Skip to main content

Advertisement

Log in

A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall

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

Abstract

While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987–2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear β-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term ‘seromucinous adenocarcinoma’ is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression.

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

Similar content being viewed by others

References

  1. Turner JH, Reh DD. Incidence and survival in patients with sinonasal cancer: a historical analysis of population-based data. Head Neck. 2012;34(6):877–85. doi:10.1002/hed.21830.

    Article  PubMed  Google Scholar 

  2. Barnes L. Intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Am J Surg Pathol. 1986;10(3):192–202.

    Article  CAS  PubMed  Google Scholar 

  3. Kleinsasser O, Schroeder HG. The pathology and clinical picture of adenocarcinoma of the nose after wood dust exposure. Strahlenther Onkol. 1989;165(6):437–40.

    CAS  PubMed  Google Scholar 

  4. Franquemont DW, Fechner RE, Mills SE. Histologic classification of sinonasal intestinal-type adenocarcinoma. Am J Surg Pathol. 1991;15(4):368–75.

    Article  CAS  PubMed  Google Scholar 

  5. Batsakis JG, Mackay B, Ordonez NG. Enteric-type adenocarcinoma of the nasal cavity. An electron microscopic and immunocytochemical study. Cancer. 1984;54(5):855–60.

    Article  CAS  PubMed  Google Scholar 

  6. Cathro HP, Mills SE. Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing CDX2 and MUC2. Am J Surg Pathol. 2004;28(8):1026–32.

    Article  PubMed  Google Scholar 

  7. Kennedy MT, Jordan RC, Berean KW, Perez-Ordonez B. Expression pattern of CK7, CK20, CDX-2, and villin in intestinal-type sinonasal adenocarcinoma. J Clin Pathol. 2004;57(9):932–7. doi:10.1136/jcp.2004.016964.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Kleinsasser O, Schroeder HG. Adenocarcinomas of the inner nose after exposure to wood dust. Morphological findings and relationships between histopathology and clinical behavior in 79 cases. Arch Otorhinolaryngol. 1988;245(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  9. Kleinsasser O. Terminal tubulus adenocarcinoma of the nasal seromucous glands. A specific entity. Arch Otorhinolaryngol. 1985;241(2):183–93.

    Article  CAS  PubMed  Google Scholar 

  10. Skalova A, Cardesa A, Leivo I, Pfaltz M, Ryska A, Simpson R, et al. Sinonasal tubulopapillary low-grade adenocarcinoma. Histopathological, immunohistochemical and ultrastructural features of poorly recognised entity. Virchows Arch. 2003;443(2):152–8. doi:10.1007/s00428-003-0844-9.

    Article  CAS  PubMed  Google Scholar 

  11. Heffner DK, Hyams VJ, Hauck KW, Lingeman C. Low-grade adenocarcinoma of the nasal cavity and paranasal sinuses. Cancer. 1982;50(2):312–22.

    Article  CAS  PubMed  Google Scholar 

  12. Neto AG, Pineda-Daboin K, Luna MA. Sinonasal tract seromucous adenocarcinomas: a report of 12 cases. Ann Diagn Pathol. 2003;7(3):154–9.

    Article  CAS  PubMed  Google Scholar 

  13. Stelow EB, Jo VY, Mills SE, Carlson DL. A histologic and immunohistochemical study describing the diversity of tumors classified as sinonasal high-grade nonintestinal adenocarcinomas. Am J Surg Pathol. 2011;35(7):971–80. doi:10.1097/PAS.0b013e31821cbd72.

    Article  PubMed  Google Scholar 

  14. Weinreb I, Gnepp DR, Laver NM, Hoschar AP, Hunt JL, Seethala RR, et al. Seromucinous hamartomas: a clinicopathological study of a sinonasal glandular lesion lacking myoepithelial cells. Histopathology. 2009;54(2):205–13. doi:10.1111/j.1365-2559.2008.03198.x.

    Article  PubMed  Google Scholar 

  15. Jo VY, Mills SE, Cathro HP, Carlson DL, Stelow EB. Low-grade sinonasal adenocarcinomas: the association with and distinction from respiratory epithelial adenomatoid hamartomas and other glandular lesions. Am J Surg Pathol. 2009;33(3):401–8. doi:10.1097/PAS.0b013e3181874ee8.

    Article  PubMed  Google Scholar 

  16. Baillie EE, Batsakis JG. Glandular (seromucinous) hamartoma of the nasopharynx. Oral Surg Oral Med Oral Pathol. 1974;38(5):760–2.

    Article  CAS  PubMed  Google Scholar 

  17. Sekine S, Shibata T, Matsuno Y, Maeshima A, Ishii G, Sakamoto M, et al. Beta-catenin mutations in pulmonary blastomas: association with morule formation. J Pathol. 2003;200(2):214–21. doi:10.1002/path.1352.

    Article  CAS  PubMed  Google Scholar 

  18. Chenevert J, Duvvuri U, Chiosea S, Dacic S, Cieply K, Kim J, et al. DOG1: a novel marker of salivary acinar and intercalated duct differentiation. Mod Pathol. 2012;25(7):919–29. doi:10.1038/modpathol.2012.57.

    Article  CAS  PubMed  Google Scholar 

  19. Ohtomo R, Mori T, Shibata S, Tsuta K, Maeshima AM, Akazawa C, et al. SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis. Mod Pathol. 2013;26(8):1041–50. doi:10.1038/modpathol.2013.54.

    Article  CAS  PubMed  Google Scholar 

  20. Nudell J, Chiosea S, Thompson LD. Carcinoma ex-Schneiderian papilloma (malignant transformation): a clinicopathologic and immunophenotypic study of 20 cases combined with a comprehensive review of the literature. Head Neck Pathol. 2014;8(3):269–86. doi:10.1007/s12105-014-0527-7.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Bilodeau EA, Weinreb I, Antonescu CR, Zhang L, Dacic S, Muller S, et al. Clear cell odontogenic carcinomas show EWSR1 rearrangements: a novel finding and a biological link to salivary clear cell carcinomas. Am J Surg Pathol. 2013;37(7):1001–5. doi:10.1097/PAS.0b013e31828a6727.

    Article  PubMed  Google Scholar 

  22. Bhaijee F, Carron J, Bell D. Low-grade nonintestinal sinonasal adenocarcinoma: a diagnosis of exclusion. Ann Diagn Pathol. 2011;15(3):181–4. doi:10.1016/j.anndiagpath.2010.10.002.

    Article  PubMed  Google Scholar 

  23. Saegusa M, Okayasu I. Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation. J Pathol. 2001;194(1):59–67. doi:10.1002/path.856.

    Article  CAS  PubMed  Google Scholar 

  24. Tanaka Y, Kato K, Notohara K, Nakatani Y, Miyake T, Ijiri R, et al. Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma. J Pathol. 2003;199(2):185–90. doi:10.1002/path.1262.

    Article  CAS  PubMed  Google Scholar 

  25. Hirokawa M, Kuma S, Miyauchi A, Qian ZR, Nakasono M, Sano T, et al. Morules in cribriform-morular variant of papillary thyroid carcinoma: immunohistochemical characteristics and distinction from squamous metaplasia. APMIS. 2004;112(4–5):275–82. doi:10.1111/j.1600-0463.2004.apm11204-0508.x.

    Article  PubMed  Google Scholar 

  26. Kurihara K, Shimizu S, Chong J, Hishima T, Funata N, Kashiwagi H, et al. Nuclear localization of immunoreactive beta-catenin is specific to familial adenomatous polyposis in papillary thyroid carcinoma. Jpn J Cancer Res. 2000;91(11):1100–2.

    Article  CAS  PubMed  Google Scholar 

  27. Nakatani Y, Masudo K, Miyagi Y, Inayama Y, Kawano N, Tanaka Y, et al. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules. Mod Pathol. 2002;15(6):617–24. doi:10.1038/modpathol.3880575.

    Article  PubMed  Google Scholar 

  28. Tilson MP, Gallia GL, Bishop JA. Among sinonasal tumors, CDX-2 immunoexpression is not restricted to intestinal-type adenocarcinomas. Head Neck Pathol. 2014;8(1):59–65. doi:10.1007/s12105-013-0475-7.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Wani Y, Notohara K, Saegusa M, Tsukayama C. Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation. Hum Pathol. 2008;39(7):1072–9. doi:10.1016/j.humpath.2007.07.019.

    Article  CAS  PubMed  Google Scholar 

  30. Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N. p40 (DeltaNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012;25(3):405–15. doi:10.1038/modpathol.2011.173.

    Article  CAS  PubMed  Google Scholar 

  31. Rooper L, Sharma R, Bishop JA. Polymorphous low grade adenocarcinoma has a consistent p63+/p40− immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol. 2014;. doi:10.1007/s12105-014-0554-4.

    PubMed Central  PubMed  Google Scholar 

  32. Fleming KE, Perez-Ordonez B, Nasser JG, Psooy B, Bullock MJ. Sinonasal seromucinous hamartoma: a review of the literature and a case report with focal myoepithelial cells. Head Neck Pathol. 2012;6(3):395–9. doi:10.1007/s12105-012-0339-6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank the UPMC Research Histology and Immunohistochemistry Laboratory for their excellent technical support. We would also like to thank Mrs. Robyn Roche for her excellent secretarial support. Some of these findings were initially presented as a poster at the United States Canadian Academy of Pathology Meeting in 2012, Vancouver, BC, Canada. This work was supported in part by the Department of Veterans Affairs, BLSR&D. This work does not reflect the views of the US Government or the Department of Veterans Affairs.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raja R. Seethala.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Purgina, B., Bastaki, J.M., Duvvuri, U. et al. A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall. Head and Neck Pathol 9, 436–446 (2015). https://doi.org/10.1007/s12105-015-0615-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-015-0615-3

Keywords

Navigation