A case of anatomically- and histologically-diagnosed intraventricular CN with molecular features of EVN was presented. Though the characteristic histological findings such as monomorphic, regular nuclear morphology, and neuronal/neurocytic differentiation were consistent with the diagnosis of CN, the presence of distinct fusion revealed by RNA sequencing and methylation profiling clearly corroborated the diagnosis of EVN. The tumor was located in the left lateral ventricle; it was an “intraventricular” neurocytoma and was in an apparent contradiction to the nomenclature “extraventricular” neurocytoma.
We postulate two hypotheses to explain this phenomenon: One is the possibility that an EVN emerged close to the ventricular system and mainly grew into it instead of invading the brain parenchyma. In our case, the tumor partially occupied the caudate head, and the adhesion to the septum pellucidum was modest. Of note, CN is most often attached to the septum pellucidum near the foramen of Monro[7]. EVN may arise at any site in the intracranial compartment[13]. Another hypothesis is that CN can present with molecular features of EVN. Next-generation sequencing and methylation profiling modified the histological diagnosis of CN into ganglioglioma in two cases in a certain cohort[5]. Also, methylation profiling modified the histological diagnosis of EVN into diffuse leptomeningeal glioneuronal tumor, rosette-forming glioneuronal tumor, pilocytic astrocytoma, oligodendroglioma, astrocytoma, diffuse midline glioma H3K27M-mutant and glioblastoma in thirteen cases in another cohort[13]. Although much less likely, taken in concert with the trend toward more emphasis on molecularly-based diagnosis, we presume that definitive histological diagnosis of CN and EVN still may include heterogeneous molecular pathologies.
In fact, the treatment course would not have been different whether the diagnosis was CN or EVT in the current case. A maximal safe resection is the cornerstone of the treatment for both tumors[11], and gross-total resection provides an excellent prognosis and minimizes the chances of recurrence[7]. The overall survival of CN is 95.3% (mean follow-up 90.5 months) for gross-total resection[8], and the 5-year overall survival rate of EVN without atypia is reported as 96%[6]. In cases with subtotal resection, postoperative adjuvant radiotherapy can prevent tumor progression and recurrence in both tumors. We treated the patient with maximal safe resection and postoperative adjuvant radiotherapy without tumor recurrence for 25 years.
However, most histologically-proven EVN patients possess the fusion gene FGFR1-TACC1[13]. FGFR has garnered attention as a therapeutic target recently[3]. Irreversible inhibitor of FGFR has developed for the treatment of several solid cancers; cholangiocarcinoma, breast cancer, gastric cancer, urothelial cancer, oesophageal cancer, and non-small cell lung cancer, especially for previously treated, unresectable cases[14,9]. Hence, EVN has the potential to be treated with novel monoclonal antibodies. We, therefore, pose that distinguishing the biological behavior of CN and EVN not by the histopathological features but by the molecular markers would provide therapeutic benefits.
While classically diagnosed by the anatomical location and the histopathology, potential overlap between CN and EVT was suggested in our case. Further studies may reclassify neurocytoma and provide therapeutic benefits for certain patients.
Molecularly-diagnosed “extraventricular” neurocytoma in the ventricular system was presented. Imaging, pathological diagnosis, and molecular diagnosis may show a mismatch. Our case raises questions about the current definition of CN and EVN, and further reclassification of neurocytoma may provide therapeutic benefits for certain patients.