Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was >20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to > 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus

Primary Esophageal Melanoma with Aberrant CD56 Expression: A Potential Diagnostic Pitfall

Primary esophageal malignant melanoma (MM) is rare and extremely aggressive. For pathologists, it can be challenging to diagnose and differentiate from other poorly differentiated malignant neoplasms in the esophagus. Complicating this fact, MM can have divergent differentiation and express nonmelanocytic immunohistochemical markers including epithelial markers (cytokeratins) and rarely neuroendocrine markers. Lack of awareness of this fact by a pathologist can lead to an erroneous diagnosis and delay treatment for an already aggressive disease. Herein, we report a case of primary esophageal malignant melanoma with aberrant CD56 expression without accompanying synaptophysin or chromogranin expression