BACKGROUND: Basaloid neoplasms of the sinonasal tract represent a significant group of tumors with histological overlap but often with different etiologies (i.e., viral, genetics), clinical management, and prognostic significance. METHODS: Review. RESULTS: "Basaloid" generally refers to cells with coarse chromatin in round nuclei and sparse cytoplasm, resembling cells of epithelial basal layers or imparting an "immature" appearance. Tumors with this characteristic in the sinonasal tract are represented by a spectrum of benign to high-grade malignant neoplasms, such as adenoid cystic carcinoma, NUT carcinoma, sinonasal undifferentiated carcinoma, SWI/SNF complex-deficient carcinomas, and adamantinoma-like Ewing sarcoma. CONCLUSION: In some instances, histology alone may be sufficient for diagnosis. However, limited biopsy material or fine-needle aspiration specimens may be particularly challenging. Therefore, often other diagnostic procedures, including a combination of histology, immunohistochemistry (IHC), DNA and RNA testing, and molecular genetics are necessary to establish an accurate diagnosis.

Bioptic Laboratory Ltd Plzen Czech Republic

Department of Pathology Faculty of Medicine in Plzen Charles University Plzen Czech Republic

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

University of Pacific Arthur A Dugoni School of Dentistry San Francisco CA USA

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Bishop JA, Brandwein-Gensler M, Nicolai P, et al Non-keratinizing squamous cell carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO classification of head and neck tumours 2017; 9:15–17.

Ansa B, Goodman M, Ward K, et al. Paranasal sinus squamous cell carcinoma incidence and survival based on Surveillance, Epidemiology, and End Results data, 1973 to 2009. Cancer. 2013;119:2602–10. doi: 10.1002/cncr.28108. PubMed DOI

El-Mofty SK, Lu DW. Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2005;29:1367–72. doi: 10.1097/01.pas.0000173240.63073.fe. PubMed DOI

Bishop JA, Guo TW, Smith DF, et al. Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol. 2013;37:185–92. doi: 10.1097/PAS.0b013e3182698673. PubMed DOI PMC

Lewis JS, Jr, Westra WH, Thompson LD, et al. The sinonasal tract: another potential “hot spot” for carcinomas with transcriptionally-active human papillomavirus. Head Neck Pathol. 2014;8:241–9. doi: 10.1007/s12105-013-0514-4. PubMed DOI PMC

Laco J, Sieglova K, Vosmikova H, et al. The presence of high-risk human papillomavirus (HPV) E6/E7 mRNA transcripts in a subset of sinonasal carcinomas is evidence of involvement of HPV in its etiopathogenesis. Virchows Arch. 2015;467:405–15. doi: 10.1007/s00428-015-1812-x. PubMed DOI

Yang W, Lee KW, Srivastava RM, et al. Immunogenic neoantigens derived from gene fusions stimulate T cell responses. Nat Med. 2019;25:767–75. 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;44:1244–50. doi: 10.1097/PAS.0000000000001498. 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;34:1820–30. doi: 10.1038/s41379-021-00846-2. 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;45:1682–93. doi: 10.1097/PAS.0000000000001741. PubMed DOI

Thompson LDR, Bishop JA. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Nasal Cavity, Paranasal Sinuses and Skull Base. Head Neck Pathol. 2022;16:1–18. doi: 10.1007/s12105-021-01406-5. PubMed DOI PMC

Lewis JS, Jr, Chernock RD, Bishop JA. Squamous and neuroendocrine specific immunohistochemical markers in head and neck squamous cell carcinoma: a tissue microarray study. Head Neck Pathol. 2018;12:62–70. doi: 10.1007/s12105-017-0825-y. PubMed DOI PMC

Jiromaru R, Yamamoto H, Yasumatsu R, et al. HPV-related sinonasal carcinoma: clinicopathologic features, diagnostic utility of p16 and Rb immunohistochemistry, and EGFR copy number alteration. Am J Surg Pathol. 2020;44:305–15. doi: 10.1097/PAS.0000000000001410. 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;35:1587–95. doi: 10.1038/s41379-022-01117-4. PubMed DOI

Larque AB, Hakim S, Ordi J, et al. High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas. Mod Pathol. 2014;27:343–51. doi: 10.1038/modpathol.2013.155. PubMed DOI

Wadsworth B, Bumpous JM, Martin AW, et al. Expression of p16 in sinonasal undifferentiated carcinoma (SNUC) without associated human papillomavirus (HPV) Head Neck Pathol. 2011;5:349–54. doi: 10.1007/s12105-011-0285-8. PubMed DOI PMC

Alos L, Hakim S, Larque AB, et al. p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas. Virchows Arch. 2016;469:277–84. doi: 10.1007/s00428-016-1982-1. PubMed DOI

Chowdhury N, Alvi S, Kimura K, et al. Outcomes of HPV-related nasal squamous cell carcinoma. Laryngoscope. 2017;127:1600–3. doi: 10.1002/lary.26477. PubMed DOI

Schlussel Markovic E, Marqueen KE, Sindhu KK, et al. The prognostic significance of human papilloma virus in sinonasal squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2020;5:1070–8. doi: 10.1002/lio2.468. PubMed DOI PMC

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;45:718–20. doi: 10.1097/PAS.0000000000001596. PubMed DOI

Stenman G, Licitra L, S-A-N N,, et al. Adenoid cystic carcinoma. In: Chan JKC, Grandis JR, Takata T, Slootweg PJ, et al., editors. El-Naggar AK. Lyon: WHO classification of head and neck tumours. IARC Press; 2017. pp. 164–165.

Thompson LD, Penner C, Ho NJ, et al. Sinonasal tract and nasopharyngeal adenoid cystic carcinoma: a clinicopathologic and immunophenotypic study of 86 cases. Head Neck Pathol. 2014;8:88–109. doi: 10.1007/s12105-013-0487-3. PubMed DOI PMC

Perzin KH, Gullane P, Clairmont AC. Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer. 1978;42:265–82. doi: 10.1002/1097-0142(197807)42:1<265::AID-CNCR2820420141>3.0.CO;2-Z. PubMed DOI

Szanto PA, Luna MA, Tortoledo ME, et al. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer. 1984;54:1062–9. doi: 10.1002/1097-0142(19840915)54:6<1062::AID-CNCR2820540622>3.0.CO;2-E. PubMed DOI

van Weert S, van der Waal I, Witte BI, et al. Histopathological grading of adenoid cystic carcinoma of the head and neck: analysis of currently used grading systems and proposal for a simplified grading scheme. Oral Oncol. 2015;51:71–6. doi: 10.1016/j.oraloncology.2014.10.007. PubMed DOI

Morita N, Murase T, Ueda K, et al. Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system. Cancer Sci. 2021;112:1184–95. doi: 10.1111/cas.14790. PubMed DOI PMC

Seethala RR. An update on grading of salivary gland carcinomas. Head Neck Pathol. 2009;3:69–77. doi: 10.1007/s12105-009-0102-9. PubMed DOI PMC

Brill LB, Kanner WA, Fehr A, et al. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24:1169–76. doi: 10.1038/modpathol.2011.86. PubMed DOI

Stenman G, Sandros J, Dahlenfors R, et al. 6q- and loss of the Y chromosome–two common deviations in malignant human salivary gland tumors. Cancer Genet Cytogenet. 1986;22:283–93. doi: 10.1016/0165-4608(86)90021-X. PubMed DOI

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;106:18740–4. doi: 10.1073/pnas.0909114106. PubMed DOI PMC

Mitani Y, Liu B, Rao PH, et al. Novel MYBL1 gene rearrangements with recurrent MYBL1-NFIB Fusions in salivary adenoid cystic carcinomas lacking t(6;9) translocations. Clin Cancer Res. 2016;22:725–33. doi: 10.1158/1078-0432.CCR-15-2867-T. PubMed DOI PMC

Drier Y, Cotton MJ, Williamson KE, et al. An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet. 2016;48:265–72. doi: 10.1038/ng.3502. PubMed DOI PMC

Andersson MK, Afshari MK, Andren Y, et al. Targeting the oncogenic transcriptional regulator MYB in adenoid cystic carcinoma by inhibition of IGF1R/AKT Signaling. J Natl Cancer Inst. 2017 doi: 10.1093/jnci/djx017. PubMed DOI

Frerich CA, Sedam HN, Kang H, et al. N-terminal truncated myb with new transcriptional activity produced through use of an alternative MYB promoter in salivary gland adenoid cystic carcinoma. Cancers. 2019;12(1):45. doi: 10.3390/cancers12010045. PubMed DOI PMC

Andersson MK, Mangiapane G, Nevado PT, et al. ATR is a MYB regulated gene and potential therapeutic target in adenoid cystic carcinoma. Oncogenesis. 2020;9:5. doi: 10.1038/s41389-020-0194-3. PubMed DOI PMC

Bjorndal K, Krogdahl A, Therkildsen MH, et al. Salivary adenoid cystic carcinoma in Denmark 1990–2005: outcome and independent prognostic factors including the benefit of radiotherapy. results of the danish head and neck cancer group (DAHANCA) Oral Oncol. 2015;51:1138–42. doi: 10.1016/j.oraloncology.2015.10.002. PubMed DOI

Hang JF, Hsieh MS, Li WY, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features: a series of five cases expanding the pathological spectrum. Histopathology. 2017;71:887–96. doi: 10.1111/his.13301. PubMed DOI

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;37:836–44. doi: 10.1097/PAS.0b013e31827b1cd6. PubMed DOI PMC

Bjørndal K, Krogdahl A, Therkildsen MH, et al. WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 9). https://publications.iarc.fr/

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;41:1690–701. doi: 10.1097/PAS.0000000000000944. PubMed DOI PMC

Bishop JA, Westra WH. Human papillomavirus-related multiphenotypic sinonasal carcinoma: An emerging tumor type with a unique microscopic appearance and a paradoxical clinical behaviour. Oral Oncol. 2018;87:17–20. doi: 10.1016/j.oraloncology.2018.10.011. PubMed DOI

Thompson LDR. HPV-related multiphenotypic sinonasal carcinoma. Ear Nose Throat J. 2020;99:94–5. doi: 10.1177/0145561319871711. PubMed DOI

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:e41–3. doi: 10.1055/s-0039-3399571. PubMed DOI PMC

Rooper LM, McCuiston AM, Westra WH, et al. SOX10 immunoexpression in basaloid squamous cell carcinomas: a diagnostic pitfall for ruling out salivary differentiation. Head Neck Pathol. 2019;13:543–7. doi: 10.1007/s12105-018-0990-7. PubMed DOI PMC

Andreasen S, Bishop JA, Hansen TV, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features of the sinonasal tract: clinical and morphological characterization of six new cases. Histopathology. 2017;70:880–8. doi: 10.1111/his.13162. PubMed DOI

Antony VM, Kakkar A, Sikka K, et al. p16 Immunoexpression in sinonasal and nasopharyngeal adenoid cystic carcinomas: a potential pitfall in ruling out HPV-related multiphenotypic sinonasal carcinoma. Histopathology. 2020;77:989–93. doi: 10.1111/his.14212. PubMed DOI

Moya-Plana A, Auperin A, Obongo R, et al. Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France. Eur J Cancer. 2019;123:1–10. doi: 10.1016/j.ejca.2019.09.007. PubMed DOI

Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–21. doi: 10.1038/nature12477. PubMed DOI PMC

Furney SJ, Turajlic S, Stamp G, et al. The mutational burden of acral melanoma revealed by whole-genome sequencing and comparative analysis. Pigment Cell Melanoma Res. 2014;27:835–8. doi: 10.1111/pcmr.12279. PubMed DOI

Hayward NK, Wilmott JS, Waddell N, et al. Whole-genome landscapes of major melanoma subtypes. Nature. 2017;545:175–80. doi: 10.1038/nature22071. PubMed DOI

Chlopek M, Lasota J, Thompson LDR, et al. Alterations in key signaling pathways in sinonasal tract melanoma. A molecular genetics and immunohistochemical study of 90 cases and comprehensive review of the literature. Mod Pathol. 2022;35:1609–17. doi: 10.1038/s41379-022-01122-7. PubMed DOI

Merkel EA, Gerami P. Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features. Lab Invest. 2017;97:630–5. doi: 10.1038/labinvest.2016.147. PubMed DOI

Salari B, Foreman RK, Emerick KS, et al. Sinonasal mucosal melanoma: an update and review of the literature. Am J Dermatopathol. 2022;44:424–32. doi: 10.1097/DAD.0000000000002157. PubMed DOI

Thompson LD, Wieneke JA, Miettinen M. Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system. Am J Surg Pathol. 2003;27:594–611. doi: 10.1097/00000478-200305000-00004. PubMed DOI

Lee H, Torres FX, McLean SA, et al. Immunophenotypic heterogeneity of primary sinonasal melanoma with aberrant expression of neuroendocrine markers and calponin. Appl Immunohistochem Mol Morphol. 2011;19:48–53. doi: 10.1097/PAI.0b013e3181ee8dcb. PubMed DOI

Smith SM, Schmitt AC, Carrau RL, et al. Primary sinonasal mucosal melanoma with aberrant diffuse and strong desmin reactivity: a potential diagnostic pitfall! Head Neck Pathol. 2015;9:165–71. doi: 10.1007/s12105-014-0553-5. PubMed DOI PMC

Zebary A, Jangard M, Omholt K, et al. KIT, NRAS and BRAF mutations in sinonasal mucosal melanoma: a study of 56 cases. Br J Cancer. 2013;109:559–64. doi: 10.1038/bjc.2013.373. PubMed DOI PMC

Wroblewska JP, Mull J, Wu CL, et al. SF3B1, NRAS, KIT, and BRAF mutation; CD117 and cMYC expression; and tumoral pigmentation in sinonasal melanomas: an analysis with newly found molecular alterations and some population-based molecular differences. Am J Surg Pathol. 2019;43:168–77. doi: 10.1097/PAS.0000000000001166. PubMed DOI

Na’ara S, Mukherjee A, Billan S, et al. Contemporary multidisciplinary management of sinonasal mucosal melanoma. Onco Targets Ther. 2020;13:2289–98. doi: 10.2147/OTT.S182580. PubMed DOI PMC

Lewis JS, Bishop JA, Gillison M, et al. Sinonasal undifferentiated carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, et al., editors. WHO classification of head and neck tumours. Lyon: IARC; 2017. pp. 18–20.

Zhou M, Yuan J, Deng Y, et al. Emerging role of SWI/SNF complex deficiency as a target of immune checkpoint blockade in human cancers. Oncogenesis. 2021;10:3. doi: 10.1038/s41389-020-00296-6. PubMed DOI PMC

Hodges C, Kirkland JG, Crabtree GR. The many roles of BAF (mSWI/SNF) and PBAF complexes in cancer. Cold Spring Harb Perspect Med. 2016;6(8):026930. doi: 10.1101/cshperspect.a026930. 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;20:21–7. doi: 10.1158/1078-0432.CCR-13-0280. PubMed DOI PMC

Shah AA, Jain D, Ababneh E, et al. SMARCB1 (INI-1)-deficient adenocarcinoma of the sinonasal tract: a potentially under-recognized form of sinonasal adenocarcinoma with occasional yolk sac tumor-like features. Head Neck Pathol. 2020;14:465–72. doi: 10.1007/s12105-019-01065-7. 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;41:458–71. doi: 10.1097/PAS.0000000000000797. PubMed DOI PMC

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;44:703–10. doi: 10.1097/PAS.0000000000001428. PubMed DOI

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;38:1274–81. 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;38:1282–9. doi: 10.1097/PAS.0000000000000285. PubMed DOI PMC

Agaimy A, Bishop JA. SWI/SNF-deficient head and neck neoplasms: An overview. Semin Diagn Pathol. 2021;38:175–82. doi: 10.1053/j.semdp.2021.02.002. PubMed DOI

Kasajima A, Konukiewitz B, Schlitter AM, et al. Mesenchymal/non-epithelial mimickers of neuroendocrine neoplasms with a focus on fusion gene-associated and SWI/SNF-deficient tumors. Virchows Arch. 2021;479:1209–19. doi: 10.1007/s00428-021-03156-9. PubMed DOI PMC

Pasricha S, Kamboj M, Jajodia A, et al. High grade myoepithelial carcinoma of maxillary sinus with extensive rhabdoid differentiation and INI-1 loss: expanding the histopathological spectrum of sinonasal carcinoma. Head Neck Pathol. 2021;16(3):876–80. doi: 10.1007/s12105-021-01397-3. PubMed DOI PMC

Agaimy A, Weichert W. SMARCA4-deficient Sinonasal Carcinoma. Head Neck Pathol. 2017;11:541–5. doi: 10.1007/s12105-017-0783-4. PubMed DOI PMC

Kakkar A, Ashraf SF, Rathor A, et al. SMARCA4/BRG1-deficient sinonasal carcinoma: morphologic spectrum of an evolving entity. Arch Pathol Lab Med. 2021;146(9):1122–30. doi: 10.5858/arpa.2021-0001-OA. PubMed DOI

Dogan S, Cotzia P, Ptashkin RN, et al. Genetic basis of SMARCB1 protein loss in 22 sinonasal carcinomas. Hum Pathol. 2020;104:105–16. doi: 10.1016/j.humpath.2020.08.004. PubMed DOI PMC

French CA, Bishop JA, Lewis JE, et al. NUT carcinoma. In: El-Naggar AK, Chan JKC, Takata Grandis JR., T, Slootweg PJ,, et al., editors. WHO classification of head and neck tumours. Lyon: IARC; 2017.

Bishop JA, Westra WH. NUT midline carcinomas of the sinonasal tract. Am J Surg Pathol. 2012;36:1216–21. doi: 10.1097/PAS.0b013e318254ce54. 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

French CA, Kutok JL, Faquin WC, et al. Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol. 2004;22:4135–9. doi: 10.1200/JCO.2004.02.107. PubMed DOI

Haack H, Johnson LA, Fry CJ, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol. 2009;33:984–91. doi: 10.1097/PAS.0b013e318198d666. PubMed DOI PMC

Yang S, Liu L, Yan Y, et al. CIC-NUTM1 sarcomas affecting the spine. Arch Pathol Lab Med. 2022;146:735–41. doi: 10.5858/arpa.2021-0153-OA. PubMed DOI

Matsuda K, Kashima J, Yatabe Y. The isoform matters in NUT carcinoma: a diagnostic pitfall of p40 immunohistochemistry. J Thorac Oncol. 2020;15:e176–8. doi: 10.1016/j.jtho.2020.07.017. PubMed DOI

Zhu B, Laskin W, Chen Y, et al. NUT midline carcinoma: a neoplasm with diagnostic challenges in cytology. Cytopathology. 2011;22:414–7. doi: 10.1111/j.1365-2303.2010.00838.x. PubMed DOI

Morrison-Smith CD, Knox TM, Filic I, et al. Combined targeting of the BRD4-NUT-p300 Axis in NUT midline carcinoma by dual selective bromodomain inhibitor, NEO2734. Mol Cancer Ther. 2020;19:1406–14. doi: 10.1158/1535-7163.MCT-20-0087. PubMed DOI

Frierson HF, Jr, Mills SE, Fechner RE, et al. Sinonasal undifferentiated carcinoma. an aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma. Am J Surg Pathol. 1986;10:771–9. doi: 10.1097/00000478-198611000-00004. PubMed DOI

Stelow EB, Bellizzi AM, Taneja K, et al. NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract. Am J Surg Pathol. 2008;32:828–34. doi: 10.1097/PAS.0b013e31815a3900. 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

Franchi A, Moroni M, Massi D, et al. Sinonasal undifferentiated carcinoma, nasopharyngeal-type undifferentiated carcinoma, and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns. Am J Surg Pathol. 2002;26:1597–604. doi: 10.1097/00000478-200212000-00007. PubMed DOI

Singh L, Ranjan R, Arava S, et al. Role of p40 and cytokeratin 5/6 in the differential diagnosis of sinonasal undifferentiated carcinoma. Ann Diagn Pathol. 2014;18:261–5. doi: 10.1016/j.anndiagpath.2014.01.003. PubMed DOI

Lopategui JR, Gaffey MJ, Frierson HF, Jr, et al. Detection of Epstein-Barr viral RNA in sinonasal undifferentiated carcinoma from Western and Asian patients. Am J Surg Pathol. 1994;18:391–8. doi: 10.1097/00000478-199404000-00007. PubMed DOI

Cerilli LA, Holst VA, Brandwein MS, et al. Sinonasal undifferentiated carcinoma: immunohistochemical profile and lack of EBV association. Am J Surg Pathol. 2001;25:156–63. doi: 10.1097/00000478-200102000-00003. PubMed DOI

Gray ST, Herr MW, Sethi RK, et al. Treatment outcomes and prognostic factors, including human papillomavirus, for sinonasal undifferentiated carcinoma: a retrospective review. Head Neck. 2015;37:366–74. doi: 10.1002/hed.23606. PubMed DOI

Wooff JC, Weinreb I, Perez-Ordonez B, et al. Calretinin staining facilitates differentiation of olfactory neuroblastoma from other small round blue cell tumors in the sinonasal tract. Am J Surg Pathol. 2011;35:1786–93. doi: 10.1097/PAS.0b013e3182363b78. PubMed DOI

Dogan S, Frosina D, Fayad M, et al. The role of a monoclonal antibody 11C8B1 as a diagnostic marker of IDH2-mutated sinonasal undifferentiated carcinoma. Mod Pathol. 2019;32:205–15. doi: 10.1038/s41379-018-0126-3. PubMed DOI PMC

Dogan S, Chute DJ, Xu B, et al. Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. J Pathol. 2017;242:400–8. doi: 10.1002/path.4915. PubMed DOI PMC

Smith SL, Hessel AC, Luna MA, et al. Sinonasal teratocarcinosarcoma of the head and neck: a report of 10 patients treated at a single institution and comparison with reported series. Arch Otolaryngol Head Neck Surg. 2008;134:592–5. doi: 10.1001/archotol.134.6.592. PubMed DOI

Chapurin N, Totten DJ, Morse JC, et al. Treatment of sinonasal teratocarcinosarcoma: a systematic review and survival analysis. Am J Rhinol Allergy. 2021;35:132–41. doi: 10.1177/1945892420959585. PubMed DOI PMC

Su SY, Bell D, Hanna EY. Esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma: differentiation in diagnosis and treatment. Int Arch Otorhinolaryngol. 2014;18:149–56. doi: 10.1055/s-0034-1390014. PubMed DOI PMC

Franchi A, Wenig BM. Teratocarcinosarcoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO classification of head and neck tumours. Lyon: IARC; 2017.

Fatima SS, Minhas K, Din NU, et al. Sinonasal teratocarcinosarcoma: a clinicopathologic and immunohistochemical study of 6 cases. Ann Diagn Pathol. 2013;17:313–8. doi: 10.1016/j.anndiagpath.2013.01.003. PubMed DOI

Rooper LM, Bishop JA, Westra WH. INSM1 is a sensitive and specific marker of neuroendocrine differentiation in head and neck tumors. Am J Surg Pathol. 2018;42:665–71. doi: 10.1097/PAS.0000000000001037. PubMed DOI

Rooper LM, Uddin N, Gagan J, et al. Recurrent loss of SMARCA4 in sinonasal teratocarcinosarcoma. Am J Surg Pathol. 2020;44:1331–9. doi: 10.1097/PAS.0000000000001508. PubMed DOI

Birkeland AC, Burgin SJ, Yanik M, et al. Pathogenetic analysis of sinonasal teratocarcinosarcomas reveal actionable beta-catenin overexpression and a beta-catenin Mutation. J Neurol Surg B Skull Base. 2017;78:346–52. doi: 10.1055/s-0037-1601320. PubMed DOI PMC

Minasi S, De Vincentiis L, D’Ecclesia A, et al. Pathogenetic analysis of sinonasal teratocarcinosarcomas reveal actionable beta-catenin overexpression and a beta-catenin mutation. J Neurol Surg B Skull Base. 2021;82:e112–3. doi: 10.1055/s-0039-3400228. PubMed DOI PMC

Compton ML, Lewis JS, Jr, Faquin WC, et al. SALL-4 and beta-catenin expression in sinonasal teratocarcinosarcoma. Head Neck Pathol. 2022;16:229–35. doi: 10.1007/s12105-021-01343-3. PubMed DOI PMC

Xiong J, Todorova D, Su NY, et al. Stemness factor Sall4 is required for DNA damage response in embryonic stem cells. J Cell Biol. 2015;208:513–20. doi: 10.1083/jcb.201408106. PubMed DOI PMC

Aras S, Saladi SV, Basuroy T, et al. BAF60A mediates interactions between the microphthalmia-associated transcription factor and the BRG1-containing SWI/SNF complex during melanocyte differentiation. J Cell Physiol. 2019;234:11780–91. doi: 10.1002/jcp.27840. PubMed DOI PMC

Bridge JA, Fidler ME, Neff JR, et al. Adamantinoma-like Ewing’s sarcoma: genomic confirmation, phenotypic drift. Am J Surg Pathol. 1999;23:159–65. doi: 10.1097/00000478-199902000-00004. PubMed DOI

Bishop JA, Alaggio R, Zhang L, et al. Adamantinoma-like Ewing family tumors of the head and neck: a pitfall in the differential diagnosis of basaloid and myoepithelial carcinomas. Am J Surg Pathol. 2015;39:1267–74. doi: 10.1097/PAS.0000000000000460. PubMed DOI PMC

Rooper LM, Jo VY, Antonescu CR, et al. Adamantinoma-like Ewing sarcoma of the salivary glands: a newly recognized mimicker of basaloid salivary carcinomas. Am J Surg Pathol. 2019;43:187–94. doi: 10.1097/PAS.0000000000001171. PubMed DOI PMC

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

Folpe AL, Goldblum JR, Rubin BP, et al. Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol. 2005;29:1025–33. doi: 10.1097/01.pas.0000167056.13614.62. PubMed DOI

McCuiston A, Bishop JA. Usefulness of NKX2.2 immunohistochemistry for distinguishing Ewing sarcoma from other sinonasal small round blue cell tumors. Head Neck Pathol. 2018;12:89–94. doi: 10.1007/s12105-017-0830-1. PubMed DOI PMC

Shibuya R, Matsuyama A, Nakamoto M, et al. The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma. Virchows Arch. 2014;465:599–605. doi: 10.1007/s00428-014-1627-1. PubMed DOI

Antonescu CR, Zhang L, Chang NE, 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. PubMed DOI PMC

Brandal P, Panagopoulos I, Bjerkehagen B, et al. t(19;22)(q13;q12) Translocation leading to the novel fusion gene EWSR1-ZNF444 in soft tissue myoepithelial carcinoma. Genes Chromosomes Cancer. 2009;48:1051–6. doi: 10.1002/gcc.20706. PubMed DOI

Agaram NP, Chen HW, Zhang L, et al. EWSR1-PBX3: a novel gene fusion in myoepithelial tumors. Genes Chromosomes Cancer. 2015;54:63–71. doi: 10.1002/gcc.22216. PubMed DOI PMC

Shibuya R, Matsuyama A, Nakamoto M, et al. Myoepithelioma, myoepithelial crcinoma and mixed tumour. In: World Health Organization classification of tumours 5th edition Soft tissue and bone tumours Lyon, France: IARC Press 2020:277–279.

Trojanowski JQ, Lee V, Pillsbury N, et al. Neuronal origin of human esthesioneuroblastoma demonstrated with anti-neurofilament monoclonal antibodies. N Engl J Med. 1982;307:159–61. doi: 10.1056/NEJM198207153070305. PubMed DOI

Bell D, Franchi A, Gillison M, et al. Olfactory neuroblastoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, et al., editors. WHO classification of head and neck tumours. Lyon: IARC; 2017.

Hartmann W, LH. S, Tumors of the upper respiratory tract and ear. In: Hyams VJ, Batsakis JG, Michaels L, editors. AFIP atlas of tumor pathology, 2nd series, Fascicle 25. Washington: Armed Forces Institute of Pathology; 1988.

Cracolici V, Wang EW, Gardner PA, et al. SSTR2 expression in olfactory neuroblastoma: clinical and therapeutic implications. Head Neck Pathol. 2021;15:1185–91. doi: 10.1007/s12105-021-01329-1. PubMed DOI PMC

Mills SE. Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol. 2002;15:264–78. doi: 10.1038/modpathol.3880522. PubMed DOI

Holbrook EH, Wu E, Curry WT, et al. Immunohistochemical characterization of human olfactory tissue. Laryngoscope. 2011;121:1687–701. doi: 10.1002/lary.21856. PubMed DOI PMC

Bourne TD, Bellizzi AM, Stelow EB, et al. p63 Expression in olfactory neuroblastoma and other small cell tumors of the sinonasal tract. Am J Clin Pathol. 2008;130:213–8. doi: 10.1309/TEDD2FCWH8W0H4HA. PubMed DOI

Bishop JA, Thompson LD, Cardesa A, et al. Rhabdomyoblastic differentiation in head and neck malignancies other than rhabdomyosarcoma. Head Neck Pathol. 2015;9:507–18. doi: 10.1007/s12105-015-0624-2. PubMed DOI PMC

Mehta GU, Raza SM, Su SY, et al. Management of olfactory neuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma involving the skullbase. J Neurooncol. 2020;150:367–75. doi: 10.1007/s11060-020-03537-1. PubMed DOI