Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease

Abstract

Rosai-Dorfman disease is a rare subtype of non-Langerhans cell histiocytosis. With the last major report published in 1990, there is a paucity of contemporary data on this disease. Our objective was to report the clinicopathological features, treatments and outcomes of patients seen at a tertiary referral center. Sixty-four patients with histopathological diagnosis of Rosai-Dorfman disease were identified from 1994 to 2017 (median age 50 years; range, 2-79). The median duration from symptom onset to diagnosis was seven months (range, 0-128), which was also reflected in the number of biopsies required to establish the diagnosis (median 2; range, 1-6). The most common presentation was subcutaneous masses (40%). Of the 64 patients, 8% had classical (nodal only) and 92% had extra-nodal disease (67% extra-nodal only). The most common organs involved were skin and subcutaneous tissue (52%), followed by lymph nodes (33%). Three patients had an overlap with Erdheim-Chester disease, which had not been described before. Two of these were found to have MAP2K1 mutations. Commonly utilized first line treatments were surgical excision (38%) and systemic corticosteroids (27%). Corticosteroids led to a response in 56% of the cases. Of those treated initially, 15 (30%) patients developed recurrent disease. The most commonly used systemic agent was cladribine (n=6), with 67% overall response rate. Our study demonstrates that Rosai-Dorfman disease has diverse clinical manifestations and outcomes. While this disease has been historically considered a benign entity, a subset of patients endures an aggressive course necessitating the use of systemic therapies.

The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease

“…29 In contrast, bone involvement in RDD is less common (10%-20%) and rarely occurs in isolation. 30,31 When present, RDD of the bone is usually evident clinically as pain, compressive neuropathy with spinal disease, or headache with skull involvement. 32 Skeletal RDD lesions are usually lytic, yet less aggressive and centered in the medullary space.…”

“…49 Rosai-Dorfman disease involving the CNS is rare (10%) and involves the dura far more frequently than the brain parenchyma. 31,52 A potential clue to the diagnosis is emperipolesis (lymphocytes engulfed by histiocytes) in spinal fluid. 53 Dural, parenchymal, spinal cord, and nerve roots…”

“…In addition, sinus involvement can be seen occasionally as well, with maxillary sinus wall thickening similar to that seen with ECD. 31 Dermatologic Erdheim-Chester disease can affect the skin in up to 30% of patients. Half of these patients have cutaneous involvement at diagnosis.…”

“…77 Rosai-Dorfman disease involving the skin and subcutaneous tissue can be seen in a large proportion of patients (50%). 31 Solitary or multiple red-to-brown macules or papules or xanthomatous papules, nodules, and plaques usually around the orbits (eyelids) or malar region can be seen. Panniculitis (tender subcutaneous nodules) and isolated cutaneous involvement have been reported as well.…”

“…In our own cohort, cardiac involvement was seen in less than 5% of patients. 31 Arterial Arterial involvement in histiocytic neoplasms rarely causes symptoms that lead to diagnosis. 85,86 Nevertheless, periarterial fibrosis of the thoracic or abdominal aorta is notably present in 56% to 85% of patients with ECD, with sheathing of the entire thoraco-abdominal aorta (ie, "coated aorta") in 23% to 30%.…”