Primary leptomeningeal histiocytic lymphoproliferative disorder associated with SARS-CoV-2 brain infection in k18-hACE2 mouse: a case report

Abstract

Background Histiocytic proliferative disorders in the central nervous system are rare, and their potential association with viral infections remains largely unexplored. This case is relevant because it suggests a potential interaction between SARS-CoV-2 neuroinvasion and tumor development, providing insights into how viral infections might influence oncogenesis. Case presentation A 4.5-month-old male k18-hACE-2 mouse, part of an experimental study of SARS-CoV-2, displayed a small mass in leptomeningeal area composed by neoplastic round cells. This process is associated with typical acute inflammatory and neurodegenerative lesions according to viral neuroinvasion. Histopathology revealed a well-demarcated tumor composed of lymphoblasts and intermixed with abundant histiocytic-like cells. Immunohistochemistry showed high expression of Iba-1 in histiocytes but negative PAX5, CD3 and IRF-4 labeling. Due to the critical role of PAX-5 in maintaining B-cell function, its reduction or inactivation may favor this loss of identity and differentiation to macrophages, which supports the possibility of a lymphoma undergoing transdifferentiation into a histiocytic/dendritic cells neoplasm. Additionally, SARS-CoV-2 was detected within the tumor histiocytes and adjacent neurons, raising questions about potential interactions between viral infection and tumor development. Conclusions While the underlying mechanisms remain uncertain, this finding highlights the need for further investigation into the interplay between SARS-CoV-2 infection and oncogenesis. This case represents the first report of a primary brain histiocytic lymphoproliferative disorder associated with SARS-CoV-2 in k18-hACE2 mouse.