Recurrent Soft Tissue Rosai Dorfman Disease of Right Medial Thigh Lipoma With Lymph Node Involvement
Background: Rosai Dorfman disease is a rare non-Langerhans cell histiocytosis that affects lymph nodes, soft tissues, and other organs. The etiology of Rosai Dorfman disease is poorly understood, though it may involve an immunologic processes or infection. Treatment varies according to the disease presentation.
Case Presentation: A male aged 56 years was evaluated for a cutaneous mass on his right medial thigh. Initially, the patient received surgical debulking with subsequent observation and no systemic therapy. However, the mass recurred, prompting another surgical removal 9 years after the initial surgery. A mass biopsy showed infiltration of plasma cells, lymphocytes, histiocytes, and occasional neutrophils with noted reactivity of S-100 protein and CD163, but not CD1a. No systemic therapy was initiated, and the patient agreed to a period of watchful waiting.
Conclusions: Rosai Dorfman disease of soft tissue occurs in older adults and is often associated with soft tissue abnormalities, and more rarely, in lipomas. Multidisciplinary management of the disease and research for mutations and microenvironment is needed to better understand its clinicopathological nature and improve novel therapies.
Discussion
RDD is rare with a prevalence of 1:200,000. It has been reported that multisystem involvement occurs in 19% of cases and the prognosis of RDD correlates with the number of extranodal systems involved in the disease process.7 Although sporadic RDD is usually self-limited with favorable outcomes, it is estimated that 10% of patients may die of RDD due to direct complications, infections, and amyloidosis.2,7 RDD commonly affects young male children and young adults with a mean age of 20 years and has a higher incidence among African American children.2,7,8 Although patients with RDD present bilateral, painless cervical lymphadenopathy in 90% of cases, about 43% of patients with RDD and associated adenopathy present with ≥ 1 site of extranodal involvement, and only 23% of patients with RDD present with isolated extranodal sites without adenopathy.9 As was the case with our patient, the most common extranodal sites are found in the skin and soft tissue (16%).6,9 However, histopathologic diagnosis of RDD in a lipoma is exceedingly rare. We found only 1 other case report of a patient with a history of multiple lipomas who developed a new solitary nodule that was excised and demonstrated RDD upon immunohistochemical staining.4 There has been no documented association between multiple lipomas and RDD.4
Histologically, RDD is often characterized by emperipolesis (the presence of an intact cell within the cytoplasm of anther cell) and a mixed cell infiltrate that includes S100 positive histiocytes, mononuclear cells, plasma cells, and lymphocytes.10 Despite these shared histologic features among the various phenotypes of RDD, other type-specific characteristics may also be present. When compared to nodal RDD, extranodal disease tends to demonstrate a lack of nodal architecture, more fibrosis and collagen deposition, fewer RDD cells, a lower degree of emperipolesis, and alternating pale (histiocyte rich) and dark (lymphocyte rich) regions with notable polygonal histiocytes arranged in a storiform pattern.5,10
Our patient’s histology showed an overall IgG4:IgG plasma cell ratio > 40%. RDD frequently presents with IgG4-positive plasma cells, which has confounded the diagnosis of IgG4-related diseases and hyper-IgG4 disease.11 Given this association, the Histiocyte Society revised classification recommends that all cases of RDD be evaluated for IgG4-positive cell infiltration.2,3 Further discussion on this matter was recently provided after an expert panel published a consensus statement in 2015 detailing the evaluation of IgG4. The panel advocates for stricter terminology and criteria on this issue, advises that isolated IgG4-positive plasma cells are nonspecific, and states that the diagnosis of IgG4 disease should be based on careful judgment and correlation with the clinical scenario and supportive findings.12 Therefore, while IgG4 positivity continues to be misleading in RDD cases, further evaluation for IgG4 disease is recommended.
Sporadic RDD is usually self-limited with a reported remission rate of up to 50%, according to a case series of 80 patients with RDD.13 This leads to the recommendation of a period of watchful monitoring in patients with limited disease.13 In patients with unifocal extranodal disease, surgical excision has shown positive remission results; however, local recurrence of soft tissue lesions can occur at a rate of 21.4% to 51%.14 Although initiation of systemic therapy should be considered in patients with recurrent disease, there is currently no standardized regimen or medication of choice for treatment. Treatment with steroids, including prednisone 40 to 70 mg daily or dexamethasone 8 to 20 mg daily, have been shown to be effective in reducing the nodal size and symptoms, especially in cases of nonresectable multifocal extranodal disease of the central nervous system, bone, and orbital.7,15,16 However, cases of orbital, tracheal, renal, or soft tissue RDD have reported failure in treatment with steroids.17,18
According to the consensus recommendations for the treatment of RDD released in 2018, treatment with chemotherapy has shown mixed results. Anthracycline and alkylating agents have shown minimal efficacy, but combination regimens with vinca alkaloids, methotrexate, and 6-mercaptopurine have helped patients experience remission.19,20 Due to the rarity of RDD and lack of clinical trials, the exact efficacy of these treatment regimens remains unknown and is largely limited to case reports described within the medical literature. Treatment with nucleoside analogs, such as cladribine 2.1 to 5 mg/m2 or clofarabine 25 mg/m2 per day for 5 days every 28 days for 6 months, have shown promising results and helped achieve complete remission in patients with refractory or recurrent RDD.7,21-23 Immunomodulator therapies including TNF-α inhibitor, such as thalidomide and lenalidomide, have also shown to be effective, particularly in patients with refractory disease.24,25 Low-dose thalidomide (100 mg daily) was effective for cases of refractory cutaneous RDD, though no standard dosing regimen exists. Lenalidomide has shown to be effective in patients with multiple refractory nodal or bone RDD, but is associated with more complications given that it is more myelosuppressive than thalidomide.7 Radiotherapy has also been initiated in patients with refractory soft tissue disease or persistent symptoms after resection and in patients who are not candidates for surgery or systemic therapy, though no standard doses of radiotherapy have been established.7,26,27
Conclusions
RDD is a rare histiocytic disorder that presents in a wide range of age groups, different locations in the body, and with variable disease behavior. Multidisciplinary management of the disease and research for mutations and microenvironment of RDD is needed to better understand its clinicopathological nature and improve targeted novel therapies.
Acknowledgments
The authors thank Veterans Affairs Central Texas Health Care Section Chief of Rheumatology, Swastika Jha, MD, for her guidance in this case and Bo Wang, MD, for his preparation of the pathological specimens.
