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Pathology – Research and Practice 203 (2007) 741–744

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TEACHING CASES

Rosai–Dorfman disease of the breast mimicking cancer

Benedito Borges da Silvaa,�, Pedro Vitor Lopes-Costaa, Cleicilene Gomes Piresa,Cleriston Silva Mouraa, Rafael Soares Borgesa, Raimundo Geronimo da Silvab

aDepartment of Gynecology, Federal University of Piauı, Teresina, Piauı, BrazilbDepartment of Pathology, Federal University of Piauı, Teresina. Piauı, Brazil

Received 11 September 2006; accepted 24 May 2007

Abstract

Rosai–Dorfman disease or sinus histiocytosis with massive lymphadenopathy is a rare proliferative histiocyticdisorder of the lymph nodes. Extranodal involvement occurs in a considerable number of cases; however, involvementof the breast is very rare, and it is even rarer for the lesion to be localized in the breast alone without affecting any othersites. This report describes the case of a 50-year-old Brazilian woman with a lump confined to her left breast that hadclinical and radiological characteristics indistinguishable from cancer. The proliferation of histiocytes, displayinglymphophagocytosis and an S-100 protein immunophenotype on a core biopsy of the lesion, led to a diagnosis ofRosai–Dorfman disease and permitted conservative therapy. Recognition of this rare condition, when occurring at anunexpected site such as the breast, is difficult, and the correct diagnosis is important prior to therapeutic management.r 2007 Elsevier GmbH. All rights reserved.

Keywords: Breast; Histiocytosis; Rosai–Dorfman disease; Cancer

1. Introduction

Rosai–Dorfman disease, also referred to as sinushistiocytosis with massive lymphadenopathy, is aclinical-pathological entity [1–12]. This entity was firstdescribed by Rosai and Dorfman in 1969 [11]. It is abenign histiocytosis of unknown etiology and presumedreactive nature. The condition is characterized by aproliferation of histiocytes showing distinctive lympho-phagocytosis or emperipolesis and strong immunoreac-tivity to the S-100 protein [1,3].

Although the lymphadenopathy is often the moststriking manifestation of this disorder, extranodal invol-

e front matter r 2007 Elsevier GmbH. All rights reserved.

p.2007.05.012

ng author. Benedito Borges da Silva, Av. Elias Joao

t. 600, Jockey Club, 64049-300, Teresina, Piauı, Brazil.

2 5063; fax: +55 86 3215 0470.

ss: beneditoborges@globo.com (B.B. da Silva).

vement is observed in up to 43% of cases, irrespective ofthe nodal disease [1,3]. The skin is the most commonextranodal site [2,12]. Rosai–Dorfman disease affectingthe breast is very rare, and it is even rarer for the breastalone to be affected without the involvement of any othersites [4–10]. For this reason and since the conditionmimics breast cancer both clinically and radiologically,diagnosis can be difficult as in the present case.

2. Case report

A 50-year-old Brazilian woman presented at theMastology Department of the Getulio Vargas Hospitalof the Federal University of Piauı in January 2002 with apalpable lump in her left breast. At the physicalexamination, the lesion appeared firm and with irregularborders. There was not axillary lymphadenopathy.

ARTICLE IN PRESSB.B. da Silva et al. / Pathology – Research and Practice 203 (2007) 741–744742

Mammography revealed an ill-defined lesion measuring5.0� 4.5 cm in diameter situated in the upper outerquadrant of the left breast, highly suspicious ofmalignancy (BIRADS, category 4) (Fig. 1). A corebiopsy revealed the benign nature of the lesion, and ledus to the diagnosis of Rosai–Dorfman disease. However,in face of the strong clinical suspicion and volume of thelump, an excisional biopsy was then carried out, andgross examination of the specimen revealed a lesionmeasuring 5.0� 3.5� 2.5 cm with irregular borders anda cut section grayish–brown in color. Histology revealedmononuclear inflammatory cell infiltrate with plasmacells, lymphocytes, and proliferation of large andpolygonal histiocytes with pale cytoplasm, showingdistinctive lymphophagocytosis (emperipolesis) admixedwith fragments of fibrous tissue (Figs. 2 and 3).

Fig. 1. Mammography showing a lump in the left breast with

irregular borders, highly suspicious of malignancy.

Fig. 2. Photomicrograph of a histological section of the lesion

showing inflammatory infiltrate consisting of lymphocytes,

plasma cells, and histiocytes (HE, original magnification

� 100).

Fig. 3. Photomicrograph of a histological section of the lesion

showing histiocytes with large, pale cytoplasm and lympho-

phagocytosis (HE, original magnification � 400).

Fig. 4. At immunohistochemistry, histiocytes expressed S-100

protein. Emperipolesis is enhanced by the strong immuno-

reactivity (original magnification � 400).

Immunohistochemistry revealed histiocytes with astrong reaction to S-100 protein (Fig. 4) and a negativereaction to CD1a, which, together with the histopatho-logical findings, led to a diagnosis of Rosai–Dorfmandisease. Hematological investigations were normal, andthe patient had no other systemic diseases. A generalphysical examination, imaging tests such as chest X-ray,abdominal sonography, and bone scintigraphy werecarried out, and all results were normal, confirming thatthe disease was confined to the breast. Diagnosis of abenign condition therefore permitted a conservativetreatment (excision of the lesion). The patient iscurrently being followed-up and shows no signs ofrecurrence.

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3. Discussion

Rosai–Dorfman disease is a benign disorder, primar-ily confined to the lymph nodes; however, in up to 43%of cases, this disease affects extranodal organs or tissues,irrespective of whether or not the lymph nodes areaffected [3,7,8]. The most common sites of extranodalinvolvement are the skin, upper respiratory tract, andbone [2]. However, localization of the disease in thebreast is extremely rare, and it is even rarer for thecondition to be present in the breast without affectingany other sites. Following the first two reports publishedin the literature on Rosai–Dorfman disease affecting thebreast, in which no follow-up information was provided[7,9], the first report of a series of seven cases ofextranodal Rosai–Dorfman disease affecting the breastwas published by Green et al. in 1997 [3]. In every caseof that series, the clinical and radiographic presentationof the breast lesion was suggestive of a malignanttumor [3].

Most of the cases of Rosai–Dorfman disease of thebreast reported in the literature, as well as the clinicaland radiographic presentation of the breast lesion raisedthe possibility of a malignant tumor [3,6]. In all casesreported by Green et al. [3], the radiographic presenta-tion of the breast lesion was suspicious of malignancy[3]. Kuzmiak et al. [6] reported a case of Rosai–Dorfmandisease of the breast in which the sonography showed asuspicious irregular mass, and the mammogram showedan irregular mass of high density with ill-definedmargins (BI-RADS, category 4) [6]. In the present case,it was not different. The patient presented a breast massthat was suspicious of malignancy both clinically andradiologically.

The histological diagnosis is based on the presence oftypical histiocytes together with a background of mixedinflammatory cells and fibrosis. The microscopic appear-ance of the Rosai–Dorfman disease has distinct featuresof sinus histiocytes, with abundant pale pink cytoplasmwith round or oval vesicular nuclei [2,6]. The cytoplasmof many of the histiocytes contains lymphocytes. Thehistiocytes usually occur in a background of predomi-nantly mature lymphocytes and plasma cells [2], as seenin the present case. These sheets of characteristic largehistiocytes displaying emperipolesis are a microscopichallmark of this disease [2,3]. Immunohistochemicalexamination confirms the diagnosis by showing histio-cytes with strong cytoplasmic staining for the S-100protein [2–4,7,8]. In the present case, the histiocytes wereCD1a antigen-negative and S-100 protein-positive. Thehistiocytes in Rosai–Dorfman disease are CD68 antigenand S-100 protein-positive [4]. In our study, antibodyclone for CD68 antigen was not used.

Despite similar pathological features at both nodaland extranodal sites, diagnosis of the extranodal diseaseis often overlooked, particularly when the lymph nodes

are not affected [2,7]. The microscopic differentialdiagnosis should consider idiopathic granulomatousmastitis, infectious granulomas, Langerhans’ cell histio-cytosis, Erdheim–Chester disease, fibrous histiocytoma,and malignant melanoma [3,7]. However, Rosai–Dorfman disease can be distinguished from otherentities because of its cell populations, rare mitosis,and strongly positive staining for the S-100 protein [2,3].Rosai–Dorfman disease is a self-limiting disorder, andregression of symptoms and complete recovery oftenoccur spontaneously; however, well-documented caseshave been published in which multisystem involvementhas resulted in the death of the patient [3].

It should be emphasized that although the morpho-logical characteristics of Rosai–Dorfman disease havebeen well defined in the literature, recognition of thisrare condition, when occurring at an unexpected sitesuch as the breast, is difficult [3,12]. In the present case,the lesion was situated in the breast alone andmasqueraded as cancer both clinically and radiologi-cally. The tumor was excised following diagnosticconfirmation in a core biopsy sample. The patient iscurrently being followed-up and shows no signs ofrelapse.

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