Skip to main content

Advertisement

SpringerLink
Log in

Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature

  • Case Report
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Sinonasal intestinal-type adenocarcinomas (ITACs) are rare neoplasms histologically resembling intestinal adenocarcinomas. Although a neuroendocrine differentiation in ITACs has been described, true mixed exocrine-neuroendocrine carcinomas, neoplasms in which each component represents at least 30 % of the lesion, are extremely rare and their molecular alterations are largely unknown. We describe herein the clinico-pathologic features, the methylation profile, chromosomal gains and losses, and mutation analysis of KRAS, BRAF and p53 in a nasal mixed exocrine-neuroendocrine carcinoma resected in a 79-year-old man. The tumor was composed of an ITAC and a poorly differentiated neuroendocrine carcinoma. Both exocrine and neuroendocrine components were CK8, CK20, CDX2 and p53 positive, and CK7 and TTF1 negative. The neuroendocrine component also showed immunoreactivity for chromogranin A, synaptophysin, serotonin and glicentin. Gains and losses were found at following chromosome regions: 17p13 (TP53), 14q24 (MLH3), 19q13 (KLK3), 5q21 (APC), 7q21 (CDK6), 9q34 (DAPK1), 12p13 (TNFRSF 1A, CDKN1B), 13q12 (BRCA2), 17p13.3 (HIC1), 18q21 (BCL2), and 22q12 (TIMP3). Aberrant methylation was detected only in the neuroendocrine component and involved APC and DAPK1 genes. No mutation of KRAS (exons 2–4), BRAF (exon 15), and p53 (exons 4–10) was found in both components. The results suggest a monoclonal origin of the tumor from a pluripotent cell undergoing a biphenotypic differentiation and that the neuroendocrine differentiation may be from an exocrine to an endocrine pathway. We have also reviewed the literature on sinonasal mixed exocrine-neuroendocrine carcinomas to give to the reader a comprehensive overview of these very rare tumor types.

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
Fig. 3

References

  1. Barnes L, Eveson JW, Reichart P, Sidransky D. WHO classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005.

    Google Scholar 

  2. Franchi A, Santucci M, Wenig BM. Adenocarcinoma. In: Eveson JW, Reichart P, Sidransky D, Barnes L, editors. WHO classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005. p. 20–3.

    Google Scholar 

  3. Abecasis J, Viana G, Pissarra C, et al. Adenocarcinomas of the nasal cavity and paranasal sinuses: a clinicopathological and immunohistochemical study of 14 cases. Histopathology. 2004;45:254–9.

    Article  PubMed  CAS  Google Scholar 

  4. Batsakis JG, Mackay B, Ordonez NG. Enteric-type adenocarcinomas of the nasal cavity. An electron microscopic and immunohistochemical study. Cancer. 1984;54:855–60.

    Article  PubMed  CAS  Google Scholar 

  5. McKinney CD, Mills SE, Fraquemont DW. Sinonasal intestinal-type adenocarcinoma: immunohistochemical profile and comparison with colonic adenocarcinoma. Mod Pathol. 1995;8:421–6.

    PubMed  CAS  Google Scholar 

  6. Simard LC, Jean A. Adenocarcinoma with argentaffin cells of the nasal cavity, giving widespread metastases. Cancer. 1953;6:699–703.

    Article  PubMed  CAS  Google Scholar 

  7. La Rosa S, Marando A, Sessa F, et al. Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: an update. Cancers. 2012;4:11–30.

    Article  Google Scholar 

  8. Rindi G, Arnold R, Bosman FT, et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Lyon: IARC Press; 2010. p. 13–4.

    Google Scholar 

  9. Babin E, Rouleau V, Vedrine PO, et al. Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. J Laryngol Otol. 2006;120:289–97.

    Article  PubMed  CAS  Google Scholar 

  10. Bonato M, Frigerio B, Capella C, et al. Composite enteric-type adenocarcinoma-carcinoid of the nasal cavity. Endocr Pathol. 1993;4:40–7.

    Article  Google Scholar 

  11. Jain R, Gramigna V, Sanchez-Marull R, et al. Composite intestinal-type adenocarcinoma and small cell carcinoma of sinonasal tract. J Clin Pathol. 2009;62:634–7.

    Article  PubMed  CAS  Google Scholar 

  12. Silva EG, Butler JJ, Mackay B, et al. Neuroblastomas and neuroendocrine carcinomas of the nasal cavity. A proposed new classification. Cancer. 1982;50:2388–405.

    Article  PubMed  CAS  Google Scholar 

  13. Smith SR, Som P, Fahmy A, et al. A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma. Laryngoscope. 2000;110:1617–22.

    Article  PubMed  CAS  Google Scholar 

  14. Ariza M, Llorente JL, Alvarez-Marcos C, et al. Comparative genomic hybridization in primary sinonasal adenocarcinomas. Cancer. 2004;100:335–41.

    Article  PubMed  CAS  Google Scholar 

  15. Douglas EJ, Fiegler H, Rowan A, et al. Array comparative genomic hybridization analysis of colorectal cancer cell lines and primary carcinomas. Cancer Res. 2004;64:4817–25.

    Article  PubMed  CAS  Google Scholar 

  16. Korinth D, Pacyna-Gengelbach M, Deutschmann N, et al. Chromosomal imbalances in wood dust-related adenocarcinomas of the inner nose and their associations with pathological parameters. J Pathol. 2005;207:207–15.

    Article  PubMed  CAS  Google Scholar 

  17. Llorente JL, Pérez-Escuredo J, Alvarez-Marcos C, et al. Genetic and clinical aspects of wood dust related intestinal-type sinonasal adenocarcinoma: a review. Eur Arch Otorhinolaryngol. 2009;266:1–7.

    Article  PubMed  Google Scholar 

  18. Perrone F, Oggionni M, Birindelli S, et al. TP53, p14ARF, p16INK4A and H-ras gene molecular analysis in intestinal-type adenocarcinomas of the nasal cavity and paranasal sinuses. Int J Cancer. 2003;105:196–203.

    Article  PubMed  CAS  Google Scholar 

  19. La Rosa S, Marando A, Furlan D, et al. Colorectal poorly differentiated neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs): insights into the diagnostic immunophenotype, assessment of methylation profile and search for prognostic markers. Am J Surg Pathol. 2012;36:601–11.

    Article  PubMed  Google Scholar 

  20. Miyaki M, Iijima T, Yasuno M, et al. High incidence of protein-truncating mutations of the p53 gene in liver metastases of colorectal carcinomas. Oncogene. 2002;21:6689–93.

    Article  PubMed  CAS  Google Scholar 

  21. Kao HL, Chang WC, Li WY, et al. Head and neck large cell neuroendocrine carcinoma should be separated from atypical carcinoid on the basis of different clinical features, overall survival, and pathogenesis. Am J Surg Pathol. 2012;36:185–92.

    Article  PubMed  Google Scholar 

  22. Solcia E, Klöppel G, Sobin LH, et al. Histological typing of endocrine tumours. WHO international histological classification of tumours. 2nd ed. Berlin: Springer; 2000.

    Book  Google Scholar 

  23. Brambilla E, Lantuejoul S, Sturm N. Divergent differentiation in neuroendocrine lung tumors. Semin Diagn Pathol. 2000;17:138–48.

    PubMed  CAS  Google Scholar 

  24. di Sant’Agnese A. Divergent neuroendocrine differentiation in prostatic carcinoma. Semin Diagn Pathol. 2000;17:149–61.

    Google Scholar 

  25. Sapino A, Righi L, Cassoni P, et al. Expression of the neuroendocrine phenotype in carcinomas of the breast. Semin Diagn Pathol. 2000;17:127–37.

    PubMed  CAS  Google Scholar 

  26. Volante M, Rindi G, Papotti M. The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrine-endocrine neoplasms. Virchows Arch. 2006;449:499–506.

    Article  PubMed  Google Scholar 

  27. Klöppel G. Mixed exocrine-endocrine tumors of the pancreas. Semin Diagn Pathol. 2000;17:104–8.

    PubMed  Google Scholar 

  28. Franchi A, Massi D, Baroni G, Santucci M. CDX-2 homeobox gene expression. Am J Surg Pathol. 2003;27:1390–1.

    Article  PubMed  Google Scholar 

  29. Resto VA, Krane JF, Faquin WC, et al. Immunohistochemical distinction of intestinal-type sinonasal adenocarcinoma from metastatic adenocarcinoma of intestinal origin. Ann Otol Rhinol Laryngol. 2006;115:59–64.

    PubMed  Google Scholar 

  30. Komminoth P, Walch A, Werner M, et al. Methods in cellular and molecular pathology. In: Lloyd RV, editor. Endocrine pathology. Differential diagnosis and molecular advances. New York: Springer; 2010. p. 1–44.

    Google Scholar 

  31. Fiocca R, Rindi G, Capella C, et al. Glucagon, glicentin, proglucagon, PYY, PP and proPP-icosapeptide immunoreactivities of rectal carcinoid tumors and related non-tumor cells. Regul Pept. 1987;17:9–29.

    Article  PubMed  CAS  Google Scholar 

  32. Frattini M, Perrone F, Suardi S, et al. Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Head Neck. 2006;28:909–15.

    Article  PubMed  Google Scholar 

  33. Yom SS, Rashid A, Rosenthal DI, et al. Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance. Mod Pathol. 2005;18:315–9.

    Article  PubMed  CAS  Google Scholar 

  34. Wong TS, Chang HW, Tang KC, et al. High frequency of promoter hypermethylation of the death-associated protein-kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients. Clin Cancer Res. 2002;8:433–7.

    PubMed  CAS  Google Scholar 

  35. Hutajulu SH, Indrasari SR, Indrawati LP, et al. Epigenetic markers for early detection of nasopharyngeal carcinoma in a high risk population. Mol Cancer. 2011;10:48.

    Article  PubMed  CAS  Google Scholar 

  36. Wong TS, Kwong DL, Sham JS, et al. Quantitative plasma hypermethylated DNA markers of undifferentiated nasopharyngeal carcinoma. Clin Cancer Res. 2004;10:2401–6.

    Article  PubMed  CAS  Google Scholar 

  37. Fukui T, Tsuta K, Furuta K, et al. Epidermal growth factor receptor mutation status and clinicopathological features of combined small cell carcinoma with adenocarcinoma of the lung. Cancer Sci. 2007;98:1714–9.

    Article  PubMed  CAS  Google Scholar 

  38. Furlan D, Cerutti R, Genasetti A, et al. Microallelotyping defines the monoclonal or the polyclonal origin of mixed and collision endocrine-exocrine tumors of the gut. Lab Invest. 2003;83:963–71.

    Article  PubMed  Google Scholar 

  39. Huang J, Behrens C, Wistuba II, et al. Clonality of combined tumors. Arch Pathol Lab Med. 2002;126:437–41.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a grant from the University of Insubria, Varese.

Author information

Authors and Affiliations

  1. Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy

    Stefano La Rosa & Carlo Capella

  2. Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy

    Daniela Furlan, Francesca Franzi, Alessandro Marando, Nora Sahnane & Carlo Capella

  3. Department of Otorhinolaryngology, University of Insubria, Varese, Italy

    Paolo Battaglia, Mario Turri-Zanoni & Paolo Castelnuovo

  4. Laboratory of Molecular Diagnostic, Institute of Pathology, Locarno, Switzerland

    Milo Frattini & Elena Zanellato

Authors
  1. Stefano La Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Furlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesca Franzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Milo Frattini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elena Zanellato
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alessandro Marando
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nora Sahnane
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mario Turri-Zanoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paolo Castelnuovo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carlo Capella
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefano La Rosa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

La Rosa, S., Furlan, D., Franzi, F. et al. Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature. Head and Neck Pathol 7, 76–84 (2013). https://doi.org/10.1007/s12105-012-0379-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-012-0379-y

Keywords

Search

Navigation