RNA-seq of seven non-neoplastic/inflammatory lymphadenitis entities identify potential molecular diagnostic markers

Lymphadenopathy is a common mode of presentation for various disorders. While malignancy must be considered, there is a broad spectrum of causes that are infectious or of autoimmune origin. Clinical testing and morphological assessment are required to distinguish between neoplasms and benign pathologies. However, many causes of lymphadenopathy have similar histological presentations, making definitive diagnoses and categorization challenging. While DNA sequencing have enabled the accurate diagnosis of certain disorders, such as the genetic origin of ALPS (autoimmune lymphoproliferative syndrome), other causes of lymphadenopathy such as benign sinus histiocytosis, or Rosai-Dorfman disease (RDD), cannot be diagnosed with current technologies. Likewise, several modes of infection, including Toxoplasmosis gondii, Epstein-Barr virus (EBV), and Bartonella henselae (Cat-scratch disease) require further investigation. RNA sequencing enables the assessment of differentially expressed genes (DEG) that reveal up or downregulated pathways. These DEG signatures and pathways can help differentiate lymphadenopathies that appear similar histologically. In this study, RNA sequencing of 46 cases of lymphadenopathies were performed and analyzed. ALPS and RDD cases provided confirmation that RNA sequencing can identified expected gene expression and activated pathways. Our results showed the unique activation of the interferon pathway was identified in sinus histiocytosis cases. Through advances in RNA sequencing, potential genetic signatures can be discovered in a gamut of varying conditions.