Thymoma-Associated Paraneoplastic Polymyositis

Abstract

We read with interest the recent commentary by Inoue et al describing the first reported case of thymic carcinoma–associated paraneoplastic polymyositis. We agree with Inoue et al that this is an extremely difficult complication to manage in this rare histological subtype of thymic malignanices. The authors report that only 23 cases of polymyositis associated with thymoma have previously been described. We have recently encountered a similar constellation of symptoms in a 24-year-old white woman, and wish to summarize her case briefly. She was originally diagnosed with a grade B2 stage IVA malignant thymoma in 2003 with coexistent autoimmune myasthenia gravis and diabetes mellitus. Before attending our clinic in November 2008, she had received extensive prior therapy including three separate debulking surgeries followed by adjuvant radiation on two occasions. Previous chemotherapeutic regimens included six cycles of cisplatin, adriamycin, vincristine, and cyclophoshamide, and three cycles of carboplatin/paclitaxel. In November 2008, she was enrolled on a phase I clinical trial of the histone deacetylase inhibitor belinostat 1,000 mg/m days 1 to 5 every 3 weeks. She attained stable disease on belinostat for 10 months until September 2009, when she presented with an urticarial rash, recurrence of myasthenia gravis, and generalized myalgias predominantly in her shoulder and bilateral thigh muscles. Computed tomography scan at that time revealed stable disease; however, her creatinine kinase was markedly elevated at 2,020 U/L (range, 38 to 252 U/L). Magnetic resonance imaging of her thighs revealed an unusual pattern of edema for an inflammatory myopathy with a fascial distribution in the right vastus lateralis. A muscle biopsy of her anterior thigh confirmed myositis. Despite aggressive therapy, which included intravenous immunoglobulin (IVIG), plasmapharesis, pulsed steroids, and rituximab, she continued to deteriorate and developed progressive bulbar symptoms, finally requiring ventilator support for respiratory failure and a prolonged intensive care unit admission. While myasthenia gravis and other autoimmune phenomena tend to be more closely associated with thymomas, our patient demonstrated a range of autoimmune phenomena including myasthenia gravis, type I diabetes mellitus, and autoantibodies to interferon and interferon . Interestingly, patients with autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy caused by autosomal recessive mutations in the autoimmune regulator (AIRE) gene also have endocrinopathies and autoantibodies against type I interferons. AIRE is known to promote negative selection of autoreactive T cells and apoptosis of thymic medullary epithelial cells. The suggestion that AIRE expression may be altered in thymic tumors provides a fascinating link between autoimmunity and malignancy as demonstrated by our patient.