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Case Report
2021
:12;
292
doi:
10.25259/SNI_918_2020
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Rosai-Dorfman disease mimicking images of meningiomas: Two case reports and literature review

, , , , , ,
1Department of Medicine, Albert Einstein Israeli Faculty of Health Sciences, São Paulo, Brazil.
2Department of Medicine, Catanduva Medical School (FAMECAUNIFIPA), Catanduva, Brazil.
3Department of Medicine, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, Brazil.
4Department of Medicine, São Leopoldo Mandic, Campinas, Brazil.
5Department of Neurosurgery, Hospital Saúde de Caxias do Sul, Caxias do Sul, Brazil.
6Department of Neurology, Pontifical Catholic University of São Paulo, Sorocaba, Brazil.
*Corresponding author: Rafael Trindade Tatit, Department of Medicine, Albert Einstein Israeli Faculty of Health Sciences, Sao Paulo, Brazil. rtrindadetatit@gmail.com
Received: , Accepted: ,
Copyright: © 2021 Surgical Neurology International
Licence

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Tatit RT, Raffa PE, de Almeida Motta GC, Bocchi AA, Guimaraes JL, Franceschini PR, et al. Rosai-Dorfman disease mimicking images of meningiomas: Two case reports and literature review. Surg Neurol Int 2021;12:292.

Abstract

Background:

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferative disorder classically as a massive cervical lymphadenopathy. However, over the years, extranodal locations were confirmed with the central nervous system involvement in less than 5% of cases, which is marked as a significant differential diagnosis of meningiomas, with which they are widely confused due to the similarity of their radiological images.

Case Description:

We report a 37-year-old man and 45-year-old man who were diagnosed with intracranial RDD but whose radiological images mimic meningiomas, requiring anatomopathological and tumor’s immunohistochemistry for definitive diagnosis. Moreover, a review of 184 publications with 285 cases of intracranial involvement of this disease was also performed, comparing these findings with those brought in the previous studies.

Conclusion:

Intracranial Rosai-Dorfman tumors should always be remembered as differential diagnosis of meningiomas since they are similar radiologically and macroscopically. Once remembered and diagnosed, the lesion must be treated following the same pattern of resection done in meningiomas and, treatment’s differences will not occur in the surgical excision technique, but in complementary chemotherapy implementation, radiotherapy, and even with radiosurgery aid, depending on the case. Thus, it is possible to obtain better results than with just the isolated surgical procedure.

Keywords

Central nervous system
Histiocytosis
Magnetic resonance imaging
Meningioma
Rosai-Dorfman disease
PubMed
Show Related Articles from PubMed

INTRODUCTION

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes in the affected tissues. Widely heterogeneous and with a variety of clinical phenotypes, it may be present from the isolated form to the form in association with other diseases such as autoimmune,[49,197] hereditary,[125,131,211] or malignant.[6,69,112,116,136] Its importance is marked as a significant differential diagnosis of meningiomas, with which they are widely confused due to the similarity of their radiological images, being differentiated by surgically resected tissue histopathological analysis.[63,132,148,180]

His first description dates back to 1965 by a French pathologist - Pierre Paul Louis Lucien Destombes,[40] and 4 years later was exhaustively studied by Rosai and Dorfman, who analyzed 34 cases of the same disease under the name of sinus histiocytosis with massive lymphadenopathy.[155] Classically, RDD presents as a bilateral cervical lymphadenopathy, but in 43% of patients the disease presents as an extranodal location.[49] It is important to point out that RDD is a rare disease, with prevalence of approximately 1:200,000 people,[122] with involvement of the central nervous system (CNS) occurring in less than 5% of cases of RDD and, within this portion, approximately 75% present themselves as intracranial lesions and 25% as spinal lesions.[14] As for the age group, nodal RDD is more frequently observed in children and young adults (mean age 20.6 years), being more present in men (male/female ratio 1.4:1).[99,105,149] However, when intracranial RDD is involved, the age group most affected changes, generally affecting adult men in the fourth and fifth decades of life (mean age 39.5 years).[27,63]

In intracranial RDD, the most involved structures are the suprasellar region, cerebral convexity, parasagittal region, cavernous sinus, and petroclival region,[99,149] with infratentorial parenchymal lesions being the most frequent,[198] while supratentorial, intraventricular, and multifocal lesions are observed with significantly lower frequency.[130,148] Radiologically, intracranial RDD is commonly confused with meningioma[63,132,148,180] and requires tumor histopathology and immunohistochemistry for its definitive diagnosis. In anatomopathological examination of the lesions, histiocytes with large and discolored cytoplasm with large hypochromatic nucleus and prominent nucleolus are present.[40] Emperipolesis is a useful finding, although not necessary for diagnosis.[42] In immunohistochemical examination, histiocytes are positive for S-100 and CD-68 protein and negative for CD1a[27,99,156] and moreover for symptoms, usual presentations of intracranial RDD include seizures, headache, cranial nerve deficits, hemiparesis, and dysphasia,[87] usually evolving over weeks or months.[161]

The present study reports two cases of RDD with intracranial involvement, one of them with follow-up of more than 15 years. A review of 184 publications with 285 cases of RDD with CNS involvement (CNS-RDD) was also performed, comparing these findings with those brought in the previous studies. For identifying the studies, the MeSH tool from PubMed database was used, using the keywords “Histiocytosis, Sinus” restrict to MeSH Major Topic (entry terms: histiocytoses, Sinus; Sinus Histiocytoses; Sinus Histiocytosis; RDD; Disease, Rosai-Dorfman; RDD; Sinus Histiocytosis with Massive Lymphadenopathy; DestombesRosai-Dorfman Syndrome; Destombes Rosai Dorfman Syndrome; and Syndrome, Destombes-Rosai-Dorfman) and the keyword “Central Nervous System;” no filter was used for languages, date of publication or type of study. In addition, manual searches were performed based on the studies found by the initial electronic search. All articles including new cases of the disease and containing basic information (sex, age, location of the pathology, and if there was isolated involvement of the CNS) were included in the study.

CASES REPORTS

First case report

Male patient, 37 years old, presented 4 years before with painless left supraclavicular adenomegaly, with progressive increase followed by intense pain in the left clavicle after physical activity. Imaging examinations demonstrated the presence of bone infiltration, supraclavicular and infraclavicular adenomegaly, as well as lesions in the orbit and cranial cap. Biopsy of supraclavicular lymph node confirmed lymphadenitis with massive sinus histiocytosis compatible with RDD, with immunohistochemical examination demonstrating CD68 and S100 positive and CD30 and CD1a negative. The patient initially presented an excellent response with corticoids using, noting significant regression of adenomegaly, and general improvement of symptoms. In the last year, however, he began to refer to migratory arthralgia with an increase in cervical adenomegalies, requiring the continuous use of corticoids and increased doses in exacerbations, and he presented with pulsatile headache which was often disabling. A skull MRI was performed which revealed an expansive lesion in the left frontal region [Figure 1], requiring hospitalization, and use of prophylactic anticonvulsant. A microsurgery was performed for total resection of the brain tumor [Figure 2], which in the anatomopathological examination showed proliferation of histiocytes of ample cytoplasm and vesicular nuclei with prominent nucleoli, forming aggregates surrounded by lymphoplasmocytic infiltrate and with emperipolesis. The immunohistochemical examination demonstrated histiocytes positive for S-100 and CD-68 protein and negative for CD1a, thus confirming the diagnosis of RDD. A panel of mutations for solid tumors was also performed by Next-Generation Sequencing, with no relevant changes in the areas of interest of the analyzed genes. The patient was discharged 3 days later, remaining in follow-up until now well and without recurrence.

Figure 1:: Magnetic resonance imaging showing expansive lesion in the left frontal region with left to right mass effect and surrounding edema. (a) Axial gadolinium-enhanced image. (b) Axial FLAIR. (c) Axial T2-weighted.
Figure 2:: Magnetic resonance imaging at the post operated showed total resection of the left frontal tumor associated with edema, determining deletion of the local cortical grooves, compression of the frontal horn of the left lateral ventricle and contralateral midline deviation. (a) Axial gadolinium-enhanced image. (b) Axial T2-weighted.

Second case report

Male patient, 45 years old, receives specialized neurological care with convergent strabismus and complaint of diplopia, headache, ringing in the left ear and hypoacusis for 6 months. A gadolinium-contrasted MRI examination was requested, which demonstrated a lesion in the petroclival region invading the cavernous sinus with extension into the posterior fossa, with contrast uptake compatible with meningioma. MRI also showed that the lesion reached the cervical region, descending through the petroclival portion, and bordering the clivus [Figure 3]. The patient was then submitted to a combined subtemporal and presigmoid route for partial resection – leaving only part of the lesion in the middle fossa [Figure 4] – of the possible meningioma, which after anatomopathological analysis was concluded it was not a meningioma but a case of RDD. Then, continuous chemotherapy treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and radiotherapy in specialized oncology services was started for 2 years and submitted to several sections throughout this period. The patient was operated on with tumor partial resection in 2005, remaining in follow-up until now without recurrence.

Figure 3:: Magnetic resonance imaging preoperated showing expansive lesion in the left petroclival region with left to right mass effect, invading the cavernous sinus with extension into the posterior fossa and reach the cervical region, descending through the petroclival portion, bordering the clivus. Lesion with contrast enhances compatible with meningioma. (a) Coronal gadolinium-enhanced image (GEI). (b and c) Axial GEI.
Figure 4:: (a-c) Magnetic resonance imaging at the post operated showed parcial resection of the left petroclival tumor with remaining lesion in the middle fossa. Axial gadolinium-enhanced image.

DISCUSSION

According to 285 RDD literature reviewed cases [1–5,7,9,10,12–24,26–39,41,44-48,50-54,56-68,70,72-96,98,99,102-111,113-115,117-123,126-129,130,132-135,137-142,144,146-148,150-154,157-161,163-175,177,178,181-185,187-191,193-196,198,200,202-210,212-215,217-221] added two newly cases presented in this study [Tables 1 and 2], we obtained a male/female ratio of 1.9:1 and a mean of 38.51 years and a median of 38 years of age, with 50% of patients aged between 26 and 53 years. The exclusively intracranial involvement was present in 77% (n = 221) of RDD cases, with a mean age of 39.5 years, while the exclusively spinal involvement was present in only 14% (n = 40) of them and with a mean age of 36.4 years. The mean age values obtained are quite close to the mean of 39.5 years described in the previous studies,[27,63] mainly in cases with exclusive intracranial involvement. However, the 1.9:1 male/female ratio obtained in our review was much more remarkable in the prevalence of men than the 1.4:1 in the previous studies.[99,105,149]

Table 1:: Characteristics of CNS-RDD cases according to present and previous reports from references.[1-5,7,9,10,12-24,26-39,41,44-48,50-54,56-68,70,72-96,98,99,102-111,113-115,117-123,126-129,130,132-135,137-142,144,146-148,150-154,157-161,163-1-75,177,178,181-185,187-191,193-196,198,200,202-210,212-215,217-221]
Table 2:: Central nervous system involvement in 287 cases of Rosai-Dorfman disease.[1-5,7,9,10,12-24,26-39,41,44-48,50-54,56-68,70,72-96,98,99,102-111,113-115,117-123,126-129,130,132-135,137-142,144,146-148,150-154,157-161,163-175,177,178,181-185,187-191,193-196,198,200,202-210,212-215,217-221]

On the other hand, comparing the frequencies of intracranial or spinal involvement according to the systemic or non-systemic involvement of the disease, RDD with isolated CNS involvement, reported in 77% (n = 221) of all cases of CNS-RDD, showed that 84% (n = 186) of isolated cases of the CNS had exclusively intracranial involvement and only 10% (n = 23) had exclusively spinal involvement. As for systemics CNS-RDD cases, the exclusively intracranial involvement occurred in 56% (n = 37) of the cases, while the exclusively spinal involvement was present in 26% (n = 17) of them. Therefore, it should be noted that comparing RDD with isolated CNS involvement, systemic CNS-RDD has a lower prevalence of exclusively intracranial involvement and a greater involvement of the spinal cord; in 26% (n = 17) of the cases with systemic presentation there was exclusive involvement of the spinal and in approximately 18% (n = 12) of the cases there was intracranial and spinal involvement. Thus, it is interesting to note that when RDD has systemic involvement, spinal cord involvement is more frequent than in relation to RDD with exclusive CNS involvement, which may have different explanations, such as perhaps because of systemic disease focus origin, usually sinus and with massive lymphadenopathy in the region, be closer to the spinal cord, this will somehow facilitate the disease spread to this nearest neural structure. This would mean that, once systemic RDD was present, it could spread more easily to any location in the CNS, without maintaining the preferential intracranial involvement of CNS exclusive cases.

The typical radiological findings of intracranial RDD show dural-based, extra-axial, well-circumscribed masses mimicking meningioma with MRI usually reveals multiple well-defined, dural-based or intraventricular, extra-axial masses with possible perilesional cerebral edema.[80] Intracranial RDD CT typically presents homogeneous hyperdense or isodense masses, but MRI is currently the optimal diagnostic modality for evaluating lesions. On T1-weighted images, the lesions usually appear as isointense or hyperintense masses with clear borders relative to the peripheral brain parenchyma[56,150,187,196,201] and possible perilesional cerebral edema hypo or isointense.[80] While on T2-weighted images, the lesions usually appear as isointense masses with possible intralesional hypointense foci,[56,150,187,196,201] although studies have described rather low signal intensity on in this type of image.[7,87,196] On the other hand, meningiomas on T2-weighted MR images show low to high signal intensity, varying this according to the histological subtype, and on angiograms are commonly seen as hypervascular lesions,[25] whereas in RDD this results are variable.[76,96] On RDD, in addition, on contrast-enhanced T1-weighted images with gadolinium, the lesions are markedly enhanced, homogeneously or inhomogeneously, and the dural tail sign can commonly be found.[1,47,56,94,150,184,187,196,201] Recently, new MRI sequences have been recommended for the diagnosis of RDD, such as diffusion tensor imaging (DTI), susceptibility-weighted imaging, and perfusion-weighted imaging,[71,77] in addition, the use of 18F-FDG PET/CT has been described to diagnose relapsed intracranial RDD of the hypothalamus in a patient.[39] MRI spectroscopy meningiomas have been shown to have elevated Cho and decreased NAA, which is also seen in many other neoplastic processes, decrease in Cr and prominent Ala, much more so than in other neoplastic processes and is considered a spectroscopic signature for meningiomas.[176] On the other hand, in RDD lesions, spectroscopy generally shows elevated lipid and N-acetyl aspartate peaks, suggestive of granulomatous inflammatory pathology, and a raised choline peak.[199] Furthermore, perfusion MRI imaging can provide useful information on meningioma vascularity which is not available from conventional MRI. Measurement of maximal rCBV and corresponding rMTE values in the peritumoral edema is useful in the preoperative differentiation between benign and malignant meningiomas[216] and the relatively low rCBV perfusion values in CNS-RDD.[199] Regarding to the neuroimaging, the best diagnostic clues for diagnosing CNSRDD appear to be represented by hypo-isointensity in the T2-weighted sequences and the relatively low rCBV perfusion values, likely due to abundant fibrous tissue; however, these findings are not specific and not always present, and the final diagnosis is often still histological.[199] Therefore, preoperative radiological findings using current MRI sequences are difficult to distinguish between meningiomas and RDD; however, it has already been described that the absence of hyperostosis, bony erosion, or calcification – characteristically absent in the RDD[177] – should suggest RDD as a differential diagnosis of meningiomas.[150]

As for the two reported cases of RDD, they were very similar to the expected age group and sex grouping, according to the literature and our review. As for the location of the lesion, which can happen in many regions, including the supratentorial region, where meningiomas occur and in which one of them mimics, the two cases presented in this study are very representative, especially the second one, since at first moment it was thought that it was one of those. Furthermore, the involvement reaching the cervical portion of the second case is compatible with a higher prevalence location of spinal cord injuries according to previous studies.[101] Regarding its severity, although the involvement of CNS is often progressive and fatal, patients undergoing surgical resection have favorable prognosis in many cases.[180] However, surgical resection without complementary or additional therapy is frequently associated with recurrences of the disease[47] and should be associated with complementary or adjuvant treatments. As examples of these, chemotherapy and radiotherapy, which were very successful in the present case, may be indicated and instituted as several authors suggest,[8,9,43,55,97,124,145,153,162,179,186] especially when radical surgical resection of the tumor is not possible – which would be the best approach as several authors defend.[70,151,165] Treatment of resectable intracranial RDD and high risk by means of radiosurgery may also be a therapeutic option to be instituted,[45] obtaining very favorable results when combined with neurosurgical excision.[65,163,201] Furthermore, possibly promising, the use of Brachytherapy, a special way of applying radiation, may be a possible option to be analyzed, having already well documented therapeutic results in the treatment of other pathologies such as gliomas and some extracranial solid tumors.[11,100,143,192,222] Alternatively, the use of glucocorticoids has also shown quite beneficial effects on the regression and resolution of multiple and isolated intracranial lesions[47,126,217] and should be considered as an effective option in the treatment of RDD in certain cases where surgical resection is not applicable.

More importantly, surgical resection should follow the same pattern as meningiomas, since the texture of both is very similar, and it is extremely unlikely that with only radiological images the two pathologies can be differentiated before neurosurgical removal for anatomopathological analysis. At present, the best treatment for intracranial RDD involves surgical excision,[201] as employed in the two cases reported here.

CONCLUSION

Thus, we conclude that intracranial Rosai-Dorfman tumors should always be remembered as differential diagnosis of meningiomas, since they are similar radiologically and macroscopically. Once remembered and diagnosed, the lesion must be treated following the same pattern of resection done in meningiomas and, treatment’s differences will not occur in the surgical excision technique, but in complementary chemotherapy implementation, radiotherapy, and even with radiosurgery aid, depending on the case. Thus, it is possible to obtain better results than with just the isolated surgical procedure.

Declaration of patient consent

Patient’s consent not required as patients identity is not disclosed or compromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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