1. The MYD88 mutation was associated with a shorter survival rate in primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT).
2. The MYD88 mutation was positive in 59% of patients with PCLBCL-LT and was associated with older initial presentation and had higher likelihood of leg involvement.
Evidence Rating Level: 2 (Good)
Study Rundown: PCLBCL-LT is an aggressive malignancy of the skin. Recently, a protein that is normally involved in the innate immune system, MYD88, was found to be mutated in approximately 70% of PCLBCL-LTs; however, it was unknown how this mutation affected disease course or survival rate. In this study, authors reviewed data from multiple centers in an effort to identify epidemiological and clinical trends in PCLBCL-LT patients with the MYD88 L265P mutation. An association was demonstrated between the MYD88 mutation and an earlier death, whether as a result of the cancer or a result from a separate cause. Furthermore, patients with the mutation, on average, were older at the time of initial presentation and were more likely to have disease affecting the legs. A strength of this study was the complex statistical analysis of data from a relatively large patient cohort for a less prevalent disease. A weakness of the study was the quality of the samples used in mutation detection; the tissue was fixed in formalin and embedded in paraffin, which may damage the quality of tissue DNA.
In-Depth [retrospective cohort]: Records from the French Study Group for Cutaneous Lymphomas were scanned for individuals diagnosed with PCLBCL-LT between January 1, 1988 and December 31, 2010. 58 patient records with available tumor tissue were identified, DNA was extracted from the samples and PCR-amplification was performed. Of the original 58 patient samples, 34 (59%) were positive for the mutation. Clinical and follow-up data were then stratified based on mutation status and were analyzed using univariate and multivariate models. MYD88 L265P mutation was associated with older age at initial presentation (p = 0.006) and with frequent involvement of the leg (p = 0.008). Furthermore, patients who were positive for the mutation had 3- and 5-year disease-specific survival rates of 65.7% and 60.2% vs 85.4% and 71.7% in patients with wild-type PCLBCL-LT (p = 0.03). Shorter disease-specific survival rates were confirmed through univariate analysis (p =0.03) as well as multivariate analysis (OR 3.01; 95% CI, 1.03-8.78; p = 0.04). These findings may suggest that activation of MYD88 in the nuclear factor-κB pathway may serve as a critical therapeutic target for patients with a positive MYD88 L265P mutation.
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