Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis

• Published in: Human pathology 2014, Vol.45 (1), p.119-126
• Main Authors: Murakami, Ichiro, MD, PhD, Matsushita, Michiko, MT, MA, Iwasaki, Takeshi, MD, Kuwamoto, Satoshi, MD, PhD, Kato, Masako, MD, PhD, Horie, Yasushi, MD, PhD, Hayashi, Kazuhiko, MD, PhD, Imamura, Toshihiko, MD, PhD, Morimoto, Akira, MD, PhD, Imashuku, Shinsaku, MD, PhD, Gogusev, Jean, MD, PhD, Jaubert, Francis, MD, PhD, Takata, Katsuyoshi, MD, PhD, Oka, Takashi, PhD, DMSc, Yoshino, Tadashi, MD, PhD
• Format: Article
• Language: English
• Subjects: Age; Antigens, Polyomavirus Transforming - analysis; Child; Child, Preschool; Cysts; Dermatopathic lymphadenopathy; Disease; DNA, Viral - analysis; Female; Histiocytosis, Langerhans-Cell - virology; HIV; Hospitals; Human immunodeficiency virus; Humans; Immunohistochemistry; Infant; Infant, Newborn; Langerhans cell histiocytosis; Langerhans cells; Laser Capture Microdissection; Male; Merkel cell polyomavirus; Multiplex quantitative real-time PCR; Mutation; Pathology; Polyomavirus; Polyomavirus Infections - complications; Polyomavirus Infections - virology; Real-Time Polymerase Chain Reaction; Viral Load
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.05.028

Summary Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO− patients ( P = . 029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P = . 0007), skin diseases not related to LCH in children younger than 2 years (0/11; P = . 0007), or dermatopathic lymphadenopathy (5/20; P = . 0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection.