OBJECTIVE: To improve the diagnosis and treatment of central neuroblastoma. METHODS: To review and summarize the clinical manifestations, diagnostic modalities and microsurgical treatment results of 11 cases of central neuroblastoma. RESULTS: Eight of the 11 patients were completely resected and three were mostly resected, and radiation therapy was routinely performed after surgery. Conclusion: Microsurgical resection of the tumor can effectively reduce the disability and mortality rate, and postoperative radiotherapy can reduce the recurrence of the disease.
Central neuroblastoma is relatively rare in clinical practice. We summarize the experience of 11 cases admitted to our department in recent years that were confirmed by surgery, pathology and electron microscopy, and review the relevant literature to report the following.
Data and Methods
I. General information
Among the 11 cases, 6 were male and 5 were female; age ranged from 15 to 37 years, with an average of 24.5 years. The clinical manifestations were headache, nausea, vomiting and other intracranial pressure increase in 10 cases; among them, 6 cases were accompanied by vision loss and 3 cases were diplopia; all patients had varying degrees of optic nerve papilledema. 1 patient had psychiatric symptoms due to tumor involvement of frontal cortex.
Imaging examination
All 11 patients underwent cranial MRI enhanced anterior and posterior scans, and 10 cases underwent CT scan at the same time. The tumors were located in the body of the lateral ventricle in 9 cases, some tumors invaded the interventricular foramen and the septum pellucidum, 2 cases protruded into the third ventricle, and the midline structures were obviously shifted to the opposite side. The tumor was a homogeneous substantial mass in 8 cases, and there were multiple cystic cavities separated from each other in 3 cases, and the tumor was enhanced in the enhanced scan. Enhancement scan showed moderate enhancement. All cases had ventricular enlargement and hydrocephalus.
Surgical methods
All 11 cases were resected under the microscope. In 6 cases, the tumor located in the lateral ventricular septum was resected through a transfrontal-lateral ventricular approach by opening the frontal cortex and entering the lateral ventricle, releasing the cerebrospinal fluid in the lateral ventricle on the side of the tumor to collapse the tumor cavity, and then opening the septum so that the cerebrospinal fluid in the lateral ventricle on the opposite side of the tumor would also flow out, and then the tumor was clearly revealed and resected in small pieces along the tumor border under the microscope. -In 3 cases, the main part of the tumor was located in the posterior horn of the lateral ventricle, and the specific operation was similar to the previous one. Eight cases were completely resected by the naked eye; three cases were mostly resected. The cerebrospinal fluid circulation pathways were opened in all patients.
Pathological examination
The tumor cells in 8 cases were round in shape, relatively uniform in size, with transparent cytoplasm, no anomalous hyperplasia and necrosis, and there were obvious perinuclear haloes and calcification in tumor tissues. 3 cases showed necrosis, active vascular endothelial proliferation and mitosis, suggesting malignant transformation. The ultrastructure of the tumor cells showed abundant polyribosomes, parallel microtubules, well-developed Golgi complexes, and neurofelt-like structures consisting of abundant cell protrusions, especially the formation of atypical synapses and a large number of clear and dense core neurodegenerative granules in the synapses. Immunohistochemical analysis revealed positive reactions for concentrated neuronal markers such as synaptic small proteins, enolase, calmodulin phosphatase, positive Syn (100%) and positive NSE (30%).
V. Results
All 11 patients were routinely treated with radiation therapy after surgery at a dose of 40-60 GY. 1 patient developed headache, nausea, vomiting and other symptoms of increased intracranial pressure again in January after surgery, and a repeat cranial CT showed obstructive hydrocephalus, which completely disappeared after ventriculo-abdominal shunt. The above symptoms completely disappeared after the ventriculo-abdominal shunt was performed. After 6-31 months of post-operative follow-up, all patients recovered well and no significant tumor recurrence was observed.
Discussion
Central neuroblastoma is relatively rare, accounting for about 1% of intracranial nervous system tumors. In previous classifications, Bailey and Cushing classified neuronal cell tumors derived from primitive medullary epithelium by tumor histology; Kernohan tumor classification classified it as neuroastromal cell tumor grade 1. Hassoun proposed the concept of central neuroblastoma in 1992 and analyzed it and found that it was often misdiagnosed as an intra-lateral ventricular oligodendroglioma, ventricular meningioma, meningioma, or The latest WHO classification in 1999 classified it as a neuronal and mixed neuronal glioma belonging to the neuroepithelial tissue tumors, with a grade II malignancy [1]. Due to the existence of a process of recognition of this disease, there has been disagreement in the diagnosis and treatment methods [4, 5, 7, 8, 10]. We summarize the clinical treatment experience of 11 patients with surgically resected plus pathologically confirmed central neuroblastoma in recent years and combine it with domestic and international literature reports to summarize this tumor as follows.
I. Age of onset and prevalent sites: The disease is most common in young and middle-aged people aged 12-40 years, with a mean age of 27 years; there is no significant difference in onset between males and females. The main part of the tumor is located in the lateral ventricle, and the base of the tumor is on the wall of the lateral ventricle. Sometimes it can also originate from the pellucid septum and corpus callosum area, or from within the frontal lobe.
Clinical manifestations: The main clinical manifestations of patients are headache and discomfort, nausea and vomiting and other symptoms of increased intracranial pressure, as well as obstructive hydrocephalus caused by tumor blocking cerebrospinal fluid circulation pathway. The main reason is that the interventricular foramen is blocked or the third ventricle is blocked by the tumor after enlargement, patients may have obvious headache, frequent vomiting and optic nerve papillary edema. Some patients have symptoms of frontal lobe damage such as slow reaction, memory loss and excitement due to tumor involvement in frontal lobe.
Pathological features: tumor cells are round in shape, relatively uniform in size, transparent in cytoplasm, and generally less likely to undergo heterogeneous proliferation and necrosis, with obvious hollow corona around the nucleus and calcification in tumor tissue. Very few tumor cells showed necrosis, vascular endothelial proliferation and active mitosis, suggesting the possibility of malignant transformation [8]. Electron microscopic ultrastructure revealed abundant polyribosomes, parallel microtubules, well-developed Golgi complexes, and neurofelt-like structures consisting of abundant cellular protrusions, especially atypical synapse formation and a large number of clear and dense core neurosecretory granules within the synapses. Immunohistochemical analysis revealed positive reactions for concentrated neuronal markers such as synaptic small proteins, enolase, and calmodulin phosphatase [6].
IV. Imaging: CT scan showed the tumor to be well-defined, with an intact envelope, richly vascularized, and dark red irregular and substantial spherical shape. A well-defined, mixed-density mass shadow can be found in the lateral ventricles and/or the third ventricle, and the enhancement scan is obvious. Irregular small calcified spots within the tumor are seen on CT films in the vast majority of patients with tumors. The tumor is usually 3.0-7.0 cm in diameter, and most of them are associated with obstructive hydrocephalus.MRI scans show the tumor to be isosignal, located in the lateral ventricles with clear borders, attached to the ventricular floor, wall or hyaline septum, and moderately enhanced [2, 3].
V. Diagnostic methods: The possibility of intracerebroventricular neuroblastoma should be considered if an intra-lateral ventricular tumor starting with increased intracranial pressure is found in young and middle-aged patients, especially if the tumor is large with punctate calcification on CT and MRI scans. The diagnosis of this disease cannot be determined pathologically by light microscopy alone and must rely on electron microscopy and/or immunocytochemistry to confirm the diagnosis [4, 5, 6].
VI. Treatment and prognosis: Yi Zhangchao et al. 1998 reported the treatment experience of two cases of central neuroblastoma without microscopic resection, in which one case was mostly resected and the other case was only partially resected due to the huge tumor, but the patient died due to excessive reaction after surgery [4]. Zhang Jun et al. 2000 reported the experience of 7 cases of tumor resection by direct surgery, among which 3 cases were completely resected under the microscope, 2 cases were mostly resected, and 2 cases died [5]. We resected all 11 patients under microscope and suggested that different surgical approaches should be used for tumors at different sites for total resection as far as possible, including the transfrontal-lateral ventricular approach, the transparietal-occipital-lateral ventricular approach and the transverse mediastinal-callosal approach. Before removing the tumor, both lateral ventricles are opened to drain the cerebrospinal fluid and open the hyaline septum to collapse the brain tissue to facilitate the surgical operation. Microscopic operation after exposing the tumor can clearly show the boundary between the tumor and the surrounding brain tissue and reduce the damage. The tumor base is carefully separated and electrocoagulated, and the tumor is gradually removed in small pieces. If the tumor is large and closely adhered to the surrounding thalamus, hypothalamus, large cerebral vein and other important structures, total resection is not required, but attention should be paid to make sure to open the cerebrospinal fluid circulation pathway and release obstructive hydrocephalus; tumor located in one side of lateral ventricle should be opened together with transparent septum after total resection under microscope to make the cerebrospinal fluid circulation unobstructed, and ventriculo-abdominal shunt surgery is necessary for patients who cannot have total resection of tumor.
Surgical resection of central neuroblastoma combined with post-surgical radiotherapy is currently considered the best treatment method. Foreign literature reports the use of r-knife or X-knife treatment for patients with incompletely resected tumors, and the longest survival time for patients with such tumors has been reported in the literature to be 37 years. We routinely performed radiation therapy after surgery in 11 patients. The dose was 40-60 GY. There are also reports from abroad that surgery and radiotherapy followed by chemotherapy are more effective [9]. It should be noted that there is a possibility of infiltrative growth in some of the tumor wall attachments, and complete resection of the tumor by surgery alone cannot completely prevent tumor recurrence effectively. Yasargil reported that all patients with total tumor resection alone had recurrence within 3 years, while in combination with postoperative radiotherapy, most patients could be cured in the long term even if the tumor was partially resected. The longest follow-up period was about 19 years. Eight of the 11 patients in this group were completely resected and three were mostly resected, and radiation therapy was routinely administered after surgery, with good results through 6-31 months of follow-up.