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Adenoid Cystic Carcinoma: Clinical and Molecular Features

  • North American Society of Head and Neck Pathology Companion Meeting, March 3, 2013, Baltimore, Maryland
  • Published:
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Abstract

The clinical features and common molecular alterations of adenoid cystic carcinoma (ACC) are reviewed in this paper. ACC is an uncommon neoplasm that most frequently arises in salivary glands and related tissue in the head and neck region. ACC has distinct histologic features, with cribriform and tubular growth patterns of basaloid cells displaying a predominantly myoepithelial cellular phenotype. This neoplasm also has uncommon clinical features of rare regional lymph node metastasis and a prolonged but relentlessly progressive clinical course. Clinical outcome in ACC is correlated to histologic grade, which is correlated to the degree of aneuploidy and genetic alterations present in the tumor genomes. Recent studies have identified that the majority of ACC contain alterations of the MYB gene, usually resulting in a fusion gene product with the NFIB gene by a t(6;9) translocation event. The molecular consequences of this alteration are incompletely understood, as are secondary molecular alterations that contribute to the neoplastic phenotype of ACC.

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References

  1. Bonaparte JP, Hart R, Trites J, Taylor MS. Incidence of adenoid cystic carcinoma in nova scotia: 30-year population-based epidemiologic study. J Otolaryngol Head Neck Surg. 2008;37:642–8.

    PubMed  Google Scholar 

  2. Vander Poorten VL, Balm AJ, Hilgers FJ, Tan IB, Loftus-Coll BM, Keus RB, Hart AA. Prognostic factors for long term results of the treatment of patients with malignant submandibular gland tumors. Cancer. 1999;85:2255–64.

    Article  PubMed  CAS  Google Scholar 

  3. Spiro RH. Salivary neoplasms, overview of a 35 year experience with 2,807 patients. Head Neck Surg. 1986;8:177–84.

    Article  PubMed  CAS  Google Scholar 

  4. Isacsson G, Shear M. Intraoral salivary gland tumors: a retrospective study of 201 cases. J Oral Pathol. 1983;12:57–62.

    Article  PubMed  CAS  Google Scholar 

  5. Eveson JW, Cawson RA. Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol. 1985;146:51–8.

    Article  PubMed  CAS  Google Scholar 

  6. Font RL, Smith SL, Bryan RG. Malignant epithelial tumors of the lacrimal gland: a clinicopathologic study of 21 cases. Arch Ophthalmol. 1998;116:613–6.

    PubMed  CAS  Google Scholar 

  7. Chen JC, Gnepp DR, Bedrossian CW. Adenoid cystic carcinoma of the salivary glands: an immunohistochemical analysis. Oral Surg, Oral Med Oral Pathol. 1988;65:316–26.

    Article  CAS  Google Scholar 

  8. Prasad AR, Savera AT, Gown AM, Zarbo RJ. The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma. Arch Pathol Lab Med. 1999;123:801–6.

    PubMed  CAS  Google Scholar 

  9. Cheng J, Saku T, Okabe H, Furthmayr H. Basement membranes in adenoid cystic carcinoma. An immunohistochemical study. Cancer. 1992;69:2631–40.

    Article  PubMed  CAS  Google Scholar 

  10. Frierson HF Jr, El-Naggar AK, Welsh JB, Sapinoso LM, Su AI, Cheng J, Saku T, Moskaluk CA, Hampton GM. Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma. Am J Pathol. 2002;161:1315–23.

    Article  PubMed  CAS  Google Scholar 

  11. Kimura S, Cheng J, Ida H, Hao N, Fujimori Y, Saku T. Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma. Virchows Arch. 2000;437:122–8.

    Article  PubMed  CAS  Google Scholar 

  12. Szanto PA, Luna MA, Tortoledo ME, White RA. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer. 1984;54:1062–9.

    Article  PubMed  CAS  Google Scholar 

  13. Greiner TC, Robinson RA, Maves MD. Adenoid cystic carcinoma clinicopathologic study with flow cytometric analysis. Am J Clin Pathol. 1989;92:711–20.

    PubMed  CAS  Google Scholar 

  14. Lloyd S, Yu JB, Wilson LD, Decker RH. 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. 2011;34:76–81.

    Article  PubMed  Google Scholar 

  15. Rutherford S, Yu Y, Rumpel CA, Frierson HF, Jr., Moskaluk CA: Chromosome 6 deletion and candidate tumor suppressor genes in adenoid cystic carcinoma. Cancer Lett. 2006;236:309–17.

    Google Scholar 

  16. Zarbo RJ. Salivary gland neoplasia: a review for the practicing pathologist. Mod Pathol. 2002;15:298–323.

    Article  PubMed  Google Scholar 

  17. Yamamoto Y, Saka T, Makimoto K, Takahashi H. Histological changes during progression of adenoid cystic carcinoma. J Laryngol Otol. 1992;106:1016–20.

    Article  PubMed  CAS  Google Scholar 

  18. Seethala RR, Hunt JL, Baloch ZW, Livolsi VA, Leon Barnes E. Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature. Am J Surg Pathol. 2007;31:1683–94.

    Article  PubMed  Google Scholar 

  19. Cheuk W, Chan JKC, Ngan RKC. Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon complication associated with an accelerated clinical course. Am J Surg Pathol. 1999;23:465–72.

    Article  PubMed  CAS  Google Scholar 

  20. Nagao T, Gaffey TA, Serizawa H, Sugano I, Ishida Y, Yamazaki K, Tokashiki R, Yoshida T, Minato H, Kay PA, Lewis JE. Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases. Mod Pathol. 2003;16:1265–72.

    Article  PubMed  Google Scholar 

  21. Fordice J, Kershaw C, el-Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck. Predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg. 1999;125:149–52.

    PubMed  CAS  Google Scholar 

  22. Mendenhall WM, Morris CG, Amdur RJ, Werning JW, Hinerman RW, Villaret DB. Radiotherapy alone or combined with surgery for adenoid cystic carcinoma of the head and neck. Head Neck. 2004;26:154–62.

    Article  PubMed  Google Scholar 

  23. Chen AM, Bucci MK, Weinberg V, Garcia J, Quivey JM, Schechter NR, Phillips TL, Fu KK, Eisele DW. 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. 2006;66:152–9.

    Article  PubMed  Google Scholar 

  24. Barrett AW, Speight PM. Perineural invasion in adenoid cystic carcinoma of the salivary glands: anatomical influences on oncological management. Curr Cancer Ther Rev. 2011;7:78–82.

    Article  Google Scholar 

  25. Conley J, Dingman DL. Adenoid cystic carcinoma in the head and neck (cylindroma). Arch Otolaryngol. 1974;100:81–90.

    Article  PubMed  CAS  Google Scholar 

  26. Spiro RH. Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg. 1997;174:495–8.

    Article  PubMed  CAS  Google Scholar 

  27. Nordkvist A, Mark J, Gustavsson H, Bang G, Stenman G. Nonrandom chromosome rearrangements in adenoid cystic carcinoma of the salivary glands. Genes Chromosom Cancer. 1994;10:115–21.

    Article  PubMed  CAS  Google Scholar 

  28. Jin Y, Mertens F, Limon J, Mandahl N, Wennerberg J, Dictor M, Heim S, Mitelman F. Characteristic karyotypic features in lacrimal and salivary gland carcinomas. Br J Cancer. 1994;70:42–7.

    Article  PubMed  CAS  Google Scholar 

  29. Jin C, Martins C, Jin Y, Wiegant J, Wennerberg J, Dictor M, Gisselsson D, Strombeck B, Fonseca I, Mitelman F, Tanke HJ, Hoglund M, Mertens F. Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH. Genes Chromosom Cancer. 2001;30:161–7.

    Article  PubMed  CAS  Google Scholar 

  30. Higashi K, Jin Y, Johansson M, Heim S, Mandahl N, Biorklund A, Wennerberg J, Hambraeus G, Johansson L, Mitelman F. Rearrangement of 9p13 as the primary chromosomal aberration in adenoid cystic carcinoma of the respiratory tract. Genes Chromosom Cancer. 1991;3:21–3.

    Article  PubMed  CAS  Google Scholar 

  31. Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA. 2009;106:18740–4.

    Article  PubMed  CAS  Google Scholar 

  32. Mitani Y, Li J, Rao PH, Zhao YJ, Bell D, Lippman SM, Weber RS, Caulin C, El-Naggar AK. Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance. Clin Cancer Res. 2010;16:4722–31.

    Article  PubMed  CAS  Google Scholar 

  33. Mitani Y, Rao PH, Futreal PA, Roberts DB, Stephens PJ, Zhao YJ, Zhang L, Mitani M, Weber RS, Lippman SM, Caulin C, El-Naggar AK. Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. Clin Cancer Res. 2011;17:7003–14.

    Article  PubMed  CAS  Google Scholar 

  34. West RB, Kong C, Clarke N, Gilks T, Lipsick JS, Cao H, Kwok S, Montgomery KD, Varma S, Le QT. MYB expression and translocation in adenoid cystic carcinomas and other salivary gland tumors with clinicopathologic correlation. Am J Surg Pathol. 2011;35:92–9.

    Article  PubMed  Google Scholar 

  35. Moskaluk CA, Baras AS, Mancuso SA, Fan H, Davidson RJ, Dirks DC, Golden WL, Frierson HF Jr. Development and characterization of xenograft model systems for adenoid cystic carcinoma. Lab Invest. 2011;91:1480–90.

    Article  PubMed  CAS  Google Scholar 

  36. Brill LB, 2nd, Kanner WA, Fehr A, Andren Y, Moskaluk CA, Loning T, Stenman G, Frierson HF, Jr.: Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24:1169–76.

    Google Scholar 

  37. Bell D, Roberts D, Karpowicz M, Hanna EY, Weber RS, El-Naggar AK. Clinical significance of Myb protein and downstream target genes in salivary adenoid cystic carcinoma. Cancer Biol Ther. 2011;12:569–73.

    Article  PubMed  CAS  Google Scholar 

  38. Bernheim A, Toujani S, Saulnier P, Robert T, Casiraghi O, Validire P, Temam S, Menard P, Dessen P, Fouret P. High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma. Lab Invest. 2008;88:464–73.

    Article  PubMed  CAS  Google Scholar 

  39. Rao PH, Roberts D, Zhao YJ, Bell D, Harris CP, Weber RS, El-Naggar AK. Deletion of 1p32-p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14:5181–7.

    Article  CAS  Google Scholar 

  40. Vekony H, Ylstra B, Wilting SM, Meijer GA, van de Wiel MA, Leemans CR, van der Waal I, Bloemena E. DNA copy number gains at loci of growth factors and their receptors in salivary gland adenoid cystic carcinoma. Clin Cancer Res. 2007;13:3133–9.

    Article  PubMed  CAS  Google Scholar 

  41. El-Rifai W, Rutherford S, Knuutila S, Frierson HF Jr, Moskaluk CA. Novel DNA copy number losses in chromosome 12q12–q13 in adenoid cystic carcinoma. Neoplasia. 2001;3:173–8.

    Article  PubMed  CAS  Google Scholar 

  42. Yu Y, Baras AS, Shirasuna K, Frierson HF Jr, Moskaluk CA. Concurrent loss of heterozygosity and copy number analysis in adenoid cystic carcinoma by SNP genotyping arrays. Lab Invest. 2007;87:430–9.

    Article  PubMed  CAS  Google Scholar 

  43. Freier K, Flechtenmacher C, Walch A, Ohl S, Devens F, Burke B, Hassfeld S, Lichter P, Joos S, Hofele C. Copy number gains on 22q13 in adenoid cystic carcinoma of the salivary gland revealed by comparative genomic hybridization and tissue microarray analysis. Cancer Genet Cytogenet. 2005;159:89–95.

    Article  PubMed  CAS  Google Scholar 

  44. Moskaluk CA, Frierson HF, Jr., El-Naggar AK, Futreal PA: C-kit gene mutations in adenoid cystic carcinoma are rare, Mod Pathol 2010, 23:905–906; Author reply 906–907.

    Google Scholar 

  45. Aubry MC, Heinrich MC, Molina J, Lewis JE, Yang P, Cassivi SD, Corless CL. Primary adenoid cystic carcinoma of the lung: absence of KIT mutations. Cancer. 2007;110:2507–10.

    Article  PubMed  Google Scholar 

  46. Holst VA, Marshall CE, Moskaluk CA, Frierson HF Jr. KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma. Mod Pathol. 1999;12:956–60.

    PubMed  CAS  Google Scholar 

  47. Jeng YM, Lin CY, Hsu HC. Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma. Cancer Lett. 2000;154:107–11.

    Article  PubMed  CAS  Google Scholar 

  48. Lin CH, Yen RF, Jeng YM, Tzen CY, Hsu C, Hong RL. Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate. Head Neck. 2005;27:1022–7.

    Article  PubMed  Google Scholar 

  49. Sorensen KB, Godballe C, de Stricker K, Krogdahl A. Parotid carcinoma: expression of kit protein and epidermal growth factor receptor. J Oral Pathol Med. 2006;35:286–91.

    Article  PubMed  Google Scholar 

  50. Vila L, Liu H, Al-Quran SZ, Coco DP, Dong HJ, Liu C: Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Mod Pathol. 2009;22:1296–302.

    Google Scholar 

  51. Saka T, Yamamoto Y, Takahashi H. Comparative cytofluorometric DNA analysis of pleomorphic adenoma and adenoid cystic carcinoma of the salivary glands. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61:255–61.

    Article  PubMed  CAS  Google Scholar 

  52. Franzen G, Nordgard S, Boysen M, Larsen PL, Halvorsen TB, Clausen OP. DNA content in adenoid cystic carcinomas. Head Neck. 1995;17:49–55.

    Article  PubMed  CAS  Google Scholar 

  53. Seethala RR, Cieply K, Barnes EL, Dacic S. Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation. Arch Pathol Lab Med. 2011;135:123–30.

    PubMed  Google Scholar 

  54. Londono-Vallejo JA. Telomere length heterogeneity and chromosome instability. Cancer Lett. 2004;212:135–44.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Christopher A. Moskaluk.

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Moskaluk, C.A. Adenoid Cystic Carcinoma: Clinical and Molecular Features. Head and Neck Pathol 7, 17–22 (2013). https://doi.org/10.1007/s12105-013-0426-3

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