Unnecessary Cost of Post-Mohs Permanent Pathology.

BACKGROUND: By providing tumor-free margins, Mohs micrographic surgery (MMS) results in high cure rates in the treatment of nonmelanoma skin cancers (NMSCs). However, when closure of the post-MMS defect is coordinated with reconstructive surgery, redundant tissue is sometimes submitted for permanent section evaluation. OBJECTIVE: The purpose of our study was to investigate the frequency and effect of this practice. MATERIALS AND METHODS: Patients (12 years and older) with NMSCs cleared by MMS with coordinated closures from 2014 to 2016 were identified. Cost analysis was performed using the 2016 Current Procedural Terminology codes and averaged nation-wide Medicare reimbursement rates. RESULTS: During the study period, 408 cases were coordinated with reconstructive surgeons post-MMS. Of these, 125 had specimens were submitted for permanent section with none showing residual malignancy. There were no significant differences between the cases sent for permanent section and the remaining coordinated MMS cases, with respect to patient age, to basal cell and squamous cell carcinoma histology, or to defect size (p > .05). The marginal cost of sending specimens for permanent section was $121 per case. CONCLUSION: Sending post-MMS redundant tissue for permanent sections may be of limited utility and should not be performed routinely. Additional work is warranted to determine when this practice should be used in conjunction with MMS.

Association of Indoor Tanning Frequency With Risky Sun Protection Practices and Skin Cancer Screening.

IMPORTANCE: Indoor tanning is prevalent among young adults and women and is associated with increased risk of melanoma. Evidence suggests that indoor tanners may be more inclined to adopt poor photoprotective practices that further increase their risk of skin cancer; however, gaps in the literature exist in young adults and by indoor tanning frequency. OBJECTIVE: To examine the association between indoor tanning frequency and behaviors related to skin cancer prevention and to investigate whether these associations vary by age group or sex. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional population-based study of US 2015 National Health Interview Survey data including 10 262 non-Hispanic white adults aged 18 to 60 years without a history of skin cancer. MAIN OUTCOMES AND MEASURES: Rare/never use of sunscreen, protective clothing, shade; multiple sunburns within the past year; previous full-body skin examination. RESULTS: Of the 10 262 individuals in our study population (49% female; median age, 39 y), 787 (7.0%) reported having tanned indoors in the past year. Among individuals aged 18 to 34 years, frequent indoor tanners (≥10 times in the past year) were more likely to report never/rare use of protective clothing (adjusted prevalence ratio [aPR], 1.28; 95% CI, 1.10-1.49) and shade (aPR, 1.32; 95% CI, 1.03-1.70), compared with individuals who did not tan indoors. Among women aged 18 to 60 years, those who frequently tanned indoors were more likely to rarely/never use sunscreen (aPR, 1.34; 95% CI, 1.11-1.62), protective clothing (aPR, 1.27; 95% CI, 1.15-1.42), and shade (aPR, 1.54; 95% CI, 1.25-1.90) on a warm sunny day, as well as more likely to report multiple sunburns in the past year (aPR, 1.21; 95% CI, 1.00-1.45) compared with those who did not tan indoors. Individuals who tanned indoors in the past year were not significantly more likely to have undergone a previous full-body skin examination in any subpopulation examined. CONCLUSIONS AND RELEVANCE: Individuals who tan indoors often exhibited a concurrent tendency to sunburn, avoid sun protection, and avoid skin cancer screening. Thus, the findings highlight that in addition to tanning bed avoidance, it is critical to emphasize sun protection and skin cancer screening in individuals who tan indoors.

Basal Cell Skin Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study.

BACKGROUND: Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. OBJECTIVE: We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. METHODS: We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. RESULTS: Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. LIMITATIONS: Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. CONCLUSION: Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen.

Cutaneous Rosai-Dorfman Disease in a Patient with Human Immunodeficiency Virus.

Rosai-Dorfman disease rarely presents in a solely cutaneous form. A subset of patients with skin limited disease have associated immune disorders such as lupus, autoimmune hemolytic anemia, and Crohn disease. We report an interesting case of cutaneous Rosai Dorfman disease in a patient with human immunodeficiency virus (HIV).

Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin.

BACKGROUND: Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans. RESULTS: We compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples. CONCLUSIONS: These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.

Dermatofibrosarcoma protuberans, version 1.2014.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

Managing the skin toxicities from new melanoma drugs.

Patients treated with ipilimumab or targeted inhibitors of the RAF-MEK-ERK pathway (vemurafenib, dabrafenib, and trametinib) for advanced cutaneous melanoma often experience drug-related skin toxicities denoted as dermatologic adverse events (DAEs). Although rarely life-threatening, DAEs may emerge dramatically and potentially compromise oncologic therapy if not managed in a timely and effective manner. Early recognition of DAEs is critical to providing optimal skin care and prompt consultation with a dermatologist should be obtained when a diagnosis is unclear. The expanding utilization of new melanoma drugs compels physicians to maintain a watchful eye for both known and novel DAEs and to adopt a low threshold to biopsy worrisome skin findings. Numerous therapeutic options are available to manage DAEs including topical and systemic agents as well as surgical and destructive modalities. Applying such methods improves overall patient care and optimizes the effectiveness of new therapies for advanced cutaneous melanoma.

Merkel cell carcinoma, version 1.2014.

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.

PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival.

Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have demonstrated objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression in the tumor microenvironment. To investigate whether MCC might be a target for PD-1/PD-L1 blockade, we examined MCC PD-L1 expression, its association with tumor-infiltrating lymphocytes (TILs), Merkel cell polyomavirus (MCPyV), and overall survival. Sixty-seven MCC specimens from 49 patients were assessed with immunohistochemistry for PD-L1 expression by tumor cells and TILs, and immune infiltrates were characterized phenotypically. Tumor cell and TIL PD-L1 expression were observed in 49% and 55% of patients, respectively. In specimens with PD-L1(+) tumor cells, 97% (28/29) demonstrated a geographic association with immune infiltrates. Among specimens with moderate-severe TIL intensities, 100% (29/29) demonstrated PD-L1 expression by tumor cells. Significant associations were also observed between the presence of MCPyV DNA, a brisk inflammatory response, and tumor cell PD-L1 expression: MCPyV(-) tumor cells were uniformly PD-L1(-). Taken together, these findings suggest that a local tumor-specific and potentially MCPyV-specific immune response drives tumor PD-L1 expression, similar to previous observations in melanoma and head and neck squamous cell carcinomas. In multivariate analyses, PD-L1(-) MCCs were independently associated with worse overall survival (hazard ratio 3.12; 95% CI, 1.28-7.61; p=0.012). These findings suggest that an endogenous immune response promotes PD-L1 expression in the MCC microenvironment when MCPyV is present, and provide a rationale for investigating therapies blocking PD-1/PD-L1 for patients with MCC.

Merkel cell carcinoma: update and review.

Merkel cell carcinoma (MCC) is a rare, aggressive, and often fatal cutaneous malignancy that is not usually suspected at the time of biopsy. Because of its increasing incidence and the discovery of a possible viral association, interest in MCC has escalated. Recent effort has broadened our breadth of knowledge regarding MCC and developed instruments to improve data collection and future study. This article provides an update on current thinking about the Merkel cell and MCC.

Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta3-catenin signaling.

Constitutive Hedgehog (Hh) signaling underlies several human tumors, including basal cell carcinoma (BCC) and basaloid follicular hamartoma in skin. Intriguingly, superficial BCCs arise as de novo epithelial buds resembling embryonic hair germs, collections of epidermal cells whose development is regulated by canonical Wnt/beta-catenin signaling. Similar to embryonic hair germs, human BCC buds showed increased levels of cytoplasmic and nuclear beta-catenin and expressed early hair follicle lineage markers. We also detected canonical Wnt/ beta-catenin signaling in epithelial buds and hamartomas from mice expressing an oncogene, M2SMO, leading to constitutive Hh signaling in skin. Conditional overexpression of the Wnt pathway antagonist Dkk1 in M2SMO-expressing mice potently inhibited epithelial bud and hamartoma development without affecting Hh signaling. Our findings uncover a hitherto unknown requirement for ligand-driven, canonical Wnt/ beta-catenin signaling for Hh pathway-driven tumorigenesis, identify a new pharmacological target for these neoplasms and establish the molecular basis for the well-known similarity between early superficial BCCs and embryonic hair germs.

The effects of a professionally produced videotape on education and anxiety/distress levels for patients with newly diagnosed melanoma: a randomized, prospective clinical trial.

OBJECTIVE: Little is known about the effects of videotape-based education on knowledge and anxiety levels among patients with melanoma. We sought to evaluate effects of a professionally produced videotape on the knowledge and distress levels among patients with newly diagnosed melanoma. Secondarily, we sought to compare these effects with those of a traditional clinic visit. METHODS: We conducted a randomized controlled trial involving 217 patients. An intervention group underwent questionnaire-based testing of melanoma knowledge and anxiety/distress levels before and after viewing an educational videotape. A control group underwent similar testing before and after a clinic visit. RESULTS: The videotape and clinical encounter significantly increased knowledge and decreased anxiety. Improvement in knowledge levels was significantly greater after viewing the videotape compared with the clinic visit, whereas anxiety levels decreased to a greater degree after the clinical encounter. Whether or not a synergistic relationship may exist between exposure to an educational videotape and a physician visit was not specifically evaluated in this study. CONCLUSION: Videotape-based education may be more effective than that provided by a clinic visit, whereas the clinical encounter appears to be more effective in alleviating patient anxiety/distress.

Patterns of Internet use and impact on patients with melanoma.

BACKGROUND: Patients with cancer and their families frequently, and increasingly, turn to outside sources for information, particularly the World Wide Web. Our objective was to examine the use of the Internet and its impact among patients with melanoma. METHODS: A prospective survey was obtained from 1613 consecutive patients with cutaneous melanoma seen at our institution between August 2001 and February 2003. Main outcome measures included the ability to access the Internet, Internet use to search for melanoma information, and responses to such Internet searches. Further analysis of whether there were differences based on age, sex, or disease severity was performed. RESULTS: Of patients with melanoma, 39% indicated that they had used the Internet to research their disease, 30% themselves and 9% had someone else do it for them. Nearly half (47%) of patients younger than 40 years researched melanoma on the Internet compared with only 12% of patients 60 years or older. Neither sex nor disease severity impacted Internet use. The vast majority of patients (94%) thought the Internet was useful, 67% believed it helped them better understand their condition, and 45% said they would recommend using the Internet to others to find information about medical conditions. Roughly a third thought it decreased their anxiety, whereas a similar proportion believed the Internet made them more anxious. Increased anxiety correlated with decreasing age and increasing disease severity. CONCLUSIONS: The use of the Internet is common among patients with melanoma. Anxiety attributed to online information about their disease suggests that clinicians caring for patients with melanoma should familiarize themselves with online melanoma information, and be proactive in assisting their patients in using this resource.

Microstaging accuracy after subtotal incisional biopsy of cutaneous melanoma.

BACKGROUND: A significant portion of cutaneous melanoma may remain after subtotal incisional biopsy. The accuracy of microstaging and impact on clinical practice in this scenario are unknown. OBJECTIVE: Our purpose was to examine microstaging accuracy of an initial incisional biopsy with a significant portion of the clinical lesion remaining (> or =50%). METHODS: Patients with cutaneous melanoma, diagnosed by incisional biopsy with > or =50% of the lesion remaining, were prospectively evaluated for microstaging accuracy, comparing initial Breslow depth (BD1) to final depth (BD2) after excision of the residual lesion. Impact on prognosis and treatment was also evaluated. RESULTS: Two hundred fifty of 1783 patients (14%) presented with > or =50% residual clinical lesion after incisional biopsy. The mean BD1 was 0.66 mm; the mean BD2, 1.07 mm (P = .001). After complete excision of the residual lesion, upstaging occurred in 21% and 10% became candidates for sentinel node biopsy. CONCLUSION: An incisional biopsy with > or =50% clinical lesion remaining afterward may be inadequate for accurate microstaging of melanoma. This scenario is relatively uncommon but clinically significant.

An education theory-based method to teach a procedural skill.

OBJECTIVE: To determine the effectiveness of an education theory-based method to teach students to place and tie a simple interrupted stitch. DESIGN: A teaching intervention before-after trial. SETTING: Dermatology department, academic university. PARTICIPANTS: Fourth-year medical students and dermatology residents. MAIN OUTCOME MEASURES: Scores on a 12-criterion grading instrument before and after instruction. RESULTS: The scores for medical students and residents in each class showed significant improvement. The mean score for all participants (N = 23) rose by 24% after instruction (P< .001). Scores in 9 of the 12 graded performance areas improved significantly after instruction, including scores in tissue damage/teeth marks (P<.001), needle dulled/bent (P< .001), needle loaded properly and knots square (P = .01), throws done correctly (P = .01), stitch tension and needle entry/exit angle (P = .02), amount of suture used (P = .03), and correct number of throws (P = .04). In addition, participants' confidence increased significantly after instruction (P<.001). No difference was noted between men and women in preinstruction vs postinstruction score improvement. CONCLUSIONS: This teaching method can be effectively used to teach students to place and tie a simple interrupted stitch. Once validated and expanded, it may prove useful in shortening and standardizing procedural skill training and in objectively documenting competency.

Evaluation of staging chest radiographs and serum lactate dehydrogenase for localized melanoma.

BACKGROUND: Radiographic and laboratory evaluations are often routinely used in the initial work-up for melanoma. PURPOSE: To examine the yield of a chest radiograph and serum lactate dehydrogenase (LDH), in the work-up for newly diagnosed localized melanoma. METHODS: Patients with a new diagnosis of localized invasive melanoma were entered into a prospective database. The status of the chest radiograph, LDH, and sentinel lymph node (SLN) was assessed. RESULTS: Two-hundred-twenty-four patients were entered into the study and 210 had chest radiograph data for analysis. The true positive chest radiograph rate, defined as the percent of chest radiographs interpreted as "positive or equivocal possibly melanoma related" with subsequent confirmed melanoma metastases, was 0%. The false positive chest radiograph rate, defined as the percent of chest radiographs interpreted as "positive or equivocal possibly melanoma related" with melanoma metastases excluded based on previous or subsequent studies or other known medical conditions, was 7%. Ninety-six patients (melanoma> or =1 mm) had LDH results for analysis. Elevations in LDH were found in 15% and did not lead to detection of occult disease in any patients. Seventy-seven patients underwent SLN biopsy. A positive SLN did not correlate with abnormal chest radiograph or LDH. CONCLUSION: Low yield, high rate of false-positive tests and lack of significant impact of early detection of metastases on survival argue that chest radiographs and serum lactate dehydrogenase should probably not be accepted into routine clinical practice in patients with clinically localized melanoma in the absence of data supporting their use.

Desmoplastic and neurotropic melanoma.

BACKGROUND: Desmoplastic and neurotropic melanoma (DNMM) occasionally metastasizes to regional lymph nodes and extranodal sites. The value of sentinel lymph node biopsy (SLNB) has not been demonstrated clearly for patients with DNMM. The authors report on the utility of SLNB in the management of patients with DNMM. METHODS: The authors identified 33 patients with DNMM who were seen during a 5-year period in their institution who underwent lymphatic mapping and SLNB. Clinical and histopathologic data were reviewed. RESULTS: Thirty-three patients with DNMM underwent SLNB (mean Breslow depth, 4.0 mm; median, 2.8 mm). There were 25 male patients and 8 female patients with a median age of 61 years (range, 31-86 years). Fifty-two percent of tumors presented in the head and neck region, and 24% were associated with lentigo maligna. Four of 33 patients (12%) without clinical evidence of metastatic disease who underwent SLNB had at least 1 positive sentinel lymph node. No additional positive lymph nodes were found in subsequent therapeutic regional lymphadenectomy in any of these four patients. CONCLUSIONS: SLNB detected subclinical metastases of DNMM to regional lymph nodes. SLNB at the time of resection can provide useful information to guide early treatment and, coupled with lymphadenectomy in positive patients, may limit tumor spread and prevent recurrence at the draining lymph node basin.