Whole genome sequencing of matched primary and metastatic acral melanomas.

Next generation sequencing has enabled systematic discovery of mutational spectra in cancer samples. Here, we used whole genome sequencing to characterize somatic mutations and structural variation in a primary acral melanoma and its lymph node metastasis. Our data show that the somatic mutational rates in this acral melanoma sample pair were more comparable to the rates reported in cancer genomes not associated with mutagenic exposure than in the genome of a melanoma cell line or the transcriptome of melanoma short-term cultures. Despite the perception that acral skin is sun-protected, the dominant mutational signature in these samples is compatible with damage due to ultraviolet light exposure. A nonsense mutation in ERCC5 discovered in both the primary and metastatic tumors could also have contributed to the mutational signature through accumulation of unrepaired dipyrimidine lesions. However, evidence of transcription-coupled repair was suggested by the lower mutational rate in the transcribed regions and expressed genes. The primary and the metastasis are highly similar at the level of global gene copy number alterations, loss of heterozygosity and single nucleotide variation (SNV). Furthermore, the majority of the SNVs in the primary tumor were propagated in the metastasis and one nonsynonymous coding SNV and one splice site mutation appeared to arise de novo in the metastatic lesion.

Limb salvage surgery in the excision of a massive fibromatosis.

Fibromatosis is a rare fibroproliferative disorder with a tendency for local infiltrative and destructive growth. Local recurrence is frequent, despite apparent complete resection after radical excision. We present a case of a 22-year-old woman with massive recurrent thoracic fibromatosis extending into the neck and impairing the function of her right upper limb. This required a multidisciplinary approach to surgery to salvage the limb. The case highlights the fact that while every attempt should be made to achieve negative histologic margins, local recurrence is not uncommon. Therefore, if fibromatosis occurs adjacent to or involves vital structures, these should not be sacrificed to achieve negative margins. Function and structure preserving procedures are important as the primary goal, if not even more important.