Intraparenchymal Schwannoma: A Rare Entity

ABSTRACT

A 60-year-old woman noted headaches, transient visual obscurations and pulsatile tinnitus. She had Frisén grade 4 papilloedema. Brain magnetic resonance imaging showed a large subfrontal cystic mass with ring enhancement. Tumour pathology was in-keeping with an intraparenchymal schwannoma. This uniquely rare tumour is discussed.

Introduction

A 60-year-old woman reported headaches, transient visual obscurations and pulsatile tinnitus for 2 weeks. She had been fatigued for 4 months and had been prescribed levothyroxine for hypothyroidism. Her past medical history also included osteoporosis for which she was taking alendronate and calcium. She did not smoke nor consume alcohol.

Examination showed an alert and orientated woman with normal vital signs. Her visual acuity was 20/25 in each eye (OU) and colour vision was intact OU. Automated perimetry showed enlarged blind spot and nasal defects OU. Her pupils measured 5 mm in each eye with 2+ reactivity and there was no relative afferent pupillary defect (RAPD). Her eye movements were intact and the slit lamp examination was normal. There was Frisén grade 4 papilloedema with retinal haemorrhages and exudates OU (Figure 1).

Figure 1.

Fundus photographs. There is Frisén grade 4 papilloedema with splinter and dot-and-blot haemorrhages OU and retinal exudates OD (left image)

Magnetic resonance imaging (MRI) of the brain and orbits with and without fat suppression and gadolinium showed a subfrontal cystic mass with peripheral ring enhancement (Figure 2).

Figure 2.

Upper images left to right: Axial and coronal T1-weighted brain MRI after contrast and lower images left to right: mid-sagittal T1-weighted brain MRI before and following intravenous contrast showing a large subfrontal cystic mass with peripheral ring enhancement

Complete blood count, metabolic panel, glucose, thyroid function testing, adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinising hormone (LH), cortisol and prolactin were all normal. A contrast-enhanced computed tomography (CT) scan of the chest, abdomen and pelvis was normal.

The patient underwent a bicoronal craniotomy for tumour resection with the use of stealth navigation. An MRI day 1 post-operation showed a residual cystic cavity in the frontal interhemispheric region with surrounding oedema (Figure 3). Histological examination of the tumour showed a spindle cell neoplasm with collagen stroma. There was nuclear regimentation consistent with a poorly formed Verocay body. Cytoplasmic and nuclear staining for S-100 protein was present with characteristic pericellular staining with basal lamina protein Collagen Type IV. Epithelial membrane antigen (EMA) was negative. This was all in-keeping with a WHO Grade I schwannoma (Figure 4).

Figure 3.

Left to right: Post-op day 1, coronal T1-weighted MRI after contrast and fluid attenuated inversion recovery (FLAIR) MRI showing a residual cystic cavity in the frontal interhemispheric region with surrounding oedema shown as hyperintensity on the FLAIR image

Figure 4.

Intraparenchymal schwannoma – histology. (a). Appearance of a spindle cell neoplasm with collagen stroma (haematoxylin and eosin stain x 100). (b). Neoplasm exhibits nuclear regimentation consistent with poorly formed Verocay body (circle) (haematoxylin and eosin stain x 200). (c). Neoplastic cells exhibit cytoplasmic and nuclear staining for S-100 protein (x 200). (d). Neoplastic cells exhibit characteristic pericellular staining with basal lamina protein Collagen type IV (x 200)

One month later the patient had normal acuity, colour vision, visual fields and a 0.9 log RAPD right eye (OD). The optic discs appeared normal and there was residual macular exudate OD greater than in her left eye (OS). The patient’s RAPD soon resolved and her brain MRI continues to be free of tumour recurrence 10 years later.

Discussion

Intracranial schwannomas represent approximately 8% of all intracranial tumours with 80 to 90% being in the cerebellopontine angle in association with the vestibular nerve.¹ The trigeminal nerve is also frequently involved.¹ Less commonly, in descending order they arise from the 9^th, 10^th and 7^th cranial nerves.² Intraparenchymal schwannomas, however only account for 8% of all primary cerebral neoplasms,³ and for < 1% of intracranial schwannomas.⁴ It is exceedingly rare for a schwannoma to occur within the neuraxis, with a brainstem location being much rarer than a cerebral hemisphere one,⁵ and an intraspinal location being far more likely than an intracerebral one.⁶ The first report of an intraparenchymal schwannoma was by Gibson et al. in 1966.⁷ Since then, the literature consists of case reports and small series. A conservative estimate of the total number of cases reported is approximately 120 (including this report)^1–21 with a large case contribution from Luo et al. of 18 patients in 2013.¹¹ Males are affected more often than females. These tumours are more common in patients younger than 25 years, and tend to have an indolent course in this age group.^8,12,13 They have rarely been reported in the middle age and elderly, as in our patient, but if present, they usually have rapidly evolving symptoms.¹² With their unique intraparenchymal location, the commonest presentation of these tumours is with headache followed by seizures, visual disturbances, nasal stuffiness and epistaxis.¹² They have rarely been associated with neurogenic pulmonary oedema.⁴

The diagnosis of intraparenchymal schwannoma is almost never made preoperatively.⁵ On neuroimaging, the differential diagnosis includes meningioma (most common mimicker), glioma and pilocytic astrocytoma among a wide variety of aetiologies including ganglioglioma, pleomorphic xanthoastrocytoma, and dysembryoplastic neuroepithelial tumour.^2,9

On non-contrast enhanced CT scans, these tumours are iso to hypodense, and they enhance uniformly with contrast.^12,14 On MRI, the tumours are hypointense on T1-weighted images and heterogeneously hyperintense on T2-weighted images. The walls of the tumours enhance after gadolinium, and the borders are usually distinct. Frequently, the tumours are also cystic in nature,¹² with the presence of a cyst being the most consistent finding in 60% of patients.^2,15 The cysts may not always be present however, and when the tumours are solid and attached to the dura, they may easily be mistaken for meningiomas.^1,16 These tumours may be intraventricular,^11,17,21 contain calcification,^1–3 are generally solitary and may be associated with neurofibromatosis.^11,18

Pathologic findings are typical of acoustic neurinomas.⁵ Microscopically, schwannomas have a highly ordered cellular component (Antoni A) that palisades (Verocay bodies) and have myxoid hypocellular components (Antoni B). Intracranial examples of schwannomas are frequently lacking in Antoni B tissue, but often demonstrate some level of Antoni A that palisades (Verocay body formation). They may be infiltrated by foamy macrophages and undergo vascular hyalinisation. Strong staining reaction with S-100 and lack of immunoreactivity with EMA (positivity is a characteristic feature of meningiomas), and negative glial fibrillary acidic protein (GFAP) stains often confirms the diagnosis of schwannoma.^2,11,15 No systematic differences in morphology between the rare intraparenchymal schwannoma and the more typical extra-axial, cranial nerve schwannoma generally exist.

In our patient, the diagnosis of schwannoma was based on the presence of rich, diffuse cytoplasm and nuclear staining with the S-100 marker, and the presence of positive collagen IV staining in a membranous pattern around each individual tumour cell. Collagen IV is a major component of basement membranes, and Schwann cells are known to produce pericellular basal lamina, an ability that is characteristically retained in the neoplastic counterpart.²² Our patient did not display Antoni B tissue but did display Antony A that palisades (Verocay body formation). Intracranial schwannomas are frequently lacking in Antoni B tissue, but often demonstrate some level of Verocay body formation.

There were several alternative histological diagnostic possibilities including cystic meningioma, pilocytic astrocytoma or other astrocytic neoplasm (potentially seeded into the meninges), metastatic carcinoma, metastatic melanoma, a primary meningeal sarcoma and neurofibroma. All of these alternatives were eliminated based on the immunohistochemical profile, the histological appearance of the lesion or both. Although astrocytic neoplasms are S100 positive, they should be GFAP immunoreactive. Further, the extensive collagen type IV staining evident in this tumour is not characteristic of astrocytic neoplasms. The morphological features of this tumour, together with the absence of cytokeratin and/or EMA immunoreactivity, mitigates against metastatic carcinoma. Likewise, the morphology and immunophenotype of this tumour are inconsistent with metastatic melanoma. Meningiomas, the main differential diagnosis, should be EMA positive and S100 negative. Our patient was EMA negative and S-100 positive. Finally, this tumour does not show the characteristic mixture of cell types and the presence of axons scattered throughout the tumour; features that are typically present in neurofibromas.

The histogenesis of intracranial schwannomas not arising from cranial nerves remains uncertain. Schwann cells commonly exist in the peripheral nervous system, but not in the parenchyma of the brain.²³ Perhaps ectopic migration of Schwann cells during embryogenesis to brain parenchyma or possible proliferation of mesenchymal pial cells showing histological similarities to Schwann cells may be responsible for these tumours occurrence in the brain parenchyma (developmental theory).^14,19,23 Non-developmental theories suggest that these tumours originate from Schwann cells, which have been detected around arteries in the intracranial perivascular nerve plexuses in the subarachnoid space and the brain parenchyma.^2,19

Because most of these tumours are benign, complete excision is the treatment of choice, and if achieved, usually results in relief of clinical symptoms and excellent long-term outcome.^{2,11,15,19–21} Chemotherapy, and radiotherapy have been utilised in rare cases of recurrence.^10,11

Funding Statement

This work was supported in part by an unrestricted grant from the Research to Prevent Blindness, Inc. New York, NY, USA.

Declaration of interest statement

The authors report no conflicts of interest.