al. Brief report: Anti-RNPC-3 antibodies as a marker of cancer-associated scleroderma. Arthritis Rheumatol. 2017;69(6):1306-1312. doi:10.1002/art.40065 DOI: https://doi.org/10.1002/art.40065

Fritzler MJ, Rattner JB, Luft LM, Edworthy SM, Casiano CA, Peebles C, et al. Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F. Autoimmun Rev. 2011;10(4):194-200. doi:10.1016/j.autrev.2010.09.025 DOI: https://doi.org/10.1016/j.autrev.2010.09.025

Lilleker JB, Naddaf E, Saris CGJ, Schmidt J, de Visser M, Weihl CC. 272nd ENMC international workshop: 10 Years of progress - revision of the ENMC 2013 diagnostic criteria for inclusion body myositis and clinical trial readiness. 16-18 June 2023, Hoofddorp, The Netherlands. Neuromuscul Disord. 2024;37:36–51. doi:10.1016/j.nmd.2024.03.001 DOI: https://doi.org/10.1016/j.nmd.2024.03.001

Paltiel AD, Ingvarsson E, Lee DK, Leff RL, Nowak RJ, Petschke KD, et al. Demographic and clinical features of inclusion body myositis in North America. Muscle Nerve. 2015;52(4):527–533. doi:10.1002/mus.24562 DOI: https://doi.org/10.1002/mus.24562

Dobloug GC, Garen T, Brunborg C, Gran JT, Molberg Ø. Survival and cancer risk in an unselected and complete Norwegian idiopathic inflammatory myopathy cohort. Semin Arthritis Rheum. 2015;45(3):301–308. doi:10.1016/j.semarthrit.2015.06.005 DOI: https://doi.org/10.1016/j.semarthrit.2015.06.005

Greenberg SA, Pinkus JL, Amato AA, Kristensen T, Dorfman DM. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia. Brain. 2016;139(Pt 5):1348–1360. doi:10.1093/brain/aww024 DOI: https://doi.org/10.1093/brain/aww024

Amato AA, Griggs RC. Unicorns, dragons, polymyositis, and other mythological beasts. Neurology. 2003;61(3):288–289. doi:10.1212/wnl.61.3.288 DOI: https://doi.org/10.1212/WNL.61.3.288

Chow WH, Gridley G, Mellemkjaer L, McLaughlin JK, Olsen JH, Fraumeni JF, Jr. Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark. Cancer Causes Control. 1995;6(1):9–13. doi:10.1007/bf00051675 DOI: https://doi.org/10.1007/BF00051675

Gunawardena H, Wedderburn LR, North J, Betteridge Z, Dunphy J, Chinoy H, et al. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology (Oxford). 2008;47(3):324–328. doi:10.1093/rheumatology/kem359 DOI: https://doi.org/10.1093/rheumatology/kem359

Na SJ, Kim SM, Sunwoo IN, Choi YC. Clinical characteristics and outcomes of juvenile and adult dermatomyositis. J Korean Med Sci. 2009;24(4):715–721. doi:10.3346/jkms.2009.24.4.715 DOI: https://doi.org/10.3346/jkms.2009.24.4.715

Tsaltskan V, Aldous A, Serafi S, Yakovleva A, Sami H, Mamyrova G, et al. Long-term outcomes in Juvenile Myositis patients. Semin Arthritis Rheum. 2020;50(1):149–155. doi:10.1016/j.semarthrit.2019.06.014 DOI: https://doi.org/10.1016/j.semarthrit.2019.06.014

Morris P, Dare J. Juvenile dermatomyositis as a paraneoplastic phenomenon: an update. J Pediatr Hematol Oncol. 2010;32(3):189–191. doi:10.1097/MPH.0b013e3181bf29a2 DOI: https://doi.org/10.1097/MPH.0b013e3181bf29a2

Chen YJ, Wu CY, Shen JL. Predicting factors of malignancy in dermatomyositis and polymyositis: a case-control study. Br J Dermatol. 2001;144(4):825–831. doi:10.1046/j.1365-2133.2001.04140.x DOI: https://doi.org/10.1046/j.1365-2133.2001.04140.x

Antiochos BB, Brown LA, Li Z, Tosteson TD, Wortmann RL, Rigby WF. Malignancy is associated with dermatomyositis but not polymyositis in Northern New England, USA. J Rheumatol. 2009;36(12):2704–2710. doi:10.3899/jrheum.090549 DOI: https://doi.org/10.3899/jrheum.090549

Stone CJ, Faden DF, Xie L, Lopes Almeida Gomes L, Hejazi EZ, Werth VP, et al. Application of risk-based cancer screening in patients with dermatomyositis. JAMA Dermatol. 2024;160(11):1248–1251. doi:10.1001/jamadermatol.2024.3355 DOI: https://doi.org/10.1001/jamadermatol.2024.3355

Teh I, Huang V, Oon S, Day J. Real-world implications of IMACS malignancy screening guidelines for idiopathic inflammatory myopathies: an evaluation of compliance and economic impact at a tertiary referral center. Int J Rheum Dis. 2024;27(5):e15198. doi:10.1111/1756-185x.15198 DOI: https://doi.org/10.1111/1756-185X.15198

Fiorentino D, Mecoli CA, Igusa T, Albayda J, Paik JJ, Tiniakou E, et al. Association of Anti-CCAR1 autoantibodies with decreased cancer risk relative to the general population in patients with anti-transcriptional intermediary factor 1γ-positive dermatomyositis. Arthritis Rheumatol. 2023;75(7):1238–1245. doi:10.1002/art.42474 DOI: https://doi.org/10.1002/art.42474

Hosono Y, Sie B, Pinal-Fernandez I, Pak K, Mecoli CA, Casal-Dominguez M, et al. Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies. Ann Rheum Dis. 2023;82(2):246–252. doi:10.1136/ard-2022-222441 DOI: https://doi.org/10.1136/ard-2022-222441

Mecoli CA, Fiorentino D, Albayda J, Paik JJ, Tiniakou E, Adler B, et al. The relationship between anti-cell division cycle and apoptosis regulator 1 autoantibodies, anti-Sp4 autoantibodies, and cancer in anti-transcription intermediary factor 1γ-positive dermatomyositis. ACR Open Rheumatol. 2024;6(12):912–917. doi:10.1002/acr2.11750 DOI: https://doi.org/10.1002/acr2.11750

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2025-08-28

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Krustev E. Idiopathic Inflammatory Myopathy-Associated Cancer: A Review of Risk Factors and Screening Recommendations. Can Rheumatol Today [Internet]. 2025 Aug. 28 [cited 2025 Aug. 31];2(2):22–31. Available from: https://canadianrheumatologytoday.com/article/view/2-2-Krustev

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