Abstract
Although traditional morphological evaluation remains the cornerstone for the diagnosis of soft tissue tumors, ancillary diagnostic modalities such as immunohistochemistry and molecular genetic analysis are of ever-increasing importance in this field. New insights into the molecular pathogenesis of soft tissue tumors, often obtained from high-throughput sequencing technologies, has enabled significant progress in the characterization and biologic stratification of mesenchymal neoplasms, expanding the spectrum of immunohistochemical tests (often aimed towards recently discovered genetic events) and molecular genetic assays (most often fluorescence in situ hybridization and reverse transcription-polymerase chain reaction). This review discusses selected novel molecular and immunohistochemical assays with diagnostic applicability in mesenchymal neoplasms, with emphasis on diagnosis, refinement of tumor classification, and treatment stratification.
Similar content being viewed by others
References
Andrici J, Gill AJ, Hornick JL (2018) Next generation immunohistochemistry: Emerging substitutes to genetic testing? Semin Diagn Pathol 35(3):161–169
Le Loarer F, Laffont S, Lesluyes T, Tirode F, Antonescu C, Baglin AC et al (2019) Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum. Am J Surg Pathol 43(6):747–754
Wong WJ, Lauria A, Hornick JL, Xiao S, Fletcher JA, Marino-Enriquez A (2016) Alternate PAX3-FOXO1 oncogenic fusion in biphenotypic sinonasal sarcoma. Genes Chromosom Cancer 55(1):25–29
Alaggio R, Rosolen A, Sartori F, Leszl A, d'Amore ES, Bisogno G et al (2007) Spindle cell tumor with EWS-WT1 transcript and a favorable clinical course: a variant of DSCT, a variant of leiomyosarcoma, or a new entity? Report of 2 pediatric cases. Am J Surg Pathol 31(3):454–459
Ud Din N, Pekmezci M, Javed G, Horvai AE, Ahmad Z, Faheem M et al (2015) Low-grade small round cell tumor of the cauda equina with EWSR1-WT1 fusion and indolent clinical course. Hum Pathol 46(1):153–158
Kohashi K, Oda Y (2017) Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer Sci 108(4):547–552
Wilson BG, Roberts CW (2011) SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 11(7):481–492
Biegel JA (2006) Molecular genetics of atypical teratoid/rhabdoid tumor. Neurosurg Focus 20(1):E11
Biegel JA, Tan L, Zhang F, Wainwright L, Russo P, Rorke LB (2002) Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin Cancer Res : Off J Am Assoc Cancer Res 8(11):3461–3467
Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B (1999) Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59(1):74–79
Hoot AC, Russo P, Judkins AR, Perlman EJ, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors. Am J Surg Pathol 28(11):1485–1491
Sigauke E, Rakheja D, Maddox DL, Hladik CL, White CL, Timmons CF et al (2006) Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis. Mod Pathol 19(5):717–725
Judkins AR, Burger PC, Hamilton RL, Kleinschmidt-DeMasters B, Perry A, Pomeroy SL et al (2005) INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol 64(5):391–397
Perry A, Fuller CE, Judkins AR, Dehner LP, Biegel JA (2005) INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas. Mod Pathol 18(7):951–958
Judkins AR, Mauger J, Ht A, Rorke LB, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. Am J Surg Pathol 28(5):644–650
Kosemehmetoglu K, Kaygusuz G, Bahrami A, Raimondi SC, Kilicarslan K, Yildiz Y et al (2011) Intra-articular epithelioid sarcoma showing mixed classic and proximal-type features: report of 2 cases, with immunohistochemical and molecular cytogenetic INI-1 study. Am J Surg Pathol 35(6):891–897
Hollmann TJ, Hornick JL (2011) INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 35(10):e47–e63
Raoux D, Peoc'h M, Pedeutour F, Vaunois B, Decouvelaere AV, Folpe AL (2009) Primary epithelioid sarcoma of bone: report of a unique case, with immunohistochemical and fluorescent in situ hybridization confirmation of INI1 deletion. Am J Surg Pathol 33(6):954–958
Orrock JM, Abbott JJ, Gibson LE, Folpe AL (2009) INI1 and GLUT-1 expression in epithelioid sarcoma and its cutaneous neoplastic and nonneoplastic mimics. Am J Dermatopathol 31(2):152–156
Hornick JL, Dal Cin P, Fletcher CD (2009) Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 33(4):542–550
Carter JM, O'Hara C, Dundas G, Gilchrist D, Collins MS, Eaton K et al (2012) Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1 mutation. Am J Surg Pathol 36(1):154–160
Patil S, Perry A, Maccollin M, Dong S, Betensky RA, Yeh TH et al (2008) Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas. Brain Pathol 18(4):517–519
Jo VY, Fletcher CDM (2017) SMARCB1/INI1 Loss in Epithelioid Schwannoma: A Clinicopathologic and Immunohistochemical Study of 65 Cases. Am J Surg Pathol 41(8):1013–1022
Hasselblatt M, Thomas C, Hovestadt V, Schrimpf D, Johann P, Bens S et al (2016) Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis. Acta Neuropathol 132(1):149–151
Knutson SK, Warholic NM, Wigle TJ, Klaus CR, Allain CJ, Raimondi A et al (2013) Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci U S A 110(19):7922–7927
Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ et al (2010) Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18(4):316–328
Bookhout C, Bouldin TW, Ellison DW (2017) Atypical teratoid/rhabdoid tumor with retained INI1 (SMARCB1) expression and loss of BRG1 (SMARCA4). Neuropathology.
Kohashi K, Yamamoto H, Yamada Y, Kinoshita I, Taguchi T, Iwamoto Y et al (2018) SWI/SNF Chromatin-remodeling Complex Status in SMARCB1/INI1-preserved Epithelioid Sarcoma. Am J Surg Pathol 42(3):312–318
Karanian-Philippe M, Velasco V, Longy M, Floquet A, Arnould L, Coindre JM et al (2015) SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas. Am J Surg Pathol 39(9):1197–1205
Agaimy A, Hartmann A, Antonescu CR, Chiosea SI, El-Mofty SK, Geddert H et al (2017) SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphologic and Clinicopathologic Spectrum of a Recently Described Entity. Am J Surg Pathol 41(4):458–471
Agaimy A, Fuchs F, Moskalev EA, Sirbu H, Hartmann A, Haller F (2017) SMARCA4-deficient pulmonary adenocarcinoma: clinicopathological, immunohistochemical, and molecular characteristics of a novel aggressive neoplasm with a consistent TTF1(neg)/CK7(pos)/HepPar-1(pos) immunophenotype. Virchows Arch 471(5):599–609
Agaimy A, Daum O, Markl B, Lichtmannegger I, Michal M, Hartmann A (2016) SWI/SNF Complex-deficient Undifferentiated/Rhabdoid Carcinomas of the Gastrointestinal Tract: A Series of 13 Cases Highlighting Mutually Exclusive Loss of SMARCA4 and SMARCA2 and Frequent Co-inactivation of SMARCB1 and SMARCA2. Am J Surg Pathol 40(4):544–553
Sauter JL, Graham RP, Larsen BT, Jenkins SM, Roden AC, Boland JM (2017) SMARCA4-deficient thoracic sarcoma: a distinctive clinicopathological entity with undifferentiated rhabdoid morphology and aggressive behavior. Mod Pathol 30(10):1422–1432
Kuwamoto S, Matsushita M, Takeda K, Tanaka N, Endo Y, Yamasaki A et al (2017) SMARCA4-deficient thoracic sarcoma: report of a case and insights into how to reach the diagnosis using limited samples and resources. Hum Pathol 70:92–97
Le Loarer F, Watson S, Pierron G, de Montpreville VT, Ballet S, Firmin N et al (2015) SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nat Genet 47(10):1200–1205
Perret R, Chalabreysse L, Watson S, Serre I, Garcia S, Forest F et al (2019) SMARCA4-deficient Thoracic Sarcomas: Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses. Am J Surg Pathol 43(4):455–465
Antonescu C (2014) Round cell sarcomas beyond Ewing: emerging entities. Histopathology. 64(1):26–37
Italiano A, Sung YS, Zhang L, Singer S, Maki RG, Coindre JM et al (2012) High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. Genes Chromosom Cancer 51(3):207–218
Graham C, Chilton-MacNeill S, Zielenska M, Somers GR (2012) The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas. Hum Pathol 43(2):180–189
Kao YC, Owosho AA, Sung YS, Zhang L, Fujisawa Y, Lee JC et al (2018) BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas. Am J Surg Pathol 42(5):604–615
Gambarotti M, Benini S, Gamberi G, Cocchi S, Palmerini E, Sbaraglia M et al (2016) CIC-DUX4 fusion-positive round-cell sarcomas of soft tissue and bone: a single-institution morphological and molecular analysis of seven cases. Histopathology. 69(4):624–634
Sugita S, Arai Y, Tonooka A, Hama N, Totoki Y, Fujii T et al (2014) A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma. Am J Surg Pathol 38(11):1571–1576
Yoshimoto M, Graham C, Chilton-MacNeill S, Lee E, Shago M, Squire J et al (2009) Detailed cytogenetic and array analysis of pediatric primitive sarcomas reveals a recurrent CIC-DUX4 fusion gene event. Cancer Genet Cytogenet 195(1):1–11
Solomon DA, Brohl AS, Khan J, Miettinen M (2014) Clinicopathologic features of a second patient with Ewing-like sarcoma harboring CIC-FOXO4 gene fusion. Am J Surg Pathol 38(12):1724–1725
Specht K, Sung YS, Zhang L, Richter GH, Fletcher CD, Antonescu CR (2014) Distinct transcriptional signature and immunoprofile of CIC-DUX4 fusion-positive round cell tumors compared to EWSR1-rearranged Ewing sarcomas: further evidence toward distinct pathologic entities. Genes Chromosom Cancer 53(7):622–633
Hung YP, Fletcher CD, Hornick JL (2016) Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics. Mod Pathol 29(11):1324–1334
Antonescu CR, Owosho AA, Zhang L, Chen S, Deniz K, Huryn JM et al (2017) Sarcomas With CIC-rearrangements Are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases. Am J Surg Pathol 41(7):941–949
Yamada Y, Kuda M, Kohashi K, Yamamoto H, Takemoto J, Ishii T et al (2017) Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes. Virchows Arch 470(4):373–380
Le Guellec S, Velasco V, Perot G, Watson S, Tirode F, Coindre JM (2016) ETV4 is a useful marker for the diagnosis of CIC-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions. Mod Pathol 29(12):1523–1531
Machado I, Yoshida A, Lopez-Guerrero JA, Nieto MG, Navarro S, Picci P et al (2017) Immunohistochemical analysis of NKX2.2, ETV4, and BCOR in a large series of genetically confirmed Ewing sarcoma family of tumors. Pathol Res Pract 213(9):1048–1053
Siegele B, Roberts J, Black JO, Rudzinski E, Vargas SO, Galambos C (2017) DUX4 Immunohistochemistry Is a Highly Sensitive and Specific Marker for CIC-DUX4 Fusion-positive Round Cell Tumor. Am J Surg Pathol 41(3):423–429
Pierron G, Tirode F, Lucchesi C, Reynaud S, Ballet S, Cohen-Gogo S et al (2012) A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion. Nat Genet 44(4):461–466
Puls F, Niblett A, Marland G, Gaston CL, Douis H, Mangham DC et al (2014) BCOR-CCNB3 (Ewing-like) sarcoma: a clinicopathologic analysis of 10 cases, in comparison with conventional Ewing sarcoma. Am J Surg Pathol 38(10):1307–1318
Kao YC, Sung YS, Zhang L, Chen CL, Huang SC, Antonescu CR (2017) Expanding the molecular signature of ossifying fibromyxoid tumors with two novel gene fusions: CREBBP-BCORL1 and KDM2A-WWTR1. Genes Chromosom Cancer 56(1):42–50
Specht K, Zhang L, Sung YS, Nucci M, Dry S, Vaiyapuri S et al (2016) Novel BCOR-MAML3 and ZC3H7B-BCOR Gene Fusions in Undifferentiated Small Blue Round Cell Sarcomas. Am J Surg Pathol 40(4):433–442
Kao YC, Sung YS, Zhang L, Huang SC, Argani P, Chung CT et al (2016) Recurrent BCOR Internal Tandem Duplication and YWHAE-NUTM2B Fusions in Soft Tissue Undifferentiated Round Cell Sarcoma of Infancy: Overlapping Genetic Features With Clear Cell Sarcoma of Kidney. Am J Surg Pathol 40(8):1009–1020
Cohen-Gogo S, Cellier C, Coindre JM, Mosseri V, Pierron G, Guillemet C et al (2014) Ewing-like sarcomas with BCOR-CCNB3 fusion transcript: a clinical, radiological and pathological retrospective study from the Societe Francaise des Cancers de L'Enfant. Pediatr Blood Cancer 61(12):2191–2198
Ludwig K, Alaggio R, Zin A, Peron M, Guzzardo V, Benini S et al (2017) BCOR-CCNB3 Undifferentiated Sarcoma-Does Immunohistochemistry Help in the Identification? Pediatr Dev Pathol 20(4):321–329
Matsuyama A, Shiba E, Umekita Y, Nosaka K, Kamio T, Yanai H et al (2017) Clinicopathologic Diversity of Undifferentiated Sarcoma With BCOR-CCNB3 Fusion: Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for BCOR and CCNB3. Am J Surg Pathol 41(12):1713–1721
Kao YC, Sung YS, Zhang L, Jungbluth AA, Huang SC, Argani P et al (2016) BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities. Am J Surg Pathol 40(12):1670–1678
Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG et al (2011) A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosom Cancer 50(8):644–653
Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ et al (2011) Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med 3(98):98ra82
Huentelman MJ, Papassotiropoulos A, Craig DW, Hoerndli FJ, Pearson JV, Huynh KD et al (2007) Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance. Hum Mol Genet 16(12):1469–1477
Shibuya R, Matsuyama A, Shiba E, Harada H, Yabuki K, Hisaoka M (2015) CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma. Histopathology. 67(6):827–835
Doyle LA, Fletcher CD, Hornick JL (2016) Nuclear Expression of CAMTA1 Distinguishes Epithelioid Hemangioendothelioma From Histologic Mimics. Am J Surg Pathol 40(1):94–102
Yusifli Z, Kosemehmetoglu K (2014) CAMTA1 immunostaining is not useful in differentiating epithelioid hemangioendothelioma from its potential mimickers. Turk Patoloji Derg 30(3):159–165
Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, Chen CL et al (2013) Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosom Cancer 52(8):775–784
Sharain RF, Gown AM, Greipp PT, Folpe AL (2019) Immunohistochemistry for TFE3 lacks specificity and sensitivity in the diagnosis of TFE3-rearranged neoplasms: a comparative, 2-laboratory study. Hum Pathol 87:65–74
Billings SD, Folpe AL, Weiss SW (2003) Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol 27(1):48–57
Hornick JL, Fletcher CD (2011) Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol 35(2):190–201
Fittall MW, Mifsud W, Pillay N, Ye H, Strobl AC, Verfaillie A et al (2018) Recurrent rearrangements of FOS and FOSB define osteoblastoma. Nat Commun 9(1):2150
Milde-Langosch K (2005) The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer 41(16):2449–2461
Trombetta D, Magnusson L, von Steyern FV, Hornick JL, Fletcher CD, Mertens F (2011) Translocation t(7;19)(q22;q13)-a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? Cancer Gene Ther 204(4):211–215
Walther C, Tayebwa J, Lilljebjorn H, Magnusson L, Nilsson J, von Steyern FV et al (2014) A novel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic haemangioendothelioma. J Pathol 232(5):534–540
Agaram NP, Zhang L, Cotzia P, Antonescu CR (2018) Expanding the Spectrum of Genetic Alterations in Pseudomyogenic Hemangioendothelioma With Recurrent Novel ACTB-FOSB Gene Fusions. Am J Surg Pathol 42(12):1653–1661
Panagopoulos I, Lobmaier I, Gorunova L, Heim S (2019) Fusion of the Genes WWTR1 and FOSB in Pseudomyogenic Hemangioendothelioma. Cancer Genomics Proteomics 16(4):293–298
Walther C, Tayebwa J, Lilljebjorn H, Magnusson L, Nilsson J, von Steyern FV et al (2013) A novel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic hemangioendothelioma. J Pathol
Antonescu CR, Chen HW, Zhang L, Sung YS, Panicek D, Agaram NP et al (2014) ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features. Genes Chromosom Cancer 53(11):951–959
Huang SC, Zhang L, Sung YS, Chen CL, Krausz T, Dickson BC et al (2015) Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases With Morphologic Reappraisal. Am J Surg Pathol 39(10):1313–1321
Ide YH, Tsukamoto Y, Ito T, Watanabe T, Nakagawa N, Haneda T et al (2015) Penile pseudomyogenic hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma with a novel pattern of SERPINE1-FOSB fusion detected by RT-PCR--report of a case. Pathol Res Pract 211(5):415–420
Sugita S, Hirano H, Kikuchi N, Kubo T, Asanuma H, Aoyama T et al (2016) Diagnostic utility of FOSB immunohistochemistry in pseudomyogenic hemangioendothelioma and its histological mimics. Diagn Pathol 11(1):75
Hung YP, Fletcher CD, Hornick JL (2017) FOSB is a Useful Diagnostic Marker for Pseudomyogenic Hemangioendothelioma. Am J Surg Pathol 41(5):596–606
Ortins-Pina A, Llamas-Velasco M, Turpin S, Soares-de-Almeida L, Filipe P, Kutzner H (2018) FOSB immunoreactivity in endothelia of epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia). J Cutan Pathol 45(6):395–402
Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H et al (1996) Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. Genomics. 37(1):1–8
Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer 11(8):541–557
Hallor KH, Mertens F, Jin Y, Meis-Kindblom JM, Kindblom LG, Behrendtz M et al (2005) Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. Genes Chromosom Cancer 44(1):97–102
Chen G, Folpe AL, Colby TV, Sittampalam K, Patey M, Chen MG et al (2011) Angiomatoid fibrous histiocytoma: unusual sites and unusual morphology. Mod Pathol 24(12):1560–1570
Rossi S, Szuhai K, Ijszenga M, Tanke HJ, Zanatta L, Sciot R et al (2007) EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clin Cancer Res 13(24):7322–7328
Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD et al (2007) EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosom Cancer 46(12):1051–1060
Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F et al (1993) EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet 4(4):341–345
Hisaoka M, Ishida T, Kuo TT, Matsuyama A, Imamura T, Nishida K et al (2008) Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol 32(3):452–460
Wang WL, Mayordomo E, Zhang W, Hernandez VS, Tuvin D, Garcia L et al (2009) Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol 22(9):1201–1209
Thway K, Nicholson AG, Lawson K, Gonzalez D, Rice A, Balzer B et al (2011) Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity. Am J Surg Pathol 35(11):1722–1732
Thway K, Fisher C (2012) Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol 36(7):e1–e11
Flucke U, Mentzel T, Verdijk MA, Slootweg PJ, Creytens DH, Suurmeijer AJ et al (2012) EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report. Hum Pathol 43(5):764–768
Tanguay J, Weinreb I (2013) What the EWSR1-ATF1 fusion has taught us about hyalinizing clear cell carcinoma. Head Neck Pathol 7(1):28–34
Kao YC, Sung YS, Zhang L, Chen CL, Vaiyapuri S, Rosenblum MK et al (2017) EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location. Am J Surg Pathol 41(4):482–490
Bale TA, Oviedo A, Kozakewich H, Giannini C, Davineni PK, Ligon K et al (2018) Intracranial myxoid mesenchymal tumors with EWSR1-CREB family gene fusions: myxoid variant of angiomatoid fibrous histiocytoma or novel entity? Brain Pathol 28(2):183–191
Chapman E, Skalova A, Ptakova N, Martinek P, Goytain A, Tucker T et al (2018) Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion: Report of 3 Cases. Am J Surg Pathol 42(9):1182–1189
Watson S, Perrin V, Guillemot D, Reynaud S, Coindre JM, Karanian M et al (2018) Transcriptomic definition of molecular subgroups of small round cell sarcomas. J Pathol 245(1):29–40
Koelsche C, Kriegsmann M, Kommoss FKF, Stichel D, Kriegsmann K, Vokuhl C et al (2019) DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma. J Cancer Res Clin Oncol 145(5):1273–1281
Diaz-Perez JA, Nielsen GP, Antonescu C, Taylor MS, Lozano-Calderon SA, Rosenberg AE (2019) EWSR1/FUS - NFATc2 rearranged round cell sarcoma: Clinicopathological series of four cases and literature review. Hum Pathol
Wang GY, Thomas DG, Davis JL, Ng T, Patel RM, Harms PW et al (2019) EWSR1-NFATC2 Translocation-associated Sarcoma Clinicopathologic Findings in a Rare Aggressive Primary Bone or Soft Tissue Tumor. Am J Surg Pathol
Michal M, Berry RS, Rubin BP, Kilpatrick SE, Agaimy A, Kazakov DV et al (2018) EWSR1-SMAD3-rearranged Fibroblastic Tumor: An Emerging Entity in an Increasingly More Complex Group of Fibroblastic/Myofibroblastic Neoplasms. Am J Surg Pathol 42(10):1325–1333
Kao YC, Flucke U, Eijkelenboom A, Zhang L, Sung YS, Suurmeijer AJH et al (2018) Novel EWSR1-SMAD3 Gene Fusions in a Group of Acral Fibroblastic Spindle Cell Neoplasms. Am J Surg Pathol 42(4):522–528
Agaram NP, Zhang L, Sung YS, Cavalcanti MS, Torrence D, Wexler L et al (2019) Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 Distinct Gene Fusions and Phenotype. Am J Surg Pathol 43(5):695–702
Dashti NK, Wehrs RN, Thomas BC, Nair A, Davila J, Buckner JC et al (2018) Spindle cell rhabdomyosarcoma of bone with FUS-TFCP2 fusion: confirmation of a very recently described rhabdomyosarcoma subtype. Histopathology. 73(3):514–520
Suurmeijer AJ, Dickson BC, Swanson D, Zhang L, Sung YS, Huang HY et al (2019) The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements. Genes Chromosom Cancer
Hung YP, Fletcher CDM, Hornick JL (2018) Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics. Histopathology. 73(4):634–644
Rudzinski ER, Lockwood CM, Stohr BA, Vargas SO, Sheridan R, Black JO et al (2018) Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. Am J Surg Pathol 42(7):927–935
Hechtman JF, Benayed R, Hyman DM, Drilon A, Zehir A, Frosina D et al (2017) Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol 41(11):1547–1551
Wong D, Yip S, Sorensen PH (2019) Methods for Identifying Patients with Tropomyosin Receptor Kinase (TRK) Fusion Cancer. Pathol Oncol Res
Author information
Authors and Affiliations
Contributions
Dr Folpe contributed to the writing of manuscript and the production of the figures. Dr. Thway contributed to the writing of the manuscript.
Corresponding author
Ethics declarations
Drs. Folpe and Thway attest that this manuscript was produced in accordance with the ethical standards of the institutional research committees of Mayo Clinic and The Royal Marsden NHS Trust and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Thway, K., Folpe, A.L. Update on selected advances in the immunohistochemical and molecular genetic analysis of soft tissue tumors. Virchows Arch 476, 3–15 (2020). https://doi.org/10.1007/s00428-019-02678-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-019-02678-7