Journal of Cytology
Home About us Ahead of print Instructions Submission Subscribe Advertise Contact e-Alerts Login 
Users Online:129
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size

CASE REPORT Table of Contents   
Year : 2009  |  Volume : 26  |  Issue : 2  |  Page : 83-85
Diagnosis of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease) by fine needle aspiration cytology

Department of Pathology, Safdarjung Hospital and VMMC, New Delhi, India

Click here for correspondence address and email

Date of Web Publication26-Aug-2009


Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a rare benign disease of unknown etiology presenting with massive lymphadenopathy. These cases can often be misdiagnosed as lymphoma. Hence, it is important to distinguish Rosai-Dorfman disease from lymphoma and other causes of histiocytosis because of the different treatment modalities. We report here a case of Rosai-Dorfman presenting with massive bilateral cervical lymphadenopathy. We conclude that fine needle aspiration cytology is a useful and reliable tool for the diagnosis of Rosai-Dorfman disease due to which biopsy can be avoided in these patients, thus, reducing inconvenience to patients.

Keywords: Emperipolesis; fine needle aspiration cytology; sinus histiocytosis with massive lymphadenopathy.

How to cite this article:
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

How to cite this URL:
Kushwaha R, Ahluwalia C, Sipayya V. Diagnosis of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease) by fine needle aspiration cytology. J Cytol [serial online] 2009 [cited 2022 Dec 7];26:83-5. Available from:

   Introduction Top

Sinus histiocytosis with massive lymphadenopathy (SHML), is a benign, self-limiting disorder that commonly involves the lymph nodes. [1] First described by Rosai and Dorfman in 1969, many more cases have been added to the literature but the cytomorphology has been documented in relatively few cases. [2] It is characterised by painless, bilateral, cervical lymphadenopathy accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate (ESR), and hypergammaglobulinemia. [1] Other lymph nodes as well as extranodal sites such as the eyes and ocular adnexa, head and neck, upper respiratory tract, skin, subcutaneous tissue, bone, skeletal muscle, central nervous system, gastrointestinal tract, salivary glands, genitourinary tract, thyroid, breast, liver, kidney, heart, uterine cervix, etc., may also be involved. [3] Whereas patients presenting with lymphadenopathy are commonly diagnosed as having malignant lymphomas, cases with extranodal involvement are suspected of having various neoplasms, depending on the site of involvement. [1]

Cytological features of SHML are virtually diagnostic and can obviate the need for a biopsy in most cases. [3]

   Case Report Top

A 23 year-old male presented in the fine needle aspiration cytology (FNAC) clinic with multiple, bilateral, soft to firm, nontender, upper, deep cervical and submandibular lymphadenopathy of eight months' duration, accompanied by low-grade fever. The lymph nodes had been gradually increasing in size and number during this period; there was no history of weight loss. Clinical examination showed multiple, enlarged, bilateral, cervical and submandibular lymph nodes, ranging in size from 1 x 1cm to 3 x 3 cm. They were nontender, discrete, firm, and mobile. The peripheral blood cell count showed leukocytosis (15,000/cu. mm) with neutrophilia. ESR was 40 mm at the end of one hour and the serum gammaglobulins were raised. Ultrasonography of the abdomen did not reveal any organomegaly; the patient was clinically diagnosed as having Hodgkin's lymphoma.

FNAC of the cervical nodes was performed from multiple sites. Smears were stained with giemsa stain and found to be cellular. Low-power microscopic examination revealed the presence of diffusely distributed histiocytes throughout the smears. These cells showed single to multilobated or multiple nuclei; no nuclear atypia or nuclear grooving was noted. Histiocytes had fine chromatin and inconspicuous to prominent nucleoli. These histiocytes had abundant pale cytoplasm and exhibited numerous intact lymphocytes (emperipolesis) and plasma cells [Figure 1]. A few histiocytes also showed the presence of neutrophils in their cytoplasm. In some histiocytes, the phagocytosed cells were so numerous that they obscured the nucleus. The background had mature lymphocytes, plasma cells, neutrophils, and tingible body macrophages. Based on this characteristic cytomorphology, a diagnosis of Rosai-Dorfman was made.

Subsequently, biopsy of a cervical lymph node was done wherein paraffin-embedded sections of lymph node biopsy showed fibrous thickening of the lymph node capsule and an altered nodal architecture. The sinuses were dilated and packed with large histiocytes having abundant pale cytoplasm and phagocytosed lymphocytes (emperipolesis), plasma cells, and occasional neutrophils.

The patient was put on steroids which resulted in marked clinical improvement.

   Discussion Top

SHML or  Rosai-Dorfman Disease More Details is a rare but well-defined, histiocytic, proliferative disorder of unknown etiology. Some investigators consider it to be of bone marrow stem cell origin. [1]

Most cases of SHML occur during the first or second decade of life. However, any age group may be affected; males are affected more than females. [3]

The clinical presentation of this entity, as described in the initial publications, consists of painless, bilateral, cervical lymphadenopathy associated with fever, leukocytosis, elevated ESR, and hypergammaglobulinemia, but a wide range of extranodal presentation has been noted in recent years. [1] Most common extranodal sites involved are the eyes and ocular adnexa, head and neck, upper respiratory tract including the nose, skin, subcutaneous tissue, bone, skeletal muscle, central nervous system, gastrointestinal tract, salivary glands, genitourinary tract, thyroid, breast, liver, kidney, heart, uterine cervix, etc. [3]

Exact pathogenesis of the disease is still not known. Theories implicating an infectious cause and immunodeficiency state have been suggested. The presence of human herpes virus 6 genome was demonstrated by in situ hybridization; [3] relationship with Klebsiella, Epstein-Barr virus,  Brucella More Details, or Cytomegalovirus were also suggested. [3],[4]

Our case was a young male who presented with multiple cervical and submandibular lymphadenopathy, fever, leukocytosis, hypergammaglobulinemia, and an elevated ESR. However, the possibility of Rosai-Dorfman disease was not considered until FNAC was performed.

Cytological features of SHML usually reveal numerous large histiocytes with abundant, pale cytoplasm, and phagocytosed lymphocytes (emperipolesis). The background typically shows lymphocytes, plasma cells, and occasional neutrophils [1],[2] [Figure 2]. These features were also present in our case.

Histiocytes show positive immunostaining for S100 protein; CD11c, CD14, CD33, and CD68 antigens in cytological smears. [3]

Although histological findings are well documented, there have been few reports on FNAC. [2]

Differential diagnoses include reactive sinus histiocytosis, malignant histiocytosis, hemophagocytic syndrome, tuberculosis, and lymphoma. [3]

In Langerhans cell histiocytosis, Langerhans cells have grooved and twisted nuclei and the background has eosinophilic microabscess. Reactive sinus histiocytosis shows loose clusters of histiocytes, accompanying which are reactive lymphocytes, germinal center cells, immunoblasts, and tingible body macrophages; emperipolesis is absent. Hemophagocytic syndromes should be differentiated from Rosai-Dorfman disease on the basis of the presence of hemophagocytosis, absence of emperipolesis, and the presence of pancytopenia and hepatosplenomegaly. Tuberculous lymphadenitis show epithelioid cell granuloma with or without caseous necrosis, which are absent in Rosai-Dorfman disease. [2],[3]

Smears from patients with Hodgkin's disease show lymphocytes, plasma cells, histiocytes, eosinophils, and  Reed-Sternberg cells More Details. In Rosai-Dorfman disease, Reed-Sternberg cells and eosinophils are not seen. [2],[3]

Thus, the cytomorphology of Rosai-Dorfman disease is so distinctive that it can be diagnosed by FNAC. FNAC is a reliable and sensitive means to establish conclusive diagnosis, obviating the need for biopsy.

   References Top

1.Das DK, Gulati A, Bhatt NC, Sethi RG. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Report of two cases with fine needle aspiration cytology. Diagn Cytopathol 2001;24:42-5.  Back to cited text no. 1    
2.Deshpande AH, Nayak S, Munshi MM. Cytology of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Diagn Cytopathol 2000;22:181-5.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.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. 3  [PUBMED]  [FULLTEXT]
4.Lampert F, Lennert K. Sinus histiocytosis with massive lymphadenopathy: Fifteen new cases. Cancer 1976;37:783-9.  Back to cited text no. 4  [PUBMED]  

Correspondence Address:
Rashmi Kushwaha
House No. F130/4, 2nd Floor, Gautam Nagar, New Delhi - 110 049
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.55229

Rights and Permissions


  [Figure 1], [Figure 2]

This article has been cited by
1 Histocytopathological diagnosis of Rosai–Dorfman disease: Case report
Zephania Saitabau Abraham, Zerd Francis, Advera Isaac Ngaiza, Aveline Aloyce Kahinga, Faustine Bukanu
Clinical Case Reports. 2022; 10(2)
[Pubmed] | [DOI]
2 Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman Disease) - A rare case of isolated axillary lympadenopathy diagnosed on FNAC
Vineet Banga
IP Journal of Diagnostic Pathology and Oncology. 2022; 7(3): 191
[Pubmed] | [DOI]
3 ROSE in Rosai–Dorfman–Destombes (RDD) disease: a cytological diagnosis
Santosh Tummidi, Hemant Kumar Singh, Prudhvinath A Reddy, Manda Sindhura, Navya Kosaraju, Arundhathi Shankaralingappa, Naresh P Kumar
European Journal of Medical Research. 2021; 26(1)
[Pubmed] | [DOI]
4 Rosai-Dorfman disease in 6-year-old child: Presentation, diagnosis, and treatment
Kalpana Giri, Ashok Baral, Niva Tiwari, Krishna Sagar Sharma
Clinical Case Reports. 2021; 9(9)
[Pubmed] | [DOI]
5 Rosai Dorfman Disease —A rare case of cervical lymphadenopathy
Insiyah Amiji, Ummulkheir Mohammed, Hajaj Salum, Emilia Karugaba, Luka Mkeni, Livin Mumburi, Anna Msafiri, Higgins Massawe
Clinical Case Reports. 2020; 8(12): 2712
[Pubmed] | [DOI]
6 A case of Rosai-Dorfman disease with many emperipolesis experienced by liquid-based cytology
Eriko NOSE, Keita MATSUKURA, Hiroshi ARAI, Toshikazu GONDO
The Journal of the Japanese Society of Clinical Cytology. 2020; 59(6): 320
[Pubmed] | [DOI]
7 Subdural haematoma mimics
M. Lim,S.W. Kheok,K.C. Lim,N. Venkatanarasimha,J.E. Small,R.C. Chen
Clinical Radiology. 2019; 74(9): 663
[Pubmed] | [DOI]
8 Generalized erythematous and scaly plaques and papules: a rare case of Rosai-Dorfman disease accompanied by multiple myeloma
Anoosh Shafiee,Soheila Nasiri
Anais Brasileiros de Dermatologia. 2018; 93(3): 432
[Pubmed] | [DOI]
9 Intraosseous Rosai-Dorfman disease diagnosed by touch imprint cytology evaluation: A case series
Avani A. Pendse,Sara E. Wobker,Kevin G. Greene,Scott V. Smith,Robert J. Esther,Leslie G. Dodd
Diagnostic Cytopathology. 2018; 46(1): 83
[Pubmed] | [DOI]
10 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]
11 Answers of catechism (Quiz 8)
Kenneth B. Calder, Wang Cheung, James N. Lampros, Mark R. Wick, Bruce R. Smoller
Indian Journal of Pathology and Microbiology. 2015; 63(3): 291
[Pubmed] | [DOI]
12 Rosai-Dorfman disease: A case report with extranodal thyroid involvement
Sonia Chhabra, Ruchi Agarwal, Shilpa Garg, Harpreet Singh, Sunita Singh
Diagnostic Cytopathology. 2012; 40(5): 447
[VIEW] | [DOI]
13 Rosai-Dorfman disease with extranodal thyroid involvement
Sonia Chhabra, Ruchi Agarwal, Shilpa Garg, Harpreet Singh, Sunita Singh
Diagnostic Cytopathology. 2011; : n/a
[VIEW] | [DOI]
14 Diagnosis of Rosai-Dorfman disease by fine needle aspiration cytology in a case with cervical lymphadenopathy and nasal mass
Jena, M.
Online Journal of Health and Allied Sciences. 2011; 10(2)
15 Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement
Kala, C., Agarwal, A., Kala, S.
Journal of Cytology. 2011; 28(3): 131-133
16 Rosai-dorfman disease
Santra, G., Das, B.K., Mandal, B., Kundu, S.S., Bandopadhyay, A.
Singapore Medical Journal. 2010; 51(10): e173-e175
17 Rosai-Dorfman Disease
Sharma, S., Bhardwaj, S., Hans, D.
JK Science. 2010; 12(4): 194-196


    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 Downloaded428    
    Comments [Add]    
    Cited by others 17    

Recommend this journal