title: Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report.
abstract: BACKGROUND
  Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature.
  
  
  METHODS
  Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A) mutation was detected in exon 15 of the BRAF gene.
  
  
  CONCLUSIONS
  Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations.
authors.affiliation: Molecular Biopathology Lab, Castellon Province Hospital, Ave, Doctor Clara 19, Castellon, 12002, Spain. martinezconrado@yahoo.es
authors.forename: Conrado
authors.initials: C
authors.lastname: Martinez-Cadenas
authors.forename: Nuria
authors.initials: N
authors.lastname: Bosch
authors.forename: Lucas
authors.initials: L
authors.lastname: Peñas
authors.forename: Esther
authors.initials: E
authors.lastname: Flores-Couce
authors.forename: Enrique
authors.initials: E
authors.lastname: Ochoa
authors.forename: Javier
authors.initials: J
authors.lastname: Munárriz
authors.forename: Juan P
authors.initials: JP
authors.lastname: Aracil
authors.forename: Marcos
authors.initials: M
authors.lastname: Tajahuerce
authors.forename: Ramón
authors.initials: R
authors.lastname: Royo
authors.forename: Rafael
authors.initials: R
authors.lastname: Lozoya
authors.forename: Enrique
authors.initials: E
authors.lastname: Boldó
mesh_terms: D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012003:Rectal Fistula / Q000150:complications*
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf