Abstract
The World Health Organization recently published the 4th edition of the Classification of Head and Neck Tumors, including several new entities, emerging entities, and significant updates to the classification and characterization of tumor and tumor-like lesions, specifically as it relates to nasal cavity, paranasal sinuses, and skull base in this overview. Of note, three new entities (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were added to this section, while emerging entities (SMARCB1-deficient carcinoma and HPV-related carcinoma with adenoid cystic-like features) and several tumor-like entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal hamartoma) were included as provisional diagnoses or discussed in the setting of the differential diagnosis. The sinonasal tract houses a significant diversity of entities, but interestingly, the total number of entities has been significantly reduced by excluding tumor types if they did not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. Refinements to nomenclature and criteria were provided to sinonasal papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall, the new WHO classification reflects the state of current understanding for many relatively rare neoplasms, with this article highlighting the most significant changes.
Similar content being viewed by others
References
El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors (2017) WHO classification of head and neck tumours. Lyon, France: IARC
Bishop JA, Bell D, Westra WH (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: carcinomas: keratinizing squamous cell carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 14–15
Bishop JA, Brandwein-Gensler M, Nicolai P, Steens S, Syrjänen S, Westra WH (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: carcinomas: non-keratinizing squamous cell carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 15–17
French CA, Bishop JA, Lewis JS Jr, Müller S, Westra WH (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: carcinomas: NUT carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 20–21
Thompson LDR, Bell D, Bishop JA (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: neuroendocrine carcinomas. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 21–23
Stelow EB, Franchi A, Wenig BM (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: carcinomas: intestinal-type adenocarcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 23–24
Stelow EB, Brandwein-Gensler M, Franchi A, Nicolai P, Wenig BM (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: carcinomas: non-intestinal-type adenocarcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 24–26
Franchi A, Wenig BM (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: teratocarcinosarcoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 26–27
Hunt JL, Bell D, Sarioglu S (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: sinonasal papillomas: Sinonasal papilloma, inverted type. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 28–31
Hunt JL, Chiosea S, Sarioglu S (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: sinonasal papillomas: Sinonasal papilloma, oncocytic type. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 29–30
Hunt JL, Lewis JS Jr, Richardson M, Sarioglu S, Syrjanen K (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: sinonasal papillomas: Sinonasal papilloma, exophytic type. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 30–31
Wenig BM, Franchi A, Ro JY (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: respiratory epithelial lesions: respiratory epithelial adenomatoid hamartoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 31–32
Ro JY, Franchi A (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: respiratory epithelial lesions: seromucinous hamartoma. In: El-Naggar AK, JKC C, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, p 32
Lewis JE, Oliveira AM (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: malignant soft tissue Tumours: biphenotypic sinonasal sarcoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 40–41
Toner M, Hunt JL (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: other tumours: chondromesenchymal hamartoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 51–52
El-Mofty SK, Lu DW (2005) 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 29:1367–1372
Alos L, Moyano S, Nadal A et al (2009) Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome. Cancer 115:2701–2709
Larque AB, Hakim S, Ordi J et al (2014) High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas. Mod Pathol 27:343–351
Bishop JA, Guo TW, Smith DF et al (2013) Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol 37:185–192
Laco J, Sieglova K, Vosmikova H et al (2015) 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 467:405–415
Lewis JS Jr (2016) Sinonasal squamous cell carcinoma: a review with emphasis on emerging histologic subtypes and the role of human papillomavirus. Head Neck Pathol. 10:60–67
Chung CH, Guthrie VB, Masica DL et al (2015) Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol 26:1216–1223
Bishop JA, Ogawa T, Stelow EB et al (2013) 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 37:836–844
Andreasen S, Bishop JA, Hansen TV, et al (2016) Human papillomavirus-related carcinoma with adenoid cystic-like features of the sinonasal tract: clinical and morphological characterization of six new cases. Histopathol doi: 10.1111/his.13162
Udager AM, Rolland DC, McHugh JB et al (2015) High-frequency targetable EGFR mutations in sinonasal squamous cell carcinomas arising from inverted sinonasal papilloma. Cancer Res 75:2600–2606
Udager AM, McHugh JB, Betz BL et al (2016) Activating KRAS mutations are characteristic of oncocytic sinonasal papilloma and associated sinonasal squamous cell carcinoma. J Pathol 239:394–398
Bishop JA, Westra WH (2012) NUT midline carcinomas of the sinonasal tract. Am J Surg Pathol 36:1216–1221
Haack H, Johnson LA, Fry CJ et al (2009) Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol 33:984–991
Stathis A, Zucca E, Bekradda M et al (2016) Clinical response of carcinomas harboring the BRD4-NUT oncoprotein to the targeted bromodomain inhibitor OTX015/MK-8628. Cancer Discov. 6:492–500
Lewis JS Jr, Bishop JA, Gillison M, Westra WH, Yarborough WG (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: carcinomas: sinonasal undifferentiated carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 18–20
Bishop JA, Antonescu CR, Westra WH (2014) SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol 38:1282–1289
Agaimy A, Koch M, Lell M et al (2014) SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms. Am J Surg Pathol 38:1274–1281
Bell D, Hanna EY, Agaimy A, Weissferdt A (2015) Reappraisal of sinonasal undifferentiated carcinoma: SMARCB1 (INI1)-deficient sinonasal carcinoma: a single-institution experience. Virchows Arch 467:649–656
Jo VY, Chau NG, Hornick JL, Krane JF, Sholl LM (2017) Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma. Mod Pathol doi: 10.1038/modpathol.2016.239
Patel TD, Vazquez A, Dubal PM, Baredes S, Liu JK, Eloy JA (2015) Sinonasal neuroendocrine carcinoma: a population-based analysis of incidence and survival. Int Forum Allergy Rhinol. 5:448–453
Chai L, Ying HF, Wu TT et al (2014) Clinical features and hypoxic marker expression of primary sinonasal and laryngeal small-cell neuroendocrine carcinoma: a small case series. World J Surg Oncol 12:199
Huang S, Zhao Y, He L, Dan LV, Yang F (2013) Clinical analysis and review of 8 cases with sinonasal neuroendocrine carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 27:751–753
Qian GH, Shang JB, Wang KJ, Tan Z (2011) Diagnosis and treatment of 11 cases with sinonasal neuroendocrine carcinoma. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 46:1033–1035
Su SY, Bell D, Hanna EY (2014) Esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma: differentiation in diagnosis and treatment. Int Arch Otorhinolaryngol 18:S149–S156
Mitchell EH, Diaz A, Yilmaz T et al (2012) Multimodality treatment for sinonasal neuroendocrine carcinoma. Head Neck. 34:1372–1376
Likhacheva A, Rosenthal DI, Hanna E, Kupferman M, Demonte F, El-Naggar AK (2011) Sinonasal neuroendocrine carcinoma: impact of differentiation status on response and outcome. Head Neck Oncol 3:32
Weinreb I, Perez-Ordonez B (2007) Non-small cell neuroendocrine carcinoma of the sinonasal tract and nasopharynx. Report of 2 cases and review of the literature. Head Neck Pathol. 1:21–26
Sugita Y, Kusano K, Tokunaga O et al (2006) Olfactory neuroepithelioma: an immunohistochemical and ultrastructural study. Neuropathology 26:400–408
Cordes B, Williams MD, Tirado Y et al (2009) Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification. Hum Pathol 40:283–292
Wooff JC, Weinreb I, Perez-Ordonez B, Magee JF, Bullock MJ (2011) Calretinin staining facilitates differentiation of olfactory neuroblastoma from other small round blue cell tumors in the sinonasal tract. Am J Surg Pathol 35:1786–1793
Chapman-Fredricks J, Jorda M, Gomez-Fernandez C (2009) A limited immunohistochemical panel helps differentiate small cell epithelial malignancies of the sinonasal cavity and nasopharynx. Appl Immunohistochem Mol Morphol 17:207–210
van der Laan TP, Bij HP, van Hemel BM et al (2013) The importance of multimodality therapy in the treatment of sinonasal neuroendocrine carcinoma. Eur Arch Otorhinolaryngol 270:2565–2568
Menon S, Pai P, Sengar M, Aggarwal JP, Kane SV (2010) Sinonasal malignancies with neuroendocrine differentiation: case series and review of literature. Indian J Pathol Microbiol 53:28–34
Holmila R, Bornholdt J, Heikkila P et al (2010) Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer. Int J Cancer 127:578–588
Perrone F, Oggionni M, Birindelli S et al (2003) TP53, p14ARF, p16INK4a and H-ras gene molecular analysis in intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Int J Cancer 105:196–203
Perez-Escuredo J, Martinez JG, Vivanco B et al (2012) Wood dust-related mutational profile of TP53 in intestinal-type sinonasal adenocarcinoma. Hum Pathol 43:1894–1901
Franchi A, Innocenti DR, Palomba A et al (2014) Low prevalence of K-RAS, EGF-R and BRAF mutations in sinonasal adenocarcinomas. Implications for anti-EGFR treatments. Pathol Oncol Res 20:571–579
Garcia-Inclan C, Lopez F, Perez-Escuredo J et al (2012) EGFR status and KRAS/BRAF mutations in intestinal-type sinonasal adenocarcinomas. Cell Oncol (Dordr) 35:443–450
Lopez F, Garcia Inclan C, Perez-Escuredo J et al (2012) KRAS and BRAF mutations in sinonasal cancer. Oral Oncol 48:692–697
Franchi A, Fondi C, Paglierani M, Pepi M, Gallo O, Santucci M (2009) Epidermal growth factor receptor expression and gene copy number in sinonasal intestinal type adenocarcinoma. Oral Oncol 45:835–838
Zur KB, Brandwein M, Wang B, Som P, Gordon R, Urken ML (2002) Primary description of a new entity, renal cell-like carcinoma of the nasal cavity: van Meegeren in the house of Vermeer. Arch Otolaryngol Head Neck Surg. 128:441–447
Storck K, Hadi UM, Simpson R, Ramer M, Brandwein-Gensler M (2008) Sinonasal renal cell-like adenocarcinoma: a report on four patients. Head Neck Pathol. 2:75–80
Shen T, Shi Q, Velosa C et al (2015) Sinonasal renal cell-like adenocarcinomas: robust carbonic anhydrase expression. Hum Pathol 46:1598–1606
Stelow EB, Jo VY, Mills SE, Carlson DL (2011) A histologic and immunohistochemical study describing the diversity of tumors classified as sinonasal high-grade nonintestinal adenocarcinomas. Am J Surg Pathol 35:971–980
Hunt JL, Bell D, Chiosea S et al (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: sinonasal papillomas. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 28–31
Anari S, Carrie S (2010) Sinonasal inverted papilloma: narrative review. J Laryngol Otol 124:705–715
Krouse JH (2001) Endoscopic treatment of inverted papilloma: safety and efficacy. Am J Otolaryngol 22:87–99
Nudell J, Chiosea S, Thompson LD (2014) Carcinoma ex-Schneiderian papilloma (malignant transformation): a clinicopathologic and immunophenotypic study of 20 cases combined with a comprehensive review of the literature. Head Neck Pathol. 8:269–286
Barnes L (2002) Schneiderian papillomas and nonsalivary glandular neoplasms of the head and neck. Mod Pathol 15:279–297
Rodic N, Maleki Z (2012) Cytomorphologic findings of Schneiderian papilloma: a case report. Diagn Cytopathol 40:1100–1103
Sarioglu S (2007) Update on inverted epithelial lesions of the sinonasal and nasopharyngeal regions. Head Neck Pathol. 1:44–49
Weinreb I, Gnepp DR, Laver NM et al (2009) Seromucinous hamartomas: a clinicopathological study of a sinonasal glandular lesion lacking myoepithelial cells. Histopathology 54:205–213
Ozolek JA, Hunt JL (2006) Tumor suppressor gene alterations in respiratory epithelial adenomatoid hamartoma (REAH): comparison to sinonasal adenocarcinoma and inflamed sinonasal mucosa. Am J Surg Pathol 30:1576–1580
McDermott MB, Ponder TB, Dehner LP (1998) Nasal chondromesenchymal hamartoma: an upper respiratory tract analogue of the chest wall mesenchymal hamartoma. Am J Surg Pathol 22:425–433
Stewart DR, Messinger Y, Williams GM et al (2014) Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition disorder. Hum Genet 133:1443–1450
Ozolek JA, Carrau R, Barnes EL, Hunt JL (2005) Nasal chondromesenchymal hamartoma in older children and adults: series and immunohistochemical analysis. Arch Pathol Lab Med 129:1444–1450
Heffner DK, Gnepp DR (1992) Sinonasal fibrosarcomas, malignant schwannomas, and “triton” tumors. A clinicopathologic study of 67 cases. Cancer 70:1089–1101
Igwe OJ (2006) Agents that act by different mechanisms modulate the activity of protein kinase CbetaII isozyme in the rat spinal cord during peripheral inflammation. Neuroscience 138:313–328
Hellquist HB, Lundgren J (1991) Neurogenic sarcoma of the sinonasal tract. J Laryngol Otol 105:186–190
Patel TD, Carniol ET, Vazquez A, Baredes S, Liu JK, Eloy JA (2016) Sinonasal fibrosarcoma: analysis of the surveillance, epidemiology, and end results database. Int Forum Allergy Rhinol 6:201–205
Lewis JT, Oliveira AM, Nascimento AG et al (2012) Low-grade sinonasal sarcoma with neural and myogenic features: a clinicopathologic analysis of 28 cases. Am J Surg Pathol 36:517–525
Wang X, Bledsoe KL, Graham RP et al (2014) Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma. Nat Genet 46:666–668
Powers KA, Han LM, Chiu AG, Aly FZ (2015) Low-grade sinonasal sarcoma with neural and myogenic features—diagnostic challenge and pathogenic insight. Oral Surg Oral Med Oral Pathol Oral Radiol 119:e265–e269
Huang SC, Ghossein RA, Bishop JA et al (2016) Novel PAX3-NCOA1 fusions in biphenotypic sinonasal sarcoma with focal rhabdomyoblastic differentiation. Am J Surg Pathol 40:51–59
Sumegi J, Streblow R, Frayer RW et al (2010) Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family. Genes Chromosomes Cancer. 49:224–236
Wong WJ, Lauria A, Hornick JL, Xiao S, Fletcher JA, Marino-Enriquez A (2016) Alternate PAX3-FOXO1 oncogenic fusion in biphenotypic sinonasal sarcoma. Genes Chromosomes Cancer. 55:25–29
Bullerdiek J, Bell D (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: synovial sarcoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 41–42
Bettio D, Rizzi N, Colombo P, Bianchi P, Gaetani P (2004) Unusual cytogenetic findings in a synovial sarcoma arising in the paranasal sinuses. Cancer Genet Cytogenet 155:79–81
Gil Z, Orr-Urtreger A, Voskoboinik N, Trejo-Leider L, Shomrat R, Fliss DM (2008) Cytogenetic analysis of 101 skull base tumors. Head Neck. 30:567–581
Wenig BM, Flucke U, Thompson LDR (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: boderline/low-grade malignant soft tissue tumours. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 43–46
Huss S, Nehles J, Binot E et al (2013) Beta-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology 62:294–304
Le Guellec S, Soubeyran I, Rochaix P et al (2012) CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics. Mod Pathol 25:1551–1558
Flucke U, Tops BB, van Diest PJ, Slootweg PJ (2014) Desmoid-type fibromatosis of the head and neck region in the paediatric population: a clinicopathological and genetic study of seven cases. Histopathology 64:769–776
Coffin CM, Hornick JL, Zhou H, Fletcher CD (2007) Gardner fibroma: a clinicopathologic and immunohistochemical analysis of 45 patients with 57 fibromas. Am J Surg Pathol 31:410–416
Colombo C, Foo WC, Whiting D et al (2012) FAP-related desmoid tumors: a series of 44 patients evaluated in a cancer referral center. Histol Histopathol 27:641–649
Schiessling S, Kihm M, Ganschow P, Kadmon G, Buchler MW, Kadmon M (2013) Desmoid tumour biology in patients with familial adenomatous polyposis coli. Br J Surg 100:694–703
Thway K, Gibson S, Ramsay A, Sebire NJ (2009) Beta-catenin expression in pediatric fibroblastic and myofibroblastic lesions: a study of 100 cases. Pediatr Dev Pathol 12:292–296
Bhattacharya B, Dilworth HP, Iacobuzio-Donahue C et al (2005) Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol 29:653–659
Carlson JW, Fletcher CD (2007) Immunohistochemistry for beta-catenin in the differential diagnosis of spindle cell lesions: analysis of a series and review of the literature. Histopathology 51:509–514
Thompson LD, Miettinen M, Wenig BM (2003) Sinonasal-type hemangiopericytoma: a clinicopathologic and immunophenotypic analysis of 104 cases showing perivascular myoid differentiation. Am J Surg Pathol 27:737–749
Lasota J, Felisiak-Golabek A, Aly FZ, Wang ZF, Thompson LD, Miettinen M (2015) Nuclear expression and gain-of-function beta-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker. Mod Pathol 28:715–720
Haller F, Bieg M, Moskalev EA et al (2015) Recurrent mutations within the amino-terminal region of beta-catenin are probable key molecular driver events in sinonasal hemangiopericytoma. Am J Pathol 185:563–571
Agaimy A, Barthelmess S, Geddert H et al (2014) Phenotypical and molecular distinctness of sinonasal haemangiopericytoma compared to solitary fibrous tumour of the sinonasal tract. Histopathology 65:667–673
Doyle LA, Vivero M, Fletcher CD, Mertens F, Hornick JL (2014) Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 27:390–395
Mohajeri A, Tayebwa J, Collin A et al (2013) Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. Genes Chromosomes Cancer. 52:873–886
Akaike K, Kurisaki-Arakawa A, Hara K et al (2015) Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential. Hum Pathol 46:347–356
Demicco EG, Wani K, Fox PS et al (2015) Histologic variability in solitary fibrous tumors reflects angiogenic and growth factor signaling pathway alterations. Hum Pathol 46:1015–1026
Yoshida A, Tsuta K, Ohno M et al (2014) STAT6 immunohistochemistry is helpful in the diagnosis of solitary fibrous tumors. Am J Surg Pathol 38:552–559
Demicco EG, Harms PW, Patel RM et al (2015) Extensive survey of STAT6 expression in a large series of mesenchymal tumors. Am J Clin Pathol 143:672–682
Weiss SW, Enzinger FM (1982) Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer 50:970–981
Bruder E, Alaggio R, Kozakewich HP, Jundt G, Dehner LP, Coffin CM (2012) Vascular and perivascular lesions of skin and soft tissues in children and adolescents. Pediatr Dev Pathol 15:26–61
Errani C, Zhang L, Sung YS et al (2011) A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer. 50:644–653
Flucke U, Vogels RJ, de Saint Aubain Somerhausen N et al (2014) Epithelioid hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. Diagn Pathol 9:131
Mentzel T, Beham A, Calonje E, Katenkamp D, Fletcher CD (1997) Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am J Surg Pathol 21:363–374
Deyrup AT, Tighiouart M, Montag AG, Weiss SW (2008) Epithelioid hemangioendothelioma of soft tissue: a proposal for risk stratification based on 49 cases. Am J Surg Pathol 32:924–927
Tanas MR, Sboner A, Oliveira AM et al (2011) Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med 3:98ra82
Antonescu CR, Le Loarer F, Mosquera JM et al (2013) Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer. 52:775–784
Chuang SS, Ferry JA, Gaulard P, Jaffe ES, Ko Y-H (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: haematolymphoid tumours. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 52–55
Dubal PM, Dutta R, Vazquez A, Patel TD, Baredes S, Eloy JA (2015) A comparative population-based analysis of sinonasal diffuse large B-cell and extranodal NK/T-cell lymphomas. Laryngoscope 125:1077–1083
Aoki R, Karube K, Sugita Y et al (2008) Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006. Pathol Int 58:174–182
Laurini JA, Perry AM, Boilesen E et al (2012) Classification of non-Hodgkin lymphoma in cCentral and South America: a review of 1028 cases. Blood 120:4795–4801
Crane GM, Duffield AS (2016) Hematolymphoid lesions of the sinonasal tract. Semin Diagn Pathol 33:71–80
Kreisel FH (2016) Hematolymphoid lesions of the sinonasal tract. Head Neck Pathol. 10:109–117
Hoffman HT, Karnell LH, Funk GF, Robinson RA, Menck HR (1998) The National Cancer Data Base report on cancer of the head and neck. Arch Otolaryngol Head Neck Surg. 124:951–962
Cooper JS, Porter K, Mallin K et al (2009) National Cancer Database report on cancer of the head and neck: 10-year update. Head Neck 31:748–758
Pongpruttipan T, Sukpanichnant S, Assanasen T et al (2012) Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and alphabeta, gammadelta, and alphabeta/gammadelta T-cell origin: a comprehensive clinicopathologic and phenotypic study. Am J Surg Pathol 36:481–499
Jhuang JY, Chang ST, Weng SF et al (2015) Extranodal natural killer/T-cell lymphoma, nasal type in Taiwan: a relatively higher frequency of T-cell lineage and poor survival for extranasal tumors. Hum Pathol 46:313–321
Au WY, Weisenburger DD, Intragumtornchai T et al (2009) Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the international peripheral T-cell lymphoma project. Blood 113:3931–3937
Li S, Feng X, Li T et al (2013) Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center. Am J Surg Pathol 37:14–23
Chuang SS, Ko YH (2014) Cutaneous nonmycotic T- and natural killer/T-cell lymphomas: diagnostic challenges and dilemmas. J Am Acad Dermatol 70:724–735
Swerdlow SH, Jaffe ES, Brousset P et al (2014) Cytotoxic T-cell and NK-cell lymphomas: current questions and controversies. Am J Surg Pathol 38:e60–e71
Chuang SS (2014) In situ hybridisation for Epstein-Barr virus as a differential diagnostic tool for T- and natural killer/T-cell lymphomas in non-immunocompromised patients. Pathology 46:581–591
Jaffe ES, Nicolae A, Pittaluga S (2013) Peripheral T-cell and NK-cell lymphomas in the WHO classification: pearls and pitfalls. Mod Pathol 26(Suppl 1):S71–S87
Coppo P, Gouilleux-Gruart V, Huang Y et al (2009) STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma. Leukemia 23:1667–1678
Koo GC, Tan SY, Tang T et al (2012) Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov 2:591–597
Lee S, Park HY, Kang SY et al (2015) Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type. Oncotarget 6:17764–17776
Chen YW, Guo T, Shen L et al (2015) Receptor-type tyrosine-protein phosphatase kappa directly targets STAT3 activation for tumor suppression in nasal NK/T-cell lymphoma. Blood 125:1589–1600
Wenig BM, Flucke U, Thompson LDR et al (2017) Tumours of the nasal cavity, paranasal sinuses and skull base: neuroectodermal/melanocytic tumours. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumours. IARC, Lyon, pp 56–61
Windfuhr JP (2004) Primitive neuroectodermal tumor of the head and neck: incidence, diagnosis, and management. Ann Otol Rhinol Laryngol. 113:533–543
Howarth KL, Khodaei I, Karkanevatos A, Clarke RW (2004) A sinonasal primary Ewing’s sarcoma. Int J Pediatr Otorhinolaryngol 68:221–224
Hafezi S, Seethala RR, Stelow EB et al (2011) Ewing’s family of tumors of the sinonasal tract and maxillary bone. Head Neck Pathol. 5:8–16
Folpe AL, Goldblum JR, Rubin BP et al (2005) Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 29:1025–1033
Bishop JA, Alaggio R, Zhang L, Seethala RR, Antonescu CR (2015) 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 39:1267–1274
Machado I, Mayordomo-Aranda E, Scotlandi K, Picci P, Llombart-Bosch A (2014) Immunoreactivity using anti-ERG monoclonal antibodies in sarcomas is influenced by clone selection. Pathol Res Pract 210:508–513
Tomlins SA, Palanisamy N, Brenner JC et al (2013) Usefulness of a monoclonal ERG/FLI1 antibody for immunohistochemical discrimination of Ewing family tumors. Am J Clin Pathol 139:771–779
Wang WL, Patel NR, Caragea M et al (2012) Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma. Mod Pathol 25:1378–1383
Gu M, Antonescu CR, Guiter G, Huvos AG, Ladanyi M, Zakowski MF (2000) Cytokeratin immunoreactivity in Ewing’s sarcoma: prevalence in 50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 24:410–416
Italiano A, Sung YS, Zhang L et al (2012) High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. Genes Chromosomes Cancer. 51:207–218
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 Chromosomes Cancer 53:622–633
Jethanamest D, Morris LG, Sikora AG, Kutler DI (2007) Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 133:276–280
Platek ME, Merzianu M, Mashtare TL et al (2011) Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database. Radiat Oncol 6:41
Broich G, Pagliari A, Ottaviani F (1997) Esthesioneuroblastoma: a general review of the cases published since the discovery of the tumour in 1924. Anticancer Res 17:2683–2706
Thompson LD (2009) Olfactory neuroblastoma. Head Neck Pathol. 3:252–259
Kadish S, Goodman M, Wang CC (1976) Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 37:1571–1576
Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM (1993) Esthesioneuroblastoma: prognosis and management. Neurosurgery 32:706–714 discussion 714-705
Llombart-Bosch A, Carda C, Peydro-Olaya A, Noguera R, Boix J, Pellin A (1989) Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice. An immunohistochemical, electron microscopical, and cytogenetic analysis. Virchows Arch A Pathol Anat Histopathol 414:199–208
Bates T, Plessis DD, Polvikoski T et al (2012) Ganglioneuroblastic transformation in olfactory neuroblastoma. Head Neck Pathol. 6:150–155
Miyagami M, Katayama Y, Kinukawa N, Sawada T (2002) An ultrastructural and immunohistochemical study of olfactory neuroepithelioma with rhabdomyoblasts. Med Electron Microsc 35:160–166
Faragalla H, Weinreb I (2009) Olfactory neuroblastoma: a review and update. Adv Anat Pathol 16:322–331
Bishop JA, Thompson LD, Cardesa A et al (2015) Rhabdomyoblastic differentiation in head and neck malignancies other than rhabdomyosarcoma. Head Neck Pathol 9:507–518
Holbrook EH, Wu E, Curry WT, Lin DT, Schwob JE (2011) Immunohistochemical characterization of human olfactory tissue. Laryngoscope 121:1687–1701
Thompson LD (2017) Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach. Mod Pathol 30:S1–s26
Saade RE, Hanna EY, Bell D (2015) Prognosis and biology in esthesioneuroblastoma: the emerging role of Hyams grading system. Curr Oncol Rep 17:423
Tajudeen BA, Arshi A, Suh JD, St John M, Wang MB (2014) Importance of tumor grade in esthesioneuroblastoma survival: a population-based analysis. JAMA Otolaryngol Head Neck Surg 140:1124–1129
Gallagher KK, Spector ME, Pepper JP, McKean EL, Marentette LJ, McHugh JB (2014) Esthesioneuroblastoma: updating histologic grading as it relates to prognosis. Ann Otol Rhinol Laryngol 123:353–358
Kaur G, Kane AJ, Sughrue ME et al (2013) The prognostic implications of Hyam’s subtype for patients with Kadish stage C esthesioneuroblastoma. J Clin Neurosci 20:281–286
Mao L, Xia YP, Zhou YN et al (2009) Activation of sonic hedgehog signaling pathway in olfactory neuroblastoma. Oncology 77:231–243
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors have contributed to this work and they declare that there are no financial conflicts associated with this study.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
Not applicable.
Copyright transfer agreement
We transfer the right to publish this manuscript in the journal Virchows Archives if accepted for publication. This article is an original work, is not under consideration, and has not been published previously in any form.
Rights and permissions
About this article
Cite this article
Thompson, L.D.R., Franchi, A. New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull base. Virchows Arch 472, 315–330 (2018). https://doi.org/10.1007/s00428-017-2116-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-017-2116-0