Rosai- Dorfman Disease (Sinus histiocytosis with massive lymphadenopathy) A Case Report

Oral Pathology Case Report

A. V. Asanka De Silva D/05/10

2011

FACULTY OF DENTAL SCIENCES- UNIVERSITY

OF

PERADENIYA

Rosai- Dorfman Disease A Case Report

Rosai- Dorfman Disease (Sinus histiocytosis with massive lymphadenopathy) A Case Report

area diagnosed as Rosai-Dorfman disease after histopathological analysis of the excision biopsy. Currently on follow up after 3rd month post operatively. Key words: emperipolesis, Rosai Dorfman disease, sinus histiocytosis with massive lymphadenopathy, nodal, head and neck.

Abstract
Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis with massive lymphadenopathy is a rare disease of unknown aetiology. First described in 1969 with painless cervical lymph node enlargement in association with fever, weight loss and sweating. 43% of cases were reported extra nodally that commonly involving skin, upper airway, and salivary glands . RDD is usually seen in young patients. Cutaneous lesions are the common form of extranodal diseases, but cases of purely cutaneous lesions without nodal or other extranodal involvement are rare, Proliferation of large pale or foamy histiocytes exhibiting enlarged vesicular nuclei, prominent nucleoli, and distinctive lymphophagocytosis or emperipolesis is the basis of the diagnosis. S-100 protein immunophenotype is useful in confirming the disease entity. This case report is about a 52 yrs old male patient presented with asymptomatic diffuse swelling on left side pre auricular
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Introduction
Rosai-Dorfman disease (RDD) is a benign systemic proliferative disorder of histiocytes resembling the sinus histiocytes of lymph nodes. The typical clinical features of this disease include bilateral painless lymphadenopathy, fever, and polycolonal hyperglobulinaemia. The condition with the head and neck involvement reported in 22% of cases, most commonly the nasal cavity followed by the parotid gland 10. Extranodal involvement in 43% (500 pts) of cases, and cutaneous lesions are the most common form of extranodal diseases. The disease is not confined to a particular race or geographical area, although African Negroes are more commonly involved than whites9. Purely cutaneous RDD occur rarely, particularly among Orientals10. Nodal lesions are classified as an inflammatory/hyperplasic disorder which usually undergoes spontaneous regression; extranodal lesion natural history is

Rosai- Dorfman Disease A Case Report

associated with indolent growth and recurrences along years or decades. It is often confused with lymphoma.

where FNAC was done. Microscopically FNAC smear reveal mixed lymphoid cells and many macrophages with engulfed debris and, no oncocytic cells or atypical

RDD First described in 1969 with painless cervical lymph node enlargement in association with fever, weight loss and sweating that commonly affects children and adolescents. The most common sites affected are the soft tissues of the head and neck and the paranasal sinuses and nasal cavity 10-4.

cells were seen. The report concluded giving differential diagnosis as reactive lymph node and Warthins tumour. Then he attended to Dental Institute Colombo for his convenience. On examination firm, non tender swelling apprx.34 cm with demarcated margins on palpation was noted on the left side angle of the mandiblular region extending to sub

Case report
A 52 year old male presented to the dental institute Colombo (DIC) with an asymptomatic swelling on lower left side of the cheek for 2 months duration (first noted in November 2010). This lesion had a sudden onset and the size of the lesion gradually increased with time. He first got treatment from general hospital Mathra

mandibular region.[figure 1] He had history of leptospirosis 5years back and no relevant family history.

Following investigations were done.WBC/DC and blood picture were normal, ESR was slightly elevated (24mm/h), FNAC concluded as inflammatory lesion and suggested histology, Ultra sound scan left side neck suggested Warthins tumour and MRI suggested biopsy. There were no radiological abnormalities. Differential diagnosis at surgery was tuberculosis or lymphoma. The lesion was excised including level one lymph nodes and sent for histopathological examination on 27/02/2011. Mantoux test was done later and the result was negative.

Figure 1

Rosai- Dorfman Disease A Case Report

Figure 2 Macroscopic appearance of the lesion

Figure 4- Immunoreactivity for S-100

Macroscopically lesions presented as soft nodule and a lymph node. Microscopic examination of the lymph node [Figure 3] and the lesion revealed partial effacement of architecture with marked capsular fibrosis and sinus histiocytosis. Emperipolesis of lymphocytes and plasma cells is marked immunehistochemically histiocytes showed nuclear and cytoplasmic positivity for S-100 protein [figure 4]. The histopathological examination confirmed the diagnosis Rosai- Dorfman Disease After the surgery patient was on antibiotics [IV augmentin 1.2g tds] to prevent infection and analgesics on normal regimes. Patient is currently on review appointments without any complaints.

Discussion
Rosai-Dorfman disease (RDD) or Sinus histiocytosis with massive lymphadenopathy is a rare benign systemic proliferative disorder of unknown aetiology. RDD belongs to broad family of disorders known as lympho reticular disorders which consist of 1.Reactive changes caused by infection and inflammation 2.Autoimmune disorders3.Immunosupression and 4.Neoplasia. Reactive hyperplasia is one of the disease sub types that belong to Reactive disorders of lymph nodes which consist of following categories 1.Follicular hyperplasia in a predominantly humoral response there is a hyperplasia of the cortical follicles manly composed of B lymphocytes. With development of B cell germinal centres. 2.Parafollicular/ paracoticle hyperplasia - in a predominantly cell mediated response there is a hyperplasia of the

Figure 3 Histiocyte cells (H&E, 40)

Rosai- Dorfman Disease A Case Report

paracortical follicles manly composed of T lymphocytes. 3. Sinus hyperplasia/ sinus histiocytosis -Certain stimuli evoke intense phagocytic activity leading to dilatation of subacapsular and medullary sinuses with increased numbers and activity of macrophages and phagocytic lining cells. This reaction is seen in nodes draining tissues from which endogenous particulate matters such as lipid is released. e.g. Necrotic tumour It is characterised by overproduction of histiocytes or tissue macrophages. This condition was first described by RobbSmith in children and was termed as giant cell sinus reticulosis in 19479. Sinus histiocytosis with massive lymphadenopathy (SHML) has been recognized as a distinct clinicopathological entity, though first given this name by Rosai and Dorfman in 1969. Incidences very rare, probably less than 1000 cases reported in the literature. The disease is not confined to a particular race or geographical area, although African Negroes are more commonly involved than whites9, 17. Although RDD may occur in any age group, it is most frequently seen in children and young adults14. More than two thirds of registry patients are younger than 10 years. Patients presenting with isolated intracranial disease tend to be older4. The disease is more common in

males16 ranging from 1.4:1 to 3:18, 17. Although there is no evidence on aetiology but viruses like Herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV) have been suggested as potential causative agents6. The natural history is that of a regression and resurgence followed eventually by complete resolution. The clinical picture of RDD is hardly distinguishable from malignant lymphomas which histopathology usually comes as a surprise9. Head and neck involvement has been reported in 22% of cases; most commonly the nasal cavity followed by the parotid gland14, the paranasal sinuses, the nasopharynx, submandibular glands,the larynx, the temporal bone, the intratemporal fossa, the pterygoid fossa, the meninges and the orbit are the other possible sites.Because of gradual awareness of this disease entity, more and more extranodal cases with or without nodal involvement had been documented. To date, extranodal RosaiDorfman diseases are still on the rise and accounted for approximately 43% of 600 registry cases, which manifested at least one site of extranodal involvement12. Clinical Features in most typical forms are painless, bilateral, lymph node enlargement in neck associated with fever, leukocytosis, elevated erythrocyte sedimentation rate in 88.5% of cases,

Table-1
Rosai- Dorfman Disease A Case Report

Classical cases of RDD Clinical features painless, bilateral, lymph node enlargement Fever leukocytosis Elevation in ESR Autoimmune haemolysis

This case

Painless Unilateral lymph node enlargement Fever absent No leukocytosis ESR slight elevation Autoimmune haemolysis absent

Classical histopathology Emperipolesis Moderately abundant plasma cells and lymphocytes Effacement of involved organ architecture Positivity for CD68, alpha -1 antitrypsin,s-100, cathepsin E

In this case Emperipolesis marked Moderately abundant plasma cells and lymphocytes Partial effacement of lymph node architecture Positivity being checked for S-100 and positive results gained.

polyclonal hypergammaglobulinaemia. Autoimmune hemolysis can also occur. Most common sites involving are eyes and ocular adnexa (especially orbit), head and neck region, upper respiratory tract, skin and subcutaneous tissues, skeletal system and central nervous system. Other sites are gastrointestinal tract, salivary glands, genitourinary tract, thyroid, breast and uterine cervix. There are different clinical presentations in RDD in head and neck region that reported as Neck mass, facial swelling, Eye swelling, facial pain, Headache and Ataxia, difficulty walking and falls.

The differential diagnosis of extranodal SHML may be a challenge15. Comparison of classical clinical case with this case done in table- 1Imaging (CT and magnetic resonance imaging) may be used to assess disease extension. If there is cervical lymph node enlargement, FNAB or lymph node biopsies may be useful for the diagnosis11.The final diagnosis of RDD usually made on characteristic histopathological and cytological features. La Barge et al presented a case series of 13 patients with RDD in head and neck region in 2008 that was reported within 1997 20075. Table 3 gives the summery.

Rosai- Dorfman Disease A Case Report

Table-2

Deferential diagnosis Hodgkins lymphoma Langerhans cell histiocytosis

Rosai-Dorfman disease Atypical monocytes, Reed-Sternberg cells + Emperipolesis absent, Birbeck granules identified by electron microscopy

Inflammatory pseudotumor

Emperipolesis absent, positivity for S-100 protein rare

Malignant histiocytosis and lymphoma with feature of malignant histiocytosis Hemophagocytic syndrome associated with Tcell lymphoma and/or viral infection Eruptive xanthoma Generalized eruptive histiocytoma Juvenile xanthogranuloma Inflammatory malignant fibrous histiocytoma Lepromatous leprosy

Atypia, cellular pleomorphism

Lymphomatous infiltrate, lobular panniculitis, negativity for S-100 protein Emperipolesis and plasma cells absent

Atypia, cellular pleomorphism Poorly defined infiltrate, plasma cells rare, positivity for organisms on Fite stain The characteristic histopathological feature

The cells have histochemical and phenotypic features of macrophages. Large amounts of esterases and acid phosphatase are contained by the cells. Show positivity for CD 68 and alpha-1 antitrypsin. They also exhibit some of the phenotypic features of dendritic cells such as S100, cathepsin E, fascin and at times CD 1a.6, 71, 8, 13. Skin biopsy non-specific unless emperipolesis is present but lymph node pathology is characteristic. emperipolesis is the presence of an intact cell within the cytoplasm of another cell.

of RDD is the proliferation of distinctive histiocytic cells that demonstrate lymphophagocytosis in the background a mixed inflammatory infiltrate consisting of moderately abundant plasma cells and lymphocytes. As a result effacement of involved organ architecture leading to fibrous band formation can be noted19. No Birbeck granules. Birbeck granules are a characteristic microscopic finding in Langerhans cell histiocytosis (Histiocytosis X), which present as shaped or "tennis-racket" cytoplasmic organelles

Rosai- Dorfman Disease A Case Report

Age 2.5

Sex M

Clinical presentation Neck masses, autoimmune haemolytic Anaemia

Location of the disease involvament Nodal

5 38 30 33 56 75

F M F M M M

Neck masses Neck mass Neck mass, elevated ESR Neck mass, facial swelling Neck masses Left parotid and left neck mass

Nodal Nodal Nodal and extranodal Nodal and extranodal Nodal and extranodal Nodal and extranodal

12 51 68

F M M

Right eye swelling Left-sided headaches Difficulty walking, ataxia, falls

Nodal and extranodal Extranodal without lymphadenopathy Extranodal without lymphadenopathy

20 22

F F

Facial pain Right cheek mass, sinus disease, no palpable lymph enlargement

Extranodal without lymphadenopathy Extranodal without lymphadenopathy

19 Table- 3

Facial swelling, sinus disease

Extranodal without lymphadenopathy

with a central linear density and a striated appearance. The differential diagnosis is made with lymphoreticular malignancies such as lymphomas, Hodgkin's disease, malignant histiocytosis and monocytic leukaemia, all of which have similar histopathological features. Atypias in cytology and the aggressive clinical course establish the diagnosis in most cases. Other histiocytoses, such as rhinoscleromas, Wegener's granulomatosis, may also be included in the differential diagnosis (Table-2).Although in most patients the extent of SHML does not appear to determine disease outcome, recent reports have documented that infiltrates of SHML can cause death.

Rosai- Dorfman Disease A Case Report

Management of the Rosai-Dofman disease has no ideal protocol, because it is an uncommon, self-limited disease, frequently requires no therapy. When lymph node or extranodal tissue enlargement causes significant symptoms, such as airway obstruction or compression of vital organs treatment is mandatory. Pulsone at al. reviewed 80 cases published between 1969 and 2000; 50% of these cases required no treatment, of which 82% had full remission18.The role of surgery is mostly for biopsies and to relieve obstruction. Local recurrence is frequent following surgical resection. The role of radiotherapy is not well understood; some reports have described full resolution with this treatment, while others have shown no response1. Steroids often resolve fever and reduce lymph node size. Chemotherapy has yielded controversial results. Further investigations need to study the possible efficacy of methotrexate and 6mercaptopurine. Use of alpha-interferon has been limited because of its side effects. Higher mortality rate is seen in patients with immunological abnormalities at or before presentation. If a diagnosis of RosaiDorfman disease is made, the patient can be initially observed with the hope of spontaneous remission. For tumours exclusively located in an anatomic site amenable to surgery,

surgical excision may be considered when: (i) the lesion persists or recurs; (ii) cytologic findings are inconclusive; or (iii) the patient has symptoms or desire for removal. References 1. Carpenter RJ III, Banks PM, Mc Donald TJ, Sanderson DR. Sinus histiocytosis with massive Lynphadenopathy (Rosai-Dorfman disease): Report of a case with respiratory tract involvement. Laryngoscope 1978;88:1963-9. 2. Cheng SP, Jeng KS, Liu CL. Subcutaneous Rosai-Dorfman disease: is surgical excision justified? J Eur Acad Dermatol Venereol. 2005;19:747-50. 3. Chu P, LeBoit PE. Histologic features of cutaneous sinus histiocytosis (Rosai-Dorfman disease): study of cases both with and without systemic involvement. J Cutan Pathol 1992; 19: 201206. 4. Deodhare SS, Ang LC, and Bilbao JM. Isolated intracranial involvement in Rosai-Dorfman disease: a report of two cases and a review of the literature. Arch Pathol Lab Med 1998; 122: 161165.

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5. Donald V. La Barge III,Karen L. Salzman,H. Ric HarnsbergerSinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease): Imaging Manifestations in the Head and Neck AJR:191; December 2008;299-306. 6. Eiras JC, Schettini APM, de Lima LL. Cutaneous Rosai-Dorfman disease ; a case report. An Bras Dermatol. 2010;85(5):687-690 7. Eisen R N, Buckley PJ, Rosai J: Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai- Dorfman disease): Semin Diagn Patho 1990;7:74. 8. Foucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol 1990; 7:1973 9. GULL MOHD BHAT, SURENDER KUMAR, ATUL SHARMA, Rosaidorfman disease : a case report with review of literature. Indian journal of medical & paediatric oncology 2004 vol. 25 no.4; 39-41.

10. H Y Huang,, C L Yang, W J Chen Rosai-Dorfman Disease with Primary Cutaneous ManifestationsA Case Report,Ann Acad Med Singapore 1998; 27:589-93 11. Hazarika P, Nayak DR, Balakrishnan R, Kundaje HG, Rao PL. Rosai-Dorfman disease of the subglottis. J Laryngol Otol 2000; 114:970-3. 12. Huang HY, Yang C L, Chen W J Rosai-Dorfman Disease with Primary Cutaneous ManifestationsA Case Report Annals Academy of Medicine July 1998, Vol. 27 No. 4: 589-91. 13. Jaffe R,Vaughan De.,Langhoff E:Fascin and differential diagnosis of childhood histiocytic lesions. Pediatrol &Dev Pathol 1998;1:216. 14. Juskevicius R, and Finlay JL. Rosai-Dorfman disease of the parotid gland, cytologic and histopathologic findings with immunohistochemical correlation. Arch Pathol Lab Med 2001; 125: 1348-1350.

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15. Kroumpouzos G, Demierre M. F. Cutaneous Rosai-Dorfman Disease: Histopathological Presentation as Inflammatory Pseudotumor: A Literature Review. Acta Derm Venereol 2002; 82: 292296. 16. Lauwers GY, Perez-Atayde A, Dorfman RF, et al. The digestive system manifestations of RosaiDorfman disease (sinus histiocytosis with massive lymphadenopathy): review of 11 cases. Hum Pathol 2000; 31: 380385. 17. McAlister WH, Herman T, Dehner LP. Sinus histiocytosis with massive lymphadenopathy (RosaiDorfman disease). Pediatr Radiol 1990; 20:425432 18. Pulsoni A, Anghel G, Falcucci P, Matera, R Pescarmona, Ribersani M: Treatment of Sinus Histiocytosis Whit Massive Lynfadenopathy (Rosai-Dorfman Disease): Report of a case and literature Review. Am J Hematol 2000; 69:61-71. 19. Siriwardena . B.S.M.S., Tilakaratne W.M., Amaratunga E.A.P.D, Peiris A.M.O.A case report of Rosai Dorfman Disease of the parotid gland Sri Lanka

Journal of Medicine 2004; 13(02) 41-43 Acknowledgement I would be gratefully acknowledging the collaboration of Dr. A. M.O Peiris for providing assistance in making this project a reality and Dr. Amith and Dr. Samadara Siriwardena for providing valuable information, photographs for the project report. I would give my sincerer gratitude for the academic staff of the department of oral pathology Prof. W.M Thilakarathne, Prof. E. A. P. Amarathunga, Dr.Primali jayasooriya, and Dr. Samadara Siriwardena for sharing their priceless knowledge and precious experience. Last but not least I thank for all who contributed including dental library staff, technicians.

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