: 2022  |  Volume : 5  |  Issue : 2  |  Page : 77--79

Cerebral CD1a positive Rosai–Dorfman disease with coexistent granulomatous angiitis: A case report

Sweety Vijay Shinde1, Asha Sharad Shenoy2,  
1 Department of Pathology, T. N Medical College and B.Y.L Nair Hospital, Mumbai, Maharashtra, India
2 Department of Pathology, Seth G.S Medical College and K.E.M Hospital, Mumbai, Maharashtra, India

Correspondence Address:
Dr. Sweety Vijay Shinde
Department of Pathology, B.Y. L Nair Hospital, Mumbai - 400 008, Maharashtra


Rosai–Dorfman disease (RDD) is a nonneoplastic histiocytic proliferation. RDD is CD1a negative as opposed to Langerhans cell histiocytosis (LCH). The lesion was positive for CD1a immunohistochemistry in our RDD patient, suggesting an overlap with LCH. In addition, our case exhibited granulomatous angiitis (GA) on microscopy. We report the first triad of coexistent intracranial RDD-LCH-GA. A 30-year-old man presented with seizures, limb weakness, and violent behavior for 3 months. There was no fever, lymphadenopathy, or hepatosplenomegaly. Laboratory test results were normal. Radioimaging revealed an 8.6 cm × 7.4 cm × 3.2 cm mass in the parietotemporal lobe. It was hypointense on T1W1 and hypointense on T2W1, suggestive of glioma or tumefactive demyelination. A subtotal resection was performed. Histopathology exhibited mature lymphocytes, plasma cells, and histiocytes with emperipolesis. Vessels showed transmural granulomatous inflammation. Fungal and mycobacterial stains were negative. Immunohistochemistry revealed positivity for CD68, S100, and CD1a. The patient refused to undergo postoperative adjuvant radiotherapy. He remained asymptomatic for 6 months but was lost to follow-up thereafter. RDD-LCH concurrence may represent a clonal transformation in a common precursor histiocyte. Coexistent GA requires resection followed by steroid or cyclophosphamide therapy to prevent disease progression.

How to cite this article:
Shinde SV, Shenoy AS. Cerebral CD1a positive Rosai–Dorfman disease with coexistent granulomatous angiitis: A case report.Glioma 2022;5:77-79

How to cite this URL:
Shinde SV, Shenoy AS. Cerebral CD1a positive Rosai–Dorfman disease with coexistent granulomatous angiitis: A case report. Glioma [serial online] 2022 [cited 2023 Feb 5 ];5:77-79
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Full Text


Rosai–Dorfman disease (RDD) is a nonneoplastic histiocytic proliferation. Isolated cerebral RDD is reported in only 5%.[1] Our RDD case exhibited additional features of granulomatous angiitis (GA) and Langerhans cell histiocytosis (LCH). RDD-GA concurrence has therapeutic implications since both respond to surgical resection followed by steroid therapy. Coexistent CD1a positivity on immunohistochemistry (IHC) could suggest a clonal transformation of reactive RDD into neoplastic LCH. The triad of RDD-GA-LCH has not been reported prior in literature. This case report describes a patient exhibiting the coexistence of these two rare cerebral entities.

 Case Report

A 30-year-old male Indian-origin patient with chronic alcoholism was a businessman by occupation. He presented with seizures for 6 months with bilateral limb weakness and violent behavior for 3 months. There was no fever, neck rigidity, lymphadenopathy, or hepatosplenomegaly. On examination, the fundi and cranial nerves were normal. There were no cerebellar signs or sensorimotor deficits. Complete hemogram, erythrocyte sedimentation rate, and hepatic and renal function test results were normal. He had no comorbid conditions, or past medical or surgical illness.

Radioimaging [Figure 1]A revealed right parietotemporal lobe mass with marked perilesional edema and subfalcine herniation. Magnetic resonance spectroscopy (MRS) revealed reversed N-acetyl aspartate/creatine and increased choline/creatine ratio suggestive of primary central nervous system lymphoma, glioblastoma multiforme, or tumefactive demyelination.

On frontal craniotomy, the mass was found infiltrating into adjacent brain tissue, hence subtotal resection was performed. Histopathology revealed sheets of mononuclear cells and foamy histiocytes with emperipolesis [Figure 1]B and [Figure 1]C. Background stroma showed fibrosclerosis [Figure 1]D. Arterial and venous channels showed florid GA [Figure 2]A and [Figure 2]B. The adjacent brain exhibited coagulative “infarct” necrosis and reactive astrogliosis. Histologic differentials included tuberculosis, tumefactive demyelination, lymphomatoid granulomatosis, IgG4-related disease, and Wegener's granulomatosis. Eosinophils, Langerhans “grooved nuclei” cells, and atypical lymphoid cells were absent. Fungal and mycobacterial stains were negative. Luxol fast blue stain did not reveal demyelination. Serology was negative for retrovirus and autoantibodies. On IHC, the cells were positive for S100, CD68, and focally for CD1a [Figure 2]C and [Figure 2]D, while being negative for Epstein–Barr virus and IgG4. IHC for Langerin, electron microscopy, and molecular studies were not possible due to economic constraints.{Figure 1}{Figure 2}

The patient was advised low-dose radiotherapy, which he refused. During a 6-month follow-up, there was no recurrence or disease progression. Thereafter, the patient was lost to follow-up.

Our institutional ethics approval is given for clinical studies only. This is a case report, hence no ethics approval. The requirement for informed consent was waived considering the retrospective nature of this study.


Rosai Dorfman is a polyclonal, nonneoplastic histiocytic proliferation commonly affecting the lymph nodes. Only 5% of cases reported isolated intracranial RDD presenting as dural (71%), lobar, and sellar (29%) mass.[1] Clinical presentations include seizures, cranial nerve palsies, and pituitary dysfunction. There is accompanying fever, leukocytosis, anemia, raised erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Intracranial RDD presents in elder age (mean 34.9 years) and has a strong male preponderance, unlike nodal RDD, which presents with a male: female ratio of 1.4:1 and an average age of 20.6 years.[1]

Radiologically, T2 hypointensity is due to the free radicals produced by histiocytes. RDD can simulate granulomatous lesions on MRS and on histopathology.[1]

Intracranial RDD requires total resection. Subtotal resection performed due to multiple or infiltrative masses may lead to disease progression. Adjuvant gamma knife irradiation, low-dose methotrexate, 6 mercaptopurine, or steroids are advocated for surgically untreated and residual RDD.[1] Intracranial RDD tends to progress or recur, unlike nodal RDD that tends to resolve spontaneously.[1]

Microscopic mimics of RDD[1],[2] include lymphoplasmacytic meningioma, granulomatous lesions, and LCH. RDD shows emperipolesis, namely histiocytes with intact engulfed cytoplasmic lymphocytes, red corpuscles, plasma cells, and neutrophils.[3],[4] This differentiates it from hemophagocytosis having lysosomal digestion. A defective Fas/Fas L signaling with altered apoptosis is postulated to cause uncontrolled histiocytic proliferation. The activated macrophages release interleukin-1 and tumor necrosis factor-alpha, which lead to gammaglobulinemia and systemic symptoms.[3],[4]

The characteristic IHC pattern includes positive CD68, S100, and acid phosphatase, while being negative for CD1a and langerin. This pattern distinguishes polyclonal, reactive RDD from the CD1a positive, clonal LCH.[1],[2],[3],[4]

O'Malley et al.[5] reported concurrent foci of RDD (80%–95%) and LCH (5%–15%) within the lymph nodes. Foci having RDD showed the absence of genetic mutations while LCH foci showed loss of 1p, 5q, 9p, and 16p.[5] They speculated that cytokine-mediated alteration in a common precursor histiocyte may lead to clonal transformation into LCH. Our case exhibited CD1 positivity. Our institute did not have the facility for Langerin antibody and array comparative genomic hybridization, as used by O'Malley et al.[5] Causal association between RDD-LCH, if any, can only be established in future studies using molecular techniques and clinical follow-up.

Our case exhibited exuberant GA along with tumefactive RDD. Only two publications have reported GA with RDD.[6],[7] Tumefactive GA requires surgical resection along with adjuvant steroid or cyclophosphamide therapy. GA and RDD, thus, have overlapping therapeutic modalities for the prevention of disease recurrence and progress.

Tumefactive obliterative phlebitis, fibrosclerosis, and lymphoplasmacytic cell infiltration, as noted in our case, are also features of IgG4-related disease. Definitive diagnosis requires demonstration of >50 IgG4 plasma cells per high-power field and IgG4: IgG ratio >40%.[8] T regulatory cells stimulate IgG4 production. Zhang et al.[9] found higher numbers of T regulatory cells in extranodal RDD than those in nodal RDD, thus suggesting a connection between RDD and IgG4 disease. Lui et al.[10] estimated that steroid therapy may obviate the need for neurosurgical resection. In our case, IgG4 was negative.

To date, literature has not reported a concurrent triad of RDD-LCH-GA. Intracranial RDD, being rare itself, has a worse prognosis than nodal RDD. RDD-GA has common therapeutic modalities. CD1a positivity in RDD should be further confirmed with the Langerin antibody. Any proven coexistence requires close clinical follow-up and molecular studies to rule out the clonal transformation of reactive RDD into neoplastic LCH.



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Institutional review board statement

Our institutional ethics approval is given for clinical studies only. This is a case report, hence no ethics approval.

Declaration of patient consent

The authors certify that they have obtained the patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity.

Conflicts of interest

There are no conflicts of interest.


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