Recent advances in targeting BRAFV600E mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes.
A man in his 30s had been monitored with whole-body dermoscopy at roughly 7-month intervals as part of a nevus surveillance study. Fourteen months after his initial visit, metastases were found, and the patient entered a clinical trial of dabrafenib with or without trametinib therapy. Continued dermoscopic monitoring for the next 12 months revealed that approximately 50% of the existing acquired melanocytic nevi involuted, while the remaining nevi did not change. Biopsy findings from 1 unchanged and 1 involuted nevus showed BRAF wild type in the unchanged nevus, BRAFV600E mutation in the involuting nevus, and no malignant histopathologic characteristics in either one.
Conclusions and Relevance
Our observations indicate that a previously suggested hypothesis regarding involuting nevi in BRAF inhibitor therapy is correct: Nevi that involute while a patient is undergoing BRAF V600E inhibitor therapy possess the BRAF V600E mutation, while others that grow or remain unchanged are wild type. However larger-scale trials are required to gather conclusive data and create a more complete clinical picture.
A-C, Three nevi have undergone involution 7 months after initiation of BRAFV600E inhibitor therapy. D and E, The other 2 nevi remain unchanged. Excisional shave biopsies and numerous ex vivo microbiopsies were performed on nevi C and E. Images to the left of the vertical red line were obtained before the patient commenced participation in the BRAF inhibitor trial; images to the right of the line were obtained after he entered the trial. F, Clinical image of the back shows nevi locations: white arrow indicates biopsied involuting nevus; white circles indicate involuting nevi; black arrow indicates biopsied unchanged nevus; black circles indicate unchanged nevi.
A-D, Workup of an involuting nevus. E-H, Workup of a noninvoluting nevus. C and G, Dermoscopic images show microbiopsy sites 1 through 5 (scale bar = 1 mm); site 6 in each panel is a control biopsy site adjacent to the nevus. D and H, Molecular analysis charts for microbiopsy sites shown in panels C and G, respectively. A and E, Histopathologic images of the nevi, neither of which shows any histopathological criteria for melanoma (scale bars = 200 µm; boxes enclose areas shown at higher magnification in panels B and F). The involuted nevus in panel A is a benign, predominantly junctional nevus with few discrete nests of nonpigmented nevus cells at the dermal-epidermal junction; subtle lymphatic infiltration around suprapapillary vascular plexus; and no obvious signs of fibrosis or regression; sequencing (D) reveals that the nevus is heterogeneous for BRAFV600E mutation at sites 1 and 5. The noninvoluted nevus in panel E is a benign lentiginous melanocytic nevus with elongated pigmented rete ridges and slightly increased numbers of melanocytes at the dermal-epidermal junction; small junctional nests of melanocytes are also present; and sequencing (H) reveals no presence of BRAFV600E mutation. B and F, Greater magnifications of the boxed areas of panels A and E, respectively (scale bars = 200 μm).
Thank you for submitting a comment on this article. It will be reviewed by JAMA Dermatology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 1
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.