The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases.

BACKGROUND: Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles. METHODS: Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan-Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant. RESULTS: A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%. CONCLUSIONS: This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.

Merkel cell carcinoma: epidemiology, clinical features, diagnosis and treatment of a rare disease

Abstract Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment.

Vegetative chronic genital herpes with satisfactory response to imiquimod.

Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.

Vegetative chronic genital herpes with satisfactory response to imiquimod

Abstract Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.