SCLC is frequently associated with paraneoplastic syndromes, including dermatomyositis. Patients with malignancyassociated dermatomyositis express a specific autoantibody pattern usually positive for anti-transcription intermediary factor 1-g (TIF1-g), suggesting anti-TIF1-g plays a role in development of malignancy-associated dermatomyositis. We present a case of a patient with SCLC, paraneoplastic dermatomyositis, positive anti-TIF1-g, and a point mutation in TIF1-g coding gene, with prominent clinical response to chemoradiation. We suggest that this point mutation is pathogenic, providing evidence for the development of paraneoplastic dermatomyositis through immune cross-reactivity.

Introduction Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis for both locally advanced and metastatic disease. Standard treatment with combination Etoposide-Doxorubicin-Cisplatin-Mitotane (EDP-M) is highly toxic and some patients benefit from mitotane monotherapy. However, identification of these patients remains challenging. We present a summary of the Israeli national referral center’s 20 years of experience in treating advanced ACC, with the aim of identifying prognostic factors and assisting in treatment decision making. Methods We conducted a retrospective multivariate analysis of patients treated for metastatic or locally advanced ACC at Hadassah Medical Center between 2000 and 2020 to determine clinical, pathological and treatment factors correlated with overall survival (OS). Results In our cohort of 37 patients, a combination of modified European Network for the study of Adrenal Tumors (mENSAT) staging with either grade and R-Status, or age and symptoms (GRAS) was validated to stratify prognosis (p= 0.01 and p= 0.03, respectively). Patients who underwent R0-resection followed by radiotherapy or metastasectomy for oligometastatic disease had longer OS as compared with patients with residual disease: median OS of 55 months versus 14 months, respectively, hazard ratio 3.1 (CI 1.4–6.7, p= .005). Patients treated with mitotane monotherapy had a significantly better prognosis, yet this result was attenuated in a multivariate analysis controlling for mENSAT and R-status. Of patients treated with EDP-M, 41.4% experienced grade 3 or higher adverse events. Conclusion Advanced ACC patients achieving R0-status have a better prognosis and might benefit from mitotane monotherapy.