Avelumab, a programmed cell death ligand 1 blocking antibody, was approved for its first indication in Japan in September 2017 to treat unresectable Merkel cell carcinoma (MCC). Given that the pivotal JAVELIN Merkel 200 study only included a few Japanese patients, this post-marketing surveillance (PMS) evaluated the safety and effectiveness outcomes of patients with MCC who received avelumab in general clinical practice in Japan. This prospective, non-comparative, multicenter PMS included data from all patients with unresectable MCC who received avelumab between November 22, 2017 (avelumab launch date) and October 31, 2019.
View Article and Find Full Text PDFBackground: Although anti-PD-1 antibody monotherapy (PD-1) is commonly used to treat advanced acral melanoma (AM), its efficacy is limited. Further, data on the efficacy of PD-1 plus anti-CTLA-4 antibody (PD-1+CTLA-4) for the treatment of AM are limited. Therefore, we compared the efficacy of PD-1+CTLA-4 and PD-1 in the treatment of Japanese patients with advanced AM.
View Article and Find Full Text PDFBackground: Immune checkpoint inhibitors (ICIs) have a lower efficacy in mucosal melanoma (MUM) than in cutaneous melanoma. The use of combination treatments with radiotherapy (RT) to improve the efficacy in MUM, however, requires further investigation.
Methods: We retrospectively evaluated 225 advanced MUM patients treated with anti-PD-1 monotherapy (PD1; 115) or anti-PD-1 + anti-CTLA-4 combination therapy (PD1+CTLA4; 42) with or without RT (56 and 12, respectively).
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin associated with Merkel cell polyomavirus and immunosuppression. Although MCC incidence is rising worldwide, MCC has not been sufficiently investigated in Japan. This study aimed to determine MCC demographics in Japan, including incidence, age, sex, location, spontaneous regression, and pure/combined MCC.
View Article and Find Full Text PDFBackground: Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes.
View Article and Find Full Text PDFBackground: Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Few patients with cSCC experience metastases, but the prognosis of advanced cSCC (acSCC) is dismal. Evidence regarding systemic therapy for acSCC is limited.
View Article and Find Full Text PDFIn skin containing hair follicles, specialized epithelial structures known as "touch domes (TDs)" are located where the Merkel cells are clustered. We explored the histogenetic relationship between intraepidermal and dermal Merkel cell carcinomas (MCCs) and investigated which transformed progenitor cells can develop into intraepidermal MCC. We encountered an association between an extremely rare case of dermal and intraepidermal MCC with squamous cell carcinoma, which was examined using standard immunohistochemical methods with various epithelial, neuroendocrine, and TD markers including several immunohistochemical markers.
View Article and Find Full Text PDFMerkel cell carcinoma is a rare neuroendocrine carcinoma of the skin that is associated with Merkel cell polyomavirus (MCPyV). The clinical appearance and demographic characteristics of this tumor have been described using the mnemonic AEIOU: asymptomatic, expanding rapidly, immune suppression, older than 50 years, and ultraviolet-exposed fair skin. In addition, MCC can be categorized based on morphology as pure MCC or combined MCC that exhibits neuroendocrine and other phenotypic elements.
View Article and Find Full Text PDFThe cellular origin of Merkel cell carcinoma (MCC) is controversial. We previously hypothesized that MCC originates from hair follicle stem cells or Merkel cell (MC) progenitors residing within the hair follicle bulge. Examination of three cases of combined MCC led to the unexpected discovery that numerous keratin 20 (CK20)-positive MCs within the squamous cell carcinoma (SCC) component of combined MCC appeared morphologically normal with dendritic and oval shapes.
View Article and Find Full Text PDFMerkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate. For primary or locoregional MCC, a wide local excision followed by radiation therapy is the basic treatment modality for preventing recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy has been commonly used to treat patients with metastatic MCC, but not as an adjuvant therapy for high-risk resected MCC.
View Article and Find Full Text PDFMerkel cell carcinoma (MCC) is a rare but more lethal cutaneous cancer than melanoma. However, spontaneous regression of a number of MCC has been reported, although the cause of this regression remains unclear. In most cases, MCC regresses after a surgical procedure, for example, biopsy.
View Article and Find Full Text PDFMerkel cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy associated with the Merkel cell polyomavirus (MCPyV). Multiple studies have shown that the incidence of MCC is higher among immunocompromised individuals than among the general population. In fact, immunosuppressed individuals account for approximately 10% of the MCC patient population.
View Article and Find Full Text PDFLarge-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive neuroendocrine tumor, found mainly in the lung. Although LCNEC has been reported in various organs, LCNEC of the skin is extremely rare, poorly recognized and probably underestimated. Here we report a case of LCNEC of the skin, focusing on the histopathological and ultrastructural findings in detail.
View Article and Find Full Text PDFThe regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA(-)Foxp3(++)CCR4(+) phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs.
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