Complete regression of primary melanoma associated with nevi involution under BRAF inhibitors: A case report and review of the literature

Abstract

Melanoma is one of the most immunogenic tumors among human neoplasms, with numerous clinical observations of partial or completely regressed tumors. It is an aggressive tumor, with the greatest reported number of somatic mutations, BRAF mutation being the most common one. BRAF mutation is also present in a higher percentage in benign nevi. Complete regression of primary tumor and involution of nevi are, however, rare phenomenon in melanoma that can appear in relation with UV exposure, surgical trauma, target therapy in melanoma, pregnancy or host immune response to an evolving melanoma tumor. We present the case of a 58-year-old man with a completely regressed metastatic melanoma who developed a second melanoma with concomitant involution of papillomatous nevi under BRAF inhibitors treatment. In reviewed literature we have found 53 cases of completely regressed primary melanomas, neither of them reporting nevi involution. Complete regression of primary tumor can occur as an immune response to tumor progression. Nevi can involute under BRAF inhibitor therapy, but development of new malignant lesions under BRAF inhibitors is linked to BRAF wild-type. Documentation of primary tumor and dynamic changes in nevi highlight the need of a good clinical skin examination and increase the utility of baseline and sequential dermoscopy in melanoma.

In-Depth Characterisation of Real-World Advanced Melanoma Patients Receiving Immunotherapies and/or Targeted Therapies: A Case Series

“…With respect to naevus change in those undergoing immuno- and/or targeted therapies, several case reports have described hypopigmentation of naevi, regression/involution of naevi with and without the halo effect and, in a few cases, appearance of new naevi [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. An Italian study of 11 patients receiving dabrafenib observed the appearance of new naevi in 4/11 patients, and hyperkeratosis/hyperpigmentation in 6/11 patients [ 39 ].…”

“…There was also lesion lightening observed in those receiving anti-PD1 therapies with and without ipilimumab. In some cases, regression of naevi has been observed alongside regression of both primary [ 31 ] and metastatic melanomas [ 33 , 36 , 37 ], and it has been suggested that regression of many naevi may be a prognostic marker, highlighting the importance of including dermatologist follow-up in clinical trials and the real-world setting [ 33 , 35 , 40 ]. Our study supports the above findings, largely showing regressing naevi but also a small number of increasing naevi.…”

Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma

“…On the other hand, fading of nevi, characterized upon dermoscopy by a globular-structureless pattern but not a reticular pattern, is a well-documented phenomenon in patients with melanoma receiving targeted therapy. This phenomenon is the result of involution/apoptosis and oncogene-induced sentence, and it is not due to immune-mediated regression [4,5]. This can be explained by the fact that globular and structureless pattern nevi commonly exhibit BRAF mutations [3] and, accordingly, they undergo senescence during inhibition of the MAP kinase pathway.…”

“…Interestingly, the latter has been associated with recession of the metastatic tumor and prolonged survival, configuring vitiligo as a positive response-predictive biomarker to the treatment [1,2]. Moreover, clinical fading of globular-structureless nevi is often reported in patients receiving BRAF-inhibitors alone or BRAFand MEK-inhibitors, because these categories of nevi frequently exhibit BRAF mutations [3][4][5].…”

Breast Metastasis of a Completely Regressed Cutaneous Melanoma – Case Report and Review of Literature

“…Most of the patients with diabetes mellitus (DM) in childhood suffer from DM type 1 (DMT1) that is of autoimmune etiology [1,2]. This form of diabetes appears after the first 6 months of life, and reaches the highest incidence in the 9-14 years age group, with the rising incidence in the age group before 4 years of age [3]. The persisting hyper-glycemia is due to autoimmune destruction of insulin producing β-cells in the endocrine pancreas leading to insulin deficiency.…”