Skip to main content

Advertisement

Log in

Salivary Duct Carcinoma: New Developments—Morphological Variants Including Pure In Situ High Grade Lesions; Proposed Molecular Classification

  • Invited Review: An Update on Salivary Gland Pathology
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Salivary duct carcinoma (SDC) is an aggressive primary salivary malignancy which microscopically resembles high-grade ductal carcinoma of the breast, with both in situ and invasive patterns. It is typically found in older men, most often in the parotid. It can arise de novo or as the malignant component of carcinoma ex pleomorphic adenoma. SDC is generally a hematoxylin and eosin stain-based diagnosis, with special stains and immunohistochemistry acting mainly in a confirmatory role. Other than epithelial markers, SDC expresses androgen receptors in most cases, with true HER2 positivity seen in about 15 %. Based on these data and analogous to similar schemes in the breast, it is suggested that SDCs can be classified into three main groups: luminal androgen receptor positive, HER2+ and basal phenotype. This may form the basis for prognostic information and new therapeutic possibilities. In addition to the usual type of SDC, a few less common morphological variants have been reported: papillary, micropapillary, mucin-rich, sarcomatoid and oncocytic, as well as pure in situ cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Kleinsasser O, Klein HH, Hübner G. Speichelgangcarcinom: ein den milchgangcarcinomen der brüstdruse analoge gruppe von speicheldrüsentumoren [Salivary duct carcinoma. A group of salivary gland tumors analogous to mammary duct carcinoma]. Archiv für Klin Exper Ohren Nasen Kehlkopfheilkunde. 1968;192:100–15.

    Article  CAS  Google Scholar 

  2. Ellis GL, Auclair PL. Salivary duct carcinoma. In: AFIP, editor. Atlas of tumor pathology, fourth series, fascicle 9: tumors of the salivary glands. Washington DC: American Registry of Pathology; 2008. p. 322–32.

    Google Scholar 

  3. Brandwein-Gensler MS, Skálová A, Nagao T. Salivary duct carcinoma. In: Barnes EL, Eveson JW, Reichart P, Sidransky D, editors. Chapter 5, tumours of the salivary glands world health organization classification of tumours pathology and genetics of head and neck tumours. Lyon, France: IARC Press; 2005. p. 236–7.

    Google Scholar 

  4. Simpson RHW, Di Palma S. Selected recent advances in the pathology of salivary neoplasms. Diagn Histopathol. 2010;16:276–86.

    Article  Google Scholar 

  5. van Heerden WFP, Raubenheimer EJ, Swart TJP, Boy SC. Intraoral salivary duct carcinoma: a report of 5 cases. J Oral Maxillofac Surg. 2003;61:126–31.

    Article  PubMed  Google Scholar 

  6. Simpson RHW, Reis-Filho JS, Pereira EM, Ribeiro AC, Abdulkadir A. Polymorphous low grade adenocarcinoma of the salivary glands with transformation to high grade carcinoma. Histopathology. 2002;41:250–9.

    Article  PubMed  CAS  Google Scholar 

  7. Lewis JE, McKinney BC, Weiland LH, Ferreiro JA, Olsen KD. Salivary duct carcinoma: clinicopathologic and immunohistochemical review of 26 cases. Cancer. 1996;77:223–30.

    Article  PubMed  CAS  Google Scholar 

  8. Gnepp DR, Henley JD, Simpson RHW, Eveson JW. Salivary gland (major and minor) and lacrimal gland. Chapter 6. In: Gnepp DR, editor. Diagnostic surgical pathology of the head and neck. 2nd ed. Philadelphia: WB Saunders; 2009. p. 413–562.

    Chapter  Google Scholar 

  9. Hogg RP, Ayshford C, Watkinson JC. Parotid duct carcinoma arising in bilateral chronic sialadenitis. J Laryngol Otol. 1999;113:686–8.

    PubMed  CAS  Google Scholar 

  10. Gill J, Angelo N, Yeong ML, McIvor N. Salivary duct carcinoma arising in IgG4- related autoimmune disease of the parotid gland. Hum Pathol. 2009;40:881–6.

    Article  PubMed  CAS  Google Scholar 

  11. Di Palma S, Simpson RHW, Skálová A, Leivo I. Chapter 5: major and minor salivary glands. In: Cardesa A, Slootweg PJ, editors. Pathology of the head and neck pathology. Berlin: Springer; 2006. p. 131–70.

    Chapter  Google Scholar 

  12. de Araújo VC, Loducca SVL, Sobral APV, Kowalski AL, Soares F, de Araújo NS. Salivary duct carcinoma: cytokeratin 14 as a marker of in situ intraductal growth. Histopathology. 2002;41:244–9.

    Article  PubMed  Google Scholar 

  13. Afzelius LE, Cameron WR, Svensson C. Salivary duct carcinoma–a clinicopathologic study of 12 cases. Head Neck Surg. 1987;9:151–6.

    Article  PubMed  CAS  Google Scholar 

  14. Brandwein MS, Jagirdar J, Patil J, Biller H, Kaneko M. Salivary duct carcinoma (cribriform salivary carcinoma of excretory ducts): a clinicopathologic and immunohistochemical study of 12 cases. Cancer. 1990;65:2307–14.

    Article  PubMed  CAS  Google Scholar 

  15. Garland TA, Innes DJ Jr, Fechner RE. Salivary duct carcinoma: an analysis of four cases with review of literature. Am J Clin Pathol. 1984;81:436–41.

    PubMed  CAS  Google Scholar 

  16. Guzzo M, Di Palma S, Grandi C, Molinari R. Salivary duct carcinoma: clinical characteristics and treatment strategies. Head Neck. 1997;19:126–33.

    Article  PubMed  CAS  Google Scholar 

  17. Martinez-Barba E, Cortes-Guardiola JA, Minguela-Puras A, Torroba-Caron A, Mendez-Trujillo S, Bermejo-Lopez J. Salivary duct carcinoma: clinicopathological and immunohistochemical studies. J Cranio Maxillofac Surg. 1997;25:328–34.

    Article  CAS  Google Scholar 

  18. Simpson RHW, Clarke TJ, Sarsfield PTL, Babajews AV. Salivary duct adenocarcinoma. Histopathology. 1991;18:229–35.

    Article  PubMed  CAS  Google Scholar 

  19. Simpson RHW, Robertson NJ, Arora DS, Saunders MW. Salivary duct carcinoma: a cytological and histopathological study. Cytopathology. 1996;7:141–4.

    Article  PubMed  CAS  Google Scholar 

  20. Simpson RHW, Prasad A, Lewis JE, Skálová A, David L. Mucin-rich variant of salivary duct carcinoma: a clinicopathological and immunohistochemical study of four cases. Am J Surg Pathol. 2003;27:1070–9.

    Article  PubMed  Google Scholar 

  21. Nikitakis NG, Tosios KI, Papanikolaou VS, Rivera H, Papanicolaou SI, Ioffe OB. Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary gland tumors. Modern Pathol. 2004;17:407–15.

    Article  Google Scholar 

  22. Kapadia SB, Barnes L. Expression of androgen receptor, gross cystic disease fluid protein, and CD44 in salivary duct carcinoma. Modern Pathol. 1998;11:1033–8.

    CAS  Google Scholar 

  23. Di Palma S, Skálová A, Vanĕček T, Simpson RHW, Stárek I, Leivo I. Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/neu and MIB1 immunohistochemistry. Histopathology. 2005;46:144–52.

    Article  PubMed  Google Scholar 

  24. Jaehne M, Jäkel KT, Röser K, Ußmüller J, Löning T. Pilotstudie zur prognostischen Wertigkeit der Her-2 Genamplifikation und Proliferationsaktivität beim Speichelgangkarzinom der großen Kopfspeicheldrüsen [About the prognostic value of Her-2 gene-amplification and cell-proliferation in salivary duct carcinoma of the major salivary glands—a pilot-study]. Laryngorhinootologie. 2001;80:525–9.

    Article  PubMed  CAS  Google Scholar 

  25. Skálová A, Stárek I, Vanĕček T, Kučerová V, Plank L, Szépe P, Di Palma S, Leivo I. 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;42:348–56.

    Article  PubMed  Google Scholar 

  26. Sugano S, Mukai K, Tsuda H, et al. Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. Laryngoscope. 1992;102:923–7.

    Article  PubMed  CAS  Google Scholar 

  27. Johnson CJ, Barry MB, Vasef MA, De Young BR. HER-2/neu expression in salivary duct carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Appl Immunohistochem Mol Morphol. 2008;16:54–8.

    PubMed  CAS  Google Scholar 

  28. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF. American society of clinical oncology/college of American pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.

    Article  PubMed  CAS  Google Scholar 

  29. Di Palma S, Simpson RHW, Marchiò C, Skálová A, Ungari M, Sandison A, Whitaker S, Parry S, Reis-Filho JS. Salivary duct carcinomas can be classified into luminal andogen receptor-positive, HER2 and basal-like phenotypes. Histopathology. 2012;61:629–43.

    PubMed  Google Scholar 

  30. Williams MD, Roberts DB, Kies MS, Mao L, Weber RS, El-Naggar AK. Genetic and expression analysis of HER-2 and EGFR genes in salivary duct carcinoma: empirical and therapeutic significance. Clin Cancer Res. 2010;16:2266–74.

    Article  PubMed  CAS  Google Scholar 

  31. Williams MD, Roberts D, Blumenschein GR Jr, Temam S, Kies MS, Rosenthal DI, Weber RS, El-Naggar AK. Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients. Am J Surg Pathol. 2007;31:1645–52.

    Article  PubMed  Google Scholar 

  32. Delgado R, Vuitch F, Albores-Saavedra J. Salivary duct carcinoma. Cancer. 1993;72:1503–12.

    Article  PubMed  CAS  Google Scholar 

  33. Nasser SM, Faquin WC, Dayal Y. Expression of androgen, estrogen and progesterone receptors in salivary gland tumors: frequent expression of androgen receptor in a subset of malignant salivary gland tumors. Am J Clin Pathol. 2003;119:801–6.

    Article  PubMed  CAS  Google Scholar 

  34. Barnes L, Rao U, Contis L, Krause J, Schwartz A, Scalamogna P. Salivary duct carcinoma. Part II. Immunohistochemical evaluation of 13 cases for estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein. Oral Surg Oral Med Oral Pathol. 1994;78:74–80.

    Article  PubMed  CAS  Google Scholar 

  35. Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE. Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma. Am J Clin Pathol. 1998;109:75–84.

    PubMed  CAS  Google Scholar 

  36. Fan CY, Wang J, Barnes EL. Expression of androgen receptor and prostatic specific markers in salivary duct carcinoma: an immunohistochemical analysis of 13 cases and review of the literature. Am J Surg Pathol. 2000;24:579–86.

    Article  PubMed  CAS  Google Scholar 

  37. Isola JJ. Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol. 1993;170:31–5.

    Article  PubMed  CAS  Google Scholar 

  38. Moinfar F, Okcu M, Tsybrovskyy O, et al. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer. 2003;98:703–11.

    Article  PubMed  CAS  Google Scholar 

  39. Moriki T, Ueta S, Takahashi T, Mitani M, Ichien M. Salivary duct carcinoma: cytologic characteristics and application of androgen receptor immunostaining for diagnosis. Cancer (Cancer Cytopathol). 2001;93:344–50.

    CAS  Google Scholar 

  40. Kay PA, Roche PC, Olsen KD, Lewis JE. Salivary duct carcinoma: immunohistochemical analysis of androgen receptor, prostate markers and HER-2/neu oncoprotein in 40 cases. [Abstract]. Mod Pathol. 2001;14:150A.

    Article  Google Scholar 

  41. Fan C-Y, Melhem MF, Hosal S, Grandis R, Barnes EL. Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor α in salivary duct carcinoma. Arch Otolaryngol Head Neck Surg. 2001;127:1075–9.

    Article  PubMed  CAS  Google Scholar 

  42. Mukunyadzi P, Ai L, Portilla D, Barnes EL, Fan C-Y. Expression of peroxisome proliferators-activated receptor gamma in salivary duct carcinoma: immunohistochemical analysis of 15 cases. Mod Pathol. 2003;16:1218–23.

    Article  PubMed  Google Scholar 

  43. Hui KK, Batsakis JG, Luna MA, MacKay B, Byers RM. Salivary duct adenocarcinoma: a high grade malignancy. J Laryngol Otol. 1986;100:105–14.

    Article  PubMed  CAS  Google Scholar 

  44. Cerilli LA, Swartzbaugh JR, Saadut R, Marshall CE, Rumpel CA, Moskaluk CA, Frierson HF Jr. Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas. Hum Pathol. 1999;30:1242–6.

    Article  PubMed  CAS  Google Scholar 

  45. Hoang MP, Callender DL, Sola-Gallego JJ, Huang Z, Sneige N, Luna MA, Batsakis JG, El-Naggar AK. Molecular and biomarker analyses of salivary duct carcinomas: comparison with mammary duct carcinoma. Int J Oncol. 2001;19:865–71.

    PubMed  CAS  Google Scholar 

  46. Mutoh H, Nagata H, Ohno K, Numata T, Nagao T, Nagao K, Konno A. Analysis of the p53 gene in parotid gland cancers: a relatively high frequency of mutations in low- grade mucoepidermoid carcinomas. Int J Oncol. 2001;18:781–6.

    PubMed  CAS  Google Scholar 

  47. Jaehne M, Roeser K, Jaekel T, Schepers JD, Albert N, Löning T. Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer. 2005;103:2526–33.

    Article  PubMed  Google Scholar 

  48. Leivo I, Jee KJ, Heikinheimo K, Laine M, Ollila J, Nagy B, Knuutila S. Characterization of gene expression in major types of salivary gland carcinomas with epithelial differentiation. Cancer Genet Cytogenet. 2005;156:104–15.

    Article  PubMed  CAS  Google Scholar 

  49. 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;34:1106–21.

    Article  PubMed  Google Scholar 

  50. Brill LB, Kanner WA, Fehr A, Andrén Y, Moskaluk CA, Löning T, Stenman G, Frierson HF. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24:11691176.

    Article  Google Scholar 

  51. Michal M, Skálová A, Mukenšnabl P. Invasive micropapillary carcinoma of the parotid gland arising in mucinous cystadenoma. Virchow Archiv. 2000;437:465–8.

    Article  CAS  Google Scholar 

  52. Nagao T, Gaffey TA, Visscher DW, Kay PA, Minato H, Serizawa H, Lewis JE. Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance. Am J Surg Pathol. 2004;28:319–26.

    Article  PubMed  Google Scholar 

  53. Henley JD, Summerlin D-J, Potter D, Tomich C. Intraoral mucin-rich salivary duct carcinoma. Histopathology. 2005;47:436–7.

    Article  PubMed  CAS  Google Scholar 

  54. Kaku T, Ohuchi T, Satoh M, Ikeda T, Asanuma H, Azuma K, Kobayashi H. A case of mucin-rich salivary duct carcinoma ex pleomorphic adenoma. [Abstract]. Virchows Arch. 2005;447:341–2.

    Google Scholar 

  55. Yakirevich E, Sabo E, Klorin G, Alos L, Cardesa A, Ellis GL, Shumway BS, Gnepp DR. Primary mucin-producing tumours of the salivary glands: a clinicopathological and morphometric study. Histopathology. 2010;57:395–409.

    Article  PubMed  Google Scholar 

  56. Henley JD, Seo IS, Dayan D, Gnepp DR. Sarcomatoid salivary duct carcinoma of the parotid gland. Hum Pathol. 2000;31:208–13.

    Article  PubMed  CAS  Google Scholar 

  57. Nagao T, Gaffey TA, Serizawa H, Iwaya K, Watanabe A, Yoshida T, Yamazaki K, Sageshima M, Lewis JE. Sarcomatoid variant of salivary duct carcinoma: clinicopathologic and immunohistochemical study of eight cases and review of the literature. Am J Clin Pathol. 2004;122:222–31.

    Article  PubMed  Google Scholar 

  58. Tse LLY, Finkelstein SD, Siegler RW, Barnes LE. Osteoclast-type giant cell neoplasm of salivary gland. A microdissection-based comparative genotyping assay and literature review. Am J Surg Pathol. 2004;28:953–61.

    Article  PubMed  Google Scholar 

  59. Simpson RHW, Di Palma S. Carcinomas of the salivary gland. In: Pignatelli M, Underwood JCE, editors. Recent advances in histopathology 22. London: Royal Society of Medicine Press; 2007. p. 17–43.

    Google Scholar 

  60. Anderson C, Muller R, Piorkowski R, Knibbs DR, Vignoti P. Intraductal carcinoma of major salivary gland. Cancer. 1992;69:609–14.

    Article  PubMed  CAS  Google Scholar 

  61. Cheuk W, Miliauskas JR, Chan JKC. Intraductal carcinoma of the oral cavity: a case report and a reappraisal of the concept of pure ductal carcinoma in situ in salivary duct carcinoma. Am J Surg Pathol. 2004;28:266–70.

    Article  PubMed  Google Scholar 

  62. Tatemoto Y, Ohno A, Osaki T. Low malignant intraductal carcinoma on the hard palate: a variant of salivary duct carcinoma? Oral Oncol Eur J Cancer. 1996;32B:275–7.

    Article  CAS  Google Scholar 

  63. Watatani K, Shirasuna K, Aikawa T, Matsuya T. Intraductal carcinoma of the tongue: report of a case. Int J Oral Maxillofac Surg. 1991;20:175–6.

    Article  PubMed  CAS  Google Scholar 

  64. Chen KTK. Intraductal carcinoma of the minor salivary gland. J Laryngol Otol. 1983;97:189–91.

    Article  PubMed  CAS  Google Scholar 

  65. Cheuk W, Chan JKC. Advances in salivary pathology. Histopathology. 2007;51:1–20.

    Article  PubMed  CAS  Google Scholar 

  66. Simpson RHW, Desai S, Di Palma S. Salivary duct carcinoma in situ of the parotid gland. Histopathology. 2008;53:416–25.

    Article  PubMed  CAS  Google Scholar 

  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;78:958–67.

    Article  PubMed  CAS  Google Scholar 

  68. Brandwein-Gensler M, Hille J, Wang BY, Urken M, Gordon R, Wang LJ, Simpson JR, Simpson RH, Gnepp DR. Low-grade salivary duct carcinoma: description of 16 cases. Am J Surg Pathol. 2004;28:1040–4.

    Article  PubMed  Google Scholar 

  69. Weinreb I. Intraductal carcinoma of salivary gland (so-called low-grade cribriform cystadenocarcinoma) arising in an intraparotid lymph node. Head Neck Pathol. 2011;5:321–5.

    Article  PubMed  Google Scholar 

  70. Weinreb I, Tabanda-Lichauco R, van der Kwast T, Perez-Ordonez B. Low-grade intraductal carcinoma of salivary gland: report of 3 cases with marked apocrine differentiation. Am J Surg Pathol. 2006;30:1014–21.

    Article  PubMed  Google Scholar 

  71. Kusafuka K, Itoh H, Sugiyama C, Nakajima T. Low-grade salivary duct carcinoma of the parotid gland: report of a case with immunohistochemical analysis. Med Mol Morphol. 2010;43:178–84.

    Article  PubMed  Google Scholar 

  72. Chu PG, Weiss LM. Review. Keratin expression in human tissues and neoplasms. Histopathology. 2002;40:403–39.

    Article  PubMed  CAS  Google Scholar 

  73. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  PubMed  CAS  Google Scholar 

  74. Farmer P, Bonnefoi H, Becette V, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005;24:4660–71.

    Article  PubMed  CAS  Google Scholar 

  75. Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006;7:96.

    Article  PubMed  Google Scholar 

  76. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.

    Article  PubMed  CAS  Google Scholar 

  77. Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.

    Article  PubMed  CAS  Google Scholar 

  78. Hungermann D, Roeser K, Buerger H, Jäkel T, Löning T, Herbst H. Speichelgangkarzinome. Pathologe. 2005;26:353–8.

    Article  PubMed  CAS  Google Scholar 

  79. Locati LD, Bossi B, Rinaldi GR, Bergamini CB, Quattrone Q, Staurengo S, Pilotti S, Licitra L. Anti-androgen therapy in recurrent and/or metastatic salivary glands carcinoma (RSGC). [Abstract]. Ann Oncol 2006; 16: iii–38.

  80. di Palma S, Whitaker S, Potter K, Pitkin L. Carcinoma ex pleomorphic adenoma successfully treated with trastuzumab and radiotherapy [abstract]. Virchow Archiv. 2012;461(Suppl 1):S144.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roderick H. W. Simpson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simpson, R.H.W. Salivary Duct Carcinoma: New Developments—Morphological Variants Including Pure In Situ High Grade Lesions; Proposed Molecular Classification. Head and Neck Pathol 7 (Suppl 1), 48–58 (2013). https://doi.org/10.1007/s12105-013-0456-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-013-0456-x

Keywords

Navigation