Clinical Features Of Central Nervous System Tumors In Schwannomatosis

BackgroundSchwannomatosis, characterized by predisposition to develop multiple schwannomas, is a newly recognized third form of neurofibromatosis. Unlike neurofibromatosis 2(NF2), vestibular schwannomas and other kinds of tumors are rarely seen in schwannomatosis. As phenotype of schwannomatosis overlaps with NF2, initially schwannomatosis was thought to be a mild form of NF2. Schwannomatosis has been recognized in about only two decades. In 1997, the first research criteria for schwannomatosis were proposed. Schwannomatosis is uncommon, the annual incidence is 0.58 cases per 1,000,000 persons. As schwannomatosis has been recognized in a very short time and its incidence is quite low, its clinical features have not been well known. Schwannomatosis has not been reported in China. Merker et al. recently reported the largest cohort of 87 schwannomatosis patients. Although central nervous system tumors are common in schwannomatosis and they are more likely to cause functional disabilities than peripheral schwannomas, their clinical features have not been fully studied except for several case or small series reports. In order to improve the treatment strategy for schwannomatosis, it is important to know the clinical features of central nervous system tumors in schwannomatosis. Materials and MethodsClinical records of 951 patients with pathologically confirmed spinal schwannomas seen at Beijing Tian Tan Hospital between January 2008 and August 2014 were retrospectively reviewed. The patients were divided into three groups: solitary, NF2 and schwannomatosis. Additional 38 NF2 patients with whole-spine MRI scan and 14 patients with lumbar-spine MRI scan were also included into the cohort to analyze the location of spinal tumors, although they did not undergo operations for spinal schwannomas. Clinical, radiographic, and pathologic data were extracted with specific attention to age at onset, location of tumors, initial symptoms, family history and other stigmata of neurofibromatosis 1(NF1) or NF2. If possible, blood samples of schwannomatosis patients were taken to exclude constitutional NF2 mutation. The clinical features of spinal tumors in these three groups were compared thoroughly. Results1. Of 951 patients underwent operations for spinal schwannomas in our institution. 831 were solitary patients, and 50 were NF2 patients. Seventy patients could be diagnosed as schwannomatosis, but only 65 were included into the schwannomatosis cohort. The mean age at the first spinal schwannoma operation of NF2 patients(24.7±10.2 years) was significantly younger than that of solitary(44.8±13.2 years) and schwannomatosis(44.4±14.1 years) patients(one-way ANOVA, p<0.001).2. The initial symptoms among the three groups were different but not statistically significant(chi-squared test, p= 0.209). The most common initial symptom was pain followed by paresthesia/numbness, motor weakness and others. The median duration of preoperative symptoms in NF2 patients(6 months) was shorter than that in solitary(12 months) and schwannomatosis(18 months) patients.3. The distribution of spinal tumors among the three groups was significantly different from each other(chi-squared test, p<0.001; solitary vs. Sch: p<0.001; Sch vs. NF2: p=0.001; solitary vs. NF2: p=0.011). The intradural-extramedullary tumors of NF2 did not have a preferred spinal location; only a slight prominence in the lumbar area could be observed. We observed the most common location in solitary patients to be at the high cervical and thoracic-lumbar segments; the peak of distribution was at C1-3 and T12-L3. The spinal schwannomas of our schwannomatosis patients were most common in the lumbar area; the peak of distribution was at T12-L5.4. Gross-total resection was achieved in 780(93.9%) solitary, 44(88.0%) NF2 and 60(92.3%) schwannomatosis patients. The patients among the three groups obtained similar benefits from the operation(chi-squared test, p=0.290). Among 65 schwannomatosis patients, the result of surgical intervention was recovery in 35 cases(53.9%), improved in 23 cases(35.4%), stable in 5 cases(7.7%), and worsened in 2 cases(3.1%).5. The prognosis varied in spinal schwannomas of schwannomatosis. Until the last date of follow up, most schwannomatosis patients(81.5%) underwent a single spinal operation; 12 patients(18.5%) underwent multiple spinal operations. Among 65 schwannomatosis patients, schwannomas of 22(33.8%) patients were limited to five or fewer contiguous spinal segments; they could be diagnosed as segmental schwannomatosis. Patients with multiple spinal operations were all non-segmental schwannomatosis. The mean age at the first spinal operation in patients with multiple spinal operations was significantly younger than that in patients with a single spinal operation(34.8±13.6 years vs. 46.5±13.4 years, respectively; 2-tailed T test, respectively, p=0.008). However, family history and gender did not affect the prognosis.6. Of 51 schwannomatosis patients who underwent cranial MRI, 5(9.8%) had cranial non-vestibular schwannomas, and 2(3.9%) had intracranial meningioma. On the other hand, one suspicious schwannomatosis patient had unilateral vestibular schwannoma, and one suspicious schwannomatosis patient had bilateral trigeminal schwannomas. NF2 mutations were detected in their blood sample, and they were diagnosed as NF2. Conclusions1. The progression of spinal schwannomas in NF2 seems to be more aggressive than those of other two groups. Schwannomatosis patients seemed to have a similar clinical course with solitary patients.2. The distribution of spinal schwannomas varies among the three groups. The intradural-extramedullary tumors of NF2 do not have a preferred spinal location. The most common location in solitary patients is at the high cervical and thoracic-lumbar segments. The spinal schwannomas of schwannomatosis patients are most common in the lumbar area.3. Most schwannomatosis patients can get satisfactory treatment outcome after the spinal operation. Non-segmental schwannomatosis patients or patients with early onset usually have a poor prognosis; they are more likely to undergo multiple spinal operations. However, family history and gender do not affect the prognosis.4. The intracranial tumors are not common in schwannomatosis patients. When suspicious schwannomatosis patients have intracranial tumors, they should be cautioned for NF2.