A Rapidly Developing Nodule in a Patient With Hairy Cell Leukemia in Remission: Merkel Cell Carcinoma: A Case Report.

BACKGROUND/AIM: Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients. CASE REPORT: We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells. CONCLUSION: Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.

Merkel Cell Carcinoma.

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.

Merkel Cell Carcinoma With Extensive Bone Marrow Metastasis and Peripheral Blood Involvement: A Case Report With Immunohistochemical and Mutational Studies.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer of neuroendocrine origin that is typically associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet (UV) light. We report a case of relapsed MCC that presented with new symptoms of fatigue, back pain, and myeloid left shift identified during scheduled follow-up. The patient was found to have circulating neoplastic cells in the peripheral blood and bone marrow metastasis. Immunohistochemistry for synaptophysin, CD56, INSM-1, CK20, CD117 were positive, whereas CD34, TdT, Chromogranin, CD10, myeloperoxidase, CD3 and CD19 were negative. Flow cytometry of the peripheral blood confirmed the presence of an abnormal nonhematopoietic cell population expressing CD56 positivity. A next-generation sequencing (NGS) panel revealed the presence of variants in RB1, TP53, and other genes, some of which have not been previously described in MCC. This rare presentation highlights the challenges in the diagnosis and management of MCC.

The Clinical Utility of Teledermatology in Triaging and Diagnosing Skin Malignancies: Case Series.

With the increasing utilization of telemedicine since the COVID-19 pandemic, it is critical that clinicians have an appropriate understanding of the application of virtual care resources, including teledermatology. We present a case series of 3 patients to demonstrate the clinical utility of teledermatology in reducing the time to diagnosis of various rare and/or aggressive cutaneous malignancies, including Merkel cell carcinoma, malignant melanoma, and atypical fibroxanthoma. Cases were obtained from one large Midwestern medical center during the month of July 2021. Each case presented includes a description of the initial teledermatology presentation and reviews the clinical timeline from initial consultation submission to in-person clinic visit with lesion biopsy. This case series demonstrates real-world examples of how teledermatology can be utilized to expedite the care of specific vulnerable patient populations.

Upper and Lower Eyelid Malignancies: Differences in Clinical Presentation, Metastasis, and Treatment.

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.

The prognostic value of the Merkel cell polyomavirus serum antibody test: A dual institutional observational study.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cancer with often poor outcomes. Limited biomarkers exist for predicting clinical outcomes. The Merkel cell polyomavirus (MCPyV) serum antibody test (AMERK) has shown potential for indicating better recurrence-free survival in a single-institution study. The study aimed to evaluate the link between initial AMERK serostatus and survival. Secondary objectives included examining the relationship between initial AMERK titer levels and tumor burden. METHODS: A retrospective cohort study across two institutions analyzed patients tested with AMERK within 90 days of MCC diagnosis. Regression models assessed the association of survival outcomes with serostatus, considering various factors. The relationship between AMERK titer and tumor burden indicators was evaluated using ANOVA. Significance testing was exploratory, without a fixed significance level. RESULTS: Of 261 MCC patients tested, 49.4% were initially seropositive (titer ≥75). Multivariable analysis showed that seropositivity improved recurrence, event-free, overall, and MCC-specific survival rates. Strong associations were found between initial AMERK titer and clinical, tumor, and nodal stages, tumor size, and disease extent. Notably, improved survival with seropositivity was observed only in patients with localized disease at initial presentation. CONCLUSION: Circulating antibodies to MCPyV oncoproteins, as indicated by the AMERK test, are linked with better survival in MCC patients with localized disease at presentation. This could enhance patient risk profiling and treatment personalization. The study's retrospective nature and exploratory analysis are key limitations. PLAIN LANGUAGE SUMMARY: Merkel cell carcinoma (MCC) is a potentially aggressive skin cancer, and tools to predict patient outcomes are limited. A blood test called anti-Merkel cell panel (AMERK), which checks for specific antibodies related to this cancer, might give us some clues. In this study, we looked at 261 MCC patients who took the AMERK test within 90 days of diagnosis. We found that patients with an initial positive AMERK result tended to have better outcomes, especially if their cancer was in the early stages. However, it is important to note that this study has limitations, including using retrospective data and exploratory analyses.

Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

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.     doi:10.36849/JDD.8234  .

Merkel cell carcinoma overlapping Bowen's disease: two cases report and literature review.

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.

Unusual Metastasis to Eyelid from Extraocular Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is an unusual skin tumor that has a significant rate of distant and local metastases. It is known that primary MCC of the eyelid usually occurs at the upper eyelid. Here we report an unusual case of MCC metastasis to the eyelid. A 63-year-old male was diagnosed with MCC three years earlier after initially presenting with a mass in his right thigh. After histopathological diagnosis, the patient received medical therapy. During treatment, he developed multiple distant metastases and a firm, purple, vascularized lesion on the upper eyelid. We confirmed the lesion was an eyelid metastasis of MCC by histopathological examination and imaging methods. This case shows that extraocular MCC can metastasize to the eyelids, particularly the upper eyelid, where primary periocular MCC usually appears.

Systematic evaluation of Merkel cell carcinoma clinical practice guidelines using the AGREE II instrument.

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.

Merkel Cell Carcinoma: Integrating Epidemiology, Immunology, and Therapeutic Updates.

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.