Abdominal Tumor Requiring Surgical Resection in a Young Patient with Neurofibromatosis Type 1
DOI:
https://doi.org/10.34635/rpc.1137Keywords:
Neurofibromatosis 1/complications, Retroperitoneal Neoplasms/surgeryAbstract
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects approximately 1 in 3000 births. Retroperitoneal tumors occur in 2%-5% of NF1 patients and pose diagnostic and therapeutic challenges. We report a 25-year-old male from Cape Verde with confirmed NF1 who presented with progressive abdominal pain and a 15 x 11 x 12 cm retroperitoneal mass in the left psoas muscle. He underwent a successful complete surgical resection. Histologically, it was a malignant peripheral nerve sheath tumor (MPNST), high-grade, with foci of heterologous rhabdomyosarcomatous differentiation (malignant triton tumor). Molecular testing confirmed a likely pathogenic variant (c.288+5G>A) in the NF1 gene. This case highlights the importance of early diagnosis, appropriate surgical intervention, molecular confirmation for family genetic counseling, and the development of emerging systemic therapies, including targeted treatments for NF1-associated tumors.
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Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44:81-8. doi: 10.1136/j.jmg.2006.045906.
Cichowski K, Jacks T. NFI tumor suppressor gene function: narrowing the GAP. Cell. 2001;104:593-604.
Ratner N, Miller SJ. A RA/Sopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer. 2015;15:290-301.
Reilly KM, Kim A, Blakely J, Ferner RE, Gutmann DH, Legius E, et al. Neurofibromatosis Type 1-Associated MPNST State of the Science: Outlining a Research Agenda for the Future. J Natl Cancer Inst. 2017;109:dpA124. doi: 10.1093/jnci/dpA124.
Khosrotehranni K, Bastuji-Garin S, Riccardi VM, Birch P, Friedman JM, Wolkenstein P. Subcutaneous neurofibromas are associated with mortality in neurofibromatosis 1a cohort study of 703 patients. Am J Med Genet A. 2005;132:A49-53. doi: 10.1002/ajmg.a.30394.
Evans DG, Baser ME, McGaughan J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002;39:311-4. doi: 10.1136/jmg.39.5.311.
Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Istrup DM. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 120 cases. Cancer. 1986;57:2006-21.
Farid M, Demicco EG, Garcia R, Ahn L, Merola PR, Cioffi A, et al. Malignant peripheral nerve sheath tumors. Oncologist. 2014;19:193-201. doi: 10.1634/theoncologist.2013-0328.
Johannessen CM, Rezeek EE, James MF, rems H, Legius E, Cichowski K. The NFI tumor suppressor critically regulates TSG2 and mTOR. Proc Natl Acad Sci U S A. 2005;102:8573-8. doi: 10.1073/pnas.0503224102. Erratum in: Proc Natl Acad Sci U S A. 2005;102:1619.
Anghielli M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, et al. Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer. 2006;107:1065-74. doi: 10.1002/cncr.22098. PMID: 16881077.
Kroep JR, Ouali M, Gelderblom H, Le Cesne A, Dekker TJA, Van Glabbeke M, et al. First-line chemotherapy for malignant peripheral nerve sheath tumor (MPNST) versus other histological soft tissue sarcoma subtypes and as a prognostic factor for MPNST: an EORTC soft tissue and bone sarcoma group study. Ann Oncol. 2011;22:207-14. doi: 10.1093/annonc/mda338.
Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, et al. Dosovolition alone versus intensified dosovolition plus ifostamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15:415-23. doi: 10.1016/S1470-2045(14)70063-4.
Valentin T, Fournier C, Penel N, Bompas E, Chaigneau L, Isambert N, et al. Sorafenib in patients with progressive malignant solitary fibrous tumors: a subgroup analysis from a phase II study of the French Sarcoma Group (GSF/GETO). Invest New Drugs. 2013;31:626-7. doi: 10.1007/s10637-013-0023-z.
Maki RG, Wahlen JK, Patel SR, Priebat DA, Okuno SH, Samuels B, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study O02. J Clin Oncol. 2007;25:2755-63. doi: 10.1200/J.CO.2006.10.4177.
Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016;387:629-37. doi: 10.1016/S0140-6736(15)01283-0.
Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetz SMA, Staddon A, et al. Efficacy and safety of trabecetain or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016;34:786-93. doi: 10.1200/J.CO.2015.62.4734.
de Blank PM, Gross AM, Akshintala S, Blakeley JO, Bolleg G, Cannon A, et al. MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus. Neuro Oncol. 2022;24:1845-56. doi: 10.1093/neurore/node165.
U.S. Food and Drug Administration. FDA approves telumetinib for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. April 10, 2020. [accessed Jan 205] Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-neurofibromatosis-type-1-symptomatic-inoperable-plexiform-neurofibromas
Fisher MJ, Shin CS, Rhodes SD, Armstrong AE, Wolters PL, Dombi E, et al. Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial. Nat Med. 2021;27:165-73. doi: 10.1038/s41591-020-01935-6.
Subbiah V, Slopis J, Hong DS. Treatment of patients with advanced neurofibromatosis type 1 (NFI)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) with the MEK inhibitor colimetinib. J Clin Oncol. 2018;36:11559.
Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367:107-14. doi: 10.1056/NEMoao.1203421.
Weiss BD, Wolters PL, Plotkin SR, Widemann BC, Tonagard JH, Blakeley J, et al. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NFI-Related Plexiform Neurofibromas. J Clin Oncol. 2021;39:797-806. doi: 10.1200/J.CO.20.02220.
Perreault S, Larouche V, Tabori U, Hawkin C, Lippe S, Ellezam B, et al. A phase 2 study of trimetinib for patients with pediatric glioma or plexiform neurofibromas with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01. BMC Cancer. 2019;19:1250. doi: 10.1186/s12885-019-6442-2.
Johannessen CM, Johnson BW, Williams SM, Chan AW, Rezeek EE, Lynch RC, et al. TORCI is essential for NFI-associated malignancies. Curr Biol. 2008;18:56-62. doi: 10.1016/j.cub.2007.11.066.
Weiss B, Widemann BC, Wolters P, Dombi E, Vinks A, Cantor A, et al. Strolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study. Neuro Oncol. 2015;17:596-603. doi: 10.1093/neuonc/nou235. Erratum in: Neuro Oncol. 2015;17:905. doi: 10.1093/neuonc/nov068.
De Raedt T, Walton Z, Yecies JL, Li D, Chen Y, Malone CF, et al. Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors. Cancer Cell. 2011;20:400-13. doi: 10.1016/j.ccr.2011.08.014.
Subbiah V, Westin SN, Wang K, Araujo D, Wang WL, Miller VA, et al. Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein. J Hematol Oncol. 2014;78. doi: 10.1186/1756-8722-7-8.
Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetz SMA, Hu J, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;18:1493-501. doi: 10.1016/S1470-2045(17)30624-1.
D’Angelo SP, Mahoney MR, Van Tine BA, Atkins J, Milhem MM, Jahagirdar BN, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol. 2018;19:416-26. doi: 10.1016/S1470-2045(18)30006-8.
Pollack SM, Redman MW, Baker KK, Wagner MJ, Schroeder BA, Loggers ET, et al. Assessment of doxorubicin and pembrolizumab in patients with advanced anthracycline-naive sarcoma: a phase 1/2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1778-82. doi: 10.1001/jamanocol.2020.3689.
Sait S, Modak S. Anti-GD2 immunotherapy for osteosarcoma. Adv Exp Med Biol. 2014;80:4291-304.
Mayes DA, Hu Y, Teng Y, Siegel E, Wu X, Panda K, et al. PAX6 suppresses the invasiveness of glioblastoma cells and the expression of the matrix metalloproteinase-2 gene. Cancer Res. 2006;66:9809-17. doi: 10.1158/0008-5472 CAN-05-3877.
Patel AV, Eaves D, Jessen WJ, Rizvi TA, Ecsedy JA, Qian MG, et al. Ras-driven transcriptome analysis identifies aurora kinase A as a potential malignant peripheral nerve sheath tumor therapeutic target. Clin Cancer Res. 2012;18:5020-30. doi: 10.1158/1078-0432. CCR-12-1072.
De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRDA-based therapies. Nature. 2014;514:247-51. doi: 10.1038/nature15561.
Jousma E, Rizvi TA, Wu J, Janhofer D, Dombi E, Dunn RS, et al. Preclinical assessments of the MEK inhibitor PD-0325901 in a mouse model of Neurofibromatosis type 1. Pediatr Blood Cancer. 2015;62:1709-16. doi: 10.1002/jbc.25546
Miettinen MM, Antonescu CR, Fletcher CD, Kim A, Lazar AJ, Quezado MM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview. Hum Pathol. 2017;67:1-10. doi: 10.1016/j.humpath.2017.05.010.
Stucky CC, Johnson KN, Gray RJ, Pockaj BA, Ocal IT, Rose PS, et al. Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Ann Surg Oncol. 2012;19:878-85. doi: 10.1245/s10434-011-1978-7.
Perwitz N, Colterjohn N, Farrokhyar F, Tozer R, Figueredo A, Ghert M. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113:573-81. doi: 10.1002/cncr.23592.
Martin E, Muskiewicz KM, Claramunt-Alonso R. Clinical, pathological, and genetic features of malignant peripheral nerve sheath tumor: a systematic review with meta-analysis and pooled mutation analysis. Front Oncol. 2022;12:745952.
Carli M, Ferrari A, Mattie A, Zanetti I, Casanova M, Bisogno G, et al. Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol. 2005;23:8422-30. doi: 10.1200/JCCO.2005.01.4886.
Ferner RE, Gutmann DH. Neurofibromatosis type 1 (NFI): diagnosis and management. Handb Clin Neurol. 2013;115:939-55.
Madanikia SA, Bergner AL, Ye X, Blakeley JO. Increased risk of breast cancer in women with NFI. Am J Med Genet A. 2012;158A:3056-60. doi: 10.1002/ajmg.a.35550.
Uustalo E, Rentanen M, Kallionpaa RA, Poyhönen M, Leppskirta J, Ylä-Outinen H, et al. Distinctive cancer associations in patients with neurofibromatosis type 1. J Clin Oncol. 2016;34:1978-86. doi: 10.1200/JCCO.2015.65.3576.
Stasi C, Tawfik O. Malignant Peripheral Nerve Sheath Tumor With Rhabdomyosarcomatous Differentiation (Malignant Triton Tumor). Arch Pathol Lab Med. 2006;130:1878-81.
McConnell YJ, Giacomantonio CA. Malignant triton tumors--complete surgical resection and adjuvant radiotherapy associated with improved survival. J Surg Oncol. 2012;106:51-6.
Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, listrup DM. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer. 1986;57:2006-21.
Orphanet: Malignant triton tumor. Orphanet Report Series. 2014. [accessed Jan 2024] https://www.orpha.net/en/disease/detail/252212
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