Clinical, histopathologic, immunohistochemical and electron microscopic findings in cutaneous monkeypox: A multicenter retrospective case series in Spain

Background: The worldwide outbreak of monkeypox has evidenced the usefulness of the dermatologic manifestations for its diagnosis. Objective: To describe the histopathologic and immunohistochemical findings of monkeypox cutaneous lesions. Methods: This is a retrospective histopathologic and immunohistochemical study of 20 patients with positive Monkeypox virus DNA polymerase chain reaction (PCR) and immunohistochemical positivity for Vaccinia virus in cutaneous lesions. Four cases were also examined by electron microscopy. Results: The most characteristic histopathologic findings consisted of full-thickness epidermal necrosis with hyperplasia and keratinocytic ballooning at the edges. In some cases, the outer root sheath of the hair follicle and the sebaceous gland epithelium were affected. Intraepithelial cytoplasmic inclusion bodies and scattered multinucleated keratinocytes were occasionally found. Immunohistochemically, strong positivity with anti-Vaccinia virus antibody was seen in the cytoplasm of ballooned keratinocytes. Electron microscopy study demonstrated numerous viral particles of Monkeypox virus in affected keratinocytes. Limitations: Small sample size. Electron microscopic study was only performed in four cases. Conclusion: Epidermal necrosis and keratinocytic ballooning are the most constant histopathologic findings. Immunohistochemical positivity for Vaccinia virus was mostly detected in the cytoplasm of the ballooned keratinocytes. These findings support the usefulness of histopathologic and immunohistochemical studies of cutaneous lesions for diagnosis of monkeypox.背景：全球范围内的猴痘暴发凸显了皮肤临床表现对该病诊断的实用价值。目的：描述猴痘皮肤病变的组织病理学与免疫组织化学特征。方法：本研究为一项回顾性组织病理学及免疫组织化学研究，纳入20例皮肤病变样本经猴痘病毒DNA聚合酶链式反应（PCR）检测呈阳性、且免疫组织化学检测牛痘病毒呈阳性的患者，另有4例患者接受了电子显微镜检查。结果：最具特征性的组织病理学表现为全层表皮坏死，伴病变边缘区域表皮增生及角质形成细胞气球样变。部分病例可见毛囊外根鞘与皮脂腺上皮受累。偶见上皮内胞质包涵体及散在分布的多核角质形成细胞。免疫组织化学检测显示，抗牛痘病毒抗体可在气球样变角质形成细胞的胞质中呈现强阳性信号。电子显微镜检查可见受累角质形成细胞内存在大量猴痘病毒颗粒。局限性：本研究样本量较小，且仅4例患者接受了电子显微镜检查。结论：表皮坏死与角质形成细胞气球样变是最为恒定的组织病理学特征。牛痘病毒免疫组织化学阳性信号多检测于气球样变角质形成细胞的胞质中。上述结果证实，皮肤病变的组织病理学与免疫组织化学检查可辅助猴痘的诊断。