Merkel Cell Carcinoma Research Articles

Merkel Cell Carcinoma Case Reports With Merkel Cell Polyomavirus Test and Review of the Literature.

Merkel cell carcinoma (MCC) is known as a rare and highly malignant neuroendocrine skin cancer and often occurs in the sun-exposed parts of the elderly individuals. In this article, we reported 2 cases of MCC and reviewed relative literature. Case 1 was a 91-year-old woman who presented with a half-year history of a brown nodule on the left temple. The histopathological and immunohistochemistry examination diagnosis was MCC with negative staining of Merkel cell polyomavirus large T antigen (CM2B4). Case 2 was a 76-year-old man with a nodule on his right buttock that gradually increased from approximately 3 mm to 1.5 cm in diameter in 1 month without pain. The biopsy diagnosis was MCC with positive staining of CM2B4. Previous studies have found that the genetic mutation and prognosis of polyomavirus-associated MCC (MCCP) and nonviral MCC (MCCN) are significantly different. Large T antigen plays a crucial role in Merkel cell polyomavirus (MCPyV) oncogenesis. Testing for the MCPyV at the onset of MCC is recommended, which is helpful in predicting the prognosis of patients.

Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation. Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05. Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS. In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

Monoclonal antibodies for inflammatory, autoimmune and oncological skin diseases

In 1997 rituximab, agenetically engineered chimeric monoclonal antibody (mAb) targeting CD20 expressed on Bcells was approved for treatment of non-Hodgkin's lymphoma. Since then, pharmacological improvements combined with increased knowledge on the immunopathogenesis of diseases led to the development of specific mAb targeting different antigens (e.g., interleukins or transmembrane receptors). This approach reshaped the therapeutic methodology in many fields, including dermatology. Nowadays, the treatment of frequent and possibly impairing inflammatory disorders such as psoriasis, atopic dermatitis or hidradenitis suppurativa have different mAbs approved for both adult and pediatric patients. This class of drugs often shows amore favorable outcome and abetter safety profile than routine immunosuppressants, such as steroids and steroid-sparing substances. For many years mAbs also represented apillar of oncological treatment for severe diseases such as malignant melanoma or Merkel cell carcinoma. This review summarizes the current knowledge on already approved and promising new mAbs for the treatment of inflammatory and oncological skin diseases.

Personalised PET imaging in oncology: an umbrella review of meta-analyses to guide the appropriate radiopharmaceutical choice and indication.

For several years, oncological positron emission tomography (PET) has developed beyond 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). This umbrella review of meta-analyses aims to provide up-to-date, comprehensive, high-level evidence to support appropriate referral for a specific radiopharmaceutical PET/computed tomography (CT) or PET/magnetic resonance (MR) in the diagnosis and staging of solid cancers other than brain malignancies. We performed a systematic literature search on the PubMed/MEDLINE and EMBASE databases for meta-analyses assessing the accuracy of PET/CT and/or PET/MRI with [18F]FDG, somatostatin- receptor-targeting 68Ga-DOTA-peptides, 18F-labelled dihydroxyphenylalanine ([18F]DOPA), prostate-specific membrane antigen (PSMA)-targeted radioligands, and fibroblast activation protein inhibitors (FAPI) in the diagnosis/disease characterisation and staging of solid cancers other than brain tumours. The literature search yielded 449 scientific articles. After screening titles and abstracts and applying inclusion and exclusion criteria, we selected 173 meta-analyses to assess the strength of evidence. One article was selected from references. Sixty-four meta-analyses were finally considered. The current evidence corroborates the role of [18F]FDG as the main player in molecular imaging; PSMA tracers are useful in staging and re-staging prostate cancer; somatostatin-targeting peptides (e.g. [68Ga]Ga- DOTA-TOC and -TATE) or [18F]DOPA are valuable in neuroendocrine tumours (NETs). FAPI has emerged in gastric cancer assessment. According to search and selection criteria, no satisfactory meta-analysis was selected for the diagnosis/detection of oesophageal cancer, the diagnosis/detection and N staging of small cell lung cancer and hepatic cell carcinoma, the diagnosis/detection and M staging of melanoma and Merkel cell carcinoma, cervical, vulvar and penis cancers, the N and M staging of lung and gastroenteropancreatic NET, testicular cancer, and chondrosarcoma, and the M staging of differentiated thyroid, bladder and anal cancers. The comprehensive high-level evidence synthesised in the present umbrella review serves as a guiding compass for clinicians and imagers, aiding them in navigating the increasingly intricate seascape of PET examinations.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy.

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.

Knowledge of Jimmy Buffett's Merkel cell carcinoma and the impact on self‐reported expected skin cancer prevention behaviours

Knowledge of Jimmy Buffett's Merkel cell carcinoma and the impact on self‐reported expected skin cancer prevention behaviours

Metastatic Merkel cell carcinoma to the colon: a case report and literature review

Metastatic Merkel cell carcinoma to the colon: a case report and literature review

Merkel Cell Polyomavirus-Pathophysiology and Treatment in the Era of Gene-Targeted Therapies.

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.

54433 Second Merkel cell carcinoma - Primary vs. late recurrence: When to de-escalate surveillance?

54433 Second Merkel cell carcinoma - Primary vs. late recurrence: When to de-escalate surveillance?

1133P Only early adjuvant radiotherapy, particularly of the tumor bed rather than the lymph node region, improves prognosis in Merkel cell carcinoma: Results from the prospective German MCC registry

1133P Only early adjuvant radiotherapy, particularly of the tumor bed rather than the lymph node region, improves prognosis in Merkel cell carcinoma: Results from the prospective German MCC registry

The association between infectious agents and breast cancer: a review of the epidemiologic evidence.

Several viruses have been casually linked to human cancers, including cervical, nasopharyngeal, liver, sarcoma, and Merkel cell carcinomas. However, the etiologic contribution of viral infections to breast cancer, the number one incident cancer among women worldwide, is not well established. Among studies exploring associations of viruses with breast cancer, potential linkages have been identified between breast cancer and five viruses: beta retrovirus, (i.e., mouse mammary tumor virus), human papillomavirus, Epstein Barr virus. bovine leukemia virus, and human cytomegalovirus. In this review, we provide a comprehensive evaluation of epidemiological ecologic, case-control, case-only, and cohort studies investigating these associations. Wediscuss results from several existing reviews and meta-analyses, evaluate epidemiological studies published in the past five years, and assess the relationship between these viruses and breast tumor clinicopathological factors. The strongest epidemiological evidence for a viral role in breast cancer exists for MMTV and HPV, though limitations include lack of prospective studies for MMTV and potential detection bias in HPV studies. Viral detection challenges have limited studies of EBV and HCMV. Fewer studies have evaluated BLV, and though it has been associated with higher risk of breast cancer, sample sizes are quite small. CONCLUSION: While epidemiologic evidence exists for an association between these five viruses and breast cancer, various methodological issues and lack of prospective studies preclude robustconclusions. Future research should prioritize establishing a temporal relationship between infection and disease, minimizing misclassification of detection assays, and further exploring the influence of co-infections.

178 Merkel Cell Carcinoma (MCC) of the Skin: When is Local Radiotherapy (RT) Without Nodal Coverage is Adequate? Comprehensive Analysis of Aggregate Patient Data from Literature

178 Merkel Cell Carcinoma (MCC) of the Skin: When is Local Radiotherapy (RT) Without Nodal Coverage is Adequate? Comprehensive Analysis of Aggregate Patient Data from Literature

177 Merkel Cell Carcinoma (MCC) of the Skin: Comprehensive Analysis of Radiation (RT) Doses of Aggregate Patient Data from Literature

177 Merkel Cell Carcinoma (MCC) of the Skin: Comprehensive Analysis of Radiation (RT) Doses of Aggregate Patient Data from Literature

1135P Multi-modal and longitudinal characterization of the tumor and immune microenvironment of Merkel cell carcinoma

1135P Multi-modal and longitudinal characterization of the tumor and immune microenvironment of Merkel cell carcinoma

1134P Avelumab in metastatic Merkel cell carcinoma (mMCC): Conditional survival and long-term safety in patients treated for ≥1 or ≥2 years in JAVELIN Merkel 200

1134P Avelumab in metastatic Merkel cell carcinoma (mMCC): Conditional survival and long-term safety in patients treated for ≥1 or ≥2 years in JAVELIN Merkel 200

933P Prediction of survival in patients with head and neck merkel cell carcinoma: Statistical and machine-learning approaches

933P Prediction of survival in patients with head and neck merkel cell carcinoma: Statistical and machine-learning approaches

Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment.

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. The Brazilian Society of Surgical Oncologydeveloped this document aiming to guide the surgical oncology role in multimodal MCC management. The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up. 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 positronemission 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. 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.

Lymphotropic polyomavirus and Merkel cell polyomavirus in patients infected with HIV or hepatitis B or C virus

BackgroundLPV and MCV emerge as recent additions to the Polyomaviridae family, capable of inducing important infections. Studies have suggested the presence of LPV in human populations, with potential involvement in central nervous system (CNS) diseases. Additionally, MCV, closely related to LPV, has been implicated in Merkel cell carcinoma (MCC). This study aimed to explore the prevalence of LPV and MCV in individuals with compromised immunity due to chronic viral infections. Methods340 specimens, including HIV PCR-positive, HBV PCR-positive, HCV PCR-positive, and HIV/HBV/HCV negative sera, underwent screening via PCR technique to identify LPV and MCV genomes. Subsequently, sequencing was employed to validate the viral identity. ResultsOut of all specimens, MCV DNA was detected in 8.52 % of participants, with a significantly higher prevalence in HIV-positive individuals (26.4 %). LPV was detected in only one HIV-positive patient. No co-detection of MCV and LPV was observed. Phylogenetic analysis confirmed the genetic similarity of the detected MCV strains to known references, while the LPV sequence showed 99 % identity to the published sequences of LPV-K38. ConclusionThis research provides insights into the prevalence of LPV and MCV in individuals with chronic viral infections. The study highlights the potential association between MCV and immunocompromised states, emphasizing the need for comprehensive investigations to understand the epidemiology, transmission routes, and clinical implications of these polyomaviruses in human populations.

The Role of the Large T Antigen in the Molecular Pathogenesis of Merkel Cell Carcinoma.

The large T antigen (LT) of the Merkel cell polyomavirus (MCPyV) is crucial for Merkel cell carcinoma (MCC), a rare but very aggressive form of neuroendocrine skin cancer. The clonal integration of MCPyV DNA into the host genome is a signature event of this malignancy. The resulting expression of oncogenes, including the small T (sT) antigen and a truncated form of the LT (truncLT), directly contribute to carcinogenesis. The truncation of the C-terminus of LT prevents the virus from replicating due to the loss of the origin binding domain (OBD) and the helicase domain. This precludes cytopathic effects that would lead to DNA damage and ultimately cell death. At the same time, the LxCxE motif in the N-terminus is retained, allowing truncLT to bind the retinoblastoma protein (pRb), a cellular tumor suppressor. The continuously inactivated pRb promotes cell proliferation and tumor development. truncLT exerts several classical functions of an oncogene: altering the host cell cycle, suppressing innate immune responses to viral DNA, causing immune escape, and shifting metabolism in favor of cancer cells. Given its central role in MCC, the LT is a major target for therapeutic interventions with novel approaches, such as immune checkpoint inhibition, T cell-based immunotherapy, and cancer vaccines.