Strategies for Reducing Final Surgical Defect Sizes in the Treatment of Lentigo Maligna.

BACKGROUND: Lentigo maligna (LM) is associated with disproportionately high surgical morbidity. OBJECTIVE: The authors report on 2 strategies to reduce the surgical morbidity associated with LM. METHODS: Forty LM lesions were removed with excisional biopsies without margins and closed with purse-string sutures. Invasive cases underwent staged excisions with 10-mm margins. Cases without invasion were treated with neoadjuvant topical imiquimod 5% cream (5 d/wk × 8 weeks) followed by conservative staged excisions with 2-mm margins using radial sections stained with hematoxylin and eosin and immunostaining with Mart-1, with or without SOX10. RESULTS: Invasion was detected in 12/40 (30%) of the excisional biopsy specimens (average depth 0.45 mm). No invasion was detected in 28/40 (70%). All 24 patients who completed neoadjuvant topical imiquimod 5% cream before staged excisions had negative first-stage margins at 2 mm. Compared with average published margins for LM, this represents a 71.4% reduction in the required margin and an average reduction in the final surgical defect by 74%. CONCLUSION: LM treatment by excisional biopsies with a purse-string closure enables accurate tumor staging and contracts the tumor footprint to its minimal size. Subsequent neoadjuvant imiquimod followed by a conservative staged excision with 2-mm margins allows for removal of LM with decreased surgical morbidity.

Current controversies in early-stage melanoma: Questions on management and surveillance.

There are a number of controversies and uncertainties relating to the management and surveillance of patients with early-stage, localized (ie, stage 0, I, and II) cutaneous melanoma. While tumor stage is a critical predictor of clinical outcome and guides treatment, accurate determination of stage may be affected by the biopsy technique used and the method of sectioning before histologic review. A new molecular prognostic test is available but has not been formally incorporated into staging or treatment guidelines. There are no randomized controlled clinical trials to support guidelines for surveillance following the treatment of early-stage melanoma. In the second article in this continuing medical education series, we review the controversies and uncertainties relating to these issues. The questions we address are controversial because they speak to clinical scenarios for which there are no evidence-based guidelines or randomized clinical trials with the consequence of considerable variability in clinical practice. Our goal is to provide the clinician with up-to-date contextual knowledge to appreciate the multiple sides of each controversy and to suggest pathways to resolution.

Opioid Prescribing Patterns After Micrographic Surgery: A Follow-up Retrospective Chart Review.

BACKGROUND: The abuse of opioids has reached epidemic proportions in the United States, and leftover medications are a primary source for nonmedical pain relievers. A past study at the University of Utah showed that micrographic surgeons were likely overprescribing opioids, with 35% of patients receiving a postoperative prescription. OBJECTIVE: To examine the current opioid prescribing habits of the micrographic surgeons at the University of Utah compared with those in 2010. METHODS: Retrospective chart review of the patient records of 4 micrographic surgeons between February and May 2017. RESULTS: Four hundred patient visits were reviewed. An opioid prescription was provided after 12% of encounters, 23% lower than in 2010 (p = .004). Younger patient age, increased number of stages and defect size, repair of the defect, and particular surgeons predicted opioid prescription. CONCLUSION: The percentage of patients who received an opioid prescription after undergoing micrographic surgery at the University of Utah decreased from 35% in 2010 to 12% in 2017. Reports of the minimal need of opioids after micrographic surgery, the authors' past study showing an institutional tendency to overprescribe, and reports of the national opioid epidemic likely all contributed to the decrease in opioid prescriptions at the authors' institution.

Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

Similar survival of patients with multiple versus single primary melanomas based on Utah Surveillance, Epidemiology, and End Results data (1973-2011).

BACKGROUND: Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). OBJECTIVES: We compared MPM versus SPM patient survival using a matching method that avoids potential biases associated with other analytic approaches. METHODS: Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End Results registry of all melanomas diagnosed or treated in Utah between 1973 and 2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. RESULTS: Survival curves (n = 887 for both MPM and SPM groups) without covariates showed a significant survival disadvantage for MPM patients (chi-squared 39.29, P < .001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio 1.07, P = .55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio 0.99, P = .96). LIMITATIONS: Breslow depth, ulceration status, and specific cause of death were not available for all patients. CONCLUSIONS: Patients with MPM had similar survival times as patients with SPM.

Cutaneous carcinosarcoma: a series of six cases and a review of the literature.

BACKGROUND: Cutaneous carcinosarcoma is a rare tumor with distinct malignant epithelial and mesenchymal cell populations. The histologic subtypes of epithelial and mesenchymal components in cutaneous carcinosarcoma are variable, as an assortment of carcinomatous and sarcomatous patterns have been described in the literature. METHODS: Clinical information was obtained from patient charts and archival slides were retrieved and reviewed. RESULTS: We present a novel series of six distinct cases of cutaneous carcinosarcoma and review the literature. Our cases consisted of basal cell, pilomatrical, squamous cell, and trichoblastic variants. These cases occurred in elderly men on sun exposed skin with treatment and follow up was available for 4 of 6 cases. The four cases were treated with Mohs micrographic surgery with mean follow up of nine months. CONCLUSION: We report six cases of cutaneous carcinosarcoma with distinctive clinical and histologic characterization not previously described in a single series.

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.

Metastatic melanoma - a review of current and future treatment options.

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.

Mohs appropriate use criteria: retrospectively applied to nonmelanoma skin cancers at a single academic center.

BACKGROUND: In September 2012, appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) were released by a collaboration of dermatology organizations including the American College of Mohs Surgery. OBJECTIVE: The group sought to determine adherence to the Mohs AUC at the academic institution. MATERIALS AND METHODS: The authors performed a retrospective chart review of all nonmelanoma skin cancers (NMSCs) treated within the University of Utah, Department of Dermatology, from January through March of 2012. They applied the Mohs AUC to analyze these cases. RESULTS: In total, the authors identified 724 patients and 1,026 cases of NMSCs, including 557 (54.3%) basal cell carcinomas and 469 (45.7%) squamous cell carcinomas. Of the 1,026 NMSCs, 350 (34.1%) were treated with MMS. Of these cases treated with MMS, there were 339 cases (96.9%) deemed appropriate, 4 (1.1%) uncertain, and 7 (2.0%) inappropriate per AUC. Also examined were 611 cases treated with modalities other than MMS, of which 60.7% would have met AUC for MMS. CONCLUSION: In a 3-month review of all NMSC cases at the academic center, there is a low percentage of cases performed that are inappropriate for MMS by AUC. At the institution, there is a large percentage of NMSC that meet AUC but are treated by other modalities. The use is highly appropriate for MMS, and these data suggest possible underutilization of MMS for certain NMSCs. Further studies are required to determine the effectiveness of other treatment modalities for NMSC that meet Mohs AUC.

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.

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.

Patterns of failure and predictors of outcome in cutaneous malignant melanoma of the scalp.

BACKGROUND: Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. OBJECTIVE: We sought to characterize survival and patterns of failure for patients with scalp melanoma. METHODS: Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases-free survival, and disease-free survival. RESULTS: Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases-free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. LIMITATIONS: This is a retrospective review. CONCLUSION: Distant metastases-free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods.

Sentinel lymph node biopsy for melanoma in pregnant women.

BACKGROUND: The incidence of melanoma is rising in young women of childbearing age. Melanoma diagnosed during pregnancy presents unique challenges. This study was conducted to determine the effect of sentinel lymph node biopsy (SLNB) for melanoma on maternal and fetal outcomes in pregnant women. METHODS: A prospective melanoma database was retrospectively queried for women diagnosed with melanoma during or immediately before pregnancy as well as SLNB in pregnant women. The outcomes of SLNB for the mothers and fetuses were evaluated. RESULTS: Fifteen pregnant women underwent wide local excision (WLE) and SLNB for melanoma from 1997 to 2012. The median gestational age was 20 weeks. More than half of the women noticed changes in the primary melanoma lesion during the pregnancy. The median Breslow thickness was 1.00 mm. Lymphatic mapping and SLNB were performed with some combination of radiocolloid or vital blue dye without adverse effects. Three patients had micrometastatic disease and underwent a completion lymphadenectomy. Sixteen children were born at a median gestational age of 39 weeks. The median 1- and 5-minute Apgar scores were 8 and 9, respectively. At a median follow-up of 54.4, months none of the patients had experienced recurrence, and all children were healthy and free of melanoma. CONCLUSIONS: In this series of pregnant women with melanoma, SLNB was performed safely during pregnancy without adverse effects to the mothers and fetuses. We recommend that clinicians explain the risks and benefits of the SLNB procedure to pregnant women so an informed decision can be made about the procedure.

Surgical management of melanoma.

Historically, the surgical management for melanoma was ossified for nearly 50 years with the standard of care being wide local excisions with 5-cm margins. Several clinical studies have now brought to light new data that have enabled academic groups such as the American Joint Committee on Cancer and the National Comprehensive Cancer Network to update surgical guidelines reliant on evidence with long-term follow-up. In addition, basic research at the bench has dispelled the myth that all melanomas are genetically identical and behave in a homogeneous way on the basis of the Breslow depth of the original tumor. It is now known that although all melanomas arise from the melanocyte, melanoma encompasses a variety of cancers that are genetically distinct with variable predicted outcomes often associated with the anatomic location of the tumor. This article cites the evidence on which the current surgical guidelines are based and it addresses some of the ongoing controversies regarding the surgical management of the various types of melanoma.

Immunohistochemical staining with Melan-A of uninvolved sun-damaged skin shows features characteristic of lentigo maligna.

BACKGROUND: The greater density and unusual patterning of melanocytes in chronically sun-exposed skin complicates interpretation of intraoperative Melan-A immunohistochemical stained margins during margin-controlled surgery for lentigo maligna (LM) and lentigo maligna melanoma (LMM). OBJECTIVE: To identify the immunohistochemical similarities and differences in melanocyte distribution between LM and LMM and chronically sun-exposed skin. METHODS: Retrospective review of Melan-A-stained original biopsy specimens of LM and LMM and uninvolved sun-damaged skin (negative controls), from 70 LM and LMM cases from the University of Utah in 2008. RESULTS: Histologic features commonly associated with LM were common in negative controls from chronically sun-exposed skin. Melanocyte confluence (27/70, 39%), stacking (34/70, 49%), theque formation (9/70, 13%), adnexal extension (59/68, 87%), and suprabasilar scatter (23/70, 33%) were observed in the negative controls from sun-damaged skin. Such features were present nearly uniformly in the LM and LMM specimens. Epidermal melanocyte density in LM and LMM differed significantly from that in negative controls (82.7 ± 29.3 and 25.6 ± 9.3 per × 400 field, respectively; p<.001). CONCLUSION: Epidermal melanocytic features often ascribed to LM, such as melanocyte confluence, stacking, theque formation, adnexal extension, and suprabasilar scatter, are frequently observed in chronically sun-exposed Caucasian skin and may lead to overestimation of surgical margins.

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor that primarily affects elderly patients. Despite aggressive treatment, overall survival (OS) remains low. METHODS: This study is a multi-institutional, retrospective review of 102 patients with MCC. We evaluated OS, disease-specific survival (DSS), and risk factors for recurrence. RESULTS: Median age of patients was 71.46% of patients recurred. Patients with stage I disease had median 5-year OS of 59.3%, compared to 68.1% DSS. For stage III, median 5-year OS was 46.0% vs 58.2% DSS. Disease stage and advanced age were risk factors for recurrence and decreased OS. Immunocompromised status and disease stage were the strongest predictors of DSS. CONCLUSIONS: DSS is significantly better than OS for patients with MCC. Many elderly patients with newly diagnosed MCC have low remaining life expectancy, regardless of their MCC diagnosis. Patient age and overall health status should be considered to personalize care plans for patients with MCC.