RDD is an uncommon histiocytosis that may be sporadic or familial. Sporadic RDD is the more common form and includes classical (nodal) RDD, extranodal RDD, neoplasia-associated RDD, and autoimmune disease-associated RDD [1, 2]. Neoplasms associated with RDD include lymphoma, Langerhans cell histiocytosis (LCH), and Erdheim-Chester disease (ECD) [2]. At least a subset of cases is clonal with mutations in MAP2K1, KRAS, NRAS, ARAF, CSF1R, and rarely, BRAF p.V600E [3, 4].

Breast involvement by RDD is unusual and often occurs in adult females, with a median age in the early 50s at the time of presentation, which may mimic neoplastic and non-neoplastic processes on clinical, imaging, and pathologic evaluations. Patients usually present with a solid, painless, slow-growing, oval or irregular breast mass of variable size (range 1.0 to 6.6 cm) [5]. In most patients, RDD is confined to the breast, with a minority having concurrent axillary lymph node involvement or systemic disease [5]. Patients with bilateral breast involvement are more likely to have extramammary RDD than those with unilateral involvement [5].

A few cases of RDD of the breast diagnosed on FNA cytology have been reported [6, 7], characterized by mononucleated and multinucleated large histiocytes with emperipolesis and associated with background plasma cells and small mature lymphocytes. Co-expression of CD68 and S100 with CD1a negativity in the lesional histiocytes was confirmatory for a diagnosis of breast RDD, noting that most prior cases predated use of Cyclin D1 and OCT2 immunohistochemistry, which are now known to be useful additional confirmatory markers [8, 9].

Complete excision was performed in this patient. At 40 months follow-up, the patient had a negative MG; however, numerous scattered soft tissue nodules and multiregional lymphadenopathy were demonstrated on Positron Emission Tomography and Computed Tomography (PET/CT), clinically compatible with systemic RDD. The patient is currently undergoing imaging surveillance and has not received additional treatment.