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Background There is a need to improve prognostic accuracy for patients with cutaneous melanoma (CM). A 31-gene expression profile (31-GEP) test uses the molecular biology of primary tumors to identify individual patient metastatic risk. Objective Develop a nomogram incorporating 31-GEP with relevant clinical factors to improve prognostic accuracy. Methods In an IRB-approved study, 1,124 patients from nine Mohs micrographic surgery centers were prospectively enrolled, treated with Mohs micrographic surgery, and had 31-GEP testing. Data from 684 of those patients with at least one-year follow-up or a metastatic event were included in nomogram development to predict metastatic risk. Results Logistic regression modeling of 31-GEP results and T stage provided the simplest nomogram with the lowest Bayesian information criteria score. Validation in an archival cohort (n=901) demonstrated a significant linear correlation between observed and nomogram-predicted risk of metastasis. The resulting nomogram more accurately predicts the risk for CM metastasis than T stage or 31-GEP alone. Limitations The patient population is representative of Mohs micrographic surgery centers. Sentinel lymph node biopsy was not performed for most patients and could not be used in the nomogram. Conclusions 31-GEP and T stage can be integrated to gain clinically useful prognostic information from data obtained non-invasively.

PURPOSE Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2). Prospective analysis of CM outcomes was performed to test the hypotheses that the 31-GEP provides prognostic value for patients with stage I-III CM, and that patients with stage I-IIA melanoma and class 2 31-GEP results have metastatic risk similar to patients for whom surveillance is recommended. MATERIALS AND METHODS Two multicenter registry studies, INTEGRATE (ClinicalTrials.gov identifier: NCT02355574 ) and EXPAND (ClinicalTrials.gov identifier: NCT02355587 ), were initiated under institutional review board approval, and 323 patients with stage I-III CM and median follow-up time of 3.2 years met inclusion criteria. Primary end points were 3-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS The 31-GEP was significant for RFS, DMFS, and OS in a univariate analysis and was a significant, independent predictor of RFS, DMFS, and OS in a multivariable analysis. GEP class 2 results were significantly associated with lower 3-year RFS, DMFS, and OS in all patients and those with stage I-IIA disease. Patients with stage I-IIA CM and a class 2 result had recurrence, distant metastasis, and death rates similar to patients with stage IIB-III CM. Combining 31-GEP results and AJCC staging enhanced sensitivity over each approach alone. CONCLUSION These data provide a rationale for using the 31-GEP along with AJCC staging, and suggest that patients with stage I-IIA CM and a class 2 31-GEP signature may be candidates for more intense follow-up.

Background A 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. Methods Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS), distant metastasis-free (DMFS), and overall survival (OS). Results Median follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18–87) and median Breslow thickness was 1.2 mm (range 0.2–12.0). Eighty-eight percent (282/322) of cases had stage I/II disease and 74% (237/322) had a SLN biopsy. Seventy-seven percent (248/322) had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p

9519 Background: A 31-GEP test is a validated prognostic tool for predicting the risk of metastasis in CM, classifying patients (pts) as Class 1 (low risk) or Class 2 (high risk). Here we report updated survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in patients for whom the GEP test was part of their clinical care. Methods: Eleven US dermatologic and surgical centers participated using IRB-approved protocols. Participants were CM pts ≥16 years old who had successful 31-GEP test results. Recurrence-free (RFS), distant metastasis-free (DMFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox regression analysis. Results: At data censoring, 340 pts were accrued who had completed at least one follow-up visit. Median age was 58 years (range 18-87), 53.5% were male, median Breslow thickness was 1.2mm (range 0.2-12mm), 18.2% (62/340) were ulcerated, and 11.2% (38/340) had a positive sentinel lymph node (SLN). Median follow-up was 3.2 years for pts without an event. Six percent (16/265) of Class 1 pts had a recurrence compared to 33% (25/75) of Class 2 pts (p < 0.001). Three-year RFS was 96%, 91%, 80%, and 62% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Three-year DMFS was 97%, 93%, 84%, and 80% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Three-year OS was 98%, 90%, 96%, and 74% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Class 2 was an independent predictor of RFS and OS in multivariate analysis (respective HRs: 2.28 and 3.70, p < 0.05). Conclusions: Consistent with results from previous studies, this analysis demonstrates that the GEP test complements conventional staging and improves the ability to identify high-risk CM pts. These results support use of the test for guiding decisions related to follow-up, surveillance, and treatment in CM pts. Clinical trial information: NCT02355574/NCT02355587.

BACKGROUND Residual melanoma and melanoma in situ (MIS), also referred to as marginally recurrent melanoma, continues to be a concern for all dermatologic surgeons. Little is known about the potential of these tumors to recur with a deeper invasive histology measured according to Breslow depth. OBJECTIVE To identify the clinical features and histologic, invasive potential of marginally recurrent melanoma and MIS. By having a more accurate understanding of marginally recurrent melanoma, we can better appreciate the consequence of inadequate excision and recognize the importance of improving initial treatments. MATERIALS AND METHODS An analysis was performed of 108 marginally recurrent melanoma and MIS cases based on prospective data collection. For each case, clinical data, including a comparison of Breslow depth from the time of primary treatment and salvage surgery for marginally recurrent tumor, were tabulated. RESULTS Of the 84 lesions initially treated as MIS, 19 (22.6%) recurred marginally with a histologically invasive component and a mean Breslow depth of 0.94 mm. Of the 24 patients diagnosed with invasive melanoma, eight (33.3%) had a deeper Breslow depth at the time of clinical recurrence than at the time of primary treatment. The change in Breslow depth for these eight cases was 1.53 to 2.83 mm. CONCLUSIONS Our findings demonstrate the invasive growth potential of MIS and invasive melanoma inadequately excised at the time of primary treatment. This finding illustrates the consequences of marginal recurrence and stresses the importance of accurate and complete removal of melanoma at the time of initial diagnosis and treatment.

BACKGROUND High-viscosity 2-octyl cyanoacrylate (HVOCA) is a rapidly polymerizing liquid topical adhesive indicated for epidermal approximation of superficial lacerations and surgical wounds. Use of HVOCA in repair of facial wounds after Mohs micrographic surgery (MMS) has not been reported. OBJECTIVE To compare aesthetic outcome of HVOCA versus sutured epidermal closure of linearly repaired facial wounds following MMS. METHODS Patients undergoing MMS for facial tumors with postoperative wounds >3 cm appropriate for linear closure were recruited. After placement of dermal sutures, half the wound was randomly selected for closure with HVOCA and the other half was closed with 5-0 polypropylene suture. RESULTS Fourteen patients (13 men and 1 woman; mean age, 72±8.8 years; range, 52–81 years) with basal cell or squamous cell carcinoma of the face (n=12) or neck (n=2) were enrolled. The mean wound length was 4.9±1.9 cm (range, 3.1–10 cm). No postoperative complications, including bleeding, infection, or dehiscence, occurred. Using photographs obtained 3 months postoperatively, five dermatologists (including two Mohs surgeons) blinded to the intervention rated cosmesis using a visual analog scale from 1 (worst) to 10 (best). The mean ratings for HVOCA half (6.64±1.55) versus sutured half (6.77±1.88) were not significantly different (p=.35). Paired comparisons of rater preferences similarly showed no cosmetic differences. All 14 patients preferred OCA for ease of postoperative care. CONCLUSION HVOCA tissue adhesive is cosmetically equivalent to epidermal sutures in the linear repair of facial wounds following MMS. This technique represents an additional option for Mohs surgeons.

Although typically presenting renally, angiomyolipomas can rarely present in the skin. The tumors are composed of an admixture of blood vessels, smooth muscle and adipose tissue and are often seen in the setting of tuberous sclerosis. We describe a case of angiomyolipoma presenting on the thigh of a 50-year-old white female. This is the 17th reported case of cutaneous angiomyolipoma. As with all previously described cases, our patient did not present with the stigmata of tuberous sclerosis. Angiomyolipoma should be considered within the differential for subcutaneous nodules and work-up for tuberous sclerosis should not be pursued when presenting in the skin.

Not Available Study supported by Castle Biosciences.

9573 Background: DecisionDx-Melanoma has been validated as an accurate prognosticator of cutaneous melanoma (CM) metastasis risk. The GEP test classifies CM pts as Class 1 (low risk) or Class 2 (high risk). Interim survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in pts for whom the GEP test was performed is described. Methods: Eleven US dermatologic and surgical centers participated in the IRB-approved protocols. Physicians enrolled CM pts who were ≥16 years old and had successful GEP test results. Endpoints of recurrence-free (RFS), distant metastasis-free (DMFS) and melanoma-specific survival (MSS) were assessed using Kaplan-Meier and Cox regression analysis. As an interim analysis at year 3 of an expected 5-year study, the critical alpha level (p-value) was 0.01. Results: At the time of data extraction, 322 pts were accrued and completed at least one follow-up visit. Median age was 58 years (range 18-87), median Breslow thickness (BT) was 1.2mm, 55% were male, 20% (58/296) were ulcerated, and 15% (36/237 biopsied) had a positive sentinel lymph node (SLN). Median follow-up time was 1.5 years for pts without a recurrence. Of 25 recurrent cases, 80% (20/25) were Class 2 and 40% (10/25) were SLN-positive. Two percent of Class 1 pts had a recurrence compared to 6% (12/201 biopsied) of SLN-negative pts. Of the SLN-negative pts who recurred, 75% (9/12) were called Class 2. Combined GEP and SLN risk prediction identified 88% (21/24) of recurrences. Kaplan-Meier event rates for each class are shown in the table. In Cox multivariate analysis, BT and GEP Class 2 were significant predictors of recurrence (p

Over 90 mutant alleles of the alpha-1-antitrypsin (AAT) gene are recognized and classified by mobility on an acid starch gel. The four major categories include: F=fast, M=medium, S=slow, Z=very slow. Among 41 reported cases of AAT panniculitis, most have the ZZ phenotype with AAT levels below normal. We report two cases of AAT panniculitis with MS phenotype and normal AAT levels. In addition, we review the pathophysiology, epidemiology, and extracutaneous manifestations of AAT disease and propose a diagnostic algorithm for ulcerative panniculitis. A 42-year-old man presented with a solitary plaque on the left thigh exacerbated by trauma or excessive activity. The lesion frequently suppurated with a yellowish oily material. Twenty years before, he had fractured his left femur which was repaired with a metal plate. X-rays, histology with special stains for organisms, and cultures were negative. AAT phenotype was MS and AAT value was normal. A 43-year-old woman presented with multiple plaques on the proximal extremities which suppurated with exercise or trauma. AAT phenotype was MS and AAT level was normal. Histologic exam for both patients showed a dense neutrophilic infiltrate with septal and lobular panniculitis and areas of necrobiosis in the lower reticular dermis.