Skip to main content

Advertisement

SpringerLink
Log in

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

  • Original Paper
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Polymorphous low grade adenocarcinoma (PLGA) is a tumor of minor salivary glands that exhibits considerable morphologic overlap with adenoid cystic carcinoma and cellular pleomorphic adenoma, especially in small biopsy specimens. Unlike these other tumor types. PLGAs do not harbor a myoepithelial component, yet their frequent positivity for p63 diminishes the usefulness of this particular myoepithelial marker as a discriminating immunostain. p40 is an antibody that recognizes ΔNp63, a p63 isoform that is more specific for true myoepithelial differentiation. As such, p40 immunostaining could help distinguish PLGAs from adenoid cystic carcinomas and pleomorphic adenomas. In this study, p63 and p40 immunohistochemistry was performed on paraffin embedded, formalin fixed tissue from 11 PLGAs, 101 adenoid cystic carcinomas, and 31 pleomorphic adenomas. All 11 PLGAs (100 %) were positive for p63 but completely negative for p40. Among adenoid cystic carcinomas, 91 of 101 (90 %) were positive for p63 and 90/101 (89 %) were positive for p40. The single discordant p63+/p40− adenoid cystic carcinoma exhibited solid architecture and high grade features not typically seen in PLGA. Among pleomorphic adenomas, 21/31 (68 %) were positive for p63 and 13/31 (42 %) were positive for p40. For the pleomorphic adenomas, the discordant p63+/p40− staining pattern was seen only in the overtly mesenchymal chondromyxoid stroma. The cellular epithelial component of the pleomorphic adenomas demonstrated concordant p63+/p40+ or p63−/p40− immunophenotypes. PLGA consistently exhibits a p63+/p40− immunophenotype that can help distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma, tumors that characteristically demonstrate concordant p63 and p40 immunostaining patterns. A p63/p40 immunohistochemical panel can provide a valuable tool for making the distinction between these morphologically similar but clinically divergent entities.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Luna MA, Wenig BM. Polymorphous low-grade adenocarcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. Pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005. p. 223–4.

    Google Scholar 

  2. Ellis GL, Auclair PL. Polymorphous low-grade adenocarcinoma. AFIP atlas of tumor pathology: tumors of the salivary glands. Washington, DC: ARP Press; 2008. p. 246–259.

  3. Frierson HF Jr, Mills SE, Garland TA. Terminal duct carcinoma of minor salivary glands. A nonpapillary subtype of polymorphous low-grade adenocarcinoma. Am J Clin Pathol. 1985;84:8–14.

    PubMed  Google Scholar 

  4. Aberle AM, Abrams AM, Bowe R, et al. Lobular (polymorphous low-grade) carcinoma of minor salivary glands. A clinicopathologic study of twenty cases. Oral Surg Oral Med Oral Pathol. 1985;60:387–95.

    Article  CAS  PubMed  Google Scholar 

  5. Venkata V, Irulandy P. The frequency and distribution pattern of minor salivary gland tumors in a government dental teaching hospital, Chennai, India. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:e32–9.

    Article  PubMed  Google Scholar 

  6. Kakarala K, Bhattacharyya N. Survival in oral cavity minor salivary gland carcinoma. Otolaryngol Head Neck Surg. 2010;143:122–6.

    Article  PubMed  Google Scholar 

  7. Pires FR, Pringle GA, de Almeida OP, et al. Intra-oral minor salivary gland tumors: a clinicopathological study of 546 cases. Oral Oncol. 2006;43:463–70.

    Article  PubMed  Google Scholar 

  8. Castle JT, Thompson LD, Frommelt RA, et al. Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases. Cancer. 1999;86:207–19.

    Article  CAS  PubMed  Google Scholar 

  9. Gnepp DR, S el-Mofty. Polymorphous low-grade adenocarcinoma: glial fibrillary acidic protein staining in the differential diagnosis with cellular mixed tumors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;83:691–5.

    Article  CAS  PubMed  Google Scholar 

  10. Loducca SV, Raitz R, Araujo NS, et al. Polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma: distinct architectural composition revealed by collagen IV, laminin and their integrin ligands (alpha2beta1 and alpha3beta1). Histopathology. 2000;37:118–23.

    Article  CAS  PubMed  Google Scholar 

  11. Araujo VC, Loducca SV, Sousa SO, et al. The cribriform features of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma: cytokeratin and integrin expression. Ann Diagn Pathol. 2001;5:330–4.

    Article  CAS  PubMed  Google Scholar 

  12. Curran AE, White DK, Damm DD, et al. Polymorphous low-grade adenocarcinoma versus pleomorphic adenoma of minor salivary glands: resolution of a diagnostic dilemma by immunohistochemical analysis with glial fibrillary acidic protein. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:194–9.

    Article  CAS  PubMed  Google Scholar 

  13. Darling MR, Schneider JW, Phillips VM. Polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma: a review and comparison of immunohistochemical markers. Oral Oncol. 2002;38:641–5.

    Article  PubMed  Google Scholar 

  14. Edwards PC, Bhuiya T, Kelsch RD. 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. 2003;95:586–93.

    Article  PubMed  Google Scholar 

  15. Penner CR, Folpe AL, Budnick SD. C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. Mod Pathol. 2002;15:687–91.

    Article  PubMed  Google Scholar 

  16. Epivatianos A, Iordanides S, Zaraboukas T, et al. Adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of minor salivary glands: a comparative immunohistochemical study using the epithelial membrane and carcinoembryonic antibodies. Oral Dis. 2005;11:175–80.

    Article  CAS  PubMed  Google Scholar 

  17. Woo VL, Bhuiya T, Kelsch R. Assessment of CD43 expression in adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, and monomorphic adenomas. Oral Surg Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:495–500.

    Article  Google Scholar 

  18. Beltran D, Faquin WC, Gallagher G, et al. Selective immunohistochemical comparison of polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma. J Oral Maxillofac Surg. 2006;64:415–23.

    Article  PubMed  Google Scholar 

  19. Curran AE, Allen CM, Beck FM, et al. Distinctive pattern of glial fibrillary acidic protein immunoreactivity useful in distinguishing fragmented pleomorphic adenoma, canalicular adenoma and polymorphous low grade adenocarcinoma of minor salivary glands. Head Neck Pathol. 2007;1:27–32.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Epivatianos A, Poulopoulos A, Dimitrakopoulos I, et al. Application of alpha-smooth muscle actin and c-kit in the differential diagnosis of adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. Oral Oncol. 2007;43:67–76.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  22. Araujo V, Sousa S, Jaeger M, et al. Characterization of the cellular component of polymorphous low-grade adenocarcinoma by immunohistochemistry and electron microscopy. Oral Oncol. 1999;35:164–72.

    Article  CAS  PubMed  Google Scholar 

  23. Prasad ML, Barbacioru CC, Rawal YB, et al. Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Mod Pathol. 2008;21:105–14.

    Article  CAS  PubMed  Google Scholar 

  24. Crum CP, McKeon FD. P63 in epithelial survival, germ cell surveillance, and neoplasia. Ann Rev Pathol. 2010;5:349–71.

    Article  CAS  Google Scholar 

  25. Edwards PC, Bhuiya T, Kelsch RD. 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. 2004;97:613–9.

    Article  PubMed  Google Scholar 

  26. Foschini MP, Gaiba A, Cocchi R, et al. p63 expression in salivary gland tumors: role of DeltaNp73L in neoplastic transformation. Int J Surg Pathol. 2005;13:329–35.

    Article  CAS  PubMed  Google Scholar 

  27. Park CK, Oh YH. Expression of p63 in reactive hyperplasias and malignant lymphomas. J Korean Med Sci. 2005;20:752–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Fukushima N, Satoh T, Sueoka N, et al. Clinico-pathological characteristics of p63 expression in B-cell lymphoma. Cancer Sci. 2006;97:1050–5.

    Article  CAS  PubMed  Google Scholar 

  29. Bishop JA, Teruya-Feldstein J, Westra WH, et al. p40 (DeltaNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012;25:405–15.

    Article  CAS  PubMed  Google Scholar 

  30. Bishop JA, Montgomery EA, Westra WH. Use of p40 and p63 immunohistochemistry and human papillomavirus testing as ancillary tools for the recognition of head and neck sarcomatoid carcinoma and its distinction from benign and malignant mesenchymal processes. Am J Surg Pathol. 2014;38:257–64.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Tilson MP, Bishop JA. Utility of p40 in the differential diagnosis of small round blue cell tumors of the sinonasal tract. Head Neck Pathol. 2014;8:141–5.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Pelosi G, Fabbri A, Rossi G, et al. A two-hit minimalist diagnostic algorithm based on p40 (deltaNp63) and TTF-1 immunostaining upon small biopsy/cellblock samples for differentiating main subtypes of non-small cell lung cancer and sparing material. J Thorac Oncol. 2011;6:S335–6.

    Google Scholar 

  33. Pogodzinski MS, Sabri AN, Lewis JE, et al. Retrospective study and review of polymorphous low-grade adenocarcinoma. The Laryngoscope. 2006;116:2145–9.

    Article  PubMed  Google Scholar 

  34. Seethala RR, Johnson JT, Barnes EL, et al. Polymorphous low-grade adenocarcinoma: the University of Pittsburgh experience. Arch Otolaryngol Head Neck Surg. 2010;136:385–92.

    Article  PubMed  Google Scholar 

  35. Lee SY, Kim BH, Choi EC. Nineteen-year oncologic outcomes and the benefit of elective neck dissection in salivary gland adenoid cystic carcinoma. Head Neck. 2013. doi:10.1002/hed.23537.

  36. Skalova A, Simpson RH, Lehtonen H, et al. 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. 1997;193:695–703.

    Article  CAS  PubMed  Google Scholar 

  37. Vargas H, Sudilovsky D, Kaplan MJ, et al. Mixed tumor, polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma of the salivary gland. Pathogenic implications and differential diagnosis by Ki-67 (MIB1), BCL2, and S-100 immunohistochemistry. Appl Immunohistochem. 1997;5:8–16.

    Article  Google Scholar 

  38. Lazzaro B, Cleveland D. P53 and Ki-67 antigen expression in small oral biopsy specimens of salivary gland tumors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:613–7.

    Article  CAS  PubMed  Google Scholar 

  39. de Araujo VC, Passador-Santos F, Turssi C, et al. Polymorphous low-grade adenocarcinoma: an analysis of epidemiological studies and hints for pathologists. Diagn Pathol. 2013;8:6.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded in part by the National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR) Head and Neck SPORE Grant P50 DE019032.

Author information

Authors and Affiliations

  1. Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Lisa Rooper, Rajni Sharma & Justin A. Bishop

  2. Departments of Otolaryngology/Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Justin A. Bishop

  3. The Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg 2249, Baltimore, MD, 21231, USA

    Justin A. Bishop

Authors
  1. Lisa Rooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajni Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Justin A. Bishop
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Justin A. Bishop.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rooper, L., Sharma, R. & Bishop, J.A. Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma. Head and Neck Pathol 9, 79–84 (2015). https://doi.org/10.1007/s12105-014-0554-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-014-0554-4

Keywords

Search

Navigation