title: High frequency and clinical prognostic value of MYD88 L265P mutation in primary cutaneous diffuse large B-cell lymphoma, leg-type.
abstract: OBJECTIVE
  The activating mutation of MYD88 L265P is a frequent feature of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT), reported in up to 69% of the cases. Whether patients with MYD88 mutation display specific clinical and evolutive features has not been evaluated.
  
  
  OBJECTIVE
  To identify the clinical characteristics associated with MYD88 mutation, confirm its high prevalence, and evaluate its effect on prognosis in patients with PCLBCL-LT.
  
  
  METHODS
  A retrospective multicenter study was conducted using the medical records of patients from dermatology departments belonging to the French Study Group for Cutaneous Lymphomas. Sixty-one patients with a diagnosis of PCLBCL-LT made between 1988 and 2010 who were available for molecular study were included. Of these, 58 patients displaying interpretable results constituted the study group. Median follow-up was 33 months, and 39 patients (67%) were monitored until death.
  
  
  METHODS
  Clinical features (age, sex, number of skin lesions, tumor stage, and location as leg vs elsewhere), MYD88 mutation (allele-specific TaqMan polymerase chain reaction assay), treatment regimen, and outcome were recorded. Baseline characteristics and outcome were compared according to the status of MYD88.
  
  
  RESULTS
  The median age of the patients was 79 years, and 59% were female. Skin lesions were located on the leg in 76% of the cases. Thirty-four of 58 patients (59%) harbored the MYD88 L265P mutation. Patients had similar clinical characteristics at presentation regardless of their MYD88 status, except that those harboring the MYD88 mutation were older (P = .006) and had more frequent involvement of the leg (P = .008). Patients harboring the MYD88 mutation had 3- and 5-year-specific survival rates of 65.7% and 60.2% vs 85.4% and 71.7% in patients with the wild-type allele. The MYD88 mutation was significantly associated with shorter disease-specific survival in univariate (P = .03) and multivariate (odds ratio, 3.01; 95% CI, 1.03-8.78; P = .04) analysis. There was no significant difference between the groups in their treatment regimens. Considering overall survival, in univariate (P = .002) and multivariate (odds ratio, 2.94; 95% CI, 1.18-7.30; P = .02) analysis, MYD88 L265P mutation was an independent adverse prognostic factor.
  
  
  CONCLUSIONS
  This study confirms the high prevalence of MYD88 L265P mutation in PCLBCL-LT and shows its association with shorter survival. The clinical effect of MYD88 mutation activating the nuclear factor-κB pathway supports the use of targeted therapies at the time of relapse after conventional therapies.
authors: Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France2Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
authors: Anne
authors: A
authors: Pham-Ledard
authors: Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France2Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France3French Study Group for Cutaneous Lymphomas, France.
authors: Marie
authors: M
authors: Beylot-Barry
authors: Unité d'Aide Méthodologique, Hôpital Robert Debré, Reims, France.
authors: Coralie
authors: C
authors: Barbe
authors: Department of Clinical Research, Hôpital Maison Blanche, Centre Hospitalier Universitaire Reims, Reims, France.
authors: Marion
authors: M
authors: Leduc
authors: French Study Group for Cutaneous Lymphomas, France6Department of Pathology, Centre Hospitalier Universitaire Dijon, Dijon, France.
authors: Tony
authors: T
authors: Petrella
authors: Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France3French Study Group for Cutaneous Lymphomas, France7Department of Pathology, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
authors: Béatrice
authors: B
authors: Vergier
authors: Tumor Bank and Tumor Biology Laboratory, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
authors: Fabian
authors: F
authors: Martinez
authors: Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France8Tumor Bank and Tumor Biology Laboratory, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
authors: David
authors: D
authors: Cappellen
authors: Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France3French Study Group for Cutaneous Lymphomas, France8Tumor Bank and Tumor Biology Laboratory, Centre Hospitalier Universitaire Bordeaux, Bordeaux, F.
authors: Jean-Philippe
authors: JP
authors: Merlio
authors: French Study Group for Cutaneous Lymphomas, France9Department of Dermatology, Hôpital Robert Debré, Centre Hospitalier Universitaire Reims, Reims, France.
authors: Florent
authors: F
authors: Grange
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007866:Leg; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D015996:Survival Rate
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B