Key clinical point: The addition of gemtuzumab ozogamycin (GO) to standard chemotherapy (SC) did not improve survival in younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk (IR) cytogenetics but was associated with significantly higher toxicities.

Major finding: During a median follow-up of 35 months, event-free survival (hazard ratio [HR], 1.35; P = .116) and overall survival (HR, 1.35; P = .146) were not different in patients receiving GO+SC vs. SC alone. Duration of neutropenia (P = .03) and thrombopenia (P less than .001) and grade 3/4 liver toxicities (P = .03) were significantly higher in patients receiving GO vs. SC alone.

Study details: Phase 3 AML 2006-IR trial included 238 younger patients (age, 18-60 years) with de novo AML and IR cytogenetics randomly assigned to receive cytarabine and daunorubicin with or without GO. GO arm was prematurely closed after 254 inclusions because of toxicity and early deaths.

Disclosures: This study was supported by the French government PHRC 2006 and PFIZER group. Some investigators reported being on advisory boards, receiving research and travel funding, honoraria, and personal fees from various pharmaceutical companies, including Pfizer.

Source: Bouvier A et al. Eur J Haematol. 2021 Mar 25. doi: 10.1111/ejh.13626.

Key clinical point: The addition of gemtuzumab ozogamycin (GO) to standard chemotherapy (SC) did not improve survival in younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk (IR) cytogenetics but was associated with significantly higher toxicities.

Major finding: During a median follow-up of 35 months, event-free survival (hazard ratio [HR], 1.35; P = .116) and overall survival (HR, 1.35; P = .146) were not different in patients receiving GO+SC vs. SC alone. Duration of neutropenia (P = .03) and thrombopenia (P less than .001) and grade 3/4 liver toxicities (P = .03) were significantly higher in patients receiving GO vs. SC alone.

Study details: Phase 3 AML 2006-IR trial included 238 younger patients (age, 18-60 years) with de novo AML and IR cytogenetics randomly assigned to receive cytarabine and daunorubicin with or without GO. GO arm was prematurely closed after 254 inclusions because of toxicity and early deaths.

Disclosures: This study was supported by the French government PHRC 2006 and PFIZER group. Some investigators reported being on advisory boards, receiving research and travel funding, honoraria, and personal fees from various pharmaceutical companies, including Pfizer.

Source: Bouvier A et al. Eur J Haematol. 2021 Mar 25. doi: 10.1111/ejh.13626.

Key clinical point: The addition of gemtuzumab ozogamycin (GO) to standard chemotherapy (SC) did not improve survival in younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk (IR) cytogenetics but was associated with significantly higher toxicities.

Major finding: During a median follow-up of 35 months, event-free survival (hazard ratio [HR], 1.35; P = .116) and overall survival (HR, 1.35; P = .146) were not different in patients receiving GO+SC vs. SC alone. Duration of neutropenia (P = .03) and thrombopenia (P less than .001) and grade 3/4 liver toxicities (P = .03) were significantly higher in patients receiving GO vs. SC alone.

Study details: Phase 3 AML 2006-IR trial included 238 younger patients (age, 18-60 years) with de novo AML and IR cytogenetics randomly assigned to receive cytarabine and daunorubicin with or without GO. GO arm was prematurely closed after 254 inclusions because of toxicity and early deaths.

Disclosures: This study was supported by the French government PHRC 2006 and PFIZER group. Some investigators reported being on advisory boards, receiving research and travel funding, honoraria, and personal fees from various pharmaceutical companies, including Pfizer.

Source: Bouvier A et al. Eur J Haematol. 2021 Mar 25. doi: 10.1111/ejh.13626.

Key clinical point: In patients with acute myeloid leukemia (AML), incomplete count recovery (CRi) or presence of measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (allo-HCT) was associated with inferior posttransplant outcomes vs. those in complete remission (CR) or without MRD.

Major finding: Patients in CRi vs. CR were at a higher risk for death (hazard ratio [HR], 1.27; P less than .001) and nonrelapse mortality (HR, 1.33; P = .002). Additionally, presence vs. absence of MRD was associated with shorter overall survival (HR, 1.52; P less than .001) and increased relapse (HR, 1.78; P less than .001).

Study details: This observational study included 2,492 adult patients with AML (CR, n=1,799; CRi, n=693) from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry, who underwent first allo-HCT between 2007 and 2015.

Disclosures: CIBMTR is primarily supported by the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research. The lead author had no disclosures. Some coinvestigators reported ties with various pharmaceutical companies.

Source: Percival ME et al. Bone Marrow Transplant. 2021 Apr 16. doi: 10.1038/s41409-021-01261-6.

Key clinical point: In patients with acute myeloid leukemia (AML), incomplete count recovery (CRi) or presence of measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (allo-HCT) was associated with inferior posttransplant outcomes vs. those in complete remission (CR) or without MRD.

Major finding: Patients in CRi vs. CR were at a higher risk for death (hazard ratio [HR], 1.27; P less than .001) and nonrelapse mortality (HR, 1.33; P = .002). Additionally, presence vs. absence of MRD was associated with shorter overall survival (HR, 1.52; P less than .001) and increased relapse (HR, 1.78; P less than .001).

Study details: This observational study included 2,492 adult patients with AML (CR, n=1,799; CRi, n=693) from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry, who underwent first allo-HCT between 2007 and 2015.

Disclosures: CIBMTR is primarily supported by the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research. The lead author had no disclosures. Some coinvestigators reported ties with various pharmaceutical companies.

Source: Percival ME et al. Bone Marrow Transplant. 2021 Apr 16. doi: 10.1038/s41409-021-01261-6.

Key clinical point: In patients with acute myeloid leukemia (AML), incomplete count recovery (CRi) or presence of measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (allo-HCT) was associated with inferior posttransplant outcomes vs. those in complete remission (CR) or without MRD.

Major finding: Patients in CRi vs. CR were at a higher risk for death (hazard ratio [HR], 1.27; P less than .001) and nonrelapse mortality (HR, 1.33; P = .002). Additionally, presence vs. absence of MRD was associated with shorter overall survival (HR, 1.52; P less than .001) and increased relapse (HR, 1.78; P less than .001).

Study details: This observational study included 2,492 adult patients with AML (CR, n=1,799; CRi, n=693) from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry, who underwent first allo-HCT between 2007 and 2015.

Disclosures: CIBMTR is primarily supported by the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research. The lead author had no disclosures. Some coinvestigators reported ties with various pharmaceutical companies.

Source: Percival ME et al. Bone Marrow Transplant. 2021 Apr 16. doi: 10.1038/s41409-021-01261-6.

Key clinical point: Prior treatment with gemtuzumab ozogamicin (GO) before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with acute myeloid leukemia (AML) increased risk for veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) but did not affect survival.

Major finding: Compared with nonexposure, exposure to GO was associated with increased risk for VOD/SOS at 100 days (odds ratio, 2.26; P = .004). However, posttransplant overall survival (P = .43), disease-free survival (P = .20), relapse (P = .32), and nonrelapse mortality (P = .51) did not differ in patients with or without prior GO treatment.

Study details: Findings are from retrospective assessment of pediatric patients with AML who received myeloablative allo-HCT between 2008 and 2011 with (n=148) or without (n=348) prior GO treatment.

Disclosures: This study was funded by Pfizer. D Chirnomas, CJ Hoang, and FR Loberiza Jr declared being current/former employees of and/or had equity ownership in Pfizer. Other authors declared no conflicts of interest.

Source: Duncan C et al. Pediatr Blood Cancer. 2021 Apr 19. doi: 10.1002/pbc.29067.

Key clinical point: Prior treatment with gemtuzumab ozogamicin (GO) before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with acute myeloid leukemia (AML) increased risk for veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) but did not affect survival.

Major finding: Compared with nonexposure, exposure to GO was associated with increased risk for VOD/SOS at 100 days (odds ratio, 2.26; P = .004). However, posttransplant overall survival (P = .43), disease-free survival (P = .20), relapse (P = .32), and nonrelapse mortality (P = .51) did not differ in patients with or without prior GO treatment.

Study details: Findings are from retrospective assessment of pediatric patients with AML who received myeloablative allo-HCT between 2008 and 2011 with (n=148) or without (n=348) prior GO treatment.

Disclosures: This study was funded by Pfizer. D Chirnomas, CJ Hoang, and FR Loberiza Jr declared being current/former employees of and/or had equity ownership in Pfizer. Other authors declared no conflicts of interest.

Source: Duncan C et al. Pediatr Blood Cancer. 2021 Apr 19. doi: 10.1002/pbc.29067.

Key clinical point: Prior treatment with gemtuzumab ozogamicin (GO) before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with acute myeloid leukemia (AML) increased risk for veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) but did not affect survival.

Major finding: Compared with nonexposure, exposure to GO was associated with increased risk for VOD/SOS at 100 days (odds ratio, 2.26; P = .004). However, posttransplant overall survival (P = .43), disease-free survival (P = .20), relapse (P = .32), and nonrelapse mortality (P = .51) did not differ in patients with or without prior GO treatment.

Study details: Findings are from retrospective assessment of pediatric patients with AML who received myeloablative allo-HCT between 2008 and 2011 with (n=148) or without (n=348) prior GO treatment.

Disclosures: This study was funded by Pfizer. D Chirnomas, CJ Hoang, and FR Loberiza Jr declared being current/former employees of and/or had equity ownership in Pfizer. Other authors declared no conflicts of interest.

Source: Duncan C et al. Pediatr Blood Cancer. 2021 Apr 19. doi: 10.1002/pbc.29067.

Key clinical point: Survival outcomes have improved significantly in patients with de novo acute myeloid leukemia (AML) over a 4-decade period from 1980 to 2017; however, least improvement was observed in patients aged 70 years or older.

Major finding: Overall, 5-year survival increased from 9% during 1980-1989 to 15% in 1990-1999, 22% in 2000-2009, and 28% in 2010-2017 (all P less than .001). However, improvement in 5-year survival was poorest in patients aged 70 years or older with 1% in 1980-1989 to 5% in 2010-2017.

Study details: Findings are from a U.S. population-based study that evaluated 29,107 patients from the Surveillance, Epidemiology, and End Results registries, who were diagnosed with de novo AML between 1980 and 2017.

Disclosures: No funding source was identified. Some investigators including the lead author reported personal fees, research funding, honoraria, or other support from various pharmaceutical companies.

Source: Sasaki K et al. Cancer. 2021 Apr 5. doi: 10.1002/cncr.33458.

Key clinical point: Survival outcomes have improved significantly in patients with de novo acute myeloid leukemia (AML) over a 4-decade period from 1980 to 2017; however, least improvement was observed in patients aged 70 years or older.

Major finding: Overall, 5-year survival increased from 9% during 1980-1989 to 15% in 1990-1999, 22% in 2000-2009, and 28% in 2010-2017 (all P less than .001). However, improvement in 5-year survival was poorest in patients aged 70 years or older with 1% in 1980-1989 to 5% in 2010-2017.

Study details: Findings are from a U.S. population-based study that evaluated 29,107 patients from the Surveillance, Epidemiology, and End Results registries, who were diagnosed with de novo AML between 1980 and 2017.

Disclosures: No funding source was identified. Some investigators including the lead author reported personal fees, research funding, honoraria, or other support from various pharmaceutical companies.

Source: Sasaki K et al. Cancer. 2021 Apr 5. doi: 10.1002/cncr.33458.

Key clinical point: Survival outcomes have improved significantly in patients with de novo acute myeloid leukemia (AML) over a 4-decade period from 1980 to 2017; however, least improvement was observed in patients aged 70 years or older.

Major finding: Overall, 5-year survival increased from 9% during 1980-1989 to 15% in 1990-1999, 22% in 2000-2009, and 28% in 2010-2017 (all P less than .001). However, improvement in 5-year survival was poorest in patients aged 70 years or older with 1% in 1980-1989 to 5% in 2010-2017.

Study details: Findings are from a U.S. population-based study that evaluated 29,107 patients from the Surveillance, Epidemiology, and End Results registries, who were diagnosed with de novo AML between 1980 and 2017.

Disclosures: No funding source was identified. Some investigators including the lead author reported personal fees, research funding, honoraria, or other support from various pharmaceutical companies.

Source: Sasaki K et al. Cancer. 2021 Apr 5. doi: 10.1002/cncr.33458.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

According to National Institutes of Health estimates, more than 90,000 new cases of melanoma were diagnosed in 2018.¹ Overall 5-year survival for patients with melanoma exceeds 90%, but individual survival estimates are highly dependent on stage at diagnosis, and survival decreases markedly with metastasis. Therefore, early and accurate diagnosis is critical.

Diagnosis of melanocytic neoplasms usually is performed by dermatopathologists through microscopic examination of stained tissue biopsy sections, a technically simple and effective method that enables a definitive diagnosis of benign nevus or malignant melanoma to be made in most cases. However, approximately 15% of all biopsied melanocytic lesions will exhibit some degree of histopathologic ambiguity,^2-4 meaning that some of their microscopic features will be characteristic of a benign nevus while others will suggest the possibility of malignant melanoma. Diagnostic interpretations often vary in these cases, even among experts, and a definitive diagnosis of benign or malignant may be difficult to achieve by microscopy alone.^2-4 Because of the marked reduction in survival once a melanoma has metastasized, these diagnostically ambiguous lesions often are treated as possible malignant melanomas with complete surgical excision (or re-excision). However, some experts suggest that many histopathologically ambiguous melanocytic neoplasms are, in fact, benign,⁵ a notion supported by epidemiologic evidence.^6,7 Therefore, excision of many ambiguous melanocytic neoplasms might be avoided if definitive diagnosis could be achieved.

A gene expression signature was developed and validated for use as an adjunct to traditional methods of differentiating malignant melanocytic neoplasms from their benign counterparts.^8-11 This test quantifies the RNA transcripts produced by 14 genes known to be overexpressed in malignant melanomas by comparison to benign nevi. These values are then combined algorithmically with measurements of 9 reference genes to produce an objective numerical score that is classified as benign, malignant, or indeterminate. When used by board-certified dermatopathologists and dermatologists confronting ambiguous melanocytic lesions, the test produces substantial increases in definitive diagnoses and prompts changes in treatment recommendations.^12,13 However, the long-term consequences of foregoing surgical excision of melanocytic neoplasms that are diagnostically ambiguous but classified as benign by this test have not yet been formally assessed. In the current study, prospectively tested patients whose ambiguous melanocytic neoplasms were classified as benign by the gene expression signature were followed for up to 4.5 years to evaluate the long-term safety of treatment decisions aligned with benign test results.

Methods

Study Population
As part of a prior study,¹² US-based dermatopathologists submitted tissue sections from biopsied melanocytic neoplasms determined to be diagnostically ambiguous by histopathology for analysis with the gene expression signature (Myriad Genetics, Inc). Diagnostically ambiguous lesions were those lesions that were described as ambiguous, uncertain, equivocal, indeterminate, or other synonymous terms by the submitting dermatopathologist and therefore lacked a confident diagnosis of benign or malignant prior to testing. Patients initially were tested between May 2014 and August 2014, with samples submitted through a prospective clinical experience study designed to assess the impact of the test on diagnosis and treatment decisions. This study was performed under an institutional review board waiver of consent (Quorum #33403/1).

Patients were eligible for inclusion in the current study if their biopsy specimens (1) had an uncertain preliminary diagnosis according to the submitting dermatopathologist (pretest diagnosis of indeterminate); (2) received a negative (benign) score from the gene expression test; (3) were treated as benign by the dermatologist(s) involved in follow-up care; and (4) were submitted by a single site (St. Joseph Medical Center, Houston, Texas). Although a single dermatopathology site was used for this study, multiple dermatologists were involved in the final treatment of these patients. Patients with benign scores who received additional intervention were excluded, as they may have a lower rate of adverse events (ie, metastasis) than those who did not receive intervention and would therefore skew the analysis population. A total of 25 patients from the prior study met these inclusion criteria. The previously collected¹² pretest and posttest de-identified data were compiled from the commercial laboratory databases, and the patients were followed from the time of testing via medical record review performed by the dermatology providers at participating sites. Clinical follow-up data were collected using study-specific case report forms (CRFs) that captured the following: (1) the dates and results of clinical follow-up visits; (2) the type(s) of treatment and interventions (if any) performed at those visits; (3) the specific indication for any intervention performed; (4) any evidence of persistent, locally recurrent, and/or distant melanocytic neoplasia (whether definitively attributable to the tested lesion or not); and (5) death from any cause. The CRF assigned interventions to 1 of 5 categories: excision, excision with sentinel lymph node biopsy, referral to dermatologic or other surgeon, examination only (without surgical intervention), and other. Selection of other required a free-text description of the treatment and indications. Pertinent information not otherwise captured by the CRF also was recordable as free text.

Gene Expression Testing
Gene expression testing was carried out at the time of specimen submission in the prior study¹² as described previously.¹⁴ Briefly, formalin-fixed, paraffin-embedded, unstained tissue sections and/or tissue blocks were submitted for testing along with a single hematoxylin and eosin–stained slide used to identify and designate the representative portion(s) of the lesion to be tested. These areas were macrodissected from unstained tissue sections and pooled for RNA extraction. Expression of 14 biomarker genes and 9 reference genes was measured via quantitative reverse transcription–polymerase chain reaction, performed in triplicate for each individual gene. The assay score was generated through application of a weighted algorithm to the expression values generated through quantitative reverse transcription–polymerase chain reaction. Scores were plotted on a scale ranging from −16.7 to 11.1, with scores from 0.0 to 11.1 classified as malignant, scores from −16.7 to −2.1 as benign, and scores from −2.1 to −0.1 as indeterminate.

Statistical Analysis
Demographic and other baseline characteristics of the patient population were summarized. Follow-up time was calculated as the interval between the date a patient’s gene expression test result was first issued to the provider and the date of the patient’s last recorded visit during the study period. All patient dermatology office visits within the designated follow-up period were documented, with a nonstandard number of visits and follow-up time across all study patients. Statistical analyses were conducted using SAS software (SAS Institute Inc), R software version 3.5.0 (R Foundation for Statistical Computing), and IBM SPSS Statistics software (IBM SPSS Statistics for Windows, Version 25).

Results

Patient Sample
A total of 25 ambiguous melanocytic neoplasms from 25 patients met the study inclusion criteria of a benign gene expression result with subsequent treatment as a benign neoplasm during follow-up. The patient sample statistics are summarized in Table 1. Most patients were younger than 65 years, with an average age at the time of biopsy of 48.4 years. All 25 neoplasms produced negative (benign) gene expression signature scores, all were diagnosed as benign nevi posttest by the submitting dermatopathologist, and all patients were initially treated in accordance with the benign diagnosis by the dermatologist(s) involved in clinical follow-up care. Prior to testing with the gene expression signature, most of these histopathologically indeterminate lesions received differential diagnoses, the most common of which were dysplastic nevus (84%), melanoma arising from a nevus (72%), and superficial spreading melanoma (64%; eTable). After testing with the gene expression signature and receiving a benign score, most lesions received a single differential diagnosis of dysplastic nevus (88%).

Follow-up and Survival
Clinical follow-up time ranged from 0.6 to 53.3 months, with a mean duration (SD) of 38.5 (16.6) months, and patients attended an average of 4 postbiopsy dermatology appointments (mean [SD], 4.6 [3.6]). According to the participating dermatology care providers, none of the 25 patients developed any indication during follow-up that the diagnosis of benign nevus was inaccurate. No patient had evidence of locally recurrent or metastatic melanoma, and none died during the study period.

Treatment/Interventions
The treatment recorded in the CRF was examination only for 21 of 25 patients, excision for 3, and other for 1 (Table 2). Because the explanation for the selection of other in this case described an excision performed at the same anatomic location as the biopsy, this treatment also was considered an excision for purposes of the study analyses. The 3 excisions all occurred at the first postbiopsy dermatology encounter. Across all follow-up visits, no additional surgical interventions occurred (Table 2).

The third excision (case 3) involved a 32-year-old woman with a pigmented lesion on the abdomen (Table 3; Figure, E and F). The clinical description was irregular-appearing black papule, nevus with atypia, and the histopathologic differential diagnosis again included dysplastic nevus, superficial spreading melanoma, and melanoma arising within a preexisting nevus. The gene expression signature result was benign (score, −7.2), and the final diagnosis issued within the accompanying pathology report was nevus with moderate junctional dysplasia. Despite the benign diagnosis, excision was performed 89 days after test result availability, with apparent residual pigmentation as the specified indication. As with the other 2 cases, the treating dermatologist confirmed that neither clinical features nor follow-up events suggested malignancy.

Comment

This study followed a cohort of 25 patients with histopathologically ambiguous melanocytic neoplasms that were classified as benign by a diagnostic gene expression test with the intent of determining the outcomes of patients whose treatment aligned with their benign test result. All patients initially were managed according to their test result. During an average posttest clinical follow-up time of more than 3 years (38.5 months), the 25 biopsied lesions, most of which received a differential diagnosis of dysplastic nevus, were regarded as benign nevi by their dermatologists, and the vast majority (88%) received no further surgical intervention. Three patients underwent subsequent excision of the biopsied lesion, with patient or physician preference as the indication in each instance. None of the 25 patients developed evidence of local recurrence, metastasis, or other findings that prompted doubt of the benign diagnosis. The absence of adverse events during clinical follow-up, particularly given that most lesions were not subjected to further intervention, supports use of the gene expression test as a safe and effective adjunct to the diagnosis and treatment of ambiguous melanocytic neoplasms by dermatologists and dermatopathologists.

Ambiguous melanocytic neoplasms evaluated without the aid of molecular adjuncts often result in equivocal or less-than-definitive diagnoses, and further surgical intervention is commonly undertaken to mitigate against the possibility of a missed melanoma.¹³ In this study, treatment that was aligned with the benign test result allowed most patients to avoid further surgical intervention, which suggests that adjunctive use of the gene signature can contribute to reductions in the physical and economic burdens imposed by unnecessary surgical interventions.^15,16 Moreover, any means of increasing accurate and definitive diagnoses may produce an immediate impact on health outcomes by reducing the anxiety that uncertainty often provokes in patients and health care providers alike.

Study Limitations
This study must be interpreted within the context of its limitations. Obtaining meaningful patient outcome data is a common challenge in health care research due to the requisite length of follow-up and sometimes the lack of definitive evidence of adverse events. This is particularly difficult for melanocytic neoplasms because of an apparent inclination for patients with benign diagnoses to abandon follow-up and an increasing tendency for even minimal diagnostic uncertainty to prompt complete excision. Additionally, the only definitive clinical outcome for melanocytic neoplasms is distant metastasis, which (fortunately for patients) is relatively rare. Not surprisingly, studies documenting clinical outcomes of patients with ambiguous melanocytic neoplasms tested prospectively with diagnostic adjuncts are scarce, and this study’s sample size and clinical follow-up compare favorably with the few that exist.^17,18 Although most melanomas declare themselves through recurrence or metastasis within several years of initial biopsy,^1,19 some are clinically dormant for as long as 10 years after initial detection.^20,21 This may be particularly true for the small or early-stage lesions that now comprise the majority of biopsied neoplasms, and such events would go undetected by this study and many others. It also must be recognized that uneventful follow-up, regardless of duration, cannot prove that a biopsied melanocytic neoplasm was benign. Although only 5 patients had a follow-up time of less than 2 years (the time frame in which most recurrence or metastasis will occur), it cannot be definitively proven that a minimum of 2 years recurrence- or metastasis-free survival indicates a benign lesion. Many early-stage malignant melanomas are eradicated by complete excision or even by the initial biopsy if margins are uninvolved.

Because these limitations are intrinsic to melanocytic neoplasms and current management strategies, they pertain to all investigations seeking insights into biological potential through clinical outcomes. Similarly, all current diagnostic tools and procedures have the potential for sampling error, including histopathology. The rarity of adverse outcomes (recurrence and metastasis) in patients with benign test results within this cohort indicates that false-negative results are uncommon, which is further evidenced by a similar rarity of adverse events in prior studies of the gene expression signature.^8-10,22 A particular strength of this study is that most of the ambiguous melanocytic neoplasms followed did not undergo excision after the initial biopsy, an increasingly uncommon situation that may increase their likelihood to be informative.

It must be emphasized that the gene expression test, similar to other diagnostic adjuncts, is neither a replacement for histopathologic interpretation nor a substitute for judgment. As with all tests, it can produce false-positive and false-negative results. Therefore, it should always be interpreted within the constellation of the many other data points that must be considered when making a distinction between benign nevus and malignant melanoma, including but not limited to patient age, family and personal history of melanoma, anatomic location, clinical features, and histopathologic findings. As is the case for many diseases, careful consideration of all relevant input is necessary to minimize the risk of misdiagnosis that might occur should any single data point prove inaccurate, including the results of adjunctive molecular tests.

Conclusion

Ancillary methods are emerging as useful tools for the diagnostic evaluation of melanocytic neoplasms that cannot be assigned definitive diagnoses using traditional techniques alone. This study suggests that patients with ambiguous melanocytic neoplasms may benefit from diagnoses and treatment decisions aligned with the results of a gene expression test, and that for those with a benign result, simple observation may be a safe alternative to surgical excision. This expands upon prior observations of the test’s influence on diagnoses and treatment decisions and supports its role as part of dermatopathologists’ and dermatologists’ decision-making process for histopathologically ambiguous melanocytic lesions.

According to National Institutes of Health estimates, more than 90,000 new cases of melanoma were diagnosed in 2018.¹ Overall 5-year survival for patients with melanoma exceeds 90%, but individual survival estimates are highly dependent on stage at diagnosis, and survival decreases markedly with metastasis. Therefore, early and accurate diagnosis is critical.

Diagnosis of melanocytic neoplasms usually is performed by dermatopathologists through microscopic examination of stained tissue biopsy sections, a technically simple and effective method that enables a definitive diagnosis of benign nevus or malignant melanoma to be made in most cases. However, approximately 15% of all biopsied melanocytic lesions will exhibit some degree of histopathologic ambiguity,^2-4 meaning that some of their microscopic features will be characteristic of a benign nevus while others will suggest the possibility of malignant melanoma. Diagnostic interpretations often vary in these cases, even among experts, and a definitive diagnosis of benign or malignant may be difficult to achieve by microscopy alone.^2-4 Because of the marked reduction in survival once a melanoma has metastasized, these diagnostically ambiguous lesions often are treated as possible malignant melanomas with complete surgical excision (or re-excision). However, some experts suggest that many histopathologically ambiguous melanocytic neoplasms are, in fact, benign,⁵ a notion supported by epidemiologic evidence.^6,7 Therefore, excision of many ambiguous melanocytic neoplasms might be avoided if definitive diagnosis could be achieved.

A gene expression signature was developed and validated for use as an adjunct to traditional methods of differentiating malignant melanocytic neoplasms from their benign counterparts.^8-11 This test quantifies the RNA transcripts produced by 14 genes known to be overexpressed in malignant melanomas by comparison to benign nevi. These values are then combined algorithmically with measurements of 9 reference genes to produce an objective numerical score that is classified as benign, malignant, or indeterminate. When used by board-certified dermatopathologists and dermatologists confronting ambiguous melanocytic lesions, the test produces substantial increases in definitive diagnoses and prompts changes in treatment recommendations.^12,13 However, the long-term consequences of foregoing surgical excision of melanocytic neoplasms that are diagnostically ambiguous but classified as benign by this test have not yet been formally assessed. In the current study, prospectively tested patients whose ambiguous melanocytic neoplasms were classified as benign by the gene expression signature were followed for up to 4.5 years to evaluate the long-term safety of treatment decisions aligned with benign test results.

Methods

Study Population
As part of a prior study,¹² US-based dermatopathologists submitted tissue sections from biopsied melanocytic neoplasms determined to be diagnostically ambiguous by histopathology for analysis with the gene expression signature (Myriad Genetics, Inc). Diagnostically ambiguous lesions were those lesions that were described as ambiguous, uncertain, equivocal, indeterminate, or other synonymous terms by the submitting dermatopathologist and therefore lacked a confident diagnosis of benign or malignant prior to testing. Patients initially were tested between May 2014 and August 2014, with samples submitted through a prospective clinical experience study designed to assess the impact of the test on diagnosis and treatment decisions. This study was performed under an institutional review board waiver of consent (Quorum #33403/1).

Patients were eligible for inclusion in the current study if their biopsy specimens (1) had an uncertain preliminary diagnosis according to the submitting dermatopathologist (pretest diagnosis of indeterminate); (2) received a negative (benign) score from the gene expression test; (3) were treated as benign by the dermatologist(s) involved in follow-up care; and (4) were submitted by a single site (St. Joseph Medical Center, Houston, Texas). Although a single dermatopathology site was used for this study, multiple dermatologists were involved in the final treatment of these patients. Patients with benign scores who received additional intervention were excluded, as they may have a lower rate of adverse events (ie, metastasis) than those who did not receive intervention and would therefore skew the analysis population. A total of 25 patients from the prior study met these inclusion criteria. The previously collected¹² pretest and posttest de-identified data were compiled from the commercial laboratory databases, and the patients were followed from the time of testing via medical record review performed by the dermatology providers at participating sites. Clinical follow-up data were collected using study-specific case report forms (CRFs) that captured the following: (1) the dates and results of clinical follow-up visits; (2) the type(s) of treatment and interventions (if any) performed at those visits; (3) the specific indication for any intervention performed; (4) any evidence of persistent, locally recurrent, and/or distant melanocytic neoplasia (whether definitively attributable to the tested lesion or not); and (5) death from any cause. The CRF assigned interventions to 1 of 5 categories: excision, excision with sentinel lymph node biopsy, referral to dermatologic or other surgeon, examination only (without surgical intervention), and other. Selection of other required a free-text description of the treatment and indications. Pertinent information not otherwise captured by the CRF also was recordable as free text.

Gene Expression Testing
Gene expression testing was carried out at the time of specimen submission in the prior study¹² as described previously.¹⁴ Briefly, formalin-fixed, paraffin-embedded, unstained tissue sections and/or tissue blocks were submitted for testing along with a single hematoxylin and eosin–stained slide used to identify and designate the representative portion(s) of the lesion to be tested. These areas were macrodissected from unstained tissue sections and pooled for RNA extraction. Expression of 14 biomarker genes and 9 reference genes was measured via quantitative reverse transcription–polymerase chain reaction, performed in triplicate for each individual gene. The assay score was generated through application of a weighted algorithm to the expression values generated through quantitative reverse transcription–polymerase chain reaction. Scores were plotted on a scale ranging from −16.7 to 11.1, with scores from 0.0 to 11.1 classified as malignant, scores from −16.7 to −2.1 as benign, and scores from −2.1 to −0.1 as indeterminate.

Statistical Analysis
Demographic and other baseline characteristics of the patient population were summarized. Follow-up time was calculated as the interval between the date a patient’s gene expression test result was first issued to the provider and the date of the patient’s last recorded visit during the study period. All patient dermatology office visits within the designated follow-up period were documented, with a nonstandard number of visits and follow-up time across all study patients. Statistical analyses were conducted using SAS software (SAS Institute Inc), R software version 3.5.0 (R Foundation for Statistical Computing), and IBM SPSS Statistics software (IBM SPSS Statistics for Windows, Version 25).

Results

Patient Sample
A total of 25 ambiguous melanocytic neoplasms from 25 patients met the study inclusion criteria of a benign gene expression result with subsequent treatment as a benign neoplasm during follow-up. The patient sample statistics are summarized in Table 1. Most patients were younger than 65 years, with an average age at the time of biopsy of 48.4 years. All 25 neoplasms produced negative (benign) gene expression signature scores, all were diagnosed as benign nevi posttest by the submitting dermatopathologist, and all patients were initially treated in accordance with the benign diagnosis by the dermatologist(s) involved in clinical follow-up care. Prior to testing with the gene expression signature, most of these histopathologically indeterminate lesions received differential diagnoses, the most common of which were dysplastic nevus (84%), melanoma arising from a nevus (72%), and superficial spreading melanoma (64%; eTable). After testing with the gene expression signature and receiving a benign score, most lesions received a single differential diagnosis of dysplastic nevus (88%).

Follow-up and Survival
Clinical follow-up time ranged from 0.6 to 53.3 months, with a mean duration (SD) of 38.5 (16.6) months, and patients attended an average of 4 postbiopsy dermatology appointments (mean [SD], 4.6 [3.6]). According to the participating dermatology care providers, none of the 25 patients developed any indication during follow-up that the diagnosis of benign nevus was inaccurate. No patient had evidence of locally recurrent or metastatic melanoma, and none died during the study period.

Treatment/Interventions
The treatment recorded in the CRF was examination only for 21 of 25 patients, excision for 3, and other for 1 (Table 2). Because the explanation for the selection of other in this case described an excision performed at the same anatomic location as the biopsy, this treatment also was considered an excision for purposes of the study analyses. The 3 excisions all occurred at the first postbiopsy dermatology encounter. Across all follow-up visits, no additional surgical interventions occurred (Table 2).

The third excision (case 3) involved a 32-year-old woman with a pigmented lesion on the abdomen (Table 3; Figure, E and F). The clinical description was irregular-appearing black papule, nevus with atypia, and the histopathologic differential diagnosis again included dysplastic nevus, superficial spreading melanoma, and melanoma arising within a preexisting nevus. The gene expression signature result was benign (score, −7.2), and the final diagnosis issued within the accompanying pathology report was nevus with moderate junctional dysplasia. Despite the benign diagnosis, excision was performed 89 days after test result availability, with apparent residual pigmentation as the specified indication. As with the other 2 cases, the treating dermatologist confirmed that neither clinical features nor follow-up events suggested malignancy.

Comment

This study followed a cohort of 25 patients with histopathologically ambiguous melanocytic neoplasms that were classified as benign by a diagnostic gene expression test with the intent of determining the outcomes of patients whose treatment aligned with their benign test result. All patients initially were managed according to their test result. During an average posttest clinical follow-up time of more than 3 years (38.5 months), the 25 biopsied lesions, most of which received a differential diagnosis of dysplastic nevus, were regarded as benign nevi by their dermatologists, and the vast majority (88%) received no further surgical intervention. Three patients underwent subsequent excision of the biopsied lesion, with patient or physician preference as the indication in each instance. None of the 25 patients developed evidence of local recurrence, metastasis, or other findings that prompted doubt of the benign diagnosis. The absence of adverse events during clinical follow-up, particularly given that most lesions were not subjected to further intervention, supports use of the gene expression test as a safe and effective adjunct to the diagnosis and treatment of ambiguous melanocytic neoplasms by dermatologists and dermatopathologists.

Ambiguous melanocytic neoplasms evaluated without the aid of molecular adjuncts often result in equivocal or less-than-definitive diagnoses, and further surgical intervention is commonly undertaken to mitigate against the possibility of a missed melanoma.¹³ In this study, treatment that was aligned with the benign test result allowed most patients to avoid further surgical intervention, which suggests that adjunctive use of the gene signature can contribute to reductions in the physical and economic burdens imposed by unnecessary surgical interventions.^15,16 Moreover, any means of increasing accurate and definitive diagnoses may produce an immediate impact on health outcomes by reducing the anxiety that uncertainty often provokes in patients and health care providers alike.

Study Limitations
This study must be interpreted within the context of its limitations. Obtaining meaningful patient outcome data is a common challenge in health care research due to the requisite length of follow-up and sometimes the lack of definitive evidence of adverse events. This is particularly difficult for melanocytic neoplasms because of an apparent inclination for patients with benign diagnoses to abandon follow-up and an increasing tendency for even minimal diagnostic uncertainty to prompt complete excision. Additionally, the only definitive clinical outcome for melanocytic neoplasms is distant metastasis, which (fortunately for patients) is relatively rare. Not surprisingly, studies documenting clinical outcomes of patients with ambiguous melanocytic neoplasms tested prospectively with diagnostic adjuncts are scarce, and this study’s sample size and clinical follow-up compare favorably with the few that exist.^17,18 Although most melanomas declare themselves through recurrence or metastasis within several years of initial biopsy,^1,19 some are clinically dormant for as long as 10 years after initial detection.^20,21 This may be particularly true for the small or early-stage lesions that now comprise the majority of biopsied neoplasms, and such events would go undetected by this study and many others. It also must be recognized that uneventful follow-up, regardless of duration, cannot prove that a biopsied melanocytic neoplasm was benign. Although only 5 patients had a follow-up time of less than 2 years (the time frame in which most recurrence or metastasis will occur), it cannot be definitively proven that a minimum of 2 years recurrence- or metastasis-free survival indicates a benign lesion. Many early-stage malignant melanomas are eradicated by complete excision or even by the initial biopsy if margins are uninvolved.

Because these limitations are intrinsic to melanocytic neoplasms and current management strategies, they pertain to all investigations seeking insights into biological potential through clinical outcomes. Similarly, all current diagnostic tools and procedures have the potential for sampling error, including histopathology. The rarity of adverse outcomes (recurrence and metastasis) in patients with benign test results within this cohort indicates that false-negative results are uncommon, which is further evidenced by a similar rarity of adverse events in prior studies of the gene expression signature.^8-10,22 A particular strength of this study is that most of the ambiguous melanocytic neoplasms followed did not undergo excision after the initial biopsy, an increasingly uncommon situation that may increase their likelihood to be informative.

It must be emphasized that the gene expression test, similar to other diagnostic adjuncts, is neither a replacement for histopathologic interpretation nor a substitute for judgment. As with all tests, it can produce false-positive and false-negative results. Therefore, it should always be interpreted within the constellation of the many other data points that must be considered when making a distinction between benign nevus and malignant melanoma, including but not limited to patient age, family and personal history of melanoma, anatomic location, clinical features, and histopathologic findings. As is the case for many diseases, careful consideration of all relevant input is necessary to minimize the risk of misdiagnosis that might occur should any single data point prove inaccurate, including the results of adjunctive molecular tests.

Conclusion

Ancillary methods are emerging as useful tools for the diagnostic evaluation of melanocytic neoplasms that cannot be assigned definitive diagnoses using traditional techniques alone. This study suggests that patients with ambiguous melanocytic neoplasms may benefit from diagnoses and treatment decisions aligned with the results of a gene expression test, and that for those with a benign result, simple observation may be a safe alternative to surgical excision. This expands upon prior observations of the test’s influence on diagnoses and treatment decisions and supports its role as part of dermatopathologists’ and dermatologists’ decision-making process for histopathologically ambiguous melanocytic lesions.

According to National Institutes of Health estimates, more than 90,000 new cases of melanoma were diagnosed in 2018.¹ Overall 5-year survival for patients with melanoma exceeds 90%, but individual survival estimates are highly dependent on stage at diagnosis, and survival decreases markedly with metastasis. Therefore, early and accurate diagnosis is critical.

Diagnosis of melanocytic neoplasms usually is performed by dermatopathologists through microscopic examination of stained tissue biopsy sections, a technically simple and effective method that enables a definitive diagnosis of benign nevus or malignant melanoma to be made in most cases. However, approximately 15% of all biopsied melanocytic lesions will exhibit some degree of histopathologic ambiguity,^2-4 meaning that some of their microscopic features will be characteristic of a benign nevus while others will suggest the possibility of malignant melanoma. Diagnostic interpretations often vary in these cases, even among experts, and a definitive diagnosis of benign or malignant may be difficult to achieve by microscopy alone.^2-4 Because of the marked reduction in survival once a melanoma has metastasized, these diagnostically ambiguous lesions often are treated as possible malignant melanomas with complete surgical excision (or re-excision). However, some experts suggest that many histopathologically ambiguous melanocytic neoplasms are, in fact, benign,⁵ a notion supported by epidemiologic evidence.^6,7 Therefore, excision of many ambiguous melanocytic neoplasms might be avoided if definitive diagnosis could be achieved.

A gene expression signature was developed and validated for use as an adjunct to traditional methods of differentiating malignant melanocytic neoplasms from their benign counterparts.^8-11 This test quantifies the RNA transcripts produced by 14 genes known to be overexpressed in malignant melanomas by comparison to benign nevi. These values are then combined algorithmically with measurements of 9 reference genes to produce an objective numerical score that is classified as benign, malignant, or indeterminate. When used by board-certified dermatopathologists and dermatologists confronting ambiguous melanocytic lesions, the test produces substantial increases in definitive diagnoses and prompts changes in treatment recommendations.^12,13 However, the long-term consequences of foregoing surgical excision of melanocytic neoplasms that are diagnostically ambiguous but classified as benign by this test have not yet been formally assessed. In the current study, prospectively tested patients whose ambiguous melanocytic neoplasms were classified as benign by the gene expression signature were followed for up to 4.5 years to evaluate the long-term safety of treatment decisions aligned with benign test results.

Methods

Study Population
As part of a prior study,¹² US-based dermatopathologists submitted tissue sections from biopsied melanocytic neoplasms determined to be diagnostically ambiguous by histopathology for analysis with the gene expression signature (Myriad Genetics, Inc). Diagnostically ambiguous lesions were those lesions that were described as ambiguous, uncertain, equivocal, indeterminate, or other synonymous terms by the submitting dermatopathologist and therefore lacked a confident diagnosis of benign or malignant prior to testing. Patients initially were tested between May 2014 and August 2014, with samples submitted through a prospective clinical experience study designed to assess the impact of the test on diagnosis and treatment decisions. This study was performed under an institutional review board waiver of consent (Quorum #33403/1).

Patients were eligible for inclusion in the current study if their biopsy specimens (1) had an uncertain preliminary diagnosis according to the submitting dermatopathologist (pretest diagnosis of indeterminate); (2) received a negative (benign) score from the gene expression test; (3) were treated as benign by the dermatologist(s) involved in follow-up care; and (4) were submitted by a single site (St. Joseph Medical Center, Houston, Texas). Although a single dermatopathology site was used for this study, multiple dermatologists were involved in the final treatment of these patients. Patients with benign scores who received additional intervention were excluded, as they may have a lower rate of adverse events (ie, metastasis) than those who did not receive intervention and would therefore skew the analysis population. A total of 25 patients from the prior study met these inclusion criteria. The previously collected¹² pretest and posttest de-identified data were compiled from the commercial laboratory databases, and the patients were followed from the time of testing via medical record review performed by the dermatology providers at participating sites. Clinical follow-up data were collected using study-specific case report forms (CRFs) that captured the following: (1) the dates and results of clinical follow-up visits; (2) the type(s) of treatment and interventions (if any) performed at those visits; (3) the specific indication for any intervention performed; (4) any evidence of persistent, locally recurrent, and/or distant melanocytic neoplasia (whether definitively attributable to the tested lesion or not); and (5) death from any cause. The CRF assigned interventions to 1 of 5 categories: excision, excision with sentinel lymph node biopsy, referral to dermatologic or other surgeon, examination only (without surgical intervention), and other. Selection of other required a free-text description of the treatment and indications. Pertinent information not otherwise captured by the CRF also was recordable as free text.

Gene Expression Testing
Gene expression testing was carried out at the time of specimen submission in the prior study¹² as described previously.¹⁴ Briefly, formalin-fixed, paraffin-embedded, unstained tissue sections and/or tissue blocks were submitted for testing along with a single hematoxylin and eosin–stained slide used to identify and designate the representative portion(s) of the lesion to be tested. These areas were macrodissected from unstained tissue sections and pooled for RNA extraction. Expression of 14 biomarker genes and 9 reference genes was measured via quantitative reverse transcription–polymerase chain reaction, performed in triplicate for each individual gene. The assay score was generated through application of a weighted algorithm to the expression values generated through quantitative reverse transcription–polymerase chain reaction. Scores were plotted on a scale ranging from −16.7 to 11.1, with scores from 0.0 to 11.1 classified as malignant, scores from −16.7 to −2.1 as benign, and scores from −2.1 to −0.1 as indeterminate.

Statistical Analysis
Demographic and other baseline characteristics of the patient population were summarized. Follow-up time was calculated as the interval between the date a patient’s gene expression test result was first issued to the provider and the date of the patient’s last recorded visit during the study period. All patient dermatology office visits within the designated follow-up period were documented, with a nonstandard number of visits and follow-up time across all study patients. Statistical analyses were conducted using SAS software (SAS Institute Inc), R software version 3.5.0 (R Foundation for Statistical Computing), and IBM SPSS Statistics software (IBM SPSS Statistics for Windows, Version 25).

Results

Patient Sample
A total of 25 ambiguous melanocytic neoplasms from 25 patients met the study inclusion criteria of a benign gene expression result with subsequent treatment as a benign neoplasm during follow-up. The patient sample statistics are summarized in Table 1. Most patients were younger than 65 years, with an average age at the time of biopsy of 48.4 years. All 25 neoplasms produced negative (benign) gene expression signature scores, all were diagnosed as benign nevi posttest by the submitting dermatopathologist, and all patients were initially treated in accordance with the benign diagnosis by the dermatologist(s) involved in clinical follow-up care. Prior to testing with the gene expression signature, most of these histopathologically indeterminate lesions received differential diagnoses, the most common of which were dysplastic nevus (84%), melanoma arising from a nevus (72%), and superficial spreading melanoma (64%; eTable). After testing with the gene expression signature and receiving a benign score, most lesions received a single differential diagnosis of dysplastic nevus (88%).

Follow-up and Survival
Clinical follow-up time ranged from 0.6 to 53.3 months, with a mean duration (SD) of 38.5 (16.6) months, and patients attended an average of 4 postbiopsy dermatology appointments (mean [SD], 4.6 [3.6]). According to the participating dermatology care providers, none of the 25 patients developed any indication during follow-up that the diagnosis of benign nevus was inaccurate. No patient had evidence of locally recurrent or metastatic melanoma, and none died during the study period.

Treatment/Interventions
The treatment recorded in the CRF was examination only for 21 of 25 patients, excision for 3, and other for 1 (Table 2). Because the explanation for the selection of other in this case described an excision performed at the same anatomic location as the biopsy, this treatment also was considered an excision for purposes of the study analyses. The 3 excisions all occurred at the first postbiopsy dermatology encounter. Across all follow-up visits, no additional surgical interventions occurred (Table 2).

The third excision (case 3) involved a 32-year-old woman with a pigmented lesion on the abdomen (Table 3; Figure, E and F). The clinical description was irregular-appearing black papule, nevus with atypia, and the histopathologic differential diagnosis again included dysplastic nevus, superficial spreading melanoma, and melanoma arising within a preexisting nevus. The gene expression signature result was benign (score, −7.2), and the final diagnosis issued within the accompanying pathology report was nevus with moderate junctional dysplasia. Despite the benign diagnosis, excision was performed 89 days after test result availability, with apparent residual pigmentation as the specified indication. As with the other 2 cases, the treating dermatologist confirmed that neither clinical features nor follow-up events suggested malignancy.

Comment

This study followed a cohort of 25 patients with histopathologically ambiguous melanocytic neoplasms that were classified as benign by a diagnostic gene expression test with the intent of determining the outcomes of patients whose treatment aligned with their benign test result. All patients initially were managed according to their test result. During an average posttest clinical follow-up time of more than 3 years (38.5 months), the 25 biopsied lesions, most of which received a differential diagnosis of dysplastic nevus, were regarded as benign nevi by their dermatologists, and the vast majority (88%) received no further surgical intervention. Three patients underwent subsequent excision of the biopsied lesion, with patient or physician preference as the indication in each instance. None of the 25 patients developed evidence of local recurrence, metastasis, or other findings that prompted doubt of the benign diagnosis. The absence of adverse events during clinical follow-up, particularly given that most lesions were not subjected to further intervention, supports use of the gene expression test as a safe and effective adjunct to the diagnosis and treatment of ambiguous melanocytic neoplasms by dermatologists and dermatopathologists.

Ambiguous melanocytic neoplasms evaluated without the aid of molecular adjuncts often result in equivocal or less-than-definitive diagnoses, and further surgical intervention is commonly undertaken to mitigate against the possibility of a missed melanoma.¹³ In this study, treatment that was aligned with the benign test result allowed most patients to avoid further surgical intervention, which suggests that adjunctive use of the gene signature can contribute to reductions in the physical and economic burdens imposed by unnecessary surgical interventions.^15,16 Moreover, any means of increasing accurate and definitive diagnoses may produce an immediate impact on health outcomes by reducing the anxiety that uncertainty often provokes in patients and health care providers alike.

Study Limitations
This study must be interpreted within the context of its limitations. Obtaining meaningful patient outcome data is a common challenge in health care research due to the requisite length of follow-up and sometimes the lack of definitive evidence of adverse events. This is particularly difficult for melanocytic neoplasms because of an apparent inclination for patients with benign diagnoses to abandon follow-up and an increasing tendency for even minimal diagnostic uncertainty to prompt complete excision. Additionally, the only definitive clinical outcome for melanocytic neoplasms is distant metastasis, which (fortunately for patients) is relatively rare. Not surprisingly, studies documenting clinical outcomes of patients with ambiguous melanocytic neoplasms tested prospectively with diagnostic adjuncts are scarce, and this study’s sample size and clinical follow-up compare favorably with the few that exist.^17,18 Although most melanomas declare themselves through recurrence or metastasis within several years of initial biopsy,^1,19 some are clinically dormant for as long as 10 years after initial detection.^20,21 This may be particularly true for the small or early-stage lesions that now comprise the majority of biopsied neoplasms, and such events would go undetected by this study and many others. It also must be recognized that uneventful follow-up, regardless of duration, cannot prove that a biopsied melanocytic neoplasm was benign. Although only 5 patients had a follow-up time of less than 2 years (the time frame in which most recurrence or metastasis will occur), it cannot be definitively proven that a minimum of 2 years recurrence- or metastasis-free survival indicates a benign lesion. Many early-stage malignant melanomas are eradicated by complete excision or even by the initial biopsy if margins are uninvolved.

Because these limitations are intrinsic to melanocytic neoplasms and current management strategies, they pertain to all investigations seeking insights into biological potential through clinical outcomes. Similarly, all current diagnostic tools and procedures have the potential for sampling error, including histopathology. The rarity of adverse outcomes (recurrence and metastasis) in patients with benign test results within this cohort indicates that false-negative results are uncommon, which is further evidenced by a similar rarity of adverse events in prior studies of the gene expression signature.^8-10,22 A particular strength of this study is that most of the ambiguous melanocytic neoplasms followed did not undergo excision after the initial biopsy, an increasingly uncommon situation that may increase their likelihood to be informative.

It must be emphasized that the gene expression test, similar to other diagnostic adjuncts, is neither a replacement for histopathologic interpretation nor a substitute for judgment. As with all tests, it can produce false-positive and false-negative results. Therefore, it should always be interpreted within the constellation of the many other data points that must be considered when making a distinction between benign nevus and malignant melanoma, including but not limited to patient age, family and personal history of melanoma, anatomic location, clinical features, and histopathologic findings. As is the case for many diseases, careful consideration of all relevant input is necessary to minimize the risk of misdiagnosis that might occur should any single data point prove inaccurate, including the results of adjunctive molecular tests.

Conclusion

Ancillary methods are emerging as useful tools for the diagnostic evaluation of melanocytic neoplasms that cannot be assigned definitive diagnoses using traditional techniques alone. This study suggests that patients with ambiguous melanocytic neoplasms may benefit from diagnoses and treatment decisions aligned with the results of a gene expression test, and that for those with a benign result, simple observation may be a safe alternative to surgical excision. This expands upon prior observations of the test’s influence on diagnoses and treatment decisions and supports its role as part of dermatopathologists’ and dermatologists’ decision-making process for histopathologically ambiguous melanocytic lesions.

Recent advances in the immunopathogenesis and therapy of cutaneous T-cell lymphoma (CTCL) have shown great promise for the care of patients with mycosis fungoides (MF) and Sézary syndrome (SS).^1-3 Research into the tumor microenvironment, microbiome, and molecular genetics may yield further information as we strive to develop MF/SS therapy from the bench to the bedside.³ Although progress has been made on multiple fronts in MF, some important—particularly epidemiologic and clinical—questions remain unanswered.

Racial disparities are well known to exist in CTCLs, particularly MF and SS.^4-7 The incidence of MF and SS in the United States is higher in African American/Black patients than in White patients⁴; in addition, MF has an earlier age at onset in Black patients compared with White patients.^4,5 Gender disparities also exist, with relatively more Black females than males affected with MF^4-6; in particular, early-onset MF (ie, <40 years of age) is more common in Black females than Black males.^6,7 According to Surveillance, Epidemiology, and End Results (SEER) data⁴ and the US National Cancer Database,⁵ African American/Black patients with MF have worse outcomes compared with other races (shorter overall survival and higher mortality) and also exhibit higher stages of disease at presentation (stage IIb or higher).⁵ Black race also was found to be a predictor of poor overall survival after accounting for disease characteristics, socioeconomicfactors, and types of treatment. The factors responsible for these racial disparities remain unclear.

A fortuitous collision of interests and technology may have helped to shed light on some of the reasons for these racial disparities in MF. Nearly 2 decades ago, high-quality, whole-body digital cutaneous photography was implemented by the Dermatology Service at Memorial Sloan Kettering Cancer Center Dermatology Service (New York, New York).⁸ Although the standardized 20-pose positioning images initially were used for the follow-up evaluation of patients with multiple nevi and melanomas, we incorporated the same photography technique into our multidisciplinary Cutaneous Lymphoma Clinic at Memorial Sloan Kettering Cancer Center. The multiplicity and clinical heterogeneity of MF lesions is well known, as is the fact that individual MF lesions may develop, respond to therapy, or change independently of other lesions in a given patient. We regularly reviewed these digital images with patients during their visits to assess treatment responses, discussed the need for changes in therapy in the face of progressive disease, and provided encouragement and positive reinforcement for those who improved with time-consuming regimens (eg, phototherapy).

Ultimately, as we became more familiar with looking at images in skin of color, we recognized different clinical features among our Black patients. In the literature, hypopigmented MF is a variant that typically is characterized by CD8⁺-predominant T cells and is seen more frequently in dark-skinned patients.⁹ In contrast, hyperpigmented MF has been considered a relatively rare presentation of MF.¹⁰ However, using only clinical and demographic information, we were able to identify 2 very different prognostic groups: those with hypopigmented lesions and those with only hyperpigmented and/or erythematous skin lesions.¹¹ In our retrospective review of 157 African American/Black MF patients at our institution—122 with early-stage and 35 with late-stage MF—45% of patients had hypopigmented lesions vs 52% with hyperpigmented and/or erythematous lesions but no hypopigmentation. Those with hypopigmentation had superior outcomes, with better overall survival (P=.002) and progression-free survival (P=.014). In addition, more than 80% of patients who progressed or died from disease had hyperpigmented and/or erythematous lesions without hypopigmentation.¹¹

Sometimes we have to go backward to go forward. Going from the bedside to the bench in our Black MF/SS patients—initially through the clinical recognition of prognostically different lesions, and then through clinicopathologic correlation with immunophenotyping and molecular studies—should provide important clues. Further investigation of Black patients who share similar pigmentary phenotypes of MF also may shed light on the pathogenetic mechanisms responsible for these prognostically significant skin findings. Through these efforts, we hope to identify higher-risk patients, which ultimately will lead to earlier intervention, more effective therapeutic regimens, and improved outcomes.

Recent advances in the immunopathogenesis and therapy of cutaneous T-cell lymphoma (CTCL) have shown great promise for the care of patients with mycosis fungoides (MF) and Sézary syndrome (SS).^1-3 Research into the tumor microenvironment, microbiome, and molecular genetics may yield further information as we strive to develop MF/SS therapy from the bench to the bedside.³ Although progress has been made on multiple fronts in MF, some important—particularly epidemiologic and clinical—questions remain unanswered.

Racial disparities are well known to exist in CTCLs, particularly MF and SS.^4-7 The incidence of MF and SS in the United States is higher in African American/Black patients than in White patients⁴; in addition, MF has an earlier age at onset in Black patients compared with White patients.^4,5 Gender disparities also exist, with relatively more Black females than males affected with MF^4-6; in particular, early-onset MF (ie, <40 years of age) is more common in Black females than Black males.^6,7 According to Surveillance, Epidemiology, and End Results (SEER) data⁴ and the US National Cancer Database,⁵ African American/Black patients with MF have worse outcomes compared with other races (shorter overall survival and higher mortality) and also exhibit higher stages of disease at presentation (stage IIb or higher).⁵ Black race also was found to be a predictor of poor overall survival after accounting for disease characteristics, socioeconomicfactors, and types of treatment. The factors responsible for these racial disparities remain unclear.

A fortuitous collision of interests and technology may have helped to shed light on some of the reasons for these racial disparities in MF. Nearly 2 decades ago, high-quality, whole-body digital cutaneous photography was implemented by the Dermatology Service at Memorial Sloan Kettering Cancer Center Dermatology Service (New York, New York).⁸ Although the standardized 20-pose positioning images initially were used for the follow-up evaluation of patients with multiple nevi and melanomas, we incorporated the same photography technique into our multidisciplinary Cutaneous Lymphoma Clinic at Memorial Sloan Kettering Cancer Center. The multiplicity and clinical heterogeneity of MF lesions is well known, as is the fact that individual MF lesions may develop, respond to therapy, or change independently of other lesions in a given patient. We regularly reviewed these digital images with patients during their visits to assess treatment responses, discussed the need for changes in therapy in the face of progressive disease, and provided encouragement and positive reinforcement for those who improved with time-consuming regimens (eg, phototherapy).

Ultimately, as we became more familiar with looking at images in skin of color, we recognized different clinical features among our Black patients. In the literature, hypopigmented MF is a variant that typically is characterized by CD8⁺-predominant T cells and is seen more frequently in dark-skinned patients.⁹ In contrast, hyperpigmented MF has been considered a relatively rare presentation of MF.¹⁰ However, using only clinical and demographic information, we were able to identify 2 very different prognostic groups: those with hypopigmented lesions and those with only hyperpigmented and/or erythematous skin lesions.¹¹ In our retrospective review of 157 African American/Black MF patients at our institution—122 with early-stage and 35 with late-stage MF—45% of patients had hypopigmented lesions vs 52% with hyperpigmented and/or erythematous lesions but no hypopigmentation. Those with hypopigmentation had superior outcomes, with better overall survival (P=.002) and progression-free survival (P=.014). In addition, more than 80% of patients who progressed or died from disease had hyperpigmented and/or erythematous lesions without hypopigmentation.¹¹

Sometimes we have to go backward to go forward. Going from the bedside to the bench in our Black MF/SS patients—initially through the clinical recognition of prognostically different lesions, and then through clinicopathologic correlation with immunophenotyping and molecular studies—should provide important clues. Further investigation of Black patients who share similar pigmentary phenotypes of MF also may shed light on the pathogenetic mechanisms responsible for these prognostically significant skin findings. Through these efforts, we hope to identify higher-risk patients, which ultimately will lead to earlier intervention, more effective therapeutic regimens, and improved outcomes.

Recent advances in the immunopathogenesis and therapy of cutaneous T-cell lymphoma (CTCL) have shown great promise for the care of patients with mycosis fungoides (MF) and Sézary syndrome (SS).^1-3 Research into the tumor microenvironment, microbiome, and molecular genetics may yield further information as we strive to develop MF/SS therapy from the bench to the bedside.³ Although progress has been made on multiple fronts in MF, some important—particularly epidemiologic and clinical—questions remain unanswered.

Racial disparities are well known to exist in CTCLs, particularly MF and SS.^4-7 The incidence of MF and SS in the United States is higher in African American/Black patients than in White patients⁴; in addition, MF has an earlier age at onset in Black patients compared with White patients.^4,5 Gender disparities also exist, with relatively more Black females than males affected with MF^4-6; in particular, early-onset MF (ie, <40 years of age) is more common in Black females than Black males.^6,7 According to Surveillance, Epidemiology, and End Results (SEER) data⁴ and the US National Cancer Database,⁵ African American/Black patients with MF have worse outcomes compared with other races (shorter overall survival and higher mortality) and also exhibit higher stages of disease at presentation (stage IIb or higher).⁵ Black race also was found to be a predictor of poor overall survival after accounting for disease characteristics, socioeconomicfactors, and types of treatment. The factors responsible for these racial disparities remain unclear.

A fortuitous collision of interests and technology may have helped to shed light on some of the reasons for these racial disparities in MF. Nearly 2 decades ago, high-quality, whole-body digital cutaneous photography was implemented by the Dermatology Service at Memorial Sloan Kettering Cancer Center Dermatology Service (New York, New York).⁸ Although the standardized 20-pose positioning images initially were used for the follow-up evaluation of patients with multiple nevi and melanomas, we incorporated the same photography technique into our multidisciplinary Cutaneous Lymphoma Clinic at Memorial Sloan Kettering Cancer Center. The multiplicity and clinical heterogeneity of MF lesions is well known, as is the fact that individual MF lesions may develop, respond to therapy, or change independently of other lesions in a given patient. We regularly reviewed these digital images with patients during their visits to assess treatment responses, discussed the need for changes in therapy in the face of progressive disease, and provided encouragement and positive reinforcement for those who improved with time-consuming regimens (eg, phototherapy).

Ultimately, as we became more familiar with looking at images in skin of color, we recognized different clinical features among our Black patients. In the literature, hypopigmented MF is a variant that typically is characterized by CD8⁺-predominant T cells and is seen more frequently in dark-skinned patients.⁹ In contrast, hyperpigmented MF has been considered a relatively rare presentation of MF.¹⁰ However, using only clinical and demographic information, we were able to identify 2 very different prognostic groups: those with hypopigmented lesions and those with only hyperpigmented and/or erythematous skin lesions.¹¹ In our retrospective review of 157 African American/Black MF patients at our institution—122 with early-stage and 35 with late-stage MF—45% of patients had hypopigmented lesions vs 52% with hyperpigmented and/or erythematous lesions but no hypopigmentation. Those with hypopigmentation had superior outcomes, with better overall survival (P=.002) and progression-free survival (P=.014). In addition, more than 80% of patients who progressed or died from disease had hyperpigmented and/or erythematous lesions without hypopigmentation.¹¹

Sometimes we have to go backward to go forward. Going from the bedside to the bench in our Black MF/SS patients—initially through the clinical recognition of prognostically different lesions, and then through clinicopathologic correlation with immunophenotyping and molecular studies—should provide important clues. Further investigation of Black patients who share similar pigmentary phenotypes of MF also may shed light on the pathogenetic mechanisms responsible for these prognostically significant skin findings. Through these efforts, we hope to identify higher-risk patients, which ultimately will lead to earlier intervention, more effective therapeutic regimens, and improved outcomes.

Practice Gap

Reconstruction of a lip defect poses challenges to the dermatologic surgeon. The lip is a free margin, where excess tension can cause noticeable distortion in facial aesthetics. Distortion of that free margin might not only disrupt the appearance of the lip but affect function by impairing oral competency and mobility; therefore, when choosing a method of reconstruction, the surgeon must take free margin distortion into account. Misalignment of the vermilion border upon reconstruction will cause a poor aesthetic result in the absence of free margin distortion. When a surgical defect involves more than one cosmetic subunit of the lip, great care must be taken to repair each subunit individually to achieve the best cosmetic and functional results.

The suitability of traditional approaches to reconstruction of a defect that crosses the vermilion border—healing by secondary intention, primary linear repair, full-thickness wedge repair, partial-thickness wedge repair, and combined cutaneous and mucosal advancement¹—depends on the depth of the lesion.

Clinical Presentation

A 66-year-old woman with a 4×6-mm, invasive, well-differentiated squamous cell carcinoma of the left lower lip was referred for Mohs micrographic surgery. Removal of the tumor required 2 stages to obtain clear margins, leaving a 1.0×1.2-cm defect that crossed the vermilion border (Figure, A). How would you repair this defect?

Selecting a Technique to Close the Surgical Defect

For this patient, we had several options to consider in approaching closure, including several that we rejected. Because the defect crossed cosmetic subunit boundaries, healing by secondary intention was avoided, as it would cause contraction, obliterate the vermilion border, and result in poor functional and cosmetic results. We decided against primary closure, even with careful attention to reapproximation of the vermilion border, because the width of the defect would have required a large Burow triangle that extended into the oral cavity. For defects less than one-third the width of the lip, full-thickness wedge repair can yield excellent cosmetic results but, in this case, would decrease the oral aperture and was deemed too extensive a procedure for a relatively shallow defect.²

Instead, we chose to perform repair with V to Y advancement of skin below the cutaneous defect, up to the location of the absent vermilion border, combined with small, horizontal, linear closure of the mucosal portion of the defect. This approach is a variation of a repair described by Jin et al,³ who described using 2 opposing V-Y advancement flaps to repair defects of the lip. This repair has provided excellent cosmetic results for a small series of our patients, preserving the oral aperture and maintaining the important aesthetic location of the vermilion border. In addition, the technique makes it unnecessary for the patient to undergo a much larger repair, such as a full- or partial-thickness wedge when the initial defect is relatively shallow.

Closure Technique

It is essential to properly outline the vermilion border of the lip before initiating the repair, ideally before any infiltration of local anesthesia if the surgeon anticipates that tumor extirpation might cross the vermilion border.

Repair
Closing then proceeds as follows:

• The cutaneous portion of the defect is drawn out in standard V to Y fashion, carrying the incision through the dermis and into subcutaneous tissue. The pedicle of the flap is maintained at the base of the island, serving as the blood supply to the flap.

• The periphery of the flap and surrounding tissue is undermined to facilitate movement superiorly into the cutaneous portion of the defect.

• A single buried vertical mattress suture can be placed at the advancing border of the island, holding it in place at the anticipated location of the vermilion border. The secondary defect created by the advancing V is closed to help push the island into place and prevent downward tension on the free margin of the lip.

• The remaining defect of the vermilion lip is closed by removing Burow triangles at the horizontal edges on each side of the remaining defect (Figure, B). The triangles are removed completely within the mucosal lip, with the inferior edge of the triangle placed at the vermilion border.

• The defect is closed in a primary linear horizontal fashion, using buried vertical mattress sutures and cutaneous approximation.

The final appearance of the sutured defect yields a small lateral extension at the superior edge of the V to Y closure, giving the appearance of wings on the Y, prompting us to term the closure V-to-flying-Y (Figure, C).

Although the limited portion of the mucosal lip that is closed in this fashion might appear thinner than the remaining lip, it generally yields a cosmetically acceptable result in the properly selected patient. Our experience also has shown an improvement in this difference in the months following repair. A full mucosal advancement flap might result in a more uniform appearance of the lower lip, but it is a larger and more difficult procedure for the patient to endure. Additionally, a full mucosal advancement flap risks uniformly creating a much thinner lip.

Postoperative Course
Sutures were removed 1 week postoperatively. Proper location of the vermilion border, without distortion of the free margin, was demonstrated. At 11-month follow-up, excellent cosmetic and functional results were noted (Figure, D).

Practice Implications

This repair (1) demonstrates an elegant method of closing a relatively shallow defect that crosses the vermilion border and (2) allows the surgeon to address each cosmetic subunit individually. We have found that this repair provides excellent cosmetic and functional results, with little morbidity.

The lip is a common site of nonmelanoma squamous cell carcinoma. Poorly planned closing after excision of the tumor risks notable impairment of function or cosmetic distortion. When a defect of the lip crosses cosmetic subunits, it is helpful to repair each subunit individually. V-to-flying-Y closure is an effective method to close defects that cross the vermilion border, resulting in well-preserved cosmetic appearance and function.

Practice Gap

Reconstruction of a lip defect poses challenges to the dermatologic surgeon. The lip is a free margin, where excess tension can cause noticeable distortion in facial aesthetics. Distortion of that free margin might not only disrupt the appearance of the lip but affect function by impairing oral competency and mobility; therefore, when choosing a method of reconstruction, the surgeon must take free margin distortion into account. Misalignment of the vermilion border upon reconstruction will cause a poor aesthetic result in the absence of free margin distortion. When a surgical defect involves more than one cosmetic subunit of the lip, great care must be taken to repair each subunit individually to achieve the best cosmetic and functional results.

The suitability of traditional approaches to reconstruction of a defect that crosses the vermilion border—healing by secondary intention, primary linear repair, full-thickness wedge repair, partial-thickness wedge repair, and combined cutaneous and mucosal advancement¹—depends on the depth of the lesion.

Clinical Presentation

A 66-year-old woman with a 4×6-mm, invasive, well-differentiated squamous cell carcinoma of the left lower lip was referred for Mohs micrographic surgery. Removal of the tumor required 2 stages to obtain clear margins, leaving a 1.0×1.2-cm defect that crossed the vermilion border (Figure, A). How would you repair this defect?

Selecting a Technique to Close the Surgical Defect

For this patient, we had several options to consider in approaching closure, including several that we rejected. Because the defect crossed cosmetic subunit boundaries, healing by secondary intention was avoided, as it would cause contraction, obliterate the vermilion border, and result in poor functional and cosmetic results. We decided against primary closure, even with careful attention to reapproximation of the vermilion border, because the width of the defect would have required a large Burow triangle that extended into the oral cavity. For defects less than one-third the width of the lip, full-thickness wedge repair can yield excellent cosmetic results but, in this case, would decrease the oral aperture and was deemed too extensive a procedure for a relatively shallow defect.²

Instead, we chose to perform repair with V to Y advancement of skin below the cutaneous defect, up to the location of the absent vermilion border, combined with small, horizontal, linear closure of the mucosal portion of the defect. This approach is a variation of a repair described by Jin et al,³ who described using 2 opposing V-Y advancement flaps to repair defects of the lip. This repair has provided excellent cosmetic results for a small series of our patients, preserving the oral aperture and maintaining the important aesthetic location of the vermilion border. In addition, the technique makes it unnecessary for the patient to undergo a much larger repair, such as a full- or partial-thickness wedge when the initial defect is relatively shallow.

Closure Technique

It is essential to properly outline the vermilion border of the lip before initiating the repair, ideally before any infiltration of local anesthesia if the surgeon anticipates that tumor extirpation might cross the vermilion border.

Repair
Closing then proceeds as follows:

• The cutaneous portion of the defect is drawn out in standard V to Y fashion, carrying the incision through the dermis and into subcutaneous tissue. The pedicle of the flap is maintained at the base of the island, serving as the blood supply to the flap.

• The periphery of the flap and surrounding tissue is undermined to facilitate movement superiorly into the cutaneous portion of the defect.

• A single buried vertical mattress suture can be placed at the advancing border of the island, holding it in place at the anticipated location of the vermilion border. The secondary defect created by the advancing V is closed to help push the island into place and prevent downward tension on the free margin of the lip.

• The remaining defect of the vermilion lip is closed by removing Burow triangles at the horizontal edges on each side of the remaining defect (Figure, B). The triangles are removed completely within the mucosal lip, with the inferior edge of the triangle placed at the vermilion border.

• The defect is closed in a primary linear horizontal fashion, using buried vertical mattress sutures and cutaneous approximation.

The final appearance of the sutured defect yields a small lateral extension at the superior edge of the V to Y closure, giving the appearance of wings on the Y, prompting us to term the closure V-to-flying-Y (Figure, C).

Although the limited portion of the mucosal lip that is closed in this fashion might appear thinner than the remaining lip, it generally yields a cosmetically acceptable result in the properly selected patient. Our experience also has shown an improvement in this difference in the months following repair. A full mucosal advancement flap might result in a more uniform appearance of the lower lip, but it is a larger and more difficult procedure for the patient to endure. Additionally, a full mucosal advancement flap risks uniformly creating a much thinner lip.

Postoperative Course
Sutures were removed 1 week postoperatively. Proper location of the vermilion border, without distortion of the free margin, was demonstrated. At 11-month follow-up, excellent cosmetic and functional results were noted (Figure, D).

Practice Implications

This repair (1) demonstrates an elegant method of closing a relatively shallow defect that crosses the vermilion border and (2) allows the surgeon to address each cosmetic subunit individually. We have found that this repair provides excellent cosmetic and functional results, with little morbidity.

The lip is a common site of nonmelanoma squamous cell carcinoma. Poorly planned closing after excision of the tumor risks notable impairment of function or cosmetic distortion. When a defect of the lip crosses cosmetic subunits, it is helpful to repair each subunit individually. V-to-flying-Y closure is an effective method to close defects that cross the vermilion border, resulting in well-preserved cosmetic appearance and function.

Practice Gap

Reconstruction of a lip defect poses challenges to the dermatologic surgeon. The lip is a free margin, where excess tension can cause noticeable distortion in facial aesthetics. Distortion of that free margin might not only disrupt the appearance of the lip but affect function by impairing oral competency and mobility; therefore, when choosing a method of reconstruction, the surgeon must take free margin distortion into account. Misalignment of the vermilion border upon reconstruction will cause a poor aesthetic result in the absence of free margin distortion. When a surgical defect involves more than one cosmetic subunit of the lip, great care must be taken to repair each subunit individually to achieve the best cosmetic and functional results.

The suitability of traditional approaches to reconstruction of a defect that crosses the vermilion border—healing by secondary intention, primary linear repair, full-thickness wedge repair, partial-thickness wedge repair, and combined cutaneous and mucosal advancement¹—depends on the depth of the lesion.

Clinical Presentation

A 66-year-old woman with a 4×6-mm, invasive, well-differentiated squamous cell carcinoma of the left lower lip was referred for Mohs micrographic surgery. Removal of the tumor required 2 stages to obtain clear margins, leaving a 1.0×1.2-cm defect that crossed the vermilion border (Figure, A). How would you repair this defect?

Selecting a Technique to Close the Surgical Defect

For this patient, we had several options to consider in approaching closure, including several that we rejected. Because the defect crossed cosmetic subunit boundaries, healing by secondary intention was avoided, as it would cause contraction, obliterate the vermilion border, and result in poor functional and cosmetic results. We decided against primary closure, even with careful attention to reapproximation of the vermilion border, because the width of the defect would have required a large Burow triangle that extended into the oral cavity. For defects less than one-third the width of the lip, full-thickness wedge repair can yield excellent cosmetic results but, in this case, would decrease the oral aperture and was deemed too extensive a procedure for a relatively shallow defect.²

Instead, we chose to perform repair with V to Y advancement of skin below the cutaneous defect, up to the location of the absent vermilion border, combined with small, horizontal, linear closure of the mucosal portion of the defect. This approach is a variation of a repair described by Jin et al,³ who described using 2 opposing V-Y advancement flaps to repair defects of the lip. This repair has provided excellent cosmetic results for a small series of our patients, preserving the oral aperture and maintaining the important aesthetic location of the vermilion border. In addition, the technique makes it unnecessary for the patient to undergo a much larger repair, such as a full- or partial-thickness wedge when the initial defect is relatively shallow.

Closure Technique

It is essential to properly outline the vermilion border of the lip before initiating the repair, ideally before any infiltration of local anesthesia if the surgeon anticipates that tumor extirpation might cross the vermilion border.

Repair
Closing then proceeds as follows:

• The cutaneous portion of the defect is drawn out in standard V to Y fashion, carrying the incision through the dermis and into subcutaneous tissue. The pedicle of the flap is maintained at the base of the island, serving as the blood supply to the flap.

• The periphery of the flap and surrounding tissue is undermined to facilitate movement superiorly into the cutaneous portion of the defect.

• A single buried vertical mattress suture can be placed at the advancing border of the island, holding it in place at the anticipated location of the vermilion border. The secondary defect created by the advancing V is closed to help push the island into place and prevent downward tension on the free margin of the lip.

• The remaining defect of the vermilion lip is closed by removing Burow triangles at the horizontal edges on each side of the remaining defect (Figure, B). The triangles are removed completely within the mucosal lip, with the inferior edge of the triangle placed at the vermilion border.

• The defect is closed in a primary linear horizontal fashion, using buried vertical mattress sutures and cutaneous approximation.

The final appearance of the sutured defect yields a small lateral extension at the superior edge of the V to Y closure, giving the appearance of wings on the Y, prompting us to term the closure V-to-flying-Y (Figure, C).

Although the limited portion of the mucosal lip that is closed in this fashion might appear thinner than the remaining lip, it generally yields a cosmetically acceptable result in the properly selected patient. Our experience also has shown an improvement in this difference in the months following repair. A full mucosal advancement flap might result in a more uniform appearance of the lower lip, but it is a larger and more difficult procedure for the patient to endure. Additionally, a full mucosal advancement flap risks uniformly creating a much thinner lip.

Postoperative Course
Sutures were removed 1 week postoperatively. Proper location of the vermilion border, without distortion of the free margin, was demonstrated. At 11-month follow-up, excellent cosmetic and functional results were noted (Figure, D).

Practice Implications

This repair (1) demonstrates an elegant method of closing a relatively shallow defect that crosses the vermilion border and (2) allows the surgeon to address each cosmetic subunit individually. We have found that this repair provides excellent cosmetic and functional results, with little morbidity.

The lip is a common site of nonmelanoma squamous cell carcinoma. Poorly planned closing after excision of the tumor risks notable impairment of function or cosmetic distortion. When a defect of the lip crosses cosmetic subunits, it is helpful to repair each subunit individually. V-to-flying-Y closure is an effective method to close defects that cross the vermilion border, resulting in well-preserved cosmetic appearance and function.

Intentional tanning—through sun exposure and tanning beds—is an easily avoidable contributor to skin cancer development and an important area for public education. Since the advent of social media, a correlation between social media use and increased indoor tanning behaviors has been reported.¹ In 2010, 11.3% of US adults aged 18 to 29 years reported using a tanning bed in the last 12 months.² The American Academy of Dermatology first published their “Position Statement on Indoor Tanning” in 1998, endorsing a ban on the sale of indoor tanning equipment for nonmedical purposes.³

Although there has been no outright ban on indoor tanning, regulations have been put in place in many states—including Texas, where (as of 2013) a person younger than 18 years must have written consent from their parent(s) to use a tanning bed. Despite efforts of organizations including the American Academy of Dermatology and the government to educate the public on skin cancer prevention and sun safety, the skin cancer rate has been steadily increasing over the last 20 years.

There is a constant campaign among dermatologists to educate their patients on how to reduce or avoid the risk for skin cancer, including the use of sunscreen and avoidance of tanning. Adolescents and young adults are an especially important demographic to reach and educate because increased UV light exposure during these years leads to a greatly increased risk for skin cancer later in life.⁴ Data on the overall prevalence of tanning and the demographics of participation in tanning activities are important to capture and can be used to efficiently target higher-risk populations.

In this study, we aimed to investigate the attitudes and behaviors of adolescents and young adults regarding sun protection and tanning. We also aimed to determine which avenues, including social media, would be most effective at educating about skin cancer awareness and sun protection to the higher-risk younger population.

Materials and Methods

We developed an institutional review board–approved protocol for the prospective collection of data from registered patients at the dermatology clinic of the Mays Cancer Center at the University of Texas Health at San Antonio. A paper survey containing 15 rating-scale questions was administered to 60 patients aged 13 to 27 years. Surveys were administered during intake, prior to the patients’ visit with a dermatologist; all visits were of a functional (not cosmetic) nature. Data collection spanned June to August 2018. Survey results were entered into Research Electronic Data Capture (REDCap) software for qualitative analysis.

Results

Sixty patients responded to the survey. The mean age of respondents was 19.5 years. No surveys were excluded from the data set. Table 1 provides baseline characteristics of respondents. Some respondents left questions unanswered, resulting in questions with fewer than 60 responses.

Among respondents to the survey, 70% (42/60) reported it is very important to protect their skin from sun exposure, and 30% (18/60) reported it is somewhat important. Regarding sunscreen use, 70% (42/60) indicated they use sunscreen only before outdoor activities, 12% (7/60) use sunscreen daily, and 17% (10/60) never use sunscreen. Of those who use sunscreen, 52% (28/54) do so to prevent skin damage and aging and 44% (24/54) to prevent skin cancer. Twenty-three percent (13/56) of respondents reported finding tanned skin attractive; 26% (14/55) reported wanting to be tan. Looking at race, 28% (10/36) of Whites, 25% (5/20) of Spanish/Hispanic/Latinos, and 22% (2/9) of Asians found tanned skin attractive; no Black respondents found tanned skin attractive.

Regarding tanning, 12% (7/57) reported using a tanning bed in their lifetime and 4% (2/57) in the last year; 34% (19/56) reported deliberately tanning outdoors; and 9% (5/56) reported using sunless or spray-on tanning. Dermatologists (75% [42/56]), primary care physicians (69.6% [39/56]), and parents (46.4% [26/56]) were perceived as more effective sources of skin care education; among media modalities, television (33.9% [19/56]), Instagram (30.4% [17/60]), and YouTube (23.2% [13/60]) were perceived as more effective sources of skin care education (Table 2).

Comment

Perceptions of Tanning
Almost one-quarter of respondents found tanned skin attractive, which might reflect a shift from prior generations. Compared to the 11% of respondents in the 2010 survey,² only 3.5% (2/57) of our respondents reported using a tanning bed in the last year, which could reflect the results of recent Texas legislation restricting the use of tanning beds by adolescents.

An alarming number of respondents reported going outdoors with the intention of tanning; although it appears that indoor tanning education has been successful, this finding shows that there is still a need for sun protection education because outdoor tanning is not a suitable alternative. A small number of respondents reported getting a sunless or spray-on tan, which is a risk-free alternative to indoor tanning.

Despite all respondents stating that protecting skin from the sun is important, most respondents surveyed do not use sunscreen daily. More respondents use sunscreen to prevent damage and aging than to prevent skin cancer. Young people might be more alarmed by the threat of early aging and losing their “youthful appearance” than by the possibility of developing skin cancer in the distant future. This discrepancy might indicate a lack of knowledge and be an important focus for future education efforts.

Perceptions of Trustworthiness of Education Sources
Our findings show dermatologists and primary care physicians are important educators on skin protection. Primary care physicians should remain vigilant to recognize at-risk patients who would benefit from skin protection education, especially those who do not see a dermatologist. Education of young people focusing on their concern over maintaining a youthful appearance instead of the possibility of developing skin cancer in the future might be more effective.

Although education provided by a physician is effective, using media—particularly social media—might be more efficient. Television, Instagram, and YouTube were listed by respondents as the 3 most preferred media outlets for skin health education, which shows important areas of focus for future advertising. Facebook was listed at a surprisingly low level, possibly showing the change in use of certain social media websites among this age group. According to the Pew Research Center, the most widely used social media apps among young adults aged 18 to 29 years are YouTube (91%), Facebook (63%), Instagram (67%), and Snapchat (62%). More than half of the same demographic visit Facebook (74%), Instagram (63%), Snapchat (61%), and YouTube (51%) daily.⁵ Although respondents to our survey were not specifically asked about the frequency of their use of social media and our data set includes patients younger than 18 years, we know that social media use has been increasing over the last decade among adolescents.¹ Therefore, we assume that more than one-half of respondents to our survey use their reported social media platforms daily.

Social media is an underused medium for skin cancer prevention education and can reach those who do not regularly see a dermatologist. Unlike printed pamphlets and posters, advertisements through social media can use metrics such as age, race, gender, and interests to target high-risk individuals.

Study Limitations
This was a single-site study of currently enrolled dermatology patients who might be more aware of skin protection than the general population because they are being treated by a dermatologist. Survey questions regarding demographics, required by our institution, could not effectively differentiate Hispanic and White patients. Respondents could have been subject to the Hawthorne effect—awareness that their behavior is being observed—when responding to the survey because it was administered in the office prior to being seen by a dermatologist.

Intentional tanning—through sun exposure and tanning beds—is an easily avoidable contributor to skin cancer development and an important area for public education. Since the advent of social media, a correlation between social media use and increased indoor tanning behaviors has been reported.¹ In 2010, 11.3% of US adults aged 18 to 29 years reported using a tanning bed in the last 12 months.² The American Academy of Dermatology first published their “Position Statement on Indoor Tanning” in 1998, endorsing a ban on the sale of indoor tanning equipment for nonmedical purposes.³

Although there has been no outright ban on indoor tanning, regulations have been put in place in many states—including Texas, where (as of 2013) a person younger than 18 years must have written consent from their parent(s) to use a tanning bed. Despite efforts of organizations including the American Academy of Dermatology and the government to educate the public on skin cancer prevention and sun safety, the skin cancer rate has been steadily increasing over the last 20 years.

There is a constant campaign among dermatologists to educate their patients on how to reduce or avoid the risk for skin cancer, including the use of sunscreen and avoidance of tanning. Adolescents and young adults are an especially important demographic to reach and educate because increased UV light exposure during these years leads to a greatly increased risk for skin cancer later in life.⁴ Data on the overall prevalence of tanning and the demographics of participation in tanning activities are important to capture and can be used to efficiently target higher-risk populations.

In this study, we aimed to investigate the attitudes and behaviors of adolescents and young adults regarding sun protection and tanning. We also aimed to determine which avenues, including social media, would be most effective at educating about skin cancer awareness and sun protection to the higher-risk younger population.

Materials and Methods

We developed an institutional review board–approved protocol for the prospective collection of data from registered patients at the dermatology clinic of the Mays Cancer Center at the University of Texas Health at San Antonio. A paper survey containing 15 rating-scale questions was administered to 60 patients aged 13 to 27 years. Surveys were administered during intake, prior to the patients’ visit with a dermatologist; all visits were of a functional (not cosmetic) nature. Data collection spanned June to August 2018. Survey results were entered into Research Electronic Data Capture (REDCap) software for qualitative analysis.

Results

Sixty patients responded to the survey. The mean age of respondents was 19.5 years. No surveys were excluded from the data set. Table 1 provides baseline characteristics of respondents. Some respondents left questions unanswered, resulting in questions with fewer than 60 responses.

Among respondents to the survey, 70% (42/60) reported it is very important to protect their skin from sun exposure, and 30% (18/60) reported it is somewhat important. Regarding sunscreen use, 70% (42/60) indicated they use sunscreen only before outdoor activities, 12% (7/60) use sunscreen daily, and 17% (10/60) never use sunscreen. Of those who use sunscreen, 52% (28/54) do so to prevent skin damage and aging and 44% (24/54) to prevent skin cancer. Twenty-three percent (13/56) of respondents reported finding tanned skin attractive; 26% (14/55) reported wanting to be tan. Looking at race, 28% (10/36) of Whites, 25% (5/20) of Spanish/Hispanic/Latinos, and 22% (2/9) of Asians found tanned skin attractive; no Black respondents found tanned skin attractive.

Regarding tanning, 12% (7/57) reported using a tanning bed in their lifetime and 4% (2/57) in the last year; 34% (19/56) reported deliberately tanning outdoors; and 9% (5/56) reported using sunless or spray-on tanning. Dermatologists (75% [42/56]), primary care physicians (69.6% [39/56]), and parents (46.4% [26/56]) were perceived as more effective sources of skin care education; among media modalities, television (33.9% [19/56]), Instagram (30.4% [17/60]), and YouTube (23.2% [13/60]) were perceived as more effective sources of skin care education (Table 2).

Comment

Perceptions of Tanning
Almost one-quarter of respondents found tanned skin attractive, which might reflect a shift from prior generations. Compared to the 11% of respondents in the 2010 survey,² only 3.5% (2/57) of our respondents reported using a tanning bed in the last year, which could reflect the results of recent Texas legislation restricting the use of tanning beds by adolescents.

An alarming number of respondents reported going outdoors with the intention of tanning; although it appears that indoor tanning education has been successful, this finding shows that there is still a need for sun protection education because outdoor tanning is not a suitable alternative. A small number of respondents reported getting a sunless or spray-on tan, which is a risk-free alternative to indoor tanning.

Despite all respondents stating that protecting skin from the sun is important, most respondents surveyed do not use sunscreen daily. More respondents use sunscreen to prevent damage and aging than to prevent skin cancer. Young people might be more alarmed by the threat of early aging and losing their “youthful appearance” than by the possibility of developing skin cancer in the distant future. This discrepancy might indicate a lack of knowledge and be an important focus for future education efforts.

Perceptions of Trustworthiness of Education Sources
Our findings show dermatologists and primary care physicians are important educators on skin protection. Primary care physicians should remain vigilant to recognize at-risk patients who would benefit from skin protection education, especially those who do not see a dermatologist. Education of young people focusing on their concern over maintaining a youthful appearance instead of the possibility of developing skin cancer in the future might be more effective.

Although education provided by a physician is effective, using media—particularly social media—might be more efficient. Television, Instagram, and YouTube were listed by respondents as the 3 most preferred media outlets for skin health education, which shows important areas of focus for future advertising. Facebook was listed at a surprisingly low level, possibly showing the change in use of certain social media websites among this age group. According to the Pew Research Center, the most widely used social media apps among young adults aged 18 to 29 years are YouTube (91%), Facebook (63%), Instagram (67%), and Snapchat (62%). More than half of the same demographic visit Facebook (74%), Instagram (63%), Snapchat (61%), and YouTube (51%) daily.⁵ Although respondents to our survey were not specifically asked about the frequency of their use of social media and our data set includes patients younger than 18 years, we know that social media use has been increasing over the last decade among adolescents.¹ Therefore, we assume that more than one-half of respondents to our survey use their reported social media platforms daily.

Social media is an underused medium for skin cancer prevention education and can reach those who do not regularly see a dermatologist. Unlike printed pamphlets and posters, advertisements through social media can use metrics such as age, race, gender, and interests to target high-risk individuals.

Study Limitations
This was a single-site study of currently enrolled dermatology patients who might be more aware of skin protection than the general population because they are being treated by a dermatologist. Survey questions regarding demographics, required by our institution, could not effectively differentiate Hispanic and White patients. Respondents could have been subject to the Hawthorne effect—awareness that their behavior is being observed—when responding to the survey because it was administered in the office prior to being seen by a dermatologist.

Intentional tanning—through sun exposure and tanning beds—is an easily avoidable contributor to skin cancer development and an important area for public education. Since the advent of social media, a correlation between social media use and increased indoor tanning behaviors has been reported.¹ In 2010, 11.3% of US adults aged 18 to 29 years reported using a tanning bed in the last 12 months.² The American Academy of Dermatology first published their “Position Statement on Indoor Tanning” in 1998, endorsing a ban on the sale of indoor tanning equipment for nonmedical purposes.³

Although there has been no outright ban on indoor tanning, regulations have been put in place in many states—including Texas, where (as of 2013) a person younger than 18 years must have written consent from their parent(s) to use a tanning bed. Despite efforts of organizations including the American Academy of Dermatology and the government to educate the public on skin cancer prevention and sun safety, the skin cancer rate has been steadily increasing over the last 20 years.

There is a constant campaign among dermatologists to educate their patients on how to reduce or avoid the risk for skin cancer, including the use of sunscreen and avoidance of tanning. Adolescents and young adults are an especially important demographic to reach and educate because increased UV light exposure during these years leads to a greatly increased risk for skin cancer later in life.⁴ Data on the overall prevalence of tanning and the demographics of participation in tanning activities are important to capture and can be used to efficiently target higher-risk populations.

In this study, we aimed to investigate the attitudes and behaviors of adolescents and young adults regarding sun protection and tanning. We also aimed to determine which avenues, including social media, would be most effective at educating about skin cancer awareness and sun protection to the higher-risk younger population.

Materials and Methods

We developed an institutional review board–approved protocol for the prospective collection of data from registered patients at the dermatology clinic of the Mays Cancer Center at the University of Texas Health at San Antonio. A paper survey containing 15 rating-scale questions was administered to 60 patients aged 13 to 27 years. Surveys were administered during intake, prior to the patients’ visit with a dermatologist; all visits were of a functional (not cosmetic) nature. Data collection spanned June to August 2018. Survey results were entered into Research Electronic Data Capture (REDCap) software for qualitative analysis.

Results

Sixty patients responded to the survey. The mean age of respondents was 19.5 years. No surveys were excluded from the data set. Table 1 provides baseline characteristics of respondents. Some respondents left questions unanswered, resulting in questions with fewer than 60 responses.

Among respondents to the survey, 70% (42/60) reported it is very important to protect their skin from sun exposure, and 30% (18/60) reported it is somewhat important. Regarding sunscreen use, 70% (42/60) indicated they use sunscreen only before outdoor activities, 12% (7/60) use sunscreen daily, and 17% (10/60) never use sunscreen. Of those who use sunscreen, 52% (28/54) do so to prevent skin damage and aging and 44% (24/54) to prevent skin cancer. Twenty-three percent (13/56) of respondents reported finding tanned skin attractive; 26% (14/55) reported wanting to be tan. Looking at race, 28% (10/36) of Whites, 25% (5/20) of Spanish/Hispanic/Latinos, and 22% (2/9) of Asians found tanned skin attractive; no Black respondents found tanned skin attractive.

Regarding tanning, 12% (7/57) reported using a tanning bed in their lifetime and 4% (2/57) in the last year; 34% (19/56) reported deliberately tanning outdoors; and 9% (5/56) reported using sunless or spray-on tanning. Dermatologists (75% [42/56]), primary care physicians (69.6% [39/56]), and parents (46.4% [26/56]) were perceived as more effective sources of skin care education; among media modalities, television (33.9% [19/56]), Instagram (30.4% [17/60]), and YouTube (23.2% [13/60]) were perceived as more effective sources of skin care education (Table 2).

Comment

Perceptions of Tanning
Almost one-quarter of respondents found tanned skin attractive, which might reflect a shift from prior generations. Compared to the 11% of respondents in the 2010 survey,² only 3.5% (2/57) of our respondents reported using a tanning bed in the last year, which could reflect the results of recent Texas legislation restricting the use of tanning beds by adolescents.

An alarming number of respondents reported going outdoors with the intention of tanning; although it appears that indoor tanning education has been successful, this finding shows that there is still a need for sun protection education because outdoor tanning is not a suitable alternative. A small number of respondents reported getting a sunless or spray-on tan, which is a risk-free alternative to indoor tanning.

Despite all respondents stating that protecting skin from the sun is important, most respondents surveyed do not use sunscreen daily. More respondents use sunscreen to prevent damage and aging than to prevent skin cancer. Young people might be more alarmed by the threat of early aging and losing their “youthful appearance” than by the possibility of developing skin cancer in the distant future. This discrepancy might indicate a lack of knowledge and be an important focus for future education efforts.

Perceptions of Trustworthiness of Education Sources
Our findings show dermatologists and primary care physicians are important educators on skin protection. Primary care physicians should remain vigilant to recognize at-risk patients who would benefit from skin protection education, especially those who do not see a dermatologist. Education of young people focusing on their concern over maintaining a youthful appearance instead of the possibility of developing skin cancer in the future might be more effective.

Although education provided by a physician is effective, using media—particularly social media—might be more efficient. Television, Instagram, and YouTube were listed by respondents as the 3 most preferred media outlets for skin health education, which shows important areas of focus for future advertising. Facebook was listed at a surprisingly low level, possibly showing the change in use of certain social media websites among this age group. According to the Pew Research Center, the most widely used social media apps among young adults aged 18 to 29 years are YouTube (91%), Facebook (63%), Instagram (67%), and Snapchat (62%). More than half of the same demographic visit Facebook (74%), Instagram (63%), Snapchat (61%), and YouTube (51%) daily.⁵ Although respondents to our survey were not specifically asked about the frequency of their use of social media and our data set includes patients younger than 18 years, we know that social media use has been increasing over the last decade among adolescents.¹ Therefore, we assume that more than one-half of respondents to our survey use their reported social media platforms daily.

Social media is an underused medium for skin cancer prevention education and can reach those who do not regularly see a dermatologist. Unlike printed pamphlets and posters, advertisements through social media can use metrics such as age, race, gender, and interests to target high-risk individuals.

Study Limitations
This was a single-site study of currently enrolled dermatology patients who might be more aware of skin protection than the general population because they are being treated by a dermatologist. Survey questions regarding demographics, required by our institution, could not effectively differentiate Hispanic and White patients. Respondents could have been subject to the Hawthorne effect—awareness that their behavior is being observed—when responding to the survey because it was administered in the office prior to being seen by a dermatologist.

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].