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Published in: Head and Neck Pathology 2/2020

01-06-2020 | Ameloblastoma | Proceeding of the North American Society of Head and Neck Pathology Companion Meeting, March 1, 2020, Los Angeles, California

Salivary Gland Cancer in the Era of Routine Next-Generation Sequencing

Authors: Emilija Todorovic, Brendan C. Dickson, Ilan Weinreb

Published in: Head and Neck Pathology | Issue 2/2020

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Abstract

Next-Generation Sequencing (NGS) is being utilized with increasing frequency in the characterization of salivary gland tumours. The potential scenarios which may be encountered by using this technique in routine practice will be outlined in further text by drawing from our own clinical experience. These include oncocytic mucoepidermoid carcinomas with unusual variant morphology (and negative MAML2 fluorescent in-situ hybridization results), a diagnosis of ameloblastoma changed to adenoid cystic carcinoma (due to MYBL1 fusion presence), a salivary duct carcinoma with an ETV6-NTRK3 fusion (otherwise seen in secretory carcinomas) and novel fusion partners such as EWSR1-BEND2 (otherwise seen in pancreatic neuroendocrine carcinomas). As NGS continues to develop and more widespread clinical implementation increases, we must be cognisant of the need for proper interpretation and in some cases verification using a secondary technique, the limitations of this technique, and the ethical dilemmas one faces when encountering a novel fusion.
Literature
1.
go back to reference World Health Organization classification of tumours: pathology and genetics of head and neck tumours. 4th Edition [press release]. Lyon2017. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. 4th Edition [press release]. Lyon2017.
2.
go back to reference Foote FW Jr, Frazell EL. Tumors of the major salivary glands. Cancer. 1953;6(6):1065–133.PubMed Foote FW Jr, Frazell EL. Tumors of the major salivary glands. Cancer. 1953;6(6):1065–133.PubMed
3.
go back to reference Skalova A, Stenman G, Simpson RHW, Hellquist H, Slouka D, Svoboda T, et al. The role of molecular testing in the differential diagnosis of salivary gland carcinomas. Am J Surg Pathol. 2018;42(2):e11–e27.PubMed Skalova A, Stenman G, Simpson RHW, Hellquist H, Slouka D, Svoboda T, et al. The role of molecular testing in the differential diagnosis of salivary gland carcinomas. Am J Surg Pathol. 2018;42(2):e11–e27.PubMed
4.
go back to reference Griffith CC, Schmitt AC, Little JL, Magliocca KR. New developments in salivary gland pathology: clinically useful ancillary testing and new potentially targetable molecular alterations. Arch Pathol Lab Med. 2017;141(3):381–95.PubMed Griffith CC, Schmitt AC, Little JL, Magliocca KR. New developments in salivary gland pathology: clinically useful ancillary testing and new potentially targetable molecular alterations. Arch Pathol Lab Med. 2017;141(3):381–95.PubMed
5.
go back to reference Dickson BC, Swanson D. Targeted RNA sequencing: A routine ancillary technique in the diagnosis of bone and soft tissue neoplasms. Genes Chromosomes Cancer. 2019;58(2):75–877.PubMed Dickson BC, Swanson D. Targeted RNA sequencing: A routine ancillary technique in the diagnosis of bone and soft tissue neoplasms. Genes Chromosomes Cancer. 2019;58(2):75–877.PubMed
6.
go back to reference Bishop JA, Weinreb I, Swanson D, Westra WH, Qureshi HS, Sciubba J, et al. Microsecretory adenocarcinoma: a novel salivary gland tumor characterized by a recurrent MEF2C-SS18 fusion. Am J Surg Pathol. 2019;43(8):1023–32.PubMed Bishop JA, Weinreb I, Swanson D, Westra WH, Qureshi HS, Sciubba J, et al. Microsecretory adenocarcinoma: a novel salivary gland tumor characterized by a recurrent MEF2C-SS18 fusion. Am J Surg Pathol. 2019;43(8):1023–32.PubMed
7.
go back to reference Cipriani NA, Lusardi JJ, McElherne J, Pearson AT, Olivas AD, Fitzpatrick C, et al. Mucoepidermoid Carcinoma: A Comparison Of Histologic grading systems and relationship to MAML2 rearrangement and prognosis. Am J Surg Pathol. 2019;43(7):885–97.PubMed Cipriani NA, Lusardi JJ, McElherne J, Pearson AT, Olivas AD, Fitzpatrick C, et al. Mucoepidermoid Carcinoma: A Comparison Of Histologic grading systems and relationship to MAML2 rearrangement and prognosis. Am J Surg Pathol. 2019;43(7):885–97.PubMed
8.
go back to reference Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50(7):559–70.PubMed Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50(7):559–70.PubMed
9.
go back to reference Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731–47.PubMedPubMedCentral Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731–47.PubMedPubMedCentral
10.
go back to reference Santana T, Pavel A, Martinek P, Steiner P, Grossmann P, Baneckova M, et al. Biomarker Immunoprofile and molecular characteristics in salivary duct carcinoma: Clinicopathologic and prognostic implications. Hum Pathol. 2019. Santana T, Pavel A, Martinek P, Steiner P, Grossmann P, Baneckova M, et al. Biomarker Immunoprofile and molecular characteristics in salivary duct carcinoma: Clinicopathologic and prognostic implications. Hum Pathol. 2019.
11.
go back to reference Thierauf J, Ramamurthy N, Jo VY, Robinson H, Frazier RP, Gonzalez J, et al. Clinically integrated molecular diagnostics in adenoid cystic carcinoma. Oncologist. 2019. Thierauf J, Ramamurthy N, Jo VY, Robinson H, Frazier RP, Gonzalez J, et al. Clinically integrated molecular diagnostics in adenoid cystic carcinoma. Oncologist. 2019.
12.
go back to reference Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731–9.PubMedPubMedCentral Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731–9.PubMedPubMedCentral
13.
go back to reference Italiano A, Di Mauro I, Rapp J, Pierron G, Auger N, Alberti L, et al. Clinical effect of molecular methods in sarcoma diagnosis (GENSARC): a prospective, multicentre, observational study. Lancet Oncol. 2016;17(4):532–8.PubMed Italiano A, Di Mauro I, Rapp J, Pierron G, Auger N, Alberti L, et al. Clinical effect of molecular methods in sarcoma diagnosis (GENSARC): a prospective, multicentre, observational study. Lancet Oncol. 2016;17(4):532–8.PubMed
14.
go back to reference Dogan S. Novel rearrangements in salivary gland tumors detected by an RNA-based targeted next-generation sequencing assay. Lab Investig. 2019;99:10. Dogan S. Novel rearrangements in salivary gland tumors detected by an RNA-based targeted next-generation sequencing assay. Lab Investig. 2019;99:10.
15.
go back to reference Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, et al. NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2019. Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, et al. NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2019.
16.
go back to reference Solomon JP, Hechtman JF. Detection of NTRK fusions: merits and limitations of current diagnostic platforms. Cancer Res. 2019;79(13):3163–8.PubMed Solomon JP, Hechtman JF. Detection of NTRK fusions: merits and limitations of current diagnostic platforms. Cancer Res. 2019;79(13):3163–8.PubMed
17.
go back to reference Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the association for molecular pathology, american society of clinical oncology, and college of american pathologists. J Mol Diagn. 2017;19(1):4–23.PubMedPubMedCentral Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the association for molecular pathology, american society of clinical oncology, and college of american pathologists. J Mol Diagn. 2017;19(1):4–23.PubMedPubMedCentral
18.
go back to reference Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, et al. A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol. 2016;40(2):224–35.PubMedPubMedCentral Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, et al. A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol. 2016;40(2):224–35.PubMedPubMedCentral
19.
go back to reference Moller E, Stenman G, Mandahl N, Hamberg H, Molne L, van den Oord JJ, et al. POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. J Pathol. 2008;215(1):78–86.PubMed Moller E, Stenman G, Mandahl N, Hamberg H, Molne L, van den Oord JJ, et al. POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. J Pathol. 2008;215(1):78–86.PubMed
20.
go back to reference Garcia JJ, Hunt JL, Weinreb I, McHugh JB, Barnes EL, Cieply K, et al. Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test. Hum Pathol. 2011;42(12):2001–9.PubMed Garcia JJ, Hunt JL, Weinreb I, McHugh JB, Barnes EL, Cieply K, et al. Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test. Hum Pathol. 2011;42(12):2001–9.PubMed
21.
go back to reference Bishop JA, Cowan ML, Shum CH, Westra WH. MAML2 rearrangements in variant forms of mucoepidermoid carcinoma: ancillary diagnostic testing for the ciliated and warthin-like variants. Am J Surg Pathol. 2018;42(1):130–6.PubMedPubMedCentral Bishop JA, Cowan ML, Shum CH, Westra WH. MAML2 rearrangements in variant forms of mucoepidermoid carcinoma: ancillary diagnostic testing for the ciliated and warthin-like variants. Am J Surg Pathol. 2018;42(1):130–6.PubMedPubMedCentral
22.
go back to reference Seethala RR, Dacic S, Cieply K, Kelly LM, Nikiforova MN. A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. Am J Surg Pathol. 2010;34(8):1106–21.PubMed Seethala RR, Dacic S, Cieply K, Kelly LM, Nikiforova MN. A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. Am J Surg Pathol. 2010;34(8):1106–21.PubMed
23.
go back to reference Luk PP, Wykes J, Selinger CI, Ekmejian R, Tay J, Gao K, et al. Diagnostic and prognostic utility of Mastermind-like 2 (MAML2) gene rearrangement detection by fluorescent in situ hybridization (FISH) in mucoepidermoid carcinoma of the salivary glands. Oral Surg. 2016;121(5):530–41. Luk PP, Wykes J, Selinger CI, Ekmejian R, Tay J, Gao K, et al. Diagnostic and prognostic utility of Mastermind-like 2 (MAML2) gene rearrangement detection by fluorescent in situ hybridization (FISH) in mucoepidermoid carcinoma of the salivary glands. Oral Surg. 2016;121(5):530–41.
24.
go back to reference Kang H, Tan M, Bishop JA, Jones S, Sausen M, Ha PK, et al. Whole-exome sequencing of salivary gland mucoepidermoid carcinoma. Clin Cancer Res. 2017;23(1):283–8.PubMed Kang H, Tan M, Bishop JA, Jones S, Sausen M, Ha PK, et al. Whole-exome sequencing of salivary gland mucoepidermoid carcinoma. Clin Cancer Res. 2017;23(1):283–8.PubMed
25.
go back to reference Lee H, Roh JL, Choi YJ, Choi J, Cho KJ. High grade transformation in mucoepidermoid carcinoma of the minor salivary gland with polyploidy of the rearranged MAML2 gene. Head Neck Pathol. 2019. Lee H, Roh JL, Choi YJ, Choi J, Cho KJ. High grade transformation in mucoepidermoid carcinoma of the minor salivary gland with polyploidy of the rearranged MAML2 gene. Head Neck Pathol. 2019.
26.
go back to reference Doumas S, Barrett AW, Carrillo M, Tighe JV. Synchronous metastatic adenoid cystic and squamous cell carcinoma of the cervical lymph nodes 31 years after ablation of the primary palatal tumour. Br J Oral Maxillofac Surg. 2013;51(7):e190–e191191.PubMed Doumas S, Barrett AW, Carrillo M, Tighe JV. Synchronous metastatic adenoid cystic and squamous cell carcinoma of the cervical lymph nodes 31 years after ablation of the primary palatal tumour. Br J Oral Maxillofac Surg. 2013;51(7):e190–e191191.PubMed
27.
go back to reference van der Wal JE, Snow GB, Karim AB, van der Waal I. Adenoid cystic carcinoma of the palate with squamous metaplasia or basaloid-squamous carcinoma? Report of a case. J Oral Pathol Med. 1994;23(10):461–4.PubMed van der Wal JE, Snow GB, Karim AB, van der Waal I. Adenoid cystic carcinoma of the palate with squamous metaplasia or basaloid-squamous carcinoma? Report of a case. J Oral Pathol Med. 1994;23(10):461–4.PubMed
28.
go back to reference Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, et al. Adenoid cystic carcinoma of the head and neck—An update. Oral Oncol. 2015;51(7):652–61.PubMed Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, et al. Adenoid cystic carcinoma of the head and neck—An update. Oral Oncol. 2015;51(7):652–61.PubMed
29.
go back to reference Skalova A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34(5):599–608.PubMed Skalova A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34(5):599–608.PubMed
30.
go back to reference Xu B, Haroon Al Rasheed MR, Antonescu CR, Alex D, Frosina D, Ghossein R, et al. Pan-Trk immunohistochemistry is a sensitive and specific ancillary tool in diagnosing secretory carcinoma of salivary gland and detecting ETV6-NTRK3 fusion. Histopathology. 2019. https://doi.org/10.1111/his.13981.PubMed Xu B, Haroon Al Rasheed MR, Antonescu CR, Alex D, Frosina D, Ghossein R, et al. Pan-Trk immunohistochemistry is a sensitive and specific ancillary tool in diagnosing secretory carcinoma of salivary gland and detecting ETV6-NTRK3 fusion. Histopathology. 2019. https://​doi.​org/​10.​1111/​his.​13981.PubMed
31.
go back to reference Dalin MG, Desrichard A, Katabi N, Makarov V, Walsh LA, Lee KW, et al. comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to apocrine breast cancer. Clin Cancer Res. 2016;22(18):4623–33.PubMedPubMedCentral Dalin MG, Desrichard A, Katabi N, Makarov V, Walsh LA, Lee KW, et al. comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to apocrine breast cancer. Clin Cancer Res. 2016;22(18):4623–33.PubMedPubMedCentral
32.
go back to reference Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017;543(7643):65–71.PubMed Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017;543(7643):65–71.PubMed
Metadata
Title
Salivary Gland Cancer in the Era of Routine Next-Generation Sequencing
Authors
Emilija Todorovic
Brendan C. Dickson
Ilan Weinreb
Publication date
01-06-2020
Publisher
Springer US
Published in
Head and Neck Pathology / Issue 2/2020
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-020-01140-4

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