Rosai-Dorfmann Disease: A Rare Disease Presenting as a Unilateral Neck Swelling

Abstract

Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of unknown etiology. Usually it presents with massive painless cervical lymph node enlargement. Histologically, it shows proliferation of distinctive histiocytic cells that demonstrate emperipolesis in the background of a mixed inflammatory infiltrates. Immunohistochemically, the cells are positive for markers such as CD68 and S100. A 14-year-old boy presented with painless right sided cervical lymphadenopathy without any systemic and other ear, nose, and throat manifestations. The biopsy report of the lymph node showed infiltration of sheets of histiocytes showing emperipolesis with areas of fibrosis and hyalinisation. The sinus histiocytes were strongly positive for S-100 protein. RDD must be considered in the differential diagnosis of massive or multiple lymphadenopathies.

Introduction

Pediatric cervical lymphadenopathy is a common disease entity, with multiple processes ranging from benign and self-resolving to malignant. The most common cause of cervical lymphadenopathy in the pediatric population is reactivity to known and unknown viral agents. The second most common cause includes bacterial infections ranging from aerobic to anaerobic to mycobacterial infections. Malignancies are the most concerning cause of cervical lymphadenopathy.^[1]These swellings can be divided into midline swellings and lateral neck swellings.The common swellings are lymph node swellings, salivary gland enlargement, thyroid enlargement and branchial cyst.The gold-standard procedure for the diagnosis of a neck swelling is open biopsy of the swelling with histopathological examination of the excised tissue.^[2]

Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare proliferative histiocytic disease characterized by non-neoplastic proliferation of histiocytes/phagocytes in the sinusoids of lymph nodes and in extranodal tissues. Although rare in children, RDD can mimic malignant lymphoproliferative disorders.^[8]

In this report, we present a case of 14 year old male child with this rare disease entity.

Case Report

A 14 year old boy presented to our hospital with chief complaints of right sided painless neck swelling since 2 months. Patient denied any other history of fever, weight loss, difficulty in swallowing or breathing. On examination, there was a right sided solitary neck swelling of size 4 × 3 cm(Fig. 1), non tender, mobile, firm in consistency, was extending superiorly to the angle of the mandible. There was no other cutaneous or organ involvement, including salivary gland swelling, and neurological examination was otherwise normal at the date of examination. Nasal endoscopy and 70° Video-laryngoscopy showed no abnormality. Total leucocyte count was 12,500cells/cumm. Mantoux test was negative.Ultrasonography of neck suggested right cervical lymphadenopathy with infective etiology. On further evaluation, FNAC of the mass suggested reactive changes in right submandibular lymph node. Patient underwent excision biopsy (Fig. 2) and excised tissue was sent for histopathological examination.

Fig. 1.

Right sided neck swelling

Fig.2.

Excised tissue

Histopathological reports showed infiltration of sheets of histiocytes showing emperipolesis with areas of fibrosis and hyalinisation. (Fig. 3)

Fig. 3.

Showing sheets of histiocytes and emperipolesis(black arrow)

Morphological features suggested Rosai- Dorfmann syndrome/sinus histiocytosis with lymphadenopathy. Immunohistochemistry showed multinucleated giant cells marked by S100, CD68 and negative for PanCk,CD30,LMP1,PAX5,ALK1.

Once the daiagnosis was made, low dose Oral prednisone was started. It showed a complete response and good progress, and after a follow-up period of 12-months he experienced no episodes of recurrence.

Discussion

We present a case report of RDD patient at our hospital to report our experience of this rare disease and share the treatment for our patient to contribute to the pool of data and recommendations.

Cervical lymphadenopathy is a very common disorder in paediatric age group. Rosai Dorfman syndrome is a rare disease entity which can present as massive cervical lymphadenopathy. These cases are frequently misdiagnosed as lymphoma, and thus it is important to distinguish Rosai–Dorfman disease from other causes of neck swelling because of different treatment modalities [3]. RDD also known as sinus histiocytosis was first described in 1965 in four African children with lymphadenopathy by Destombes, and was called “adenitis with lipid excess”, owing to the lipid-laden histiocytes in the tissue specimen [4].

RDD is generally described as a benign, self-limiting disease [12]. For example, Pulsoni reported that 32 out of 40 cases showed spontaneous resolution [5] However, recurrence and even fatal outcomes have been reported. Chen reported that among 126 RDD patients, 69 patients (54.8%) followed a recurrent, persistent, or progressive course, and 6 patients (4.8%) died of the disease [6]. Therefore, treatment is especially required in cases with complications, for example, in cases involving compression of vital organs or airway obstruction by the enlarged lymph nodes, or cases with systemic dissemination. Various treatment modalities including surgical excision, steroid therapy, and radiotherapy have been described and have shown variable responses [5]. A review article by Dalia et al. [7] suggests that surgical resection remains the mainstay of treatment for symptomatic disease. In our case, we performed resection of the lesion, and after 12 months of observation, the patient remained healthy.

The disease can affect any age group, but the majority of reported cases have occurred in the first two decades of life. Clinically, males are more likely to be affected with a male-to-female ratio of 5:1. Bilateral, massive and painless cervical lymphadenopathy is the most frequent initial symptom of the disease and is present in 87% of the cases.

The pathogenesis of RDD remains still unknown, but several theories have been proposed. A disturbance of cell-mediated immunity, a primary viral infection, and autoimmune mechanisms have all been proposed as possible etiologies of this disorder. Moreover, some infectious agents, such as Epstein-Barr virus and herpesvirus 6 have been identified in visceral and cutaneous lesions and related to the pathogenesis and clinical manifestations of RDD, although a viral genesis has not yet been confirmed [9].

Some studies have shown that the disease might be related to viral infections such as cytomegalovirus (CMV), human immunodeficiency virus (HIV), and Epstein-Barr virus (EBV) [10]. The literature has also reported the genetic mutation of BRAF-V600E in 23 RDD patients which is a mutation associated with another non- Langerhans cell histiocytosis named Erdheim-Chester disease (ECD) [11].

Histologically, there is infiltration of the tissue by lymphocytes, histiocytes and plasma cells. Presence of emperipolesis, i.e.engulfment of lymphocytes and erythrocytes by histiocytes, is usually diagnostic of Rosai–Dorfman disease. It is non-Langerhans cell histiocytosis characterized histopathologically by the accumulation of CD68-positive, S100-positive, and CD1a-negative histiocytes.The anatomopathological evaluation of our patient revealed, among other things, emperipolesis, positivity for S100 and CD68. The common differential diagnosis includes infectious lesions, granulomatous lesion, reactive lymphoid hyperplasia with sinus histiocytes (RLHSH), Langerhans cell histiocytosis (LCH), hemophagocytic syndrome and malignant lymphoma.The treatment includes corticosteroids, chemotherapy, low dose interferon, antibiotics and radiation therapy. Radiation therapy is indicated for threatened function, such as cord compression and respiratory insufficiency [3]. Surgical excision was chosen as the first-line treatment for our patient followed by low dose oral prednisolone.

Conclusion

Rosai Dorfman disease should always be kept as differential diagnosis in a young male presenting with cervical lymphadenopathy. Diagnosis is usually made by clinical examination and histopathological analysis and immunohistochemistry.

Funding

None.

Declarations

Conflict of interest

None.

Ethical approval

The study was approved by the Institutional Ethics Committee.

Informed consent

Obtained from the patient/ relatives