Extranodal manifestation of Rosai-Dorfman disease in the breast tissue.

A 71-year-old asymptomatic female with a history of breast cancer status after right total mastectomy had interval development of several new nodules in the left breast in a 1-year time span. Stereotactic biopsy was performed, which revealed multifocal Rosai Dorfman disease in the left breast. The patient was referred to hematology, and computed tomography of the chest/abdomen/pelvis did not demonstrate any lymphadenopathy elsewhere in the body. This case report discusses incidences of extranodal Rosai Dorfman disease and the differential for breast lesions that can present the same way.

Case report

A 71-year-old woman with a history of breast cancer s/p right total mastectomy, hypertension, hypothyroidism, and right knee osteoarthritis presented to the clinic for a regularly scheduled annual screening mammogram. On comparison with previous mammograms (Fig. 1), several new nodules were noted in the left breast (Fig. 2). Diagnostic mammography confirmed the persistence of 2 new nodules within the left breast. Ultrasonography confirmed the presence of an oval parallel 5 × 3 × 5 mm3 mass with slightly irregular margins at the 12:00 position, as well as a 4 × 4 × 3 mm3 hypoechoic nodule near the 2:00 position (Fig. 3). A Breast Imaging Reporting and Data System of 4 was given, and biopsy of these nodules was recommended.

Fig. 1

7/3/2014: Mammogram demonstrates no evidence of malignancy.

Fig. 2

Mammogram 7/9/2015: 2 new nodules within the upper left breast, one at the 12:00 position and the other at the 1 to 2:00 position posteriorly.

Fig. 3

At the 12:00 position 10 cm from the nipple, there is an oval parallel 5 × 3 × 5 mm3 mass with slightly irregular margins. At the 2:00 position 4 cm from the nipple, there is a 4 × 4 × 3 mm3 new hypoechoic nodule.

A stereotactic core biopsy of the left breast was chosen over ultrasound guidance because of close proximity of these nodules, and a total of 9 core samples were obtained. The pathology of these nodules was later found to be extranodal Rosai-Dorfman disease (RDD; Figs. 4 and 5). This finding was deemed benign, but further evaluation for additional involvement of nonbreast areas was recommended, and patient follow-up with the hematology service was advised as well. Subsequent computed tomography (CT) of the chest abdomen pelvis did not demonstrate any evidence of systemic lymphadenopathy. Because of the patient’s history of breast carcinoma and isolated locus of disease, it was ultimately determined by the patient’s multidisciplinary team to perform a curative resection of the involved site.

Fig. 4

Immunoperoxidase stain panel performed on with results: s100 (A1 and C1) strongly positive in histiocytes; CD1a (A1) negative in histiocytes; CD138 (A1) highlights plasma cells; kappa (A1) and lambda (A1) fail to demonstrate evidence of clonality.

Fig. 5

Hematoxylin and eosin stain shows well-demarcated infiltrates of prominent histiocytes intermixed with small mature lymphocytes and plasma cells. Histiocytes are large, irregularly shaped with abundant vacuolated cytoplasm. Engulfed lymphocytes as shown by a clear halo of cytoplasm surrounding lymphocytes is a characteristic of emperipolesis (arrow). Plasma cells demonstrate binucleation. Evidence of intact nodal architecture is not identified.

Discussion

Sinus histiocytosis and massive lymphadenopathy also known as RDD is characterized by an uncontrolled proliferation of the non-Langerhans sinus histiocyte [1]. Pathologically, these histiocytes harbor what are presumably engulfed, intact lymphocytes lending the appearance of “cell within a cell” or emperipolesis [2]. Identification of cell surface S-100 and CD68 receptors and the lack of CD1a expression are the cardinal histologic characteristics of this cell type [1]. This rare disease demonstrates predominance in young adults; however, adult cases have also been documented. Most patients present with profound cervical lymphadenopathy in addition to headaches and seizures if the intracranial space is involved. The most commonly reported extranodal sites include the skin, central nervous system, upper respiratory tract, orbit and eyelid, and gastrointestinal tract [3], [4]. The exact inciting factor is unknown, but immune system dyscrasias and viral infections, specifically herpesvirus 6, have been implicated [5].

Infiltration into breast tissue by RDD is a very rare occurrence [6], [7]. Moreover, disease isolated solely to the breast is rarer still, as RDD commonly presents with lymphadenopathy and involves multiple organs at the time of diagnosis [8]. Although RDD tends to present most commonly in young males (average age 39 years) involving multiple organs, most of the cases isolated to the breast occur in female patients older than 50 years [9]. This is especially significant because women after 50 years are screened regularly because of increased risk of breast carcinoma, and initial radiographic and clinical presentation of RDD can masquerade as lesions running the gamut of benign cysts and fibroadenomas to carcinoma [10], [11]. Differential considerations of mass-like, histiocytic invasion into breast tissue should always include RDD among other entities such as Langerhans’ cell histiocytosis, Erdheim-Chester disease, diabetic mastopathy, and granulomatous lobular mastitis [12], [13].

In reference to the patient presented in this case, the discovery of 2 new nodular lesions in the left breast in the setting of right breast cancer status after mastectomy were cogent indications to proceed with stereotactic biopsy. RDD can have a high rate of recurrence which could potentially lead to repeated biopsies and excisions in the breast tissue [14]. Notably, incidental discovery of RDD in the breast parenchyma necessitates establishing the full extent of disease elsewhere in the body with full body CT and abdominal ultrasound [15]. Positron emission tomography/CT can also be useful for characterization because areas of involvement by RDD can possess fludeoxyglucose avidity [16].

Parkin et al recently described a patient with isolated RDD of the breast in a 56-year-old healthy patient [11]. Similar to our case, the patient had an intermediate density of the lateral left breast discovered incidentally on routine mammography, with no apparent lymphadenopathy; however, unlike this presented case report, the patient had no history of breast carcinoma. Histologically, their specimen showed emperipolesis and staining for S-100 and CD68. In contrast to surgical intervention, their patient was followed with regular follow-up and screening. These cases are of note as patients with RDD typically present with fever, leukocytosis, and nonpainful adenopathy—symptoms not seen in either of the cases.

After an indolent, benign course, RDD is not an entity that compels aggressive management, and in most cases, will exhibit spontaneous regression [3]. Recognizing the unique microscopic and histologic presentation of RDD may save both providers and patients from invasive, costly, and unnecessary investigative procedures.