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Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment.

Background The success of Mohs micrographic surgery depends on the surgeon's ability to correctly interpret intraoperative frozen sections. Objective This retrospective study analyzed the rate of concordance between Mohs surgeons and dermatopathologists in reading slides from Mohs surgery cases. Methods A dermatopathologist reviewed all the frozen sections and the corresponding Mohs map for every 30 th Mohs case at a practice employing 6 different Mohs surgeons from 2001-2017. Cases in which the dermatopathologist and the Mohs surgeon disagreed on the interpretation were noted. Results The concordance rate between Mohs surgeons and dermatopathologists was 99.79%. The three discordant cases included one case each of squamous cell carcinoma, superficial basal cell carcinoma, and hypertrophic squamous cell carcinoma in situ. Limitations This analysis is limited to fellowship-trained Mohs surgeons and therefore may not be applicable to all physicians who perform Mohs. Conclusions Fellowship-trained Mohs surgeons show very high concordance with board-certified dermatopathologists in the accurate and precise interpretation of histology slides in the setting of Mohs micrographic surgery.

Cutaneous mesenchymal sarcomas are rare malignancies that include dermatofibrosarcoma protuberans, atypical fibroxanthoma, pleomorphic dermal sarcoma, cutaneous angiosarcoma, myofibrosarcoma, and leiomyosarcoma. These tumors lack consensus guidelines on staging and management. Treatment of local disease involves complete surgical removal but recurrence rates are higher compared with more common forms of nonmelanoma skin cancer. Cutaneous angiosarcoma, pleomorphic dermal sarcoma, and subcutaneous leiomyosarcoma have increased risk of metastatic spread and lower survival rate. Further research is needed on targeted therapies for these more aggressive sarcomas.

This review of cutaneous B-cell lymphoma (CBCL) is focused on the clinical presentation, treatment, and workup of each type of lymphoma. Part 1 is an overview of each of the CBCLs, including clinical presentation, recent advances in the pathobiology, and evidence regarding treatment strategies. Part 2 is a detailed guide to the steps in diagnosis and workup of a newly diagnosed CBCL according to the International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer and NCCN guidelines.

Cutaneous T-cell lymphomas are a clinically and histopathologically heterogenous group of disorders, encountered in dermatologic practice. In this article, we provide a detailed practical guide to the evaluation, diagnosis, and management of common cutaneous T-cell lymphomas. Emphasis is placed on the clinical evaluation including the role of the dermatologist in the accurate assessment of body surface area involvement for disease staging, appropriate biopsy techniques, and key considerations, recent advances in the molecular genetic characteristics of disease, and common treatment approaches.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine (NE) carcinoma arising from integration of Merkel cell polyomavirus (MCPyV) DNA into a host cell or from ultraviolet light-induced genetic damage (proportions vary geographically). Tumors in the latter group include those with "pure" NE phenotype and those "combined" with other elements, most often squamous cell carcinoma (SCC). We performed comprehensive genomic profiling (CGP) of MCPyV+ and MCPyV- (pure and combined) tumors, to better understand their mutational profiles and shed light on their pathogenesis. Supplemental immunohistochemistry for Rb expression was also undertaken. After eliminating low quality samples, 37 tumors were successfully analyzed (14 MCPyV+, 8 pure MCPyV- and 15 combined MCPyV-). The SCC and NE components were sequenced separately in 5 combined tumors. Tumor mutational burden was lower in MCPyV+ tumors (mean 1.66 vs. 29.9/Mb, P 0.0001). MCPyV- tumors featured frequent mutations in TP53 (95.6%), RB1 (87%), and NOTCH family genes (95.6%). No recurrently mutated genes were identified in MCPyV+ tumors. Mutational overlap in the NE and SCC components of combined tumors was substantial ('similarity index'24% in 4/5 cases). Loss of Rb expression correlated with RB1 mutational (P 0.0001) and MCPyV- status (P 0.0001) in MCCs and it was observed more frequently in the SCC component of combined MCC than in a control group of conventional cutaneous SCC (P = 0.0002). Our results (i) support existing evidence that MCPyV+ and MCPyV- MCCs are pathogenetically distinct entities (ii) concur with earlier studies linking the NE and SCC components of combined MCCs via shared genetic profiles and (iii) lend credence to the proposal that an Rb-deficient subset of SCC's is the source of phenotypically divergent combined MCCs.

Axillary and inguinal lymph node dissection (LND) are performed in metastatic skin tumors with several local complications, such as lymphorrhea, lymphoceles, and lymphedema. The purpose of this study is to determine whether negative pressure wound therapy (NPWT) applied as a preventive measure could improve outcomes.A monocentric study included patients who underwent axillary or inguinal LND from May 2010 to March 2020, with a retrospective evaluation of prospectively collected data. Patients were divided into two groups: the conventional wound care (CWC) and the NPWT groups. Patients were systematically reviewed at D7, D30, and at 1 year postoperative, and data regarding lymphorrhea, lymphoceles, and lymphedema were collected.A total of 109 axillary and inguinal LND were performed. NPWT was applied on 68 LND and CWC on 41 LND. The variables, diabetes, smoking, gender, associated treatments, and primary pathology (melanoma, squamous cell carcinoma, or Merkel tumors) were similar in both groups. Analyses have shown a significant difference in the rate of scar disunion during the first month between the two groups (p=0.045 between D1 and D7; p=0.011 between D8 and D30), as well as the presence of lymphorrhea (p=0.000 between D1 and D7; p=0.002 between D8 and D30). The rate of lymphoedema was significantly reduced in the NPWT group versus CWC (p=0.000 between D8 and D30; p=0.034 between D31 and 1 year).NPWT reduces local complications (scar disunion, lymphorrhea, and lymphedema) during the first year following LND in the management of node metastatic skin tumors.

The aim of this study was to describe a series of patients who have undergone a medial canthal reconstruction with a glabellar superciliary bilobed flap. A series of 30 patients were included with medial canthal defects after excision of medial canthal tumour who underwent reconstruction using a glabellar-superciliary bilobed flap of adjoining skin and subcutaneous tissue. Eighteen procedures were performed under local anaesthesia. The remaining 12 cases were combined with major lid reconstruction and performed under general anaesthesia. Complete closure of the defect, aesthetic outcome, complications, and re-operations were all used as outcome measures. Primary closure of the donor site was achieved in all cases without wound dehiscence. In all cases, the cosmetic appearance was highly satisfactory to the surgeons and patients and there were no intraoperative complications. The glabellar superciliary bilobed flap is an effective, quick, simple, and single-stage technique for medial canthal region reconstruction. It provides excellent cosmesis and is associated with minimal complications. It can be modified according to the nature of the periorbital skin, location, size, and depth of the defect.

Extra-axial chordomas are rare malignant tumours. As a subcategory of axial chordomas, these tumours arise outside the axial skeleton. This report describes the case of a 13-year-old male patient with a gingival mass in the left upper jaw, who was referred to Hannover Medical School with a preliminary diagnosis of a calcifying epithelial odontogenic tumour (CEOT). Pathological examination of the enucleated tumour led to the final diagnosis of a chordoma. Thereafter, a stepwise radical resection was performed with the aim of complete resection of the tumour with wide safety margins. The main tumour mass was found to be located on the maxillary gingiva, with focal infiltration into the maxillary bone. Following resection, reconstruction was performed with a free latissimus dorsi flap. Follow-up after 1 year revealed no signs of recurrence or metastasis. This case highlights that although extremely rare, extra-axial chordoma may occur at sites distant from the midline and as such must be included in the differential diagnosis of bone and soft tissue tumours in the maxillofacial region.

Desmoplastic melanoma (DM) is a less common form of cutaneous melanoma that has been described for decades; however, controversy remains regarding the management and use of sentinel lymph node biopsy (SLNB). The purpose of this study is to identify whether SLNB is indicated in all cases of DM, including the pure subtype.A systematic review was conducted using PubMed (with access to MEDLINE) along with the Cochrane Central Register of Controlled Trials from 2001 to 2019. Case series and case-control studies were included.Eighteen studies were included for a total population of 3,914 patients. SLNB was performed in 2229 patients. The percentage of positive SLNB results was 8.5%. However, patients with pure DM (90% desmoplastic component) were found to have a significantly lower rate of occult metastatic node positivity when compared with that of mixed DM (4.9% and 14.8%, respectively).Our findings underscore the importance of the pathologist reporting percentage of desmoplastic component in melanoma. SLNB should be strongly considered for patients with mixed DM. However, the low rate of occult metastatic node positivity in pure DM is beneath the threshold for using SLNB as a staging procedure.Previous studies have suggested that desmoplastic melanoma is less likely to metastasize to regional lymph nodes when compared with conventional melanoma. This review suggests that it is imperative to distinguish the histologic subtype of desmoplastic melanoma to determine if staging procedure is indicated.

Systematic literature searches on POT1/POLE/BAP1 found that limited skin phenotypic characteristics have been documented in mutation carriers; 248 variants were annotated, and high-cluster variant regions associated with cutaneous melanoma were found in all three genes. Genotype-phenotype correlations can be used to identify patient disease predisposition based on mutation position and cluster regions.

BCL11B is an essential transcription factor for T-cell lineage commitment and differentiation, and its dysregulation has been shown to be associated with T-cell tumourigenesis. In this study, we investigated BCL11B expression by immunohistochemical analysis in 120 cases of mature T-cell lymphoma, 34 B-cell lymphomas, 11 NK-cell neoplasms and 17 reactive cutaneous conditions. All cases of mycosis fungoides (n=23), primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (n=8) and T-prolymphocytic leukaemia (n=6) were positive for BCL11B and the staining intensity was higher than that of reactive T-cells. Fourteen of 15 (93%) cases of angioimmunoblastic T-cell lymphoma, 10 of 12 (83%) T-large granular lymphocytic leukaemia and 14 of 20 (70%) peripheral T-cell lymphoma, not otherwise specified, were also positive for BCL11B with an intensity comparable to reactive T-cells. Other T-cell neoplasms were uncommonly positive including one of three (33%) cases of primary cutaneous gamma delta T-cell lymphoma, one of four (25%) cases of subcutaneous panniculitis-like T-cell lymphoma, one of four (25%) cases of hepatosplenic T-cell lymphoma, and one of 20 (5%) cases of anaplastic large cell lymphoma (8 ALK-positive, 12 ALK-negative). T-cells in reactive cutaneous infiltrates were also positive for BCL11B, but staining intensity was much weaker than in mycosis fungoides. All NK-cell (n=11) and B-cell neoplasms (n=34) were negative for BCL11B. In conclusion, BCL11B shows a distinct expression pattern in various T-cell neoplasms. BCL11B appears to have utility as another T-cell marker and may be useful in the differential diagnosis of lymphoid neoplasms.

As a surgical discipline without anatomic boundaries, plastic surgery overlaps with several other specialties. This study aims to measure longitudinal trends in the proportion of commercially reimbursed procedures performed by plastic surgeons compared to other specialists. We hypothesize that there is encroachment in commercial market share by anatomically defined subspecialists within otolaryngology, ophthalmology, and dermatology.The IBM® MarketScan® Research Databases were queried to extract patients who underwent rhinoplasty, eyelid procedures, and skin cancer reconstruction covered by commercial insurance from 2007 to 2016 in the USA. Surgeon specialty was identified. Poisson regression modeled predictors of provider specialty for each procedure over time, adjusting for patient gender, region, facility setting, and diagnosis.A total of 430,472 rhinoplasty, eyelid, and skin cancer procedures were performed during the study period. For each year, the proportion of cases performed by plastic surgeons decreased by 2.1% for rhinoplasty compared to otolaryngologists, 2.0% for eyelid procedures compared to ophthalmologists, and 3.0% for skin cancer reconstruction compared to dermatologists (p0.001). Plastic surgeons were less likely to perform the procedure if the underlying diagnosis or preceding procedure drew from referral bases of "anatomic" specialists, such as sinonasal disease for otolaryngologists (incidence rate ratio [IRR] 0.829), disorders of the eyelid or orbit for ophthalmologists (IRR 0.646), and Mohs excision for dermatologists (IRR 0.381) (p0.001).Plastic surgeons are losing ground on commercially reimbursed facial reconstructive procedures historically performed by the specialty. Plastic surgeons must develop strategies to preserve the commercial market share of these procedures and avoid compromise to academic centers and resident education.

Although immunocompromised patients have a higher risk of developing cutaneous squamous cell carcinomas, it is unknown whether immune status is an independent risk factor for poor outcomes.To compare cutaneous squamous cell carcinoma outcomes in immunocompromised and immunocompetent patients when controlling for T-stage.We performed a retrospective cohort study at 2 tertiary care centers, examining 989 primary tumors from 814 immunocompromised patients (solid organ transplant: 259 [31.7%], chronic lymphocytic leukemia: 113 [13.9%]) and 6608 tumors from 4198 immunocompetent patients. Our primary outcome was the composite of disease-specific death or tumor metastasis ("poor outcomes").Immunocompromised patients had 50% more high T-stage tumors (ie, Brigham and Women's Hospital stage T2b and T3), than immunocompetent patients (3.3% vs 4.9%, respectively; P .001). Significant predictors of poor outcomes included tumor stage (sub hazards ratio [SHR], 14.8 for high T-stage tumors; 95% confidence interval [CI], 8.0-27.6; P .001) and male sex (SHR, 2.3; 95% CI, 1.4-3.8; P = .002). Immune status was not a significant predictor (SHR, 1.04; 95% CI, 0.69-1.6; P = .85).This study is retrospective.Although immunocompromised patients had 50% more high T-stage tumors than immunocompetent patients, immunocompromised patients had a similar chance of metastasis and disease-specific death when adjusting for T-stage in our cohort of primary tumors.

This retrospective cohort study enrolled 385 patients diagnosed with cutaneous melanoma from 1980 to 2021 in National Taiwan University Hospital (NTUH). The aim of this study was to investigate the relationship between thickness of primary melanoma lesions and disease outcome of melanoma patients, in particular, those diagnosed with acral lentiginous melanoma (ALM). The association between important clinicopathological characteristics other than tumor thickness and disease outcome was also analyzed. Survival analyses with the Kaplan-Meier method were utilized to investigate the prognoses of patients with different lesion thickness. The male-to-female ratio was 1.12:1. The median age at diagnosis was 63 years old (mean: 62.2 years). There were 283 cases (73.5%) of acral lentiginous melanoma (ALM) with a male-to-female ratio of 1.04:1. Between patients with primary ALM lesions 4.1 millimeters (mm) to 8.0 mm thick and those with lesions over 8.0 mm thick, significant differences in prognostic outcomes including incidence of second recurrences within 1 year (raw p = 0.003, Bonferroni corrected p = 0.009) and distant metastases within 1 year (raw p = 0.003, Bonferroni corrected p = 0.008), were observed. Significantly worse 1-year (raw p = 0.01, Bonferroni corrected p=0.03) and 2-year survival (raw p = 0.006, Bonferroni corrected p = 0.02) were found in ALM patients with lesions of over 8 mm thick than those with lesions 4.1 mm to 8.0 mm at diagnosis. Vigilant short-term follow-up is warranted in ALM patients with lesions of over 8.0 mm thick at diagnosis due to higher risks of adverse outcome.

High-dose-rate (HDR) electronic brachytherapy (EBT) has been shown to be effective for non-melanoma skin cancer (NMSC) in Caucasian patients. However, its efficacy remains unknown in Asian patients. To analyze the clinical outcome of HDR EBT for NMSC in a Taiwanese medical center.Medical records over a 5-year period between January 2015 to December 2019 were retrospectively analyzed.Forty-seven patients with 54 NMSC including 42 basal cell carcinomas (BCCs) and 12 squamous cell carcinomas (SCCs) were treated with HDR EBT. The average age was 73.8 years. The mean radiation dose was 45.3 Gy (40-80 Gy). Mean follow-up duration was 33.1 months. Adequate local control was achieved in 50 lesions (92.6%). Grade 1 acute skin toxicity was noted in 63.0% of lesions, while no tumors had Grade 4 acute toxicity. No ulceration was observed six months after completion of treatment. At the last follow-up visit, all lesions were rated to have "fair" to "excellent" cosmetic outcomes.HDR EBT provides adequate clinical outcomes and cosmetic results for NMSC in Asian patients. Further investigation of the dosage guidelines is needed for Asian patients with NMSC.

To investigate the prognostic factors to developing parotid and neck metastasis in locally advanced and relapsed Cutaneous Squamous Cell Carcinoma (CSCC) of the head and neck region.Single-center retrospective cohort study enrolling consecutive patients with advanced CSCC from 2009 to 2019. Seventy-four cases were identified. Study variables demographic data, clinical skin tumor stage, neck stage, parotid stage (P stage), surgical treatment features, and parotid, regional, and distant metastases. Survival measures: Overall Survival (OS) and Disease-Specific Survival (DSS).The study group included 72.9% men (median age, 67 years); 67.5% showed T2/T3 tumors, 90.5% comorbidities, 20.2% immunosuppressed, with median follow-up: 35.8 months. The most frequent skin primary were auricular and eyelid regions, 75% underwent primary resection with flap reconstruction. Parotid metastasis was present in 50%, 32.4% showing parotid extracapsular spread, multivariate analysis found OR = 37.6 of positive parotid metastasis evolving into positive neck metastasis, p = 0.001. Occult neck metastasis, neck metastasis, and neck extracapsular spread were observed in 13.5%, 51.3%, and 37.8%, respectively. Kaplan-Meier survival: Clinical T4 versus T1, p = 0.028, P1 stage: 30% and 5% survival at 5 and 10 years, P3 stage: 0%, p = 0.016; OS and DSS showed negative survival for the parotid metastasis group, p = 0.0283.Our outcomes support a surgically aggressive approach for locally advanced and relapsed CSCC, with partial parotidectomy for P0, total parotidectomy for P1-3, selective I-III neck dissection for all patients and adjuvant radiochemotherapy to appropriately treat these patients with advanced CSCC of the head and neck region.II b - Retrospective Cohort Study - Oxford Centre for Evidence-Based Medicine (OCEBM).

Melanoma is the most malignant form of skin cancer across the globe. Conventional therapies are currently ineffective which could be attributed to the rampant chemo-resistance, metastasis, inability to cross the skin barriers and accumulate within the tumor microenvironment. This advent brings in the principles of drug repurposing by repositioning Niclosamide (NIC), an anthelmintic drug for skin cancer. Incorporation into the liposomes facilitated enhanced melanoma cell uptake and apoptosis. Cytotoxicity studies revealed 1.756-fold enhancement in SK-MEL-28 cytotoxicity by NIC-loaded liposomes compared to free drug. Qualitative and quantitative cell internalization indicated greater drug uptake within the melanoma cells illustrating the efficacy of liposomes as efficient carrier systems. Nuclear staining showed blebbing and membrane shrinkage. Elevated ROS levels and apoptosis shown by DCFDA and acridine orange-ethidium bromide staining revealed greater melanoma cell death by liposomes compared to free drug. Incorporating NIC liposomes into the thermogel system restricted the liposomes as a depot onto the upper skin layers. Sustained zero order release up to 48 h with liposomes and 23.58-fold increase in viscosity led to the sol-to-gel transition at 33℃ was observed with liposomal thermogel. Ex vivo gel permeation studies revealed that C-6 loaded liposomes incorporated within the thermogel successfully formed a depot over the upper skin layer for 6 h to prevent transdermal delivery and systemic adverse effects. Thus, it could be concluded that NIC loaded liposomal thermogel system could be an efficacious therapeutic alternative for the management of melanoma.

High-risk congenital melanocytic nevi (CMN) are associated with abnormalities of the central nervous system (CNS), prompting magnetic resonance imaging (MRI) screening guidelines.Describe MRI brain and spine abnormalities in children with CMN and report trends between nevus features, MRI findings, and neurologic outcomes.Retrospective review of individuals aged ≤18 years with an MRI of the brain and/or spine and at least 1 dermatologist-diagnosed CMN.Three hundred fifty-two patients were identified. Forty-six children had CMN that prompted an MRI of the brain and/or spine (50% male, average age at first image, 354.8 days). In these children, 8 (17%) had melanin detected in the CNS, of whom all had4 CMN. One developed brain melanoma (fatal). In patients without CNS melanin, 4 had concerning imaging. Concerning MRI patients had more neurodevelopmental problems, seizures, neurosurgery, and death than individuals with unremarkable imaging. Three hundred six patients received MRIs for other reasons; none detected melanin. No children with only multiple small CMN (n = 15) had concerning imaging.Lack of a control group, cohort size, and retrospective methods.MRI of the brain and spine is useful for detecting intervenable abnormalities in high-risk children. Healthy infants with few small CMN may not require screening MRI.

Great advances in deep learning have provided effective solutions for prediction tasks in the biomedical field. However, accurate prognosis prediction using cancer genomics data remains challenging due to the severe overfitting problem caused by curse of dimensionality inherent to high-throughput sequencing data. Moreover, there are unique challenges to perform survival analysis, arising from the difficulty in utilizing censored samples whose events of interest are not observed. Convolutional neural network (CNN) models provide us the opportunity to extract meaningful hierarchical features to characterize cancer subtype and prognosis outcomes. On the other hand, feature selection can mitigate overfitting and reduce subsequent model training computation burden by screening out significant genes from redundant genes. To accomplish model simplification, we developed a concise and efficient survival analysis model, named CNN-Cox model, which combines a special CNN framework with prognosis-related feature selection cascaded Wx, with the advantage of less computation demand utilizing light training parameters. Experiment results show that CNN-Cox model achieved consistent higher C-index values and better survival prediction performance across seven cancer type datasets in The Cancer Genome Atlas cohort, including bladder carcinoma, head and neck squamous cell carcinoma, kidney renal cell carcinoma, brain low-grade glioma, lung adenocarcinoma (LUAD), lung squamous cell carcinoma, and skin cutaneous melanoma, compared with the existing state-of-the-art survival analysis methods. As an illustration of model interpretation, we examined potential prognostic gene signatures of LUAD dataset using the proposed CNN-Cox model. We conducted protein-protein interaction network analysis to identify potential prognostic genes and further analyzed the biological function of 13 hub genes, including ANLN, RACGAP1, KIF4A, KIF20A, KIF14, ASPM, CDK1, SPC25, NCAPG, MKI67, HJURP, EXO1, HMMR, whose high expression is significantly associated with poor survival of LUAD patients. These findings confirmed that CNN-Cox model is effective in extracting not only prognosis factors but also biologically meaningful gene features. The codes are available at the GitHub website: https://github.com/wangwangCCChen/CNN-Cox .

The effect of treatment delays on melanoma outcomes remains unclear.To assess the impact of surgical treatment delays on melanoma-specific mortality (MSM) and overall mortality (OM).Patients with stage I to III cutaneous melanoma were identified through the Surveillance, Epidemiology, and End Results database (N = 108,689). Included cases had time from diagnosis to definitive surgery and follow-up time. Cox proportional hazards and Fine-Gray competing risks analyses were used to assess the impact of treatment delays on mortality.Across all stages, treatment delays of 3 to 5 months were associated with worse MSM and any delay beyond 1 month was associated with worse OM. In a subgroup analysis of patients with stage I disease, delays of 3 to 5 months were associated with worse MSM and any delay beyond 1 month was associated with worse OM. In patients with stage II disease, worse MSM was found with delays of 6+ months and worse OM was seen with delays of 3 to 5 months. No significant effect of treatment delays was noted in stage III disease.The Surveillance, Epidemiology, and End Results database does not collect comprehensive data on adjuvant treatments, disease recurrence, or treatment failure.Timely treatment of melanoma may be associated with improved OM and MSM.

Sentinel node biopsy is a key procedure to predict prognosis in melanoma. In a prospective study we compare reporting on melanoma cell densities in cytospin preparations with semiquantitative histopathology for predicting outcome.Sentinel nodes from 900 melanoma patients were bisected. One half of each node was disaggregated mechanically. The melanoma cell density (number of HMB45 positive cells per million lymphocytes with at least one cell showing morphological features of a melanoma cell) was recorded after examining two cytospins. For the second half the maximum diameter of metastasis was determined after haematoxylin and eosin (Hamp;E) and immunohistological staining of three slides.Cytospins were positive for melanoma in 218 of 900 patients (24%). Routine pathology was positive in 111 of 900 (12%) patients. A more extensive pathological workup in cytospin-only positive patients led to a revised diagnosis (from negative to positive) in 23 of 101 patients (22.7%). We found a moderate but significant correlation between melanoma cell densities (determined in cytospins) and the maximum diameter of metastasis (determined by pathology) (rho = 0.6284, p lt; 0.001). At a median follow-up of 37 months (IQR 25-53 months) melanoma cell density (cytospins) (p lt; 0.001), thickness of melanoma (p = 0.008) and ulceration status (p = 0.026) were significant predictors for melanoma specific survival by multivariable testing and were all confirmed as key predictive factors by the random forest model. Maximum diameter of metastases, age and sex were not significant by multivariable testing (all p gt; 0.05).Recording melanoma cell densities by examining two cytospins accurately predicts melanoma outcome and outperforms semiquantitative histopathology.

Approval of adjuvant anti-programmed cell death protein 1 therapy for pathologic stage IIB/C cutaneous melanoma has led some to question the role of sentinel lymph node (SLN) biopsy in the clinical stage IIB/C disease.To determine the prognostic significance of SLN staging on disease-specific survival (DSS) for clinical stage IIB/C primary cutaneous melanoma in the preimmunotherapy era.A retrospective cohort study was performed evaluating patients who underwent excision of clinical stage IIB/C cutaneous melanoma using the Surveillance, Epidemiology, and End Results database (2004-2011). Patients who did and did not undergo SLN biopsy were compared using propensity matching, and among those who underwent SLN biopsy, matched patients were further stratified by SLN status (SLN positive [SLN+] or SLN negative [SLN-]).Of the 8562 patients evaluated, 6021 (70.3%) underwent SLN biopsy. SLN positivity was associated with significantly reduced 5-year DSS among matched patients who underwent SLN biopsy (47.1% SLN+ vs 75.5% SLN-; P .001). Five-year DSS remained significantly different across matched T-stages: T3b (54.2% SLN+ vs 64.8% SLN-; P = .004), T4a (55.5% SLN+ vs 71.6% SLN-; P = .001), and T4b (38.6% SLN+ vs 60.9% SLN-; P .001).Retrospective study.For patients with clinical stage IIB/C cutaneous melanoma, SLN status provides essential prognostic information.

Basal cell carcinoma (BCC) is common cutaneous malignancy.To examine the expression patterns of CD10, p63, BCL-2, and epithelial membrane antigen (EMA) proteins in BCC.We used immunohistochemistry to evaluate the expression pattern of these proteins in 45 BCC specimens and their adjacent normal skin.We found variations in the expression pattern of these proteins among normal skins and BCC. In normal skins, we found strong EMA cytoplasmic expression (adnexal structures). A strong nuclear p63 protein expression was found in basal and some suprabasal keratinocytes, external root sheath cells of the hair follicles, basal cells of the sebaceous glands, and in sweat glands.CD10 protein expression was seen in peri-adnexal mesenchymal spindle cells and myoepithelial cells of sweat glands.BCL-2 protein expression was confined to the basal cell keratinocytes, epidermal melanocytes, outer root sheath, and infundibulum of the hair follicle. In BCC, we found p63 (diffuse, strong nuclear staining), CD10 (focal, moderate cytoplasmic reactivity), and BCL-2 (focal, moderate cytoplasmic reactivity) protein expression in the neoplastic cells. BCC was consistently negative for EMA (except in areas of squamous differentiation).There is an altered expression of these proteins in BCC. The underlying molecular mechanisms are open to further investigations.

To assess Hispanic participants' ratings of intervention materials and examine differences by language preference.Participants on a skin cancer prevention trial were randomized to receive generic (n = 457) or precision prevention materials conveying average (n = 195) or higher genetic risk (n = 268) based on MC1R genotype. Three months after receiving either English or Spanish language prevention materials, participants reported amount read, believability and clarity of materials, and intention to change preventive behavior.Participants reported high levels on all four outcomes, but the precision prevention groups noted lower clarity than the generic group (p = 3.2 ×10Skin cancer prevention materials were well-received by Hispanic participants. Higher scores among participants preferring Spanish may indicate acquiescence bias, or that translated prevention materials met their linguistic needs. Participants in the precision prevention groups with English language preference may have challenges in the uptake of genetic risk results.Availability of Spanish materials may have facilitated higher scores. Additional strategies should be explored to optimize participants' believability and clarity of precision prevention materials.

To explore the clinical effect of allogeneic sclera transplantation combined with tarso-conjunctival flap in total excision of divided eyelid nevus.Eleven patients (three male and eight female patients) who experienced divided nevus of the eyelids between January 2014 and April 2020 were recruited to this retrospective study. All lesions were thick, darkly pigmented, presented with a wart-like appearance, and invaded the eyelid margin and tarsal conjunctiva. The surgical method involved a full-thickness lesion excision; then, the posterior defect was reconstructed by sliding the residual tarso-conjunctival flap forward and allogeneic sclera transplantation, and the anterior defect was reconstructed with sliding flaps, rotating flaps, and free skin grafts.Neither malignant transformations nor recurrences were observed after a follow-up of more than one year. The eyelid shape was normal, the rim of the eyelid was smooth, there was no dissolution or rejection of the allogeneic sclera, and the eyelid had good mobility. All the flaps used were viable, soft, and thin. The most frequent complication was the loss of eyelashes in the reconstructed area.For divided nevus of the eyelids invaded the eyelid margin and tarsal conjunctiva, total excision is a better decision, regardless of tumor recurrence or aesthetic considerations. The posterior defect reconstruction through sliding residual tarso-conjunctival flaps combined with allogeneic sclera transplantation is simple and effective.

Oral mucosal melanoma (OMM) is the subject of few studies, resulting in a lack of understanding. The aim of this study is to review the current literature on OMM. The term searched was "oral mucosal melanoma" between 01/01/2000 and 03/15/2021 in the PubMed Database (MEDLINE). Patients presenting with OMM and treated in our center between January 2009 and January 2020 were included in a case series. Demographics, location, risk factors, genetic mutations, treatment performed, and overall survival (OS) rates were evaluated. The PubMed database search yielded a total of 513 results, thirty-eight articles were finally included, which amounted to 2230 cases of OMM. 13 patients were included in the case series. A male-to-female ratio of 1.28:1.00 was found with a mean age at first diagnosis of 58.2 years old. Hard palate (1060 cases) and then gingiva (794 cases) were the two main locations. No risk factors could be identified. OMM were staged III or IV at diagnosis. Mutations were described as such: KIT in 14.6% of cases, BRAF in 7%, and NRAS in 5.6%. Treatment protocols varied but radical surgery was the cornerstone treatment associated with adjuvant therapies. Immunotherapy has not been evaluated for OMM. OS rates were 43.4% at 3 years, 33.1% at 5 year and 15.4% at 10 years. OMM show distinct features from cutaneous melanoma (CM): typical locations, no identified risk factors, different mutations profile, worse prognosis with advanced stage at diagnosis. Targeted therapies are still underused compared to CM.

Malignant melanoma is rare in the pediatric population and management is largely extrapolated from adult guidelines. Adult data have shown that immediate completion lymph node dissection (CLND) does not improve overall survival in selected patients with clinically node negative, sentinel lymph node-positive disease. Current nodal management in children is unknown.The National Cancer Database (NCDB) was queried for patients with melanoma from 2012-2017 and patients categorized as pediatric (≤18 years, n=962) or adult (n=327,987). Factors associated with CLND in children with positive SLNB were evaluated in multivariable analysis. Kaplan-Meier survival analysis was performed.Compared to adults, children present with thicker primary tumors (T3 or T4 26.5% vs 15.5%, p0.001), resulting in higher rates of nodal assessment with SLN biopsy or LND (60.2% vs 36.6%, p0.001) and higher rates of regional nodal disease (35.1% vs 23.4%, p0.001). Children underwent higher rates of CLND after SLN biopsy (10.4% vs 4.1%) and upfront lymph node dissection (15.2% vs 8.7%). A decreased rate of CLND was noted in 2017 compared to 2012 (odds ratio (OR) 0.16 (p=0.005). CLND was performed more often on multivariable analysis for older pediatric age (12 years, OR=1.6, p=0.037) and lower extremity primary (OR=0.29, p0.001). Children with regional nodal disease have improved 3-year overall survival compared to adults (96.5% vs 71.0%, p0.001).Children with melanoma have higher rates of nodal disease but better survival than adults. As in adults, there has been a recent increase in close nodal observation rather than CLND for patients with positive SLN. Further study of nodal surveillance for pediatric patients is warranted.

Mycosis fungoides (MF) and primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30LPD) are the most frequent primary cutaneous T-cell lymphomas. Our objective was to study pan-T-cell antigens and PD-1 expression in a large cohort of MF and CD30LPD with a special interest in antigen losses as a diagnostic tool. We retrospectively reviewed 160 consecutive samples from 153 patients over a 3 year period, including 104 with MF and 49 with CD30LPD. As controls, benign inflammatory dermatoses (BID, n=19) were studied. A semi-quantitative evaluation of CD2, CD3, CD4, CD5, CD7, CD8 expression was performed. PD-1 and double stainings (CD3+CD7 and PD-1+CD7) were performed in a subset of MF cases. CD8+ MF was frequent (23%) and CD7 was the most frequently lost antigen in both MF (45%) and CD30LPD (86%), while no significant T-cell antigen loss was observed in BID. CD7 loss was less frequent in folliculotropic MF (p0.001). PD-1 was variably expressed in MF with no differences with BID. The CD3+/CD7- and PD-1+/CD7- neoplastic lymphocytes were highlighted by the use of chromogenic double staining experiments in MF with a CD7 loss identified with single staining. Multiple pan T-cell antigen losses were mostly seen in CD30LPD with CD2 being the most frequently preserved marker (90%). While PD-1 does not discriminate between MF and BID, CD7 is frequently lost in MF infiltrates as well as other pan-T-cell antigens in CD30LPD, which can be used as routine markers for diagnosis. We recommend the use of CD7 in addition to CD3, CD4 and CD8 as a minimal immunohistochemical panel for MF assessment, and the use of double stainings for CD3 and CD7 in difficult cases.

The aim of this publication is the assessment of the existing guidelines for non-melanoma skin cancer (NMSC) superficial brachytherapy (BT) and make a critical review based on the existing literature about the maximum dose prescription depth, bolus thickness and maximum skin surface dose (D

Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. They develop during the first few weeks of life and naturally progress by proliferating over several months before they involute and resolve; this renders them inconsequential in many cases, but sometimes IHs can have detrimental consequences on function and disfigurement. Hence, systemic propranolol has become a crucial element in IH management, alongside various other medical, procedural, and surgical options that aim to promote their quicker resolution and prevent and alleviate complications.

Adoptive transfer of PD-1 knockout T cells mediated by CRISPR/Cas9 technology has been used in various cancers and got satisfactory treatment effectiveness. However, the effectiveness was limited due to the low proliferation ability, antigen recognition ability and short lifetime of T cells in vivo.In this study, PD-1 knockout T cells mediated by CRISPR/Cas9 system were transferred into lymphopenic mice after sub-lethal dose of total body irradiation. The antitumor effects of PD-1 knockout T cells were comprehensively analyzed by flow cytometry. Moreover, PD-L1 knockout B16 cells were inoculated subcutaneously in lymphopenic mice receiving infusion of naïve T cells to value the role of PD-1/PD-L1 axis on lymphopenia-induced antitumor immunity RESULT: In this study, we found that the PD-1-knockout T cells underwent several rounds of homeostatic proliferation in vivo when they were transferred into lymphopenic mice. The number of IFN-γ-releasing CTL was significantly increased and the tumor growth was remarkably inhibited in lymphopenic mice receiving infusion of PD-1 knockout T cells. The expression of PD-L1 on tumor cells rose smartly in lymphopenic mice undergoing homeostatic proliferation. PD-L1 gene knockout on B16 melanoma cells could effectively enhance the antitumor immunity mediated by the homeostatic proliferation of T cells and significantly inhibited the growth of tumor CONCLUSION: These findings suggested that lymphopenic condition after total body irradiation might be able to create an environment to promote the PD-1 knockout T cells to recognize tumor antigen and undergo homeostatic proliferation, thus induced a more powerful antitumor immunity than adoptively transferring into immunocompetent hosts.

Pigmented nail lesions are challenging problems. The differential diagnosis is broad and ranges from common self-limiting conditions, such as subungual hematoma and infection, to potentially fatal conditions, such as subungual melanoma. Clinical assessment and adjuncts, such as dermoscopy and imaging, are usually insufficient to establish a diagnosis, and a nail bed biopsy is often required. However, this is not an innocuous procedure and may result in permanent nail deformity. In addition, subjecting every patient with nail pigmentation to a biopsy will result in an unacceptably high rate of negative test results. Furthermore, histopathologic diagnosis of subungual melanoma remains challenging for several reasons. Once the diagnosis of subungual melanoma is established, the definitive treatment is controversial because the existing guidelines have largely been adapted from those for cutaneous melanoma. This review presents an approach to the diagnosis and management of pigmented subungual lesions and subungual melanoma, in particular, on the basis of the latest available evidence.

The brisk remodeling in healthcare delivery observed after the COVID-19 outbreak led us to evaluate how the pandemic affected non-melanoma skin cancer's (NMSC) care and tumor burden. To address this topic, we set up a retrospective real-life multi-center study based on the cities of Bergamo and Varese, whose provinces were the worst hit in Italy by the pandemic. We analyzed medical and pathological data from patients that underwent surgery in the two months preceding the outbreak in Italy and compared them to those who did in the corresponding bimester of the following year, reaching 214 patients and 274 lesions. We observed a considerable and significant increase in NMSC's diameter, as well as in the proportion of squamous cell carcinomas. Both the average waiting time to obtain an evaluation visit and the average time in the surgical waiting list was shorter after the COVID-19 outbreak: the reason is that we evaluated and operated near-exclusive patients affected by high-priority lesions, who benefited from "fast-track" referrals. Conversely, less-concerning lesions were, and still are, left on hold, until they will become advanced enough to be labeled as "urgent". Plastic surgery departments should evade as soon as possible from this downward spiral, in order to provide our patients with timely cancer care and to be able to treat all plastic surgery-requiring pathologies.

Several types of immune checkpoint inhibitors (ICIs) are approved to treat advanced melanoma, but their effectiveness has not been compared in older patients treated outside of a clinical trial. Moreover, evidence suggests that a patient's response to ICI therapy may vary by age and type of ICI. The purpose of this study was to compare survival by ICI type in older patients with melanoma and to investigate treatment effect modification by age.Using the SEER-Medicare database, we identified patients with cutaneous melanoma (2012-2015) treated with an ICI (CTLA-4, PD-1, or combination CTLA-4 + PD-1 inhibitors). Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for ICI types. We used an interaction term and stratified models to test for treatment effect modification by age.Of the 1435 patients included in our analysis, 790 (55.1%) received CTLA-4 inhibitors, 512 (35.7%) received PD-1 inhibitors, and 133 (9.3%) were treated with combination ICIs. Median survival ranged from 13.4 months (95%CI: 10.7-16.3) for CTLA-4 inhibitors to 23.5 months (95%CI: 16.2-30.0) for combination ICIs. In multivariable models, the risk of death was lower with PD-1 inhibitors compared to CTLA-4 inhibitors (HR = 0.78, 95%CI: 0.68-0.89). An age*ICI type interaction term was significant (p 0.001), and survival gains were greater the older age group (≥80) compared to the younger group (65-79).In a population-based setting, we identified important differences in survival by ICI type in older patients with melanoma treated with ICIs, with prolonged survival associated with PD-1 inhibitors compared to CTLA-4 inhibitors.

Eccrine spiradenoma (ES) is a rare benign cutaneous adnexal tumor. The aim of our study was to discuss the clinical presentation, cytomorphologic features, and differential diagnosis of a series of 3 cases of ES diagnosed by fine needle aspiration (FNA).The pathology databases were searched for cases of ES diagnosed by FNA and confirmed by follow-up surgical excision. FNA smears, cell blocks, and histologic sections were examined.Three cases of ES that had presented as a soft tissue mass from 3 patients were reviewed. The sites included the left forearm, left leg, and left ankle. Cytology smears showed the presence of hypercellular 3-dimensional dense cell clusters and smaller loose cell aggregates, single cells, and bare nuclei. Most cells had round to oval nuclei, scant cytoplasm, and indistinct cell borders. A second population of cells had more spindled nuclei and were often dispersed as single cells. Scattered lymphocytes were present. Two cases showed the presence of pseudo-rosettes composed of hyaline globules of basement membrane-like material with a surrounding row of basaloid cells. None of the cases showed cytologic atypia, necrosis, or mitoses. Immunohistochemistry was used in 2 cases and showed positive staining with myoepithelial markers (smooth muscle actin, calponin, S100, and CK5). The cytology diagnoses were ES, basaloid cutaneous adnexal neoplasm, and suspicious for ES.FNA cytopathology of ES demonstrated banal basaloid and spindle cells, lymphocytes, and infrequent metachromatic-stained hyaline globules. A specific diagnosis requires immunohistochemistry testing to avoid confusion with other cutaneous basaloid neoplasms.

Spider angioma refers to a type of telangiectasis that presents slightly beneath the skin surface on the face, neck, arms or upper trunk, often manifesting with a central red spot and reddish extensions that radiate outwards like a spider's web. The cutaneous spider angioma may be benign but it often indicates abnormal liver function, especially in patients with chronic cirrhosis. The spider angioma is irreversible and rarely occurred diffusely over the body or with giant sizes. Here, we report two rare multiple and giant spider angioma cases in patients with HIV/AIDS who developed chronic cirrhosis. In addition, we comprehensively reviewed related literatures and evaluated the existing possible mechanisms of spider angioma.

Bob Marley was a Jamaican singer, songwriter, and musician, considered one of the pioneers of reggae. In July 1977, he was diagnosed with acral lentiginous melanoma on his right great toe, which presented as a pigmented subungual lesion. Marley was advised to have his digit amputated, but he refused and opted for less invasive solutions. Unfortunately, he died at the age of 36 of metastatic disease in May 1981 after a 4-year battle with the disease. Marley has served as the posthumous poster child for skin cancer in people with skin of color for decades and has raised public awareness of this rare form of malignant melanoma.

This study aimed at identifying the sociodemographic and first treatment characteristics affecting time-to-treatment initiation (TTI) of patients with cutaneous melanoma assisted by the Brazilian Unified Health System (SUS).Retrospective observational study using cutaneous melanoma cases recorded in the Brazilian Hospital-Based Cancer Registries (HBCR).A total of 12,783 cutaneous melanoma cases were included in the analysis. Based on the legislation, TTI in Brazil is 60 days; therefore, the cohort was dichotomized into TTI within 60 days and over. The association among variables was evaluated through the Chi-squared test. Kaplan-Meier method and log-rank hypothesis test were used to determine the probability of initiating treatment within 60 days. Cox proportional hazards regression model was used for multivariate analysis.Median TTI was 28 days (95% CI, 25-29). First treatment in SUS provided more than 60 days after diagnosis (34.8%) was associated with females; low level of formal education; living or getting treatment in northern Brazil; being diagnosed in SUS and treated at different healthcare facilities, in addition to starting treatment with radiotherapy or systemic therapy. There were no significant differences in access to health care before and after the enactment of the 60-day law.Increased TTI for cutaneous melanoma is associated with sociodemographic and first treatment characteristics in Brazil; approximately one-third of cases did not have access to first treatment within the period established by law. Receiving the diagnosis and treatment at different healthcare facilities (transitions in care) is the main independent factor associated with TTI longer than 60 days.

BRAF-inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions including sarcoidosis and sarcoid-like-reactions have been reported as a consequence of BRAF-inhibition. It is important to adequately characterise these granulomatous reactions including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterise the spectrum of granulomatous reactions associated with BRAF-inhibitors - identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, possible correlation with cancer response, mechanisms of granuloma formation, as well as a proposed workup and management approach for these granulomatous reactions are presented.

Basal cell carcinoma (BCC) is the most common skin cancer. Removing the lesion with wide surgical margins and obtaining a microscopically intact margin is considered sufficient in the treatment of BCC. However, it may not always be possible to provide wide and intact margins in cosmetically and functionally important areas. Although recurrence rates after BCC excision vary among studies, the recurrence rate at 5 years is considered to be 2%. BCC subtype, perineural invasion, and close margin are important factors in recurrence. The aims of this study are to investigate the other factors associated with recurrence in BCC treatment and reveal the value of the "histopathological surgical margin" which can help in making the decision for re-excision. A statistically significant correlation is observed between the increase in tumour size and recurrence(p0.05). The recurrence rate after excision with a histopathologic margin of 1 mm or less is 19%. This rate is found to be 8% in patients with a histopathological margin greater than 1 mm and 3 mm or less. Reticular dermis and deeper tissue invasion statistically increase the recurrence rate. Multiple excision and the presence of residual tumour in the re-excision sample also increase the recurrence rate. In conclusion, recurrence in BCC patients is affected by more than one parameter. We highly recommend re-excision in patients with a histopathological margin of 1 mm or less. In tumours with histopathological margins between 1 mm and 3 mm, the decision for re-excision or "wait-and-see" approach should be made according to the characteristics of the tumours and patients.

Studies comparing 5-fluorouracil (5-FU), imiquimod, and photodynamic therapy with aminolevulinic acid (PDT-ALA) have evaluated the efficacy of destroying actinic keratosis (AK). However, this end point may not directly translate to cutaneous squamous cell carcinoma (cSCC) prevention. No study to date has evaluated these field therapies for cSCC prevention in the long term, defined as greater than 1-year posttreatment.Determine the time to surgically treat invasive cSCC development after treatment with 5-FU, imiquimod, or PDT-ALA beginning 1-year posttreatment.Retrospective cohort study using the Optum Clinformatics Data Mart database from 2012 to 2019 RESULTS: The rate of cSCC development in patients treated with 5-FU showed no significant difference compared with imiquimod (0.99; 95% CI, 0.90-1.08). PDT-ALA was worse than 5-FU (1.27; 95% CI, 1.19-1.36) and imiquimod (HR, 1.29; 95% CI, 1.17-1.43). Other known predictors of cSCC were consistent with previous literature.The location of field therapy could not be determined with a claims database.5-FU is not superior to imiquimod beginning 1 year posttreatment, despite previously demonstrated superior AK destruction efficacy, but was superior to PDT-ALA. Conflating AK destruction and cSCC prevention efficacy may not be appropriate. Future prospective studies should aim to use an end point of cSCC development.

The European journal of cancer : EJC 173, 307-316 (2022). doi:10.1016/j.ejca.2022.07.002, Published by Elsevier, Amsterdam [u.a.]

The treatment paradigm for patients with anorectal melanoma eligible for sphincter-sparing excision has evolved over time. This study examines outcomes across a 30-year era in this rare disease with poor prognosis.This retrospective cohort study included all patients with pelvis-confined anorectal melanoma undergoing sphincter-sparing local excision and adjuvant radiation therapy (RT) at our institution between 1989 and 2020. Patterns of care and predictors of outcome were evaluated.Of the 108 patients included, 92 (85%) presented with clinically uninvolved nodes. For clinically node-negative patients, the sentinel lymph node biopsy rate increased from 18/43 (42%) before 2008 to 38/49 (78%) subsequently and the use of inguinal nodal RT decreased from 33/35 (94%) before 2003 to 1/57 (2%) subsequently. All clinically node-positive patients treated before 2003 received inguinal nodal RT, whereas no node-positive patient treated subsequently received this treatment. Patients treated before 2016 mostly received biochemotherapy, and those treated since 2017 mostly received immune checkpoint inhibitors. With median follow-up of 32 months, 77 patients (71%) recurred. Three-year actuarial outcomes were 84% local control, 64% nodal control, 38% distant metastasis-free survival, 30% disease-free survival, and 51% melanoma-specific survival. Ostomy-free survival at last follow-up was 95%. Factors contributing to outcome were identified. Outcomes for patients treated in the contemporary era (2017+) were not significantly better than those treated earlier.Sphincter-sparing surgery followed by adjuvant RT results in excellent local control and ostomy-free survival for locally resectable anorectal melanoma. Overall oncologic outcomes continue to be poor, reinforcing the need to identify more effective therapies.

Skin melanoma is one of the most common cancer types in the United States and worldwide, and its incidence continues to grow. Primary skin melanoma can be removed surgically when feasible and if detected at an early stage. Anti-cancer drugs can be applied topically to treat skin cancer lesions and used as an adjunct to surgery to prevent the recurrence of tumor growth. We developed a topical formulation composed of Navitoclax (NAVI), a BCL-2 inhibitor that results in apoptosis, and an ionic liquid of choline octanoate (COA) to treat early-stage melanoma. NAVI is a small hydrophobic molecule that solubilizes at 20% (w/v) when dissolved in 50% COA. Although NAVI is a highly effective chemotherapeutic, it is equally thrombocytopenic. We found that COA-mediated topical delivery of NAVI enhanced its penetration into the skin and held the drug in the deeper skin layers for an extended period. Topical delivery of NAVI produced a higher cancer-cell killing efficacy than orally administrated NAVI. In vivo experiments in a mouse model of human melanoma-induced skin cancer confirmed the formulation's effectiveness via an apoptotic mechanism without any significant skin irritation or systemic absorption of NAVI. Overall, this topical approach may provide a safe and effective option for better managing skin cancer in the clinic.

Merkel cell carcinoma is among the most aggressive and lethal of primary skin cancers, with a high rate of distant metastasis. Anti-programmed death receptor 1 (anti-PD-1) and programmed death ligand 1 (PD-L1) monotherapy is currently standard of care for unresectable, recurrent, or metastatic Merkel cell carcinoma. We assessed treatment with combined nivolumab plus ipilimumab, with or without stereotactic body radiotherapy (SBRT) in patients with advanced Merkel cell carcinoma as a first-line therapy or following previous treatment with anti-PD-1 and PD-L1 monotherapy.In this randomised, open label, phase 2 trial, we randomly assigned adults from two cancer sites in the USA (one in Florida and one in Ohio) to group A (combined nivolumab and ipilimumab) or group B (combined nivolumab and ipilimumab plus SBRT) in a 1:1 ratio. Eligible patients were aged at least 18 years with histologically proven advanced stage (unresectable, recurrent, or stage IV) Merkel cell carcinoma, a minimum of two tumour lesions measureable by CT, MRI or clinical exam, and tumour tissue available for exploratory biomarker analysis. Patients were stratified by previous immune-checkpoint inhibitor (ICI) status to receive nivolumab 240 mg intravenously every 2 weeks plus ipilimumab 1 mg/kg intravenously every 6 weeks (group A) or the same schedule of combined nivolumab and ipilimumab with the addition of SBRT to at least one tumour site (24 Gy in three fractions at week 2; group B). Patients had to have at least two measurable sites of disease so one non-irradiated site could be followed for response. The primary endpoint was objective response rate (ORR) in all randomly assigned patients who received at least one dose of combined nivolumab and ipilimumab. ORR was defined as the proportion of patients with a complete response or partial response per immune-related Response Evaluation Criteria in Solid Tumours. Response was assessed every 12 weeks. Safety was assessed in all patients. This trial is registered with ClinicalTrials.gov, NCT03071406.50 patients (25 in both group A and group B) were enrolled between March 14, 2017, and Dec 21, 2021, including 24 ICI-naive patients (13 [52%] of 25 group A patients and 11 [44%] of 25 group B patients]) and 26 patients with previous ICI (12 [48%] of 25 group A patients and 14 [56%] of 25 group B patients]). One patient in group B did not receive SBRT due to concerns about excess toxicity. Median follow-up was 14·6 months (IQR 9·1-26·5). Two patients in group B were excluded from the analysis of the primary endpoint because the target lesions were irradiated and so the patients were deemed non-evaluable. Of the ICI-naive patients, 22 (100%) of 22 (95% CI 82-100) had an objective response, including nine (41% [95% CI 21-63]) with complete response. Of the patients who had previously had ICI exposure, eight (31%) of 26 patients (95% CI 15-52) had an objective response and four (15% [5-36]) had a complete response. No significant differences in ORR were observed between groups A (18 [72%] of 25 patients) and B (12 [52%] of 23 patients; p=0·26). Grade 3 or 4 treatment-related adverse events were observed in 10 (40%) of 25 patients in group A and 8 (32%) of 25 patients in group B.First-line combined nivolumab and ipilimumab in patients with advanced Merkel cell carcinoma showed a high ORR with durable responses and an expected safety profile. Combined nivolumab and ipilimumab also showed clinical benefit in patients with previous anti-PD-1 and PD-L1 treatment. Addition of SBRT did not improve efficacy of combined nivolumab and ipilimumab. The combination of nivolumab and ipilimumab represents a new first-line and salvage therapeutic option for advanced Merkel cell carcinoma.Bristol Myers Squibb Rare Population Malignancy Program.

Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.