Hair Repigmentation as a Melanoma Warning Sign
Practice Points
- Localized repigmentation of the hair is a rare phenomenon that may indicate underlying melanoma.
- Careful clinicopathologic correlation is necessary to appropriately diagnose and manage this unusual presentation of melanoma.
In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.6 In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.8 If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.6
Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.31,32
The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.3 One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.9 The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.33 There was complete clearing of the lesion as well as the hair pigmentation,9 which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.5
In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.34 Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.
