Does Lack of EWSR1-ATF1 Fusion Exclude Diagnosis of Salivary Gland Clear Cell Carcinoma?

Sibel Sensu, Nusret Erdogan, Kayhan Basak, Egzona Qipa, Murat Buyukdogan


Introduction: Ewing sarcoma breakpoint region 1- activating transcription factor 1 (EWSR1-ATF1) fusion is mentioned as a diagnostic marker in favor of clear cell carcinoma in the differential diagnosis of clear cell neoplasms of salivary glands. However, in literature, its positivity is reported between 82% and 93%. In salivary glands, various benign and malignant primary tumors, as well as odontogenic neoplasms and metastatic cases, present with a varied number of clear cells. Clear cell carcinoma of the salivary gland is a rare entity with distinct histochemistry and immunohistochemistry features.

Case Presentation: We present a clear cell carcinoma of the salivary gland showing cytoplasmic Periodic acid–Schiff (PAS) (+), mucin (-) staining, cytokeratin (CK), CK7, and P63 immunoreactivity without EWSR1-ATF1 fusion.

Conclusions: We conclude that clinical, morphological, and immunohistochemical analyses should be the guide for diagnosis even though molecular analysis does not support it.


clear cell carcinoma, ESWR1-ATF1, immunohistochemistry, salivary gland


Ant A, Toprak F, Duran A, et al. The demographic and clinicopathological features of salivary gland tumors in Turkey. Ortadogu Tıp Derg. 2019;11(4):450-5.

Bhamjee F, Jeftha A, Holmes H, et al. Hyalinising clear cell carcinoma of the maxilla in a young adult female. SADJ. 2018;73(2):86–8.

Devaraju RR, Reddy S, Yashoda, et al. Clear cell odontogenic carcinoma versus hyalinizing clear cell carcinoma: A diagnostic dilemma. J Indian Acad Oral Med. 2014;26(3):319-22.

Albergotti WG, Bilodeau EA, Byrd JK, et al. Hyalinizing clear cell carcinoma of the head and neck: Case series and update. Head Neck. 2016;38:426–33.

Seethala RR, Stenman G. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland. Head and Neck Pathol. 2017;11(1):55-67.

Yang XH, Liu L, Shi YY, et al. Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck: clinical and histopathological analysis. Int J Oral Maxillofac Surg. 2018;47:692–8.

Shah AA, LeGallo RD, Zante A, et al. EWSR1 genetic rearrangements in salivary gland tumors. a specific and very common feature of hyalinizing clear cell carcinoma. Am J Surg Pathol. 2013;37:571–8.

Weinreb I. Hyalinizing clear cell carcinoma of salivary gland: a review and update. Head and Neck Pathol. 2013;7:S20–S29.

Nakano T, Yamamoto H, Nishijima T, et al. Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses. Virchows Arch. 2015;466(1):37-43.

Vogels R, Baumhoer D, van Gorp J, et al. Clear cell odontogenic carcinoma: occurrence of EWSR1-CREB1 as alternative fusion gene to EWSR1-ATF1. Head Neck Pathol. 2019;13(2):225-30.

Skalova A, Weinreb I, Hyrzca M, et al. Clear cell myoepithelial carcinoma of salivary glands showing EWSR1 rearrangement: Molecular analysis of 94 salivary gland carcinomas with prominent clear cell component. Am J Surg Pathol. 2015;39(3):338-48.

Sanjai K, Shivalingaiah D, Sharath R, Pandey B. Clear cell carcinoma of palatine salivary gland: A diagnostic challenge. J Oral Maxillofac Pathol. 2018;22:128-31.

Full Text: PDF

DOI: 10.33371/ijoc.v15i3.795

Article Metrics

Abstract view : 69 times
PDF - 39 times


  • There are currently no refbacks.

Copyright (c) 2021 Indonesian Journal of Cancer

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.