Clinical features and surgical treatments of neurofibromas associated with neurofibromatosis type 1_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LIU Hanjie , YU Lebao , WANG Bo , LIU Pi’nan , LIU Song ,  LI Dezhi

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, P. R. China;

Corresponding author：

LI Dezhi, Email: lidz000@163.com

Keywords：

Neurofibromatosis type 1; neurofibromas; malignant peripheral nerve sheath tumor; clinical feature; surgical treatment

DOI：

10.7507/1002-1892.202407007

Video：

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Objective To explore the clinical features, surgical treatment, and effectiveness of neurofibromas associated with neurofibromatosis type 1 (NF1). Methods A clinical data of 41 patients with NF1 admitted between December 2018 and April 2024 was retrospectively analyzed. There were 15 males and 26 females, with an average age of 27.5 years (range, 5-61 years). Only one type of neurofibroma existed in 3 patients and the rest of the patients had more than two types of neurofibromas. Fourteen patients had total resection of multiple cutaneous neurofibromas (CNF). Eighteen patients of diffuse neurofibromas underwent total, near-total, or subtotal resection. Among the 13 patients of localized nodular neurofibromas, 9 of benign tumors underwent total sub-capsular resection and 4 of malignant peripheral nerve sheath tumor (MPNST) underwent maginal resection, and only 1 underwent postoperative radiotherapy and chemotherapy. Among the 15 patients of plexiform neurofibromas (PNF), 5 patients underwent both superficial and deep PNF resection, 2 underwent the superficial PNF resection, and 8 underwent the large nodular lesions in the deep PNF resection. There were 8 MPNST, of which 7 cases underwent total sub-capsular resection and large tumor capsule resection under neurophysiological monitoring, and 1 case with the tumor located on the top of the head underwent wide resection and skin grafting. One patient underwent proton knife therapy after surgery, 2 patients did not receive radiotherapy, and the remaining patients received conventional radiotherapy. Results All patients were followed up after surgery, and the follow-up time was 3-66 months, with an average of 25.0 months. Patients with CNF recovered satisfactorily after surgery, and there was no recurrence during follow-up. Patients with diffuse neurofibromas relieved preoperative symptoms after surgery. Three patients with diffuse neurofibromas located in the head and face recurred during follow-up. The patients with benign localized nodular neurofibromas recovered well after surgery, and only 1 patient had transient regional neuralgia after surgery. Among the patients with MPNST, 2 patients died of recurrence and lung metastasis, while the remaining 2 patients had no recurrence and metastasis during follow-up. All preoperative symptoms disappeared in patients with benign PNF, and no tumor recurrence was observed during follow-up. Two patients with PNF located in the brachial plexus had difficulty in shoulder abduction after surgery, 1 patient with PNF located in vagus developed hoarseness after surgery. Among the 8 patients with MPNST in PNF, 1 died of lung metastases and 1 died of systemic failure. The remaining 6 patients were in stable condition during follow-up, and no tumor recurrence or metastasis was observed. Conclusion According to the clinical features of neurofibromas in patients with NF1, choosing appropriate surgical approaches can obtain good effectiveness. Because of the difficulty of completely resection, diffuse neurofibromas, especially those located in the head and face, are prone to recurrence after surgery. MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.

Citation： LIU Hanjie, YU Lebao, WANG Bo, LIU Pi’nan, LIU Song, LI Dezhi. Clinical features and surgical treatments of neurofibromas associated with neurofibromatosis type 1. Chinese Journal of Reparative and Reconstructive Surgery, 2024, 38(10): 1186-1192. doi: 10.7507/1002-1892.202407007 Copy

1.	中国罕见病联盟Ⅰ型神经纤维瘤病多学科诊疗协作组. Ⅰ型神经纤维瘤病多学科诊治指南(2023版). 罕见病研究, 2023, 2(2): 210-230.
2.	Woodruff JM. Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet, 1999, 89(1): 23-30.
3.	Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am, 2004, 15(2): 157-166.
4.	Belakhoua SM, Rodriguez FJ. Diagnostic pathology of tumors of peripheral nerve. Neurosurgery, 2021, 88(3): 443-456.
5.	Garozzo D. Peripheral nerve tumors in neurofibromatosis 1: An overview on management and indications for surgical treatment in our experience. Neurol India, 2019, 67(Supplement): S38-S44.
6.	Friedrich RE, Schmelzle R, Hartmann M, et al. Subtotal and total resection of superficial plexiform neurofibromas of face and neck: four case reports. J Craniomaxillofac Surg, 2005, 33(1): 55-60.
7.	Fisher MJ, Blakeley JO, Weiss BD, et al. Management of neurofibromatosis type 1-associated plexiform neurofibromas. Neuro Oncol, 2022, 24(11): 1827-1844.
8.	Martin E, Pendleton C, Verhoef C, et al. Morbidity and function loss after resection of malignant peripheral nerve sheath tumors. Neurosurgery, 2022, 90(3): 354-364.
9.	Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med, 2021, 23(8): 1506-1513.
10.	Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA, 1997, 278(1): 51-57.
11.	Ortonne N, Wolkenstein P, Blakeley JO, et al. Cutaneous neurofibromas: Current clinical and pathologic issues. Neurology, 2018, 91: S5-S13.
12.	Richey P, Funk M, Sakamoto F, et al. Noninvasive treatment of cutaneous neurofibromas (cNFs): Results of a randomized prospective, direct comparison of four methods. J Am Acad Dermatol, 2024, 90(4): 767-774.
13.	朱倍瑶, 魏澄江, 王薇, 等. 皮肤型神经纤维瘤的治疗方案及研究进展. 中国修复重建外科杂志, 2022, 36(9): 1064-1071.
14.	Dogra BB, Rana KS. Facial plexiform neurofibromatosis: A surgical challenge. Indian Dermatol Online J, 2013, 4(3): 195-198.
15.	Kolker S, Wunder JS, Roche-Nagle G. Hybrid resection of a giant thigh plexiform neurofibroma. Int J Surg Case Rep, 2015, 8C: 1-4.
16.	Needle MN, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr, 1997, 131: 678-682.
17.	Kim DH, Murovic JA, Tiel RL, et al. Operative outcomes of 546 Louisiana State University Health Sciences Center peripheral nerve tumors. Neurosurg Clin N Am, 2004, 15(2): 177-192.
18.	Hirose T, Scheithauer BW, Sano T. Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases. Am J Surg Pathol, 1998, 22(11): 1368-1378.
19.	Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol, 2014, 13(8): 834-843.
20.	Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med, 2016, 375(26): 2550-2560.
21.	Tiel R, Kline D. Peripheral nerve tumors: surgical principles, approaches, and techniques. Neurosurg Clin N Am, 2004, 15(2): 167-175.
22.	Tucker T, Wolkenstein P, Revuz J, et al. Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology, 2005, 65(2): 205-211.
23.	Evans DG, Huson SM, Birch JM. Malignant peripheral nerve sheath tumours in inherited disease. Clin Sarcoma Res, 2012, 2(1): 17. doi: 10.1186/2045-3329-2-17.
24.	Martin E, Geitenbeek RTJ, Coert JH, et al. A Bayesian approach for diagnostic accuracy of malignant peripheral nerve sheath tumors: a systematic review and meta-analysis. Neuro Oncol, 2021, 23: 557-571.
25.	Wasa J, Nishida Y, Tsukushi S, et al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. AJR Am J Roentgenol, 2010, 194: 1568-1574.
26.	LaFemina J, Qin LX, Moraco NH, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol, 2013, 20(1): 66-72.
27.	Kim DH, Murovic JA, Tiel RL, et al. A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center. J Neurosurg, 2005, 102: 246-255.
28.	Nelson CN, Dombi E, Rosenblum JS, et al. Safe marginal resection of atypical neurofibromas in neurofibromatosis type 1. J Neurosurg, 2019, 133: 1516-1526.
29.	Manolidis S, Higuera S, Boyd V, et al. Single-stage total and near-total resection of massive pediatric head and neck neurofibromas. J Craniofac Surg, 2006, 17(3): 506-510.
30.	Stucky CC, Johnson KN, Gray RJ, et al. Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Ann Surg Oncol, 2012, 19(3): 878-885.
31.	Kolberg M, Høland M, Agesen TH, et al. Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro Oncol, 2013, 15(2): 135-147.
32.	Hull MA, Molina G, Niemierko A, et al. Improved local control with an aggressive strategy of preoperative (with or without intraoperative) radiation therapy combined with radical surgical resection for retroperitoneal sarcoma. J Surg Oncol, 2017, 115(6): 746-751.
33.	Kelly KJ, Yoon SS, Kuk D, et al. Comparison of perioperative radiation therapy and surgery versus surgery alone in 204 patients with primary retroperitoneal sarcoma: a retrospective 2-institution study. Ann Surg, 2015, 262(1): 156-162.
34.	Zehou O, Fabre E, Zelek L, et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: A 10-year institutional review. Orphanet J Rare Dis, 2013, 8: 127. doi: 10.1186/1750-1172-8-127.
35.	Spunt SL, Million L, Chi YY, et al. A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children’s Oncology Group prospective study. Lancet Oncol, 2020, 21(1): 145-161.

1. 中国罕见病联盟Ⅰ型神经纤维瘤病多学科诊疗协作组. Ⅰ型神经纤维瘤病多学科诊治指南(2023版). 罕见病研究, 2023, 2(2): 210-230.
2. Woodruff JM. Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet, 1999, 89(1): 23-30.
3. Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am, 2004, 15(2): 157-166.
4. Belakhoua SM, Rodriguez FJ. Diagnostic pathology of tumors of peripheral nerve. Neurosurgery, 2021, 88(3): 443-456.
5. Garozzo D. Peripheral nerve tumors in neurofibromatosis 1: An overview on management and indications for surgical treatment in our experience. Neurol India, 2019, 67(Supplement): S38-S44.
6. Friedrich RE, Schmelzle R, Hartmann M, et al. Subtotal and total resection of superficial plexiform neurofibromas of face and neck: four case reports. J Craniomaxillofac Surg, 2005, 33(1): 55-60.
7. Fisher MJ, Blakeley JO, Weiss BD, et al. Management of neurofibromatosis type 1-associated plexiform neurofibromas. Neuro Oncol, 2022, 24(11): 1827-1844.
8. Martin E, Pendleton C, Verhoef C, et al. Morbidity and function loss after resection of malignant peripheral nerve sheath tumors. Neurosurgery, 2022, 90(3): 354-364.
9. Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med, 2021, 23(8): 1506-1513.
10. Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA, 1997, 278(1): 51-57.
11. Ortonne N, Wolkenstein P, Blakeley JO, et al. Cutaneous neurofibromas: Current clinical and pathologic issues. Neurology, 2018, 91: S5-S13.
12. Richey P, Funk M, Sakamoto F, et al. Noninvasive treatment of cutaneous neurofibromas (cNFs): Results of a randomized prospective, direct comparison of four methods. J Am Acad Dermatol, 2024, 90(4): 767-774.
13. 朱倍瑶, 魏澄江, 王薇, 等. 皮肤型神经纤维瘤的治疗方案及研究进展. 中国修复重建外科杂志, 2022, 36(9): 1064-1071.
14. Dogra BB, Rana KS. Facial plexiform neurofibromatosis: A surgical challenge. Indian Dermatol Online J, 2013, 4(3): 195-198.
15. Kolker S, Wunder JS, Roche-Nagle G. Hybrid resection of a giant thigh plexiform neurofibroma. Int J Surg Case Rep, 2015, 8C: 1-4.
16. Needle MN, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr, 1997, 131: 678-682.
17. Kim DH, Murovic JA, Tiel RL, et al. Operative outcomes of 546 Louisiana State University Health Sciences Center peripheral nerve tumors. Neurosurg Clin N Am, 2004, 15(2): 177-192.
18. Hirose T, Scheithauer BW, Sano T. Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases. Am J Surg Pathol, 1998, 22(11): 1368-1378.
19. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol, 2014, 13(8): 834-843.
20. Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med, 2016, 375(26): 2550-2560.
21. Tiel R, Kline D. Peripheral nerve tumors: surgical principles, approaches, and techniques. Neurosurg Clin N Am, 2004, 15(2): 167-175.
22. Tucker T, Wolkenstein P, Revuz J, et al. Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology, 2005, 65(2): 205-211.
23. Evans DG, Huson SM, Birch JM. Malignant peripheral nerve sheath tumours in inherited disease. Clin Sarcoma Res, 2012, 2(1): 17. doi: 10.1186/2045-3329-2-17.
24. Martin E, Geitenbeek RTJ, Coert JH, et al. A Bayesian approach for diagnostic accuracy of malignant peripheral nerve sheath tumors: a systematic review and meta-analysis. Neuro Oncol, 2021, 23: 557-571.
25. Wasa J, Nishida Y, Tsukushi S, et al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. AJR Am J Roentgenol, 2010, 194: 1568-1574.
26. LaFemina J, Qin LX, Moraco NH, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol, 2013, 20(1): 66-72.
27. Kim DH, Murovic JA, Tiel RL, et al. A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center. J Neurosurg, 2005, 102: 246-255.
28. Nelson CN, Dombi E, Rosenblum JS, et al. Safe marginal resection of atypical neurofibromas in neurofibromatosis type 1. J Neurosurg, 2019, 133: 1516-1526.
29. Manolidis S, Higuera S, Boyd V, et al. Single-stage total and near-total resection of massive pediatric head and neck neurofibromas. J Craniofac Surg, 2006, 17(3): 506-510.
30. Stucky CC, Johnson KN, Gray RJ, et al. Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Ann Surg Oncol, 2012, 19(3): 878-885.
31. Kolberg M, Høland M, Agesen TH, et al. Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro Oncol, 2013, 15(2): 135-147.
32. Hull MA, Molina G, Niemierko A, et al. Improved local control with an aggressive strategy of preoperative (with or without intraoperative) radiation therapy combined with radical surgical resection for retroperitoneal sarcoma. J Surg Oncol, 2017, 115(6): 746-751.
33. Kelly KJ, Yoon SS, Kuk D, et al. Comparison of perioperative radiation therapy and surgery versus surgery alone in 204 patients with primary retroperitoneal sarcoma: a retrospective 2-institution study. Ann Surg, 2015, 262(1): 156-162.
34. Zehou O, Fabre E, Zelek L, et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: A 10-year institutional review. Orphanet J Rare Dis, 2013, 8: 127. doi: 10.1186/1750-1172-8-127.
35. Spunt SL, Million L, Chi YY, et al. A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children’s Oncology Group prospective study. Lancet Oncol, 2020, 21(1): 145-161.

Chinese Journal of Reparative and Reconstructive Surgery

Clinical features and surgical treatments of neurofibromas associated with neurofibromatosis type 1

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