Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.

Bioptic Laboratory Ltd Pilsen Czech Republic

Coordinator of the International Head and Neck Scientific Group Padua Italy

Department of Anatomical Pathology University of Calgary Calgary AB Canada

Department of Head and Neck Surgery The University of Texas MD Anderson Cancer Center Houston TX USA

Department of Hematology and Medical Oncology Winship Cancer Institute Emory University School of Medicine Atlanta GA USA

Department of Oncology Section Head and Neck Oncology Leuven Cancer Institute KU Leuven Louvain Belgium

Department of Otolaryngology Head and Neck Surgery Faculty of Medicine Graduate School of Medicine Hokkaido University Hokkaido Japan

Department of Otolaryngology ISPA IUOPA CIBERONC Hospital Universitario Central de Asturias University of Oviedo Oviedo Spain

Department of Otorhinolaryngology Head and Neck Surgery Hospital Universitario Donostia Donostia San Sebastian Guipuzkoa Basque Country Spain

Department of Otorhinolaryngology Head and Neck Surgery Leuven Cancer Institute University Hospitals Leuven 3000 Louvain Belgium

Department of Otorhinolaryngology Jena University Hospital Jena Germany

Department of Pathology Turku University Hospital Turku Finland

Department of Radiation Oncology Leuven Cancer Institute University Hospitals Leuven 3000 Louvain Belgium

Department of Radiation Oncology Olivia Newton John Cancer Wellness and Research Centre Austin Health Melbourne Australia

Department of Translational Research School of Medicine University of Pisa Pisa Italy

Faculty of Medicine and Biomedical Sciences University of Algarve Faro Portugal

Institute of Biomedicine Pathology University of Turku Turku Finland

Institute of Pathology University Hospital Erlangen Friedrich Alexander University Erlangen Nürnberg Erlangen Germany

Laboratory of Experimental Radiotherapy Department of Oncology Leuven Cancer Institute University Hospitals Leuven 3000 Louvain Belgium

Sikl's Department of Pathology Faculty of Medicine in Pilsen Charles University E Benese 13 305 99 Pilsen Czech Republic

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WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer; forthcoming. (WHO classification of tumours series, 5th edn, vol 9). https://publications.iarc.fr

Chatelet F, Simon F, Bedarida V, Le Clerc N, Adle-Biassette H, Manivet P, Herman P, Verillaud B (2021) Surgical management of sinonasal cancers: a comprehensive review. Cancers (Basel) 13(16):3995. 10.3390/cancers13163995 PubMed PMC

Bossi P, Orlandi E, Resteghini C, et al. The SINTART 2 study. A phase II non-randomised controlled trial of induction chemotherapy, photon-, proton- and carbon-ion-based radiotherapy integration in patients with locally advanced unresectable sinonasal tumours. Eur J Cancer. 2023;187:134–143. doi: 10.1016/j.ejca.2023.03.034. PubMed DOI

Yang W, Lee KW, Srivastava RM, et al. Immunogenic neoantigens derived from gene fusions stimulate T cell responses. Nat Med. 2019;25:767–775. doi: 10.1038/s41591-019-0434-2. PubMed DOI PMC

Todorovic E, Truong T, Eskander A, et al. Middle ear and temporal bone nonkeratinizing squamous cell carcinomas with DEK-AFF2 fusion: an emerging entity. Am J Surg Pathol. 2020;44:1244–1250. doi: 10.1097/PAS.0000000000001498. PubMed DOI

Ruangritchankul K, Sandison A. DEK::AFF2 fusion carcinomas of head and neck. Adv Anat Pathol. 2023;30:86–94. doi: 10.1097/PAP.0000000000000376. PubMed DOI

Rooper LM, Agaimy A, Dickson BC, et al. DEK-AFF2 carcinoma of the sinonasal region and skull base: detailed clinicopathologic characterization of a distinctive entity. Am J Surg Pathol. 2021;45:1682–1693. doi: 10.1097/PAS.0000000000001741. PubMed DOI

Kuo YJ, Lewis JS, Jr, Zhai C, et al. DEK-AFF2 fusion-associated papillary squamous cell carcinoma of the sinonasal tract: clinicopathologic characterization of seven cases with deceptively bland morphology. Mod Pathol. 2021;34:1820–1830. doi: 10.1038/s41379-021-00846-2. PubMed DOI

Bishop JA, Gagan J, Paterson C, et al. Nonkeratinizing squamous cell carcinoma of the sinonasal tract with DEK-AFF2: further solidifying an emerging entity. Am J Surg Pathol. 2021;45:718–720. doi: 10.1097/PAS.0000000000001596. PubMed DOI

Kuo YJ, Lewis JS, Jr, Truong T, et al. Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract. Mod Pathol. 2022;35:1587–1595. doi: 10.1038/s41379-022-01117-4. PubMed DOI

Hellquist H, French CA, Bishop JA, et al. NUT midline carcinoma of the larynx: an international series and review of the literature. Histopathology. 2017;70:861–868. doi: 10.1111/his.13143. PubMed DOI PMC

Chau NG, Ma C, Danga K, et al. An anatomical site and genetic-based prognostic model for patients with nuclear protein in testis (NUT) midline carcinoma: analysis of 124 patients. JNCI Cancer Spectr. 2020;4:pkz094. doi: 10.1093/jncics/pkz094. PubMed DOI PMC

Haack H, Johnson LA, Fry CJ, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol. 2009;33:984–991. doi: 10.1097/PAS.0b013e318198d666. PubMed DOI PMC

Le Loarer F, Pissaloux D, Watson S, et al. Clinicopathologic features of CIC-NUTM1 sarcomas, a new molecular variant of the family of CIC-fused sarcomas. Am J Surg Pathol. 2019;43:268–276. doi: 10.1097/PAS.0000000000001187. PubMed DOI

Schaefer IM, Dal Cin P, Landry LM, et al. CIC-NUTM1 fusion: a case which expands the spectrum of NUT-rearranged epithelioid malignancies. Genes Chromosom Cancer. 2018;57:446–451. doi: 10.1002/gcc.3. PubMed DOI PMC

French CA, Miyoshi I, Kubonishi I, et al. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003;63:304–307. PubMed

Pivot-Pajot C, Caron C, Govin J, et al. Acetylation-dependent chromatin reorganization by BRDT, a testis-specific bromodomain-containing protein. Mol Cell Biol. 2003;23:5354–5365. doi: 10.1128/MCB.23.15.5354-5365.2003. PubMed DOI PMC

French CA, Ramirez CL, Kolmakova J, et al. BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. Oncogene. 2008;27:2237–2242. doi: 10.1038/sj.onc.1210852. PubMed DOI

Huang QW, He LJ, Zheng S, et al. An overview of molecular mechanism, clinicopathological factors, and treatment in NUT carcinoma. Biomed Res Int. 2019;2019:1018439. doi: 10.1155/2019/1018439. PubMed DOI PMC

French CA, Rahman S, Walsh EM, et al. NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism. Cancer Discov. 2014;4:928–941. doi: 10.1158/2159-8290.CD-14-0014. PubMed DOI PMC

Alekseyenko AA, Walsh EM, Zee BM, et al. Ectopic protein interactions within BRD4-chromatin complexes drive oncogenic megadomain formation in NUT midline carcinoma. Proc Natl Acad Sci U S A. 2017;114:E4184–E4192. doi: 10.1073/pnas.1702086114. PubMed DOI PMC

Bauer DE, Mitchell CM, Strait KM, et al. Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res. 2012;18:5773–5779. doi: 10.1158/1078-0432.CCR-12-1153. PubMed DOI PMC

Cheng ML, Huang Y, Luong N, et al. Exceptional response to bromodomain and extraterminal domain inhibitor therapy with BMS-986158 in BRD4-NUTM1 NUT carcinoma harboring a BRD4 splice site mutation. JCO Precis Oncol. 2023;7:e2200633. doi: 10.1200/PO.22.00633. PubMed DOI PMC

Ramesh U, Contrera KJ, Shakibai N, et al. Sinonasal NUT carcinoma: a consecutive case series and systematic review. Head Neck. 2024;46:29–36. doi: 10.1002/hed.27553. PubMed DOI

Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature. 2010;468:1067–1073. doi: 10.1038/nature09504. PubMed DOI PMC

Tontsch-Grunt U, Traexler PE, Baum A, et al. Therapeutic impact of BET inhibitor BI 894999 treatment: backtranslation from the clinic. Br J Cancer. 2022;127:577–586. doi: 10.1038/s41416-022-01815-5. PubMed DOI PMC

Wang X, Haswell JR, Roberts CW. Molecular pathways: SWI/SNF (BAF) complexes are frequently mutated in cancer–mechanisms and potential therapeutic insights. Clin Cancer Res. 2014;20:21–27. doi: 10.1158/1078-0432.CCR-13-0280. PubMed DOI PMC

Agaimy A, Koch M, Lell M, et al. SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms. Am J Surg Pathol. 2014;38:1274–1281. doi: 10.1097/PAS.0000000000000236. PubMed DOI PMC

Bishop JA, Antonescu CR, Westra WH. SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol. 2014;38:1282–1289. doi: 10.1097/PAS.0000000000000285. PubMed DOI PMC

Agaimy A, Hartmann A, Antonescu CR, et al. 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. 2017;41:458–471. doi: 10.1097/PAS.0000000000000797. PubMed DOI PMC

Agaimy A. SWI/SNF-deficient sinonasal carcinomas. Adv Anat Pathol. 2023;30:95–103. doi: 10.1097/PAP.0000000000000372. PubMed DOI

Skálová A, Taheri T, Bradová M, Vaněček T, Franchi A, Slouka D, Kostlivý T, de Rezende G, Michálek J, Klubíčková N, Ptáková N, Nemcová A, Michal M, Agaimy A, Leivo I (2023) SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma. Virchows Arch. 10.1007/s00428-023-03650-2 PubMed PMC

Agaimy A, Weichert W. SMARCA4-deficient sinonasal carcinoma. Head Neck Pathol. 2017;11:541–545. doi: 10.1007/s12105-017-0783-4. PubMed DOI PMC

Rooper LM, Uddin N, Gagan J, et al. Recurrent loss of SMARCA4 in sinonasal teratocarcinosarcoma. Am J Surg Pathol. 2020;44:1331–1339. doi: 10.1097/PAS.0000000000001508. PubMed DOI

Agaimy A, Jain D, Uddin N, et al. SMARCA4-deficient sinonasal carcinoma: a series of 10 cases expanding the genetic spectrum of SWI/SNF-driven sinonasal malignancies. Am J Surg Pathol. 2020;44:703–710. doi: 10.1097/PAS.0000000000001428. PubMed DOI

Contrera KJ, Shakibai N, Su SY, et al. Impact of clinical factors and treatments on SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma. Otolaryngol Head Neck Surg. 2023;169:435–440. doi: 10.1002/ohn.310. PubMed DOI

Ngo C, Postel-Vinay S (2022) Immunotherapy for SMARCB1-deficient sarcomas: current evidence and future developments. Biomedicines 10(3):650. 10.3390/biomedicines10030650 PubMed PMC

Aspeslagh S, Morel D, Soria JC, et al. Epigenetic modifiers as new immunomodulatory therapies in solid tumours. Ann Oncol. 2018;29:812–824. doi: 10.1093/annonc/mdy050. PubMed DOI

Jo VY, Chau NG, Hornick JL, et al. Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma. Mod Pathol. 2017;30:650–659. doi: 10.1038/modpathol.2016.239. PubMed DOI

Dogan S, Chute DJ, Xu B, et al. Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. J Pathol. 2017;242:400–408. doi: 10.1002/path.4915. PubMed DOI PMC

Riobello C, Lopez-Hernandez A, Cabal VN, et al. IDH2 Mutation analysis in undifferentiated and poorly differentiated sinonasal carcinomas for diagnosis and clinical management. Am J Surg Pathol. 2020;44:396–405. doi: 10.1097/PAS.0000000000001420. PubMed DOI

Mito JK, Bishop JA, Sadow PM, et al. Immunohistochemical detection and molecular characterization of IDH-mutant sinonasal undifferentiated carcinomas. Am J Surg Pathol. 2018;42:1067–1075. doi: 10.1097/PAS.0000000000001064. PubMed DOI

Chambers KJ, Lehmann AE, Remenschneider A, et al. Incidence and survival patterns of sinonasal undifferentiated carcinoma in the United States. J Neurol Surg B Skull Base. 2015;76:94–100. PubMed PMC

Amit M, Abdelmeguid AS, Watcherporn T, et al. Induction chemotherapy response as a guide for treatment optimization in sinonasal undifferentiated carcinoma. J Clin Oncol. 2019;37:504–512. doi: 10.1200/JCO.18.00353. PubMed DOI PMC

Stein EM, DiNardo CD, Fathi AT, et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood. 2021;137:1792–1803. doi: 10.1182/blood.2020007233. PubMed DOI PMC

Bishop JA, Ogawa T, Stelow EB, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract. Am J Surg Pathol. 2013;37:836–844. doi: 10.1097/PAS.0b013e31827b1cd6. PubMed DOI PMC

Bishop JA, Andreasen S, Hang JF, et al. HPV-related multiphenotypic sinonasal carcinoma: an expanded series of 49 cases of the tumor formerly known as HPV-related carcinoma with adenoid cystic carcinoma-like features. Am J Surg Pathol. 2017;41:1690–1701. doi: 10.1097/PAS.0000000000000944. PubMed DOI PMC

Rodarte AI, Parikh AS, Gadkaree SK, et al. Human papillomavirus related multiphenotypic sinonasal carcinoma: report of a case with early and progressive metastatic disease. J Neurol Surg Rep. 2019;80:e41–e43. doi: 10.1055/s-0039-3399571. PubMed DOI PMC

Persson M, Andren Y, Mark J, et al. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A. 2009;106:18740–18744. doi: 10.1073/pnas.0909114106. PubMed DOI PMC

Fujii K, Murase T, Beppu S, et al. MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma. Histopathology. 2017;71:823–834. doi: 10.1111/his.13281. PubMed DOI

Persson M, Andren Y, Moskaluk CA, et al. Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma. Genes Chromosom Cancer. 2012;51:805–817. doi: 10.1002/gcc.21965. PubMed DOI

Steiner P, Andreasen S, Grossmann P, et al. Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands. Virchows Arch. 2018;473:471–480. doi: 10.1007/s00428-018-2349-6. PubMed DOI

Mathew EP, Todorovic E, Truong T, et al. Metatypical adenoid cystic carcinoma: a variant showing prominent squamous differentiation with a predilection for the sinonasal tract and skull base. Am J Surg Pathol. 2022;46:816–822. doi: 10.1097/PAS.0000000000001850. PubMed DOI

Weinreb I, Rooper LM, Dickson BC, et al. Adenoid cystic carcinoma with striking tubular hypereosinophilia: a unique pattern associated with nonparotid location and both canonical and novel EWSR1::MYB and FUS::MYB fusions. Am J Surg Pathol. 2023;47:497–503. doi: 10.1097/PAS.0000000000002023. PubMed DOI

Ho AS, Kannan K, Roy DM, et al. The mutational landscape of adenoid cystic carcinoma. Nat Genet. 2013;45:791–798. doi: 10.1038/ng.2643. PubMed DOI PMC

Ho AS, Ochoa A, Jayakumaran G, et al. Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma. J Clin Invest. 2019;129:4276–4289. doi: 10.1172/JCI128227. PubMed DOI PMC

Miller LE, Au V, Mokhtari TE, Goss D, Faden DL, Varvares MA (2022) A contemporary review of molecular therapeutic targets for adenoid cystic carcinoma. Cancers (Basel) 14(4):992. 10.3390/cancers14040992 PubMed PMC

Ferrarotto R, Mishra V, Herz E, et al. AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling. Cell Death Dis. 2022;13:678. doi: 10.1038/s41419-022-05133-9. PubMed DOI PMC

Siqueira JM, Mitani Y, Hoff CO, et al. Analysis of B7–H4 expression across salivary gland carcinomas reveals adenoid cystic carcinoma-specific prognostic relevance. Mod Pathol. 2023;37:100371. doi: 10.1016/j.modpat.2023.100371. PubMed DOI

Ferrarotto R, Mitani Y, McGrail DJ, et al. Proteogenomic analysis of salivary adenoid cystic carcinomas defines molecular subtypes and identifies therapeutic targets. Clin Cancer Res. 2021;27:852–864. doi: 10.1158/1078-0432.CCR-20-1192. PubMed DOI PMC

Wang X, Bledsoe KL, Graham RP, et al. Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma. Nat Genet. 2014;46:666–668. doi: 10.1038/ng.2989. PubMed DOI PMC

Fritchie KJ, Jin L, Wang X, et al. Fusion gene profile of biphenotypic sinonasal sarcoma: an analysis of 44 cases. Histopathology. 2016;69:930–936. doi: 10.1111/his.13045. PubMed DOI

Le Loarer F, Laffont S, Lesluyes T, et al. Clinicopathologic and molecular features of a series of 41 biphenotypic sinonasal sarcomas expanding their molecular spectrum. Am J Surg Pathol. 2019;43:747–754. doi: 10.1097/PAS.0000000000001238. PubMed DOI PMC

Nichols MM, Alruwaii F, Chaaban M, et al. Biphenotypic sinonasal sarcoma with a novel PAX3::FOXO6 fusion: a case report and review of the literature. Head Neck Pathol. 2023;17:259–264. doi: 10.1007/s12105-022-01479-w. PubMed DOI PMC

Kominsky E, Boyke AE, Madani D, et al. Biphenotypic sinonasal sarcoma: a case report and review of literature. Ear Nose Throat J. 2023;102:385–390. doi: 10.1177/0145561321999196. PubMed DOI

Bell D, Phan J, DeMonte F, et al. High-grade transformation of low-grade biphenotypic sinonasal sarcoma: radiological, morphophenotypic variation and confirmatory molecular analysis. Ann Diagn Pathol. 2022;57:151889. doi: 10.1016/j.anndiagpath.2021.151889. PubMed DOI

Hasnie S, Glenn C, Peterson JEG, et al. High-grade biphenotypic sinonasal sarcoma: a case report. J Neurol Surg Rep. 2022;83:e105–e109. doi: 10.1055/s-0042-1755599. PubMed DOI PMC

Meyer A, Klubickova N, Mosaieby E, et al. Biphenotypic sinonasal sarcoma with PAX3::MAML3 fusion transforming into high-grade rhabdomyosarcoma: report of an emerging rare phenomenon. Virchows Arch. 2023;482:777–782. doi: 10.1007/s00428-023-03501-0. PubMed DOI PMC

Smith BC, Ellis GL, Meis-Kindblom JM, et al. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Nineteen cases of a new clinicopathologic entity. Am J Surg Pathol. 1995;19:519–530. doi: 10.1097/00000478-199505000-00003. PubMed DOI

Bubola J, Hagen K, Blanas N, et al. Expanding awareness of the distribution and biologic potential of ectomesenchymal chondromyxoid tumor. Head Neck Pathol. 2021;15:319–322. doi: 10.1007/s12105-020-01169-5. PubMed DOI PMC

Argyris PP, Bilodeau EA, Yancoskie AE, et al. A subset of ectomesenchymal chondromyxoid tumours of the tongue show EWSR1 rearrangements and are genetically linked to soft tissue myoepithelial neoplasms: a study of 11 cases. Histopathology. 2016;69:607–613. doi: 10.1111/his.12973. PubMed DOI

Dickson BC, Antonescu CR, Argyris PP, et al. Ectomesenchymal chondromyxoid tumor: a neoplasm characterized by recurrent RREB1-MKL2 fusions. Am J Surg Pathol. 2018;42:1297–1305. doi: 10.1097/PAS.0000000000001096. PubMed DOI PMC

Agaimy A, Din NU, Dermawan JK, et al. RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasms: a series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity. Genes Chromosom Cancer. 2023;62:5–16. doi: 10.1002/gcc.23082. PubMed DOI PMC

Dahlen A, Fletcher CD, Mertens F, et al. Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms: pericytoma with t(7;12) Am J Pathol. 2004;164:1645–1653. doi: 10.1016/S0002-9440(10)63723-6. PubMed DOI PMC

Papke DJ, Jr, Dickson BC, Oliveira AM, et al. Distinctive nested glomoid neoplasm: clinicopathologic analysis of 20 cases of a mesenchymal neoplasm with frequent GLI1 alterations and indolent behavior. Am J Surg Pathol. 2023;47:12–24. doi: 10.1097/PAS.0000000000001979. PubMed DOI

Agaram NP, Zhang L, Sung YS, et al. GLI1-amplifications expand the spectrum of soft tissue neoplasms defined by GLI1 gene fusions. Mod Pathol. 2019;32:1617–1626. doi: 10.1038/s41379-019-0293-x. PubMed DOI PMC

Parrack PH, Marino-Enriquez A, Fletcher CDM, et al. GLI1 Immunohistochemistry distinguishes mesenchymal neoplasms with GLI1 alterations from morphologic mimics. Am J Surg Pathol. 2023;47:453–460. doi: 10.1097/PAS.0000000000002018. PubMed DOI

Machado I, Agaimy A, Giner F, Navarro S, Michal M, Bridge J, Claramunt R, López-Guerrero JA, Alcacer J, Linos K, Llombart-Bosch A (2023) The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms. Virchows Arch. 10.1007/s00428-023-03687-3 PubMed PMC

Xu B, Chang K, Folpe AL, et al. Head and neck mesenchymal neoplasms with GLI1 gene alterations: a pathologic entity with distinct histologic features and potential for distant metastasis. Am J Surg Pathol. 2020;44:729–737. doi: 10.1097/PAS.0000000000001439. PubMed DOI PMC

Antonescu CR, Agaram NP, Sung YS, et al. A distinct malignant epithelioid neoplasm with GLI1 gene rearrangements, frequent S100 protein expression, and metastatic potential: expanding the spectrum of pathologic entities with ACTB/MALAT1/PTCH1-GLI1 fusions. Am J Surg Pathol. 2018;42:553–560. doi: 10.1097/PAS.0000000000001010. PubMed DOI PMC

WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours. Lyon (France): International Agency for Research on Cancer; 2020. (WHO classification of tumours series, 5th edn, vol 3). https://publications.iarc.fr/588

Leiner J, Le Loarer F. The current landscape of rhabdomyosarcomas: an update. Virchows Arch. 2020;476:97–108. doi: 10.1007/s00428-019-02676-9. PubMed DOI

Mosquera JM, Sboner A, Zhang L, et al. Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma. Genes Chromosom Cancer. 2013;52:538–550. doi: 10.1002/gcc.22050. PubMed DOI PMC

Alaggio R, Zhang L, Sung YS, et al. A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol. 2016;40:224–235. doi: 10.1097/PAS.0000000000000538. PubMed DOI PMC

Agaimy A, Dermawan JK, Leong I, et al. Recurrent VGLL3 fusions define a distinctive subset of spindle cell rhabdomyosarcoma with an indolent clinical course and striking predilection for the head and neck. Genes Chromosom Cancer. 2022;61:701–709. doi: 10.1002/gcc.23083. PubMed DOI PMC

Cyrta J, Gauthier A, Karanian M, et al. Infantile rhabdomyosarcomas with VGLL2 rearrangement are not always an indolent disease: a study of 4 aggressive cases with clinical, pathologic, molecular, and radiologic findings. Am J Surg Pathol. 2021;45:854–867. doi: 10.1097/PAS.0000000000001702. PubMed DOI

Watson S, Perrin V, Guillemot D, et al. Transcriptomic definition of molecular subgroups of small round cell sarcomas. J Pathol. 2018;245:29–40. doi: 10.1002/path.5053. PubMed DOI

Le Loarer F, Cleven AHG, Bouvier C, et al. A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation. Mod Pathol. 2020;33:404–419. doi: 10.1038/s41379-019-0323-8. PubMed DOI

Dehner CA, Broski SM, Meis JM, et al. Fusion-driven spindle cell rhabdomyosarcomas of bone and soft tissue: a clinicopathologic and molecular genetic study of 25 cases. Mod Pathol. 2023;36:100271. doi: 10.1016/j.modpat.2023.100271. PubMed DOI

Brunac AC, Laprie A, Castex MP, et al. The combination of radiotherapy and ALK inhibitors is effective in the treatment of intraosseous rhabdomyosarcoma with FUS-TFCP2 fusion transcript. Pediatr Blood Cancer. 2020;67:e28185. doi: 10.1002/pbc.28185. PubMed DOI

Valerio E, Furtado Costa JL, Perez Fraile NM, et al. Intraosseous spindle cell/epithelioid rhabdomyosarcoma with tfcp2 rearrangement: a recent recognized subtype with partial response to alectinib. Int J Surg Pathol. 2023;31:861–865. doi: 10.1177/10668969221140397. PubMed DOI

Bridge JA, Fidler ME, Neff JR, et al. Adamantinoma-like Ewing’s sarcoma: genomic confirmation, phenotypic drift. Am J Surg Pathol. 1999;23:159–165. doi: 10.1097/00000478-199902000-00004. PubMed DOI

Rooper LM, Bishop JA. Soft tissue special issue: Adamantinoma-like Ewing sarcoma of the head and neck: a practical review of a challenging emerging entity. Head Neck Pathol. 2020;14:59–69. doi: 10.1007/s12105-019-01098-y. PubMed DOI PMC

Agaimy A, Baneckova M, De Almeida J, et al. Recurrent EWSR1::COLCA2 fusions define a novel sarcoma with spindle/round cell morphology and strong predilection for the sinonasal tract. Am J Surg Pathol. 2023;47:361–369. doi: 10.1097/PAS.0000000000002000. PubMed DOI

Koshyk O, Dehner CA, van den Hout MFCM, Bempt IV, Sciot R, Huang HY, Agaimy A, Din NU, Klubíčková N, Mosaieby E, Skálová A, Michalová K, Schöffski P, Oliveira AM, Halling KC, Gupta S, Gross JM, Nin JWM, Michal M, Folpe AL, Kosemehmetoglu K, Torres-Mora J, Michal M (2023) EWSR1::POU2AF3(COLCA2) sarcoma: an aggressive, polyphenotypic sarcoma with a head and neck predilection. Mod Pathol 36(12):100337. 10.1016/j.modpat.2023.100337 PubMed

Hiemenz MC, Kaur J, Kuang Z, et al. POU2AF3-rearranged sarcomas: a novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2. Genes Chromosom Cancer. 2023;62:460–470. doi: 10.1002/gcc.23136. PubMed DOI

Yoshida A, Arai Y, Satomi K, et al. Identification of novel SSX1 fusions in synovial sarcoma. Mod Pathol. 2022;35:228–239. doi: 10.1038/s41379-021-00910-x. PubMed DOI