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Merkel cell polyomavirus (MCV) was named for its role as the causative agent of Merkel cell carcinoma (MCC), which is MCV positive in approximately 80% of cases. MCV is classified as a Group 2A carcinogen, which promotes carcinogenesis by integrating T-antigen into the cell genome. The prevalence of anti-MCV antibodies in the general population can be as high as 90%. MCV typically promotes cancer by integrating T-antigen genes into the host cell genome, and 80% of MCC cases are attributed to MCV activation. In immunocompetent individuals, MCV usually remains latent after infection. However, the incidence of MCC increases significantly in immunocompromised or immunodeficient patients, such as those who have undergone organ transplantation, have chronic lymphocytic leukemia, or are living with human immunodeficiency virus (HIV) infection. Acquired immunodeficiency is a particular feature of people living with HIV. Currently, research on HIV/AIDS patients with MCV infection, clinical outcomes, and treatments is quite limited. This paper reviews previous research and systematically examines the relationship between HIV/AIDS and MCV-associated diseases, with the aim of providing valuable information for the prevention, diagnosis, and treatment of MCV in vulnerable populations.

Background: Novel and highly effective drugs for non-melanoma skin cancer (NMSC) improve patient outcomes, but their high cost strains healthcare systems. Spain's decentralized public health system, managed by 17 autonomous communities (AaCc), raises concerns about equitable access., Methods: A cross-sectional survey (July-September 2023) was sent to Spanish Multidisciplinary Melanoma Group (GEM Group) members to assess access to new drugs., Findings: Fifty physicians from 15 Spanish AaCc responded to the survey. Access for drug with approved public reimbursement, Hedgehog inhibitors in basal-cell carcinoma and anti PD-L1 antibody in Merkel carcinoma, was observed in 84% and 86% of centers, respectively. For other EMA-approved treatments, but without reimbursement in Spain access decreased to 78% of centers. Heterogeneity in access was mainly observed intra regions., Conclusion: Unequal financial support for drugs for NMSC with creates a patchwork of access across Spanish hospitals, with variations even within the same AaCc., Competing Interests: Declarations. Conflict of interest: None. Research involving human participants and/or animals: This article does not conatiin any studies with human participants or animals performed by any of the authors. Informed consent: For this type of study formal consent is not required., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study., Methods: A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model., Results: Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I 2  = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS., Conclusions: Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early-onset MCC (EOMCC) and the differences between EOMCC and late-onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer-specific survival (CSS) of EOMCC., Methods: Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome., Results: The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002-5.456], P < 0.001), advanced T stage (HR 1.430 [1.139-1.797], P = 0.002), advanced N stage (HR 1.522 [1.221-1.897], P < 0.001), M1 stage (HR 2.587 [1.480-4.521], P < 0.001), and radiation (HR 0.586 [0.410-0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (P log-rank  = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone., Conclusions: We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone., (© 2024 the International Society of Dermatology.)

Although rare, Merkel cell carcinoma (MCC) is a highly aggressive and increasingly prevalent neuroendocrine cancer of the skin. While current interventions, including surgical resection, radiation, and immunotherapy have been employed in treating many patients, those who remain unresponsive to treatment are met with sparse alternatives and a grim prognosis. For this reason, it is of interest to expand the repertoire of available therapies for MCC patients who remain resistant to current primary interventions. Recently, our improved mechanistic understanding of aberrant cell signaling observed in both MCPyV-positive and -negative MCC has facilitated exploration into several small molecules and inhibitors, among them receptor tyrosine kinase inhibitors (TKIs) and somatostatin analogs (SSAs), both of which have positively improved response rates and reduced tumor volumes upon application to treatment of MCC. The introduction of such targeted therapies into treatment protocols holds promise for more personalized care tailored towards patients of diverse subtypes, thereby improving outcomes and mitigating tumor burden, especially for treatment-resistant individuals. In this review, we characterize recent findings surrounding targeted treatments that have been applied to MCC and provide an overview of emerging perspectives on translatable options that can be further developed to offer additional therapeutic avenues for patients with the disease.

Nonmelanoma skin cancers (NMSCs) are the most common cancers, with high-risk NMSCs sharing features such as poor histologic differentiation, invasion into deeper layers, and anatomic location. NMSC includes basal cell carcinoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Herein, the authors describe advances in understanding the genetic mechanisms of malignant transformation and the composition of tumor microenvironment for these cancers. They summarize recent therapeutic advances, including targeted therapy and immunotherapy for NMSCs. Effective skin protection against ultraviolet radiation-induced carcinogenesis remains an urgent unmet need for NMSC prevention. The authors highlight immune-based interventions as novel strategies to address this need., Competing Interests: Disclosure S. Demehri is an inventor on filed patents for the use of calcipotriol plus 5-fluorouracil combination for the treatment of actinic keratosis and T cell-directed HPV vaccine for skin cancer prevention. S. Demehri and T. Oka are inventors on a provisional patent for the development of topical immunotherapy for basal cell carcinoma. T. Lee does not report potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is highly radiosensitive and immunogenic. Immunotherapy is the primary treatment of advanced disease, and immune checkpoint inhibitors show promise as neoadjuvant or adjuvant therapy in patients with high-risk resectable MCC. Emerging biomarkers of tumor burden are becoming increasingly important in identifying high-risk patients and in post-treatment surveillance. Further research is needed to determine the optimal duration of anti-PD-(L)1 treatment and second-line options for patients with MCC refractory to immunotherapy. This review covers the characteristics and management of MCC including recent innovations and areas of active investigation., Competing Interests: Disclosure The authors have nothing to disclose., (Published by Elsevier Inc.)

Background: Merkel cell carcinomas are rare, aggressive skin tumors with high metastatic potential and poor prognosis. Their treatment is classically based on surgery with adjuvant external radiotherapy for localized tumors or on immunotherapy or chemotherapy, sometimes associated with radiotherapy, for metastatic stages. Those tumors are highly radiosensitive due to their neuroendocrine and undifferentiated nature, but they usually fail to rapidly respond to treatment., Case Presentation: We report the case of a 65-year-old retired female patient of Caucasian (German) origin with locally advanced Merkel cell carcinoma of the buttock, with pancreatic metastases synchronous at diagnosis, treated with local radiotherapy of the right buttock without regional lymph node irradiation followed by a sequential chemotherapy; 1 year later, the patient developed an isolated pancreatic recurrence treated with exclusive radiotherapy. The patient was still alive at 13 years with complete remission., Conclusion: External radiotherapy can be an effective alternative to surgery for locally advanced or even oligometastatic Merkel cell carcinomas., (© 2024. The Author(s).)

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1. Responders have increased type I/II interferons and preexisting tissue resident (Trm) CD8 or Vδ1 γδ T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public T-cell receptors. Spatial transcriptomics demonstrated colocalization of T cells with B and dendritic cells, which supply chemokines and costimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vδ1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC. Significance: MCC serves as a model of ICB response. We utilized the largest-to-date, multimodal MCC dataset (n = 116 patients) to uncover unique tumor-intrinsic properties and immune circuits that predict response. We identified CD8 Trm and Vδ1 T cells as clinically actionable mediators of ICB response in major histocompatibility complex-high and -low MCCs, respectively., (©2024 American Association for Cancer Research.)

Merkel cell polyomavirus (MCPyV) is a significant contributor to the development of Merkel cell carcinoma (MCC), an aggressive skin cancer with high recurrence and a low survival rate. In fact, it is the deadliest skin cancer. The precise routes of transmission for MCPyV-positive MCC remain unclear, but several factors may trigger its development. Conventional treatments for MCC are not highly effective, especially in patients with metastasis, with a clear need for new treatment options. Gene-targeted therapies hold great promise for the treatment of MCC, including the use of siRNA and CRISPR/Cas (C/Cas) but critically none have yet been translated into clinical trials. Validating this approach is the fact that several siRNA products are already FDA licenced, while C/Cas has entered clinical trial, albeit for conditions other than MCC. There are many challenges that must be overcome to move from preclinical research to the clinic. In this review, we provide a comprehensive summary of the current understanding of MCC, with a particular focus on MCPyV-positive MCC, and the status of gene-targeted therapies. Additionally, we discuss the major obstacles that impede MCC research and explore future prospects., (© 2024 The Author(s). Reviews in Medical Virology published by John Wiley & Sons Ltd.)

Background: Immunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated., Methods: For this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS)., Results: Of the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021)., Conclusion: The study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC., (© 2024. The Author(s).)

Purpose of Review: This review provides an update on approved and emerging systemic therapies in the treatment of locally advanced or metastatic non-melanoma skin cancers (squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma)., Recent Findings: Many studies demonstrate the effectiveness of immunotherapy for all types of non-melanoma skin cancer. For basal cell carcinoma (BCC), hedgehog inhibitors (HHI) remain first-line but with poor tolerability. Numerous clinical trials studying both neoadjuvant and adjuvant use of anti-PD-1 and anti-PD-L1 therapies in advanced NMSC are under investigation. There is a growing number of systemic therapies available to treat non-melanoma skin cancers. The advent of immunotherapy has revolutionized the field and greatly improved survival compared to historical survival rates with cytotoxic chemotherapy., (© 2024. The Author(s).)

Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease., Objectives: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management., Methods: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up., Results: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards., Conclusion: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil., (© 2024 Wiley Periodicals LLC.)

Competing Interests: Conflicts of interest None disclosed.

Objectives: Immune checkpoint inhibitors are a promising new therapy for advanced Merkel Cell Carcinoma (MCC). We investigated real-world utilization and survival outcomes of first-line immunotherapies in a contemporary cohort., Methods: Using the National Cancer Database (NCDB), we identified 759 patients with MCC between 2015 and 2020 with stage IV disease and known status of first-line systemic therapy. Univariable and multivariable analyses were used to determine predictors of immunotherapy usage. Overall survival (OS) was compared for patients receiving immunotherapy, chemotherapy, or no systemic therapies., Results: We identified 759 patients meeting our inclusion criteria: 329 patients received immunotherapy, 161 received chemotherapy, and 269 received no systemic therapy. Adjusting for demographic, clinical, and facility factors, high facility volume significantly predicted first-line immunotherapy use (OR 1.99; P =0.017). Median OS was 16.2, 12.3, and 8.7 months, among patients who received immunotherapy, chemotherapy, or no systemic therapy, respectively ( P <0.001). On Cox multivariable survival analysis, first-line immunotherapy treatment (HR=0.79, P =0.041) and treatment at high-volume centers (HR=0.58, P =0.004) were associated with improved OS., Conclusions: Consistent with clinical trial results, first-line immunotherapy associated with improvement in median overall survival for patients with stage IV MCC, significantly outperforming chemotherapy in this real-world cohort. Treatment at high-volume centers associated with first-line immunotherapy utilization suggesting that familiarity with this rare disease is important to achieving optimal outcomes for metastatic MCC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Merkel Cell Carcinoma is a rare and aggressive cutaneous carcinoma with a propensity for metastasis and death. Our study describes the prevalence, sociodemographics and inpatient mortality of Merkel Cell Carcinoma related hospitalizations in the United States from 2011 to 2020. We conducted an observational study using the Nationwide Inpatient Sample database, which captures a 20% sample of all hospitalizations in the United States. We utilized the International Classification of Disease Clinical Modification codes from the ninth and tenth revision to identify Merkel Cell Carcinoma and demographic factors. There was a total of 28,809 cases of Merkel Cell Carcinoma in the United States from 2011 to 2020. Merkel Cell Carcinoma was associated with white race (11.4 per 100,000) and disposition of death (26.8 per 100,000). It was most prevalent in the highest quartile income (12.5 per 100,000) and Medicare as primary payer (13.0 per 100,000). Hospitalization was lowest in nonwhite races, particularly NH-Blacks and NH-Others. Inpatient mortality was significantly associated with NH-Others (odds ratio 2.18, 95% confidence interval = 1.38-3.45) and self-pay patients (odds ratio = 2.93, 95% confidence interval 1.84-4.67).This study contributes to reported socio-demographic factors related to Merkel Cell Carcinomas and brings awareness to factors associated with increased hospitalization and inpatient mortality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with cutaneous malignancies and locoregional involvement represent a high-risk population for disease recurrence, even if they receive optimal surgery and adjuvant treatment. Here, we discuss how neoadjuvant therapy has the potential to offer significant advantages over adjuvant treatment, further improving outcomes in some patients with skin cancers, including melanoma, Merkel cell carcinoma, and cutaneous squamous-cell carcinoma. Both preclinical studies and in vivo trials have demonstrated that exposure to immunotherapy prior to surgical resection can trigger a broader and more robust immune response, resulting in increased tumor cell antigen presentation and improved targeting by immune cells, potentially resulting in superior outcomes. In addition, neoadjuvant approaches hold the possibility of providing a platform for evaluating pathological responses in the resected lesion, optimizing the prognosis and enabling personalized adaptive management, in addition to expedited drug development. However, more data are still needed to determine the ideal patient selection and the best treatment framework and to identify reliable biomarkers of treatment responses. Although there are ongoing questions regarding neoadjuvant treatment, current data support a paradigm shift toward considering neoadjuvant therapy as the standard approach for selecting patients with high-risk skin tumors.

Merkel cell carcinoma (MCC) is a rare skin cancer characterized by neuroendocrine differentiation. Its carcinogenesis is based either on the integration of the Merkel cell polyomavirus or on ultraviolet (UV) mutagenesis, both of which lead to high immunogenicity either through the expression of viral proteins or neoantigens. Despite this immunogenicity resulting from viral or UV-associated carcinogenesis, it exhibits highly aggressive behavior. However, owing to the rarity of MCC and the lack of epidemiologic registries with detailed clinical data, there is some uncertainty regarding the spontaneous course of the disease. Historically, advanced MCC patients were treated with conventional cytotoxic chemotherapy yielding a median response duration of only 3 months. Starting in 2017, four programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors-avelumab, pembrolizumab, nivolumab (utilized in both neoadjuvant and adjuvant settings), and retifanlimab-have demonstrated efficacy in treating patients with disseminated MCC on the basis of prospective clinical trials. However, generating clinical evidence for rare cancers, such as MCC, is challenging owing to difficulties in conducting large-scale trials, resulting in small sample sizes and therefore lacking statistical power. Thus, to comprehensively understand the available clinical evidence on various immunotherapy approaches for MCC, we also delve into the epidemiology and immune biology of this cancer. Nevertheless, while randomized studies directly comparing immune checkpoint inhibitors and chemotherapy in MCC are lacking, immunotherapy shows response rates comparable to those previously reported with chemotherapy but with more enduring responses. Notably, adjuvant nivolumab has proven superiority to the standard-of-care therapy (observation) in the adjuvant setting., (© 2024. The Author(s).)

Background: Merkel cell carcinoma (MCC) is an aggressive and rare neuroendocrine tumor, accounting for less than 1% of skin cancers. Metastasis primarily manifests in the cervical lymph nodes but rarely affect the thyroid., Methods: We report a case of primary head and neck cutaneous MCC with metastasis to the thyroid gland. A review of the literature of MCC with thyroid metastasis was conducted., Results: We identified five cases of MCC with thyroid metastasis. Primary sites included the distal upper and lower extremities, axilla, buttock, and groin. Treatment courses varied including thyroidectomy, immunotherapy, and expectant palliative measures. Time from initial diagnosis to thyroid metastasis ranged from four months to four years. Tissue diagnosis was achieved in 5 of 6 cases., Conclusions: MCC with thyroid metastasis is rare and likely represents aggressive disease. Despite advances in treatment and surveillance, outcomes for MCC remain poor. Ongoing research may establish predictors for treatment response., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor with a poor five-year survival rate. Yearly cases have risen nearly 350% since the early 1980s, and these are predicted to increase as the overall US population ages. MCC of the eyelid is uncommon and can be misdiagnosed as other benign inflammatory and neoplastic eyelid disorders. Although MCC of the head and neck is often more aggressive than it is at other sites, eyelid MCC shows a lower disease-specific mortality rate. A biopsy is essential for accurate diagnosis, including an immunohistochemical panel of CK20 and TTF-1, although other markers may be necessary. Staging can be assessed clinically through physical examination findings and imaging and/or pathologically with sentinel lymph node biopsy or fine-needle aspiration. Pathologic staging more accurately predicts the prognosis. Eyelid MCC treatments include Mohs micrographic surgery to allow for complete clearance and adequate reconstruction of lost tissue, followed by adjuvant radiotherapy. In advanced disease, immunotherapies are preferred over traditional chemotherapy and are a subject of ongoing research., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Merkel cell carcinoma is a rare skin cancer associated with poor survival. Based on a previous Phase II trial of adults with advanced Merkel cell carcinoma by Kim and colleagues (2022), there is now a strong rationale for combination therapy (i.e., nivolumab and ipilimumab) to become a treatment option for patients with advanced Merkel cell carcinoma. The goal of this paper was to report on the secondary outcome of quality of life (QOL) among patients on this trial., Methods: Patients receiving combined nivolumab and ipilimumab, with or without stereotactic body radiation therapy (SBRT), completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 prior to starting treatment and every 2 weeks thereafter. Changes in QOL during treatment and post-treatment were evaluated using piecewise random-effects mixed models. Exploratory analyses compared changes in QOL between study arms. The original trial was registered with ClinicalTrials.gov (NCT03071406)., Results: Study participants (n = 50) reported no changes in overall QOL (ps > 0.05), but emotional functioning improved during treatment (p = 0.01). Cognitive and social functioning worsened post-treatment (ps < 0.01). In general, patients treated with combination therapy only (n = 25) reported no change in QOL over time, whereas patients also treated with SBRT (n = 25) consistently demonstrated worsening QOL post-treatment., Conclusion: QOL is generally preserved in patients treated with combination therapy, but the addition of SBRT may worsen QOL. Combined with clinical efficacy data published previously, results support the use of combination therapy with nivolumab and ipilimumab as a treatment option for patients with advanced Merkel cell carcinoma., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Approximately 5-15% of all dermatologic malignancies manifest in the upper and lower eyelids. The primary types include basal cell carcinoma, squamous cell carcinoma, and sebaceous cell carcinoma, with Merkel cell carcinoma and melanoma following closely behind. Basal cell carcinoma predominantly affects the lower eyelid, yet various other carcinomas, melanomas, metastases, and neoplasms of diverse origins can arise on both upper and lower eyelids. Risk factors such as advanced age, smoking, and notably, exposure to UV light significantly contribute to the development of these eyelid lesions. Despite the increasing incidence, research on dermatologic eyelid malignancies remains limited. However, such study is imperative given that many systemic oncologic malignancies initially present as metastatic eyelid lesions. This paper provides an in-depth exploration of eyelid anatomy, clinical presentation, diagnosis, and treatment management.Key Points: Eyelid metastases represent less than one percent of all eyelid cancers, yet they often serve as the initial indication of an underlying systemic malignancy. Early detection and treatment is crucial in improving prognosis and quality of life for patients. Treatment options encompass a range of modalities, with Mohs surgery as the gold standard for the removal of ocular tumors. Additional treatment options include local excision as well as non-surgical interventions such as radiotherapy, cryotherapy, immunotherapy, and topical medications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Merkel cell carcinoma (MCC) is associated with high rates of recurrence and distant metastatic progression. Current guidelines for surveillance imaging are not evidence based. Better characterization of the pattern of distant metastatic spread will better inform surveillance and facilitate earlier detection of metastases., Objectives: This retrospective study aimed to assess potential relationships between primary tumour site and site of initial distant metastasis, time to distant metastasis, overall survival (OS) and MCC-specific death (MSD)., Methods: Patients with local or regional (Stage I-III) disease who were treated with curative intent and progressed to Stage IV were included in this study (n = 151). Fisher's exact test was used to assess differences in patterns of initial distant metastases based on primary tumour site. Time to initial distant metastasis was calculated from date of MCC diagnosis. OS and MSD were calculated from date of initial distant metastasis to date of death from any or MCC-related causes, respectively., Results: Of 151 patients included in analysis, 89 (58.9%) had a single initial distant metastatic site, and 62 (41.1%) had multiple sites. Patients with upper limb primary tumours were significantly less likely to develop distant lymph node or liver metastases (p = 0.02 and 0.04, respectively). Median time to distant metastasis was 11 months (IQR 6.7-17.9 months). Median OS was 15.3 months, and was shorter for patients with liver (7.0 months, p = 0.0004) or bone metastases (8.9 months, p < 0.0001). Using skin/soft tissue metastasis as a reference group, patients with multiple metastatic sites had significantly higher hazards of MSD (HR = 3.46 univariate, 3.77 multivariate analysis). Time to distant metastasis, OS and MSD did not differ by viral status., Conclusion: Sites of initial distant metastasis are related to primary tumour sites and survival outcomes. Because patients often have multiple initial metastases, full-body cross-sectional rather than region-specific imaging may facilitate earlier detection of metastatic disease., (© 2024 European Academy of Dermatology and Venereology.)

Merkel cell carcinoma (MCC) is a rare but highly aggressive and rapidly expanding malignant skin tumor. It affects the periocular region in approximately 10% of cases. The current treatment recommendation for resectable non-metastatic MCC comprises total surgical excision; however, lymph node or distant metastases are often already present by the time of the diagnosis. Since an immune checkpoint inhibitor therapy with avelumab was first approved for MCC in 2016, there has been considerable improvement in mean survival compared to cytostatic therapy; at the same time, there has been a reduction in serious treatment-associated adverse events. Other immune checkpoint inhibitors are currently still in clinical trials, with very promising initial results. Because of the complexity of the diagnosis, treatment, and prognosis, it is essential that MCC patients receive interdisciplinary care in a specialized center including consultation with a tumor review board., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

Competing Interests: Disclosure IL reports personal fees for writing engagements for ESMO and Roche; personal and institutional fees as coordinating principal investigator (PI) for Agenus, Amgen, AstraZeneca, Bristol Myers Squibb (BMS), Celon, Incyte, Janssen, Menarini, MSD, Pfizer, Rhizen, Roche, RyVu and Siropa; institutional research grants from Agenus and Roche; non-financial interests as project lead for MSCI and board member for OECI; spouse has co-ownership of Clininote. JCB reports personal fees as a data safety monitoring board member for 4SC; personal fees as an advisory board member for Almirall, Amgen, Boehringer, InProTher, Merck, Recordati and Sanofi; institutional research grants from Alcedis, IQVIA and Merck; non-financial interests for receipt of product samples from 4SC. PAA reports personal fees for consultancy roles for 4SC, AstraZeneca, Bio-AI Health, BMS, Boehringer Ingelheim, Daiichi Sankyo, Idera, Immunocore, Italfarmaco, iTeos, Lunaphone, Medicenna, Merck Serono, MSD, Nektar, Nouscom, Novartis, Oncosec, Pfizer, Pfizer/Array, Pierre Fabre, Regeneron, Replimmune, Roche Genentech, Sandoz, Sanofi, Sun Pharma and ValoTx; personal fees for advisory roles for 4SC, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Eisai, Idera, Immunocore, iTeos, Merck Serono, MSD, Nektar, Novartis, Pfizer/Array, Pierre Fabre, Regeneron, Replimmune, Roche Genentech, Sandoz, Sanofi, Seagen, Sun Pharma and ValoTx; personal fees as an advisory board member from Erasca, iTeos, Replimmune and ValoTx; personal fees as travel support from Bio-AI-Health, Pfizer/Array and Replimmune; institutional funding from BMS, Pfizer/Array, Roche Genentech and Sanofi; non-financial interests as President of SCITO (Campania Society of ImmunoTherapy of Cancer) and Fondazione Melanoma Onlus Italy; non-financial interests as a member of the board of directors of the Society for Immunotherapy of Cancer (SITC; November 2017-December 2021) and a member of the steering committee for the Society for Melanoma Research (SMR); non-financial interests as a member of the Associazione Italiana di Oncologia Medica (AIOM), American Society of Clinical Oncology (ASCO), the European Organisation for Research and Treatment of Cancer (EORTC), Melanoma Cooperative Group, SITC and SMR. MV reports no potential conflicts of interests. ABl reports personal fees for advisory board membership from Merck (consultant for revision of approval of avelumab by French authorities). CL reports personal fees as an advisory board member from Amgen, BMS, Merck Serono, MSD, Novartis, Pierre Fabre, Roche and Sanofi; funding from BMS and Roche; non-financial interests for advisory roles for Amgen, BMS, Merck Serono, MSD, Novartis, Pierre Fabre, Roche and Sanofi; honoraria from Amgen, BMS, Incyte, MSD, Novartis, Pfizer, Pierre Fabre and Roche; travel/accommodation expenses from Avantis Medical Systems, BMS, Jazz Pharmaceuticals, MSD, Novartis, Pierre Fabre and Sanofi; research funding from BMS and Roche; participation on a data safety monitoring board/advisory board for InfalRx. EM reports no potential conflicts of interests. OH-V reports no potential conflicts of interests. MG reports personal fees for expert testimony from Almirall; personal fees as an advisory board member for GSK, Leo Pharma and Pfizer; personal fees as an invited speaker from GSK, Janssen, Lilly and Novartis; personal stocks/shares in BioNTech, Novo Nordisk and Siemens Healthineers; institutional fees as coordinating PI for Argenx and as local PI for Boehringer Ingelheim, Galderma, Janssen, Novartis and UCB Pharma; non-financial interests as Treasurer of the Deutsche Dermatologische Gesellschaft (DDG) and member of the board of directors of University Hospital Würzburg. HK reports no potential conflicts of interests. PN reports personal fees as an advisory board member for 4SC, BMS, IDEAYA Biosciences, Immunocore, Merck, Novartis and Pfizer; personal fees as an invited speaker for Novartis; institutional research support from Immunocore; non-financial interests as a steering committee member (personal) for 4SC and coordinating PI (institutional) for BMS, Immunocore, Ipsen, Merck, Novartis and Pfizer. PR reports personal fees as an invited speaker for AstraZeneca, BMS, Merck, MSD, Novartis, Pierre Fabre and Sanofi; personal fees as an advisory board member for Blueprint Medicines, BMS, Merck, MSD, Philogen, Pierre Fabre and Sanofi; institutional research grants from BMS and Pfizer; non-financial interests as President of the Polish Oncological Society and a member of the board of directors of the Polish Society of Surgical Oncology. MS reports personal fees as an invited speaker for Aristo-Pharma, Medac, Novartis and Takeda; personal fees as an advisory board member for Novartis and Takeda; personal fees as a PI for Amgen, Dermira, Eli Lilly and Company, Galderma, Parexel International and Regeneron; personal fees as a sub-investigator (SI) for OBWF NIO-PIB, Eli Lilly and Takeda. DS reports personal fees as an invited speaker for BMS, Merck Serono, MSD, Novartis, Roche and Sanofi; personal fees as an advisory board member for BMS, Immunocore, MSD, Neracare, Novartis, Pfizer, Philogen, Pierre Fabre and Sanofi/Regeneron; personal fees as a steering committee member for BMS, MSD and Novartis; institutional research grants from BMS and MSD; institutional fees as coordinating PI for BMS, MSD, Novartis and Pierre Fabre; institutional fees as local PI for Philogen and Sanofi; a non-financial interest as a member of the board of directors of EORTC-MG. JMP reports personal fees as an advisory board member for Astellas, AstraZeneca, BeiGene, BMS, Janssen, MSD, Roche and VCN Biosciences; personal and institutional research grants from BeiGene, BMS, Janssen, Mirati and Pfizer. FP reports no potential conflicts of interests. ACJvA reports institutional fees as an advisory board member for 4SC, Amgen, BMS, Merck–Pfizer, MSD–Merck, Novartis, Pierre Fabre, Provectus, Sanofi and Sirius Medical; institutional research grants from Amgen and Merck–Pfizer. ABe reports personal fees as an invited speaker for Amgen and HRA; personal fees as an advisory board member for Amgen, Astellas, Ipsen and Janssen; institutional funding from Astellas and Janssen; non-financial interests for receipt of product samples from Novartis and Sanofi.

The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common non-melanoma skin cancer tumor entities are cutaneous squamous cell carcinoma and basal cell carcinoma as well as their precursor lesions. One of the less common tumors is Merkel cell carcinoma, which also occurs primarily in light-exposed areas and, in contrast to squamous and basal cell carcinoma, is more likely to metastasize. Due to the low tendency of basal cell carcinoma as well as cutaneous squamous cell carcinoma to metastasize, a cure can often be achieved by surgery. If the tumor growth exceeds certain levels it may require collaboration between dermatology and otorhinolaryngology. The primary goal of this interdisciplinary collaboration is to achieve a functional, cosmetically and aesthetically acceptable result in addition to adequate tumor treatment. Depending on the stage of the tumor and the clinical course, a case may be discussed in an interdisciplinary tumor board in order to determine a personalised, appropriate and adequate treatment concept for each patient, including prevention, therapy and follow-up., Competing Interests: Dres. Eisenburger, Leven und Rudolph erklären keine Interessenkonflikte zu haben. Prof. Schadendorf erklärt verschiedene Interessenkonflikte zu haben: Anaveon, Advisory Board, Personal AstraZeneca, Expert Testimony, Personal BioAlta, Expert Testimony, Personal BioNTech, Advisory Board, Personal BMS, Invited Speaker, Personal BMS, Advisory Board, Personal CureVac, Advisory Board, Personal Daiichi Sanyko, Expert Testimony, Personal Erasca, Advisory Board, Personal Formycon, Expert Testimony, Personal Immatics, Advisory Board, Personal Immunocore, Advisory Board, Personal InFlarX, Expert Testimony, Personal Merck Serono, Invited Speaker, Personal MSD, Invited Speaker, Personal MSD, Advisory Board, Personal Neracare, Advisory Board, Personal Neracare, Invited Speaker, Personal Novartis, Advisory Board, Personal NoviGenix, Advisory Board, Personal PamGene, Expert Testimony, Personal Pfizer, Advisory Board, Personal Philogen, Advisory Board, Personal Pierre Fabre, Advisory Board, Personal Replimune, Advisory Board, Personal Sanofi, Invited Speaker, Personal Sanofi/Regeneron, Advisory Board, Personal Seagen, Expert Testimony, Personal SunPharma, Advisory Board, Personal SunPharma, Invited Speaker, Personal Ultimovacs, Advisory Board, Personal BMS, Coordinating PI, Institutional, No financial interest BMS, Steering Committee Member, Personal, Financial interest BMS, Research Grant, Institutional, Financial interest MSD, Coordinating PI, Institutional, No financial interest MSD, Research Grant, Institutional, Financial interest MSD, Steering Committee Member, Personal, Financial interest Novartis, Coordinating PI, Institutional, No financial interest Novartis, Steering Committee Member, Personal, No financial interest Philogen, Local PI, Institutional, No financial interest Pierre Fabre, Coordinating PI, Institutional, No financial interest Sanofi, Local PI, Institutional, No financial interest Non-Financial Interests EORTC-MG, Member of Board of Directors European Melanoma Registry (EuMelaReg), Leadership Role, Founding member and SC chair Prof. Wiegand gibt an: Wissenschaftliche Präsentationen / Teilnahme an Advisory Boards / Kongressunterstützung; Astra Zeneca, Bristol-Myers Squibb, GSK, Merck Serono, MSD, Roche, Sanofi, Genzyme, (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.&nbsp; &nbsp; &nbsp;doi:10.36849/JDD.8234 &nbsp.

Purpose: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin, which mainly occurs in the sun exposed sites of white patients over 65 years, with a higher recurrence and metastasis rate. Clinically, MCC overlapping Bowen's disease (BD) is a very rare subtype of MCC. Few cases in the literature have been described and the management is not well defined. We summarize and update the epidemiology, clinical and histopathological features, metastasis characteristics, local recurrence rate and management of it by presenting two cases of MCC overlapping BD and reviewing the literature over the last 11 years., Design: We consulted databases from PubMed, ResearchGate and Google Scholar by MeSh "Merkel cell carcinoma" and "Bowen's disease", "Bowen disease" or "squamous cell carcinoma in situ", from January 2013 to December 2023 and reviewed the literatures. We reported two additional cases., Results: Total 13 cases of MCC overlapping BD were retrospectively analyzed, in whom mainly in elderly women over 70 years, the skin lesions were primarily located on the faces, followed by the extremities and trunk. Most of them were asymptomatic, firm, dark red nodules arising on rapidly growing red or dark brown patches, or presenting as isolated nodules. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. All cases were confirmed by histopathology and immunohistochemistry. The most definitive treatment was extended local excision, but local recurrences were common. Of the 13 cases, 4 cases experienced local or distant metastasis. One suffered from an in-transit recurrence of MCC on the ipsilateral leg after local excision and lymph node dissection, whose metastasis completely subsided after avelumab treatment and without recurrence or metastasis during 6 months of follow-up., Conclusions: MCC overlapping BD is a very rare skin tumor mainly predisposed on the faces, with high misdiagnosis rate and recurrence rate. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. The acronym, AEIOUN, has been proposed to aid in clinical identification. Our reports and the literature review can provide a better awareness and management of it., (© 2024. The Author(s).)

Merkel cell carcinoma (MCC) is a rare type of skin cancer that requires a multidisciplinary approach with a variety of specialists for management and treatment. Clinical practice guidelines (CPGs) have recently been established to standardize management algorithms. The objective of this study was to appraise such CPGs via the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Eight CPGs were identified via systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Four appraisers trained in AGREE II protocols evaluated each CPG and deemed two CPGs as high quality, five as moderate quality, and one as low quality. Intraclass correlation coefficients (ICCs) were calculated to verify reviewer consistency as excellent, good, and moderate across four, one, and one domain, respectively. The majority of MCC CPGs are lacking in specifying stakeholder involvement, applicability, and rigor of development. The two high quality CPGs are from the Alberta Health Services (AHS) and the collaboration between the European Dermatology Forum, the European Association of Dermato-Oncology, and the European Organization of Research and Treatment of Cancer (EDF/EADO/EORTC). The EDF/EADO/EORTC CPG had the highest overall score with no significant deficiencies across any domain. An important limitation is that the AGREE II instrument is not designed to evaluate the validity of each CPG's recommendations; conclusions therefore can only be drawn about each CPG's developmental quality. Future MCC CPGs may benefit from garnering public perspectives, inviting external expert review, and considering available resources and implementation barriers during their developmental stages., (© 2024. The Author(s).)

Merkel cell carcinoma (MCC) is an aggressive, fast-growing, highly metastatic neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is an oncogenic driver in the majority of MCC tumors. In this issue of the JCI, Hansen and authors report on their tracking of CD8+ T cells reactive to MCPyV T antigen (T-Ag) in the peripheral blood of 26 patients with MCC who were undergoing frontline anti-programmed cell death protein-1 (anti-PD-1) immunotherapy. They discovered unique T cell epitopes and used the power of bar-coded tetramers to portray immune checkpoint inhibitor-induced immunogenicity as a predictor of clinical response. These findings provide the foundation for therapeutic possibilities for MCC, including vaccines and adoptive T cell- and T cell receptor-driven (TCR-driven) treatments.

A 67-year-old female presented with 2 weeks of right eye pain, redness, and diplopia. An orbital mass was found on magnetic resonance imaging (MRI), and biopsy revealed Merkel cell carcinoma (MCC). She had no primary head or neck lesion and no previous history of MCC. Positron emission tomography (PET) scan showed hypermetabolic subcutaneous lesions of the lower extremity andmultiple osseous lesions of the axial and appendicular skeleton. She received palliative external radiation of 20 Gy in 5 fractions to the orbit. After discussing immunotherapy, she opted for comfort care and expired 1 month later. To the best of our knowledge, this is only the third case of MCC with distant metastasis to the orbit and the first case in which the patient had no previous diagnosis of MCC and no known primary tumor.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan-Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p < 0.001; 95% CI 0.548-0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC)., Objective: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients., Methods: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021., Results: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC., Limitations: Retrospective nature of the analysis and small sample size., Conclusion: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with epithelial and neuroendocrine differentiation, the incidence of which has increased substantially during the last decades. Risk factors include advanced age, fair skin type, UV exposure, and immunosuppression. Pathogenetically, a type caused by the Merkel cell polyomavirus is distinguished from a UV-induced type with a high tumor mutational burden. Clinically, MCC presents as a mostly painless, rapidly growing, reddish-violet tumor with a shiny surface, which is preferentially localized in the head-neck region and at the distal extremities. A reliable diagnosis can only be made based on histological and immunohistochemical features. At initial diagnosis, 20-26% of patients show locoregional metastases and 8-14% distant metastases, making staging examinations indispensable. If there is no clinical evidence of metastases, a sentinel lymph node biopsy is recommended. Essential columns of therapy are surgery, adjuvant or palliative radiotherapy and, in advanced inoperable stages, medicamentous tumor therapy. The introduction of immune checkpoint inhibitors has led to a paradigm shift, as they provide a considerably longer duration of response and better survival rates than chemotherapy. The PD-L1 inhibitor avelumab is approved for treatment of metastatic MCC in Germany, but the PD-1 antibodies pembrolizumab and nivolumab are also used with success. Adjuvant and neoadjuvant treatment concepts, immune combination therapies and targeted therapies as monotherapy or in combination with immune checkpoint inhibitors are in the clinical trial phase., (© 2023 Deutsche Dermatologische Gesellschaft (DDG).)

Merkel cell carcinoma (MCC) is a rare and highly aggressive primary cutaneous neuroendocrine carcinoma most often occurring in the elderly. Risk factors include chronic sun exposure and immunosuppression (1). MCC is associated with frequent recurrences and a high metastatic potential and mortality rate (1). It is the second most common cause of skin-cancer-related death after melanoma. At primary diagnosis with an apparent cutaneous tumor, loco-regional metastases are present in up to 30% of patients, and 6-12% have distant metastatic disease (2-3). Up to 5% of cases present with unknown primary origin (4). Five-year overall survival for patients with advanced or metastatic disease is 13-18% (4). We report two cases of MCC presenting without primary cutaneous involvement; first at an unusual location in the adipose tissue of the right breast, and the second one with only a clinically positive left inguinal lymph node. In October 2018, a 78-year-old woman presented with a 15-week history of a painless solitary mass in the upper outer quadrant (UOQ) of the right breast with no visible cutaneous involvement. Her medical history included hypertension, dyslipidemia, and plaque psoriasis. She underwent ultrasound guided biopsy, and histopathology confirmed the diagnosis of metastatic MCC (mMCC). Positron emission tomography/computed tomography (PET/CT) scans showed increased standardized uptake values in the mass in the UOQ and an additional mass in the lower inner quadrant (Figure 1A). The patient underwent mastectomy and lymph node dissection of the right axilla. Histopathology confirmed mMCC and negative axillary lymph nodes. Regular follow-up (clinical examination, PET/CT scan, ultrasound, mammography) every 6 months revealed no disease recurrence during this 4-year period (Figure 1B). In September 2021, a 66-year-old man was referred to our Clinic with clinically detectable painful left inguinal lymphadenopathy. Excisional biopsy was performed, and histopathology confirmed the diagnosis of mMCC (Figure 2). After an extensive clinical and imaging evaluation (PET/CT scan), which confirmed disseminated disease (Figure 3A), initial treatment with the programmed cell death ligand 1 inhibitor (anti PD-L1) avelumab was proposed. The first cycle consisting of seven intravenous applications, and was applied in October 2021. After one year and completion of the third cycle of therapy, imaging assessment (PET-CT scan) detected a solitary lesion in the pancreas. Fine needle aspiration biopsy confirmed a distant metastasis of MCC that was later treated with stereotactic radiosurgery. The fourth cycle of immunotherapy was completed in March 2023. No treatment-related adverse events were noted during these 18 months of follow-up. Recent PET/CT scans demonstrated scaring tissue in the pancreas with no signs of locoregional or distant metastatic disease (Figure 3B). Management of MCC should be individualized based on the specific pattern of disease presentation. The presence of nodal disease is one of the most powerful predictors of overall survival and risk for developing distant metastatic disease (3-4). Multidisciplinary tumor board discussions are mandatory for the management of advanced MCC. New emerging treatment options have once again returned focus to this rare and highly-aggressive entity. Until recent years, mMCC was managed with extensive surgery, radiotherapy, or chemotherapy, but responses were not durable (1). Based on new clinical trials, immunotherapy has now become a rational and promising treatment option and is considered as first-line treatment in patients with advanced MCC (5). The management of patients with MCC of unknown primary origin should adhere to that for patients with an identifiable primary tumour (6). Although cutaneous manifestations are the hallmark of MCC, only a minority of cases have been reported in the literature without any cutaneous involvement (7-10). Our cases highlight this unusual presentation of MCC that could be misleading and contribute to delayed diagnosis. We therefore emphasize the importance of considering rare forms of malignancies such as MCC even in the absence of a primary cutaneous lesion.

Background and Purpose: Clinically localized Merkel cell carcinoma (MCC) has been associated with high rates of disease relapse. This study examines how primary tumor anatomic site drives patterns of care and outcomes in a large cohort treated in the contemporary era., Materials and Methods: Patterns of care and associated outcomes were evaluated for clinically Stage I-II MCC patients treated at our institution with adjuvant radiation therapy (RT) to the primary site and/or regional nodal basin as a component of their curative intent therapy between 2014-2021., Results: Of 80 patients who met inclusion criteria, the primary tumor anatomic site was head and neck (HN) for 42 (53%) and non-head and neck (NHN) for 38 (47%). Primary tumor risk factors were similar between cohorts. Fewer patients with HN tumors had wide local excision (WLE; HN-81% vs. NHN-100% p < 0.01). Of those undergoing WLE, patients with HN tumors received higher dose adjuvant RT (>50 Gy: HN-70% vs. NHN-8%; p < 0.01). Patients with HN tumors were less likely to undergo sentinel lymph node biopsy (HN-62%vs. NHN-100%; p < 0.01) and more likely to have elective nodal RT (HN-48% vs. NHN-0%). Despite varying management strategies, there was no significant difference in local recurrence-free survival (3-yr LRFS HN-94% vs. NHN-94%; p = 0.97), nodal recurrence-free survival (3-yr NRFS HN-89% vs. NHN-85%; p = 0.71) or overall recurrence-free survival (3-yr RFS 73% HN vs. 80% NHN; p = 0.44)., Conclusions: Among patients with primary MCC who had RT as a component of their initial treatment strategy, anatomically-driven heterogeneous treatment approaches were associated with equally excellent locoregional disease control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract: Merkel cell carcinoma (MCC) is a rare and aggressive type of metastatic, nonmelanoma skin cancer derived from Merkel cells in the epidermis. MCC can be induced by sun exposure or via Merkel cell polyomavirus (MCV) gene expression. MCV is found in most patients with MCC and is associated with a lower recurrence rate of MCC. MCC has a wide range of clinical presentations that make diagnosis challenging. Histologic examination is performed using unique markers to differentiate it from other diagnoses. This article reviews the pathogenesis, clinical presentation, histopathology, differential diagnosis, and treatment of MCC., (Copyright © 2023 American Academy of Physician Associates.)

Opinion Statement: Merkel cell carcinoma (MCC) has a high risk of recurrence and requires unique treatment relative to other skin cancers. The patient population is generally older, with comorbidities. Multidisciplinary and personalized care is therefore paramount, based on patient preferences regarding risks and benefits. Positron emission tomography and computed tomography (PET-CT) is the most sensitive staging modality and reveals clinically occult disease in ~ 16% of patients. Discovery of occult disease spread markedly alters management. Newly diagnosed, localized disease is often managed with sentinel lymph node biopsy (SLNB), local excision, primary wound closure, and post-operative radiation therapy (PORT). In contrast, metastatic disease is usually treated systemically with an immune checkpoint inhibitor (ICI). However, one or more of these approaches may not be indicated. Criteria for such exceptions and alternative approaches will be discussed. Because MCC recurs in 40% of patients and early detection/treatment of advanced disease is advantageous, close surveillance is recommended. Given that over 90% of initial recurrences arise within 3 years, surveillance frequency can be rapidly decreased after this high-risk period. Patient-specific assessment of risk is important because recurrence risk varies widely (15 to > 80%: Merkelcell.org/recur) depending on baseline patient characteristics and time since treatment. Blood-based surveillance tests are now available (Merkel cell polyomavirus (MCPyV) antibodies and circulating tumor DNA (ctDNA)) with excellent sensitivity that can spare patients from contrast dye, radioactivity, and travel to a cancer imaging facility. If recurrent disease is locoregional, management with surgery and/or RT is typically indicated. ICIs are now the first line for systemic/advanced MCC, with objective response rates (ORRs) exceeding 50%. Cytotoxic chemotherapy is sometimes used for debulking disease or in patients who cannot tolerate ICI. ICI-refractory disease is the major problem faced by this field. Fortunately, numerous promising therapies are on the horizon to address this clinical need., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with high mortality. However, its clinical characteristics in Asian patients remain uncertain owing to its low incidence., Objective: To analyze the clinicopathological features of MCC and identify factors associated with its prognosis., Methods: The medical records of 62 patients with MCC were retrospectively reviewed. Data on clinical features, survival outcomes, prognostic factors, histopathology and immunohistochemical profile of the patients were collected and analyzed. Merkel cell polyomavirus status was evaluated using immunohistochemistry., Results: The incidence of MCC significantly increased over time. The mean duration of follow-up was 51.2 months, with an overall 5-year survival of 80.6%. More female patients with MCC were identified than male patients (1.3:1). Approximately half of the patients had stage I disease at the time of initial presentation. The primary tumor was frequently located in the lower extremities (40.3%), followed by the head and neck (32.3%), upper extremities (22.6%), and the trunk (4.8%). Male sex was associated with poorer overall survival (p = 0.003). Post-resection adjuvant radiotherapy significantly improved the overall survival (p = 0.023). Sentinel lymph node biopsy during surgery ameliorated the progression-free survival (p = 0.036) in patients with stage I or II cancer. Lymphovascular and perineural invasion were associated with a poor prognosis. Old age, immunohistochemical profiles, and Merkel cell polyomavirus-positivity were not associated with prognosis., Conclusion: Post-surgical adjuvant radiotherapy and sentinel lymph node biopsy significantly improve the course of MCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest None disclosed.

Merkel cell carcinoma represents a neuroendocrine tumour which can grow rapidly and metastasizes early. The median age of patients is 75-80 years. Given the continuously rising population age Merkel cell carcinoma is diagnosed more often. Besides surgery, radiotherapy and chemotherapy immunooncology plays an important role in the treatment of this aggressive tumour., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Merkel cell carcinoma is a highly aggressive skin cancer characterized by neuroendocrine differentiation. This review aimed to present updates on the knowledge and current trends of clinical management of Merkel cell carcinoma. Additionally, we focused on Asian reports of Merkel cell carcinoma because most skin cancers differ substantially between Caucasians and Asians, and researchers have reported differences in Merkel cell carcinoma in racial and ethnic groups. Owing to its rarity, there is limited evidence for the epidemiology, pathogenesis, diagnosis and Merkel cell carcinoma treatment. The development of a nationwide survey or cancer registry, the identification of Merkel cell polyomavirus and the use of immune checkpoint inhibitors allowed a better understanding of its characteristics and biology and have revolutionized the clinical management of patients with Merkel cell carcinoma. Its incidence has gradually increased worldwide; however, it depends on the geographic location, race and ethnicity. No randomized prospective studies have evaluated the significance of sentinel lymph node biopsy, complete lymph node dissection and adjuvant radiation therapy; however, most patients with localized Merkel cell carcinoma are treated surgically or with post-operative radiation. Patients with distant Merkel cell carcinoma are administered immune checkpoint inhibitors as the first-line therapy; however, there is no established second-line therapy for refractory Merkel cell carcinoma. Furthermore, it is necessary to validate the favorable results of clinical studies performed in Western countries in the patients in Asia., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)