Concurrent eruptive melanocytic nevi and metastatic melanoma secondary to encorafenib

Résumé fourni par la source

Dear Editors, The term eruptive nevi (EN) refers to the sudden appearance of multiple melanocytic lesions associated with immunosuppressive conditions or pharmacological treatments, such as BRAF inhibitors (BRAFi), which directly stimulate melanocyte proliferation.1 We herein report the first case of EN and synchronous melanomas with concurrent cutaneous melanoma metastasis in a patient with metastatic BRAF-V600E-mutant colorectal cancer. A 58-year-old man was referred to our dermatology unit due to the recent appearance of a reddish-brown solitary papule on his back and multiple erythema nodosum-like lesions (Figures 1, 2). He also reported changes in the size and color of several pre-existing nevi. The patient had previously been diagnosed with metastatic colorectal cancer harboring a BRAF V600E mutation and had undergone treatment with bevacizumab and a FOLFOXIRI regimen (5-fluorouracil, folinic acid, oxaliplatin, and irinotecan). In December 2024, due to disease progression, treatment was switched to encorafenib plus cetuximab.2 Two months after initiating the new treatment, the patient developed multiple new pigmented lesions distributed across the entire body, including the face, scalp, palms, and soles. A comprehensive dermatological evaluation, including total-body dermatoscopy and digital mapping, was performed. The papule on the back was biopsied, revealing a cutaneous melanoma metastasis of BRAF wild-type (WT). Concurrently, three dermatoscopically atypical, pigmented lesions were excised. Histopathological examination revealed two synchronous melanomas – one melanoma in situ and one pT1a melanoma, both BRAF wild-type – and one melanocytic nevus. Following multidisciplinary evaluation, treatment with binimetinib, a mitogen-activated protein kinase (MEK) inhibitor (MEKi), was recommended to modulate aberrant MAPK pathway activation in BRAF wild-type cells. The development of EN and the enlargement and pigmentation changes in pre-existing nevi during BRAFi therapy are due to a paradoxical MAPK pathway upregulation in BRAF WT melanocytes,1 which may lead to dysplastic nevi and melanoma.3, 4 The risk of a second primary melanoma is inherently elevated in patients with a history of melanoma, but this risk significantly increases in the case of BRAFi therapy, reaching an estimated incidence of approximately 21%.5 Encorafenib, a RAF kinase inhibitor, suppresses the MAPK signaling pathway in BRAF-V600E-mutant tumors.1 Reports of benign EN following encorafenib therapy remain rare, with only four cases described in patients receiving encorafenib monotherapy,1, 6-8 one case associated with encorafenib-cetuximab treatment,9 and one case following combination therapy with encorafenib, cetuximab, and binimetinib.10 Moreover, Donati et al. reported a case of multiple primary melanomas in a patient undergoing encorafenib monotherapy for metastatic melanoma.3 Cetuximab, an EGFR inhibitor that targets a tyrosine kinase upstream of the MAPK cascade, has not been independently linked to the development of EN. However, the potential role of EGFR inhibitors in modulating paradoxical MAPK pathway activation remains unclear.5 Although the addition of the MEKi binimetinib to the encorafenib-cetuximab regimen has not demonstrated a significant survival benefit in metastatic colorectal cancer, it may have potential role in modulating EN.4 Indeed, Chen et al. reported a case in which a patient treated with vemurafenib, a BRAFi, developed widespread EN, many of which regressed or faded in color following the introduction of cobimetinib, a MEKi.4 BRAF WT EN and melanomas represent known dermatologic adverse effects of BRAFi therapy, but their occurrence remains extremely rare. Patients on BRAFi therapy who develop EN lacking BRAF V600E expression exhibit a higher propensity for dysplastic nevi and melanoma.1 Therefore, before starting BRAFi, total-body skin examinations with dermatoscopic evaluation are recommended. Regular dermatologic follow-up is recommended, particularly in the event of newly appearing nevi, and the threshold for biopsy should be low due to the increased risk of melanoma. None.

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