Brewer, Jerry D.

Background: Tumoral melanosis clinically resembles metastatic melanoma, occurs in the context of regressed disease, and requires evaluation to rule out underlying melanoma and metastatic disease. Histopathology demonstrates a nodular infiltrate of melanophages in the dermis, subcutaneous tissue, deep soft tissue, or lymph nodes in the absence of viable melanocytes. Recent limited reports of tumoral melanosis in the context of immunotherapy with ipilimumab (monoclonal antibody targeting CTLA-4) as well as nivolumab and pembrolizumab (humanized monoclonal antibodies against programmed death 1 receptor) highlight a unique presentation representative of treatment-related tumor regression and an association with a favorable clinical response. Objective: To describe our experience with tumoral melanosis in the setting of immunotherapy for metastatic melanoma and elucidate the clinical and histopathological features. Methods: Retrospective case series from a single tertiary care institution. Results: We describe 10 cases of patients with metastatic melanoma who received treatment with immunotherapy before the development of tumoral melanosis. Length of time between the initiation of therapy and the onset of tumoral melanosis ranged from 2 to 20 months with a mean time of 10 months. At the end of the follow-up period, 8 patients were classified as having a complete or partial response to treatment with immunotherapy. One patient had progression of visceral and cutaneous disease on ipilimumab despite developing tumoral melanosis, and 1 patient had yet to undergo repeat imaging. Furthermore, at the end of follow-up, 3 patients were alive with no evidence of active disease, 5 patients were alive with disease, and 1 patient was deceased, although this patient died of a cardiovascular event unrelated to his underlying melanoma. Of the patients who were classified as alive with disease, 2 patients had minimal remaining disease, and 2 patients had an almost complete response on immunotherapy with recurrence of visceral metastases after immunotherapy was discontinued. One patient developed new peritoneal and cutaneous metastases on pembrolizumab despite development of tumoral melanosis. Conclusions: The underlying biologic mechanisms and prognostic implications of tumoral melanosis in the setting of immunotherapy remain to be elucidated. Further prospective studies with a larger cohort and prolonged follow-up are necessary to better understand the incidence, prevalence, and oncologic outcomes in patients with tumoral melanosis who receive immunotherapy.

AbstractBackgroundPrevious wide local excision prior to sentinel lymph node biopsy (SLNB) may have the potential to disrupt lymphatic channels, thus incorrectly identifying the sentinel node. The purpose of this study was to investigate: (1) regional recurrence rates of prior wide local excision compared to other biopsy techniques and (2) survival outcomes in patients with melanoma of the head and neck.MethodsBetween the years 2000 and 2016, 391 cases were reviewed with a median follow‐up time of 30 months in a large tertiary care center. Biopsy practices included shave, punch, wide local excision, and narrow margin excisional/Mohs, and associations with time to local or regional relapse and death from melanoma were evaluated. Main outcomes included identification of sentinel lymph nodes, overall survival, and melanoma‐specific survival.ResultsOf the 391 patients, biopsy patterns were as follows: 77 (19%) unknown biopsy, 30 (8%) prior wide local excision (WLE), 105 (27%) narrow margin excisional biopsy, 69 (18%) punch biopsy, and 110 (28%) shave biopsy. SLNB was successfully identified in all 30 patients whom had a prior WLE. There were 50 regional recurrences in the neck and 27 local recurrences with the median (IQR) at 1.2 years and 1.0 years, respectively. Multivariable associations of type of prior biopsy, depth of invasion, and nodal status with time to regional recurrence, local recurrence, overall survival, and melanoma‐specific survival were not significantly different.ConclusionsSentinel lymph node biopsy for melanoma of the head and neck can be successfully performed in patients after previous wide local excision.

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.

Background and ObjectivesTo describe the patterns of failure in patients with in‐transit (IT) melanoma undergoing surgical excision.MethodsA retrospective review of patients who underwent their first IT lesion(s) resection between May 2005 and September 2014. Cumulative incidence of local failure (new lesion within 2 cm of IT resection) was estimated. Associations between clinicopathologic characteristics, local failure, and any recurrence were analyzed.ResultsOne hundred and thirty patients presented to our institution with IT disease over the study period and met the inclusion criteria. The 2‐year cumulative incidence of local failure was 19.5%. Twenty‐four patients developed disease within 2 cm of the resected IT disease; however, only eight were isolated local events. Cumulative incidence of local failure and of any disease differed with respect to less than 1 year disease‐free interval (DFI) from primary melanoma to first IT event, and having greater than 1 IT lesion at presentation. Incidence of local failure was not found to differ with respect to gross margin greater than 5 mm, after adjusting for DFI and greater than 1 IT lesions.ConclusionsPatients with greater than 1 IT lesion and a DFI less than 1 year are at a higher risk of failure after surgical excision of a first IT event. Very few failures were isolated local disease within 2 cm of the IT resection scar, regardless of IT excision margin.

AbstractBackgroundConflicting data have been published on whether an association exists between atopic dermatitis (AD) and nonmelanoma skin cancer. This study aimed to determine whether individuals with AD had an increased risk of squamous cell carcinoma (SCC) development.MethodsWe conducted a retrospective, case–control study of patients residing in Olmsted County, Minnesota. Cases were selected from patients seen at Mayo Clinic (Rochester, Minnesota) who had an initial SCC diagnosis (either invasive SCC or SCC in situ) from January 1, 1996, through December 23, 2010. Age‐ and sex‐matched controls were selected from patients seen at Mayo Clinic with no history of SCC before the case event date.ResultsThree hundred ninety‐nine individuals with a documented history of SCC were identified and matched with 780 controls who did not have a history of SCC. After adjusting for race, smoking history, ionizing radiation exposure, corticosteroid and cyclosporine use, and non‐SCC skin cancers, the odds ratio for SCC development between patients with history of AD versus patients without history of AD was 1.75 (95% CI, 1.05–2.93).ConclusionsOur findings support an increased risk of SCC development in the setting of AD.

AbstractWomen diagnosed with cutaneous melanoma have a survival advantage compared to men, which has been hypothesized to be due to difference in behavior and/or biology (sex hormones). It remains controversial whether this advantage is dependent on age or stage of disease. We sought to compare melanoma‐specific survival between females in pre, peri, and postmenopausal age groups to males in the same age group, adjusting for stage of disease. This is a retrospective population‐based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed from 1 January 1992 through 31 January 2011 with primary invasive cutaneous melanoma were included in our cohort. Melanoma‐specific survival was the main outcome studied. Of the 106,511 subjects that were included, 45% were female. Females in all age groups (18–45, 46–54, and ≥55) with localized and regional disease, were less likely to die from melanoma compared to males in the same age group. Among patients with localized and regional disease, the relative risk of death due to melanoma increased with advancing age at diagnosis; this increase was more pronounced among females than males. In contrast, we observed no female survival advantage among patients with distant disease and no effect of age on relative risk of death from melanoma. Females with localized and regional melanoma have a decreased risk of death compared to males within all age groups. Our data show no differences in survival between men and women with metastatic melanoma, indicating that the influence of sex on survival is limited to early stage disease but not confined to pre or perimenopausal age groups.

AbstractBackgroundSecond hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy‐related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B‐cell lymphoma. Although cutaneous T‐cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non‐Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program.MethodsWe searched the SEER 13 registries for patients with a diagnosis of CLL and NHL between 1992 and 2008. Among patients identified, we evaluated the incidence of CTCL.ResultsAmong 31,286 patients with CLL, the incidence of CTCL was not significantly higher in men than women: 104.2 (95% CI, 50.0–191.8) and 28.1 (95% CI, 3.4–101.3) per 1,000,000 person‐years, respectively (P = 0.06). Among 97,691 patients with NHL, the incidence of CTCL was similar in men and women (97.9 [95% CI, 62.0–146.9] and 92.0 [95% CI, 56.2–142.1] per 1,000,000 person‐years, respectively; P = 0.84). The incidence of CTCL among males with CLL (standardized incidence ratio [SIR], 3.0 [95% CI, 1.4–5.5]), males with NHL (SIR, 3.7 [95% CI, 2.3–5.5]), and females with NHL (SIR, 5.9 [95% CI, 3.6–9.1]) was significantly higher than expected in the general population (all P < 0.001).ConclusionThe risk of CTCL is greater in men with CLL than in the general population. In patients with NHL, both men and women are at greater risk for CTCL than in the general population.