Rosai-Dorfman-Destombes disease in adults: a single center experience

Abstract

Recent advances in Rosai-Dorfman-Destombes disease (RDD), notably molecular testing, targeted therapy, and PET-CT imaging, hold promise for better recognition and improved outcomes. This study presents patients diagnosed and treated in a "real world" setting, where navigating limited resources must be considered. This retrospective single-center review includes 15 adult patients diagnosed with RDD at Vancouver General Hospital between November 2015 and October 2023. The cohort comprised five males and ten females with a median age 53 years (range 19-80 years). All 15 patients had extra-nodal disease; 11 patients exclusively had extra-nodal disease, and four patients also had lymph node involvement. Seven patients had tissue next-generation sequencing, identifying MAP2K1 mutations in four cases and a KRAS p.K117N mutation in one case that was treated with targeted therapy using trametinib. PET-CT was used for disease staging in four cases. Six patients with refractory disease tolerated lenalidomide and dexamethasone without significant toxicity; three patients achieved complete response, and three had partial response. This study highlights RDD's diverse extra-nodal manifestations. Lenalidomide combined with dexamethasone is an effective and well-tolerated treatment option for select patients, especially those with refractory disease. Broad utilization of NGS and PET-CT can positively influence management decisions.

Keywords: Cereblon; Histiocytosis; KRAS; Lenalidomide; Next-generation sequencing; Rosai-Dorfman disease.

Figure 1:. CT findings in Rosai-Dorfman-Destombes disease.

1a) Right orbital masses. 1b) Bulky pancreatic head without evidence of pancreatitis (coronal view of pancreatic head). 1c) Diffuse heterogeneous renal parenchymal enhancement with loss of normal corticomedullary differentiation; no focal lesion demonstrated.

Figure 2:. PET-CT images of Case 15.

2a) Maximum Intensity Pixel (MIP) view from baseline PET-CT demonstrating extensive multi-organ FDG-avid disease including nodal, cutaneous, subcutaneous, and parotid. 2b) Subtle lytic lesion in calcaneus on plain CT (left) better seen on fused PET-CT as an FDG-avid lesion (right). 2c) Tibial involvement not apparent on plain CT (left) but readily seen as an FDG-avid lesion on fused PET-CT (right).

Figure 3:

H&E-stained sections of 3a) lymph node and 3b) cardiac mass involved by RDD at 2X (top) and 40X magnification (bottom). The lymph node shows classic expansion of the sinuses with easily identified histiocytes containing engulfed inflammatory cells (emperipolesis). The cardiac mass shows dense fibrosis, including areas suggestive of storiform fibrosis, and chronic inflammatory cells including plasma cells.