Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1 genes, and is frequently associated with pain.In a cohort study, we assessed the mutation status of 37 patients with clinically diagnosed schwannomatosis and compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no germline mutation in 17 patients (45.9%). Peripheral schwannomas were detected in 3 LZTR1-mutant (60%) and 10 SMARCB1-mutant subjects (66.7%). Among those with peripheral tumors, the median tumor number was 4 in the LZTR1 group (median total body tumor volume 30 cc) and 10 in the SMARCB1 group (median volume 85cc), (P=.2915 for tumor number and P = .2289 for volume). mutation was associated with an increased prevalence of spinal schwannomas (100% vs 41%, P = .0197). The median pain score was 3.9/10 in the LZTR1 group and 0.5/10 in the SMARCB1 group (P = .0414), and SF-36 pain-associated quality of life was significantly worse in the LZTR1 group (P = .0106). Pain scores correlated with total body tumor volume (rho = 0.32471, P = .0499), but not with number of tumors (rho = 0.23065, P = .1696).We found no significant difference in quantitative tumor burden between mutational groups, but spinal schwannomas were more common in LZTR1-mutant patients. Pain was significantly higher in LZTR1-mutant than in SMARCB1-mutant patients, though spinal tumor location did not significantly correlate with pain. This suggests a possible genetic association with schwannomatosis-associated pain.

Background Treatment of aggressive pituitary adenomas typically involves a multimodality approach based on histopathological features and may include pharmacotherapy, surgery, and occasionally radiation therapy. In cases of treatment-refractory tumor progression, chemotherapy may be considered; however, no standard chemotherapeutic regimen has been established. Literature review suggests that temozolomide may have a beneficial role in a subset of cases. To understand the efficacy of temozolomide in progressive pituitary tumors, we reviewed the outcomes of cases at our center. Methods We performed a retrospective chart review to report the outcome and unique features of 7 patients with aggressive functioning pituitary adenomas or carcinomas treated with temozolomide. Tumor pathology included somatotroph (n = 1), corticotroph (n = 3), and lactotroph (n = 3) tumors. Results Four of the 7 patients had at least 2 prior resections, and all had prior radiation and surgery before treatment with temozolomide. Notably, all patients showed response to therapy, defined as either stable disease (43%) or partial response (57%). Median progression-free survival was 1.66 years, and median overall survival was 4 years. Conclusion Our data suggest that temozolomide has an important role in the management of aggressive functioning pituitary tumors that are resistant to standard therapies, and that optimization of therapy with temozolomide may involve individualized regimens. Future prospective clinical trials should be considered.

No abstract