Melanocytic naevi with globular and reticular dermoscopic patterns display distinct BRAF V600E expression profiles and histopathological patterns.

BACKGROUND: BRAF (v-raf murine sarcoma viral oncogene homologue B) V600E mutations have been detected with high frequency in melanocytic naevi. Few studies have stratified analyses by naevus dermoscopic pattern. OBJECTIVES: To determine the frequency of BRAF V600E expression and histopathological pattern in acquired melanocytic naevi distinguished by a globular vs. reticular dermoscopic pattern. METHODS: We retrospectively identified histologically proven melanocytic naevi with banal reticular or globular dermoscopic patterns and evaluated BRAF V600E expression using immunohistochemistry. RESULTS: BRAF V600E expression was detected in 11 of 12 globular naevi vs. four of 13 reticular naevi (91·7% vs. 30·1%, P = 0·004). A predominantly dermal growth pattern (P < 0·001) and the presence of large junctional nests (P = 0·017) were each associated with a globular dermoscopic pattern. The presence of either a predominantly dermal growth pattern or large junctional nests was found in 13 of 15 naevi positive for BRAF V600E and in two of 10 naevi negative for BRAF V600E (86·7% vs. 20%, P = 0·002). CONCLUSIONS: The frequency of BRAF V600E mutations differs in naevi distinguished by unique dermoscopic structures and microanatomical growth patterns. Globular naevi, which most often histologically correspond to a predominantly dermal growth pattern and/or the presence of large junctional nests, are significantly more likely to express BRAF V600E than reticular naevi. These preliminary results require validation, but may directly inform future studies of naevogenesis and melanoma genesis.

Evaluation of an immunoturbidimetric assay of serum digoxin without sample pretreatment.

We have evaluated a new turbidimetric immunoassay test (On Line, Roche) for the quantification of digoxin in human serum without sample pretreatment. The assay, automated on a Cobas-Mira clinical analyser, is based on the measurement of the changes in absorbance that occur when digoxin-coated microparticles aggregate with digoxin antibody; the aggregation reaction is partially inhibited by digoxin in the sample. The calibration curve extends up to 6.4 nmol/l, with a wide measuring range, and was stable at least for 10 days during the studied period. The intra- and inter-assay coefficients of variation were in all cases lower than 7%. The detection limit of the assay was 0.256 nmol/l and the linearity, assessed by measuring serial dilutions of poisoned patient sera, showed correlation coefficients higher than 0.998. There is no interference from bilirubin (up to 340 mumol/l) or haemoglobin (up to 7900 mg/l), although a positive interference by lipids was found, which can be avoided by previous delipidation of these sera. No digoxin-like factors were identified affecting digoxin values in a concentration higher than that of the sensitivity of the assay in samples of premature infants, pregnant women, or patients with renal or hepatic failure. Correlation coefficients between the turbidimetric assay and two immunoassays (fluorescence polarization and RIA) were 0.983 and 0.955 respectively, calculated from the assay of 102 and 98 samples. Nevertheless the values obtained by the evaluated assay were proportionally 20% higher, a fact probably related to differences in calibrators.