Mary Martini

Melanoma, version 4.2014: Featured updates to the NCCN guidelines

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

Polyploidy in Spitz nevi: A not uncommon karyotypic abnormality identifiable by fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) often reveals imbalanced chromosomal gains in melanoma, whereas Spitz nevi typically have a normal complement of chromosomes. However, there may be a subset of Spitz nevi that are perfectly tetraploid by FISH analysis, and these cases may be confused diagnostically with melanoma. This study evaluates 41 cases of Spitz nevi that were histologically confirmed to be benign. Four of these lesions demonstrated polyploidy by FISH. Three of the 4 cases were from the same patient, a 17-year-old woman; 1 lesion was from the wrist, whereas the other 2 were from the buttocks. The other case was from a 14-year-old man from the ankle. All 4 cases that were polyploid were confirmed using a probe for the X chromosome. This article highlights the importance of polyploidy as a feature of some benign Spitz nevi.

Skin Self-Examination Education for Early Detection of Melanoma: A Randomized Controlled Trial of Internet, Workbook, and In-Person Interventions

Background Early detection of melanoma improves survival. Since many melanoma patients and their spouses seek the care of a physician after discovering their melanoma, an ongoing study will determine the efficacy of teaching at-risk melanoma patients and their skin check partner how to conduct skin self-examinations (SSEs). Internet-based health behavior interventions have proven efficacious in creating behavior change in patients to better prevent, detect, or cope with their health issues. The efficacy of electronic interactive SSE educational intervention provided on a tablet device has not previously been determined. Objective The electronic interactive educational intervention was created to develop a scalable, effective intervention to enhance performance and accuracy of SSE among those at-risk to develop melanoma. The intervention in the office was conducted using one of the following three methods: (1) in-person through a facilitator, (2) with a paper workbook, or (3) with a tablet device used in the clinical office. Differences related to method of delivery were elucidated by having the melanoma patient and their skin check partner provide a self-report of their confidence in performing SSE and take a knowledge-based test immediately after receiving the intervention. Methods The three interventions used 9 of the 26 behavioral change techniques defined by Abraham and Michie to promote planning of monthly SSE, encourage performing SSE, and reinforce self-efficacy by praising correct responses to knowledge-based decision making and offering helpful suggestions to improve performance. In creating the electronic interactive SSE educational intervention, the educational content was taken directly from both the scripted in-person presentation delivered with Microsoft PowerPoint by a trained facilitator and the paper workbook training arms of the study. Enrollment totaled 500 pairs (melanoma patient and their SSE partner) with randomization of 165 pairs to the in-person, 165 pairs to the workbook, and 70 pairs to electronic interactive SSE educational intervention. Results The demographic survey data showed no significant mean differences between groups in age, education, or income. The tablet usability survey given to the first 30 tablet pairs found that, overall, participants found the electronic interactive intervention easy to use and that the video of the doctor-patient-partner dialogue accompanying the dermatologist’s examination was particularly helpful in understanding what they were asked to do for the study. The interactive group proved to be just as good as the workbook group in self-confidence of scoring moles, and just as good as both the workbook and the in-person intervention groups in self-confidence of monitoring their moles. While the in-person intervention performed significantly better on a skill-based quiz, the electronic interactive group performed significantly better than the workbook group. The electronic interactive and in-person interventions were more efficient (30 minutes), while the workbook took longer (45 minutes). Conclusions This study suggests that an electronic interactive intervention can deliver skills training comparable to other training methods, and the experience can be accommodated during the customary outpatient office visit with the physician. Further testing of the electronic interactive intervention’s role in the anxiety of the pair and pair-discovered melanomas upon self-screening will elucidate the impact of these tools on outcomes in at-risk patient populations. Trial Registration ClinicalTrials.gov NCT01013844; http://clinicaltrials.gov/show/NCT01013844 (Archived by WebCite at http://www.webcitation.org/6LvGGSTKK).

Two cases of multiple Spitz nevi: Correlating clinical, histologic, and fluorescence in situ hybridization findings

BACKGROUND The occurrence of multiple Spitz nevi is rare, especially the disseminated variant. Multiple Spitz nevi may be confused with, and must be differentiated from, primary spitzoid melanoma and cutaneous melanoma metastases. Over the past decade, fluorescence in situ hybridization (FISH) has emerged as a tool for studying melanocytic neoplasms, helping to differentiate between melanoma and benign melanocytic nevi. We describe 2 cases of patients with multiple Spitz nevi and their FISH results. OBSERVATIONS One case of disseminated Spitz nevi, in a 17-year-old female, showed balanced tetraploidy using FISH, while the other case, in a 51-year-old female with multiple Spitz nevi, showed normal diploid cells without significant gains or losses in chromosomes 6 or 11. CONCLUSIONS Patients may present with multiple, even disseminated, Spitz nevi. This phenotype should not be confused with melanoma and/or cutaneous metastasis. The use of FISH studies in context with careful correlation of clinical features and dermoscopic and histologic findings can assist in the diagnostic workup.

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

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 Forces 2016 Draft Recommendation Statement on skin cancer screening.

Melanoma simulation model: promoting opportunistic screening and patient counseling.

IMPORTANCE Lack of training hampers melanoma recognition by physicians. OBJECTIVE To evaluate a melanoma simulation model to teach visual assessment and counseling skills. DESIGN AND SETTING Simulation model study in an academic research setting. PARTICIPANTS A convenience sample of third-year medical students was randomly assigned to receive the intervention before or after a standardized patient. INTERVENTION During the primary care clerkship, medical students participated in melanoma skills training using 2 simulation models replicating melanomas and abnormal or benign nevi. Scoring threshold rules for visual assessment and management of pigmented lesions and videos of patient counseling were provided. MAIN OUTCOME MEASURES Identifying a melanoma moulage and counseling the standardized patient. Secondary measures were preintervention and 2-week postintervention knowledge, attitudes about and confidence in their ability to perform opportunistic surveillance and counseling, as well as identification on the model of clinically suspicious pigmented lesions, lesions needing a biopsy, and lesions to be monitored for change. RESULTS Among 74 students, confidence in their ability to perform opportunistic surveillance improved significantly after skills training (P < .05, χ2 test). Monitoring clinically suspicious lesions for change decreased from 16% (12 of 74) to 3% (2 of 74) and performing a biopsy increased from 80% (59 of 74) to 96% (71 of 74), monitoring benign lesions for change decreased from 43% (32 of 74) to 3% (2 of 74), and biopsying melanoma in situ increased from 10% (7 of 74) to 26% (20 of 74) (P < .05 for all, χ2 test). Detection of the melanoma moulage on the standardized patient occurred more often by trained students (P < .05, χ2 test). CONCLUSION AND RELEVANCE A 1-hour melanoma simulation education and skills training experience improved performance of opportunistic surveillance, management, and patient counseling by third-year medical students. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01191294.

Dermatoscopic evolution of dysplastic nevi showing high-grade dysplasia in a metastatic melanoma patient on vemurafenib

doxorubicin because of the switch of her chemotherapy to a taxol, another known trigger of SCLE. Although a paraneoplastic cause of her SCLE could not be fully excluded, chemotherapy-induced SCLE seemed more likely given the strong temporal correlation with the patient’s chemotherapy regimen. Previously, doxorubicin and cyclophosphamide combination therapy has been reported to cause SCLE-like eruptions in 3 patients and exacerbation of pre-existing SCLE in a fourth, with resolution upon discontinuation. Doxorubicin was theorized to be the primary culprit as cyclophosphamide is not a known photosensitizer, as our case supports. Other chemotherapeutic agents that have been implicated in SCLE include taxols, tamoxifen, and capecitabine. The pathogenesis of chemotherapy-induced SCLE may involve increased apoptosis, concomitant release of nucleosomes, and subsequent autoimmune sensitization. Altogether, physicians should maintain a high index of suspicion for drug-induced SCLE in patients on doxorubicin. A careful drug history is vital when evaluating all cases of SCLE.

Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma

Background: Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable. Objective: We sought to provide clinicians with such a tool. Methods: A 2‐gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy. Results were compared with standard histopathologic assessment in lesions with a consensus diagnosis among 3 experienced dermatopathologists. Results: In 398 validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME detection appropriately differentiated melanoma from nonmelanoma samples with a sensitivity of 91% and a specificity of 69%. We established LINC00518 and PRAME in both adhesive patch melanoma samples and underlying formalin fixed paraffin embedded (FFPE) samples of surgically excised primary melanomas and in melanoma lymph node metastases. Limitations: This technology cannot be used on mucous membranes, palms of hands, and soles of feet. Conclusions: This noninvasive 2‐gene pigmented lesion assay classifies pigmented lesions into melanoma and nonmelanoma groups and may serve as a tool to help with diagnostic challenges that may be inherently linked to the visual image and pattern recognition approach. Graphical abstract: Figure. No Caption available.

Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study

IntroductionControversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).ObjectiveThe aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers.MethodsThis was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses.ResultsAmong the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35).ConclusionsA safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

Comparison of Efficacy of Differing Partner-Assisted Skin Examination Interventions for Melanoma Patients: A Randomized Clinical Trial

IMPORTANCE Early detection of melanoma may improve survival. The present study continued research establishing that in-person training on skin self-examinations (SSEs) was significantly enhanced when delivered to patients with their partners present instead of to patients alone. OBJECTIVE To examine 3 alternative SSE training approaches that included partners compared with a treatment-as-usual control condition. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial with 4- and 12-month follow-up visits was conducted at the clinical offices in the ambulatory care area of a hospital. The evaluable population included 494 patients with stage 0 to IIB melanoma and their skin check partners drawn from an electronic medical record melanoma registry and advertisements in large regional newspapers. The study was conducted from June 6, 2011, to April 14, 2014, and analysis was performed between December 4 and December 11, 2014. INTERVENTIONS Pairs of patients and their partners were randomly assigned to (1) in-person intervention, (2) take-home booklet intervention, and (3) treatment-as-usual controls. An additional subgroup of patients received an electronic interactive tablet personal computer intervention. The MoleScore content was comparable across formats and consisted of demonstrations of the ABCDE (assess border, color, diameter, and evolution of pigmented lesions) rule and skills training. MAIN OUTCOMES AND MEASURES Outcomes were self-reported SSE of the total body as well as easy-to-see and difficult-to-see regions at baseline, 4 months, and 12 months. RESULTS No significant differences in SSEs were observed between the 3 intervention conditions on all of the body areas; results for all 3 intervention conditions were significantly higher than for controls at 4- and 12-month follow-ups (all P < .05). Mean (SD) body areas examined by control pairs (n = 99) at 4 months (0.98 [1.17]) and 12 months (1.82 [1.43]) were significantly less compared with examination by pairs participating in all interventions at 4 months (workbook [n = 159], 2.68 [1.19]; in-person [n = 165], 2.66 [1.11]; and tablet [n = 71], 2.53 [1.17]) and at 12 months (workbook, 2.53 [1.25]; in-person, 2.59 [1.30]; and tablet, 2.34 [1.37]) (F6,674 = 15.60; P < .001; η2 = 0.12). CONCLUSIONS AND RELEVANCE The findings of the research support the sustainability and efficacy at 12 months of partner-assisted SSE interventions for early detection targeting individuals with a history of melanoma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01432860.