LAUSR

SIR, Compelling evidence has recently been presented that SSc may occur as a paraneoplastic disease, especially for cases expressing hallmark anti-RNA polymerase III autoantibodies [1]. Elegant studies have confirmed expression of variant protein by tumours [2] and larger cohort analyses confirm that the association with malignancy is often contemporaneous with autoantibody development [3]. It would be predicted from this model that tumour removal at an early stage could interrupt the autoimmune process and be associated with resolution of the associated SSc. Such clinical improvement would confirm the role of antigen-driven adaptive autoimmunity driving the disease and strongly support current immunosuppressive treatment strategies. Here we describe the case of a 43-year-old woman with malignancy and clinical features of SSc and polymyositis [creatine kinase (CK)>2000 IU/L] associated with PM/Scl antibodies. The presence of tendon contractures, palmar skin thickening and diffuse distribution of skin disease [peak modified Rodnan skin score (mRSS) 11/51] with generalized hyperpigmentation prompted further radiological assessment for underlying malignancy and a cystic pancreatic lesion with a solid component was identified. A distal pancreatectomy and splenectomy successfully excised all tumour tissue and a diagnosis of solid pseudopapillary pancreatic neoplasm was confirmed on histological and immunohistochemical analysis. Following surgical recovery, the patient was rapidly weaned off all immunosuppression and has remained in clinical remission with resolution of both skin sclerosis (mRSS 4/51) and inflammatory muscle disease [normal CK and Medical Research Council (MRC) grade]. Immunostaining with anti-EXOSC10 antibody (anti-PM/Scl-100) demonstrated increased staining in normal exocrine pancreatic cytoplasm (negative in endocrine pancreas) when compared with tumour from this patient. However, nuclear staining was present universally in tumour tissue and found in very few nuclei in the normal pancreas (Fig. 1, arrows). Clinical remission following full resection and increased nuclear staining for PM/Scl-100 in tumour tissue lends support to a potential pathogenic link in this case, and this has not been previously demonstrated in SSc associated with this antibody subset. To confirm and extend the potential association of this hallmark scleroderma ANA pattern with malignancy we interrogated our SSc research database of 2200 patients and identified 80 patients who tested positive for PM/Scl by Hep-2 immunofluorescence and confirmatory counterimmunoelectrophoresis. Data were available for 70 of these patients, 80% of whom were female, with a mean age of 58.4 years (S.D. 14.0) and a mean age at SSc onset of 44.1 years ( S.D. 14.5). Forty-seven patients (67.1%) had limited cutaneous involvement and the remainder had diffuse disease, except three patients for whom these data were missing. More than one-third of the population showed the presence of calcinosis (38.6%) and inflammatory arthropathy (38.6%), while more than half of the patients in the study population were affected by lung involvement, gastrointestinal involvement and inflammatory myopathy (57.1, 62.9 and 61.4%, respectively). These demographic and clinical data are broadly representative of those published previously for this antibody subset [4]. However, a history of malignancy was found in 14/70 patients (20.0%), with cancer onset within 36 months from SSc diagnosis in 5 patients. This is far FIG. 1 Increased nuclear expression of EXOSC10 (PM/ Scl-100) in tumour tissue of a patient with PM/Scl-positive paraneoplastic scleroderma