Publications by authors named "Michael E Ming"

63 Publications

Age and Mitogenicity are Important Predictors of Sentinel Lymph Node Metastasis in T1a Melanoma.

Ann Surg Oncol 2021 Apr 8. Epub 2021 Apr 8.

Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

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http://dx.doi.org/10.1245/s10434-021-09929-5DOI Listing
April 2021

Association of the Affordable Care Act's Medicaid expansion with the diagnosis and treatment of clinically localized melanoma: A National Cancer Database study.

J Am Acad Dermatol 2021 Feb 4. Epub 2021 Feb 4.

Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.

Background: The Affordable Care Act's Medicaid expansion is associated with earlier diagnosis and improved care among lower socioeconomic status populations with cancer, but its impact on melanoma is undefined.

Objective: To determine the association of Medicaid expansion with stage of diagnosis and use of sentinel lymph node biopsy in nonelderly adult patients with newly diagnosed clinically localized melanoma.

Methods: Quasi-experimental, difference-in-differences retrospective cohort analysis using data from the National Cancer Database from 2010 to 2017. Patients from expansion versus nonexpansion states and diagnosed before (2010-2013) versus after (2014-2017) expansion were identified.

Results: Of 83,322 patients, 46.6% were female, and the median age was 55 years (interquartile range, 49-60). After risk adjustment, Medicaid expansion was associated with a decrease in the diagnosis of T1b stage or higher melanoma (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.88-0.98; P = .011) and decrease in uninsured status (OR, 0.61; 95% CI, 0.52-0.72; P < .001) but was not associated with a difference in sentinel lymph node biopsy performance when indicated (OR, 1.06; 95% CI, 0.95-1.20; P = .29).

Limitations: Retrospective study using a national database.

Conclusion: In this study of patients with clinically localized melanoma, Medicaid expansion was associated with a decrease in the diagnosis of later T-stage tumors.
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http://dx.doi.org/10.1016/j.jaad.2021.01.097DOI Listing
February 2021

Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit.

JAMA Dermatol 2020 09;156(9):1004-1011

Stanford University Medical Center and Cancer Institute, Stanford, California.

Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care.

Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies.

Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed.

Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility.

Conclusions And Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.
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http://dx.doi.org/10.1001/jamadermatol.2020.1729DOI Listing
September 2020

Urethral involvement is associated with higher mortality and local recurrence in vulvar melanoma: a single institutional experience.

Hum Pathol 2020 10 20;104:1-8. Epub 2020 Jul 20.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address:

Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared with approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow-up data in our institutional databases. Most patients were Caucasian (n = 35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n = 25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 years), those with thin melanomas (≤1 mm), and those with Clark's level II or III tumors had better 5-year survival rates than older patients (65-83 years) and those with thick melanomas (>1 mm) and those with Clark's level IV or V (P ≤ 0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in 15 patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (P = 0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with mortality, pathology excision specimens should be carefully reviewed with attention to urethral involvement as a potentially important prognostic factor.
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http://dx.doi.org/10.1016/j.humpath.2020.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669565PMC
October 2020

Evaluation of the Merits and Limitations of Evidence-Based Medicine.

JAMA Dermatol 2020 08;156(8):924-925

Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1001/jamadermatol.2020.1940DOI Listing
August 2020

Use of new molecular tests for melanoma by pigmented-lesion experts.

J Am Acad Dermatol 2020 01 13;82(1):245-247. Epub 2019 Aug 13.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City; Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2019.08.022DOI Listing
January 2020

Risk of Subsequent Cutaneous Melanoma in Moderately Dysplastic Nevi Excisionally Biopsied but With Positive Histologic Margins.

JAMA Dermatol 2018 12;154(12):1401-1408

Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.

Importance: Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins).

Objective: To determine outcomes and risk for the development of subsequent cutaneous melanoma (CM) from moderately dysplastic nevi with positive histologic margins observed for 3 years or more.

Design, Setting, And Participants: A multicenter (9 US academic dermatology sites) retrospective cohort study was conducted of patients 18 years or older with moderately dysplastic nevi with positive histologic margins and 3 years or more of follow-up data collected consecutively from January 1, 1990, to August 31, 2014. Records were reviewed for patient demographics, biopsy type, pathologic findings, and development of subsequent CM at the biopsy site or elsewhere on the body. The χ2 test, the Fisher exact test, and analysis of variance were used to assess univariate association for risk of subsequent CMs, in addition to multivariable logistic regression models. To confirm histologic grading, each site submitted 5 random representative slide cases for central dermatopathologic review. Statistical analysis was performed from October 1, 2017, to June 22, 2018.

Main Outcomes And Measures: Development of CM at a biopsy site or elsewhere on the body where there were moderately dysplastic nevi with positive histologic margins.

Results: A total of 467 moderately dysplastic nevi with positive histologic margins from 438 patients (193 women and 245 men; mean [SD] age, 46.7 [16.1] years) were evaluated. No cases developed into CM at biopsy sites, with a mean (SD) follow-up time of 6.9 (3.4) years. However, 100 patients (22.8%) developed a CM at a separate site. Results of multivariate analyses revealed that history of CM was significantly associated with the risk of development of subsequent CM at a separate site (odds ratio, 11.74; 95% CI, 5.71-24.15; P < .001), as were prior biopsied dysplastic nevi (odds ratio, 2.55; 95% CI, 1.23-5.28; P = .01). The results of a central dermatopathologic review revealed agreement in 35 of 40 cases (87.5%). Three of 40 cases (7.5%) were upgraded in degree of atypia; of these, 1 was interpreted as melanoma in situ. That patient remains without recurrence or evidence of CM after 5 years of follow-up.

Conclusions And Relevance: This study suggests that close observation with routine skin surveillance is a reasonable management approach for moderately dysplastic nevi with positive histologic margins. However, having 2 or more biopsied dysplastic nevi (with 1 that is a moderately dysplastic nevus) appears to be associated with increased risk for subsequent CM at a separate site.
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http://dx.doi.org/10.1001/jamadermatol.2018.3359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583364PMC
December 2018

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Cancer 2019 01 3;125(1):18-44. Epub 2018 Oct 3.

Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.
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http://dx.doi.org/10.1002/cncr.31719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860362PMC
January 2019

Piloting the Use of Smartphones, Reminders, and Accountability Partners to Promote Skin Self-Examinations in Patients with Total Body Photography: A Randomized Controlled Trial.

Am J Clin Dermatol 2018 Oct;19(5):779-785

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Objective: The aim of this study was to evaluate the use of a mobile application (app) in patients already using total body photography (TBP) to increase skin self-examination (SSE) rates and pilot the effectiveness of examination reminders and accountability partners.

Design: Randomized controlled trial with computer generated randomization table to allocate interventions.

Setting: University of Pennsylvania pigmented lesion clinic.

Participants: 69 patients aged 18 years or older with an iPhone/iPad, who were already in possession of TBP photographs.

Intervention: A mobile app loaded with digital TBP photos for all participants, and either (1) the mobile app only, (2) skin examination reminders, (3) an accountability partner, or (4) reminders and an accountability partner.

Main Outcome Measure: Change in SSE rates as assessed by enrollment and end-of-study surveys 6 months later.

Results: Eighty one patients completed informed consent, however 12 patients did not complete trial enrollment procedures due to device incompatibility, leaving 69 patients who were randomized and analyzed [mean age 54.3 years, standard deviation 13.9). SSE rates increased significantly from 58% at baseline to 83% at 6 months (odds ratio 2.64, 95% confidence interval 1.20-4.09), with no difference among the intervention groups. The group with examination reminders alone had the highest (94%) overall satisfaction, and the group with accountability partners alone accounted for the lowest (71%).

Conclusion: A mobile app alone, or with reminders and/or accountability partners, was found to be an effective tool that can help to increase SSE rates. Skin examination reminders may help provide a better overall experience for a subset of patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT02520622.
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http://dx.doi.org/10.1007/s40257-018-0372-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126944PMC
October 2018

Timing of Onset of Adverse Cutaneous Reactions Associated With Programmed Cell Death Protein 1 Inhibitor Therapy.

JAMA Dermatol 2018 09;154(9):1057-1061

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Importance: An increasing number of cutaneous adverse reactions resulting from use of programmed cell death protein 1 (PD-1) inhibitors have been described, but with relatively little focus to date on the timing of these reactions.

Objective: To determine the timing of cutaneous drug reactions after initiation of PD-1 inhibitor therapy.

Design, Setting, And Participants: This retrospective observational study included patients referred to an academic dermatology clinic by an oncologist from January 1, 2014, through February 28, 2018, with at least 1 skin biopsy specimen of a skin reaction associated with PD-1 inhibitor use. Participants were included if they had a biopsy-proven cutaneous reaction in response to a PD-1 inhibitor used alone or in combination with ipilimumab.

Exposures: All patients included in this study received pembrolizumab, nivolumab, or nivolumab with ipilimumab as immunotherapy for cancer.

Main Outcomes And Measures: The main outcome measure was time to onset of biopsy-proven cutaneous reactions that occurred during or after use of pembrolizumab or nivolumab.

Results: A total of 17 patients (12 men, 5 women; mean [SD] age, 68.6 [11.1] years) were identified who presented with cutaneous adverse reactions associated with PD-1 inhibitor therapy; these reactions included lichenoid dermatitis, bullous pemphigoid, erythema multiforme, eczema, lupus, and sarcoidosis. Twelve patients presented with reactions at least 3 months after beginning pembrolizumab or nivolumab therapy. The skin reactions presented a median (range) of 4.2 months (0.5-38.0 months) after drug initiation. In 5 cases, the cutaneous adverse reactions attributed to the PD-1 inhibitor therapy developed after the drug therapy was terminated.

Conclusions And Relevance: Diverse cutaneous adverse reactions secondary to PD-1 inhibitor use may present with delayed onsets and even after discontinuation of therapy. Dermatologists should be aware of the potential for delayed presentations of cutaneous adverse reactions.
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http://dx.doi.org/10.1001/jamadermatol.2018.1912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143042PMC
September 2018

Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

JAMA Dermatol 2018 05;154(5):574-580

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.

Importance: Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma.

Objective: To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients.

Design, Setting, And Participants: This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017.

Exposure: Marital status, categorized as married, never married, divorced, or widowed.

Main Outcomes And Measures: Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm.

Results: A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married patients were more likely to undergo SLNB in lesions with Breslow thickness greater than 1 mm, for which SLNB is routinely recommended, compared with never married (OR, 0.59; 95% CI, 0.53-0.65; P < .001), divorced (OR, 0.87; 95% CI, 0.76-0.99; P = .03), and widowed (OR, 0.69; 95% CI, 0.62-0.76; P < .001) patients.

Conclusions And Relevance: Marital status is associated with earlier presentation of localized melanoma. Moreover, never married, divorced, and widowed patients are less likely to undergo SLNB for appropriate lesions. Marital status should be considered when counseling patients for melanoma procedures and when recommending screening and follow-up to optimize patient care.
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http://dx.doi.org/10.1001/jamadermatol.2018.0233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128501PMC
May 2018

The prognostic significance of tumor-infiltrating lymphocytes for primary melanoma varies by sex.

J Am Acad Dermatol 2018 Aug 5;79(2):245-251. Epub 2018 Mar 5.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: The immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored.

Methods: Patients who had clinically localized primary melanoma with a Breslow thickness of 0.76 mm or more and underwent sentinel lymph node (SLN) biopsy at our institution were identified. The association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated by using logistic regression. Overall survival (OS) was evaluated by TIL status and sex.

Results: Among 1367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (P = .71). SLN positivity was associated with TILs among men (brisk, 3.8%; nonbrisk, 16.9%; and absent, 26.6% [P < .001]). In contrast, there was no association between SLN positivity and TILs among women (P = .49). Interaction between brisk TILs and sex on SLN positivity was significant (P = .029). Among men, presence of brisk TILs was associated with prolonged OS (P = .038) but not after adjustment for SLN status (P = .42). There was no association between TIL status and OS among women.

Limitations: Findings from this single-institution study have yet to be validated by other research groups.

Conclusions: The implications of TILs in predicting SLN positivity appear to be more relevant for men than for women.
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http://dx.doi.org/10.1016/j.jaad.2018.02.066DOI Listing
August 2018

Impact of a smartphone application on skin self-examination rates in patients who are new to total body photography: A randomized controlled trial.

J Am Acad Dermatol 2018 Sep 10;79(3):564-567. Epub 2018 Feb 10.

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2018.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086771PMC
September 2018

Management strategies of academic pigmented lesion clinic directors in the United States.

J Am Acad Dermatol 2018 Aug 4;79(2):367-369. Epub 2018 Jan 4.

Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2017.12.069DOI Listing
August 2018

Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy.

Melanoma Manag 2017 Mar 1;4(1):13-37. Epub 2017 Mar 1.

University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.
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http://dx.doi.org/10.2217/mmt-2016-0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480135PMC
March 2017

Association Between Patient Age and Lymph Node Positivity in Thin Melanoma.

JAMA Dermatol 2017 09;153(9):866-873

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.

Importance: More than half of all new melanoma diagnoses present as clinically localized T1 melanoma, yet sentinel lymph node biopsy (SLNB) is controversial in this population given the overall low yield. Guidelines for SLNB have focused on pathologic factors, but patient factors, such as age, are not routinely considered.

Objectives: To identify indicators of lymph node (LN) metastasis in thin melanoma in a large, generalizable data set and to evaluate the association between patient age and LN positivity.

Design, Setting, And Participants: A retrospective cohort study using the National Cancer Database, an oncology database representing patients from more than 1500 hospitals throughout the United States, was performed (2010-2013). Data analysis was conducted from October 1, 2016, to January 15, 2017. A total of 8772 patients with clinical stage I 0.50 to 1.0 mm thin melanoma undergoing wide excision and surgical evaluation of regional LNs were included for study.

Main Outcome And Measures: The primary outcome of interest was presence of melanoma in a biopsied regional LN. Clinicopathologic factors associated with LN positivity were characterized, using logistic regression. Age was categorized as younger than 40 years, 40 to 64 years, and 65 years or older for multivariable analysis. Classification tree analysis was performed to identify high-risk groups for LN positivity.

Results: Among the study cohort (n = 8772), 333 patients had nodal metastases, for an overall positivity rate of 3.8% (95% CI, 3.4%-4.2%). A total of 4087 (54.0%) patients were women. Median age was 56 years (interquartile range [IQR], 46-67) in patients with negative LNs and 52 years (IQR, 41-61) in those with positive LNs (P < .001). In multivariable analysis, younger age, female sex, thickness of 0.76 mm or larger, increasing Clark level, mitoses, ulceration, and lymphovascular invasion were independently associated with LN positivity. In decision tree analysis, patient age was identified as an important risk stratifier for LN metastases, after mitoses and thickness. Patients younger than 40 years with category T1b tumors 0.50 to 0.75 mm, who would generally not be recommended for SLNB, had an LN positivity rate of 5.6% (95% CI, 3.3%-8.6%); conversely, patients 65 years or older with T1b tumors 0.76 mm or larger, who would generally be recommended for SLNB, had an LN positivity rate of only 3.9% (95% CI, 2.7%-5.3%).

Conclusions And Relevance: Patient age is an important factor in estimating lymph node positivity in thin melanoma independent of traditional pathologic factors. Age therefore should be taken into consideration when selecting patients for nodal biopsy.
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http://dx.doi.org/10.1001/jamadermatol.2017.2497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710422PMC
September 2017

Risk factors for positive or equivocal margins after wide local excision of 1345 cutaneous melanomas.

J Am Acad Dermatol 2017 Aug;77(2):333-340.e1

Department of Dermatology, University of Pennsylvania Health System, Philadelphia, Pennsylvania.

Background: Positive or equivocal margins after wide local excision (WLE) complicate surgical management of cutaneous melanoma.

Objective: To identify the frequency of and risk factors for positive or equivocal margins after WLE of cutaneous melanoma.

Methods: Retrospective, single-center, cross-sectional study of 1345 consecutive melanomas treated with WLE.

Results: The overall frequency of positive or equivocal margins was 4.2% (56/1345), ranging from 2.2% to 22.6%, depending on the size of the surgical margins, patient characteristics, biopsy history, and the clinicopathology of the melanoma. In descending order, independent risk factors associated with the greatest odds for positive or equivocal margins after multivariate analysis were noncompliance with recommended surgical margins (odds ratio [OR] 5.57, P = .002); anatomic location on the head, neck, hands, feet, genitals, or pretibial leg (OR 5.07, P < .001); histologic regression (OR 2.78, P = .007); in situ melanoma (OR 2.27, P = .011); multiple biopsies at the tumor site before WLE (OR 1.92 [per biopsy], P = .004); and increasing age (OR 1.049 [per year], P < .001).

Limitations: This was a single-site, retrospective observational study.

Conclusions: Clinicopathologic factors, especially location in cosmetically or functionally sensitive areas and noncompliance with recommended surgical margins, identified melanomas at increased risk for positive or equivocal margins after WLE.
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http://dx.doi.org/10.1016/j.jaad.2017.03.025DOI Listing
August 2017

Commentary: The quest for an improved risk stratification tool for patients with melanoma.

Authors:
Michael E Ming

J Am Acad Dermatol 2017 05;76(5):826-828

Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2017.02.045DOI Listing
May 2017

Assessment of smartphone applications for total body digital photography-guided skin exams by patients.

J Am Acad Dermatol 2016 Nov;75(5):1063-1064.e1

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2016.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859953PMC
November 2016

Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma.

J Cutan Pathol 2016 Sep 1;43(9):787-91. Epub 2016 Jun 1.

Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.

Therapeutic immune checkpoint blockade for metastatic melanoma has been associated with vitiligo, pruritus and morbilliform eruptions. Reports of other autoimmune skin disease in this setting are rare. We sought to expand the spectrum of cutaneous immune-mediated effects related to immune checkpoint inhibitor therapy. In this report, we describe two unusual cutaneous reactions related to checkpoint inhibitor therapy, namely bullous pemphigoid (BP) and dermatitis herpetiformis. The development of BP and dermatitis herpetiformis in the context of checkpoint inhibitor therapy is consistent with previous investigations supporting the importance of effector and regulatory T cells in the pathogenesis of these diseases.
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http://dx.doi.org/10.1111/cup.12735DOI Listing
September 2016

Acral Lentiginous Histologic Subtype and Sentinel Lymph Node Positivity in Thin Melanoma.

JAMA Dermatol 2016 07;152(7):836-7

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1001/jamadermatol.2016.0875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955510PMC
July 2016

Identification of Patients with Intermediate Thickness Melanoma at Low Risk for Sentinel Lymph Node Positivity.

Ann Surg Oncol 2016 Jan 28;23(1):250-6. Epub 2015 Jul 28.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, USA.

Introduction: Sentinel lymph node (SLN) biopsy is recommended for all patients with intermediate-thickness melanomas. We sought to identify such patients at low risk of SLN positivity.

Methods: All patients with intermediate-thickness melanomas (1.01-4 mm) undergoing SLN biopsy at a single institution from 1995-2011 were included in this retrospective cohort study. Univariate and multivariate logistic regression determined factors associated with a low risk of SLN positivity. Classification and regression tree (CART) analysis was used to stratify groups based on risk of positivity.

Results: Of the 952 study patients, 157 (16.5 %) had a positive SLN. In the multivariate analysis, thickness <1.5 mm (odds ratio [OR] 0.29), age ≥60 (OR 0.69), present tumor-infiltrating lymphocytes (OR 0.60), absent lymphovascular invasion (OR 0.46), and absent satellitosis (OR 0.44) were significantly associated with a low risk of SLN positivity. CART analysis identified thickness of 1.5 mm as the primary cut point for risk of SLN metastasis. Patients with a thickness of <1.5 mm represented 36 % of the total cohort and had a SLN positivity rate of 6.6 % (95 % confidence interval 3.8-9.4 %). In patients with melanomas <1.5 mm in thickness, the presence of additional low risk factors identified 257 patients (75 % of patients with <1.5 mm melanomas) in which the rate of SLN positivity was <5 %.

Conclusions: Despite a SLN positivity rate of 16.5 % overall, substantial heterogeneity of risk exists among patients with intermediate-thickness melanoma. Most patients with melanoma between 1.01 and 1.5 mm have a risk of SLN positivity similar to that in patients with thin melanomas.
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http://dx.doi.org/10.1245/s10434-015-4766-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697873PMC
January 2016

Effects of tailored risk communications for skin cancer prevention and detection: the PennSCAPE randomized trial.

Cancer Epidemiol Biomarkers Prev 2015 Feb 28;24(2):415-21. Epub 2014 Nov 28.

Massachusetts General Hospital, Boston, Massachusetts.

Background: Prevention and early detection measures for melanoma, such as sun avoidance and skin examinations, are important, but are practiced inconsistently. In this replication of the Project SCAPE trial, we sought to determine whether tailored print materials were more effective at improving adherence than generic print materials for patients at increased risk of skin cancer.

Methods: Participants were randomized to receive personalized mailed communications about their skin cancer risk and recommended sun protection, or generic mailings. Participants were Caucasian adults, at moderate or high risk for skin cancer, recruited in outpatient primary care. The main outcomes were overall sun protection behaviors and specific protective behaviors including use of sunscreen, shirt, hat, sunglasses, shade, and sun avoidance; recent sunburns; and skin self-examination and provider skin examination.

Results: One hundred ninety-two (93.2%) subjects completed the study. Six outcome variables showed significant intervention condition effects in mixed effects models: overall sun protection behavior (P = 0.025); sunscreen use (P = 0.026); use of sunglasses (P = 0.011); sunburns in the past three months (P = 0.033); recency of last skin self-exam (P = 0.017); and frequency of skin exams by health care provider (P = 0.016).

Conclusions: Relative to generic communications, tailored risk communications resulted in improved adherence to six skin cancer protective behaviors, including a composite sun protection behavior measure, sunburns, and health care provider skin examinations.

Impact: Tailored interventions can be more effective in improving patient prevention behaviors than nontailored, generic information for patients at moderate to high risk of skin cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-14-0926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323936PMC
February 2015

Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement.

JAMA Dermatol 2015 Feb;151(2):212-8

Melanoma and Pigmented Lesion Clinic, Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia15Division of Dermatology, Atlanta Veterans Administration Medical Center, Decatur, Georgia.

Importance: The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence.

Objectives: To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins.

Evidence Review: The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed.

Findings: A consensus statement by the PLS of the MPWG following review of the literature, group discussions, and a structured Delphi method consensus.

Conclusions And Relevance: This consensus statement reviews the complexities of management of CAN/DN. A review of the literature and 2 rounds of a structured Delphi consensus resulted in the following recommendations: (1) mildly and moderately DN with clear margins do not need to be reexcised, (2) mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than reexcised, and (3) observation may be a reasonable option for management of moderately DN with positive histologic margins without clinically apparent residual pigmentation; however, more data are needed to make definitive recommendations in this clinical scenario.
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http://dx.doi.org/10.1001/jamadermatol.2014.2694DOI Listing
February 2015

Melanoma genetic testing, counseling, and adherence to skin cancer prevention and detection behaviors.

Cancer Epidemiol Biomarkers Prev 2013 Apr 7;22(4):607-14. Epub 2013 Feb 7.

Perelman School of Medicine and School of Nursing, University of Pennsylvania, 801 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA.

Background: Little is known about the impact of knowledge of CDKN2A and MC1R genotype on melanoma prevention behaviors like sun avoidance and skin examination in the context of familial melanoma.

Methods: Seventy-three adults with a family history of melanoma were randomly assigned to be offered individualized CDKN2A and MC1R genotyping results in the context of a genetic counseling session, or the standard practice of not being offered counseling or disclosure of genotyping results. Mixed effects or longitudinal logistic models were used to determine whether the intervention affected change in sun protection habits, skin examinations, and perception and beliefs related to melanoma risk, prevention, and genetic counseling.

Results: All participants in the intervention group who attended genetic counseling sessions chose to receive their test results. From baseline to follow-up, participants in the intervention group reported an increase in the frequency of skin self-examinations compared with a slight decrease in the control group (P = 0.002). Participants in the intervention group reported a smaller decrease in frequency of wearing a shirt with long sleeves than did participants in the control group (P = 0.047). No effect of the intervention was noted for other outcomes.

Conclusions: Feedback of CDKN2A and MC1R genotype among families without known pathogenic CDKN2A mutations does not seem to decrease sun protection behaviors.

Impact: While disclosure of CDKN2A and MC1R genotype did not have negative effects on prevention, the benefits of communicating this information remain unclear. The small number of families who tested positive for CDKN2A mutations in this study is a limitation.
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http://dx.doi.org/10.1158/1055-9965.EPI-12-1174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617083PMC
April 2013

An atypical melanocytic lesion without genomic abnormalities shows locoregional metastasis.

J Cutan Pathol 2012 Jan;39(1):21-4

Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.

A subset of difficult melanocytic lesions exists with histopathologic features that evade diagnostic consensus from even expert dermatopathologists. Comparative genomic hybridization (CGH) has emerged as a useful diagnostic tool to categorize these lesions, by identifying known chromosomal aberrations in malignant melanoma or the lack thereof in melanocytic nevi. However, determining a lesion's biological behavior primarily on CGH is limited by a relatively small series of corroborative cases without long term follow up. We present a case of a pigmented lesion on the right cheek of a 4 year old boy. The lesion had features of a deep penetrating nevus, but the presence of frequent mitoses, tumor infiltrating lymphocytes, and microscopic foci of tumor necrosis were concerning for an unusual melanoma. We termed this lesion a melanocytic tumor of uncertain potential (MELTUMP) for these reasons. High-resolution array-CGH performed elsewhere on the lesion demonstrated no melanoma-associated genomic abnormalities. A sentinel lymph node biopsy of this patient later revealed multiple small tumor deposits. Although the presence of nodal involvement in similar lesions often do not lead to progressive and fatal disease, this case illustrates that atypical melanocytic lesions with nodal involvement may not demonstrate genomic abnormalities by CGH, and that histopathologic assessment remains paramount in defining these difficult melanocytic lesions. Further comprehensive study of these lesions is needed.
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http://dx.doi.org/10.1111/j.1600-0560.2011.01849.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958928PMC
January 2012