An enigmatic clinical entity: A new case of olfactory schwannoma

Abstract

Olfactory schwannomas, also described as subfrontal or olfactory groove schwannomas, are very rare tumors, whose pathogenesis is still largely debated. We report a case of olfactory schwannoma in a 39-year-old woman who presented with anosmia and headache. The clinical examination did not show lesions in the nose-frontal region and there was no history of neurofibromatosis. Head MRI and CT scan revealed a lobulated extra-axial mass localized in the right anterior cranial fossa that elevated the ipsilateral frontal pole. Bilateral frontal craniotomy demonstrated a tumor strictly attached to the right portion of the cribriform plate that surrounded the right olfactory tract, not clearly identifiable. The immunohistochemical analysis suggested the diagnosis of typical schwannoma. The patient was discharged without any neurological deficit and a four-month postoperative MRI scan of the brain showed no residual or recurrent tumor.

Introduction

Schwannomas are usually benign, isolated and slow-growing neoplasms originating from Schwann cells of peripheral or cranial nerves. They represent about 8% of all intracranial tumors and arise most commonly from the vestibular branch of the eighth cranial nerve. Olfactory schwannomas are very rare and are considered enigmatic clinical entities because the olfactory nerve does not have a Schwann cell layer.¹ To date only 45 cases not associated with neurofibromatosis have been described in the literature and their origin is still controversial.² We report a rare case of olfactory schwannoma in a 39-year-old woman who presented with anosmia and headache.

Case report

A 39-year-old woman came to our attention with a nine-month history of frontal headache and loss of the right olfactive function. She denied other symptoms such as seizures or epistaxis; the neurological examination revealed right anosmia but was negative for other cranial nerve-associated symptoms or signs.

The physical examination did not show masses in the nose-frontal region or general cutaneous stigmata of neurofibromatosis and there was no pertinent family history.

At endoscopy, nasal fossae and oro-pharynx did not show any lesion.

A magnetic resonance imaging (MRI) scan of the brain was performed. It was carried out with a 1.5 T MR scanner (Philips Intera) using a phase-array head coil. The study consisted of spin-echo T1-weighted (repetition time (TR)/echo time (TE)/number of excitations (Nex): 542/15/2), turbo-spin-echo T2-weighted (TR/TE/Nex:2200/120/1), diffusion-weighted/single-shot (TR/TE: 2561/89, b factor: 0 s/mm² and 1000 s/mm²) and fast-field-echo (TR/TE: 760/23) sequences on the axial plane, fluid-attenuated inversion recovery (FLAIR) (TR/TE/TI: 6000/120/2000) on the coronal plane, turbo-spin-echo T2-weighted sequence on the sagittal plane and spin-echo T1-weighted sequence after intravenous (IV) administration of gadoterate meglumine (0.1 mmol/kg) on the axial, sagittal and coronal planes. It demonstrated an expansive, lobulated, extra-assial, 5 × 1.8 cm mass located in the right anterior cranial fossa, near the midline. It was localized in the right portion of the cribriform plate and elevated the frontal pole; the lesion appeared hypointense on T1-weighted images (Figure 1(a)) and hyperintense on T2-weighted images (Figure 1(b)), showing heterogeneous enhancement after gadolinium injection (Figure 2). A non-contrast head computed tomography (CT) scan, using a 64-slice scanner (Aquilion), was also performed. At CT imaging the mass was ipodense with nodular calcifications (Figure 3). Preoperative diagnosis was a subfrontal meningioma.

Figure 1.

Brain magnetic resonance (MR) axial images demonstrating an expansive, lobulated, extra-assial mass located in the right anterior cranial fossa near the midline, hypointense on T1-weighted images (a) and hyperintense on T2-weighted images (b).

Figure 2.

Brain magnetic resonance (MR) axial (a), coronal (b) and sagittal (c) T1-weighted post-contrast images demonstrating a heterogeneous enhancement of the mass.

Figure 3.

Non-contrast head computed tomography (CT) axial images demonstrating an ipodense mass with nodular calcifications.

The patient underwent bilateral frontal craniotomy and total excision of the tumor. The mass was solid and located in the intradural, extra-axial space, firmly adhered to the right cribriform plate and completely separate from the adjacent cortex. The right olfactory tract was not identifiable while the left olfactory bulb was intact. Histological examination showed that the excised tumor was composed of palisades of spindle-shaped cells with elongated nuclei and less cellular areas. The immunohistochemical analysis revealed that the tumor cells were strongly positive for S-100 protein and negative for epithelial membrane antigen (EMA) (Figure 4(a) and (b)). These findings suggested the diagnosis of typical schwannoma. The postoperative non-contrast brain CT scan showed a total resection of the tumor with a small fluid collection in the previous tumor site (Figure 5). The patient was discharged without any neurological deficit two weeks after surgery. A new MRI scan of the brain, with the same technical parameters and sequences of the first exam, was performed four months after the resection of the mass and showed no residual or recurrent tumor (Figure 6).

Figure 4.

Photomicrographs of the surgical specimen show benign spindle-shaped cells, with elongated nuclei and fibrillary cytoplasm (Antoni A pattern), and less cellular, loosely textured tumor areas (Antoni B) (hematoxylin and eosin (H&E) 200×) (a). Immunohistochemical examination shows that the tumor cells are positive for S-100 protein (400×) (b).

Figure 5.

Postoperative non-contrast head computed tomography (CT) axial image demonstrating a total resection of the tumor with a small fluid collection in the previous tumor site.

Figure 6.

Four-month postoperative brain magnetic resonance (MR) axial (a), coronal (b) and sagittal (c) T1-weighted post-contrast images demonstrating no residual or recurrent tumor.

Discussion

Intracranial schwannomas not associated with cranial nerves are extremely uncommon and their most frequent location is the anterior cranial fossa, mainly in the midline. To date, approximately 45 cases of anterior cranial fossa schwannomas have been reported in the literature and they have been described using different denominations, such as subfrontal, olfactory or olfactory groove schwannomas.³ The origin of these kinds of lesions is still ambiguous because there is no Schwann cell layer surrounding the olfactory nerve. Several hypotheses, divided into developmental and non-developmental theories, have been proposed to explain their genesis.⁴

According to the developmental theories, these tumors may derive from the transformation of mesenchymal pial cells into ectodermal Schwann cells; other theories suggest that they arise from multipotential mesenchymal cells or displaced neural crest cells forming foci of Schwann cells (schwannosis) within the central nervous system parenchyma.^5,6

The non-developmental theories propose that subfrontal schwannomas originate from Schwann cells normally present in adjacent neural structures such as perivascular nerve plexi surrounding cerebral arterioles and large arteries in the subarachnoid space, the anterior ethmoidal nerves innervating the anterior cranial fossa and the olfactory groove, the meningeal branch of the trigeminal nerve and the fila olfactoria, provided with a Schwann-cell sheath that extends 0.5 mm beyond the olfactory bulb. Furthermore, reactive pathological changes including formation of Schwann cells from multipotential mesenchymal cells have been described in patients with multiple sclerosis or infarction.⁷

Controversies also exist about the intra- or extra-axial localization of these tumors. The developmental theories could explain the origin of intraparenchymal schwannomas but subfrontal schwannomas, adherent to the cribriform plate and olfactory groove, are usually extra-axial rather than intra-axial lesions.^1,8

Recently some authors have speculated that olfactory schwannomas are not truly schwannomas. In 2006 Yasuda and collaborators introduced the concept of the olfactory ensheathing cell (OEC) tumor. OECs are localized in the nerve-fiber layer of the olfactory bulb and along the primary olfactory pathway of normal adult animals and humans; they are specialized glial cells that surround the olfactory sensory axons, promoting their growth and regeneration.^9,10

Schwann cells and OECs have a different embryological origin as the former derive from the neural crest while the latter originate from olfactory placodes. Despite that, schwannomas and OEC tumors share similar clinical, imaging and histologic characteristics.⁷

Schwannomas are encapsulated tumors, characterized by two histologic architectural patterns: Antoni type A, composed of spindle-shaped cells with elongated nuclei aligned in a row called a pallisaded appearance, and Antoni type B, showing large myxoid areas with pseudocystic structures.¹¹ At immunohistochemical analysis, they always show strong positivity for S-100 and negativity for EMA.⁷ Yasuda et al. reported that OEC tumors and schwannomas showed similar hematoxylin and eosin (H&E) staining characteristics and identical immunohistochemical reactivity for S-100 and EMA stain; the only exception was that OEC tumors were negative and schwannomas were positive for Leu-7 (CD-57).⁹ It must be considered, however, that in the literature there are few olfactory schwannoma cases reporting that Leu-7 staining has been undertaken; moreover, in 1988, Johnson et al. stated that 20% of schwannomas are negative for Leu-7.¹²

In 2007 Adachi and colleagues classified subfrontal schwannomas into two main types: schwannomas of the olfactory site (olfactory groove or cribriform plate) and “other than olfactory-site” schwannomas, arising from nonolfactory sites. In their opinion the majority of these tumors arise from the fila olfactoria and the growth of the mass distorts the anatomy, stretching the olfactory nerve and making it hard to identify during surgery.¹³ According to Figueiredo et al., considering the absence of anosmia/hyposmia in almost half of the reported cases, the individualization of the olfactory tract in 36.3% of cases and the predominant midline occurrence, meningeal branches of the trigeminal nerve and anterior ethmoidal nerves are the most probable origin of olfactory groove schwannomas.¹ Recently Okamoto et al. reported a case of subfrontal schwannoma located between the outer endosteal layer and the inner meningeal layer of the dura mater. They speculated that such schwannomas may arise from the Schwann cells of nerves that penetrate through the dura mater or from Schwann cells associated with fila olfactoria.³ In our case the mass was strictly adherent to the cribriform plate and involved extensively the right olfactory tract, so we speculated a tumor origin from the fila olfactoria. The debate about the origin of olfactory schwannomas is, evidently, still open. Subfrontal schwannomas tend to occur in patients younger than those affected by schwannomas in more common sites. The median age is 33 years while the male:female ratio is about 1:5. Clinically patients can report a history of headache, seizure, hyposmia/anosmia and visual disorders, cognitive disturbances, rhinorrhea and signs and symptoms related to elevated intracranial pressure.^1,2 The differential diagnosis of extra-axial masses located in the anterior cranial fossa, involving the cribriform plate with extension to the ethmoid sinus, should include meningioma, schwannoma, esthesioneuroblastoma, ethmoid carcinoma, lymphoma and metastatic disease. Subfrontal schwannoma and olfactory groove meningioma have similar radiological features such as calcifications, contrast enhancement and perifocal edema; however, the presence of bone scalloping on CT, the absence of a dural tail sign and hyperostosis may help to orientate the diagnosis toward schwannoma. Esthesioneuroblastoma, ethmoid carcinoma, lymphoma and metastases are more aggressive and cause marked bony destruction with invasion of the paranasal sinuses.^2,6,7,14 A T2*-weighted MRI sequence, showing multiple foci of low signal intensities (due to microbleeds) in schwannomas, can be useful in obtaining the right diagnosis.¹⁵ As to the treatment options, surgery is surely the main therapeutic modality; a complete excision of the mass is curative and can prevent local recurrence.¹¹

Conclusions

Olfactory schwannomas are rare tumors, probably often underreported or misdiagnosed, whose origin is still largely debated. Further investigations about their pathogenesis are surely needed. They must be included in the differential diagnosis of extra-axial lesions of the anterior cranial fossa, involving the cribriform plate, especially in young patients. Because of their benign nature, complete surgical removal represents a definitive treatment.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.