Journal of Cytology
Home About us Ahead of print Instructions Submission Subscribe Advertise Contact e-Alerts Login 
Users Online:350
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size

 Table of Contents    
Year : 2011  |  Volume : 28  |  Issue : 3  |  Page : 131-133
Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement

1 Department of Pathology, G.S.V.M. Medical College, Kanpur, India
2 Department of General Surgery, G.S.V.M. Medical College, Kanpur, India

Click here for correspondence address and email

Date of Web Publication4-Aug-2011


Rosai-Dorfman disease, that is, sinus histiocytosis with massive lymphadenopathy is a benign systemic proliferative disorder of histiocytes. The typical clinical presentation of the disease includes bilateral painless massive lymphadenopathy, fever and polyclonal hypergammaglobulinemia. Extranodal involvement is present in only a few cases and skin lesions are the most common form of extranodal disease. However, purely cutaneous Rosai-Dorfman disease is uncommon. In this study, we describe a 10-year-old child presenting with bilateral ocular involvement.

Keywords: Extranodal; histiocytes; S-100 protein; fine needle aspiration cytology

How to cite this article:
Kala C, Agarwal A, Kala S. Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement. J Cytol 2011;28:131-3

How to cite this URL:
Kala C, Agarwal A, Kala S. Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement. J Cytol [serial online] 2011 [cited 2022 Dec 5];28:131-3. Available from:

   Introduction Top

 Rosai-Dorfman Disease More Details is a benign systemic histioproliferative disease characterised clinically by massive bilateral cervical lymphadenopathy, fever, leukocytosis, raised erythrocyte sedimentation rate and pathologically by hyperplastic lymph node sinuses containing large histiocytosis with intact phagocytosed lymphocytes (emperipolesis). [1]

Sinus histiocytosis with massive lymphadenopathy (SHML) is generally a benign disorder in spite of its propensity to form large masses and to involve both nodal and extranodal site in 10% of the cases; skin and subcutaneous tissue being most common followed by soft tissue, upper respiratory tract, salivary gland oral cavity and genitourinary system. [1],[2],[3]

   Case Report Top

An otherwise healthy 10-year-old boy sought treatment for bilateral diffuse eyelid swelling of a few months duration. Clinical examination reveals no lymphadenopathy or other detectable abnormalities. Other laboratory tests were within normal limits. Fine needle aspiration cytology (FNAC) revealed diffusely distributed histiocytes and a few histiocytes showing emperipolesis [Figure 1]. Histiocytes had single, with occasionally multiple, nuclei, fine evenly distributed chromatin and abundant pale eosionophilic cytoplasm. Background had mature lymphocytes, plasma cells and occasional neutrophils; hence, diagnosis of extranodal Rosai-Dorfman disease was made. Biopsy was sent for histopathological examination.
Figure 1: FNA smears showing lymphocytes and histiocyte showing emperipolesis (H and E, x400)

Click here to view

Microscopic examination revealed sheets of polymorphous infiltrate in which lymphocytes and histiocytes with voluminous pale eosinophilic cytoplasm with indistinct cytoplasmic borders were the most prominent [Figure 2]. Several histiocytes contained lymphocytes in the cytoplasm, that is, showed emperipolesis [Figure 3]. A few multinucleated histiocytes, occasional plasma cells, neutrophils and rare eosinophils were also seen. Vascular channels surrounded by lymphocytes were also observed. Immunohistochemistry showed positivity to S-100 protein [Figure 4].
Figure 2: Histology showing dark-staining lymphocyte admixed with pale sinusoidal histiocytes (H and E, x100)

Click here to view
Figure 3: Lymphocytes and sinusoidal histiocytes showing emperipolesis at higher magnification (H and E, x400)

Click here to view
Figure 4: Histiocytes showing cytoplasmic positivity for S-100 (Peroxidase-antiperoxidase stain, x 100)

Click here to view

   Discussion Top

Since the original description, the Rosai-Dorfman disease has become a rare but distinct clinico-pathological entity of idiopathic proliferation of histiocytes. It is currently defined as a unique histiocyte, which are large cell containing vesicular nucleus and voluminous cytoplasm, exhibiting lymphophagocytosis (emperipolesis). [1],[2] It may affect any age group or any gender, without racial predilection, but 80% of the patients are aged 20 years or younger at onset. Most patients are characterized by bilateral painless massive lymphadenopathy with or without constitutional manifestation. Because of gradual awareness, more and more extranodal cases have been documented which manifested at least one extranodal site of involvement. Moresoever, extranodal disease may be the initial and sole manifestation of the disorder, making the eponym Rosai-Dorfman disease more appropriate than the original term SHML. [4]

Foucar et al.[2] considered the presence of emperipolesis and S-100 protein expression by the histiocytes with feathery borders to be diagnostic of Rosai-Dorfman disease. These histiocytes also showed positive immunostaining for CD11c, CD14, CD33 and CD68 antigens. [5]

Cytological features of Rosai-Dorfman disease revealed large voluminous histiocytes showing evidence of emperipolesis and lying against a mixed inflammatory background of lymphocyte, plasma cells and occasional neutrophils. Only a few well documented cases diagnosed by FNAC have been reported. [6]

To date, most authors have speculated that the histiocytes of Rosai-Dorfman disease probably derived from circulating monocytes and a sort of distinctive activated histiocytes with coexpression of partial immunophenotypic character of both monocyte/macrophage system and dendritic/Langerhans cell family. [7]

Cutaneous Rosai-Dorfman disease differs histologically from nodal disease in that there is a greater degree of fibrosis, fewer histiocytes and diminished emperipolesis. Hence, cutaneous Rosai-Dorfman disease can be overlooked if the index of suspicion for the disease is low. On morphological ground, the recognition of cutaneous form of Rosai-Dorfman disease should consider a variety of disease in the differential diagnosis including eruptive xanthoma, Langerhans cell histiocytosis, reticulohistiocytoma, juvenile xanthogranuloma, Hodgkin's lymphoma, malignant histiocytosis as well as inflammatory pseudotumor. [2]

The exact etiology of Rosai-Dorfman disease is not known. An underlying immune dysfunction has been postulated. Possibility of viruses like Human Herpes Virus 6, Klebsiella, Epstein-Barr virus, Cytomegalovirus or  Brucella More Details as a causative agent have been postulated. [5],[8]

Rosai-Dorfman disease usually follows a course of spontaneous regression and recovery; however, in a small percentage of cases, the disease may be persistent and progressive, associated with widespread dissemination and involvement of the kidney, lower respiratory tract or liver. When Rosai-Dorfman disease is limited to the skin, most reports [2] indicate a favorable long-term prognosis with spontaneous regression.

Most of the cutaneous lesions generally do not require any further treatment, although roentgen therapy has been described as a useful therapeutic modality when the cutaneous disease runs a prolong course or when the lesions are aesthetically unacceptable to the patient. [9]

   References Top

1.Rosai J, Dorfman RF. Sinus histiocytosis withmassive lymphadenopathy: A newely recognized benign clinicopathological entity. Arch Pathol 1969;87:63-70.  Back to cited text no. 1
2.Foucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman Disease): review of the entity. Semin Diagn Pathol 1990;7:19-73.  Back to cited text no. 2
3.Abdollahi A, Ardalan FA, Ayati M. Extranodal Rosai-Dorfman disease of the kidney. Ann Saudi Med 2009;29:55-7.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
4.Warnke RA, Weiss LM, Chan JK, Cleary ML, Dorfman RF. Atlas of tumor pathology. Tumors of lymph nodes and spleen. AFIP, Third series, Fascicle 4. Washington DC, USA: Juan-Rosai; 1994. p. 349-59.  Back to cited text no. 4
5.Kumar B, Karki S, Paudyal P. Diagnosis of sinus histiocytosis with massive lymphadenopathy (Rosai- Dorfman disease) by fine needle aspiration cytology. Diagn Cytopathol 2008;36:691-5.  Back to cited text no. 5
6.Kushwaha R, Ahluwalia C, Sipayya V. Diagnosis of sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease) by fine needle aspiration cytology. J Cytol 2009;26:83-5.  Back to cited text no. 6
  Medknow Journal  
7.Chu P, Lebiot PE. Histologic features of cutaneous sinus histiocytosis (Rosai Dorfman disease): study of cases both with and without systemic involvement. J Cutan Pathol 1992;19:201-6.  Back to cited text no. 7
8.Levine PH, Jahan N, Murani P, Manak M, Jaffe ES. Detection of Human herpes virus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease). J Infect Dis 1992;166:291-5.  Back to cited text no. 8
9.Annessi G, Giannetti A. Purely cutaneous Rosai- Dorfman disease. Br J Dermatol 1996;134:749-53.  Back to cited text no. 9

Correspondence Address:
Chayanika Kala
L-21, G.S.V.M. Medical College, Kanpur, U.P - 208 002
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.83473

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

This article has been cited by
1 Extranodal Intracranial Rosai-Dorfman-Destombes Disease in Children: a Literature Review
Tena Trbojevic, Lorna Stemberger Maric, Nina Barišic
SN Comprehensive Clinical Medicine. 2020; 2(4): 414
[Pubmed] | [DOI]
2 Cutaneous Hematolymphoid and Histiocytic Proliferations in Children
Alejandro A Gru,Louis P Dehner
Pediatric and Developmental Pathology. 2018; 21(2): 208
[Pubmed] | [DOI]
3 Multifocal cutaneous Rosai-Dorfman disease masquerading as lupus vulgaris in a child
Aastha Gupta,Pooja Arora,Meenakshi Batrani,Prafulla Kumar Sharma
Anais Brasileiros de Dermatologia. 2018; 93(5): 766
[Pubmed] | [DOI]
4 Histopathological and Clinical Findings in Cutaneous Manifestation of Erdheim–Chester Disease and Langerhans Cell Histiocytosis Overlap Syndrome Associated With the BRAFV600E Mutation
Julia Liersch,J. Andrew Carlson,Jörg Schaller
The American Journal of Dermatopathology. 2017; 39(7): 493
[Pubmed] | [DOI]
5 Cytological diagnosis of Rosai-Dorfman disease: A case report and revision of the literature
Raquel Garza-Guajardo,Laura Elvira García-Labastida,Iram Pablo Rodríguez-Sánchez,Gabriela Sofía Gómez-Macías,Iván Delgado-Enciso,María Marisela Sánchez Chaparro,Oralia Barboza-Quintana
Biomedical Reports. 2017; 6(1): 27
[Pubmed] | [DOI]
6 Extra Nodal Rosai–Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy) Presenting as Asymmetric Bilateral Optic Atrophy
Eesha Shukla,Anjali Nicholson,Anamika Agrawal,Darshana Rathod
Head and Neck Pathology. 2016; 10(3): 414
[Pubmed] | [DOI]
7 Intraocular xanthomatous tumor presenting as fulminant uveitis
C-Y Cheng,P-Y Chen,C-J Lin
Eye. 2015; 29(2): 296
[Pubmed] | [DOI]
8 Cutaneous Rosai-Dorfman disease: A propos of a case [Enfermedad de Rosai-Dorfman cutánea: A propósito de un caso]
Cruz-Camejo, Y. and Burgos-Aragüez, D. and Flores-Veja, Y. and cáceres-Lavernia, H.H. and Jiménez-Galainena, J. and Curbelo-Heredia, I.
Revista Cubana de Hematologia, Inmunologia y Hemoterapia. 2013; 29(1): 90-98
9 Rosai-Dorfman disease presenting as choroidal melanoma: A case report and review of the literature
Vermeulen, T.L. and Isaacs, T.W. and Spagnolo, D. and Amanuel, B.
Graefeæs Archive for Clinical and Experimental Ophthalmology. 2013; 251(1): 295-299
10 Synchronous subcutaneous and calvarial Rosai-Dorfman disease diagnosed on fine needle aspiration cytology
N. Ghosal,S. V. Furtado,S. Thakar,S. P. Kumaran
Cytopathology. 2013; : n/a
[Pubmed] | [DOI]
11 A Case of Rosai-Dorfman Disease Affecting the Palpebral Conjunctiva
Jae Yeun Lee,Hyun Min Shin,Helen Lew
Journal of the Korean Ophthalmological Society. 2013; 54(2): 346
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded131    
    Comments [Add]    
    Cited by others 11    

Recommend this journal