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JAMA Dermatol. 2014 Nov;150(11):1173-9. doi: 10.1001/jamadermatol.2014.821.

High frequency and clinical prognostic value of MYD88 L265P mutation in primary cutaneous diffuse large B-cell lymphoma, leg-type.

Author information

  • 1Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France2Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
  • 2Equipe 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.
  • 3Unité d'Aide Méthodologique, Hôpital Robert Debré, Reims, France.
  • 4Department of Clinical Research, Hôpital Maison Blanche, Centre Hospitalier Universitaire Reims, Reims, France.
  • 5French Study Group for Cutaneous Lymphomas, France6Department of Pathology, Centre Hospitalier Universitaire Dijon, Dijon, France.
  • 6Equipe 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.
  • 7Tumor Bank and Tumor Biology Laboratory, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
  • 8Equipe d'accueil 2406, Histology and Molecular Pathology of Tumors, Universitaire Bordeaux, Bordeaux, France8Tumor Bank and Tumor Biology Laboratory, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
  • 9Equipe 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.
  • 10French Study Group for Cutaneous Lymphomas, France9Department of Dermatology, Hôpital Robert Debré, Centre Hospitalier Universitaire Reims, Reims, France.

Abstract

IMPORTANCE:

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.

DESIGN, SETTING, AND PARTICIPANTS:

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.

MAIN OUTCOMES AND MEASURES:

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 AND RELEVANCE:

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.

PMID:
25055137
[PubMed - indexed for MEDLINE]
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