The online version of this article (https://doi.org/10.1186/s12885-018-4749-z) contains supplementary material, which is available to authorized users.
High-grade spindle cell sarcomas are a subtype of rare, undifferentiated pleomorphic sarcomas (UPSs) for which diagnosis is difficult and no specific treatment strategies have been established. The limited published data on UPSs suggest an aggressive clinical course, high rates of local recurrence and distant metastasis, and poor prognosis.
Here we present the unusual case of a 45-year-old male patient with a lumbosacral UPS extending into the sacrum. An initial diagnosis of a low-grade malignant spindle cell tumor was based on a tumor core biopsy. After complete extensive resection, the diagnosis of an UPS of the lumbosacral region was confirmed by excluding other types of cancers. Despite treatment with neoadjuvant radiotherapy, extensive resection, and adjuvant chemotherapy, the patient presented with multiple pulmonary metastases 3 months after surgery. The patient then began treatment with crizotinib at an oral dose of 450 mg per day, based on the detection of a LMNA-NTRK1 fusion gene in the tumor by next-generation sequencing. Over 18 months of follow-up through July 2018, the patient maintained a near-complete clinical response to crizotinib.
The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target. Molecular and cytogenetic evaluations are critical to accurate prognosis and treatment planning in cases of UPS, especially when treatment options are limited or otherwise exhausted. Molecularly targeted therapy of these rare but aggressive lesions represents a novel treatment option that may lead to fewer toxic side effects and better clinical outcomes.
Additional file 1: FISH result of MDM2 amplification. (PDF 299 kb)12885_2018_4749_MOESM1_ESM.pdf
Additional file 2: The MasterView 381 cancer-gene panel. (PDF 77 kb)12885_2018_4749_MOESM2_ESM.pdf
Additional file 3: LMNA BLAST. (PDF 42 kb)12885_2018_4749_MOESM3_ESM.pdf
Additional file 4: NTRK1 BLAST. (PDF 47 kb)12885_2018_4749_MOESM4_ESM.pdf
Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay J-Y, Tendero O, Beveridge RD, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017;18(6):812–22. CrossRefPubMed
Liegl-Atzwanger B, Hofmann G, Leithner A, Beham A. Undifferentiated high-grade pleomorphic sarcoma (UHPS): diagnostic criteria, differential diagnosis, and treatment. An attempt to erasure the misnomer “MFH”. Eur Surg. 2009;41(4):143–9. CrossRef
Savina M, Le Cesne A, Blay JY, Ray-Coquard I, Mir O, Toulmonde M, Cousin S, Terrier P, Ranchere-Vince D, Meeus P, et al. Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study. BMC Med. 2017;15(1):78. CrossRefPubMedPubMedCentral
Doebele RC, Davis LE, Vaishnavi A, Le AT, Estrada-Bernal A, Keysar S, Jimeno A, Varella-Garcia M, Aisner DL, Li Y, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov. 2015;5(10):1049–57. CrossRefPubMedPubMedCentral
Wong V, Pavlick D, Brennan T, Yelensky R, Crawford J, Ross JS, Miller VA, Malicki D, Stephens PJ, Ali SM, et al. Evaluation of a congenital infantile Fibrosarcoma by comprehensive genomic profiling reveals an LMNA-NTRK1 gene fusion responsive to Crizotinib. J Natl Cancer Inst. 2016;108(1):307–10.
Haller F, Knopf J, Ackermann A, Bieg M, Kleinheinz K, Schlesner M, Moskalev EA, Will R, Satir AA, Abdelmagid IE, et al. Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern. J Pathol. 2016;238(5):700–10. CrossRefPubMed
- A primary undifferentiated pleomorphic sarcoma of the lumbosacral region harboring a LMNA-NTRK1 gene fusion with durable clinical response to crizotinib: a case report
- BioMed Central
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