Predictor of oncological and neurological outcomes after surgery in patients with thymomatous class III myasthenia gravis.

Thymomatous myasthenia gravis represents a peculiar and severe disease. This study is aimed at evaluating if features specifically related to the neoplasm (i.e.stage, histology, biology) may be significant predictors of neurological outcome after thymomectomy and viceversaneurological variables can affect the neoplasm evolution in a precise clinical class (Class III according to the Myasthenia Gravis Foundation of America) of myasthenia gravis. Methods: We performed a retrospective analysis of 35 patients (16 male, 19 female) with thymoma and class III myasthenia gravis undergoing extended transternal thymectomy plus thymomectomy between 1985 and 2005. Class III was identified as a moderate weakness predominantly affecting limb or axial muscles (type a) or oropharyngeal muscles (type b). Patients operated before 2000 and therefore classified according to the Osserman’s classification were retrospectively re-classified. Oncological endpoints was disease-free survivals. Neurolgical out come was complete stable remission. As oncological predictors of poor outcome were considered age (>55), sex (male), Masaoka stage (II-III), histology according World Health Organization (B2-B3), incomplete resection and cell-cycle protein (p53 high-, p21 low-, p27 low) and glucose transporter-1 and vascular endothelial growth factor expressions. Neurological poor predictors were sex (male), symptom-duration (<12 months), quality of life levels (physical and mental component summaries SF-36 below median value), Myasthenia gravis score, steroid-use, oropharyngeal involvement, histology (B2-B3), hyperplastic residual thymus and evidence of ectopic thymic tissue. Results: There was no perioperative mortality. Disease-free survival rate were 67% at 5 and 56% at 10 years, respectively. At univariate analysis significant negative predictors were stage II-III (p=0.041), incomplete resection (p=0.019), B2-B3 histology (p=0.007) and cell-cycle protein expression (p=0.001), the latter resulting as the sole predictor at multivariate (p=0.003). Complete stable remission rate was 52% at 10 and 66% at 15 years, respectively. At univariate analysis significant negative predictors of complete stable remission were those related to the tumor and namely B2-B3 histology (p=0.021), incomplete resection (p=0.007) and cell-cycle protein expression (p=0.032). Traditional factors resulted marginal significant or non significant. No factor prevailed at multivariate analysis. Conclusion: Incomplete resection of thymoma, B2-B3 histology and cell-cycle protein expression resulted the most significant predictors for both oncological and neurological poor outcome. Whereas traditional neurological factors resulted marginally or non significantly affecting the neurological outcome.These findings entails that thymomatous myasthenia should be considered a different neurological entity from the nonthymomatous one.