**2. Rosai-Dorfman disease manifested as an apparent multiple meningiomatosis**

The first case presented in this chapter corresponds to an intracranial Rosai-Dorfman disease (RDD), which was manifested as an apparent multiple meningiomatosis that affected the anterior fossa, the sphenoidal plane, and the clivus. RDD is a non-Langerhans histiocytosis described in 1965 by Pierre P. Destombes and then characterized by J. Rosai and R. Dorfman [4, 5]. RDD has a prevalence of 1 in 200,000 and an incidence of 100 cases per year. It can occur at any age but is usually more common in adolescents [6]. The typical clinical manifestations of this disease are the presence of painless bilateral cervical lymphadenopathy added to the presence of fatigue, fever, and weight loss, associated with elevated erythrocyte sedimentation rate, anemia, fever, and hypergammaglobulinemia. Extranodal involvement occurs in less than 43% of cases, mostly in the skin, nasal cavity, and bone [7]. The central nervous system (CNS) is affected in less than 5% of cases, the isolated affection is possible, without systemic manifestations. There are approximately 200 reported cases of intracranial RDD [8, 9]. This case illustrates a patient with multiple intracranial lesions, where the symptoms and characteristics per image simulated the presence of multiple meningiomas, where the RDD finding was made until the moment of the histopathological study.

#### **2.1 Case presentation**

A 59-year-old male patient with a history of gradual right hearing loss that later presents the same symptoms in the contralateral ear. His current condition began 8 months ago with a high-intensity holo-cranial headache that predominated in the mornings accompanied by occasional dizziness. Three months before his hospital admission, he reported non-quantified weight loss, asthenia, and adynamia.

Two months before hospital admission, the patient reported decreased visual acuity and compromise of the temporal hemifields added to hyposmia. The reason for hospital admission in our institution was the presence of two generalized tonic– clonic seizures lasting more than one minute (less than five minutes), these seizures were characterized by the absence of aura, with a postictal period of 20 minutes. The second seizure required hospital admission for control. On physical examination, the cognitive functions were preserved, evaluation of the cranial nerves demonstrate hyposmia and bitemporal hemianopia. Fundoscopy showed edema of the papilla in the left eye and an atrophic papilla of the right eye. Regarding the complementary studies, the electroencephalogram showed abnormal bifrontal activity. Computed campimetry confirmed the bitemporal hemianopia, and regarding the neuroimaging studies, the computed tomography (CT)-scan showed three isodense with homogeneous enhancement lesions located in the midline in the floor of the anterior fossa in the cribriform plate, the sphenoidal plane with extension to the tuberculum sellae, and the middle and lower portion of clivus. The magnetic resonance imaging (MRI) revealed isointense lesions with peritumoral edema, with intense and homogeneous gadolinium-enhancement demonstrating a dural attachment (**Figure 1A–F**).

The diagnosis of multiple meningiomas was established, supported by the neuroimaging features and previous experience. The surgical plan was to resect the two main symptomatic lesions (olfactory groove and tuberculum sellae). The surgical approach was made through a bicoronal incision to perform a bifrontal craniotomy and a sub-frontal approach. The surgical approach allowed a complete resection of the lesions, after the olfactory groove lesion resection was possible to access the lesion of the tuberculum sellae. Debulking of the lesions was made

*Rare Brain Tumors with Infrequent Clinical Manifestations: Illustrative Cases DOI: http://dx.doi.org/10.5772/intechopen.101062*

#### **Figure 1.**

*Pre-operative brain magnetic resonance imaging (MRI) studies. Non-contrasted brain MRI shows an isointense olfactory groove lesion with perilesional edema in the T1-weighted (A), T2-weighted (B), and FLAIR (C). Contrasted brain MRI reveals three homogeneous enhancement lesions with dural attachment (yellow arrows in the sagittal section) in the floor of the anterior fossa in the crista Galli and cribriform plate, the sphenoidal plane with extension to the tuberculum sellae, and the middle and lower portion of clivus, observed in the coronal (D), sagittal (E), and axial sections (F). Histopathological analysis. G. Positive immunohistochemical profile for S100 protein. Furthermore, other immunochemical profiles show positive expression of CD68 (macrophages), CD20 (B lymphocytes), and CD2 (T lymphocytes), in which lymphagocytosis was observed. IgG and IgG4 positivity were also identified. A negative expression for CD30 and CD15 (reed Stenberg cells), and CD1A (Langerhans cells) was observed. H. H&E Stain: Mixed inflammatory infiltrate with plasma cells, lymphocytes, and macrophages, no evidence of meningothelial cells, emperipolesis was observed (black arrow).*

with an ultrasonic aspirator, and according to meningioma surgery principles, it was decided to perform anterior fossa drilling to reduce the recurrence probability. The tumor lesions showed low vascularity and close contact with the optic chiasm (**Figure 2**). Immediately post-operative the patient remained without complications and was discharged five days after surgery, the CT scan performed 5 days after surgery showed complete resection of the lesions (olfactory groove and tuberculum sellae), with residual lesion of the middle and lower portion of clivus (**Figure 2F**). Due to the residual lesion, the patient was observed for the clinical oncology service to decide adjuvant management.

Histopathological findings established the diagnosis of RDD (**Figure 1G** and **H**). In the subsequent follow-up, extension studies were carried out, which were ruled out other infiltrates with a thoracic and abdomen-pelvic CT. The patient received treatment with prednisone and remain asymptomatic without clivus lesion growth at 8 months follow-up.

#### **2.2 Case discussion**

For the diagnostic process of RDD, it is important to consider the observations by imaging studies that usually mimic the characteristics of a meningioma, either as one or multiple extra-axial lesions with homogeneous contrast enhancement surrounded by vasogenic perilesional edema, they can arrive to present a dural tail and its location is very diverse [1]. Proton MRI spectroscopy improves the specificity of preoperative diagnoses in some patients; for example, in meningiomas, alanine is usually elevated in spectroscopy, with a peak at 1.48 ppm, in a patient with RDD disease, spectroscopy revealed an increased choline level [10]. In a review of 10 cases, a dural tail was found in all cases. Therefore, in data suggestive

#### **Figure 2.**

*(A) Preoperative enhanced coronal head CT-scan with an olfactory groove lesion (square). Surgical procedure: Approach to the anterior fossa lesion. Perimeter dissection of the anterior cranial fossa lesion (asterisk) is shown (B-C). Debulking with ultrasonic aspiration (D) and complete resection of olfactory groove (E) is demonstrated. (F) Sagittal section of postoperative CT with complete resection (arrow).*

of meningioma obtained by neuroimaging studies, RDD is a differential diagnosis [11]. Zhu et al. [11] concluded that, unlike meningiomas, a typical hypointensity non-related to calcification on T2-weighted or fluid attenuation inversion recovery (FLAIR) images could suggest the RDD diagnosis.

#### **Figure 3.**

*Algorithm for management and diagnosis (clinical suspect) for intracranial Rosai-Dorfman disease. Clinical suspicion is obtained by clinical evaluation and imaging studies. The differential diagnosis is made with meningioma, corroborating it by the histopathological and immunohistochemical study. Relative to management, the presence of residual tumor after surgery suggests performing radiotherapy with or without chemotherapy. Strict monitoring after surgery is recommended due to the risk of recurrence.*

*Rare Brain Tumors with Infrequent Clinical Manifestations: Illustrative Cases DOI: http://dx.doi.org/10.5772/intechopen.101062*

Histopathological characteristics correspond to a large lymphohistiocytic infiltrate, with a large or vesicular nucleus, well-defined nuclear membranes and a single and prominent nucleolus. The main characteristic is the intracytoplasmic presence of lymphocytes and, to a lesser extent, intact erythrocytes, plasma cells, and neutrophils ("emperipolesis"), however, it may be absent in 30% of leptomeningeal lesions [7, 9]. Associated with histiocyte proliferation, a perivascular plasmacytic infiltrate can be observed. From the immunohistochemical point of view, they are characterized by presenting protein S100 +, CD68 +, CD11c +, MAC387 +, lysozyme +/−, being negative for CD1a, a positive marker in Langerhans cell histiocytosis [10, 12].


*RDD, Rosai-Dorfman disease; MRI, Magnetic resonance imaging; FLAIR, Fluid attenuation inversion recovery; HFS, Hemifacial spasm; EMG, Electromyography; NEC, Neuroenteric cyst; DWI, Diffusion-weighted imaging; CA 19-9, carbohydrate antigen 19-9; CSF, Cerebrospinal fluid.*

#### **Table 1.**

*Rare tumors: Pearls and pitfalls in diagnosis, surgical management, and prognosis.*

Related to the management of this disease is primarily with surgery, seeking to eliminate the mass effect and the associated neurological sequelae. Total resection is the main objective, although a partial resection is allowed in case the lesions are in complex regions. The optimal management of residual disease remains unclear due to the rarity of the disease [13]. The use of radiotherapy has shown some efficacy of residual or recurrent disease, postoperative doses of 20 Gy in 10 fractions in 2 weeks after subtotal resection has shown a good effect in reducing symptoms and reducing the size of the lesions [14]. The use of chemotherapeutic agents such as alkaloids and anthracyclines, alkylating agents, and methotrexate have shown variable efficacy [15]. Rivera et al. [16] reported the use of the modified CHOP regimen in two cases of intracranial RDD observing a long-term remission [16].

Adeleye et al. [17] reported a series of 111 cases of RDD involving the CNS [17]. Of the population studied, 77% presented intracranial disease, which received various treatments with surgery, radiotherapy and chemotherapy. 37% of the study population had a long-term follow-up beyond one year (41% of these patients had no recurrence of the disease), where a relapse or growth of the most residual tumor was determined in 12%. Therefore, active monitoring after the surgery is prudent; however, it is not well established how often to follow up with imaging studies and when it would be prudent to classify the disease as remitted. Rivera et al. [18] reported the longest reported follow-up time (7 years) [18], of two patients with intracranial RDD with surgical resection and chemotherapeutic management with the modified CHOP scheme consisting of 8 cycles of cyclophosphamide (1 g), Vincristine (2 mg), doxorubicin (50 mg), and prednisone (50 mg) for 5 days every 3 weeks. Where it was observed that during follow-up there were no recurrences. Due to the low incidence of the disease, it is difficult to standardize diagnostic, therapeutic and prognosis. For this reason, we propose a simple algorithm for the diagnosis and management of intracranial RDD (**Figure 3**). **Table 1** describes the fundamental aspects in the management of this pathology.
