The Journal of Laryngology and OtologyNovember 1997, Vol. Ill, pp. 1091-1093

Rosai-Dorfman disease presenting as a parotid mass

L. NORMAN, A. C. BATEMAN, M.R.C.PATH.*, G. W. R. WAITERS, F.R.C.S., V. SINGH, F.R.C.S.,A. V. SPEDDING, M.R.C.PATH.*

AbstractSinus histiocytosis with massive lymphadenopathy (SHML) is a rare, benign disease of unknown aetiology. Thisdisease typically presents with massive, painless cervical lymphadenopathy but may occur in a wide variety ofextranodal sites. Our report describes a 71-year-old man who presented with a discrete, unilateral parotid masswhich was clinically suggestive of a primary salivary gland tumour. Initial cytological examination of a fineneedle aspirate specimen taken from the mass demonstrated a discohesive cell population with nuclear atypia,raising the possibility of malignancy. However, excision of the mass and histological examination enabled adefinitive diagnosis to be made.

Key words: Histiocytosis, sinus; Lymph node; Neck

IntroductionRosai-Dorfman disease or sinus histiocytosis with massivelymphadenopathy (SHML) is a rare benign disorder ofuncertain aetiology. The condition was first described in1969 (Rosai and Dorfman, 1969) and a further account in1972 (Rosai and Dorfman, 1972) described the clinical andpathological features. The disease typically presents inyoung people with massive, painless cervical lymphaden-opathy and may be accompanied by malaise, fever andweight loss. Extranodal disease occurs in 43 per cent ofpatients and most commonly involves the skin, nasal cavityand paranasal sinuses. The condition may present to theear, nose and throat (ENT) department in a number ofways but isolated salivary gland disease is relativelyunusual since patients presenting with salivary glandinvolvement possess additional extranodal disease in themajority of cases (Foucar et «/., 1990).

Our report describes an atypical presentation of SHMLand the particular importance lies in the unusual appear-ance of the fine needle aspirate which initially suggested amalignancy, previously not described in cytological speci-mens in cases of SHML.

Case reportA 71-year-old male was referred to ENT outpatients

with a left-sided facial swelling. The patient had beenaware of a painless lump in the pre-auricular area for somemonths, but an increase in size in the previous month hadprecipitated his referral. There were no associatedsymptoms and the patient was a non-smoker with norelevant past medical history. On physical examination around mobile swelling approximately 1.5 cm in size waspresent over the pre-auricular area. The parotid duct andfacial nerve function were both normal. The mass wasbelieved most likely to represent a pleomorphic adenomaand a fine needle aspirate was performed for cytologicalexamination. Subsequent computed tomography (CT)scan confirmed a well-defined solid mass within the

superficial lobe of the left parotid gland and enhancedsections through the neck showed no lymph nodeenlargement. The routine full blood count and serumestimation of electrolytes and liver function were withinnormal parameters. The patient underwent a superficialparotidectomy and the specimen was sent for histologicalexamination.

Pathological findingsExamination of the fine needle aspirate specimen from

the parotid gland mass revealed numerous epithelioid cellsshowing nuclear atypia and containing mitotic figures(Figure 1). These cells were admixed with lymphocytes,plasma cells and normal parotid gland acini. The appear-ances of the atypical epithelioid cells were interpreted assuspicious of malignancy and biopsy was advised.

The excised portion of parotid gland measured 60 X 45X 5 mm. Sectioning the parotid tissue revealed a 15 mmdiameter fairly well-defined soft, white and yellow lesion.Microscopic examination revealed that this lesion was atleast partly contained within a lymph node, with a partialfibrous capsule, an underlying subcapsular sinus andperipheral foci of small lymphoid cells. However, themajority of the lymph node architecture was effaced bysheets of epithelioid histiocytes dilating the nodal sinusesand exhibiting erythrophagocytosis and lymphophago-cytosis (engulfment of intact erythrocytes and lymphocyteswithin the cytoplasm of epithelioid histiocytes, also termedemperipolesis), together with scattered small foci ofnecrosis (Figure 2). Immunohistochemical stainingrevealed that the histiocytes labelled positively with theMAC 387 antibody as well as with antibodies to S100protein and CD68. The appearances were interpreted asthose of sinus histiocytosis with massive lymphadenopathy(SHML) (Rosai-Dorfman disease) occurring within anintraparotid lymph node.

From the Departments of Otolaryngology and Histopathology*, Queen Alexandra Hospital, Cosham, Portsmouth, UK.Accepted for publication: 10 September 1997.

1091

1092 L. NORMAN, A. C. BATEMAN, G. W. R. WAITERS, V. SINGH, A. V. SPEDDING

FIG. 1Fine needle aspirate of the parotid gland mass showing amultinucleate histiocytic cell demonstrating emperipolesis,together with numerous nuclear histiocytic cells, lymphocytes

and plasma cells (Giemsa stain; x 400).

DiscussionSinus histiocytosis with massive lymphadenopathy

(SHML) was recognized as a clinicopathological entity in1969 and a registry of cases was initiated at Yale School ofMedicine in the USA. Cases have subsequently beenreported world-wide and in 1990 the registry contained 423patients (Foucar et al, 1990). The mean age of onset was20.6 years but ranged from a congenital case to diagnosis at74 years. There was an equal preponderance in black andwhite races (43.6 per cent each), 4.6 per cent in orientalraces and 8.3 per cent in other racial groups. Approxi-mately 58 per cent of patients were male and 42 per centwere female (Foucar et al, 1990).

The vast majority of patients (97 per cent) present with athree- to nine-month history of bilateral, painless cervicallymphadenopathy. The axillary and inguinal lymph nodesmay be involved by SHML in up to 38 per cent and 44 percent of cases respectively, while mediastinal and hilarlymphadenopathy is detectable in up to 40 per cent ofpatients (McAlister et al, 1990). At least one extranodalsite is involved in 43 per cent of cases and 75 per cent ofthese occur within the head and neck region (Foucar et al.,1990). Within the head and neck, the most common sites ofinvolvement are the orbit, nasal cavity and paranasalsinuses (Naidu et al., 1990). In the Yale School of MedicineRegistry, 22 patients showed involvement of a majorsalivary gland, although it is uncertain whether these casesrepresented intrasalivary lymph node or extranodaldisease (Foucar et al., 1990). Patients with extranodalSHML within the head and neck most commonly presentwith symptoms of nasal obstruction, rhinitis and epistaxis(Naidu et al., 1990). Despite the predilection of SHML forstructures within the head and neck region, SHML hasbeen reported to affect a wide variety of additional sites,including the skin, bone, kidney and central nervoussystem (Foucar et al., 1990).

The main pathological features of SHML are aproliferation of distinctive histiocytes with abundantcytoplasm, exhibiting emperipolesis, together with moder-ate numbers of lymphocytes and plasma cells (Foucaret al., 1990). When occurring within a lymph node, thisprocess commonly results in partial or complete efface-ment of the nodal architecture. Emperipolesis is a verycharacteristic finding in SHML but is not unique to thiscondition (Rosai and Dorfman, 1972). The histiocytic cellsshow positive immunoreactivity for S100 protein (Ham-mond et al., 1996) as well as the CD68 antigen as detectedin our case. The differential diagnosis of SHML includes

Histological section of the parotid gland lesion which iscomposed of sheets of histiocytic cells, some of which showemperipolesis, together with lymphocytes and plasma cells

(H & E; X 400).

non-specific reactive sinus histiocytosis in which thehistiocytic cells lack emperipolesis and do not expressS100 protein (Foucar et al., 1990). SHML occurring inextranodal sites possesses very similar appearancesalthough fibrosis is more pronounced and emperipolesisless conspicuous (Trautman et al., 1991).

The aetiology of SHML is unknown and extensive workhas searched for an infective cause, focusing particularlyon viral agents. An association with human herpesvirus 6and to a lesser extent with Epstein-Barr virus has beensuggested but conclusive proof is awaited (Levine et al.,1992).

The patient described within this report presented with awell-defined parotid mass which was clinically suggestiveof a primary salivary gland tumour. No enlarged cervicallymph nodes were clinically or radiologically evident andthere was no evidence of distant disease. The final needleaspirate (FNA) was reported as suspicious of malignancydue to the presence of a discohesive population of cellswith voluminous cytoplasm and cytologically atypicalnuclei, focally prominent nucleoli and occasional mitoticfigures. The clinical suspicion of a primary parotid lesiontogether with a FNA showing atypical cells warrantedsurgical excision of the mass. Careful histological examina-tion of the histiocytic cells revealed very similar nuclearcytological features to those identified within the FNAspecimen, together with occasional mitotic figures. Thepresence of frequent nuclear atypia within the histiocyticcells of SHML has not been previously reported and in thiscase raised the possibility of malignancy during the initialexamination of the FNA specimen. Cytological review ofthe FNA specimen once definitive histological diagnosishad been achieved revealed good correlation with thehistological appearances, with focal emperipolesis identifi-able within the characteristic histiocytic cells, as reportedin a previous case (Hammond et al, 1996).

SHML generally follows an insidious course and appearsto undergo complete remission in the majority of patients(Foucar et al., 1990). Lymph node or incisional biopsy isperformed for diagnostic purposes in most patients butmore extensive procedures due to mass effects compromis-ing life or organ function are rarely required (Goodnightet al, 1996). Chemotherapy including corticosteroids andradiotherapy has been attempted with limited success insome cases (Komp, 1990) although methotrexate and6-mercaptopurine were recently used in one case withconsiderable success (Horneff et al, 1996). The patient

PATHOLOGY IN FOCUS 1093

described in this report has remained well four monthsafter initial diagnosis and has received no furthertreatment.

SHML is an unusual condition that commonly affectsthe head and neck region but which may rarely present asvery localized disease simulating a primary salivary glandneoplasm. Examination of FNA specimens from unsus-pected cases of SHML may initially be misleading due tothe content of cytologically atypical histiocytic cells andmitotic figures. The combination of an unusual clinicalpresentation and uncertainty regarding the cytologicalappearances may necessitate excision of the lesion andhistological confirmation of the diagnosis.

Acknowledgements

We are very grateful to Dr J. Eveson and Dr J. Pawadefor providing expert assistance with the histopathologicaldiagnosis and to Miss A. Davis for giving us permission toreport this case.

ReferencesFoucar, E., Rosai, J., Dorfman, R. F. (1990) Sinus histiocytosis

with massive lymphadenopathy (Rosai-Dorfman Disease):review of the entity. Seminars in Diagnostic Pathology 7:19-73.

Goodnight, J. W., Wang, M. B., Sercarz, J. A., Fu, Y. S. (1996)Extranodal Rosai-Dorfman Disease of the head and neck.Laryngoscope 106: 253-256.

Hammond, L. A., Keh, C , Rowlands, D. C. (1996) Rosai-Dorfman disease in the breast. Histopathology 29: 582-584.

Horneff, G., Jurgens, H., Hort, W., Karitzy, D., Gobel, U.(1996) Sinus histiocytosis with massive lymphadenopathy(Rosai-Dorfman disease): response to methotrexate andmercaptopurine. Medical and Pediatric Oncology 27:187-192.

Komp, D. M. (1990) The treatment of sinus histiocytosis withmassive lymphadenopathy (Rosai-Dorfman disease).Seminars in Diagnostic Pathology 7: 83-86.

Levine, P. H., Jahan, N., Murari, P., Manak, M., Jaffe, E. S.(1992) Detection of human herpesvirus 6 in tissues involvedby sinus histiocytosis with massive lymphadenopathy(Rosai-Dorfman Disease). Journal of Infectious Diseases166: 291-295.

McAlister, W. H., Herman, T., Dehner, L. P. (1990) Sinushistiocytosis with massive lymphadenopathy (Rosai-Dorf-man Disease). Paediatric Radiology 20: 425^432.

Naidu, R. K., Urken, M. L., Som, P. M., Danon, A., Biller,H. F. (1990) Extranodal head and neck sinus histiocytosiswith massive lymphadenopathy. Otolaryngology - Headand Neck Surgery 102: 764-767.

Rosai, J., Dorfman, R. F. (1969) Sinus Histiocytosis withmassive lymphadenopathy: a newly recognised benignclinicopathological entity. Archives of Pathology 87: 63-70.

Rosai, J., Dorfman, R. F. (1972) Sinus histiocytosis withmassive lymphadenopathy: A pseudolymphomatous benigndisorder. Analysis of 34 cases. Cancer 30: 1174-1188.

Trautman, B. C, Stanley, M. W., Goding, G. S., Rosai, J.(1991) Sinus histiocytosis with massive lymphadenopathy(Rosai-Dorfman Disease): diagnosis by fine needle aspira-tion. Diagnostic Cytopathology 7: 513-516.

Address for correspondence:Dr A. C. Bateman,Department of Histopathology,Level E, South Block,Southampton General Hospital,Tremona Road,Southampton SO16 6YD.

Fax: 01703 796869