Rosai-Dorfman disease, also referred to as sinus histiocytosis, is a benign proliferative disorder of Langerhans cells that predominantly affects individuals in their twenties. The aetiology is associated with immunological alterations or pathogen-mediated responses. Definitive diagnosis is established through excisional biopsy and histopathological examination. The disease is defined by proliferative histiocytes exhibiting emperipolesis, characterised by the engulfment of one inflammatory cell by another. These histiocytes demonstrate positivity for S100 and CD68 markers. Management strategies include observation, follow-up, corticosteroid therapy, surgical intervention, and, in selected cases, chemoradiotherapy. This report describes a 39-year-old woman with Rosai-Dorfman disease of the right breast who did not respond to corticosteroid therapy and subsequently underwent surgical intervention, resulting in a favourable outcome without recurrence.
Rosai-Dorfman disease(RDD), also known as sinus histiocytosis with lymphadenopathy, is a rare, benign, proliferative, non-Langerhans cell histiocytic disorder. It most commonly affects children and young adults, with a mean age of 20.6 years, although cases have been documented in individuals aged 74 years or older. The disease demonstrates a male predominance among African and Caucasian individuals [1]. The aetiology of RDD remains under investigation. Although initially classified as a pseudolymphoma, it is now recognised as histiocytosis. Current evidence suggests that the disease may result from an immunological disorder or infection [2]. Clinically, presents as a firm, painless nodule in one or both breasts. Diagnosis is confirmed by histopathological analysis of a core needle biopsy; nevertheless, excisional biopsy remains the gold standard. The identification of proliferative histiocytes with emperipolesis, defined as an intact cell within the cytoplasm of another cell, is considered pathognomonic for RDD [3].
Treatment strategies for RDD encompass observation and follow-up, corticosteroids, surgical intervention for unifocal or symptomatic extranodal disease, radiation therapy (30–50Gy), chemotherapy, and immunomodulatory therapy [4]. This case is presented due to its rarity, distinctive clinical presentation, diagnostic complexity, unique histopathological features, and the management approach utilised.
Case reportA 39-year-old female patient with no significant medical history reported an 8-month history of a lesion in the right breast region. A core biopsy performed on 26 April 2025 revealed histological findings consistent with Rosai-Dorfman disease, with immunohistochemistry positive for S-100. The patient was evaluated by the Dermatology service and received topical corticosteroid therapy for two months without clinical improvement. Subsequently, she was referred to the Outpatient Surgery Clinic, where a physical examination identified a multilobulated, soft lesion measuring 4x5cm in R1-R4 of the right breast (Fig. 1). No axillary lymphadenopathy was palpable. Slide review confirmed a histomorphological picture compatible with Rosai-Dorfman disease.
Breast ultrasound of the right breast demonstrated a hypoechogenic, subcutaneous, cellular tissue lesion projecting to the skin, measuring 39x7mm, with increased vascularity on Doppler imaging. The axillary region showed no adenopathies. BIRADS 2. Laboratory results were as follows: haemoglobin 11.8 g/dl, leukocytes 7580/mm3, platelets 259,000/mm3, A (+), PT 14.3 s, INR 1.07, TPT 23.47 s, glucose 91.5 mg/dl, urea 32.1 mg/dl, and creatinine 0.66 mg/dl.
On 22 October 2025, the patient underwent right breast-conserving surgery with MICAP (medial intercostal artery perforator) flap rotation and placement of a hemovac drain. Operative findings revealed a multilobed, soft lesion measuring 4x5cm in the right breast. The patient tolerated the procedure without complications and was discharged three days later. At follow-up, definitive histopathological analysis confirmed Rosai-Dorfman disease, with histiocytes displaying large, hypochromatic, round and oval nuclei. The cytoplasm was eosinophilic and contained inflammatory cells, consistent with emperipolesis. The lesion involved the upper margin, while the other margins were negative. Immunohistochemistry was positive for S100, Cyclin-D1 and CD68 (Fig. 2).
Microscopy. Haematoxylin & Eosin. To.: 10X. Under the epidermis, an increase in cellularity is observed, made up of cells with clear cytoplasm of histiocytic appearance, surrounded by an inflammatory infiltrate. B. 40X. Increase in histiocytes with a large nucleus, hypochromatic, round and oval; the cytoplasm is eosinophilic and contains inflammatory cells, which is known as Emperipolesis (Arrow). C. 40X. Prominent infiltration of lymphocytes, plastic cells, and fibrosis.
Microscopy. Immunohistochemistry.: D. CD68 positive. E. S100 positive.
Due to narrow surgical margins, referral for radiotherapy was considered. After a multidisciplinary discussion, close monitoring was recommended given the benign nature of the disease. The patient currently shows no evidence of disease recurrence.
DiscussionBreast RDD is a rare extranodal manifestation of non-Langerhans histiocytosis. Although the incidence is undetermined, fewer than 5% of RDD cases involve the breast, and less than 1% of all breast lesions are due to this pathology [5]. Clinically, breast RDD usually presents as a unilateral, painless, slow-growing mass that is often indistinguishable from breast carcinoma. This similarity creates a significant diagnostic challenge and often requires excisional biopsy for definitive diagnosis [6]. In the present case, core needle biopsy established the diagnosis, with findings consistent with RDD.
Definitive diagnosis of RDD requires identification of large histiocytes exhibiting emperipolesis, positive staining for S100 and CD68, negative staining for CD1a, and absence of a clonal population on molecular studies to exclude histiocytic neoplasia [7,8]. The World Health Organisation Classification of Tumours of Haematopoietic and Lymphoid Tissues (2022) [7] and the College of American Pathologists [9] recommend a minimum immunohistochemical panel including S100, CD68, CD1a, and Langerin (CD207) to exclude Langerhans cell histiocytosis (LCH). S100 demonstrates a sensitivity of 98–100% and specificity of 94%, while CD68 shows a sensitivity of 85–92% and specificity of 78%. The lower specificity of CD68 results from its expression in other histiocytes [10,11]. Cyclin D1, a cell cycle regulator, is typically expressed in mantle cell lymphoma [11,14], luminal B breast carcinoma, and melanoma, but is rarely present in normal histiocytes. Recent studies have reported nuclear Cyclin D1 positivity in 30–50% of nodal and extranodal RDD cases [11–14].
Cyclin D1 demonstrates a specificity of 75–80% for RDD, as it may also be expressed in LCH and juvenile xanthogranulomatous histiocytosis. However, the combined presence of S100 positivity, CD1a negativity, and Cyclin D1 positivity increases RDD specificity to 96% compared with other histiocytoses [13]. Cyclin D1 positivity in this context does not indicate mantle cell lymphoma or other lymphoproliferative neoplasms and should not be interpreted as a marker of malignancy, but rather as a frequent aberrant phenotype. Fluorescence in situ hybridisation (FISH) is not required unless there is morphological suspicion of lymphoma [11,14]. Additionally, documentation of the percentage of nuclear positivity is recommended, as studies suggest an association with local recurrence when positivity exceeds 30% (HR 2.3; 95% CI 1.1–4.8) [13].
RDD treatment should be tailored to the extent of disease (unifocal or multifocal), the presence of symptoms such as pain, deformity, compression, or obstruction, evidence of disease progression (defined as a 25% increase in volume over at least 3 months), and response or toxicity to prior therapies. Management typically begins with observation of asymptomatic lesions smaller than 3 cm without growth, followed by corticosteroids such as prednisone, surgical intervention for unifocal or symptomatic extranodal disease, radiotherapy at 30–50Gy, and, as a fifth-line option, chemotherapy or biological therapy [5].
In this case, initial treatment with corticosteroids did not result in clinical improvement, a finding observed in approximately 30% of cases, particularly in extranodal forms [5]. Consequently, oncoplastic surgical resection was performed. This technique offers several advantages, including robust vascularisation via perforators of the internal intercostal artery that traverse the intercostal space and pectoralis muscle to supply the medial mammary gland. The flap's mobility, with a 60–90° clockwise rotation, enables coverage of defects up to 6 cm in the internal quadrants without excessive tension. This approach preserves vital structures and achieves favourable aesthetic outcomes [15,16]. In benign conditions such as RDD, surgical margins of ≤2 mm are acceptable if vascularized tissue is present to facilitate healing [17].
The surgical pathology report indicated that the lesion involved the superior, left, and anterior borders, with narrow margins at the remaining edges. Although no universal standard exists for benign disease, the 2021 histiocytosis consensus [17] and breast surgery experience [18] recommend a target margin of at least 2 mm. Margins of 1-2 mm are acceptable if vital structures are not involved and close monitoring is feasible, whereas margins of 0 mm are unacceptable and warrant re-excision or radiotherapy. In the largest breast RDD series, margins less than 1 mm were associated with a 3.2-fold increased risk of local recurrence [3].
Radiotherapy (RT) is considered in RDD cases with recurrence or positive margins, although its role in benign disease remains controversial. RT may ultimately be reserved for cases of local recurrence or for high-risk positive margins [5]. In this case, the decision was based on the assessment that the risks of radiotherapy outweighed the potential benefits, the non-clonal nature of the disease, and the feasibility of re-excision, as the vascularized MICAP flap allows for a second surgery without increased deformity. Furthermore, there is no consensus in current histiocytosis guidelines regarding routine radiotherapy for positive margins in RDD [17].
PET-CT is not required in all RDD cases but is recommended for patients with extranodal disease, systemic symptoms such as fever, generalised lymphadenopathy, elevated acute-phase reactants, or when planning systemic therapy to assess treatment response. In this patient, PET-CT was appropriately indicated, as up to 43% of extranodal cases may have occult involvement at other sites [5]. RDD generally has a favourable prognosis, with recurrence rates ranging from 10% to 20%. Follow-up should include clinical examination every 3–6 months, annual breast ultrasound, PET-CT in selected cases as outlined above, and patient education regarding early detection of recurrence [17,18].
A literature review (Supplementary 1) identified 69 cases of extranodal Rosai-Dorfman disease (RDD) of the breast across 45 reports. Of these, 7 cases occurred in males and 62 in females, with patient ages ranging from 15 to 84 years, reflecting a predominantly adult population. The most frequent clinical presentation was a palpable, non-tender breast nodule. Eleven patients were asymptomatic, with lesions detected incidentally during routine screening. Bilateral nodules were reported in 9 patients, while 6 patients had multiple nodules within a single breast, and 3 experienced mastalgia. Unilateral breast involvement was observed in 61 cases, most often affecting the right breast. Most cases were confined to the breast, although 9 patients demonstrated nodal or additional extranodal involvement.
ConclusionRosai-Dorfman disease of the breast is a rare clinical entity. Clinicians should maintain a high index of suspicion and include RDD in the differential diagnosis of breast lesions. Definitive diagnosis is achieved through core needle biopsy, with confirmation based on the presence of emperipolesis and positive immunohistochemical staining for S100 and CD68. Conservative management and close clinical follow-up are advised to minimise unnecessary interventions.
Ethical considerationsWe have received approval from the 2. Hospital Virgen de la Puerta, High Complexity-EsSalud, Trujillo.
FundingThis project was funded by the authors and did not receive external funding.
The authors declare that they have no financial or non-financial conflicts of interest in the publication of this article.
Author contributions
All authors have contributed, read, and approved the final manuscript for submission.
EYQ: Conceptualisation, Data Curation, Formal Analysis, Research, Methodology, Software, Supervision, Validation, Visualisation, Writing – Original Draft, Writing – Revision and Editing.
CLS: Formal Analysis, Acquisition of Funding, Research, Methodology, Resources, Software, Supervision, Writing – Review and Editing.
JTV: Conceptualisation, Data Curation, Formal Analysis, Research, Methodology, Software, Supervision, Validation, Visualisation, Writing – Original Draft, Writing – Proofreading and Editing.
Supplementary material
