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.

Recurrence risk of early-stage melanoma of the external ear: an investigation of surgical approach and sentinel lymph node status.

Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluated for recurrence risk. One hundred and fifty-six patients total had an average follow-up of 5.6 years. Twenty-nine (18.6%) patients underwent cartilage-sparing surgery and 99 (63.5%) patients underwent SLNB, 14.1% of whom had micrometastatic disease. Ten (6.4%) patients recurred loco-regionally. Recurrence was associated with Breslow depth, initial stage at diagnosis, and SLNB status. Cartilage-sparing surgery was not associated with increased recurrence. Sentinel lymph node identification rate was 100% based on clinical detection with use of lymphoscintigraphy. In addition to confirming established risk factors for melanoma recurrence, we confirm the feasibility of SLNB in stratifying recurrence risk. Although we did not see an increased recurrence risk with surgical technique and cartilage-sparing approaches, these findings are limited by small sample size.

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.

Rate of Recurrence of Lentigo Maligna Treated With Off-Label Neoadjuvant Topical Imiquimod, 5%, Cream Prior to Conservatively Staged Excision.

Importance: Staged excision of lentigo maligna (LM) often requires multiple stages and can result in significant cosmetic morbidity. Imiquimod cream has been used off-label as monotherapy in the treatment of LM and may be used in the neoadjuvant setting prior to staged excision as a strategy to reduce the size of the surgical margins required to confirm negative histologic margins. Objective: To examine the rate of recurrence of LM in patients treated with neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions. Design, Setting, and Participants: This was a retrospective medical record review of 334 patients with 345 biopsy-confirmed LM tumors from June 2004 to January 2012 who were treated with imiquimod prior to undergoing staged excisions at the University of Utah Medical Center and Huntsman Cancer Institute, large academic hospitals in Salt Lake City. Interventions: Patients were treated with off-label imiquimod, 5%, cream 5 nights per week for 2 to 3 months. Those deemed to have an inadequate inflammatory response were also treated with tazarotene, 0.1%, gel twice weekly. Conservatively staged excisions, beginning with 2-mm margins, were then performed. Main Outcomes and Measures: The rate of recurrence of LM after long-term follow-up. Results: Patients included 235 men (70%) and 99 women (30%) with a mean (SD) age of 67 (13) years. Patients were treated with imiquimod cream for a mean of 2.5 months prior to undergoing conservatively staged excisions. There were 12 local recurrences (a rate of 3.9%) with a mean time to recurrence of 4.3 years and a mean length of follow-up of 5.5 years. Conclusions and Relevance: Neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions for LM allowed for negative histologic margins with a median final margin of 2 mm and a rate of recurrence similar to reported recurrence rates with standard staged excisions by either Mohs surgery or en face permanent sections.

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.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis.

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. A total of 123 patients with BM were matched by initial presenting stage to 237 patients without BM. The characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020), and Breslow depth more than 4 mm (P=0.048), whereas location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, P=0.007) than nonscalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in the clinical outcomes between patients whose BM were detected upon routine screening versus those detected upon symptomatic presentation. In summary, factors predictive of development of BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type, and ulceration, but not detection setting, were associated with worse clinical outcomes.

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.

A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma.

PURPOSE: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality. The objective of this study was to primarily assess the safety of intratumoral ipilimumab/IL-2 combination and to obtain data on clinical efficacy. RESULTS: There was no dose limiting toxicity. While local response of injected lesions was observed in 67% patients (95% CI, 40%-93%), an abscopal response was seen in 89% (95% CI, 68%-100%). The overall response rate and clinical benefit rate by immune-related response criteria (irRC) was 40% (95% CI, 10%-70%) and 50% (95% CI, 19%-81%), respectively. Enhanced systemic immune response was observed in most patients and correlated with clinical responses. EXPERIMENTAL DESIGN: Twelve patients with unresectable stages III/IV melanoma were enrolled. A standard 3+3 design was employed to assess highest tolerable intratumoral dose of ipilimumab and IL-2 based on toxicity during the first three weeks. Escalated doses of ipilimumab was injected into only one lesion weekly for eight weeks in cohorts of three patients. A fixed dose of IL-2 was injected three times a week into the same lesion for two weeks, followed by two times a week for six weeks. CONCLUSIONS: Intratumoral injection with the combination of ipilimumab/IL-2 is well tolerated and generates responses in both injected and non-injected lesions in the majority of patients.

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.

Merkel Cell Carcinoma: Current Issues Regarding Diagnosis, Management, and Emerging Treatment Strategies.

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous tumor with a predilection for the head and neck of elderly Caucasian patients. Although much less common than melanoma, MCC has higher rates of sentinel lymph node involvement, local and regional recurrences, and mortality. The majority of MCC cases have been linked to the relatively newly discovered Merkel cell polyomavirus, which is a ubiquitous constituent of the skin flora. Recent discoveries regarding viral integration and carcinogenesis and the immunologic features of MCC have expanded the understanding of MCC. These discoveries have led to the development and application of emerging therapies such as somatostatin analogs, immune checkpoint inhibition, adoptive cell therapy, and other exciting possibilities for targeted therapy.

Local Recurrence and Ocular Adnexal Complications Following Electronic Surface Brachytherapy for Basal Cell Carcinoma of the Lower Eyelid.

IMPORTANCE: Various treatment options exist for nonmelanoma skin cancer (NMSC), including topical agents, surgery, or definitive or adjuvant radiation therapy. Recently, electronic surface brachytherapy (ESB) has been described as a noninvasive option for NMSC. We report a case of local recurrence of basal cell carcinoma (BCC) and ocular complications following ESB to the lower eyelid. OBSERVATIONS: A man in his 60s presented with a recurrent BCC within the radiation field 10 months after undergoing ESB for a biopsy-proven BCC. In addition to the recurrence, he had contracture of the conjunctiva in the socket of his previously enucleated eye, as well as lower eyelid ectropion, resulting in displacement and loss of retention of his ocular prosthesis. CONCLUSIONS AND RELEVANCE: Electronic surface brachytherapy should be used with caution, particularly in the periocular region because the late effects of hypofractionated radiation may cause ocular and orbital complications. To our knowledge, this is the first reported case of ocular complications with this modality. This case highlights a local recurrence following use of this new treatment modality, suggesting further investigation is warranted to determine the safety and efficacy of ESB.

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.