Methylation-based classification of benign and malignant peripheral nerve sheath tumors.

The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss of H3K27me3 was exclusively seen in MPNST of the main methylation cluster, which defines it as an additional useful marker for the differentiation of cellular schwannoma and MPNST.

Minimally Invasive Breast Fibroadenoma Excision Using an Ultrasound-Guided Vacuum-Assisted Biopsy Device.

Introduction We studied the extent to which an ultrasound-guided vacuum-assisted biopsy device ("hand-held Mammotome") could be used not only as a valuable tool for investigation of suspicious breast lesions, but also therapeutically for the complete removal of breast fibroadenomas. Materials and Methods 132 aspiration biopsies showing fibroadenoma on histology were collected retrospectively. We ascertained whether there were residual findings on breast ultrasound at a median follow-up of approx. 9 months following biopsy. A questionnaire was used to determine the complication rate, patient satisfaction and acceptance of the procedure. Results In this study complete fibroadenomectomy was achieved at aspiration biopsy in 76 % of cases (n = 132). Compared to fibroadenomas larger than 2.51 cm3 (59 %), those smaller than 2.5 cm3 were completely removed more often (87.6 %; p < 0.05). The procedure is associated with very little pain during and after biopsy and minimal haematoma development, both factors supporting a high rate of acceptance among patients. Conclusion Ultrasound-guided vacuum-assisted biopsy is safe and associated with very few complications. Its additional therapeutic potential is dependant on the size of the benign lesion as measured at initial ultrasound.