Trigeminal Ganglioneuroma in the Middle-posterior Cranial Fossa: a Case Report△

Ting Wang, Lin Ma, Xin Lou, and Bo Bu*



Trigeminal Ganglioneuroma in the Middle-posterior Cranial Fossa: a Case Report△

Ting Wang1, Lin Ma1, Xin Lou1, and Bo Bu2*

1Department of Radiology,2Department of neurosurgery, Chinese PLA General Hospital, Beijing 100853, China

ganglioneuroma; trigeminal nerve; computed tomography; magnetic resonance imaging; middle-posterior cranial fossa

Chin Med Sci J 2017; 32(2):123-128. DOI:10.24920/J1001-9294.2017.016

ANGLIONEUROMA is considered as the most mature and noninvasive form of neuroblastic tumors. It derives from neural crest cells, and can arise from wherever sympathetic tissue exists,1including neck, posterior mediastinum, adrenal gland, retroperitoneum and pelvis. The two most common locations for this tumor are retroperitoneum and posterior mediastinum; infrequently it occurs in the intracranial region,2-8with only three cases has been reported arising from trigeminal nerve.2-4The current paper presents a 49-year-old male patient with a ganglioneuroma arising from right trigeminal ganglion and extending to the middle-posterior cranial fossa. We summarized the clinical and diagnostic characteristics of this extremely rare tumor, in comparison with the three reported cases in literatures.

Case Description

A 49-year-old male patient with no previous comorbidities presented to our hospital with a main complaint of discontinuous dizziness for one month. The dizziness was paroxysmal onset without obvious cause. General physical examination demonstrated right facial muscle atrophic, with no other abnormality. All the neurologic examination was negative.

Computed tomography (CT) scan of the brain discovered a slight hypodensity mass (4.2cm×5.2cm) in the right middle-posterior cranial fossa with internal high- density dots in the tumor (Fig. 1A). The tumor deformed the ethmoid bone, destroyed the greater wing of the sphenoid bone and the petrous apex area, and extended to the carvernous sinus and posterior cranial fossa. The pons was compressed. CT value of the spotty high-density was about 350HU, consistent with localized intratumoral calcification and hemorrhage. CT images in bone window demonstrated absorption and thinning of the sphenoid and ethmoid bone without destruction (Fig. 1B). The brain magnetic resonance imaging (MRI) showed a 4.1cm×5.4cm×4cm well-circumscribed extra-axial mass in the parasellar and cerebellopontine angle region of right middle-posterior cranial fossa (Fig. 2). The right fifth-sixth cranial nerve was displaced by the mass. The lesion demonstrated heterogeneous isointensity or slight hypointensity on T1-weighted image (T1WI), heterogeneous hyper- to slight hypointensity on T2-weighted image (T2WI) (Fig. 2A). It compressed the right temporal lobe and pons, and caused the homolateral masseter atrophic (Fig. 2B). On diffusion-weighted image (DWI), the lesion showed no diffusion restriction (Fig. 2E), and the lesion demonstrated heterogeneous hyperintensity with mean apparent diffusion coefficient (ADC) value of 1.855×10-3mm2/s on ADC map (Fig. 2F). The solid part of the lesion demonstrated significantly enhanced and the cystic part showed no enhancement (Fig. 2C,D). Based on the clinical history, location, CT and MR findings, the preoperative diagnosis was trigeminal neuroma, with differential diagnosis of meningioma, acoustic neuroma or epidermoid cyst tumor.

Figure 1. Images of cranial CT scan and postoperative MRI.A. A heterogeneous low-density mass in size of 4.2cm×5.2cm in the right middle-posterior cranial fossa with dotty calcification inside. B. Bone window image showed absorption and thinning of the sphenoid and ethmoid bone. C. Postoperative CT image demonstrated complete resection of the tumor. D-F. Postoperative MRI images (T2WI，T1WI, and enhanced T1WI) five months after the operation showed the tumor was resected completely with no residue and recurrence.

Figure 2．MRI findings onpre- and post-contrast MRI and diffusion-weighted imaging before operation.A. Axial T2WI image and B. Axial T1WI image showed a well-defined mass with heterogeneous signal intensity in the right middle-posterior cranial fossa. C. Remarkable heterogeneous enhancement on contrast enhanced axial T1WI. D. Coronal contrast enhanced T1WI image showed the lesion surround the right internal jugular vein. E. Diffusion-weighed imaging (b=1000 s/mm2) revealed a hypointensity tumor. F. Apparent diffusion coefficient mapping showed relatively hyperintensity of the tumor.

The patient underwent a subsequent tumor resection through a preauricular subtemporal interdural approach. After the fronto-temporal craniotomy, the temporal dura was raised from skull base and dissected from the ophthalmic (V1), the maxillary (V2), mandibular division (V3) and Meckel’s cave. The tumor located within the interdural space between the dura propria and inner membranous layer, which is a natural corridor for operation. The tumor had partially grew into cavernous sinus with the main body located in the Meckel’s cave (Fig. 3A). While surgeons piecemeal resected the tumor, cystic component of the intratumoral cavity was revealed (Fig. 3B). The tumor was found partially adhering tightly to the abducens nerve, and it originated from trigeminal ganglion. Tumor resection was performed piece by piece under microscope, and V2, V3 and abducens nerves were intact.

Gross pathology revealed a rich blood supply, soft texture mass with smooth capsule. Histopathologic examination demonstrated the tumor was composed of scattered large mature ganglion cells and schwann cells, with the presence of elongated or spindle shaped cells in an abundant collagenous stroma (Fig. 4A). Additionally, slight dysplastic ganglion cell were observed in part of the tumor with binucleated cells accompanied (Fig. 4B). Calcification and hyaline degeneration were revealed (Fig. 4C). Immunohistochemical stain showed positive for S-100 protein, which is consistent with the neurogenic nature of the tumor. Staining of CD31, CD34, smooth muscle actin (SMA), vimentin were positive, epithelial membrane antigen (EMA) was negative, and Ki-67 evaluation was positive in 3%, confirming a benign neoplasm (Fig. 4D, 4E, 4F). The tumor was thus diagnosed as ganglioneuroma.

Postoperative CT scan was performed on the fifteenth day after the surgery. It confirmed a completely resection, with no residue enhancement detected (Fig. 1D). Follow-up MRI five months after operation demonstrated no residue and no recurrence of the tumor (Fig. 1D-1F). There was no special event in the postoperative period，except external visual disturbance in the left eye.

Discussion

Ganglioneuroma, accompanied with ganglioneuroblastoma and neuroblastoma, are classified as neuroblastic tumor, which arise from neural crest cells in the peripheral nervous system.1Unlike neuroblastoma or ganglioneuroblastoma that behave more invasively and usually occur in younger children, ganglioneuroma is well differentiated, benign, slow growing tumor that remains clinically silent until it become large enough to cause symptoms by compressing adjacent structures. Generally, it occurs in older children and young adults,2,9with about 80% of most series occurring in patients under 30 years old,3with no significant gender difference. However, recent studies have shown that the ages at diagnosis of ganglioneuroma were around 40 to 50 years old.1,2,4,6Up to now, the etiology of ganglioneuroma has been unclear yet. Hayespointed out that ganglioneuroma may occur spontaneously or as a result of either chemotherapy or radiation therapy for neuroblastomas.10Retroperitoneum as well as posterior mediastinum are the two typical locations for ganglioneuroma, yet it is rarely seen in spinal cord, cranial nerve ganglia, mandible, tongue, parapharyngeal tissue, gastrointestinal tract, bladder, visceral ganglia, uterus, ovary, spermatic cord, testes, prostate, skin, and bone.9Intracranial ganglioneuroma is extremely rare. It has been reported with only three cases arising from trigeminal nerve.2-4Some other intracranial locations as reported were internal auditory canal (IAC) and middle ear.5-8The case we report here is the fourth description of ganglioneuroma originating from trigeminal nerve.

Figure 3. Photographs of intra-operative findings.A. After the focal skull removed, the dura was exposed and extradural tumor was identifiable. B. Cystic component of the intratumoral cavity (asterisk). Maxillary and mandibular nerve were well reserved while the tumor was resected completely. V2, maxillary nerve; V3, mandibular nerve; T, tumor.

Figure 4. Histological findings of ganglioneuroma. A. Mixture of large ganglion cells (arrows) and spindle-shaped Schwann-like cells (H&E staining, 400×). B.Dysplastic ganglion cell with binucleated cell (arrow) (H&E staining, 400×). C. Calcification (arrow) and hyaline degeneration (asterisk) in tumor (H&E staining, 100×). D. S-100 positive cells accompanied with giant ganglion cells (arrows) supporting the neurogenic nature of the tumor (S-100 protein immunohistochemical staining, 400×). E. CD34 positive cells presented in blood vessels, indicating angiogenesis of the tumor (CD34 immunohistochemical staining, 400×). F. 3% Ki-67 positive cells confirmed the benign neoplasm (arrows) (Ki-67 immunohistochemical staining, 400×).

Histopathologically, ganglioneuroma is composed of single or clustered mature, giant ganglion cells and Schwannian stroma. It usually has no components of neuroblasts, intermediate cells, or mitotic figures that indicating malignant differentiation.9According to international neuroblastoma pathology classification of neuroblastic tumors, ganglioneuroma has been divided into two subtypes:maturing and mature subtype.9Typical ganglioneuroma is composed of mature ganglion cells and schwannian stroma; however, tumor with entirely maturated ganglion cells are rare (approximately 7%). In the present patient, lightly atypical ganglion cell with binucleated cell was detected. The immaturity of ganglion cells did not affect the diagnosis of ganglioneuroma.11Immunohistochemically, it is characterized by reactivity for S-100, vimentin, synaptophysin and neuronal markers.12Ki-67 is also a immunomarker of cellular proliferation. In this patient, Ki-67 positive cells of the tumor are as low as 3%, which highly support benign tumor. In our case, the final pathological examination confirmed the diagnosis.

Although diagnosis of ganglioneuroma mainly depends on histopathologic assessment, CT and MRI scan provide information in location, size, component of the mass, and its relationship to adjacent significant structures, which is valuable in determining a surgical plan. On CT imaging, ganglioneuroma often shows well-defined, low-density lesion with punctate calcification.9It is reported that approximate 20%-42% ganglioneuroma is accompanied with calcification.9Ichikawabelieve that the morphology of calcifications can served as a key characteristic to differentiate benign tumor from malignancies.13Scattered punctate or grain-like calcification indicates benign lesion, while large patchy or irregular calcification implies malignancy. In our case, punctate calcifications was seen in the lesion, which indicate a diagnosis of benign, although the patient only took a plain CT scan without contrast enhancement. On MRI, typical ganglioneuroma manifest as well-circumscribed mass with low signal on T1WI, heterogeneous high signal on T2WI, and progressive enhancement on dynamic contrast-enhanced images.13MRI is superior to CT in showing blood vessels surrounding and compressing.

The three cases reported were derived from trigeminal nerve. In 1999, Abe3firstly reported an 8-year-old girl who presented ganglioneuroma in the left cerebellopontine angle region, which originated from the sensory root of the trigeminal nerve. The tumor was a well-circumstanced mass with hypo-intensity on T1WI, hyper-intensity on T2WI, and relatively homogenous enhancement on post- contrast image. Another case reported by Nakaguchi4in 2012 was a 55-year-old man with sudden onset of severe headache. MR images of this patient demonstrated a slight high T2 signal and obviously heterogeneously enhanced lesion in the left middle cranial fossa. The latest case reported in 2013, was an iso-intensity on T1WI and slight hyper-intensity on T2WI, with a minimal enhancement. In our case, the mass showed slight hypointensity on T1WI and heterogeneous hyperintensity on T2WI. The different signal intensity on T2WI among these rare cases may due to the proportions of cellular quantity, fibrous components and myxoid stroma.14The histopathology of our case confirmed high proportion of hyaline degeneration among the stroma of the tumor. Besides, significant heterogeneous enhancement of the tumor was consistent with the case Nakaguchireported, but didn’t accord with the other two cases. Based on above four cases，we proposed that the enhancement pattern of ganglioneuroma on MR image vary from mild tomarked.

The apparent diffusion coefficient (ADC)，regarded as a quantitative index of diffusion function of water in the tumor on diffusion weighted imaging(DWI)，has been described for intracranial ganglioneuroma only in one report2, where the mass showed homogeneous hyperintense on DWI image, with a mean ADC value of 0.72×10-3mm2/s. In our case, the mean ADC value presented as 1.855×10-3mm2/s, which is relatively high, but is consistent with the measurement in Gahr’s study for thoracoabdominal ganglioneuromas/ganglioneuroblastomas (mean ADC: 1.60× 10-3mm2/s, range 1.13-1.99´10-3mm2/s).15The difference in ADC value may arise from tumor histopathology. We hypothesized that high amount of hyaline degeneration in histopathology may attribute to the relatively high ADC value in our case.

MRI is of great diagnostic value for their characteristic signal intensity and enhancement pattern. It was difficult to differentiate ganglioneuroma from Intracranial trigeminal schwannoma, which usually presents as a heterogeneous long T1 and T2 signal, strong but heterogeneous enhanced mass, along with a transmediposterior cranial growing pattern. However, trigeminal schwannoma rarely show intratumoral hemorrhage or calcification，whereas certain calcification and hemorrhage were revealed in our patient, which may make it distinguishable from trigeminal schwannoma. If it occurred in prepontine and cerebellopontine angle region, epidermoid cyst, meningioma, neurofibromatosis type 2 and metastasis should also be included in the differential diagnoses. Intracranial epidermoid cyst is typically diffusion restricted on DWI compared with brain parenchyma, with no or minimal margin enhancement. Meningioma often shows iso-intense on T1WI and T2WI, with homogenous enhancement. Neurofibromatosis type 2 and metastasis always present as multiple, enhanced lesions, associate with a family or clinical tumor history.

It is general accepted that surgical resection alone is curative for ganglioneuroma, while radiotherapy is not recommended, despite potential risk for malignant transformation to neuroblastoma.9With complete resection of ganglioneuroma, the patient usually can achieve a good prognosis.

In summary, we described a benign and extremely rare trigeminal ganglioneuroma, which was lack of specific imaging characteristic, and were difficult to diagnose before operation. Finial diagnosis depends on pathology. When imaging features don’t absolutely support any common diagnosis, trigeminal ganglioneuroma should be considered as a possible diagnosis. The prognosis of surgical excision of the tumor is favorable.

Conflict of Interest Statement

Acknowledgments

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for publication June 6, 2016.

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△Supported by National Natural Science Foundation of China (81101034).