The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma—a distinct type of melanoma with a unique genetic background—has not fully been investigated. We conducted a retrospective review of our acral melanoma patients. Of the 196 patients with acral melanoma, we retrieved 31 pairs of primary and matched metastatic melanomas. We immunostained the 31 pairs with VE1, a BRAFV600E-mutation-specific monoclonal antibody. Immunohistochemistry with VE1 showed a high degree of sensitivity and specificity for detecting BRAFV600E mutations compared with the real-time polymerase chain reaction method. A total of nine primary (29.0%) and eight metastatic (25.8%) acral melanomas were positive for VE1. In three patients (9.7%), we observed a discordance of VE1 staining between the primary and metastatic lesions. Of note, VE1 immunohistochemical staining revealed a remarkable degree of intra-tumor genetic heterogeneity in acral melanoma. Our study reveals that VE1 immunostaining is a useful ancillary method for detecting BRAFV600E mutations in acral melanoma and allows for a clear visualization of intra- and inter-tumor BRAF heterogeneity.

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In this retrospective review of 100 patients with primary invasive acral melanoma, we examined whether narrow-margin excision is warranted for acral melanoma. Patients treated with surgical margins recommended by the National Comprehensive Cancer Network (R-group) were compared to those treated with narrow margins (N-group). A total of 65 patients underwent narrow-margin excision. Positive margin status or local recurrence rarely occurred regardless of the excision margins, whereas fatal events frequently occurred, particularly among the patients with T4 melanoma. The mortality rates of N- and R-group with T1–3 melanomas were similar (1.36 and 1.28 per 100 person-years, respectively). However, patients with T4 melanoma treated with narrow-margin excision had a higher mortality rate (11.44 vs. 5.03 per 100 person-years). Kaplan–Meier analyses showed a worse prognosis in the N-group (p = 0.045) but this group had thicker Breslow thickness (4.21 mm vs. 2.03 mm, p = 0.0013). A multivariate analysis showed that Breslow thickness was an independent risk factor, but surgical margin was not a risk factor for melanoma-specific survival or disease-free survival. In conclusion, although we could not find a difference between the narrow-margin excision and recommended-margin excision in this study, we suggest following current recommendations of guidelines. Our study warrants the prospective collection of data on acral melanoma to better define the prognosis of this infrequent type of melanoma.

The efficacy of preoperative imaging for acral melanoma (AM) has not been fully evaluated. We examined the accuracy of imaging modalities in the detection of nodal and distant metastases in patients with AM. A retrospective review of 109 patients with AM was performed. All patients had no clinical signs suggestive of distant metastases, and underwent preoperative screening computed tomography (CT) and positron emission tomography (PET)/CT scans. Of 100 patients without lymphadenopathy, 17 patients were suspected of having nodal metastasis in CT and PET/CT, but only two of them were confirmed on histopathological analysis. On the other hand, 12 out of 83 negatively imaged patients showed histopathological signs of nodal metastasis; thus, the sensitivity and specificity of nodal detection were 14.3% and 82.6%, respectively. Regard to the detection of distant metastases, four patients were suspected of having metastasis, but this was later ruled out. The remaining 96 negatively imaged patients were confirmed to have no metastasis at the time of CT and PET/CT by the follow-up. In contrast, distant metastases were found by CT and PET/CT in four of nine patients (44.4%) with lymphadenopathy. Routine preoperative CT and PET/CT for AM patients without lymphadenopathy may not be warranted because of low sensitivity and specificity, but it can be considered for those with lymphadenopathy.

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