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Irish Journal of Medical Science (1971 -)
Published in: Irish Journal of Medical Science (1971 -) 3/2015

01-09-2015 | Review Article

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

Authors: T. Subramaniam, P. Lennon, J. P. O’Neill

Published in: Irish Journal of Medical Science (1971 -) | Issue 3/2015

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Abstract

Background

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.

Aim

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

Methods

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.

Conclusion

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.
Literature
1.
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):4444–4451CrossRefPubMed
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):3945–3953PubMedCentralCrossRefPubMed
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):1316–1318CrossRefPubMed
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):512–520CrossRefPubMed
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):509–514CrossRefPubMed
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):371–384CrossRef
8.
9.
Jaso J, Malhotra R (2011) Adenoid cystic carcinoma. Arch Pathol Lab Med 135(4):511–515PubMed
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):1683–1694CrossRefPubMed
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 225–259
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):613–619CrossRefPubMed
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):586–593CrossRefPubMed
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):695–703CrossRefPubMed
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):18740–18744PubMedCentralCrossRefPubMed
16.
Stenman G (2013) Fusion oncogenes in salivary gland tumors: molecular and clinical consequences. Head Neck Pathol 7(Suppl 1):S12–S19CrossRefPubMed
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):1169–1176
18.
Szanto PA, Luna MA, Tortoledo ME, White RA (1984) Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 54(6):1062–1069CrossRefPubMed
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):265–282CrossRefPubMed
20.
21.
22.
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):71–76CrossRefPubMed
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):791–798CrossRefPubMed
25.
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):360–363PubMedCentralCrossRefPubMed
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):376–378CrossRefPubMed
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):1232–1242PubMedCentralCrossRefPubMed
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):2965–2968PubMedCentralCrossRefPubMed
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):5417–5426PubMedCentralCrossRefPubMed
31.
Barrett AW, Speight PM (2009) Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator? Oral Oncol 45(11):936–940CrossRefPubMed
32.
Liebig C, Ayala G, Wilks JA, Berger DH, Albo D (2009) Perineural invasion in cancer: a review of the literature. Cancer 115(15):3379–3391CrossRefPubMed
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):1037–1039CrossRefPubMed
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
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):998–1004CrossRefPubMed
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):923–928CrossRefPubMed
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):312–316CrossRef
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):152–159CrossRefPubMed
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):445–449CrossRefPubMed
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):2872–2878CrossRefPubMed
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):76–81CrossRefPubMed
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):32–37CrossRef
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):364–370CrossRef
44.
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):88PubMedCentralCrossRefPubMed
46.
Spiro RH (1997) Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 174(5):495–498CrossRefPubMed
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):444–455CrossRefPubMed
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):1193–1197CrossRefPubMed
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):403–406CrossRefPubMed
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):1263–1268CrossRefPubMed
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):142–158CrossRefPubMed
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):815–824CrossRefPubMed
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 Neck
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):1796–1801CrossRefPubMed
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):952–957CrossRefPubMed
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):149–152CrossRefPubMed
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):205–210CrossRef
58.
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):311–316CrossRefPubMed
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):33–36CrossRefPubMed
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):585–590CrossRef
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):510–515CrossRefPubMed
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 14:13PubMedCentralCrossRefPubMed
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.
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):574–578CrossRefPubMed
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):1117–1122PubMedCentralCrossRefPubMed
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):3978–3984CrossRef
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):1562–1570CrossRefPubMed
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):3698–3710CrossRefPubMed
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):2696–2705CrossRefPubMed
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 14:795PubMedCentralCrossRefPubMed
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):543–550CrossRefPubMed
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 2013:257–263CrossRef
74.
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):569–573PubMedCentralCrossRefPubMed
76.
Metadata
Title
Ongoing challenges in the treatment of adenoid cystic carcinoma of the head and neck
Authors
T. Subramaniam
P. Lennon
J. P. O’Neill
Publication date
01-09-2015
Publisher
Springer London
Published in
Irish Journal of Medical Science (1971 -) / Issue 3/2015
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-015-1298-1

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