gms | German Medical Science

Common benign peripheral nerve sheath tumors such as schwannomas and neurofibromas arise both sporadically and in the setting of neurofibromatosis. They differ not only by histologic features but also by distinct molecular genetic events, leading to loss of neurofibromin in neurofibromas (NF1) and loss of merlin activity (NF2) or SMARCB1 (schwannomatosis) in schwannomas. Both tumor entities have to be distinguished, because therapy, malignant potential, and assignment to tumor syndromes are different. In most cases diagnosis is easily done by histopathology. Nevertheless, there are tumors being difficult assigned to either neurofibromas or schwannomas according to established WHO criteria: so called hybrid neurofibromas/schwannomas. We think that those tumors need to be differentiated from the aforementioned tumor types. In a previous study we elucidated the underestimated diagnosis of hybrid neurofibroma/schwannoma in a large cohort and demonstrated their frequent occurance in schwannomatosis and other neurofibromatoses. [1]Since nothing is known about the molecular background of those hybrid tumors, we performed a molecular study. Extensive mutation analysis of the SMARCB1 gene using MLPA, sequencing and FISH was carried out. Additionally an array CGH was performed for 16 different hybrid neurofibromas/schwannomas. SMARCB1 gene mutations were not seen. But, a high percentage (44%) of tumors demonstrated monosomy 22 as well as additional single genetic events. Furthermore, a constitutional deletion of CTNNA3 in one hybrid tumor was seen.In conclusion, these results elucidate monosomy 22 as a common alteration in hybrid neurofibromas/schwannomas and interestingly, point to a potential role of β-catenin/Wnt signalling for the development of those peripheral nerve sheath tumors.

Supported by IMF (Innovative Medizinische Forschung, HA121006)

► Oral presentation is preferred.