[Rosai-Dorfman disease of the breast: a clinicopathological and molecular genetic analysis of four cases].

Objective: To investigate the clinicopathological, imaging, and molecular characteristics of mammary Rosai-Dorfman disease (RDD). Methods: A retrospective analysis was performed on four cases of primary RDD in the breast diagnosed at the First Affiliated Hospital with Nanjing Medical University from January 2018 to September 2025. Clinical, histopathological, and immunohistochemical features were reviewed, next-generation sequencing (NGS) was conducted, and the findings were discussed in the context of relevant literature. Results: Among the four cases, three were female and one was male, with ages of 54, 33, 67 and 62 years respectively. Ultrasound findings suggested inflammatory changes in one case, BI-RADS category 3 in one case, and BI-RADS category 4 in two cases. Microscopic examination revealed infiltration of lymphocytes, plasma cells, and histiocytes, with characteristic emperipolesis observed in some cases. Immunohistochemically, the lesional cells were positive for CD68, CD163, cyclin D1, S-100, and OCT2, and negative for Langerin and ALK. NGS performed in all four cases identified somatic mutations in homologous recombination repair-related genes-including RAD54L, RAD50, MRE11, and BRIP1-in three cases. One case showed somatic mutations in genes associated with signaling pathways and immune inflammation, such as AXIN2, FGF19, MYD88, NF2, and TSC2. Conclusions: RDD of the breast presents with non-specific clinical manifestations and radiologically misleading features. Its histopathological characteristics (especially the emperipolesis phenomenon) and typical immunohistochemical profile (CD68+, CD163+, cyclin D1+, S-100+, Langerin-, ALK-) may aid in differential diagnosis. The high frequency of DNA homologous recombination repair-related gene mutations in mammary RDD provides new insights into its pathogenesis and supports its classification as a clonal disease.