Rare Rosai-Dorfman disease presenting with basal ganglia and bilateral cerebral peduncles—diagnosis and challenges

Introduction

Rosai-Dorfman disease (RDD) is a rare benign disorder characterized by non-Langerhans histiocytic proliferation. It was first comprehensively described and named by Rosai and Dorfman in 1969; however, its pathogenesis remains poorly understood. The classic clinical manifestation of RDD is bilateral cervical lymphadenopathy (1). It has an estimated prevalence of 1 in 200,000, and predominantly affects children and young adults (mean age: 20.6 years) (2). Based on anatomical involvement, RDD is classified into three subtypes: nodal, extranodal, and mixed. The extranodal subtype accounts for approximately 43% of all RDD cases. Common extranodal sites include the skin, paranasal sinuses, respiratory system, skeletal system, and central nervous system (CNS) (3). CNS involvement is exceedingly rare, occurring in less than 5% of all RDD cases. Among these, meningeal lesions are predominant (accounting for approximately 75% of cases), while parenchymal lesions are relatively uncommon (1,4). This case represents the first documented instance of parenchymal RDD involving the left basal ganglia and bilateral cerebral peduncles, a novel anatomical presentation. The diagnostic challenge in this case highlights the urgent need to refine diagnostic approaches for such rare and complex cases. Additionally, deeper insights into RDD clinical characteristics and pathological mechanisms are required to optimize diagnostic accuracy and therapeutic outcomes.

Case presentation

A 54-year-old male presented with a 2-month history of right-sided limb weakness and episodic syncope over 10 days. A neurological examination revealed right-sided central facial palsy, normal strength in the right upper limb, grade IV muscle power in the right lower limb, and a positive Babinski reflex on the right.

In relation to the imaging findings, cranial magnetic resonance imaging (MRI) revealed patchy abnormal signals in the left basal ganglia and bilateral cerebral peduncles. The lesions showed iso- to hypointensity on T1-weighted imaging (T1WI) (Figure 1A), iso- to hypointensity on T2-weighted imaging (T2WI) (Figure 1B), and peripheral hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging (Figure 1C). Diffusion-weighted imaging (DWI) showed no evidence of diffusion restriction (Figure 1D,1E). Post-contrast sequences revealed irregular, intense “crab claw-like” enhancement (Figures 1F,2). Positron emission tomography-computed tomography (PET-CT) demonstrated increased fluorodeoxyglucose (FDG) uptake, indicating metabolic activity in the lesion.

Figure 1 MRI findings of RDD in the left basal ganglia. (A) T1WI revealed patchy iso- to hypointense signals in the left basal ganglia. (B) T2WI demonstrated iso- to hypointense signals in the left basal ganglia. (C) T2-FLAIR sequences showed mild hyperintensity surrounding the left basal ganglia. (D,E) DWI and apparent diffusion coefficient mapping provided no evidence of restricted diffusion. (F) Post-contrast imaging revealed irregular “crab claw-like” enhancement in the left basal ganglia, with ill-defined margins. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; RDD, Rosai-Dorfman disease; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Figure 2 Post-contrast MRI sequences in the coronal (A), and sagittal (B) planes showed patchy, irregular enhancement in the left basal ganglia and bilateral cerebral peduncles, consistent with the “crab claw-like” pattern described in the text. MRI, magnetic resonance imaging.

A comprehensive physical examination and whole-body PET-CT revealed no extranodal manifestations beyond the CNS involvement. Given the deep-seated basal ganglia location of the lesion and imaging/laboratory findings suggestive of an inflammatory CNS disorder, high-dose intravenous methylprednisolone pulse therapy was initiated as follows: 500 mg/day for 5 days, reduced to 240 mg/day for 5 days, and then reduced further to 120 mg/day for 5 days, followed by transition to oral prednisone 60 mg/day tapered over 4 weeks.

A subsequent MRI examination revealed an enlargement of the left basal ganglia lesion, prompting a multidisciplinary consultation, resulting in the recommendation of a biopsy for definitive pathological diagnosis. Follow-up MRI showed lesion progression, prompting a stereotactic biopsy of the left basal ganglia lesion. Histopathology revealed histiocytic proliferation with emperipolesis (Figure 3A) and lymphocytes in the histiocyte cytoplasm (Figure 3B). Immunohistochemistry confirmed cluster of differentiation 68-positive (CD68⁺), cluster of differentiation 163-positive (CD163⁺), S100 calcium-binding protein-positive (S-100⁺), and cluster of differentiation 1a-negative (CD1a⁻), consistent with RDD (Figure 3C).

Figure 3 Histopathology of the left thalamic biopsy. (A) Hematoxylin and eosin staining (×400) revealed abundant histiocytic proliferation within an inflammatory background rich in lymphocytes and plasma cells, characteristic of RDD. (B) Hematoxylin and eosin staining (×400) showed emperipolesis, a hallmark feature of RDD, with intact lymphocytes present in the cytoplasm of histiocytes (blue arrows). (C) Immunohistochemical staining (×400) showed the positive expression of S-100. RDD, Rosai-Dorfman disease.

All the procedures in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. A copy of the written consent form is available for review by the editorial office of this journal.

Discussion

RDD is a benign histiocytic proliferative disorder characterized by diverse clinical manifestations. When the CNS is involved, patients typically present with non-specific clinical symptoms, including a wide range of neurological manifestations such as headache, dizziness, epileptic seizures, and limb weakness. In this case, the lesion was primarily located in the left basal ganglia, resulting in contralateral hemiparetic sensorimotor deficits.

The pathogenesis of RDD involves multifactorial triggers, including viral infections, autoimmune dysregulation, and genetic mutations. Notably, histological features of RDD have been identified in some malignancies, suggesting a potential link between the two (5). Additionally, while the relationship between RDD and dysregulated cytokine profiles, particularly immunoglobulin G4 (IgG4), remains controversial, emerging evidence suggests that a subset of extranodal RDD cases may be correlated with IgG4. However, further research is needed to establish a definite relationship (6). Studies have also shown that approximately 50% of RDD cases have activating mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. However, the precise cellular origin of RDD remains unclear (7).

Histopathology and immunohistochemistry remain the diagnostic gold standard for RDD, revealing distinctive pathological features, including marked sinusoidal dilatation, proliferation of histiocytes in lymphatic sinuses, and the presence of lymphocytes and plasma cells in the histiocytic cytoplasm—a phenomenon referred to as emperipolesis (Figure 3B), which is pathognomonic for RDD (5). Cyclin D1 immunostaining has recently become a valuable supplementary method for extranodal RDD (8,9). Moreover, S-100 protein positivity and CD68 positivity, combined with CD1a negativity in histiocytes, are crucial diagnostic markers (10).

Intracranial RDD commonly presents as a meningeal-based lesion. Previous MRI reports describe RDD as iso- to hypointense on T1WI, hypointense on T2WI, and homogeneously enhanced with a dural tail sign—features that often resemble meningioma (11-13). It is hypothesized that the dural tail results from the inflammatory stimulation of adjacent meninges, but its exact mechanism remains unknown (14).

Surgical resection is the primary treatment for CNS-RDD. For inoperable cases, corticosteroids are the first-line conservative treatment, while combined chemotherapy and corticosteroids are recommended for recurrent or residual lesions (5,13). CNS-RDD exhibits marked heterogeneity in terms of its management and prognosis (15). Although the natural history of this disease remains incompletely defined, the reported mortality rate is approximately 7% (16). Postoperative recurrence occurs in 25–33% of cases, with deep gray nuclei parenchymal lesions demonstrating particularly poor outcomes (3,13).

In the present case, the proximity of the basal ganglia lesion to motor pathways presented three key challenges: (I) a high surgical risk precluding complete resection; (II) a lack of response to corticosteroids (17); and (III) a significantly elevated recurrence risk coupled with a lack of alternative therapies. The current evidence remains limited to small-scale studies, necessitating multicenter collaboration to establish evidence-based management strategies.

Unlike previous reports in which 75% of CNS-RDD cases presented as meningeal-based lesions with dural tail signs, the patient in this case showed unique parenchymal involvement in the left basal ganglia and bilateral cerebral peduncles, which has not been previously documented. Further, the absence of lymphadenopathy, a characteristic present in 80% of systemic RDD cases, significantly complicated the diagnostic process. Initial MRI showed FLAIR hyperintense oedema, no diffusion restriction on DWI, and elevated FDG uptake on PET-CT, suggesting neurosarcoidosis or autoimmune encephalitis. However, disease progression despite steroid therapy ruled out these diagnoses. The “crab-like” enhancement pattern (Figure 2) and hypointensity on T2WI initially raised a suspicion of CNS lymphoma, but the absence of diffusion restriction excluded it. Although MRI features such as hypointensity on T2WI, non-restricted diffusion, and infiltrative enhancement provided important diagnostic clues, a definitive diagnosis required histopathological and immunological confirmation.

The imaging characteristics are consistent with those reported for parenchymal RDD. On T1WI, CNS-RDD shows iso- to mild hypointensity, likely reflecting dense histiocytic proliferation. On FLAIR imaging, the lesions are mainly isointense with peripheral hyperintensity, indicating inflammatory oedema—a marker of disease activity and local tissue infiltration (18). Hypointensity on T2WI, a key differentiating feature, is caused by free radicals generated by phagocytic cells (shortening the T2 relaxation time) and fibrotic restriction of water mobility (19). Conversely, inflammatory lesions typically show hyperintensity on T2WI (20). Despite the high cellularity, dense fibrosis restricts water diffusion, explaining the absence of DWI hyperintensity—a feature that differentiates RDD from lymphoma (21). Enhancement patterns vary, and the irregular “crab-like” enhancement (observed in this case) is radiologically characterized by arborescent enhancing streaks radiating centrifugally from the lesion core, mimicking crab claw extension trajectories. This imaging finding may reflect the migratory process of histiocytes along perivascular neural pathways (20,22).

Parenchymal RDD, especially when solitary, poses diagnostic challenges due to its resemblance to inflammatory conditions. Key MRI markers (i.e., hypointensity on T2W1, non-restricted diffusion, “crab-like” enhancement, and perilesional FLAIR changes) may aid in the diagnosis of RDD. Thus, RDD should be considered in the differential diagnosis of solitary CNS lesions. When imaging findings conflict with the therapeutic response, a biopsy is essential for a definitive diagnosis.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1284/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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