O’Hern, Keegan

Context.— Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma. Objective.— To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms. Design.— One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard. Results.— ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth. Conclusions.— With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.

BACKGROUND Mohs micrographic surgery (MMS) is increasingly used to treat cutaneous melanoma. However, it is unclear whether intraoperative immunohistochemistry (IHC) improves surgical outcomes. OBJECTIVE To determine whether intraoperative IHC during MMS and staged excision is associated with a decreased risk of poor surgical outcomes. MATERIALS AND METHODS Search of 6 databases identified comparative and noncomparative studies that reported local recurrence after MMS or staged excision with or without IHC for melanoma. Random-effects meta-analysis was used to estimate pooled local recurrence rates, nodal recurrence, distant recurrence, and disease-specific mortality. RESULTS Overall, 57 studies representing 12,043 patients with cutaneous melanoma and 12,590 tumors met inclusion criteria. Combined MMS and staged excision with IHC was associated with decreased local recurrence in patients with invasive melanoma (0.3%, 95% CI: 0–0.6) versus hematoxylin and eosin alone (1.8%, 95% CI: 0.8%–2.8%) [p < .001]. Secondary outcomes including nodal recurrence, distant recurrence, and disease-specific mortality were not significantly different between these 2 groups. Study heterogeneity was moderately-high. CONCLUSION Local recurrence of invasive melanoma is significantly lower after MMS and staged excision with IHC as opposed to without IHC. These findings suggest that the use of intraoperative IHC during MMS or staged excision should strongly be considered, particularly for invasive melanoma. Trial Registration PROSPERO Identifier: CRD42023435630.

BACKGROUND Although advances have been made in the understanding of recurrence patterns in dermatofibrosarcoma protuberans, the current understanding of disease-specific mortality after surgical management is limited. OBJECTIVE To understand disease-specific mortality rates associated with dermatofibrosarcoma protuberans treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS A systematic literature search was conducted on March 6, 2023, to identify patients treated with MMS or WLE for dermatofibrosarcoma protuberans. RESULTS A total of 136 studies met inclusion criteria. Overall, the disease-specific mortality rate was not significantly different after treatment with MMS (0.7%, confidence interval [CI] 0.1–1.2, p: 0.016) versus WLE (0.9%, CI 0.6–1.2, p < .001). For recurrent tumors, the MMS treatment group had a statistically significantly lower disease-specific mortality rate (1.0%, CI 0.0–2.0, p 0.046) compared with the WLE treatment group (3.5%, CI 2.0–5.1, p < .001). The mean follow-up for all studies was 57.6 months. CONCLUSION AND RELEVANCE The authors' meta-analysis suggests there is no substantial difference in disease-specific mortality between MMS and WLE in patients with dermatofibrosarcoma protuberans, except in the case of recurrent tumors, where MMS seems to confer a survival advantage.