BACKGROUND: Dermatomyositis is an autoimmune myopathy characterized by proximal muscle weakness, muscle inflammation, and typical skin findings. It is a rare disease with an incidence of ~1/100 000. About 15-30 % of adult-onset cases are caused by underlying malignancy and dermatomyositis can be the first symptom of undiagnosed cancer, mainly in the case of anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies presence. TIF-1γ is a transcriptional cofactor which is implicated in TGFβ signaling pathway that controls cell proliferation, differentiation, apoptosis, and tumorigenesis. Its expression was shown to be associated with younger age, higher tumor grade, more estrogen receptor negativity, tumors larger than 2 cm, and tendency towards poor outcome in early breast cancer. No association between anti-TIF-1γ antibodies and prognosis has been proposed yet. CASE PRESENTATION: We report a case of a 43-year-old premenopausal woman presenting with the symptoms of systemic rheumatic disease, the most prominent being a typical skin rash and muscle pain. After a series of investigations, the patient was diagnosed with anti-TIF-1γ positive dermatomyositis and concurrent triple-negative breast cancer (cT1c N3c M0) as an underlying cause. Immediate intravenous corticosteroid therapy relieved the symptoms and enabled anticancer therapy to be commenced. Considering the tumor stage, neoadjuvant therapy with 4 courses of AC (Doxorubicin/Cyclophosphamide) followed by 4 courses of Paclitaxel/Carboplatin was administered. However, no tumor regression was documented and radiotherapy was chosen as the definitive treatment. CONCLUSION: Early detection of anti-TIF-1γ autoantibodies can contribute to a rapid diagnosis of tumor-associated dermatomyositis and enable immediate anticancer treatment. We demonstrate the emerging role of anti-TIF-1γ antibodies in the diagnostics of tumor-associated dermatomyositis. Furthermore, we propose a potential role of anti-TIF-1γ antibodies as a prognostic marker in early breast cancer patients.

2nd Department of Internal Medicine Gastroenterology Charles University Prague Faculty of Medicine and University Hospital in Hradec Králové Sokolská 581 500 05 Hradec Králové Czech Republic

Department of Oncology and Radiotherapy Charles University Prague Faculty of Medicine and University Hospital in Hradec Králové Sokolská 581 500 05 Hradec Králové Czech Republic

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Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991;325(21):1487–1498. doi: 10.1056/NEJM199111213252107. PubMed DOI

Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362(9388):971–982. doi: 10.1016/S0140-6736(03)14368-1. PubMed DOI

Callen JP, Wortmann RL. Dermatomyositis. Clin Dermatol. 2006;24(5):363–373. doi: 10.1016/j.clindermatol.2006.07.001. PubMed DOI

Iaccarino L, Ghirardello A, Bettio S, Zen M, Gatto M, Punzi L, Doria A. The clinical features, diagnosis and classification of dermatomyositis. J Autoimmun. 2014;48–49:122–127. doi: 10.1016/j.jaut.2013.11.005. PubMed DOI

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

Casciola-Rosen L, Nagaraju K, Plotz P, Wang K, Levine S, Gabrielson E, Corse A, Rosen A. Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med. 2005;201(4):591–601. doi: 10.1084/jem.20041367. PubMed DOI PMC

Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, Evans SR, Felson DT. 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. PubMed DOI

Barnes BE, Mawr B. Dermatomyositis and malignancy. A review of the literature. Ann Intern Med. 1976;84(1):68–76. doi: 10.7326/0003-4819-84-1-68. PubMed DOI

Peng JC, Sheen TS, Hsu MM. Nasopharyngeal carcinoma with dermatomyositis. Analysis of 12 cases. Arch Otolaryngol Head Neck Surg. 1995;121(11):1298–1301. doi: 10.1001/archotol.1995.01890110072013. PubMed DOI

Kankeleit H. Über primäre nichteitrige Polymyositis. Dtsch Arch Klin Med. 1916;120:335–349.

Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology. 2008;52(1):108–118. doi: 10.1111/j.1365-2559.2007.02889.x. PubMed DOI

Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721–1728. doi: 10.1002/cncr.22618. PubMed DOI

Pilkington C. Tjärnlund A, Bottai M, Werth V, Visser M, Alfredsson L, Amato A, Barohn RJ, Liang M, Singh J et al.: Progress report on development of classification criteria for adult and juvenile idiopathic inflammatory myopathies. Pediatric. Rheumatology. 2014;12(Suppl 1):94.

Lu X, Yang H, Shu X, Chen F, Zhang Y, Zhang S, Peng Q, Tian X, Wang G. Factors predicting malignancy in patients with polymyositis and dermatomyostis: a systematic review and meta-analysis. PLoS One. 2014;9(4):e94128. doi: 10.1371/journal.pone.0094128. PubMed DOI PMC

Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) N Engl J Med. 1975;292(7):344–347. doi: 10.1056/NEJM197502132920706. PubMed DOI

Wakefield LM, Piek E, Bottinger EP. TGF-beta signaling in mammary gland development and tumorigenesis. J Mammary Gland Biol Neoplasia. 2001;6(1):67–82. doi: 10.1023/A:1009568532177. PubMed DOI

Kassem L, Deygas M, Fattet L, Lopez J, Goulvent T, Lavergne E, Chabaud S, Carrabin N, Chopin N, Bachelot T, et al. TIF1gamma interferes with TGFbeta1/SMAD4 signaling to promote poor outcome in operable breast cancer patients. BMC Cancer. 2015;15:453. doi: 10.1186/s12885-015-1471-y. PubMed DOI PMC

Oddis CV. Therapy of inflammatory myopathy. Rheum Dis Clin North Am. 1994;20(4):899–918. PubMed

Marie I, Mouthon L. Therapy of polymyositis and dermatomyositis. Autoimmun Rev. 2011;11(1):6–13. doi: 10.1016/j.autrev.2011.06.007. PubMed DOI

Racanelli V, Prete M, Minoia C, Favoino E, Perosa F. Rheumatic disorders as paraneoplastic syndromes. Autoimmun Rev. 2008;7(5):352–358. doi: 10.1016/j.autrev.2008.02.001. PubMed DOI

Hrncir Z. Favorable effect of methylprednisolone pulse therapy in dysphagia and primary idiopathic polymyositis/dermatomyositis. Cas Lek Cesk. 1992;131(13):399–401. PubMed