Irish Journal of Medical Science (1971 -)

, Volume 184, Issue 3, pp 583–590 | Cite as

Ongoing challenges in the treatment of adenoid cystic carcinoma of the head and neck

  • T. SubramaniamEmail author
  • P. Lennon
  • J. P. O’Neill
Review Article



Adenoid cystic carcinoma is a malignant tumour of major and minor salivary glands. Distant metastasis and poor survival are persistent in the literature, with recent publications aimed at understanding molecular pathogenesis and development of pharmaceutical therapeutic options.


Provide an update of recent studies in the management of adenoid cystic carcinoma of the head and neck.


Literature search using Medline, Scopus, Google Scholar, the Cochrane Database of Systematic Reviews and the Cochrane central register of controlled trials for articles on adenoid cystic carcinoma from January 2005 to January 2015.


Adenoid cystic carcinoma is characterized by a slow growing mass, with distant metastasis independent of local or regional control. Primary tumour resection remains the preferred option with radiotherapy having an adjuvant role. Recent advances have been made with novel targeted therapies however, limited to clinical trials and advanced disease.


Adenoid cystic carcinoma Head and neck Review Management Novel therapy Genetics 


Conflict of interest

We declare no conflict of interest and obtained no funding.


  1. 1.
    Foote FW Jr, Frazell EL (1953) Tumors of the major salivary glands. Cancer 6(6):1065–1133CrossRefPubMedGoogle Scholar
  2. 2.
    Ellington CL, Goodman M, Kono SA, Grist W, Wadsworth T, Chen AY et al (2012) Adenoid cystic carcinoma of the head and neck: incidence and survival trends based on 1973–2007 surveillance, epidemiology, and end results data. Cancer 118(18):4444–4451CrossRefPubMedGoogle Scholar
  3. 3.
    Li N, Xu L, Zhao H, El-Naggar AK, Sturgis EM (2012) A comparison of the demographics, clinical features, and survival of patients with adenoid cystic carcinoma of major and minor salivary glands versus less common sites within the surveillance, epidemiology, and end results registry. Cancer 118(16):3945–3953PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Matsuba HM, Thawley SE, Simpson JR, Levine LA, Mauney M (1984) Adenoid cystic carcinoma of major and minor salivary gland origin. Laryngoscope 94(10):1316–1318CrossRefPubMedGoogle Scholar
  5. 5.
    Spiro RH, Huvos AG, Strong EW (1974) Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg 128(4):512–520CrossRefPubMedGoogle Scholar
  6. 6.
    Saghravanian N, Mohtasham N, Jafarzadeh H (2009) Comparison of immunohistochemical markers between adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. J Oral Sci 51(4):509–514CrossRefPubMedGoogle Scholar
  7. 7.
    Simpson RH, Skalova A, Di Palma S, Leivo I (2014) Recent advances in the diagnostic pathology of salivary carcinomas. Virchows Archiv Int J Pathol 465(4):371–384CrossRefGoogle Scholar
  8. 8.
    IARC (2015) International classification of diseases for oncology, ICD-O-3, 8200/3 adenoid cystic carcinoma. WHO. Accessed 6 Jan 2015
  9. 9.
    Jaso J, Malhotra R (2011) Adenoid cystic carcinoma. Arch Pathol Lab Med 135(4):511–515PubMedGoogle Scholar
  10. 10.
    Seethala RR, Hunt JL, Baloch ZW, Livolsi VA, Leon Barnes E (2007) Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature. Am J Surg Pathol 31(11):1683–1694CrossRefPubMedGoogle Scholar
  11. 11.
    Ellis GL, Auclair PL (2008) Tumors of the salivary glands. Atlas of tumor pathology; 4th series, Fascicle 9. ARP Press, Silver Spring (MD), pp 225–259Google Scholar
  12. 12.
    Edwards PC, Bhuiya T, Kelsch RD (2004) Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97(5):613–619CrossRefPubMedGoogle Scholar
  13. 13.
    Edwards PC, Bhuiya T, Kelsch RD (2003) C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95(5):586–593CrossRefPubMedGoogle Scholar
  14. 14.
    Skalova A, Simpson RH, Lehtonen H, Leivo I (1997) Assessment of proliferative activity using the MIB1 antibody help to distinguish polymorphous low grade adenocarcinoma from adenoid cystic carcinoma of salivary glands. Pathol Res Pract 193(10):695–703CrossRefPubMedGoogle Scholar
  15. 15.
    Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G (2009) Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA 106(44):18740–18744PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Stenman G (2013) Fusion oncogenes in salivary gland tumors: molecular and clinical consequences. Head Neck Pathol 7(Suppl 1):S12–S19CrossRefPubMedGoogle Scholar
  17. 17.
    Brill LB 2nd, Kanner WA, Fehr A, Andren Y, Moskaluk CA, Loning T et al (2011) Analysis of MYB expression and MYB–NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Modern Pathol Off J US Can Acad Pathol 24(9):1169–1176Google Scholar
  18. 18.
    Szanto PA, Luna MA, Tortoledo ME, White RA (1984) Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 54(6):1062–1069CrossRefPubMedGoogle Scholar
  19. 19.
    Perzin KH, Gullane P, Clairmont AC (1978) Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer 42(1):265–282CrossRefPubMedGoogle Scholar
  20. 20.
    Patey DH, Thackray AC, Keeling DH (1965) Malignant disease of the parotid. Br J Cancer 19(4):712–737PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Thackray AC, Lucas RB (1960) The histology of cylindroma of mucous gland origin. Br J Cancer 14:612–620PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Seethala RR (2009) An update on grading of salivary gland carcinomas. Head Neck Pathol 3(1):69–77PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    van Weert S, van der Waal I, Witte BI, Leemans CR, Bloemena E (2015) Histopathological grading of adenoid cystic carcinoma of the head and neck: analysis of currently used grading systems and proposal for a simplified grading scheme. Oral Oncol 51(1):71–76CrossRefPubMedGoogle Scholar
  24. 24.
    Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N et al (2013) The mutational landscape of adenoid cystic carcinoma. Nat Genet 45(7):791–798CrossRefPubMedGoogle Scholar
  25. 25.
    Wolffe AP (2001) Chromatin remodeling: why it is important in cancer. Oncogene 20(24):2988–2990CrossRefPubMedGoogle Scholar
  26. 26.
    Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A et al (2010) Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463(7279):360–363PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y et al (2012) Mutations affecting components of the SWI/SNF complex cause Coffin–Siris syndrome. Nat Genet 44(4):376–378CrossRefPubMedGoogle Scholar
  28. 28.
    Binmadi NO, Yang YH, Zhou H, Proia P, Lin YL, De Paula AM et al (2012) Plexin-B1 and semaphorin 4D cooperate to promote perineural invasion in a RhoA/ROK-dependent manner. Am J Pathol 180(3):1232–1242PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS et al (2013) Whole exome sequencing of adenoid cystic carcinoma. J Clin Investig 123(7):2965–2968PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U et al (2002) SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J 21(20):5417–5426PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Barrett AW, Speight PM (2009) Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator? Oral Oncol 45(11):936–940CrossRefPubMedGoogle Scholar
  32. 32.
    Liebig C, Ayala G, Wilks JA, Berger DH, Albo D (2009) Perineural invasion in cancer: a review of the literature. Cancer 115(15):3379–3391CrossRefPubMedGoogle Scholar
  33. 33.
    Teymoortash A, Zieger L, Hoch S, Pagenstecher A, Hofer MJ (2014) Distinct microscopic features of perineural invasion in adenoid cystic carcinoma of the head and neck. Histopathology 64(7):1037–1039CrossRefPubMedGoogle Scholar
  34. 34.
    Amit M, Binenbaum Y, Trejo-Leider L, Sharma K, Ramer N, Ramer I et al (2014) International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck. Head Neck 2014:7. doi: 10.1002/hed.23710 Google Scholar
  35. 35.
    Amit M, Binenbaum Y, Sharma K, Ramer N, Ramer I, Agbetoba A et al (2014) Analysis of failure in patients with adenoid cystic carcinoma of the head and neck. An international collaborative study. Head Neck 36(7):998–1004CrossRefPubMedGoogle Scholar
  36. 36.
    Gao M, Hao Y, Huang MX, Ma DQ, Luo HY, Gao Y et al (2013) Clinicopathological study of distant metastases of salivary adenoid cystic carcinoma. Int J Oral Maxillofac Surg 42(8):923–928CrossRefPubMedGoogle Scholar
  37. 37.
    Shingaki S, Kanemaru S, Oda Y, Niimi K, Mikami T, Funayama A et al (2014) Distant metastasis and survival of adenoid cystic carcinoma after definitive treatment. J Oral Maxillofac Surg Med Pathol 26(3):312–316CrossRefGoogle Scholar
  38. 38.
    Chen AM, Bucci MK, Weinberg V, Garcia J, Quivey JM, Schechter NR et al (2006) Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys 66(1):152–159CrossRefPubMedGoogle Scholar
  39. 39.
    Shen C, Xu T, Huang C, Hu C, He S (2012) Treatment outcomes and prognostic features in adenoid cystic carcinoma originated from the head and neck. Oral Oncol 48(5):445–449CrossRefPubMedGoogle Scholar
  40. 40.
    Bhayani MK, Yener M, El-Naggar A, Garden A, Hanna EY, Weber RS et al (2012) Prognosis and risk factors for early-stage adenoid cystic carcinoma of the major salivary glands. Cancer 118(11):2872–2878CrossRefPubMedGoogle Scholar
  41. 41.
    Lloyd S, Yu JB, Wilson LD, Decker RH (2011) Determinants and patterns of survival in adenoid cystic carcinoma of the head and neck, including an analysis of adjuvant radiation therapy. Am J Clin Oncol 34(1):76–81CrossRefPubMedGoogle Scholar
  42. 42.
    Mizoe JE, Hasegawa A, Jingu K, Takagi R, Bessyo H, Morikawa T et al (2012) Results of carbon ion radiotherapy for head and neck cancer. Radiother Oncol J Eur Soc Ther Radiol Oncol 103(1):32–37CrossRefGoogle Scholar
  43. 43.
    Takagi M, Demizu Y, Hashimoto N, Mima M, Terashima K, Fujii O et al (2014) Treatment outcomes of particle radiotherapy using protons or carbon ions as a single-modality therapy for adenoid cystic carcinoma of the head and neck. Radiother Oncol J Eur Soc Ther Radiol Oncol 113(3):364–370CrossRefGoogle Scholar
  44. 44.
    Tsujii H, Kamada T (2012) A review of update clinical results of carbon ion radiotherapy. Jpn J Clin Oncol 42(8):670–685PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Schlaff CD, Krauze A, Belard A, O’Connell JJ, Camphausen KA (2014) Bringing the heavy: carbon ion therapy in the radiobiological and clinical context. Radiat Oncol 9(1):88PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Spiro RH (1997) Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 174(5):495–498CrossRefPubMedGoogle Scholar
  47. 47.
    Vander Poorten V, Hunt J, Bradley PJ, Haigentz M Jr, Rinaldo A, Mendenhall WM et al (2014) Recent trends in the management of minor salivary gland carcinoma. Head Neck 36(3):444–455CrossRefPubMedGoogle Scholar
  48. 48.
    Sung MW, Kim KH, Kim JW, Min YG, Seong WJ, Roh JL et al (2003) Clinicopathologic predictors and impact of distant metastasis from adenoid cystic carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 129(11):1193–1197CrossRefPubMedGoogle Scholar
  49. 49.
    Maruya S, Namba A, Matsubara A, Kakehata S, Takeda I, Shirasaki T et al (2006) Salivary gland carcinoma treated with concomitant chemoradiation with intraarterial cisplatin and docetaxel. Int J Clin Oncol 11(5):403–406CrossRefPubMedGoogle Scholar
  50. 50.
    Samant S, van den Brekel MW, Kies MS, Wan J, Robbins KT, Rosenthal DI et al (2012) Concurrent chemoradiation for adenoid cystic carcinoma of the head and neck. Head Neck 34(9):1263–1268CrossRefPubMedGoogle Scholar
  51. 51.
    Cerda T, Sun XS, Vignot S, Marcy PY, Baujat B, Baglin AC et al (2014) A rationale for chemoradiation (vs radiotherapy) in salivary gland cancers? On behalf of the REFCOR (French rare head and neck cancer network). Crit Rev Oncol Hematol 91(2):142–158CrossRefPubMedGoogle Scholar
  52. 52.
    Laurie SAAL, Matthew GF, Sherman E, Pfister DG (2010) Systematic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary gland; a systematic review. Lancet Oncol 12(8):815–824CrossRefPubMedGoogle Scholar
  53. 53.
    Amit M, Binenbaum Y, Sharma K, Ramer N, Ramer I, Agbetoba A et al (2014) Incidence of cervical lymph node metastasis and its association with outcomes in patients with adenoid cystic carcinoma. An international collaborative study. Head NeckGoogle Scholar
  54. 54.
    Lee SY, Kim BH, Choi EC (2014) Nineteen-year oncologic outcomes and the benefit of elective neck dissection in salivary gland adenoid cystic carcinoma. Head Neck 36(12):1796–1801CrossRefPubMedGoogle Scholar
  55. 55.
    Min R, Siyi L, Wenjun Y, Ow A, Lizheng W, Minjun D et al (2012) Salivary gland adenoid cystic carcinoma with cervical lymph node metastasis: a preliminary study of 62 cases. Int J Oral Maxillofac Surg 41(8):952–957CrossRefPubMedGoogle Scholar
  56. 56.
    Fordice J, Kershaw C, El-Naggar A, Goepfert H (1999) Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg 125(2):149–152CrossRefPubMedGoogle Scholar
  57. 57.
    Nobis CP, Rohleder NH, Wolff KD, Wagenpfeil S, Scherer EQ, Kesting MR (2014) Head and neck salivary gland carcinomas—elective neck dissection, yes or no? J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 72(1):205–210CrossRefGoogle Scholar
  58. 58.
    US National Institutes of Health (2015) Accessed 11 Jan 2015
  59. 59.
    Tang Y, Liang X, Zheng M, Zhu Z, Zhu G, Yang J et al (2010) Expression of c-kit and slug correlates with invasion and metastasis of salivary adenoid cystic carcinoma. Oral Oncol 46(4):311–316CrossRefPubMedGoogle Scholar
  60. 60.
    Pfeffer MR, Talmi Y, Catane R, Symon Z, Yosepovitch A, Levitt M (2007) A phase II study of imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands. Oral Oncol 43(1):33–36CrossRefPubMedGoogle Scholar
  61. 61.
    Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX et al (2005) Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. J Clin Oncol Off J Am Soc Clin Oncol 23(3):585–590CrossRefGoogle Scholar
  62. 62.
    Ghosal N, Mais K, Shenjere P, Julyan P, Hastings D, Ward T et al (2011) Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma. Br J Oral Maxillofac Surg 49(7):510–515CrossRefPubMedGoogle Scholar
  63. 63.
    Huang Y, Yu T, Fu X, Chen J, Liu Y, Li C et al (2013) EGFR inhibition prevents in vitro tumor growth of salivary adenoid cystic carcinoma. BMC Cell Biol 14:13PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Jakob JA, Kies MS, Glisson BS, Kupferman ME, Liu DD, Lee JJ et al (2014) Phase II study of gefitinib in patients with advanced salivary gland cancers. Head Neck. doi: 10.1002/hed.23647
  65. 65.
    Locati LD, Bossi P, Perrone F, Potepan P, Crippa F, Mariani L et al (2009) Cetuximab in recurrent and/or metastatic salivary gland carcinomas: a phase II study. Oral Oncol 45(7):574–578CrossRefPubMedGoogle Scholar
  66. 66.
    Hitre E, Budai B, Takacsi-Nagy Z, Rubovszky G, Toth E, Remenar E et al (2013) Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial. Br J Cancer 109(5):1117–1122PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Agulnik M, Cohen EW, Cohen RB, Chen EX, Vokes EE, Hotte SJ et al (2007) Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands. J Clin Oncol Off J Am Soc Clin Oncol 25(25):3978–3984CrossRefGoogle Scholar
  68. 68.
    Chau NG, Hotte SJ, Chen EX, Chin SF, Turner S, Wang L et al (2012) A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC. Ann Oncol 23(6):1562–1570CrossRefPubMedGoogle Scholar
  69. 69.
    Ivanov SV, Panaccione A, Brown B, Guo Y, Moskaluk CA, Wick MJ et al (2013) TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior. Oncogene 32(32):3698–3710CrossRefPubMedGoogle Scholar
  70. 70.
    Younes MN, Park YW, Yazici YD, Gu M, Santillan AA, Nong X et al (2006) Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther 5(11):2696–2705CrossRefPubMedGoogle Scholar
  71. 71.
    Kim DW, Oh DY, Shin SH, Kang JH, Cho BC, Chung JS et al (2014) A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma. BMC Cancer 14:795PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Wetterskog D, Wilkerson PM, Rodrigues DN, Lambros MB, Fritchie K, Andersson MK et al (2013) Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations. Histopathology 62(4):543–550CrossRefPubMedGoogle Scholar
  73. 73.
    Carlson J, Licitra L, Locati L, Raben D, Persson F, Stenman G (2013) Salivary gland cancer: an update on present and emerging therapies. Am Soc of Clin Oncol Educ Book 2013:257–263CrossRefGoogle Scholar
  74. 74.
    Ramsay RG, Gonda TJ (2008) MYB function in normal and cancer cells. Nat Rev Cancer 8(7):523–534CrossRefPubMedGoogle Scholar
  75. 75.
    Bell D, Roberts D, Karpowicz M, Hanna EY, Weber RS, El-Naggar AK (2011) Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma. Cancer Biol Ther 12(7):569–573PubMedCentralCrossRefPubMedGoogle Scholar
  76. 76.
    Adenoid Cystic Carcinoma Reseach Foundation (2015) Therapeutic targets. Accessed 11 Jan 2015

Copyright information

© Royal Academy of Medicine in Ireland 2015

Authors and Affiliations

  1. 1.Department of Otolaryngology, Head and Neck SurgeryBeaumont HospitalDublinIreland
  2. 2.Department of Otolaryngology, Head and Neck SurgerySt James’s HospitalDublinIreland

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