Most CNs present with features of increased intracranial tension (headache, vomiting), though visual field defects, gait abnormalities, and memory changes may also develop. Clinical suspicion of CN is rare, and the final diagnosis is confirmed only with postoperative histopathology.
Tumors arise from subependymal plate of lateral ventricles. Computed tomography (CT) typically shows a ventricular space occupying lesion, usually involving lateral ventricles; the mass is well circumscribed with attachment to septum pellucidum and enhances with iodinated contrast. Approximately 50% tumors have calcification. MRI shows a tumor that is iso- or hyperintense to cerebral cortex and enhances with contrast. Usually no draining vein is seen, and the attachments and infiltration are better visualized on MRI than on CT. Role of positron emission tomography (PET) or spectroscopy is uncertain [8].
On light microscopy, typical CNs appear as small round cells with round nuclei and scant cytoplasm resembling oligodendroglioma or ependymoma and often stain positive for synaptophysin. Electron microscopy and immunohistochemistry suggest a neuronal origin. Most cases have a favorable prognosis with benign biological behavior. However, atypical aspects have been reported in 20–25% cases [9]. This rare subgroup, termed “atypical central neurocytomas”, constitues tumors with non-central location (extraventricular or spinal), older age at presentation, MIB-1 LI over 2–3%, and/or histologic atypia with infiltrative margins, increased mitoses, necrosis, endothelial or vascular proliferation or cellular pleomorphism, and biological aggression manifesting as early recurrence and progression [3, 5, 9]. A higher cutoff for MIB-1 LI (10%) has been suggested by Qiu-lin et al., with a proposal to label them as “anaplastic neurocytoma, WHO grade III” [4].
Surgical excision is the mainstay of treatment. Gross total resection (GTR) yields a local control (LC) of 57% and 5-year survival (5y-S) of 93% without need for adjuvant treatment. For subtotal resection (STR) alone, LC and 5y-S drop to 7% and 43%, improving to 70% and 78%, respectively, with adjuvant radiation therapy [10].
Rades and Schild, after an extensive review of 438 patients, including 365 adults and 87 atypical CNs, with a minimum follow up of 1 year, gave treatment recommendations for various CN subgroups. No adjuvant therapy is required after GTR. After STR, adjuvant radiation improves survival in atypical lesions and in adults but not in children, while local control improves across all subgroups. Adults need doses exceeding 54 Gy while doses above or below 50 Gy have comparable outcomes in children. Authors recommended adjuvant RT doses of 50 Gy in children, 50–54 Gy in typical CN, and 56–60 Gy in atypical CN [11]. Stereotactic radiosurgery with peripheral doses of 9–25 Gy (mean 14.9 Gy) yields comparable control rates but slightly lower incidence of complications and higher risk of distant failures, though the difference is not significant [12].
A literature review of 19 atypical cases with malignant behavior showed MIB-1 LI above 2% in 12 of 14 cases with available data and above 10% in those progressing within a year [6]. Seventeen patients had craniospinal dissemination though CSI was given to 3 patients only after documented craniospinal dissemination. The documented disease-free follow-up information for these 3 cases was available at 3 months, 3 years, and 5.5 years, respectively [13,14,15]. In their own case, the Mozes et al. considered CSI upfront but owing to lack of robust supporting literature, delivered it only after the patient developed spinal dissemination at 3 years. They recommended that CN cases with high malignant potential should be considered for maximal tumor resection followed by adjuvant CSI, instead of only adjuvant local RT [6]. Leenstra et al. reported a 35-year experience of 45 cases, wherein 3 patients were given prophylactic CSI (2 after resection and 1 after biopsy) with CSI doses of 30–36 Gy and tumor bed boost of 20 Gy, describing long survival exceeding 7 years in one of their cases [16].
Role of chemotherapy is uncertain and has been explored in inoperable or disseminated cases, with reports of stable disease and partial response with regimens including carboplatin, vincristine, topotecan, cyclophosphamide, and temozolomide [6, 13, 17, 18]. Stem cell transplantation following high dose chemotherapy has also been tried [19].
In the present case, there was no clinical evidence of CSF dissemination at diagnosis but appeared soon after surgery, suggesting an aggressive behavior. Although CSI was given in adjuvant setting, he remained relapse-free for only 10 months, indicating that perhaps adjuvant chemotherapy should also have been considered. Additionally, we recommend spinal screening for all cases with a MIB-1 LI of > 4% or several features of atypia such as necrosis, mitoses, or vascular proliferation on microscopy.
Patient’s perspective
The patient belonged to the lower socioeconomic group. The diagnosis of malignancy at a young age was disheartening; but despite seeking medical attention in time and timely surgery, the course of disease was unpredictable and hard to manage due to mounting side effects of treatment as well as financial challenge for cost of interventions, lodging of family members away from home and loss of work as well as bleak future prospects.
