Adenoid cystic carcinoma explained

Adenoid cystic carcinoma
Synonyms:Adenocyst, Malignant cylindroma, Adenocystic, Adenoidcystic

Adenoid cystic carcinoma is a rare type of cancer that can exist in many different body sites. This tumor most often occurs in the salivary glands, but it can also be found in many anatomic sites, including the breast,[1] [2] lacrimal gland, lung, brain, Bartholin gland, trachea, and the paranasal sinuses.

It is the third-most common malignant salivary gland tumor overall (after mucoepidermoid carcinoma and polymorphous adenocarcinoma). It represents 28% of malignant submandibular gland tumors, making it the single most common malignant salivary gland tumor in this region. Patients may survive for years with metastases because this tumor is generally well-differentiated and slow growing. In a 1999 study[3] of a cohort of 160 ACC patients, disease-specific survival was 89% at 5 years, but only 40% at 15 years, reflecting deaths from late-occurring metastatic disease.

Cause

Activation of the oncogenic transcription factor gene MYB is the key genomic event of ACC and seen in the vast majority of cases.[4] [5] Most commonly, MYB is activated through gene fusion with the transcription factor encoding NFIB gene as a result of a t(6;9) translocation.[4] Alternatively, MYB is activated by copy number gain or by juxtaposition of enhancer elements in the vicinity of the MYB gene.[6] In a subset of ACCs, the closely related MYBL1 gene is fused to NFIB or to other fusion partners.[7] [8]

MYB drives proliferation of ACC cells and regulates genes involved in cell cycle control, DNA replication and repair, and RNA processing.[9] Thus, the MYB oncogene is a potential diagnostic and therapeutic target in ACC.

ACC has a relatively quiet genome with few recurrent copy number alterations or point mutations,[6] [10] [11] [12] consistent with the view that MYB and MYBL1 are the main oncogenic drivers of the disease.

Treatment

Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumor's tendency to show a perineural discontinuous growth, meaning that it follows nerves and different "nests" of the tumor can exist without a connection to the original tumor. Therefore, MRI-images should be analysed following nerve tracts up to the brainstem. Adjuvant or palliative radiotherapy is commonly given following surgery. For advanced major and minor salivary gland tumors that are inoperable, recurrent, or exhibit gross residual disease after surgery, fast neutron therapy is widely regarded as the most effective form of treatment.[13] [14] [15] [16] Chemotherapy is used for metastatic disease. Chemotherapy is considered on a case-by-case basis, as data on the positive effects of chemotherapy are limited. Clinical studies are ongoing, however.

See also

Further reading

External links

Notes and References

  1. Adenoid cystic carcinomas of the breast and salivary glands (or 'The strange case of Dr Jekyll and Mr Hyde' of exocrine gland carcinomas). Marchiò C, Weigelt B, Reis-Filho JS . Mar 2010. J Clin Pathol. 10.1136/jcp.2009.073908. 20203221. 63. 3. 220–8. free.
  2. The birth of an adenoid cystic carcinoma. Fusco N, Guerini-Rocco E, Schultheis AM, Badve SS, Reis-Filho JS, Weigelt B . Feb 2015. Int J Surg Pathol. 10.1177/1066896914548795. 25185745. 23. 1. 26–7. 1805/7652 . 5935648 . free.
  3. Fordice . Jim . Kershaw . Corey . El-Naggar . Adel . Goepfert . Helmuth . Adenoid Cystic Carcinoma of the Head and Neck: Predictors of Morbidity and Mortality . Archives of Otolaryngology–Head & Neck Surgery . 125 . 2 . 149–52 . February 1999 . 10037280 . 10.1001/archotol.125.2.149. free .
  4. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck . Persson M, Andrén Y, Mark J, Horlings HM, Persson F, Stenman G . 2009 . Proc Natl Acad Sci U S A . 10.1073/pnas.0909114106. 19841262. 106. 44. 18740–4. 2773970. 2009PNAS..10618740P . free .
  5. The landscape of gene fusions and somatic mutations in salivary gland neoplasms - Implications for diagnosis and therapy . Andersson MK, Stenman G . 2016 . Oral Oncol . 10.1016/j.oraloncology.2016.04.002. 27101980. 57. 63–9.
  6. Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma . Persson M, Andrén Y, Moskaluk CA, Frierson HF Jr, Cooke SL, Futreal PA, Kling T, Nelander S, Nordkvist A, Persson F, Stenman G . 2012 . Genes Chromosomes Cancer . 10.1002/gcc.21965. 22505352. 51. 8. 805–17. 25742114 .
  7. Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma . Brayer KJ, Frerich CA, Kang H, Ness SA. 2016 . Cancer Discov. 10.1158/2159-8290.CD-15-0859. 26631070. 622. 2. 176–87. 4744535.
  8. Novel MYBL1 Gene Rearrangements with Recurrent MYBL1-NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations . Mitani Y, Liu B, Rao PH, Borra VJ, Zafereo M, Weber RS, Kies M, Lozano G, Futreal PA, Caulin C, El-Naggar AK. 2016 . Clin Cancer Res. 10.1158/1078-0432.CCR-15-2867-T. 26631609. 22. 3. 725–33. 4807116.
  9. Targeting the Oncogenic Transcriptional Regulator MYB in Adenoid Cystic Carcinoma by Inhibition of IGF1R/AKT Signaling . Andersson MK, Afshari MK, Andrén Y, Wick MJ, Stenman G. 2017 . J Natl Cancer Inst. 10.1093/jnci/djx017. 28954282. 109. 9. free.
  10. The mutational landscape of adenoid cystic carcinoma . Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N, Ramaswami D, Walsh LA, Eng S, Huse JT, Zhang J, Dolgalev I, Huberman K, Heguy A, Viale A, Drobnjak M, Leversha MA, Rice CE, Singh B, Iyer NG, Leemans CR, Bloemena E, Ferris RL, Seethala RR, Gross BE, Liang Y, Sinha R, Peng L, Raphael BJ, Turcan S, Gong Y, Schultz N, Kim S, Chiosea S, Shah JP, Sander C, Lee W, Chan TA. 2013 . Nat Genet. 10.1038/ng.2643. 23685749. 3708595. 45. 7. 791–8.
  11. Whole exome sequencing of adenoid cystic carcinoma . Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS, Papaemmanuil E, Cheverton A, Bignell GR, Butler AP, Gamble J, Gamble S, Hardy C, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, McLaren S, McBride DJ, Menzies A, Mudie L, Maddison M, Raine K, Nik-Zainal S, O'Meara S, Teague JW, Varela I, Wedge DC, Whitmore I, Lippman SM, McDermott U, Stratton MR, Campbell PJ, El-Naggar AK, Futreal PA. 2013 . J Clin Invest. 10.1172/JCI67201. 23778141. 3999050. 123. 7. 2965–8.
  12. Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma. Rettig EM, Talbot CC Jr, Sausen M, Jones S, Bishop JA, Wood LD, Tokheim C, Niknafs N, Karchin R, Fertig EJ, Wheelan SJ, Marchionni L, Considine M, Fakhry C, Papadopoulos N, Kinzler KW, Vogelstein B, Ha PK, Agrawal N. 2013 . Cancer Prev Res (Phila). 10.1158/1940-6207.CAPR-15-0316. 26862087. 9. 4. 265–74. 4818686.
  13. Laramore . GE . Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? . International Journal of Radiation Oncology, Biology, Physics . 13 . 9 . 1421–3 . September 1987 . 3114190 . 10.1016/0360-3016(87)90240-9.
  14. Prott FJ, Haverkamp U, Willich N, Wagner W, Micke O, Pötter R . Ten years of fast neutron therapy in Münster . Bulletin du Cancer. Radiothérapie . 83 . Suppl . 115s–21s . 1996 . 8949762 . 10.1016/0924-4212(96)84895-x.
  15. Douglas . James G . Laramore . George E . Austin-Seymour . Mary . Koh . Wui-jin . Stelzer . Keith . Griffin . Thomas W . Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy . International Journal of Radiation Oncology, Biology, Physics . 46 . 3 . 551–7 . February 2000 . 10701733 . 10.1016/S0360-3016(99)00445-9.
  16. Breteau N, Wachter T, Kerdraon R . Utilisation des neutrons rapides dans le traitement des tumeurs des glandes salivaires : rationnel, revue de la littérature et expérience d'Orléans . Use of fast neutrons in the treatment of tumors of the salivary glands: rationale, review of the literature and experience in Orleans . French . Cancer/Radiothérapie . 4 . 3 . 181–90 . 2000 . 10897760 . 10.1016/S1278-3218(00)89092-7. etal.

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