0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Case Report/Case Series |

BRAFV600E Mutation Status of Involuting and Stable Nevi in Dabrafenib Therapy With or Without Trametinib

Phil McClenahan, BSc1; Lynlee L. Lin, BSc1; Jean-Marie Tan, MB, BCh, BAO (hons)1; Ross Flewell-Smith, BCom, BEng1; Helmut Schaider, MD1; Kasturee Jagirdar, MSc1,2; Victoria Atkinson, MBBS, FRACP3; Duncan Lambie, BDSc, MBBS, FRCPA4,5; Tarl W. Prow, BS, MSc, PhD1; Richard A. Sturm, PhD1,2; H. Peter Soyer, MD, FACD1
[+] Author Affiliations
1Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia
2The University of Queensland, Institute for Molecular Biosciences, Brisbane, Queensland, Australia
3Medical Oncology, Princess Alexandra Hospital, Wooloongabba, Queensland, Australia
4The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
5IQ Pathology, Brisbane, Queensland, Australia
JAMA Dermatol. 2014;150(10):1079-1082. doi:10.1001/jamadermatol.2014.436.
Text Size: A A A
Published online

Importance  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.

Observations  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.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Place holder to copy figure label and caption
Figure 1.
Surveillance of Involuting Nevi During BRAFV600E Inhibitor Therapy and Clinical Image of Back

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.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Histopathologic Images and Molecular Sequencing Charts for BRAFV600E Status of 1 Involuting Nevus and 1 Noninvoluting Nevus

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).

Graphic Jump Location

Tables

References

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
JAMAevidence.com

The Rational Clinical Examination
A patient presenting to your office informs you that he is concerned about a mole on his arm....

The Rational Clinical Examination EDUCATION GUIDES
Melanoma

brightcove.createExperiences();