Abstract
Background/Aim: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, benign, histiocytic proliferative disorder characterized by nonpainful lymphadenopathy. Nonmalignant histiocytes can also infiltrate extranodal sites such as in the skin and central nervous system. On imaging, RDD can mimic other disorders such as meningioma, which is more common, and requires histology and immunohistochemistry to elucidate diagnosis.
Case Report: Herein we report a case of a 20-year-old female who presented to the emergency department (ED) after near-syncope episode following methamphetamine and opioid use. Initial computed tomography (CT) found a 2.3 cm mass in the right frontoparietal region. Further examinations with magnetic resonance imaging (MRI) revealed findings compatible with meningioma. After one month of persistent symptoms, the “meningioma” was resected and the intraoperative frozen sections (FS) and touch preparation cytopathology of the mass showed mixed inflammatory infiltrates and scattered large, atypical appearing cells that display emperipolesis, raising suspicions of an RDD diagnosis instead of meningioma. The permanent sections confirmed the histological findings on FS. The large atypical lesional histiocytes showing emperipolesis with engulfment of lymphocytes, plasma cells and neutrophils. The lesional cells were immunoreactive for protein S100, cluster of differentiation 163 (CD163), and B cell lymphoma 1 (BCL-1), negative for CD1a. Based on histology and immunohistochemical profile, the final diagnosis was Rosai-Dorfman Disease. Postoperatively, there was immediate improvement in patient’s strength and symptoms. At the 9-month follow up post-surgery, she was doing well, and MRI revealed no evidence of residual or recurrent disease.
Conclusion: This case is a rare example of RDD clinically and radiologically mimicking meningioma and illustrates the importance of rigorous histological analysis for accurate diagnosis, particularly during the intraoperative consultation, to ensure proper treatment.
- Histiocytosis
- Rosai-Dorfman disease (RDD)
- meningioma
- intraoperative consultation
- craniotomy
- immunohistochemistry
Introduction
Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, was first described by Destombes in 1965, before its characterization as a distinct clinicopathological disorder in 1969 by Rosai and Dorfman (1, 2). The disease most commonly presents in children and young adults in the form of fever, leukocytosis, and nonpainful cervical lymphadenopathy (3). RDD can also present extranodally, most commonly in the skin, central nervous system (CNS), and gastrointestinal tract that can pose further diagnostic challenges given extensive fibrosis or scant emperipolesis (4-8). Histology and immunohistochemistry are necessary to distinguish this disorder from other more common conditions, like in rare cases where RDD appears radiologically like meningioma in brain (9, 10).
Meningioma accounts for 33.8% of all primary brain and CNS tumors reported in the United States (11). In the vast majority of cases, meningioma has a benign pathophysiology and is predominantly intracranial but extra-axial in location, though there are reported rare extracranial cases (11, 12). For differentiation of meningioma from RDD, the lesional cells are atypical histiocytes showing emperipolesis and they are positive for CD68, CD163, and S100, while negative for CD1a, which is typically found in Langerhans cell histiocytosis (5, 10). The present case study will expand on the scarce body of literature surrounding identification of extranodal RDD in the CNS from more common CNS pathologies. Based on the best of our knowledge, this is the first documented case of RDD mimicking meningioma diagnosed on the intraoperative frozen section diagnosis. The pathogenesis, diagnosis, treatment and prognosis are discussed.
Case Report
A 20-year-old female presented to the Emergency Department for evaluation of near-syncope after methamphetamine and opioid use. At the initial visit she reported feeling a tingling sensation in her left arm and felt herself starting to lose balance, but the patient denied loss of consciousness or head trauma. As the patient was being discharged, she suffered a seizure-like episode warranting a head computed tomographic (CT) and magnetic resonance imaging (MRI) scans, which revealed a 2.3×2.3×1.5 cm enhancing extra-axial mass in the right frontoparietal region, with vasogenic edema in the adjacent brain parenchyma (Figure 1A and B). Based on imaging findings, patient was diagnosed with meningioma and a seizure disorder, before being started on Keppra 500 mg twice daily. Since low-grade meningioma rarely causes adjacent brain parenchyma edema, it felt that for this patient, the meningioma is probably a more aggressive subtype like a WHO tumor grade II or III.
Brain mass of Rosai Dorfman disease mimicking meningioma. (A-B), Magnetic MRI scans showing a 2.3 cm right posterior frontoparietal mass with surrounding vasogenic edema compatible with meningioma (A, coronal, T1; B, Axial T2); C-D, intraoperative frozen sections (C) and permanent sections (D) of the mass showing a mixed inflammatory infiltrate consisting of mixed lymphoid cells, histiocytes and plasma cells infiltrating brain and scattered large atypical appearing cells that display emperipolesis (C, inset) of plasma cells, lymphocytes and neutrophils, histologically compatible with Rosai-Dorfman disease (C-D, H&E stain; C, 100×, inset 400×; D, 400×). MRI: Magnetic resonance imaging.
One month later, the patient presented to the ED after another seizure. Neurological examination was normal except for some left upper extremity weakness in the ER. Since the known right frontal extra-axial lesion was worrisome for more aggressive type of meningioma. The patient subsequently underwent craniotomy for total tumor resection. Intraoperative consultation frozen sections and touch preparation of the mass showed mixed inflammatory infiltrates with scattered large, atypical appearing cells with abundant clear to eosinophilic cytoplasm present that revealed emperipolesis of plasma cells, lymphocytes, and neutrophils (Figure 1C and D). In immunohistochemistry on the permanent section of the mass, the large atypical cells were positive for cluster of differentiation 163 (CD163) (Figure 2A), protein S100 (Figure 2B), B cell lymphoma 1 (BCL-1) (Figure 2C), and faintly for protein 53 (p53), negative for CD1a (Figure 2D). Mixed infiltrates were positive for CD3, CD20, and CD138. The final pathological diagnosis was brain Rosai-Dorfman Disease.
Immunohistochemistry of the brain Rosai-Dorfman disease. (A-D), Sections showing histiocytosis highlighted by CD163 (A), and the atypical cells with emperipolesis are positive for S100 (B) and Bcl-1 (C), and negative for CD1a (D) (A-D, 400×).
The patient tolerated the procedure well and there was immediate improvement in patient’s strength and other symptoms postoperatively. On follow up 9 months post-surgery, she was doing well, and MRI revealed no evidence of residual or recurrent disease (Figure 3A and B).
At 9-month post-surgery, repeat of magnetic resonance imaging (MRI) scans showed post-surgical changes with no recurrent disease identified (A, coronal, T1; B, axial, T2).
Discussion
RDD is a rare condition that afflicts adolescents and young adults most commonly in the lymph nodes of the head and neck (3). Extranodal cases, such as the present case, in the skin or CNS are even more uncommon (4-7). RDD in the CNS usually presents with dura-based, extra-axial involvement of the cranium, resulting in occasional confusion with more common conditions afflicting the brain, like meningioma (9-10, 13). To exclude other more common forms of adenopathy or CNS lesions, more must be understood about RDD etiology.
While the precise etiology of RDD is unknown, it is considered an idiopathic histiocytosis. RDD involves the infiltration of lymph nodes, most commonly around the head or neck region, or extranodal tissues with nonmalignant histiocytes; these cells exhibit emperipolesis, along with the typical immunophenotype is necessary for RDD diagnosis. Evidence has implicated viral infections like parvovirus B19, human herpes virus 6 (HHV-6), and Epstein-Barr Virus (EBV) in the pathogenesis of RDD (5, 14-16). Other cases have presented conflicting evidence, finding an absence of EBV-encoded RNA or HHV-6 in RDD histiocytes, making it harder to conclude a pathogenic mechanism (3, 17). As a result, laboratory workups should be broad to include viral infections possibly responsible, including blood and antibody tests. The classical indicator for RDD is emperipolesis in histiocyte cytoplasm (2, 5). Further pathological investigation often reveals positive results for immunohistochemical stains CD68, CD163, and S100 (5), negative for CD1a that is positive for Langerhans histiocytosis.
Surgery is the most effective treatment for RDD with CNS involvement and meningioma, but proper diagnosis is still vital for long-term recovery (18, 19). While resection for RDD is often sufficient treatment, followed by radiotherapy given and close monitoring if there are persistent CNS symptoms, grade II and III meningiomas are more aggressive and require more extensive therapy and surgeries to prevent recurrence (5, 18). Meningioma was excluded in our case on the intraoperative pathology frozen section and cytopathology diagnosis with observations of emperipolesis present in a mixed inflammatory infiltrate background. The immunohistochemistry on the permanent section also showed positivity of S100, CD163, and BCL-1, negative for CD1a and CD30, supporting the diagnosis as well.
The initial diagnosis of meningioma by MRI as etiology of her seizure disorder led to delayed treatment. The patient had continually worsened seizures despite regular Keppra dosage because of the RDD lesion, which is commonly associated with headaches and seizures and should be resected (13). Once the histopathology diagnosis was made, her follow-up treatment is much simpler compared to aggressive meningioma. There was immediate improvement in our patient’s strength and other symptoms postoperatively. On follow up 9 months post-surgery, she was doing well, and MRI revealed no evidence of residual or recurrent disease.
In summary, RDD is a rare brain inflammatory entity that can mimic meningioma, radiographically. This is the first documented case diagnosed during the intra-operative consultation and highlights the ambiguity that can be present in radiological imaging and documents the importance of histological investigation for accurate diagnosis to ensure proper treatment.
Footnotes
Authors’ Contributions
JH wrote the article; GM made the diagnosis and reviewed the article; JL made the diagnosis, collected and analyzed the data, and finalized the article.
Conflicts of Interest
The Authors declare that they have no conflicts of interest regarding this case report.
Artificial Intelligence (AI) Disclosure
No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.
- Received June 28, 2025.
- Revision received July 14, 2025.
- Accepted July 21, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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