ATOH1, TFAP2B, and CEACAM6 as Immunohistochemical Markers to Distinguish Merkel Cell Carcinoma and Small Cell Lung Cancer.

Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) can be histologically similar. Immunohistochemistry (IHC) for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) are commonly used to differentiate MCC from SCLC; however, these markers have limited sensitivity and specificity. To identify new diagnostic markers, we performed differential gene expression analysis on transcriptome data from MCC and SCLC tumors. Candidate markers included atonal BHLH transcription factor 1 (ATOH1) and transcription factor AP-2ß (TFAP2B) for MCC, as well as carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) for SCLC. Immunostaining for CK20, TTF-1, and new candidate markers was performed on 43 MCC and 59 SCLC samples. All three MCC markers were sensitive and specific, with CK20 and ATOH1 staining 43/43 (100%) MCC and 0/59 (0%) SCLC cases and TFAP2B staining 40/43 (93%) MCC and 0/59 (0%) SCLC cases. TTF-1 stained 47/59 (80%) SCLC and 1/43 (2%) MCC cases. CEACAM6 stained 49/59 (83%) SCLC and 0/43 (0%) MCC cases. Combining CEACAM6 and TTF-1 increased SCLC detection sensitivity to 93% and specificity to 98%. These data suggest that ATOH1, TFAP2B, and CEACAM6 should be explored as markers to differentiate MCC and SCLC.

Are DEA-waivered buprenorphine prescribers colocated with behavioral health clinicians?

BACKGROUND AND OBJECTIVES: Medication for opioid use disorder (MOUD) in primary care includes a combination of medication, behavioral therapy, and/or other psychosocial services. This study assessed rates of colocation between waivered prescribers and behavioral health clinicians across the United States to understand if rates varied by provider type and geographic indicators. METHODS: Data from the DEA-Drug Addiction Treatment Act of 2000 provider list as of March 2022 and the National Plan and Provider Enumeration System's National Provider Identifier database were gathered, cleaned, and formatted in Stata. Data were geocoded with ESRI StreetMap® database and ArcGIS software. Covariates at individual, county, and state levels were examined and compared. Chi-square statistics and a mixed-effects logistic regression were analyzed. RESULTS: The sample (N = 71, 292 prescribers) included physicians (64%), nurse practitioners (29%), and physician assistants (7%). About 48% of prescribers were colocated with a behavioral health clinician. Physicians were the least likely to be colocated (47%), but differences between provider types were modest. We observed significant geographic differences in provider colocation by provider type. Mixed effects logistic regression identified significant predictors of colocation at individual, county, and state levels. DISCUSSION AND CONCLUSIONS: Optimally distributing the workforce providing MOUD is necessary to broadly ensure the provision of comprehensive MOUD care based on practice guidelines. SCIENTIFIC SIGNIFICANCE: Less than half of all waivered prescribers, outside of hospitals, are colocated with behavioral health clinicians. Findings offer greater clarity on where integrated MOUD is occurring, among which types of providers, and where it needs to be expanded to increase MOUD uptake.

Peer Support Services in Behavioral Health Facilities: Secondary Analysis From Two National Surveys.

OBJECTIVE: Peer support providers are part of the behavioral health workforce. Research indicates that peer support helps care recipients achieve recovery and engage with behavioral health services. This article investigated how many U.S. behavioral health facilities offer peer support services and compared the frequencies of peer support services in facilities providing mental health and substance use services. METHODS: The authors conducted a secondary analysis of facilities in the Substance Abuse and Mental Health Services Administration's National Mental Health Services Survey (N=11,582) and the National Survey of Substance Abuse Treatment Services (N=13,585), including descriptive and comparative analyses on reported mental health and substance use treatment services in the 50 U.S. states in 2017. RESULTS: The findings revealed state-to-state variation in the number and availability of mental health and substance use service facilities and in facilities that reported providing peer support services. Facilities providing substance use treatment services offered peer support services at more than twice the rate (56.6%) found in mental health facilities (24.7%). The authors also identified program characteristics associated with the inclusion of peer support services in behavioral health. Provision of peer support services was more frequently reported by public facilities than by for-profit and nonprofit facilities. CONCLUSIONS: Behavioral health facilities that serve individuals with serious mental illness and co-occurring substance use and mental health conditions reported offering peer support at a higher rate than did other facilities. Inconsistent definitions of peer support in the two surveys limited the comparability of the findings between the two reports.

Mental Health Needs Due to Disasters: Implications for Behavioral Health Workforce Planning During the COVID-19 Pandemic.

Public health emergencies impact the well-being of people and communities. Long-term emotional distress is a pervasive and serious consequence of high levels of crisis exposure and low levels of access to mental health care. At highest risk for mental health trauma are historically medically underserved and socially marginalized populations and frontline health care workers (HCWs). Current public health emergency response efforts provide insufficient mental health services for these groups. The ongoing mental health crisis of the COVID-19 pandemic has implications for the resource-strained health care workforce. Public health has an important role in delivering psychosocial care and physical support in tandem with communities. Assessment of US and international public health strategies deployed during past public health emergencies can guide development of population-specific mental health care. The objectives of this topical review were (1) to examine scholarly and other literature on the mental health needs of HCWs and selected US and international policies to address them during the first 2 years of the pandemic and (2) to propose strategies for future responses. We reviewed 316 publications in 10 topic areas. Two-hundred fifty publications were excluded, leaving 66 for this topical review. Findings from our review indicate a need for flexible, tailored mental health outreach for HCWs after disasters. US and global research emphasizes the dearth of institutional mental health support for HCWs and of mental health providers who specialize in helping the health care workforce. Future public health disaster responses must address the mental health needs of HCWs to prevent lasting trauma.

Immune checkpoint inhibition and targeted therapy for melanoma: A patient-oriented cross-sectional comparative multicentre study.

BACKGROUND: Choosing the adequate systemic treatment for melanoma is driven by clinical parameters and personal preferences. OBJECTIVE: Evaluation of the impact of disease and treatment on the daily life of patients receiving systemic therapy for melanoma. METHODS: A German-wide, cross-sectional comparative study was conducted at 13 specialized skin cancer centres from 08/2020 to 03/2021. A questionnaire was distributed to assess patients' perception of disease and symptoms, the impact of their current treatment on quality of life (QOL) and activities, adverse events (AEs), therapeutic visits, as well as believe in and satisfaction with their current systemic melanoma treatment. Patient-reported outcomes (PROs) were rated on a continuous numerical rating scale or selected from a given list. RESULTS: Four hundred and fourteen patients with systemic melanoma therapy were included. 359 (87%) received immune checkpoint inhibition (ICI) and 55 (13%) targeted therapy (TT). About 1/3 of patients were adjuvantly treated, the remaining because of unresectable/metastatic melanoma. In subgroup analyses, only in the adjuvant setting, TT patients reported a significant decrease in their treatment associated QOL compared to patients with ICI (p = 0.02). Patients with TT were 1.9 times more likely to report AEs than patients with ICI, a difference being significant just for the adjuvant setting (p = 0.01). ICI treatment intervals differed significantly between adjuvant and unresectable/metastatic setting (p = 0.04), though all patients, regardless of their specific ICI drug, evaluated their treatment frequency as adequate. TT patients with dabrafenib/trametinib (n = 37) or encorafenib/binimetinib (n = 15) did not differ regarding the strain of daily pill intake. Patients older than 63 years rated various PROs better than younger patients. CONCLUSIONS: Patients evaluated their treatment mainly positively. ICI might be preferred over TT regarding QOL and patient-reported AEs in the adjuvant setting. Older melanoma patients appeared to be less impacted by their disease and more satisfied with their treatment.

Model soups improve performance of dermoscopic skin cancer classifiers.

BACKGROUND: Image-based cancer classifiers suffer from a variety of problems which negatively affect their performance. For example, variation in image brightness or different cameras can already suffice to diminish performance. Ensemble solutions, where multiple model predictions are combined into one, can improve these problems. However, ensembles are computationally intensive and less transparent to practitioners than single model solutions. Constructing model soups, by averaging the weights of multiple models into a single model, could circumvent these limitations while still improving performance. OBJECTIVE: To investigate the performance of model soups for a dermoscopic melanoma-nevus skin cancer classification task with respect to (1) generalisation to images from other clinics, (2) robustness against small image changes and (3) calibration such that the confidences correspond closely to the actual predictive uncertainties. METHODS: We construct model soups by fine-tuning pre-trained models on seven different image resolutions and subsequently averaging their weights. Performance is evaluated on a multi-source dataset including holdout and external components. RESULTS: We find that model soups improve generalisation and calibration on the external component while maintaining performance on the holdout component. For robustness, we observe performance improvements for pertubated test images, while the performance on corrupted test images remains on par. CONCLUSIONS: Overall, souping for skin cancer classifiers has a positive effect on generalisation, robustness and calibration. It is easy for practitioners to implement and by combining multiple models into a single model, complexity is reduced. This could be an important factor in achieving clinical applicability, as less complexity generally means more transparency.

A Systematic Review of the Roles and Contributions of Peer Providers in the Behavioral Health Workforce.

CONTEXT: Peer providers with lived experiences of mental health and substance use are a growing component of the workforce responsible for the prevention and treatment of behavioral health disorders. This systematic literature review aims to better define the roles of peers and their unique contributions to behavioral health care. EVIDENCE ACQUISITION: Researchers searched MEDLINE, CINAHL Complete, PsycINFO, Cochrane Central, and Scopus databases for studies published between January 1, 2013 and April 3, 2020. Studies were included if they (1) were experimental or observational studies, (2) included an adult population of people with a behavioral health disorder, and (3) used paid peer providers in addition to traditional behavioral health services. Researchers extracted sample demographics, intervention characteristics, outcome data, and significant associations from studies that met inclusion criteria and assessed the trends in these data in May 2020. EVIDENCE SYNTHESIS: A total of 23 articles assessing peer-provided services were included. Peers were employed most frequently in mental healthcare roles in the Department of Veterans Affairs, hospital, and community health facilities. A total of 14 studies observed significant clinical improvements in participants' social functioning, quality of life, patient activation, and behavioral health. A majority of studies involved the supervision of peers and required peers to have completed training in service delivery. CONCLUSIONS: Peers are effective providers of behavioral health treatment and relapse prevention services who encourage recovery through resilience building, empowerment, and self-advocacy. There remains a need for more evidence-based interventions on the efficacy of peers in substance use disorder treatment and the impact of formalized certification and training opportunities.

Telebehavioral Health During the COVID-19 Pandemic: A Qualitative Analysis of Provider Experiences and Perspectives.

Introduction: Due to the COVID-19 pandemic and prompted by recent federal and state policy shifts impacting behavioral health care delivery, the use of telebehavioral health has rapidly increased. This qualitative study describes behavioral health provider perspectives on the use of telebehavioral health before and during the pandemic and how policy changes impacted access to and utilization of behavioral health services in Michigan. Materials and Methods: A convenience sample of 31 licensed and nonlicensed behavioral health providers operating in Michigan participated in semi-structured interviews between July and August 2020. Interviews were audio-recorded, transcribed, and analyzed by using inductive methods. Results: The thematic analysis resulted in four overarching themes: (1) increased access to care; (2) maintenance of quality of care; (3) minimal privacy concerns; and (4) client and provider satisfaction. Discussion: During and post-pandemic, providers need flexibility to determine whether in-person or telebehavioral health services, including audio-only, best meet client needs. Providers identified several populations for which telebehavioral health was less accessible: clients with serious mental illness and substance use disorder, those with no broadband Internet access, children, and older adults. Additional training in telebehavioral health service provision can positively impact quality of care. Conclusion: Policies that support reimbursement parity and expand provider use of telebehavioral health services should be maintained after the COVID-19 pandemic ends to avoid imposing barriers to accessing behavioral health care barriers post-pandemic.

The Distribution of Advanced Practice Nurses Within the Psychiatric Workforce.

OBJECTIVE: To examine the size and distribution of the advanced practice psychiatric nurse workforce relative to the total psychiatry workforce to determine whether nurses are predominantly working in areas with higher or lower levels of behavioral health specialists. METHODS: State-level data for psychiatric nurses were obtained from the American Nurses Credentialing Center, and included mental health psychiatric nurse practitioners, adult psychiatric nurse practitioners, child psychiatric clinical nurse specialists, and adult psychiatric clinical nurse specialists. Supply estimates of the full psychiatry workforce were calculated for comparison purposes. State population estimates were obtained from U.S. Census Bureau data. State workforce estimates were converted to a 1:100,000 provider-to-population ratio to analyze the density of providers across states. RESULTS: In 2018, the psychiatric workforce supply was estimated to be composed of 66,740 providers, including psychiatrists (n = 47,046; 71%), psychiatric nurses (n = 17,534; 26%), physician assistants (n = 1,164; 2%), and psychiatric pharmacists (n = 966; 1%). Overall, psychiatric providers appeared to be most densely concentrated in the northeast region of the United States. A dearth of providers was most pronounced within areas in the 12-state Midwest region, southern states, California, and Nevada. The average concentration of psychiatric workers was 22.61 per 100,000 population. CONCLUSIONS: The findings of this study find inconsistent pattern of how psychiatric nurses are distributed relative to the rest of the workforce, but reinforce the idea that they are essential in addressing care needs in areas with low concentrations of psychiatry specialists-especially if they are authorized to work to the full extent of their training/education.

Systematic outperformance of 112 dermatologists in multiclass skin cancer image classification by convolutional neural networks.

BACKGROUND: Recently, convolutional neural networks (CNNs) systematically outperformed dermatologists in distinguishing dermoscopic melanoma and nevi images. However, such a binary classification does not reflect the clinical reality of skin cancer screenings in which multiple diagnoses need to be taken into account. METHODS: Using 11,444 dermoscopic images, which covered dermatologic diagnoses comprising the majority of commonly pigmented skin lesions commonly faced in skin cancer screenings, a CNN was trained through novel deep learning techniques. A test set of 300 biopsy-verified images was used to compare the classifier's performance with that of 112 dermatologists from 13 German university hospitals. The primary end-point was the correct classification of the different lesions into benign and malignant. The secondary end-point was the correct classification of the images into one of the five diagnostic categories. FINDINGS: Sensitivity and specificity of dermatologists for the primary end-point were 74.4% (95% confidence interval [CI]: 67.0-81.8%) and 59.8% (95% CI: 49.8-69.8%), respectively. At equal sensitivity, the algorithm achieved a specificity of 91.3% (95% CI: 85.5-97.1%). For the secondary end-point, the mean sensitivity and specificity of the dermatologists were at 56.5% (95% CI: 42.8-70.2%) and 89.2% (95% CI: 85.0-93.3%), respectively. At equal sensitivity, the algorithm achieved a specificity of 98.8%. Two-sided McNemar tests revealed significance for the primary end-point (p < 0.001). For the secondary end-point, outperformance (p < 0.001) was achieved except for basal cell carcinoma (on-par performance). INTERPRETATION: Our findings show that automated classification of dermoscopic melanoma and nevi images is extendable to a multiclass classification problem, thus better reflecting clinical differential diagnoses, while still outperforming dermatologists at a significant level (p < 0.001).

Evaluation of EGFR inhibitor-mediated acneiform skin toxicity within the double-blind randomized EVITA trial: A thorough gender-specific analysis using the WoMo score.

Acne-like skin reactions frequently occur in patients undergoing treatment with drugs inhibiting the epidermal growth factor receptor. Recently, the effects of vitamin K1 containing cream (Reconval K1) as prophylactic skin treatment in addition to doxycycline were explored in a double-blind randomized phase II trial (EVITA) in patients with metastatic colorectal cancer receiving cetuximab. EVITA demonstrated a trend towards less severe skin rash in Reconval K1-treated patients using the tripartite WoMo skin reaction grading score as a thorough tool for quantification of drug related skin reactions. This gender-specific analysis of the EVITA trial evaluated the application of the WoMo score for assessment of epidermal growth factor receptor (EGFR)-related skin toxicities according to treatment arm and gender. To show the robustness of results parametric and non-parametric statistical analyses were conducted. All three parts of the WoMo score independently demonstrated the superiority of the treatment arm (Reconval K1) regarding a significant reduction in acneiform skin reactions in women. Men did not benefit from Reconval K1 cream at any time point in none of the WoMo score analyses. The treatment effect in women was confirmed by the use of skin rash categories based on the final WoMo overall score and mixed effect longitudinal multiple linear regression analysis. The WoMo score represents a sensitive tool for studies exploiting treatments against EGFR mediated acne-like skin rash. Part C of the WoMo score seems to be sufficient for quantification of drug related skin toxicities in further studies. Standard WoMo skin reaction score values for future studies are provided.

Comparing artificial intelligence algorithms to 157 German dermatologists: the melanoma classification benchmark.

BACKGROUND: Several recent publications have demonstrated the use of convolutional neural networks to classify images of melanoma at par with board-certified dermatologists. However, the non-availability of a public human benchmark restricts the comparability of the performance of these algorithms and thereby the technical progress in this field. METHODS: An electronic questionnaire was sent to dermatologists at 12 German university hospitals. Each questionnaire comprised 100 dermoscopic and 100 clinical images (80 nevi images and 20 biopsy-verified melanoma images, each), all open-source. The questionnaire recorded factors such as the years of experience in dermatology, performed skin checks, age, sex and the rank within the university hospital or the status as resident physician. For each image, the dermatologists were asked to provide a management decision (treat/biopsy lesion or reassure the patient). Main outcome measures were sensitivity, specificity and the receiver operating characteristics (ROC). RESULTS: Total 157 dermatologists assessed all 100 dermoscopic images with an overall sensitivity of 74.1%, specificity of 60.0% and an ROC of 0.67 (range = 0.538-0.769); 145 dermatologists assessed all 100 clinical images with an overall sensitivity of 89.4%, specificity of 64.4% and an ROC of 0.769 (range = 0.613-0.9). Results between test-sets were significantly different (P < 0.05) confirming the need for a standardised benchmark. CONCLUSIONS: We present the first public melanoma classification benchmark for both non-dermoscopic and dermoscopic images for comparing artificial intelligence algorithms with diagnostic performance of 145 or 157 dermatologists. Melanoma Classification Benchmark should be considered as a reference standard for white-skinned Western populations in the field of binary algorithmic melanoma classification.

Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that responds to PD-1/PD-L1 immune checkpoint inhibitors. CD200 is another checkpoint modulator whose receptor is found on tumor-promoting myeloid cells, including M2 macrophages. We found high CD200 mRNA expression in MCC tumors, and CD200 immunostaining was demonstrated on 95.5% of MCC tumors. CD200R-expressing myeloid cells were present in the MCC tumor microenvironment. MCC-associated macrophages had a higher average CD163:CD68 staining ratio (2.67) than controls (1.13), indicating an immunosuppressive M2 phenotype. Accordingly, MCC tumors contained increased densities of FOXP3+ regulatory T-cells. Intravenous administration of blocking anti-CD200 antibody to MCC xenograft mice revealed specific targeting of drug to tumor. In conclusion, MCC are highly CD200 positive and associated with immunosuppressive M2 macrophages and regulatory T-cells. As anti-CD200 antibody effectively targets CD200 on MCC tumor cells in vivo, this treatment may provide a novel immunotherapy for MCC independent of PD-1/PD-L1 blockade.

MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC/CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC/CEP8 ratio ≥ 1.2-< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions.

Liquid Biopsy zur Überwachung von Melanompatienten.

In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression. Folglich werden zuverlässige Methoden zur Überwachung von Krankheitsprogression oder Behandlungsresistenz benötigt. Lokalisierte und fortgeschrittene Krebserkrankungen können zur Bildung zirkulierender Tumorzellen und Tumor-DNA (ctDNA) führen, die sich in Proben von peripherem Blut nachweisen und quantifizieren lassen (Liquid Biopsy). Im Fall von Melanompatienten können die Ergebnisse von Liquid Biopsy als neuartige prädiktive Biomarker bei therapeutischen Entscheidungen hilfreich sein, insbesondere im Zusammenhang mit mutationsbasierten zielgerichteten Therapien. Die Herausforderungen bei der Anwendung der Liquid Biopsy beinhalten strikte Kriterien für den Phänotyp der zirkulierenden MM-Zellen oder ihrer Fragmente und die Instabilität von ctDNA im Blut. In diesem Übersichtsartikel diskutieren wir die Beschränkungen der Liquid Biopsy hinsichtlich ihrer Anwendung in der Routinediagnostik.

Liquid biopsy to monitor melanoma patients.

During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression. Consequently, reliable methods for monitoring disease progression or treatment resistance are necessary. Localized and advanced cancers may generate circulating tumor cells and circulating tumor DNA (ctDNA) that can be detected and quantified from peripheral blood samples (liquid biopsy). For melanoma patients, liquid biopsy results may be useful as novel predictive biomarkers to guide therapeutic decisions, particularly in the context of mutation-based targeted therapies. The challenges of using liquid biopsy include strict criteria for the phenotypic nature of circulating MM cells or their fragments and the instability of ctDNA in blood. The limitations of liquid biopsy in routine diagnostic testing are discussed in this review.

PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. Avelumab recently became the first approved drug for metastatic MCC. Expert commentary: By conducting broad phase I studies assessing the safety of avelumab and a small phase II study demonstrating efficacy in this rare orphan tumor type, avelumab gained accelerated approval for the treatment of metastatic MCC. Additional studies are needed to determine how the antibody-dependent cellular cytotoxicity (ADCC) competent Fc region of avelumab contributes to disease control. Remaining questions: Longer follow-up will determine the durability of checkpoint blockade in controlling metastatic MCC. Additional studies will assess the utility and safety of adjuvant checkpoint blockade in patients with excised MCC. How to increase response rates by combining PD-1/PD-L1 blockade with other treatment approaches needs to be explored. In addition, treatment options for MCC patients who fail or do not respond to avelumab need to be identified.

Loss of epithelial cell adhesion molecule (EpCAM) in infiltrative basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common type of skin cancer and expresses high protein levels of the epithelial cell adhesion molecule (EpCAM, syn. CD326). Though BCCs only rarely metastasize, infiltrative and destructive growth do occur. EpCAM has been studied extensively in the context of adhesion and carcinogenesis but results of studies relating EpCAM expression to invasive potential or patient prognosis have been inconsistent. In an attempt to link EpCAM expression with infiltrative potential, we retrospectively stained paraffin embedded tissue samples of nodular and infiltrative BCCs. A total of 96 samples comprising 48 nodular and 48 infiltrative BCC cases were immuhistochemically stained with anti-EpCAM clone BerEP4. Loss of EpCAM expression along the tumor invasive front was detected in 6 of 48 (12.5%) of the nodular BCC as compared to 29 of 48 (60.4%) of the infiltrative BCC cases (P < 0.0001). These results exemplify the important role of EpCAM for cell adhesion. BCC infiltration seems to be promoted by down-regulation of EpCAM along the tumor invasion front.