Predictors of BRAF mutation in melanocytic nevi: analysis across regions with different UV radiation exposure.

BACKGROUND: BRAF mutations have been implicated in initiating promutagenic cellular melanocytic proliferation mostly based on homogeneous Western-based cohorts. Data addressing the possible interaction between exposure to different solar ultraviolet radiation (UVR) magnitudes and BRAF mutation rate (BMR) in melanocytic nevi are limited. DESIGN: Extended BRAF testing for 9 mutations in 225 melanocytic nevus (MN) cases derived from 211 patients from 4 different UVR regions: Lebanon (n = 95; 110 kJ · m(-2) · yr), Syria (n = 23; 93.5 kJ · m(-2) · yr), Kingdom of Saudi Arabia (n = 70; 139 kJ · m(-2) · yr), and Pakistan (n = 37; 118 kJ · m(-2) · yr) was performed. Data collected included age, gender, anatomic location, and lesion size. Histological parameters recorded were MN type (junctional, compound, intradermal, classical blue, cellular blue, compound and intradermal spitz, and congenital) solar elastosis grade, and nevus pigmentation degree. Cumulative 21-year erythemally effective UV averages were derived from The National Center for Atmospheric Research. RESULTS: BRAF mutation status was obtained in 210 cases (6.7% failed polymerase chain reaction). Overall, BMR was 62.4% (131/210) with V600E mutation accounting for 98.5% of cases. Discordant mutation status was found in 2 of 10 patients with multiple nevi. BMR differed significantly, yet nonsystematically, among UVR regions; the highest was detected in nevi coming from Syria (18/23 cases, 78%), followed by Pakistan (21/30 cases, 70%), Kingdom of Saudi Arabia (47/70 cases, 67%), and Lebanon (45/87 cases, 52%). Mutation rates varied significantly across MN type (P < 0.001); the highest rate was recorded in the intradermal nevus type (33/39 cases, 84.6%), followed by the compound (26/32 cases, 81.2%) and congenital (60/74 cases 81.0%) nevi. Stratified by anatomic location, nevi occurring on the face (61/82, 74%) and trunk (58/78, 74%) had more frequent BMRs compared with those occurring on the upper (7/26, 27%) and lower extremities (5/24, 21%, P < 0.001). Severe pigmentation was less frequent in BRAF mutation-positive nevi [5/131 (4%) vs. 34/79 (43%); P < 0.001]. Multivariate independent predictors of BRAF mutation in MN were age [odds ratio (95% confidence interval ) = 1.43 (1.13-1.74) per 10 years; P = 0.004], anatomic location [P = 0.043 overall], and nevus type [P < 0.001 overall]. UVR region was not an independent predictor of BRAF mutation. CONCLUSIONS: Increased BRAF mutation with age along with the lack of a UVR magnitude-BRAF mutation association suggests that duration of exposure rather than UVR exposure dose is the more likely link to acquiring the mutation.

Cutaneous leishmaniasis: an evolving disease with ancient roots.

BACKGROUND: Cutaneous leishmaniasis (CL) remains a prioritized neglected tropical disease. CL novel presentations call for updating its features. METHODS: A multiregional cohort of 396 patients with confirmed CL was reviewed. Lesion's clinical stage and eruption type were assigned. Disease was considered as extensive if numerous (≥5), large (>3 cm), disfiguring, threatening vital sensory organs, and/or older than 12 months. Microscopically, Ackerman's inflammatory pattern, Ridley's pattern (RP), and parasitic index (PI) were recorded. Microscopic variables pertaining to the organisms, epidermis, and host's inflammatory response were also assessed. All cases were confirmed and speciated molecularly. RESULTS: In our region, 71.8% of cases showed extensive disease with 15.7% exceeding 12 months duration. Leishmania tropica accounted for 91.3% of cases while Leishmania major constituted 8.7% and presented solely as dry lesions. The dominant inflammatory composite consisted of plasma cells, lymphocytes, and histiocytes. Granulomatous inflammation was present in 55.5%. Most cases showed interface changes (72.7%), spongiosis (75.3%), and marked epidermal hyperplasia (63.9%). Transepidermal elimination of organisms was present in 29.2% of cases. None of traditional classification patterns (clinical stage, microscopic pattern, and RP) showed the predicted linear correlation with lesion age. High and low PI levels correlated with early and healing microscopic patterns, respectively, but did not correlate with the corresponding RPs. PI was bimodal with peaks at 3-6 and 9-12 months. CONCLUSION: Cutaneous leishmaniasis is an evolving disease defying the traditional prediction classifications. Our study sets the ground for adopting updated clinical courses, microscopic presentation, and species mapping.