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Genomic Applications in Salivary Gland Tumors

  • Todd M. StevensEmail author
  • Justin A. Bishop
Chapter

Abstract

Molecular diagnostics have become indispensable to the pathologist’s workup of salivary gland tumors and to the treating clinician. Molecular advances have led to the identification of previously unidentified entities and variants in salivary gland pathology and are increasingly used to help guide personalized therapy. In this chapter, the salient molecular signatures of salivary gland neoplasms will be presented as they relate to diagnosis and therapy.

Keywords

Salivary gland tumors Pathogenesis Genomics Molecular pathology Histology Diagnosis Prognosis Targeted therapy 

References

  1. 1.
    Skalova A, Weinreb I, Hyrcza M, Simpson RH, Laco J, Agaimy A, 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.PubMedGoogle Scholar
  2. 2.
    Bahrami A, Perez-Ordonez B, Dalton JD, Weinreb I. An analysis of PLAG1 and HMGA2 rearrangements in salivary duct carcinoma and examination of the role of precursor lesions. Histopathology. 2013;63(2):250–62.PubMedGoogle Scholar
  3. 3.
    Bahrami A, Dalton JD, Shivakumar B, Krane JF. PLAG1 alteration in carcinoma ex pleomorphic adenoma: immunohistochemical and fluorescence in situ hybridization studies of 22 cases. Head Neck Pathol. 2012;6(3):328–35.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Voz ML, Agten NS, Van de Ven WJ, Kas K. PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II. Cancer Res. 2000;60(1):106–13.PubMedGoogle Scholar
  5. 5.
    Jo VY, Sholl LM, Krane JF. Distinctive patterns of CTNNB1 (beta-catenin) alterations in salivary gland basal cell adenoma and basal cell adenocarcinoma. Am J Surg Pathol. 2016;40(8):1143–50.PubMedGoogle Scholar
  6. 6.
    Katabi N, Ghossein R, Ho A, Dogan S, Zhang L, Sung YS, et al. Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts. Hum Pathol. 2015;46(1):26–33.PubMedGoogle Scholar
  7. 7.
    Sato M, Yamamoto H, Hatanaka Y, Nishijima T, Jiromaru R, Yasumatsu R, et al. Wnt/beta-catenin signal alteration and its diagnostic utility in basal cell adenoma and histologically similar tumors of the salivary gland. Pathol Res Pract. 2018;214(4):586–92.PubMedGoogle Scholar
  8. 8.
    El Hallani S, Udager AM, Bell D, Fonseca I, Thompson LDR, Assaad A, et al. Epithelial-myoepithelial carcinoma: frequent morphologic and molecular evidence of preexisting pleomorphic adenoma, common HRAS mutations in PLAG1-intact and HMGA2-intact cases, and occasional TP53, FBXW7, and SMARCB1 alterations in high-grade cases. Am J Surg Pathol. 2018;42(1):18–27.PubMedGoogle Scholar
  9. 9.
    Bishop AJ, Westra HW. MYB translocation status in salivary gland epithelial-myoepithelial carcinoma: evaluation of classic, variant, and hybrid forms. Am J Surg Pathol. 2018;42(3):319–25.PubMedPubMedCentralGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    Carlson J, Licitra L, Locati L, Raben D, Persson F, Stenman G. Salivary gland cancer: an update on present and emerging therapies. Am Soc Clin Oncol Educ Book. 2013;33:257–63.Google Scholar
  12. 12.
    Andersson MK, Afshari MK, Andren Y, Wick MJ, Stenman G. Targeting the oncogenic transcriptional regulator MYB in adenoid cystic carcinoma by inhibition of IGF1R/AKT signaling. J Natl Cancer Inst. 2017;109(9)  https://doi.org/10.1093/jnci/djx017.
  13. 13.
    Rettig EM, Talbot CC Jr, Sausen M, Jones S, Bishop JA, Wood LD, et al. Whole-genome sequencing of salivary gland adenoid cystic carcinoma. Cancer Prev Res. 2016;9(4):265–74.Google Scholar
  14. 14.
    Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS, et al. Whole exome sequencing of adenoid cystic carcinoma. J Clin Invest. 2013;123(7):2965–8.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Brayer KJ, Frerich CA, Kang H, Ness SA. Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 2016;6(2):176–87.PubMedGoogle Scholar
  16. 16.
    Mitani Y, Liu B, Rao PH, Borra VJ, Zafereo M, Weber RS, et al. Novel MYBL1 gene rearrangements with recurrent MYBL1-NFIB fusions in salivary adenoid cystic carcinomas lacking t(6;9) translocations. Clin Cancer Res. 2016;22(3):725–33.PubMedGoogle Scholar
  17. 17.
    Persson M, Andren Y, Moskaluk CA, Frierson HF Jr, Cooke SL, Futreal PA, et al. Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma. Genes Chromosomes Cancer. 2012;51(8):805–17.PubMedGoogle Scholar
  18. 18.
    Brill LB 2nd, Kanner WA, Fehr A, Andren Y, Moskaluk CA, Loning T, et al. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24(9):1169–76.PubMedGoogle Scholar
  19. 19.
    Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N, et al. 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 Chromosomes Cancer. 2010;49(12):1114–24.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Stevens TM, Qarmali M, Morlote D, Mikhail FM, Swensen J, Gatalica Z, et al. Malignant Ewing-like neoplasm with an EWSR1-KLF15 fusion: at the crossroads of a myoepithelial carcinoma and a Ewing-like sarcoma. A case report with treatment options. Int J Surg Pathol. 2018;26(5):440–7.  https://doi.org/10.1177/1066896918755009.PubMedGoogle Scholar
  21. 21.
    Shah AA, LeGallo RD, van Zante A, Frierson HF Jr, Mills SE, Berean KW, 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(4):571–8.PubMedGoogle Scholar
  22. 22.
    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.PubMedGoogle Scholar
  23. 23.
    Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, et al. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet. 1993;4(4):341–5.PubMedGoogle Scholar
  24. 24.
    Shinomiya H, Ito Y, Kubo M, Yonezawa K, Otsuki N, Iwae S, et al. Expression of amphiregulin in mucoepidermoid carcinoma of the major salivary glands: a molecular and clinicopathological study. Hum Pathol. 2016;57:37–44.PubMedGoogle Scholar
  25. 25.
    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.PubMedGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Wang K, McDermott JD, Schrock AB, Elvin JA, Gay L, Karam SD, et al. Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations. Ann Oncol. 2017;28(4):748–53.PubMedGoogle Scholar
  28. 28.
    Jee KJ, Persson M, Heikinheimo K, Passador-Santos F, Aro K, Knuutila S, et al. Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma. Mod Pathol. 2013;26(2):213–22.PubMedGoogle Scholar
  29. 29.
    Bishop JA, Yonescu R, Batista D, Warnock GR, Westra WH. Glandular odontogenic cysts (GOCs) lack MAML2 rearrangements: a finding to discredit the putative nature of GOC as a precursor to central mucoepidermoid carcinoma. Head Neck Pathol. 2014;8(3):287–90.PubMedPubMedCentralGoogle Scholar
  30. 30.
    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.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Behboudi A, Winnes M, Gorunova L, van den Oord JJ, Mertens F, Enlund F, et al. Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion. Genes Chromosomes Cancer. 2005;43(2):202–5.PubMedGoogle Scholar
  32. 32.
    Behboudi A, Enlund F, Winnes M, Andren Y, Nordkvist A, Leivo I, et al. Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene. Genes Chromosomes Cancer. 2006;45(5):470–81.PubMedGoogle Scholar
  33. 33.
    Anzick SL, Chen WD, Park Y, Meltzer P, Bell D, El-Naggar AK, et al. Unfavorable prognosis of CRTC1-MAML2 positive mucoepidermoid tumors with CDKN2A deletions. Genes Chromosomes Cancer. 2010;49(1):59–69.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Chiosea SI, Dacic S, Nikiforova MN, Seethala RR. Prospective testing of mucoepidermoid carcinoma for the MAML2 translocation: clinical implications. Laryngoscope. 2012;122(8):1690–4.PubMedGoogle Scholar
  35. 35.
    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.PubMedGoogle Scholar
  36. 36.
    Alassiri AH, Ali RH, Shen Y, Lum A, Strahlendorf C, Deyell R, et al. ETV6-NTRK3 is expressed in a subset of ALK-negative inflammatory myofibroblastic tumors. Am J Surg Pathol. 2016;40(8):1051–61.PubMedGoogle Scholar
  37. 37.
    Leeman-Neill RJ, Kelly LM, Liu P, Brenner AV, Little MP, Bogdanova TI, et al. ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer. 2014;120(6):799–807.PubMedGoogle Scholar
  38. 38.
    Skalova A, Vanecek T, Simpson RH, Laco J, Majewska H, Baneckova M, et al. Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 ETV6 gene rearranged tumors with lack of detection of classical ETV6-NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion. Am J Surg Pathol. 2016;40(1):3–13.PubMedGoogle Scholar
  39. 39.
    Ito Y, Ishibashi K, Masaki A, Fujii K, Fujiyoshi Y, Hattori H, et al. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion. Am J Surg Pathol. 2015;39(5):602–10.PubMedGoogle Scholar
  40. 40.
    Skalova MA, Vanecek HWT, Martinek JP, Weinreb JI, Stevens JT, Simpson JR, et al. Molecular profiling of mammary analog secretory carcinoma revealed a subset of tumors harboring a novel ETV6-RET translocation: report of 10 cases. Am J Surg Pathol. 2018;42(2):234–46.PubMedGoogle Scholar
  41. 41.
    Stevens TM, Kovalovsky AO, Velosa C, Shi Q, Dai Q, Owen RP, et al. Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study. Mod Pathol. 2015;28(8):1084–100.PubMedGoogle Scholar
  42. 42.
    Dettloff J, Seethala RR, Stevens TM, Brandwein-Gensler M, Centeno BA, Otto K, et al. Mammary analog secretory carcinoma (MASC) involving the thyroid gland: a report of the first 3 cases. Head Neck Pathol. 2017;11(2):124–30.PubMedGoogle Scholar
  43. 43.
    Bishop JA, Taube JM, Su A, Binder SW, Kazakov DV, Michal M, et al. Secretory carcinoma of the skin harboring ETV6 gene fusions: a cutaneous analogue to secretory carcinomas of the breast and salivary glands. Am J Surg Pathol. 2017;41(1):62–6.PubMedGoogle Scholar
  44. 44.
    Weinreb I, Bishop JA, Chiosea SI, Seethala RR, Perez-Ordonez B, Zhang L, et al. Recurrent RET gene rearrangements in intraductal carcinomas of salivary gland. Am J Surg Pathol. 2018;42(4):442–52.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Chiosea SI, Griffith C, Assaad A, Seethala RR. The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. Am J Surg Pathol. 2012;36(3):343–50.PubMedGoogle Scholar
  46. 46.
    Skalova A, Vanecek T, Majewska H, Laco J, Grossmann P, Simpson RH, et al. Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, beta-catenin, EGFR, and CCND1 genes. Am J Surg Pathol. 2014;38(1):23–33.PubMedGoogle Scholar
  47. 47.
    Chi HT, Ly BT, Kano Y, Tojo A, Watanabe T, Sato Y. ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412. Biochem Biophys Res Commun. 2012;429(1–2):87–92.PubMedGoogle Scholar
  48. 48.
    Tognon CE, Somasiri AM, Evdokimova VE, Trigo G, Uy EE, Melnyk N, et al. ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway. Cancer Res. 2011;71(3):1060–70.PubMedGoogle Scholar
  49. 49.
    Drilon A, Li G, Dogan S, Gounder M, Shen R, Arcila M, et al. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol. 2016;27(5):920–6.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Lei Y, Chiosea SI. Re-evaluating historic cohort of salivary acinic cell carcinoma with new diagnostic tools. Head Neck Pathol. 2012;6(2):166–70.PubMedGoogle Scholar
  51. 51.
    Skalova A, Michal M, Simpson RH. Newly described salivary gland tumors. Mod Pathol. 2017;30(s1):S27–s43.PubMedGoogle Scholar
  52. 52.
    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.PubMedGoogle Scholar
  53. 53.
    Simpson RH, Skalova A, Di Palma S, Leivo I. Recent advances in the diagnostic pathology of salivary carcinomas. Virchows Arch. 2014;465(4):371–84.PubMedGoogle Scholar
  54. 54.
    Masubuchi T, Tada Y, Maruya S, Osamura Y, Kamata SE, Miura K, et al. Clinicopathological significance of androgen receptor, HER2, Ki-67 and EGFR expressions in salivary duct carcinoma. Int J Clin Oncol. 2015;20(1):35–44.PubMedGoogle Scholar
  55. 55.
    Di Palma S, Simpson RH, Marchio C, Skalova A, Ungari M, Sandison A, et al. Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes. Histopathology. 2012;61(4):629–43.PubMedGoogle Scholar
  56. 56.
    Skalova A, Starek I, Vanecek T, Kucerova V, Plank L, Szepe P, et al. Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry. Histopathology. 2003;42(4):348–56.PubMedGoogle Scholar
  57. 57.
    Wang K, Russell JS, McDermott JD, Elvin JA, Khaira D, Johnson A, et al. Profiling of 149 salivary duct carcinomas, carcinoma ex pleomorphic adenomas, and adenocarcinomas, not otherwise specified reveals actionable genomic alterations. Clin Cancer Res. 2016;22(24):6061–8.PubMedGoogle Scholar
  58. 58.
    Seethala RR, Griffith CC. Molecular pathology: predictive, prognostic, and diagnostic markers in salivary gland tumors. Surg Pathol Clin. 2016;9(3):339–52.PubMedGoogle Scholar
  59. 59.
    Griffith CC, Seethala RR, Luvison A, Miller M, Chiosea SI. PIK3CA mutations and PTEN loss in salivary duct carcinomas. Am J Surg Pathol. 2013;37(8):1201–7.PubMedGoogle Scholar
  60. 60.
    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.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Chiosea SI, Thompson LD, Weinreb I, Bauman JE, Mahaffey AM, Miller C, et al. Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations. Cancer. 2016;122(20):3136–44.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Falchook GS, Lippman SM, Bastida CC, Kurzrock R. Human epidermal receptor 2-amplified salivary duct carcinoma: regression with dual human epidermal receptor 2 inhibition and anti-vascular endothelial growth factor combination treatment. Head Neck. 2014;36(3):E25–7.PubMedGoogle Scholar
  63. 63.
    Limaye SA, Posner MR, Krane JF, Fonfria M, Lorch JH, Dillon DA, et al. Trastuzumab for the treatment of salivary duct carcinoma. Oncologist. 2013;18(3):294–300.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Nardi V, Sadow PM, Juric D, Zhao D, Cosper AK, Bergethon K, et al. Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment. Clin Cancer Res. 2013;19(2):480–90.PubMedGoogle Scholar
  65. 65.
    Qiu W, Tong GX, Turk AT, Close LG, Caruana SM, Su GH. Oncogenic PIK3CA mutation and dysregulation in human salivary duct carcinoma. Biomed Res Int. 2014;2014:810487.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Soper MS, Iganej S, Thompson LD. Definitive treatment of androgen receptor-positive salivary duct carcinoma with androgen deprivation therapy and external beam radiotherapy. Head Neck. 2014;36(1):E4–7.PubMedGoogle Scholar
  67. 67.
    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(5):958–67.PubMedGoogle Scholar
  68. 68.
    Brandwein-Gensler M, Hille J, Wang BY, Urken M, Gordon R, Wang LJ, et al. Low-grade salivary duct carcinoma: description of 16 cases. Am J Surg Pathol. 2004;28(8):1040–4.PubMedGoogle Scholar
  69. 69.
    Weinreb I, Zhang L, Tirunagari LM, Sung YS, Chen CL, Perez-Ordonez B, et al. Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer. 2014;53(10):845–56.PubMedGoogle Scholar
  70. 70.
    Michal M, Skalova A, Simpson RH, Raslan WF, Curik R, Leivo I, et al. Cribriform adenocarcinoma of the tongue: a hitherto unrecognized type of adenocarcinoma characteristically occurring in the tongue. Histopathology. 1999;35(6):495–501.PubMedGoogle Scholar
  71. 71.
    Michal M, Kacerovska D, Kazakov DV. Cribriform adenocarcinoma of the tongue and minor salivary glands: a review. Head Neck Pathol. 2013;7(Suppl 1):S3–11.PubMedGoogle Scholar
  72. 72.
    Skalova A, Sima R, Kaspirkova-Nemcova J, Simpson RH, Elmberger G, Leivo I, et al. Cribriform adenocarcinoma of minor salivary gland origin principally affecting the tongue: characterization of new entity. Am J Surg Pathol. 2011;35(8):1168–76.PubMedGoogle Scholar
  73. 73.
    Laco J, Kamaradova K, Vitkova P, Sehnalkova E, Dvorakova S, Vaclavikova E, et al. Cribriform adenocarcinoma of minor salivary glands may express galectin-3, cytokeratin 19, and HBME-1 and contains polymorphisms of RET and H-RAS proto-oncogenes. Virchows Arch. 2012;461(5):531–40.PubMedGoogle Scholar
  74. 74.
    Weinreb I, Piscuoglio S, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, et al. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet. 2014;46(11):1166–9.PubMedGoogle Scholar
  75. 75.
    Piscuoglio S, Fusco N, Ng CK, Martelotto LG, da Cruz PA, Katabi N, et al. Lack of PRKD2 and PRKD3 kinase domain somatic mutations in PRKD1 wild-type classic polymorphous low-grade adenocarcinomas of the salivary gland. Histopathology. 2016;68(7):1055–62.PubMedPubMedCentralGoogle Scholar
  76. 76.
    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(11):2501–8.PubMedGoogle Scholar
  77. 77.
    Xu B, Aneja A, Ghossein R, Katabi N. Predictors of outcome in the phenotypic Spectrum of polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of salivary gland (CASG): a retrospective study of 69 patients. Am J Surg Pathol. 2016;40(11):1526–37.PubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of PathologyUniversity of Texas Southwestern Medical CenterDallasUSA

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