Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "Acral FibroChondroMyxoid Tumors".
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
07
11
2019
accepted:
16
01
2020
revised:
16
01
2020
pubmed:
13
2
2020
medline:
9
7
2021
entrez:
13
2
2020
Statut:
ppublish
Résumé
Acral soft tissue tumors are common neoplasms, a subset of which pose a diagnostic challenge. We report 10 cases of a previously unrecognized acral benign soft tissue tumor. These tumors arose on the fingers and toes and involved bone in half of cases. Histologically, the tumors were lobulated and displayed an abundant stroma made of variable fibrous, chondroid and myxoid material reminiscent of cartilaginous or myoepithelial differentiation. Tumor cells harbored small round to reniform nuclei with clear chromatin and inconspicuous nucleoli along with scant eosinophilic cytoplasm. The cells were mostly arranged haphazardly in the stroma but also in small clusters. No mitotic activity was detected. No specific feature was identified in recurrent cases. By immunohistochemistry, the cells consistently stained for CD34 (10/10), ERG (9/10), and SOX9 (7/10). Whole RNA sequencing identified a previously undescribed recurrent in frame THBS1-ADGRF5 gene fusion in all cases. The transcript was confirmed by RT-PCR and was not found in the control group of mimickers including soft tissue chondromas. We propose the name of Acral FibroChondroMyxoid Tumors for this new entity.
Identifiants
pubmed: 32047233
doi: 10.1038/s41379-020-0493-4
pii: S0893-3952(22)00819-5
doi:
Substances chimiques
ADGRF5 protein, human
0
Receptors, G-Protein-Coupled
0
Thrombospondin 1
0
thrombospondin-1, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1360-1368Références
Amary F, Perez-Casanova L, Ye H, Cottone L, Strobl AC, Cool P, et al. Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. Mod Pathol. 2019. https://doi.org/10.1038/s41379-019-0315-8 .
Bray NL, Pimentel H, Melsted P, Pachter L. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016;34:525–7.
doi: 10.1038/nbt.3519
Ge H, Liu K, Juan T, Fang F, Newman M, Hoeck W. FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution. Bioinformatics. 2011;27:1922–8.
doi: 10.1093/bioinformatics/btr310
Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7:562–78.
doi: 10.1038/nprot.2012.016
Le Loarer F, Watson S, Pierron G, De Montpreville VT, ballet S, Firmin N, et al. SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nat Genet. 2015;47:1200–5.
doi: 10.1038/ng.3399
Zamecnik M, Michal M. Nuchal fibrocartilaginous pseudotumor: immunohistochemical and ultrastructural study of two cases. Pathol Int. 2001;51:723–8.
doi: 10.1046/j.1440-1827.2001.01265.x
Declercq HA, Forsyth RG, Verbruggen A, Verdonk R, Cornelissen JJ, Verdonk PC, et al. CD34 and SMA expression of superficial zone cells in the normal and pathological human meniscus. J Orthop Res. 2012;30:800–8.
doi: 10.1002/jor.21582
Shon W, Folpe AL, Fritchie KJ. ERG expression in chondrogenic bone and soft tissue tumours. J Clin Pathol. 2015;68:125–9.
doi: 10.1136/jclinpath-2014-202601
Adams JC, Lawler J. The thrombospondins. Cold Spring Harb Perspect Biol. 2011;3:a009712.
doi: 10.1101/cshperspect.a009712
Rosini S, Pugh N, Bonna AM, Hulmes DJS, Farndale RW, Adams JC. Thrombospondin-1 promotes matrix homeostasis by interacting with collagen and lysyl oxidase precursors and collagen cross-linking sites. Sci Signal. 2018;11. https://doi.org/10.1126/scisignal.aar2566 .
DiCesare PE, Mörgelin M, Mann K, Paulsson M. Cartilage oligomeric matrix protein and thrombospondin 1. Purification from articular cartilage, electron microscopic structure, and chondrocyte binding. Eur J Biochem. 1994;223:927–37.
doi: 10.1111/j.1432-1033.1994.tb19070.x
Potikyan G, Savene RO, Gaulden JM, France KA, Zhou Z, Kleinerman ES, et al. EWS/FLI1 regulates tumor angiogenesis in Ewing’s sarcoma via suppression of thrombospondins. Cancer Res. 2007;67:6675–84.
doi: 10.1158/0008-5472.CAN-06-4140
Antiangiogenic activity of trabectedin in myxoid liposarcoma: involvement of host TIMP-1 and TIMP-2 and tumor thrombospondin-1.—PubMed—NCBI. https://www.ncbi.nlm.nih.gov/pubmed/?term=24917554 . Accessed 4 Oct 2019.
Haimes JD, Stewart CJR, Kudlow BA, Culver BP, Mong B, Koay E, et al. Uterine inflammatory myofibroblastic tumors frequently harbor ALK fusions with IGFBP5 and THBS1. Am J Surg Pathol. 2017;41:773–80.
doi: 10.1097/PAS.0000000000000801
Prömel S, Waller-Evans H, Dixon J, Zahn D, Colledge WH, Doran J, et al. Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Dev Dyn. 2012;241:1591–602.
doi: 10.1002/dvdy.23841
Lu S, Liu S, Wietelmann A, Kojonazarov B, Atzberger A, Tang C, et al. Developmental vascular remodeling defects and postnatal kidney failure in mice lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4). PLoS ONE. 2017;12:e0183166.
doi: 10.1371/journal.pone.0183166
Yang MY, Hilton MB, Seaman S, Haines DC, Nagashima K, Burks, et al. Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell Rep. 2013;3:1457–64.
doi: 10.1016/j.celrep.2013.04.019
Fredriksson R, Lagerström MC, Höglund PJ, Schiöth HB, et al. Novel human G protein-coupled receptors with long N-terminals containing GPS domains and Ser/Thr-rich regions. FEBS Lett. 2002;531:407–14.
doi: 10.1016/S0014-5793(02)03574-3
Tang X, Jin R, Qu G, Wang X, Li Z, Yuan Z, et al. GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63RhoGEF-Rho GTPase pathway. Cancer Res. 2013;73:6206–18.
doi: 10.1158/0008-5472.CAN-13-1049
Yang L, Lin X-L, Liang W, Fu SW, Lin WF, Tian XQ, et al. High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma. Oncotarget. 2017;8:47943–56.
doi: 10.18632/oncotarget.18203
Cho SH, Horvai A. chondro-osseous lesions of soft tissue. Surg Pathol. 2015;8:419–44.
doi: 10.1016/j.path.2015.05.004
Agaram NP, Chen H-W, Zhang L, Sung YS, Panicek D, Healey JH, et al. EWSR1-PBX3: a novel gene fusion in myoepithelial tumors. Genes Chromosomes Cancer. 2015;54:63–71.
doi: 10.1002/gcc.22216
Antonescu CR, Zhang L, Chang N-E, Pawel BR, Travis W, Katabi N, et al. EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer. 2010;49:1114–24.
doi: 10.1002/gcc.20819
Hollmann TJ, Bovée JVMG, Fletcher CDM. Digital fibromyxoma (superficial acral fibromyxoma): a detailed characterization of 124 cases. Am J Surg Pathol. 2012;36:789–98.
doi: 10.1097/PAS.0b013e31824a0b83
Moulonguet I, Goettmann S, Zaraa I. Superficial acral fibromyxoma with cartilaginous metaplasia. Am J Dermatopathol. 2019;41:316–7.
doi: 10.1097/DAD.0000000000001103
Agaimy A, Michal M, Giedl J, Hadravsky L, Michal M. Superficial acral fibromyxoma: clinicopathological, immunohistochemical, and molecular study of 11 cases highlighting frequent Rb1 loss/deletions. Hum Pathol. 2017;60:192–8.
doi: 10.1016/j.humpath.2016.10.016
Nielsen GP, Keel SB, Dickersin GR, Selig MK, Bhan AK, Rosenberg AE. Chondromyxoid fibroma: a tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation. Mod Pathol. 1999;12:514–7.
pubmed: 10349990
Nord KH, Lilljebjörn H, Vezzi F, Nilsson J, Magnusson L, Tayebwa J, et al. GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma. Nat Genet. 2014;46:474–7.
doi: 10.1038/ng.2927
Puls F, Hofvander J, Magnusson L, Nilsson J, Haywood E, Sumathi VP, et al. FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma. J Pathol. 2016;238:502–7.
doi: 10.1002/path.4683
Dickson BC, Antonescu CR, Argyris PP, Bilodeau EA, Bullock MJ, Freedman PD, et al. Ectomesenchymal chondromyxoid tumor: a neoplasm characterized by recurrent RREB1-MKL2 fusions. Am J Surg Pathol. 2018;42:1297–305.
doi: 10.1097/PAS.0000000000001096
Bitzer A, McCarthy EF, Morris CD. Extra-axial chordoma of the hand. J Hand Surg Am. 2017;42:933.e1–933.e5.
doi: 10.1016/j.jhsa.2017.05.033
Righi A, Sbaraglia M, Gambarotti M, Cocchi S, Drago G, Casadei R, et al. Extra-axial chordoma: a clinicopathologic analysis of six cases. Virchows Arch. 2018;472:1015–20.
doi: 10.1007/s00428-018-2334-0
Urbini M, Astolfi A, Pantaleo MA, Serravalle S, Dei Tos AP, Picci P, et al. HSPA8 as a novel fusion partner of NRA3 in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer. 2017;56:582–6.
doi: 10.1002/gcc.22462