Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery, genetics, and localization

Abstract

Introduction Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT). Functional preservation and pain relief are the major goals in treating these tumors. Methods This retrospective observational study investigates the clinical and functional outcome of 205 operated peripheral (n = 148, 72%) and intraspinal (n = 57, 28%) schwannomas in 85 patients (53 NF2, 32 SWNT) treated at our department between 2006 and 2017. Associated factors such as genetics, age, and location were evaluated. Results Persisting drug-resistant pain was the most common symptom (84%, n = 173) and indication for surgery (54%, n = 110). Improvement in pain intensity was postoperatively seen in 81%. Peripheral nerve schwannomas exhibited worse pain intensity preoperatively compared to intraspinal lesions (p = 0.017 NF2, p = 0.029 SWNT). More total resections could be achieved in 93% of SWNT vs. 82% of NF2-associated tumors, p = 0.030). NF2 patients with intraspinal lesions were more neurologically affected (p < 0.05). Perioperative comparison of both tumor syndromes showed more neurological deficits (p = 0.027), and less pain (p = 0.024) in NF2-associated tumors. Mosaic NF2 patients had worse pain levels before surgery, and SWNT patients had a worse neurological function and more pain compared to non-mosaic or non-mutated cases. Conclusions Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity. The influence of mutations needs to be further investigated in larger cohorts.

Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative

“…There are no prospective studies on the use of a microscope to visualize nerve fibers intraoperatively, but according to expert opinions, this is recommended as a good practice point. Surgery is effective in pain management [ 135 ], especially in sporadic tumors [ 131 ]. Rates of complete resection depends on the presence of a genetic disorder (schwannomatosis or neurofibromatosis).…”

“…Rates of complete resection depends on the presence of a genetic disorder (schwannomatosis or neurofibromatosis). In case of NF2, resection rates up to 82% are reported [ 135 ], whereas in spontaneous tumors, up to 92.5% may be achieved [ 133 ]. The risk for permanent or temporary new neurological deficits in benign lesions might be up to 15.2% [ 136 ].…”

“…Recurrence rates in genetic syndromes, such as schwannomatosis or NF2, can be as high as almost 40% [ 131 , 136 ] after 5 years and 100% after 10 years [ 131 ]. In benign nerve tumors, there is a large number of case series showing that surgery allows significant pain reduction and long-term progression-free survival, depending on the presence of a genetic disorder [ 131 , 133 , 135 , 136 ]. Despite a lack of level I or II evidence, total or subtotal resection with preservation of nerve function is recommended as therapy of choice.…”

Commentary: Surgical Management of Peripheral Nerve Pathology in Patients With Neurofibromatosis Type 2

“…By contrast, Hebert-Blouin et al 5,6 argued that NF2-associated peripheral nerve schwannomas are more difficult to resect and more likely to result in neurological deficit because of the higher rates of multinodular tumors with multifascicular involvement in NF2. Interestingly, Gugel et al 4 also observed lower rates of gross total resection in NF2-associated schwannomas compared with schwannomatosis-associated schwannomas (82% vs 93%, P = .030). Similarly, Safaee et al 7 also reported lower rates of gross total resection of NF2-associated schwannomas compared with sporadic tumors.…”

“…Mehta et al 3 demonstrated that discreet modular tumors in patients with NF2 can be safely resected, with similar risks as sporadic schwannomas. Similarly, Gugel et al 4 reported on their experience of 205 tumors removed from 53 patients with NF2 and 32 patients with schwannomatosis. Again, they showed that resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment options for patients afflicted with these genetic conditions.…”