Systemic manifestations of Rosai–Dorfman disease

A 54-year-old male patient with a history of diabetes mellitus type 2, hypertension, hyperlipidaemia, gastroesophageal reflux disease, obstructive sleep apnoea, and testosterone deficiency presented with a 4-week history of fever, cough, chills, dyspnoea on exertion, and bilateral proptosis without other visual changes.

Computed tomography (CT) of the abdomen and pelvis with intravenous contrast demonstrated bilateral adrenal masses, ill-defined soft tissue in the perirenal and pararenal spaces, and conglomerate retroperitoneal and pelvic nodes (Figures 1 and 2).

Whole body fluorodeoxyglucose (FDG) positron emission tomography (PET) CT was notable for low-level metabolic activity corresponding to mediastinal, retroperitoneal, and pelvic abnormal soft tissue (Figures 3a and 3b).

CT angiogram of the chest revealed a large pericardial effusion as well as pericardial and mediastinal masses (Figure 4).

Magnetic resonance imaging (MRI) of the brain showed bilateral homogeneously enhancing retrobulbar intraconal masses with associated proptosis (Figure 5).

Rosai–Dorfman disease (RDD) is a benign histiocytosis initially reported by Rosai and Dorfman in 1969 [1]. It has an estimated prevalence of 1 in 200,000 individuals in the United States of America [2]. The most common manifestation is massive lymphadenopathy, typically in cervical nodes [3]. Other areas of lymphadenopathy include mediastinal, axillary, and inguinal nodal stations; retroperitoneal adenopathy is less common [2]. Extranodal involvement has been reported in 43% of cases, including the skin, central nervous system, and gastrointestinal tract [2]. In the head, paranasal sinus and meningeal masses are characteristic [2].

The aetiology of RDD is unclear. Recruitment of monocytes to inflammatory sites may initiate complex signalling pathways mediated by macrophage colony-stimulating factors, leading to mass-like histiocytosis [4]. Associations with other autoimmune disorders, including IgG4-related diseases, have also been explored, though remain elusive [4].

Symptoms are nonspecific, and therefore, diagnostic imaging plays a crucial role. However, imaging features overlap with other malignant and lymphoproliferative processes, and ultimately tissue diagnosis is required. In our patient, the presumptive diagnosis of RDD based on imaging was confirmed by biopsies of mesenteric and retroperitoneal masses. Flow cytometry, cytogenetic testing, and immunohistochemistry may be required to evaluate for other lymphoproliferative disorders [2]. In our patient, the lesional histiocytes were positive for markers indicating chronic inflammatory processes, including CD68 and CD163. CD1A was negative, thereby ruling out Langerhans cell histiocytosis (LCH). While S100 and BCL1 were positive, additional flow cytometry revealed no evidence of a clonal B-cell or T-cell lymphoproliferative disorder and proliferation on Ki-67 stain was low. Laboratory evaluation—including complete blood count with differential, serum immunoglobulins, and antibody assays—should also be completed to help exclude masquerading diagnoses [2].

Following the identification of RDD on histology, staging is recommended to determine the extent of the disease, prognosis, and treatment. For staging, CT of the whole body should be completed. MRI of the brain, orbits, and spine can be performed for patients presenting with neurological symptoms. RDD generally demonstrates increased tracer uptake on FDG PET-CT, similar to lymphoma and other lymphoproliferative disorders [2]. However, the clinical utility of FDG PET-CT over conventional CT in RDD staging has not yet been demonstrated. Nonetheless, FDG PET-CT may have a role in monitoring response to treatment [5].

While there are no consensus guidelines as to treatment, RDD may be managed with surgical resection, radiation, or systemic therapy. Observation has been accepted in patients with uncomplicated lymphadenopathy and cases of asymptomatic disease in non-cutaneous areas [2]. Evidence from several case reports highlight the use of corticosteroids, chemotherapy, and immunotherapy in multifocal and refractory disease [2]. Meanwhile, radiation therapy is mostly reserved for refractory disease, disease not amenable to resection, or patients with contraindications to systemic therapy [2].

The prognosis of RDD varies widely across the literature. 20–50% of nodal/cutaneous cases reportedly undergo spontaneous remission, whereas 7–40% mortality has been reported for patients with multifocal or extranodal disease [2].