Review of Rosai-Dorfman Disease: New Insights into the Pathogenesis of This Rare Disorder

Abstract

Rosai-Dorfman disease (RDD) is a rare histiocytosis typically with bilateral painless cervical lymphadenopathy. Laboratory data are nonspecific, and the presence of emperipolesis in large foamy S-100⁺ CD1a^- histiocytes is the prominent histologic feature. The pathogenesis of RDD still remains elusive. According to published studies, we propose that RDD cells might represent intermediate recruiting monocytes with differentiation blockade. Both disturbance of homoeostasis and inherent genomic alterations could contribute to initiation of the disorder through signal transduction. Several inflammatory molecules such as macrophage colony-stimulating factor, IL-1β, IL-6, and tumor necrosis factor-α also play a pivotal role in the development of this rare entity. Additional studies are needed to further elucidate the essence of the disease.

Extranodal Rosai-Dorfman of the Pancreas Presents with Bilateral Granulomatous Anterior Uveitis

“…Patients with uveitis should also undergo full uveitis workup to rule out other etiologies. Histology is required for definitive diagnosis and shows a histiocytic proliferation that demonstrates emperipolesis and is S-100 positive, CD68 positive, and CD1a negative [1]. It has been postulated that uveitis occurs through the histiocytic infiltration of the uvea, as has been shown in an enucleated eye of a patient with orbital RDD.…”

“…There is also notable association with autoimmune conditions such as hypothyroidism [4, 7, 13]. Laboratory studies are inconsistently reported in literature and more work is necessary to elucidate the cause of this disease [1]. …”

“…It typically presents within the first 2 decades of life with self-limited painless cervical lymphadenopathy and is commonly accompanied by leukocytosis, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate. Extranodal manifestations have been noted in up to 28–43% of cases, including the involvement of the skin, gastrointestinal system, visceral organs, respiratory tract, and nervous system [1, 2]. Ocular involvement is rare, and usually involves lymphoproliferative tissue in the orbit or eyelids, with few reports of uveitis.…”

Soft Tissue Rosai-Dorfman Disease with Unusual Histopathologic Features: A Case Report

“…However, no infectious agent has been definitively linked to RDD. Recent studies suggest that several inflammatory molecules such as macrophage colony stimulating factor, IL-1, IL-6 and TNF-α play a role in the development of this disease [14]. Some authors suggested that a subset of RDD could overlap with IgG4-related Disease [15,16].…”

Sirolimus—A targeted therapy for Rosai‐Dorfman disease

“…They achieved complete resolution of autoimmunity within 1 month of treatment and the patient remained in remission 23 months after stopping sirolimus . Sirolimus inhibits the possible dysregulation of the PI(3)K/Akt/mTOR pathway, which is important for the normal development of histiocytic precursors, leading to significant reduction in these cells, as has been shown in vitro and in murine models . This is the first case report to demonstrate a response in lymphadenopathy to sirolimus therapy in two patients with RDD.…”