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Year : 2015  |  Volume : 4  |  Issue : 3  |  Page : 168-170

Rosai-Dorfman disease

Department of Biochemistry, Grant Government Medical College, Mumbai, Maharashtra, India

Date of Web Publication16-Jul-2015

Correspondence Address:
Gangadhar M Chatterjee
Department of Biochemistry, Grant Government Medical College, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-344X.160892

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Rosai-Dorfman disease (RDD) also known as sinus histiocytosis with massive lymphadenopathy is an uncommon benign condition of histiocytes of unknown etiology, most often misdiagnosed as lymphoma. Patients have bilateral cervical lymphadenopathy with the variable clinical presentation. We report a 37-year-old male presenting with massive painless bilateral cervical lymphadenopathy, turned out to be RDD after several misdiagnoses.

Keywords: Emperipolesis, Rosai-Dorfman disease, sinus histiocytosis with massive lymphadenopathy

How to cite this article:
Chatterjee GM, Chandel RS, Kamble PJ. Rosai-Dorfman disease. Int J Health Allied Sci 2015;4:168-70

How to cite this URL:
Chatterjee GM, Chandel RS, Kamble PJ. Rosai-Dorfman disease. Int J Health Allied Sci [serial online] 2015 [cited 2023 Jun 7];4:168-70. Available from: https://www.ijhas.in/text.asp?2015/4/3/168/160892

  Introduction Top

 Rosai-Dorfman Disease More Details (RDD) or sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder of histiocytes of unknown etiology, first described by Reed and Azoury in 1966. Rosai and Dorfman later described it as a benign disease of histiocytes in 1966. [1] It is usually seen in early decades of life. Clinically, it had a varied presentation from fever and elevated erythrocyte sedimentation rate (ESR) to the involvement of eye or central nervous system. Lymph nodes other than cervical region such as mediastinal, axillary or inguinal can also be affected. [2] In this condition, there is a reactive proliferation of sinus histiocytes. Histopathology of lymph node shows engulfment of lymphocytes by sinus histiocytes, known as emperipolesis. The internalized lymphocytes are located within cytoplasmic vacuoles. There is progressive filling of lymph node sinuses with histiocyte and lymphocyte, which leads to the partial effacement of lymph node architecture. With the correct clinical context presence of foamy histiocytes prompts a differential diagnosis of RDD. It is considered as a constant feature with the great diagnostic importance, which distinguishes RDD from other rare causes of lymph node enlargement. [3] Immunohistochemistry helps in confirming the diagnosis by typical finding of positive S-100 and negative CD1a staining. [4] Here, we report a case of 37-year-old Indian male with RDD who was initially misdiagnosed as tubercular lymphadenitis and lymphoma, commonly encountered mistake while diagnosing this disease.

  Case report Top

A 37-year-old non-diabetic, non-hypertensive, non-reactive to HIV Indian male came with complaints of relapsing, remitting episodes of fever and painless swelling on both side of neck since last 8 months with loss of weight with no complaints of cough, shortness of breath. No history of tuberculosis in the family was present. Before attending Tertiary care Hospital, he took advice for the same from a private practitioner for 1-month. As the complaints did not subside, he went to a local hospital where he was suggested fine-needle aspiration cytology (FNAC) of the cervical lymph nodes. The FNAC report was suggestive of necrotizing granulomatous lymphadenitis likely to be of Koch's etiology, but Ziehl Neelsen staining did not reveal any acid-fast bacilli. On the basis of FNAC report, the patient was put on Category 1 directly observed treatment, short-course (DOTS) therapy for 6 months. During this DOTS therapy, patient had recurrent episodes of high-grade fever with the painless enlargement of lymph nodes [Figure 1].
Figure 1: Enlarged multiple cervical lymph nodes of the patient in resolving stage

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Even after completion of 6 months of DOTS treatment without any remission the patient came to our tertiary hospital. On physical examination, his height was 182 cm, weight 44 kg, and BSA 1.49. Bilateral cervical lymphadenopathy was noted. Local examination of bilateral multiple grossly enlarged cervical lymph node reveled to be firm, mobile, non-tender with smooth surface. The rest of ENT and other systemic examination was essentially normal.

Hematological and other Biochemical investigations were within limits except for increased C-reactive protein (26.6 mg/l, normal-0.8-1.5 mg/l). ESR was not raised and hypergammaglobulinemia not detected.

Chest X-ray and ultrasonography of whole Abdomen were normal. FNAC was repeated, which was suggestive of Hodgkins Lymphoma. The patient was advised whole body computed tomography scan but could not afford it. Biopsy of the cervical lymph node was performed which shows marked dilatation of lymph sinuses [Figure 2], packed with histiocytic cells with vacuolated or foamy cytoplasm, lymphophagocytosis, and emperipolesis with no Reed-Sternberg Cell or any evidence of malignancy [Figure 3]. Depending on this, the patient was suspected to be suffering from RDD (SHML). For confirmation of the diagnosis, Immunohistochemistry was done, which was positive for S-100 and negative for CD1a. This is consistent of RDD. The patient was explained about the disease and its prognosis. No drug treatment was initiated. Corticosteroid treatment was not immediately started and kept in reserve. By now the patient's condition has improved, and cervical lymphadenopathy has started to resolve. The patient is still under follow-up.
Figure 2: H and E stained sections of node showing dilated sinuses and multiple giant cells

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Figure 3: H and E stained sections of cervical lymph node showing emperipolesis

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India is endemic to tuberculosis. Hence, cases of cervical lymphadenopathy with fever are thought to be Tubercular lymphadenitis for which even treatment is initiated. It makes the diagnosis of this rare condition more difficult.

  Discussion Top

Rosai-Dorfman disease or SHML is an idiopathic, uncommon, usually self-limiting disease of histiocytes, mainly of young population, characterized by massive painless enlargement of cervical lymph nodes in most of the cases. 43% cases have more than one extranodal involvement with skin and soft tissue being most common extranodal site. [5] Though the etiology is unclear, some authors suggested a role of human herpes virus 6 (HHV-6) as a causative factor depending on the expression of HHV-6 antigen over histiocytes involved in RDD. [6] Other rare causes of lymph node enlargement are Castleman's disease, dermopathic lymphadenitis, mucocutaneous lymph node syndrome (Kawasaki's disease), histiocytic necrotizing lymphadenopathy (Kikuchi's disease), vascular transformation of lymph nodes and inflammatory pseudotumor of the lymph nodes. These could be the differential diagnosis in this case. In RDD, the most useful immunohistochemical marker is positivity of histiocytes for S-100 protein, which differentiates it from non-Hodgkin's lymphoma and negativity of CD1a and Birbeck granules. An infectious cause of lymph node involvement such as Histoplasma and Mycobacteria, Langerhans cell histiocytosis, histiocytic sarcoma, Hodgkin's lymphoma and melanoma are also few of the differential diagnoses of RDD. [7] Typical clinical features, hallmark pathological finding of emperipolesis and S-100 positivity points to the diagnosis of RDD. During our literature review, we found that RDD is self-limiting diseases with half of the cases require no treatment and more than 80% of patients have spontaneous and complete remission. [8],[9] Drug treatment of RDD is rather non-specific. Corticosteroids (prednisolone), chemotherapy with vinca alkaloid and 5-FU, low-dose interferon, and antibiotic therapy constitutes therapeutic options in RDD. In our case, the middle-aged male patient was suffering from massive cervical lymphadenopathy. It was associated with relapsing and remitting episodes of fever which made it more difficult to consider as RDD and favoring diagnosis of tubercular lymphadenitis though there was no bacteriological or radiological finding supporting it. Initial histopathology reports of FNAC were also inconclusive, rather misleading in this case. Later biopsy of cervical lymph gland showed emperipolesis (hallmark of the disease) with positive staining of S-100 protein, giving a conclusive diagnosis. The patient was explained about course and prognosis of the disease and kept under observation. During the follow-up, there was a regression of lymph nodes and no relapse of the febrile episode.

  Conclusion Top

Rosai-Dorfman disease is diagnosed based on clinical findings and confirmed by cytology and histopathology. In Indian scenario cervical lymphadenopathy (hallmark of RDD) is easily mistaken for tubercular etiology and malignancy. Physician and pathologists should have a high index of suspicion for RDD in the differential diagnosis of cervical lymphadenopathy.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol 1969;87:63-70.  Back to cited text no. 1
Jani PA, Banjan D. A case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome) from western India. Mcgill J Med 2008;11:156-9.  Back to cited text no. 2
Iyer VK, Handa KK, Sharma MC. Variable extent of emperipolesis in the evolution of Rosai Dorfman disease: Diagnostic and pathogenetic implications. J Cytol 2009;26:111-6.  Back to cited text no. 3
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Raja H, Subramanyam SG, Govindaraj S, Babu MK. A rare cause of massive lymphadenopathy. Indian J Surg Oncol 2011;2:212-4.  Back to cited text no. 4
Van Zander J. Cutaneous Rosai-Dorfman disease. Dermatol Online J 2004;10:12.  Back to cited text no. 5
Luppi M, Barozzi P, Garber R, Maiorana A, Bonacorsi G, Artusi T, et al. Expression of human herpesvirus-6 antigens in benign and malignant lymphoproliferative diseases. Am J Pathol 1998;153:815-23.  Back to cited text no. 6
McClain KL, Natkunam Y, Swerdlow SH. Atypical cellular disorders. Hematology Am Soc Hematol Educ Program 2004;1:283-96.  Back to cited text no. 7
Pulsoni A, Anghel G, Falcucci P, Matera R, Pescarmona E, Ribersani M, et al. Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Report of a case and literature review. Am J Hematol 2002;69:67-71.  Back to cited text no. 8
McClain KL, Allen CE. Inflammatory and malignant histiocytosis. In: Prchal JT, Kaushansky K, Lichtman MA, Kipps TJ, Seligsohn U, editors. Williams Hematology. 8 th ed., Ch. 72. New York: McGraw-Hill; 2010.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3]

This article has been cited by
1 Rosai-Dorfman disease in a patient with cervical lymphadenopathy and associated Serratia marcescens infection
Alvaro E. Galvis,Korena Boyd,Iris S. Pecson
Clinical Infection in Practice. 2020; : 100036
[Pubmed] | [DOI]


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