Unusual progression of Rosai–Dorfman disease in a pediatric patient

Abstract

Rosai–Dorfman disease is a rare and self-limiting disease process that presents most commonly in young patients as massive, painless, cervical lymphadenopathy. CNS is a rare site for this disease, and only a few imaging appearances have been described. We report an unusual presentation of Rosai–Dorfman disease with cervical lymphadenopathy and involvement of the paranasal sinuses, intra and extracranial portions of the third division of the right trigeminal nerve, lacrimal glands and subsequent involvement of intra and extracranial portions of the third division of the left trigeminal nerve. Bilateral involvement of the trigeminal nerve with Rosai–Dorfman disease is rare and has only been described in 1 prior case. This case highlights that Rosai–Dorfman disease should be considered in pediatric patients with a mass involving the trigeminal nerve and extensive paranasal sinus disease.

Introduction

Rosai–Dorfman disease (RDD), was first described by Juan Rosai and Ronald F. Dorfman in 1969 as a rare, benign and self-limiting disease characterized by accumulation of histiocytes [1]. Patients typically present with bilateral, painless cervical lymphadenopathy and may have constitutional symptoms such as fever and weight loss. Extra-nodal involvement is seen in approximately 30% of patients and can involve the skin, nasal cavity, paranasal sinus, eyelid, orbit, bone, salivary gland and central nervous system (CNS) [2]. The disease is multifocal, and diagnosis in 1 area should prompt suspicion for involvement of other sites.

We present a rare case of RDD in an adolescent boy who initially presented with sinus congestion and developed progression of disease with involvement of intracranial and extracranial structures in an unusual pattern.

Case presentation

The patient initially presented with recurrent sinusitis at 10 years of age. A CT of the paranasal sinuses (Fig. 1) demonstrated diffuse soft tissue attenuation in the paranasal sinuses thought to be mucosal disease. At the ages of 11 and 13, the patient underwent endoscopic sinonasal surgery which demonstrated multiple nasal polyps and sinus mucosal disease. Pathology demonstrated nasal polyps with marked lymphocytic infiltration and mucosal disease with chronic inflammation. Laboratory evaluation, including complete blood count and metabolic panel, was unremarkable at the time of presentation. At the age of 14, the patient developed right facial numbness. Neurologic examination demonstrated diminished sensation in the right face, consistent with trigeminal nerve involvement, while motor function and the remainder of the cranial nerve examination were intact. A subsequent MRI brain demonstrated a right trigeminal mass (Fig. 2) which was classified as a probable schwannoma and normal sized lacrimal glands (Fig. 3). The remaining part of the intracranial compartment was unremarkable in appearance. The patient did not report constitutional symptoms such as fever, weight loss, or night sweats. The patient subsequently underwent removal of this mass.

Fig. 1.

Coronal CT image of the paranasal sinuses demonstrating soft tissue attenuation throughout the paranasal sinuses.

Fig. 2.

(A) Axial T1, (B) Axial T1 post contrast and (C) Axial T2. 3.6 cm AP × 2.4 cm TRV T1 hypointense, T2 hyperintense, and homogenously enhancing mass (blue arrow) in the right intracranial portion of the right trigeminal nerve consistent with a probable schwannoma.

Fig. 3.

Axial T1-weighted MRI of the brain and orbits demonstrating normal-sized lacrimal glands. Mild orbital deformation is noted, secondary to artifact from dental hardware.

Histopathologic evaluation demonstrated a diffuse, heterogeneous histiocytic and lymphoplasmacytic proliferative lesion composed predominantly of large histiocytes with abundant amphophilic cytoplasm within a background of fibrosis and inflammatory infiltrate. Emperipolesis was identified, although not prominent. Immunohistochemical staining showed that the lesional histiocytes were positive for S100 and CD68 and negative for CD1a, supporting the diagnosis of Rosai–Dorfman disease. Plasma cells were predominantly IgG-positive with less than 40% IgG4 positivity. Molecular testing for KRAS, BRAF, or MAP2K1 mutations and germline testing (eg, FAS or SLC29A3) were not performed in this case.

As a part of the workup, the patient (age 15) underwent a FDG PET/CT which demonstrated FDG avid lymphadenopathy at multiple sites including in the cervical chain (Fig. 4).

Fig. 4.

Axial PET/CT image demonstrating FDG-avid lymphadenopathy of the cervical lymph node chain.

The patient was treated with systemic therapy consisting of vinblastine and corticosteroids according to the LCH-3 protocol for 1 year (August 2018–August 2019). Following treatment, he experienced partial clinical response with improvement in lymphadenopathy; however, he subsequently developed progressive disease with increasing orbital and sinonasal involvement, including progressive symmetric and diffuse enlargement of the bilateral lacrimal glands due to RDD (Fig. 5, age 17) and new involvement of the V3 segment of the left trigeminal nerve extending through the foramen ovale into the masticator space (Fig. 6) at the age of 21. Subsequent CT imaging demonstrated increasing orbital involvement and PET/CT demonstrated FDG avidity in paranasal sinuses and soft tissue structures in the face consistent with RDD involvement. At most recent follow-up following bilateral orbitotomy with debulking of orbital lesions, the patient is recovering well without new symptoms. Vision remains stable, with no diplopia or evidence of optic neuropathy (see Table 1 for chronological order of clinical course, imaging findings, and intervention/outcome).

Fig. 5.

(A) Axial T1, (B) Axial T1 postcontrast and (C) Axial T2. Bilateral enlarged lacrimal glands demonstrate T1 isointense and T2 hypointense signal and diffuse homogenous enhancement.

Fig. 6.

MRI brain, coronal T1 post contrast, demonstrating masses in the intracranial and extracranial portions of the V3 segments of the bilateral trigeminal nerves.

Table 1.

Timeline of clinical course, imaging findings, and interventions.

Age/Date	Clinical event	Imaging findings	Intervention/Outcome
Age 10 (2013)	Recurrent sinusitis, nasal congestion	CT sinuses: diffuse soft tissue attenuation (Fig.1)	Medical management; later endoscopic sinus surgeries
Ages 11-13 (2014-2016)	Persistent sinonasal disease	Endoscopic findings: nasal polyps, chronic inflammation	Multiple sinonasal surgeries
Age 14 (2017)	Right facial numbness	MRI: right trigeminal mass (initially suspected schwannoma) (Fig. 2). Normal sized lacrimal glands (Fig. 3).	Surgical resection; pathology confirmed RDD
Postdiagnosis Age 15 (2018)	Systemic disease identified	PET/CT: FDG-avid cervical lymphadenopathy and sinonasal disease (Fig. 4).	Diagnosis of multifocal RDD
Ages 15-16 (2018-2019)	Systemic therapy		Vinblastine + corticosteroids (LCH-3 protocol); partial response with improvement in lymphadenopathy
Age 17 (2020)		MRI: progressive enlargement of bilateral lacrimal glands (Fig. 5)
Age 21 (2024)	Worsening periorbital swelling (L>R), headaches	MRI: increasing involvement of trigeminal nerves (Fig. 6)	Progressive disease noted
Sept 2024	ED presentation for eye swelling	CT: increased size of orbital lesions (not shown)	Treated empirically for sinusitis (limited improvement)
Sept 2024	PET/CT staging	FDG-avid lesions in paranasal sinuses (SUV up to 12.2), lacrimal glands (∼5.2), trigeminal region (∼5.7) (not shown)	Confirmed metabolically active disease
May 2025	Ophthalmology evaluation		Initiated oral prednisone; surgical vs medical options discussed
Dec 2025	Left orbital surgery		Left orbitotomy with lacrimal gland biopsy and debulking
April 2026	Right orbital surgery		Right orbitotomy with debulking of orbital masses
Latest follow-up (2026)	Postoperative recovery		Stable vision, no diplopía, no optic neuropathy

Discussion

RDD is a benign condition characterized by proliferation of foamy histiocytes, B and T lymphocytes, and phagocytosis of lymphocytes by histiocytes and can involve multiple structures. Imaging studies such as CT and MRI are useful for evaluating the extent of the disease, but no specific imaging characteristics are known. It is a disease with protean imaging manifestations. RDD masses may enhance strongly and homogenously with contrast administration on MRI and show decreased T2 weighted signal intensity which might be due to necrosis, fibrosis, and erythrophagocytosis [3]. No specific imaging characteristics allow differentiation of RDD from myriad other disease processes and in several cases, as in ours, the diagnosis is not made in the first instance due to its rarity [4,5].

The most common CNS manifestation of RDD is that of a dura-based mass or masses easily confused with meningiomas [6,7]. This case is rare as it showed bilateral involvement of the trigeminal nerve and was initially believed to represent a trigeminal schwannoma. Involvement of the trigeminal nerve by RDD has been described in a prior case [8]. where there was involvement of the trigeminal nerves at the level of the pons and, in another case, where there was an isolated left cavernous sinus mass which was initially diagnosed as a trigeminal schwannoma on MRI [9]. Elkhamary et al. [10] described MRI enlargement of multiple trigeminal nerve branches in non-neoplastic orbital disease, including Rosai–Dorfman disease cases with involvement of several divisions and at least 1 instance of bilateral perineural trigeminal involvement.

Our case is also unique since it presents the rare continuum of presentation with extensive paranasal disease due to RDD followed by involvement of the right trigeminal nerve, lacrimal glands, and then the left trigeminal nerve.

The differential diagnosis for lesions involving the trigeminal nerve and orbit includes trigeminal schwannoma, meningioma, lymphoma, sarcoidosis, and IgG4-related disease. Trigeminal schwannomas typically present as well-circumscribed masses along the course of the nerve [11]. while meningiomas are dural-based with characteristic homogeneous enhancement [12]. Lymphoma may demonstrate diffusion restriction and is often associated with systemic disease. Sarcoidosis can involve cranial nerves but is typically accompanied by systemic granulomatous involvement [13]. IgG4-related disease may present with lacrimal gland enlargement but is characterized histologically by increased IgG4-positive plasma cells. In contrast, Rosai–Dorfman disease demonstrates characteristic histopathologic features, including emperipolesis and S100-positive histiocytes, which help distinguish it from these entities.

RDD is typically self-limiting, often resolving spontaneously, though in some cases, it may be persistent and progressive, like in our case [[6], [14]]. Patients may experience recurrence and multifocal dissemination [6]. Rare fatalities have also been reported [[15], [16], [17]].

There is no standardized treatment approach for RDD. Overall prognosis is favorable, and spontaneous lesion regression has been reported [19]. Post-operative treatments such as corticosteroids, and radiotherapy have shown benefit in individual cases and a larger series has demonstrated variable treatment responses with surgical excision and systemic therapies [[18], [19]]. Surgical excision remains the most effective intervention, particularly for localized disease. Incomplete resection of the lesion could lead to RDD recurrence and relapse [19,20]. Lesion location may influence prognosis, as complete excision within the nasal cavity and paranasal sinuses can be challenging [6]. Corticosteroids have been used in select cases with variable response and symptomatic improvement, although their long-term efficacy remains uncertain [6,19]. Earlier recognition of RDD may allow for tailored management and potentially avoid unnecessary surgical intervention.

Conclusion

RDD is a rare diagnosis with a variety of imaging findings. Disease involvement may be multifocal and occur either synchronously or metachronously; therefore, diagnosis at 1 site should prompt evaluation for additional disease foci. This case demonstrates an unusual presentation of RDD involving the paranasal sinuses, intra and extracranial portions of the 3rd division of the right trigeminal nerve, and cervical lymphadenopathy with subsequent involvement of the lacrimal glands and left trigeminal nerve. It highlights that RDD should be considered in pediatric patients with a mass involving the trigeminal nerve and extensive paranasal sinus disease.

Patient consent

Written consent was obtained from the patient for publication of this case report and accompanying images.