Rosai–Dorfman disease: sinus histiocytosis with massive lymphadenopathy

Abstract

A 25-year-old man presented with a 3 month history of a painless mass on the right side of his neck. Physical examination revealed a smooth surfaced, bilobed, 4×3 cm, semimobile mass at the right and 3×2 cm at the left jugulodigastric region. Endoscopic examination of the patient showed a granular tumour in both nasal cavities. After biopsies were taken from the mass from the nasal cavity, a diagnosis of Rosai–Dorfman disease was made. A conservative approach was taken to treatment and after the 6 month follow-up period, the patient was in a stable condition.

BACKGROUND

Rosai–Dorfman disease (RDD), which is also called sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic, benign histiocytic proliferation generally seen in younger patients.¹ Massive lymphadenopathy most commonly involves the cervical lymph nodes. The diagnosis is often not considered in the first instance due to its rarity and histological similarity to other diseases. RDD usually resolves spontaneously; however, some may run a protracted course over years, with the possibility of involvement of vital organs and, in some cases, cause mortality.²

We describe here a patient with RDD who was referred to us with bilateral massive cervical lymphadenopathies; in this report, we discuss the clinical presentation, histologic characteristics, pathogenesis and treatment modalities of the disease.

CASE PRESENTATION

A 25 year-old man presented with a 3 month history of a painless mass on the right side of the neck. The mass had gradually increased in size during the past few days. He denied any pain or numbness. His medical and family histories were unremarkable. Physical examination revealed a smooth surfaced, bilobed, 4×3 cm, semimobile mass at the right and 3×2 cm at the left jugulodigastric region. Endoscopic examination of the patient showed a granular tumour in both nasal cavities. Laboratory examination included an erythrocyte sedimentation rate of 113 mm/h (normal 0–15 mm/h), C reactive protein values of 83 mg/l (normal 0–5 mg/l), white blood cell count of 11.5×10⁹/l and haematocrit of 37%. Positron emission tomography (PET) imaging revealed a mass in the ethmoid sinuses and a bilobed mass at the bilateral jugolodigastric region (fig 1). Because the findings of fine needle aspiration biopsy from the neck mass were inconclusive, an incisional biopsy from the neck mass and a punch biopsy from the nasal tumour were performed. Representative haematoxylin and eosin stained sections of the punch biopsy showed proliferation of histiocytes mixed with lymphocytes, plasma cells and rare eosinophils. Histiocytes appeared in small clusters or in broad sheets (figs 2 and 3). Immunohistochemical staining demonstrated S-100 protein in the cytoplasm of many cells of neuroectodermal origin, as well as subtypes of the macrophage/histiocyte family (fig 4). According to histopathologic examination, a diagnosis of RDD was made.

Figure 1.

Axial positron emission tomography scan of the patient.

Figure 2.

Haematoxylin and eosin stained section of the biopsy sample, showing proliferation of histiocytes mixed with lymphocytes, plasma cells and rare eosinophils.

Figure 3.

Histiocytes appeared in small clusters or in broad sheets.

Figure 4.

Immunohistochemical staining demonstrating S-100 protein in the cytoplasm of many cells of neuroectodermal origin.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis includes various malignancies, Hodgkin’s disease, rhinoscleroma, Wegener’s granulomatosis, and the histocytoses, among others. The disease is self limiting with 70–80% undergoing spontaneous remission, while other cases may be chronic with a relapsing and remitting pattern.³ Surgery is only required in life threatening or function threatening circumstances in order to decompress the upper respiratory system, to open the paranasal sinus, or to relieve pressure in the orbits.^4,5 Moreover, radiotherapy and chemotherapy have been used, but the response rate has been unsatisfactory.^4,5

OUTCOME AND FOLLOW-UP

A conservative approach was taken to treatment, and after the 6 month follow-up period the patient was in a stable condition.

DISCUSSION

RDD is an uncommon, benign systemic histioproliferative disease characterised by massive lymphadenopathy, particularly in the head and neck region, and is often associated with extranodal involvement.¹ Approximately 15% of RDD patients have ear, nose, and throat field involvements.⁶ Infectious and immunologic causes have been postulated but remain unidentified. Sixty-seven per cent of all cases occur in those <10 years of age and 80% of cases in those <20.^1,7 There is a slight male to female predominance and a higher incidence reported in those of African or West Indian descent.¹ Massive cervical lymphadenopathy is the hallmark of the disease, although reports indicate that up to 40% of all cases may have extranodal involvement.¹ RDD may affect a variety of extranodal sites including the skin, upper aerodigestive tract, eye and adnexa, external and middle ear, skeletal system, and central nervous system.^1,8 Extranodal involvement occurred in about 43% of the cases, and in these cases 75% occurred within the head and neck region.^1,4 Extranodal involvement is more frequently found among elder individuals and in those with an underlying immune deficiency status, which may contribute to a poorer prognosis.⁹ Within the head and neck, nasal cavity and paranasal sinuses are the most affected sites followed by the salivary gland, oral cavity, pharynx, tonsils, trachea, orbit, eyelid, and external and middle ear.^4,8,9

The most common symptoms in patients with RDD of the head and neck are nasal obstruction, rhinitis and epistaxis.¹⁰ When massive lymphadenopathy is present, often low grade fever, leucocytosis and neutrophilia are associated with clinical and laboratory findings.⁹ Of those tested, 88.5% have an elevated erythrocyte sedimentation rate, 83% have a polyclonal elevation of immunoglobulin G, and 65% have anemia.¹ Definitive diagnosis is based on identification of characteristic histopathologic features on surgical pathology specimens. Fine needle aspiration has been reported as efficacious in the diagnosis, especially when taken from a cervical lymph node.¹¹ Salient histopathologic findings include S-100 positive histiocytic proliferation, emperipolesis or phagocytosed lymphocytes within the histiocytic cytoplasm, fibrosis, and plasma cell infiltrates.

In conclusion, RDD is a distinct clinical and pathological entity which is an idiopathic disorder classified as a histiocytosis with massive cervical lymphadenopathy. It is important for otolaryngologists, pathologists, and other clinicians to be familiar with the head and neck manifestations of RDD.

LEARNING POINTS

• Rosai–Dorfman disease (RDD) is an uncommon disease, and mostly involves the head and neck region.

• Differential diagnosis includes various malignancies, Hodgkin’s disease, rhinoscleroma, Wegener’s granulomatosis, and the histocytoses, among others.

• The disease follows a self limiting course.