MultipleBRAFWild-Type Melanomas During Dabrafenib Treatment for MetastaticBRAF-Mutant Melanoma

Abstract

Cutaneous malignant tumors are the most frequent adverse events of BRAF inhibitors; therefore, strict dermatologic surveillance in a referral center aided by digital follow-up is mandatory, especially when multiple nevi are present and these drugs are used in an adjuvant setting. In view of our findings, the pathogenesis of the development of new melanomas seems to be different from therapy resistance. Whether paradoxical RAF activation could explain these BRAF wild-type secondary malignant tumors is still unknown.

Beyond the BRAF V 600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients

“…reported the case of a woman who developed metastatic disease during pregnancy. She presented with a melanoma that had a BRAF V600E mutation and was treated with dabrafenib but developed new metastases that were all BRAF wt except one, which harboured a BRAF S467L mutation . Similar findings have been made by Kim et al ., who unsuccessfully treated a patient with the same mutation with vemurafenib .…”

Discriminating Nevi from Melanomas

“…These patients are also at increased risk for developing new primary BRAF wild-type melanomas. 24–26 Although the natural biology of nevi changing under the influence of a BRAF inhibition remains unclear, many of these changing nevi have clinical, dermoscopic, RCM, and histopathology morphologic features that overlap with melanoma. Thus, any changing nevus that has RCM features suggestive of malignancy should be excised.…”

A case of new-onset vitiligo in a patient on tofacitinib and brief review of paradoxical presentations with other novel targeted therapies

“…Cutaneous adverse effects, including malignant neoplasms, are among the most frequently observed toxicities with the selective BRAF inhibitors vemurafenib and dabrafenib [16,17]. The development of new primary melanomas with a wild-type BRAF genotype have been reported in patients receiving treatment with BRAF inhibitors, arising as new pigmented Dermatology Online Journal || Case Report lesions or rapidly evolving, pre-existing melanocytic lesions [18][19][20][21][22][23]. In one study, up to 21% of patients on vemurafenib exhibited changes in their preexisting pigmented nevi that were consistent with melanoma [22].…”