Skip to main content
Erschienen in: Head and Neck Pathology 2/2020

02.03.2020 | 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

verfasst von: Emilija Todorovic, Brendan C. Dickson, Ilan Weinreb

Erschienen in: Head and Neck Pathology | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Salivary Gland Cancer in the Era of Routine Next-Generation Sequencing
verfasst von
Emilija Todorovic
Brendan C. Dickson
Ilan Weinreb
Publikationsdatum
02.03.2020
Verlag
Springer US
Erschienen in
Head and Neck Pathology / Ausgabe 2/2020
Elektronische ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-020-01140-4

Weitere Artikel der Ausgabe 2/2020

Head and Neck Pathology 2/2020 Zur Ausgabe

Proceeding of the North American Society of Head and Neck Pathology Companion Meeting, March 1, 2020, Los Angeles, California

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): An Update

Proceeding of the North American Society of Head and Neck Pathology Companion Meeting, March 1, 2020, Los Angeles, California

Intraoperative Margin Assessment in Head and Neck Cancer: A Case of Misuse and Abuse?

Proceeding of the North American Society of Head and Neck Pathology Companion Meeting, March 1, 2020, Los Angeles, California

Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma in 2020: Where Are We Now and Where Are We Going?

Neu im Fachgebiet Pathologie