SOX10 immunoexpression is increasingly recognized in salivary gland tumors, including but not limited to those with myoepithelial, serous acinar, and intercalated duct differentiation. However, SOX10 expression has not been extensively evaluated in other epithelial tumors that can mimic salivary origin. Basaloid squamous cell carcinoma (SCC) is a unique variant of SCC that shows morphologic overlap with several salivary tumors, including adenoid cystic carcinoma, basal cell adenocarcinoma, and myoepithelial carcinoma. We performed SOX10 immunohistochemistry on 22 basaloid SCCs and 280 non-basaloid SCCs. If tissue was available, we also performed immunohistochemistry for S100 and p16, and in-situ hybridization for high-risk HPV RNA. SOX10 was positive in 13/22 basaloid SCCs (59%), including 5/6 (83%) that were HPV-positive and 6/12 (50%) that were HPV-negative. Only 2/12 basaloid SCC (17%) demonstrated focal S100 expression. All non-basaloid SCCs were SOX10 negative. Frequent positivity for SOX10 in basaloid SCC presents a significant diagnostic pitfall for distinguishing these tumors from various basaloid salivary carcinomas. The preponderance of SOX10 expression in the basaloid variant of HPV-positive SCC also presents a diagnostic challenge in separating it from HPV-related multiphenotypic sinonasal carcinoma. SOX10 may be more broadly considered a marker of basal differentiation and should not be assumed to be specific for salivary origin in epithelial head and neck tumors.
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Karamchandani JR, Nielsen TO, van de Rijn M, West RB. Sox10 and S100 in the diagnosis of soft-tissue neoplasms. Appl Immunohistochem Mol Morphol. 2012;20(5):445–50.
Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C. SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Appl Immunohistochem Mol Morphol. 2013;21(6):506–10.
Nonaka D, Chiriboga L, Rubin BP. Sox10: a pan-schwannian and melanocytic marker. Am J Surg Pathol. 2008;32(9):1291–8.
Shin J, Vincent JG, Cuda JD, Xu H, Kang S, Kim J, et al. Sox10 is expressed in primary melanocytic neoplasms of various histologies but not in fibrohistiocytic proliferations and histiocytoses. J Am Acad Dermatol. 2012;67(4):717–26.
Hsieh MS, Lee YH, Chang YL. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma. Hum Pathol. 2016;56:134–42.
Ivanov SV, Panaccione A, Nonaka D, Prasad ML, Boyd KL, Brown B, et al. Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas. Br J Cancer. 2013;109(2):444–51.
Miettinen M, McCue PA, Sarlomo-Rikala M, Biernat W, Czapiewski P, Kopczynski J, et al. Sox10–a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol. 2015;39(6):826–35.
Ohtomo R, Mori T, Shibata S, Tsuta K, Maeshima AM, Akazawa C, et al. SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis. Mod Pathol. 2013;26(8):1041–50.
Schmitt AC, Cohen C, Siddiqui MT. Expression of SOX10 in salivary gland oncocytic neoplasms: a review and a comparative analysis with other immunohistochemical markers. Acta Cytol. 2015;59(5):384–90.
Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50.
Chernock RD, Lewis JS Jr, Zhang Q, El-Mofty SK. Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol. 2010;41(7):1016–23.
Barnes L, Ferlito A, Altavilla G, MacMillan C, Rinaldo A, Doglioni C. Basaloid squamous cell carcinoma of the head and neck: clinicopathological features and differential diagnosis. Ann Otol Rhinol Laryngol. 1996;105(1):75–82.
Lewis JS, Gillison ML, Westra WH, Zidar N. Basaloid squamous cell carcinoma. In: El-Naggar A, Chan JK, Grandis JR, Takata T, Slootweg PJ, editors. WHO Classification of Head and Neck Tumours. Lyon: International Agency for Research on Cancer; 2017. pp. 85–6.
Wain SL, Kier R, Vollmer RT, Bossen EH. Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases. Hum Pathol. 1986;17(11):1158–66.
Banks ER, Frierson HF Jr, Mills SE, George E, Zarbo RJ, Swanson PE. Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol. 1992;16(10):939–46.
Emanuel P, Wang B, Wu M, Burstein DE. p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma. Mod Pathol. 2005;18(5):645–50.
Klijanienko J, el-Naggar A, Ponzio-Prion A, Marandas P, Micheau C, Caillaud JM. Basaloid squamous carcinoma of the head and neck. Immunohistochemical comparison with adenoid cystic carcinoma and squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1993;119(8):887–90.
Morice WG, Ferreiro JA. Distinction of basaloid squamous cell carcinoma from adenoid cystic and small cell undifferentiated carcinoma by immunohistochemistry. Hum Pathol. 1998;29(6):609–12.
Serrano MF, El-Mofty SK, Gnepp DR, Lewis JS Jr. Utility of high molecular weight cytokeratins, but not p63, in the differential diagnosis of neuroendocrine and basaloid carcinomas of the head and neck. Hum Pathol. 2008;39(4):591–8.
Westra WH, Taube JM, Poeta ML, Begum S, Sidransky D, Koch WM. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2008;14(2):366–9.
Ereno C, Gaafar A, Garmendia M, Etxezarraga C, Bilbao FJ, Lopez JI. Basaloid squamous cell carcinoma of the head and neck: a clinicopathological and follow-up study of 40 cases and review of the literature. Head Neck Pathol. 2008;2(2):83–91.
Bishop JA, Andreasen S, Hang JF, Bullock MJ, Chen TY, Franchi A, 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(12):1690–701.
Bishop JA, Ogawa T, Stelow EB, Moskaluk CA, Koch WM, Pai SI, 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(6):836–44.
Hsieh MS, Lee YH, Jin YT, Huang WC. Strong SOX10 expression in HPV-related multiphenotypic sinonasal carcinoma: report of six new cases validated by high-risk HPV mRNA in situ hybridization test. Hum Pathol. 2018. https://doi.org/10.1016/j.humpath.2018.07.026
Cimino-Mathews A, Subhawong AP, Elwood H, Warzecha HN, Sharma R, Park BH, et al. Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas. Hum Pathol. 2013;44(6):959–65.
Harbhajanka A, Chahar S, Miskimen K, Silverman P, Harris L, Williams N, et al. Clinicopathological, immunohistochemical and molecular correlation of neural crest transcription factor SOX10 expression in triple-negative breast carcinoma. Hum Pathol. 2018;80:163–9.
Nelson ER, Sharma R, Argani P, Cimino-Mathews A. Utility of Sox10 labeling in metastatic breast carcinomas. Hum Pathol. 2017;67:205–10.
Fadare O, Tavassoli FA. The phenotypic spectrum of basal-like breast cancers: a critical appraisal. Adv Anat Pathol. 2007;14(5):358–73.
Conflict of interest
All authors have no potential conflicts of interest to declare. This work was performed under Johns Hopkins IRB00176170 with consent waiver.
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Rooper, L.M., McCuiston, A.M., Westra, W.H. et al. SOX10 Immunoexpression in Basaloid Squamous Cell Carcinomas: A Diagnostic Pitfall for Ruling out Salivary Differentiation. Head and Neck Pathol 13, 543–547 (2019). https://doi.org/10.1007/s12105-018-0990-7
- Basaloid squamous cell carcinoma
- Squamous cell carcinoma
- Human papillomavirus