Abstract
The next WHO classification should abandon “salivary duct carcinoma”; conventional salivary duct carcinoma should be classified as “high-grade salivary duct carcinoma”. Low-grade salivary duct carcinoma should replace the current nosology of “low-grade cribriform cystadenocarcinoma”. Cystadenocarcinoma should be classified with the descriptor “Not Otherwise Specified” and should be considered an exclusionary diagnostic category. On the other hand, “Not Otherwise Specified” does not fit for hyalinizing clear cell carcinoma (HCCC). The EWSR1-ATF1 fusion is specific for HCCC within the context of salivary neoplasia. We recommend adding “hyalinizing” even though this feature is not present in all cases; the benefit of which is the mental association with a salivary clear cell malignancy. Sinonasal Renal Cell-like Adenocarcinoma (SNRCLA) is a distinct clear cell neoplasm and should be added to the next WHO classification. Future studies will bear out whether SNRCLA is even a low-grade carcinoma, or may be reclassified as “adenoma”. Lastly, the next WHO monograph should include the Risk Model in the general introductory statements on oral squamous cell carcinoma, under a subheading of “Histological Prognosticators”. The positive predictive value for developing locoregional recurrence in patients with low-stage oral cavity squamous carcinoma (OSCC) and “worst pattern of invasion type-5” (WPOI-5) is 42 %. Low-stage high-risk OSCC with a combination of features other than WPOI-5 is associated with 32 % likelihood for locoregional progression. WPOI-5 also predicts occult metastatic disease (p = 0.0001, Chi squared, 2 DF). Thus the Risk Model can also be used to make decisions regarding staged elective neck dissections.
Similar content being viewed by others
References
Delgado R, Klimstra D, Albores-Saavedra J. Low grade salivary duct carcinoma. A distinctive variant with a low-grade histology and a predominant intraductal growth pattern. Cancer. 1996;78:958–67.
Brandwein-Gensler M, Hille J, Wang BY, Urken M, Gordon R, Wang LJ, Simpson JR, Simpson RH, Gnepp DR. Low-grade salivary duct carcinoma: description of 16 cases. Am J Surg Pathol. 2004;28:1040–4.
Brandwein-Gensler M, Gnepp DR. Low-grade cribriform cystadenocarcinoma. In: Barnes L, Eveson JW, Reichart P, et al., editors. Pathology and genetics head and neck tumors. Lyon: IARC Press; 2005. p. 233.
Kuo YJ, Weinreb I, Perez-Ordonez B. Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature. Head Neck Pathol. 2013;7(Suppl 1):S59–67.
Wang L, Liu Y, Lin X, Zhang D, Li Q, Qiu X, Wang EH. Low-grade cribriform cystadenocarcinoma of salivary glands: report of two cases and review of the literature. Diagn Pathol. 2013;8:28. doi:10.1186/1746-1596-8-28.
Chen KT. Cytology of salivary duct carcinoma. Diagn Cytopath. 2000;22:132–5.
Weinreb I. Intraductal carcinoma of salivary gland (so-called low-grade cribriform cystadenocarcinoma) arising in an intraparotid lymph node. Head Neck Pathol. 2011;5:321–5.
Kusafuka K, Itoh H, Sugiyama C, et al. Low-grade salivary duct carcinoma of the parotid gland: report of a case with immunohistochemical analysis. Med Mol Morphol. 2010;43:178–84.
Khurana KK, Pitman MB, Powers CN, et al. Diagnostic pitfalls of aspiration cytology of salivary duct carcinoma. Cancer. 1997;81:373–8.
Ide F, Mishima K, Saito I. Circumscribed salivary duct carcinoma of the palate: a non-threatening variant. Histopathology. 2004;45:89–91.
Tatemoto Y, Ohno A, Osaki T. Low malignant intraductal carcinoma on the hard palate: a variant of salivary duct carcinoma? Eur J Cancer B Oral Oncol. 1996;32B:275–7.
Weinreb I, Tabanda-Lichauco R, Van der Kwast T, Perez-Ordoñez B. Low-grade intraductal carcinoma of salivary gland: report of 3 cases with marked apocrine differentiation. Am J Surg Pathol. 2006;30:1014–21.
Nakatsuka S, Harada H, Fujiyama H, Takeda K, Kitamura K, Kimura H, Nagano T, Ito M, Asada Y. An invasive adenocarcinoma of the accessory parotid gland: a rare example developing from a low-grade cribriform cystadenocarcinoma? Diagn Pathol. 2011;6:122. doi:10.1186/1746-1596-6-122.
Laco J, Podhola M, Dolezalova H. Low-grade cribriform cystadenocarcinoma of the parotid gland: a neoplasm with favorable prognosis, distinct from salivary duct carcinoma. Int J Surg Pathol. 2010;18:369–73.
Anderson C, Muller R, Piorkowski R, Knibbs DR, Vignoti P. Intraductal carcinoma of major salivary gland. Cancer. 1992;69:609–14.
Foss RD, Ellis GL, Auclair PL. Salivary gland cystadenocarcinomas. A Clinicopathologic study of 57 cases. Am J Surg Pathol. 1996;20:1440–7.
Ellis GL, Auclair PL. Armed Forces Institute of Pathology (AFIP) Atlas of Tumor Pathology. Tumors of the Salivary Glands (fourth series fascicle 9) Maryland: ARP Press; 2008. p. 283–288.
Auclair PL. Cystadenocarcinoma. In: Barnes L, Eveson JW, Reichart P, et al., editors. Pathology and genetics head and neck tumors. Lyon: IARC Press; 2005. p. 232.
Hunter JB, Smith RV, Brandwein-Gensler M. Low-grade papillary adenocarcinoma of the palate: the significance of distinguishing it from polymorphous low-grade adenocarcinoma. Head Neck Pathol. 2008;2:316–23.
Evans HL, Luna MA. Polymorphous low-grade adenocarcinoma: a study of 40 cases with long-term follow up and an evaluation of the importance of papillary areas. Am J Surg Pathol. 2000;24:1319–28.
Castle JT, Thompson LD, Frommelt RA, Wenig BM, Kessler HP. Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases. Cancer. 1999;86:207–19.
Mitchell DA, Eveson JW, Ord RA. Polymorphous low-grade adenocarcinoma of minor salivary glands—a report of three cases. Br J Oral Maxillofac Surg. 1989;27:494–500.
Perez-Ordonez B, Linkov I, Huvos AG. Polymorphous low-grade adenocarcinoma of minor salivary glands: a study of 17 cases with emphasis on cell differentiation. Histopathology. 1998;32:521–9.
Bishop JA, Yonescu R, Batista D, Begum S, Eisele DW, Westra WH. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. Hum Pathol. 2013;44:1982–8.
Patel KR, Solomon IH, El-Mofty SK, Lewis JS Jr, Chernock RD. Mammaglobin and S-100 immunoreactivity in salivary gland carcinomas other than mammary analogue secretory carcinoma. Hum Pathol. 2013;44:2501–8.
Simpson RH, Desai S, Di Palma S. Salivary duct carcinoma in situ of the parotid gland. Histopathology. 2008;53:416–25.
Simpson RH. Salivary duct carcinoma: new developments—morphological variants including pure in situ high grade lesions; proposed molecular classification. Head Neck Pathol. 2013;7(Suppl 1):S48–58.
Thackray AC, Lucas RB, Armed Forces Institute of Pathology (AFIP) Atlas of Tumor Pathology. Tumors of the Major Salivary Glands (second series fascicle 10); Maryland: ARP Press; 1974. p. 62–63.
Milchgrub S, Gnepp DR, Vuitch F, Delgado R, Albores-Saavedra J. Hyalinizing clear cell carcinoma of salivary gland. Am J Surg Pathol. 1994;18:74–82.
Ellis G. Clear cell carcinoma, not otherwise specified. In: Barnes L, Eveson JW, Reichart P, et al., editors. Pathology and genetics head and neck tumors. Lyon: IARC Press; 2005. p. 227.
Dardick I, Leong I. Clear cell carcinoma: review of its histomorphogenesis and classification as a squamous cell lesion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:399–405.
Ellis GL, Auclair PL, Armed Forces Institute of Pathology (AFIP) Atlas of Tumor Pathology. Tumors of the Salivary Glands (fourth series fascicle 9) Maryland: ARP Press; 2008. p. 301–309.
Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, Perez-Ordoñez B, Have C, Asa SL, Leong IT, Bradley G, Klieb H, Weinreb I. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosom Cancer. 2011;50:559–70.
Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N, Edelman M, Rosenberg AE, Nielsen GP, Dal Cin P, Fletcher CD. 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 Chromosom Cancer. 2010;49:1114–24.
Thway K, Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol. 2012;36:e1–11.
Kauzman A, Tabet JC, Stiharu TI. Hyalinizing clear cell carcinoma: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:e26–34.
Solar AA, Schmidt BL, Jordan RC. Hyalinizing clear cell carcinoma: case series and comprehensive review of the literature. Cancer. 2009;115:75–83.
Weinreb I. Hyalinizing clear cell carcinoma of salivary gland: a review and update. Head Neck Pathol. 2013;7(Suppl 1):S20–9.
O’Sullivan-Mejia ED, Massey HD, Faquin WC, Powers CN. Hyalinizing clear cell carcinoma: report of eight cases and a review of literature. Head Neck Pathol. 2009;3:179–85.
Tanguay J, Weinreb I. What the EWSR1-ATF1 fusion has taught us about hyalinizing clear cell carcinoma. Head Neck Pathol. 2013;7:28–34.
O’Regan E, Shandilya M, Gnepp DR, Timon C, Toner M. Hyalinizing clear cell carcinoma of salivary gland: an aggressive variant. Oral Oncol. 2004;40:348–52.
Fulciniti F, Pia Curcio M, Liguori G, Aquino G, Botti G, Campanile AC, DeCecio R, Pavone E, Aversa C, Perri F, Caponigro F, Ionna F. Hyalinizing clear cell carcinoma of the parotid gland: Report of a recurrent case with aggressive cytomorphology and behavior diagnosed on fine-needle cytology sample. Diagn Cytopathol. 2013; doi:10.1002/dc.22956.
Wang B, Brandwein M, Gordon R, Robinson R, Urken M, Zarbo RJ. Primary salivary clear cell tumors–a diagnostic approach: a clinicopathologic and immunohistochemical study of 20 patients with clear cell carcinoma, clear cell myoepithelial carcinoma, and epithelial–myoepithelial carcinoma. Arch Pathol Lab Med. 2002;126:676–85.
Jin R, Craddock KJ, Irish JC, Perez-Ordonez B, Weinreb I. Recurrent hyalinizing clear cell carcinoma of the base of tongue with high-grade transformation and EWSR1 gene rearrangement by FISH. Head Neck Pathol. 2012;6:389–94.
Yamashita K, Kawakami F, Nakashima Y, Murakami K. Clear cell carcinoma of the minor salivary gland: an autopsy case with multiple metastases 29 years after the initial surgery and a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:819–25.
Bilodeau EA, Weinreb I, Antonescu CR, Zhang L, Dacic S, Muller S, Barker B, Seethala RR. Clear cell odontogenic carcinomas show EWSR1 rearrangements: a novel finding and a biological link to salivary clear cell carcinomas. Am J Surg Pathol. 2013;37:1001–5.
Kumar M, Fasanmade A, Barrett AW, Mack G, Newman L, Hyde NC. Metastasizing clear cell odontogenic carcinoma: a case report and review of the literature. Oral Oncol. 2003;39:190–4.
Brandwein M, Said-Al-Naief N, Gordon R, Urken M. Clear cell odontogenic carcinoma: report of a case and analysis of the literature. Arch Otolaryngol Head Neck Surg. 2002;128:1089–95.
Mosqueda-Taylor A, Meneses-García A, Ruíz-Godoy Rivera LM, de Lourdes Suárez-Roa M. Clear cell odontogenic carcinoma of the mandible. J Oral Pathol Med. 2002;31:439–41.
Bilodeau EA, Hoschar AP, Barnes EL, Hunt JL, Seethala RR. Clear cell carcinoma and clear cell odontogenic carcinoma: a comparative clinicopathologic and immunohistochemical study. Head Neck Pathol. 2011;5:101–7.
Berho M, Huvos AG. Central hyalinizing clear cell carcinoma of the mandible and the maxilla a clinicopathologic study of two cases with an analysis of the literature. Hum Pathol. 1999;30:101–5.
Zur KB, Brandwein M, Wang B, Som P, Gordon R, Urken ML. 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. 2002;128:441–7.
Moh’d Hadi U, Kahwaji GJ, Mufarrij AA, Tawil A, Noureddine B. Low grade primary clear cell carcinoma of the sinonasal tract. Rhinology. 2002;40:44–7.
Storck K, Hadi UM, Simpson R, Ramer M, Brandwein-Gensler M. Sinonasal renal cell-like adenocarcinoma: a report on four patients. Head Neck Pathol. 2008;2:75–80.
Cheng LH, Lin YS, Lee JC. Primary clear cell carcinoma of the nasopharynx. Otolaryngol Head Neck Surg. 2008;139:592–3.
Negahban S, Daneshbod Y, Khademi B, Rasekhi AR, Soleimanpour H. Sinonasal clear cell adenocarcinoma: a case report. Acta Cytol. 2009;53:597–600.
Huang XJ, Chen JD, Shi QF. One case with primary clear-cell carcinoma of nasal cavity. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011;46:245–6.
Hong J, Bi Y, Li P, Fang L. Primary nasal clear cell carcinoma: a case report and literature review. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013;27:239–40.
Li P, Yin WH, Yao XJ, Wan L, Chen GR. Primary clear cell carcinoma of nasal cavity: report of a case. Zhonghua Bing Li Xue Za Zhi. 2011;40:52–3.
Suzuki K, Wanibuchi M, Akiyama Y, Ikeda J, Minamida Y, Hasegawa T, Houkin K, Mikuni N. Primary clear cell carcinoma of the skull base and paranasal cavity: a case report. No Shinkei Geka. 2012;40:617–21.
Moran CA, Wenig BM, Mullick FG. Primary adenocarcinoma of the nasal cavity and paranasal sinuses. Ear Nose Throat J. 1991;70(12):821–8.
Newman JP, Funkhouser WK. Pathologic quiz case 1. Clear cell carcinoma of the nasal cavity. Arch Otolaryngol Head Neck Surg. 1993;119:1046–9.
Heffner DK, Hyams VJ, Hauck KW, Lingeman C. Low-grade adenocarcinoma of the nasal cavity and paranasal sinuses. Cancer. 1982;50:312–22.
Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol. 2005;29:167–78.
Brandwein-Gensler M, Smith RV, Wang B, Penner C, Theilken A, Broughel D, Schiff B, Owen RP, Smith J, Sarta C, Hebert T, Nason R, Ramer M, DeLacure M, Hirsch D, Myssiorek D, Heller K, Prystowsky M, Schlecht NF, Negassa A. Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2010;34:676–88.
Li Y, Bai S, Carroll W, Dayan D, Dort JC, Heller K, Jour G, Lau H, Penner C, Prystowsky M, Rosenthal E, Schlecht NF, Smith RV, Urken M, Vered M, Wang B, Wenig B, Negassa A, Brandwein-Gensler M. Validation of the risk model: high-risk classification and tumor pattern of invasion predict outcome for patients with low-stage oral cavity squamous cell carcinoma. Head Neck Pathol. 2013;7:211–23.
Vered M, Dayan D, Dobriyan A, Yahalom R, Shalmon B, Barshack I, Bedrin L, Talmi YP, Taicher S. Oral tongue squamous cell carcinoma: recurrent disease is associated with histopathologic risk score and young age. J Cancer Res Clin Oncol. 2010;136:1039–48.
de Matos FR, Lima E, Queiroz LM, da Silveira EJ. Analysis of inflammatory infiltrate, perineural invasion, and risk score can indicate concurrent metastasis in squamous cell carcinoma of the tongue. J Oral Maxillofac Surg. 2012;70:1703–10.
Brandwein-Gensler M, Chiosea S, unpublished data.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Brandwein-Gensler, M., Wei, S. Envisioning the Next WHO Head and Neck Classification. Head and Neck Pathol 8, 1–15 (2014). https://doi.org/10.1007/s12105-014-0529-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12105-014-0529-5