48 Year‐Old Woman With Right Leg and Arm Numbness

Clinical History and Imaging

A 48‐year‐old right handed female presented with a 6 month history of progressive decrease of sensation in right upper and lower extremities following a fall after returning from a golf course. She attributed that fall to the loss of sensation, which improved spontaneously over 10 minutes with some residual numbness in the right leg. Her symptoms progressed and she developed difficulty in walking and lifting her right leg. She also complained of neck discomfort and chronic headaches. Neurological examination revealed mild patchy loss of pinprick and light touch sensation in the right upper and lower extremity and trunk with no consistent dermatomal distribution. There was diminished vibration sensation in the right knee. Deep tendon reflex was absent in the right ankle. Plantar reflexes were downgoing. Her gait was stiff with mild circumduction of the right leg. Rest of the motor and cranial nerve examinations were grossly normal.

Magnetic Resonance Imaging (MRI) of brain and cervical spine showed a heterogeneous T2 hyper‐intense and T1 hypointense intramedullary lesion at the C1‐C2 levels. Post contrast T1 images showed heterogeneous enhancement of the mass with areas of non‐enhancement suggestive of cystic change or necrosis (Figure 1a). The T2 hyperintensity extended beyond the enhancing areas suggestive of edema. There was no other enhancing lesion. Imaging features suggested ependymoma; other possibilities were astrocytoma or less likely hemangioblastoma.

Figure 1.

 

A C1–3 laminectomy and midline myelotomy was performed with gross total resection of the tumor. Intraoperative diagnosis was ependymoma,; although this was thought to be supported on permanent sections, the case was referred in consultation to our institution before final sign‐out.

Gross and Microscopic Pathology

The specimen was received piecemeal from the operating room. Histopathological examination revealed a moderately to markedly hypercellular neoplasm, surrounded by compressed CNS tissue (Figure 1b). There were numerous conspicuous perivascular rosettes (Figure 1c) but no ependymal rosette or canal. The tumor was composed of small cells with scant finely granular eosinophilic cytoplasm and round, monomorphic nuclei with dispersed chromatin (Figure 1d). Rare mitotic figures were present. Focal areas of the neoplasm were less cellular and composed of disorganized atypical moderate to large cells with abundant basophilic cytoplasm and large nuclei with prominent nucleoli (Figure 1e); scattered cells were multinucleated.

The neoplastic cells were diffusely synaptophysin positive (Figure 1f). In the areas containing larger cells, neurofilament was also positive (Figure 1g). The tumor cells were negative for chromogranin, EMA, and CD99. Scattered cells were positive for GFAP, which showed a network of fine processes between many tumor cells (Figure 1h). Ki‐67 labeling was scant, <1%. No anaplastic features were identified. What is your diagnosis?

Diagnosis

Ganglioneurocytoma, WHO grade 2.

Discussion

Neurocytomas are uncommon WHO grade II tumors typically arising near the foramen of Monro, and in this location are designated central neurocytoma (CN) 3. Extraventricular neurocytoma (EVN) has been reported at various locations in brain 1, 2 but EVN in spinal cord 7, 8, 9 is rare; only 16 previous cases have been reported in the English literature 9, typically arising as an intramedullary lesion in the cervico‐thoracic segment of the spinal cord. Oddly, there is a strong male predilection for spinal EVNs 2, in contrast with other EVNs which exhibit a slight female predilection. EVN likely arises from neuronal precursor cells surrounding the region of central canal in fetal life, but there is no direct evidence of its lineage; the molecular underpinnings of CN/EVN have yet to be elucidated.

CN and EVN typically show uniform round cells with neurocytic differentiation; the cytoplasm often merges imperceptibly in a neuropil‐like pattern. Occasionally there is mature ganglion cell differentiation admixed with a neurocytic neoplasm, to which the designation ‘ganglioneurocytoma’ has been applied 5. While 4/16 cases of EVN reported in the spinal cord showed ganglionic differentiation (25%), this is somewhat less frequent than EVNs located in other regions (66%) 9. Herein, we report another rare case of spinal neurocytoma with ganglionic differentiation arising from the cervical spinal cord.

EVN may be similar to other intramedullary spinal tumors.. Our case was initially diagnosed as ependymoma on imaging, on frozen sections, and by the referring pathologist on permanent sections even with immunohistochemistry, since background GFAP expression had been attributed to the neoplastic cells. The distinction from ependymoma and oligodendroglioma can be suspected by careful examination of the neuropil‐like matrix, and immunohistochemical evidence of neuronal origin is definitive. Perivascular (‘pseudo’) rosette formation is a classic but non‐specific feature of ependymoma, which tends to exhibit a coarser glial fibrillary matrix, with orthogonal orientation of processes towards the surrounded vessels. Because of their consistent presence in ependymoma, perivascular rosettes may lead to a ‘first impression diagnosis’, but an appropriate differential diagnosis should be constructed to avoid an erroneous pitfall. GFAP expression should be assessed carefully to determine whether the cells of interest, rather than intervening reactive processes, are responsible for any observed immunopostivity; synaptophysin is the most suitable and reliable immunohistochemical marker of CN 10 and EVN; however oligodendrogliomas with neurocytic differentiation and synaptophysin expression have been documented 6.

In general, CN and EVN have an excellent prognosis 7. More aggressive behavior has been linked to an increased Ki‐67 index, greater than 2% being considered as clinically significant in one laboratory 4, although some reports indicate all EVNs show greater than 3% positive nuclei 1; whether Ki‐67 will be a reliable indicator of aggressive behavior thus remains unresolved.

Multiple follow up MRI have shown no evidence of residual or recurrent tumor more than 4 years since surgery. While maximal safe resection of CN and EVN is the treatment of choice, extensive surgical resection may not be appropriate 9; several reports suggest a long survival period can be expected even after subtotal resection of these tumors as they have indolent nature and low proliferative potential 7, 8, 9. Adjuvant radiotherapy is not indicated for typical spinal EVN, but can be used in exceptional cases 4.

In conclusion, EVN or ganglioneurocytoma of the spinal cord, albeit rare, should be considered in assessing a heterogeneously enhancing intramedullary spinal tumor, especially in view of the clinical and morphological resemblance to more common tumors. EVN has a favorable prognosis and even after subtotal resection of these tumors, can have long postoperative period without recurrence without adjuvant treatment. Our case describes the seventeenth case of EVN of the spinal cord, and only the fifth case justifying the designation ‘ganglioneurocytoma’.