Human cytomegalovirus infection in foci of Langerhans cell histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFalpha. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection.

Diagnosis of Langerhans Cell Histiocytosis on Fine Needle Aspiration Cytology: A Case Report and Review of the Cytology Literature

“…The disease is characterized by a clonal proliferation of the antigen-presenting dendritic cell called the Langerhans cell (LC) [5, 6]. The proliferation may be induced by a viral infection, a defect in T cell-macrophage interaction, and/or a cytokine-driven process mediated by tumor necrosis factor, interleukin 11, and leukemia inhibitory factor [2, 7–10]. …”

Developmental abnormalities and liver disease in childhood

“…717 The demonstrated clonality of LCH does not prove the neoplastic nature of the lesion. 718,719 Viral proteins and DNA sequences of human cytomegalovirus, 720 Epstein-Barr virus 721 and human herpes virus 6 722 have been detected by immunohistochemistry, in situ hybridization and PCR in LCH tissue, but whether these represent causal agents or opportunistic infections secondary to immune dysregulation remains uncertain.…”

Expansion of Regulatory T Cells in Patients with Langerhans Cell Histiocytosis

“…Cytogenetic abnormalities such as loss of heterozygosity of tumor suppressor genes and chromosomal instability have also been described as case reports [21–23], although no recurrent molecular abnormality has been yet characterized. Active viral infections such as herpesvirus infections may worsen the disease [24]; a possible causative role of herpesviruses in LCH has been debated [25–28]. …”