Spindle cell sarcoma with <em>KIAA1549‑BRAF</em> resembling infantile fibrosarcoma morphologically: A case report and literature review

Fujikawa,Tomoko; Uemura,Suguru; Yoshida,Makiko; Hyodo,Sayaka; Kozaki,Aiko; Saito,Atsuro; Kishimoto,Kenji; Ishida,Toshiaki; Mori,Takeshi; Uematsu,Ayano; Morita,Keiichi; Hatakeyama,Tadashi; Tamura,Akihiro; Yamamoto,Nobuyuki; Komatsu,Masato; Soejima,Toshinori; Hasegawa,Daiichiro; Kosaka,Yoshiyuki

doi:10.3892/ol.2022.13572

Spindle cell sarcoma with KIAA1549‑BRAF resembling infantile fibrosarcoma morphologically: A case report and literature review

Authors:
- Tomoko Fujikawa
- Suguru Uemura
- Makiko Yoshida
- Sayaka Hyodo
- Aiko Kozaki
- Atsuro Saito
- Kenji Kishimoto
- Toshiaki Ishida
- Takeshi Mori
- Ayano Uematsu
- Keiichi Morita
- Tadashi Hatakeyama
- Akihiro Tamura
- Nobuyuki Yamamoto
- Masato Komatsu
- Toshinori Soejima
- Daiichiro Hasegawa
- Yoshiyuki Kosaka
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Affiliations: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe, Hyogo 650‑0047, Japan, Department of Pathology, Kobe Children's Hospital, Kobe, Hyogo 650‑0047, Japan, Department of Surgery, Kobe Children's Hospital, Kobe, Hyogo 650‑0047, Japan, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Department of Radiation Oncology, Kobe Proton Center, Kobe, Hyogo 650‑0047, Japan
Published online on: November 1, 2022 https://doi.org/10.3892/ol.2022.13572
Article Number: 452
Copyright: © Fujikawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Infantile fibrosarcoma (IFS) commonly harbors ETS variant transcription factor 6 (ETV6)‑neurotrophic receptor tyrosine kinase 3 (NTRK3) fusion. However, the recent accessibility to clinical next‑generation sequencing (NGS) has revealed ETV6‑NTRK3 negative spindle cell sarcomas resembling IFS morphologically, involving NTRK1/2, MET, RET and BRAF. The present report describes a pediatric case of spindle cell sarcoma with KIAA1549‑BRAF resembling IFS morphologically. A 20‑month‑old female patient was referred to Kobe Children's Hospital (Kobe, Japan) for the treatment of intrathoracic spindle cell sarcoma. Pathologically, the intrathoracic tumor cells were composed of spindle cells with focal hemagiopericytomatous pattern. In immunohistochemistry analysis, the intrathoracic tumor cells focally expressed desmin and WT‑1 and were negative for pan‑tropomyosin receptor kinase (TRK), S‑100 and CD34. Fluorescence in situ hybridization analysis for ETV6 and capicua transcriptional repressor revealed negative split signals. Although the patient was initially diagnosed with IFS morphologically, KIAA1549‑BRAF fusion transcript was detected by comprehensive genomic profiling with NGS using intrathoracic tumor tissues and confirmed by reverse transcription‑PCR. Chemotherapy induced a reduction in the tumor size. At present, the patient is alive with the disease and has been receiving therapy for 8 months since the initiation of chemotherapy. Review of BRAF‑altered spindle cell sarcomas resembling IFS morphologically revealed the inconsistency in immunohistochemical expression patterns and the diversity of BRAF fusion genes and mutations. Therefore, the elucidation of genomic profiling by NGS may assist in making an appropriate diagnosis and selecting novel alternative therapies in ETV6‑NTRK3‑negative spindle cell sarcomas resembling IFS morphologically.

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1	Orbach D, Rey A, Cecchetto G, Oberlin O, Casanova M, Thebaud E, Scopinaro M, Bisogno G, Carli M and Ferrari A: Infantile fibrosarcoma: Management based on the European experience. J Clin Oncol. 28:318–323. 2010. View Article : Google Scholar : PubMed/NCBI
2	Orbach D, Brennan B, De Paoli A, Gallego S, Mudry P, Francotte N, van Noesel M, Kelsey A, Alaggio R, Ranchère D, et al: Conservative strategy in infantile fibrosarcoma is possible: The European paediatric soft tissue sarcoma study group experience. Eur J Cancer. 57:1–9. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chung EB and Enzinger FM: Infantile fibrosarcoma. Cancer. 38:729–739. 1976. View Article : Google Scholar : PubMed/NCBI
4	Davis JL, Lockwood CM, Stohr B, Boecking C, Al-Ibraheemi A, DuBois SG, Vargas SO, Black JO, Cox MC, Luquette M, et al: Expanding the spectrum of pediatric NTRK-rearranged mesenchymal tumors. Am J Surg Pathol. 43:435–445. 2019. View Article : Google Scholar : PubMed/NCBI
5	Coffin CM, Jaszcz W, O'Shea PA and Dehner LP: So-called congenital-infantile fibrosarcoma: Does it exist and what is it? Pediatr Pathol. 14:133–150. 1994. View Article : Google Scholar : PubMed/NCBI
6	Rudzinski ER, Lockwood CM, Stohr BA, Vargas SO, Sheridan R, Black JO, Rajaram V, Laetsch TW and Davis JL: Pan-Trk immunohistochemistry identifies NTRK rearrangements in pediatric mesenchymal tumors. Am J Surg Pathol. 42:927–935. 2018. View Article : Google Scholar : PubMed/NCBI
7	Pavlick D, Schrock AB, Malicki D, Stephens PJ, Kuo DJ, Ahn H, Turpin B, Allen JM, Rosenzweig M, Badizadegan K, et al: Identification of NTRK fusions in pediatric mesenchymal tumors. Pediatr Blood Cancer. 64:e264332017. View Article : Google Scholar : PubMed/NCBI
8	Davis JL, Vargas SO, Rudzinski ER, López Marti JM, Janeway K, Forrest S, Winsnes K, Pinto N, Yang SE, VanSandt M, et al: Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms. Histopathology. 76:1032–1041. 2020. View Article : Google Scholar : PubMed/NCBI
9	Flucke U, van Noesel MM, Wijnen M, Zhang L, Chen CL, Sung YS and Antonescu CR: TFG-MET fusion in an infantile spindle cell sarcoma with neural features. Genes Chromosomes Cancer. 56:663–667. 2017. View Article : Google Scholar : PubMed/NCBI
10	Penning AJ, Al-Ibraheemi A, Michal M, Larsen BT, Cho SJ, Lockwood CM, Paulson VA, Liu YJ, Plank L, Fritchie K, et al: Novel BRAF gene fusions and activating point mutations in spindle cell sarcomas with histologic overlap with infantile fibrosarcoma. Mod Pathol. 34:1530–1540. 2021. View Article : Google Scholar : PubMed/NCBI
11	Kao YC, Fletcher CDM, Alaggio R, Wexler L, Zhang L, Sung YS, Orhan D, Chang WC, Swanson D, Dickson BC and Antonescu CR: Recurrent BRAF gene fusions in a subset of pediatric spindle cell sarcomas: Expanding the genetic spectrum of tumors with overlapping features with infantile fibrosarcoma. Am J Surg Pathol. 42:28–38. 2018. View Article : Google Scholar : PubMed/NCBI
12	El-Osta H, Falchook G, Tsimberidou A, Hong D, Naing A, Kim K, Wen S, Janku F and Kurzrock R: BRAF mutations in advanced cancers: Clinical characteristics and outcomes. PLoS One. 6:e258062011. View Article : Google Scholar : PubMed/NCBI
13	Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, et al: Mutations of the BRAF gene in human cancer. Nature. 417:949–954. 2002. View Article : Google Scholar : PubMed/NCBI
14	Ross JS, Wang K, Chmielecki J, Gay L, Johnson A, Chudnovsky J, Yelensky R, Lipson D, Ali SM, Elvin JA, et al: The distribution of BRAF gene fusions in solid tumors and response to targeted therapy. Int J Cancer. 138:881–890. 2016. View Article : Google Scholar : PubMed/NCBI
15	Subbiah V, Westin SN, Wang K, Araujo D, Wang WL, Miller VA, Ross JS, Stephens PJ, Palmer GA and Ali SM: 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. 7:82014. View Article : Google Scholar : PubMed/NCBI
16	Mitsis D, Opyrchal M, Zhao Y, Kane Iii JM, Cheney R and Salerno KE: Exceptional clinical response to BRAF-targeted therapy in a patient with metastatic sarcoma. Cureus. 7:e4392015.PubMed/NCBI
17	Wegert J, Vokuhl C, Collord G, Del Castillo Velasco-Herrera M, Farndon SJ, Guzzo C, Jorgensen M, Anderson J, Slater O, Duncan C, et al: Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants. Nat Commun. 9:23782018. View Article : Google Scholar : PubMed/NCBI
18	Hughes CE, Correa H, Benedetti DJ, Smith B, Sumegi J and Bridge J: Second report of PDE10A-BRAF fusion in pediatric spindle cell sarcoma with infantile fibrosarcoma-like morphology suggesting PDE10A-BRAF fusion is a recurrent event. Pediatr Dev Pathol. 24:554–558. 2021. View Article : Google Scholar : PubMed/NCBI
19	Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, et al: Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet. 45:602–612. 2013. View Article : Google Scholar : PubMed/NCBI
20	Jones DT, Kocialkowski S, Liu L, Pearson DM, Bäcklund LM, Ichimura K and Collins VP: Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 68:8673–8677. 2008. View Article : Google Scholar : PubMed/NCBI
21	Selt F, van Tilburg CM, Bison B, Sievers P, Harting I, Ecker J, Pajtler KW, Sahm F, Bahr A, Simon M, et al: Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 149:499–510. 2020. View Article : Google Scholar : PubMed/NCBI
22	Perreault S, Larouche V, Tabori U, Hawkin C, Lippé S, Ellezam B, Décarie JC, Théoret Y, Métras MÉ, Sultan S, et al: A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01. BMC Cancer. 19:12502019. View Article : Google Scholar : PubMed/NCBI