The Clinicopathologic Spectrum of Rosai–Dorfman–Destombes Disease in Adults: An Analysis of 16 Cases

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytic proliferation with protean clinical manifestations, resulting from the accumulation of activated histiocytes within nodal and extra-nodal tissues. The diagnosis can be missed, particularly when biopsies are obtained from extra-nodal sites, where histological features may be less specific than those observed in nodal specimens. Here, we examined a case series of 16 adults diagnosed with RDD from Vancouver, Canada between 2015 and 2025. Cases were classified as diagnostically challenging if the time to a definitive pathologic diagnosis exceeded 60 days from the initial biopsy for RDD-related clinical symptoms and > 1 pathologic sampling was required to establish a diagnosis. Eight of 16 patients (50%) were classified as having diagnostically challenging cases. The median number of independent pathological samples required to establish a diagnosis of RDD was 2.0 (interquartile range: 2.3), with five patients needing three or more independent specimens. The median timeto final diagnosis was 12 days for non-diagnostically challenging cases (IQR: 15 days) and 240 days for diagnostically challenging cases (IQR: 138 days). Notably, diagnostically challenging cases tended to have specimen sampling from atypical anatomical sites (62.5% vs. 37.5%), utilized suboptimal pathological sampling techniques (87.5% vs. 25.0%; e.g., cytology), and delayed or absent consultation with hematolymphoid-specialized pathologists (25.0% vs. 87.5%). Together, this study underscores the extreme clinical heterogeneity of extra-nodal RDD, emphasizes the critical role of expert hematolymphoid pathology expertise in its diagnosis, and suggests practical strategies-such as liberal use of immunohistochemistry on atypical histiocyte-rich infiltrates-to avoid premature exclusion of RDD from the differential diagnosis.