Skip to main content

Advertisement

SpringerLink
Log in

Prognostic Significance of Granuloma and Amyloid Deposition in Nasopharyngeal Carcinoma

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

Abstract

The significance of granuloma and amyloid deposition in primary nasopharyngeal carcinoma (NPC) has yet to be investigated. This study aimed to evaluate their clinicopathologic associations. The histopathologic findings of 747 consecutive patients with primary NPC were retrospectively reviewed between January 2001 and December 2015. The presence of granulomas and amyloid deposits was observed in 68 (9.1%) and 62 (8.3%) patients, respectively. Granulomas were significantly associated with lower T classification, N classification, and overall TNM stage (p = 0.014, p = 0.006, and p = 0.001, respectively). Their presence was an independent predictor of overall survival (p = 0.033), disease-free survival (p = 0.034), and recurrence-free survival (p = 0.040). Conversely, amyloid deposition was not a predictor in any survival analyses. The present study demonstrated the prevalence of granuloma and amyloid deposition in the largest single institution cohort of primary NPC patients so far. Our results provide evidence that granulomas are significantly associated with better prognosis and treatment outcome. Further studies are needed to elucidate the mechanism of action of granuloma formation on the anti-tumor immunity of NPC.

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
Fig. 4

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available on request from the corresponding author.

References

  1. El-Naggar A, Chan J, Grandis J, Takata T, Slootweg P. WHO classification of head and neck tumours. Lyon: IARC; 2017.

    Google Scholar 

  2. Lee AW, Poon YF, Foo W, Law SC, Cheung FK, Chan DK, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys. 1992;23(2):261–70.

    Article  CAS  Google Scholar 

  3. Chang JT, Chan SH, Lin CY, Lin TY, Wang HM, Liao CT, et al. Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15. Mol Cancer Ther. 2007;6(8):2271–9. https://doi.org/10.1158/1535-7163.MCT-06-0801.

    Article  CAS  PubMed  Google Scholar 

  4. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol: Off J Am Soc Clin Oncol. 1998;16(4):1310–7. https://doi.org/10.1200/JCO.1998.16.4.1310.

    Article  CAS  Google Scholar 

  5. Lin JC, Jan JS, Chen KY, Hsu CY, Liang WM, Wang WY. Outpatient weekly 24-hour infusional adjuvant chemotherapy of cisplatin, 5-fluorouracil, and leucovorin for high-risk nasopharyngeal carcinoma. Head Neck. 2003;25(6):438–50. https://doi.org/10.1002/hed.10238.

    Article  PubMed  Google Scholar 

  6. Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol: Off J Am Soc Clin Oncol. 2003;21(4):631–7. https://doi.org/10.1200/JCO.2003.06.158.

    Article  Google Scholar 

  7. Wockel W, Wernert N. Excessive epithelioid cell granulomatous reaction associated with a lymphoepithelial carcinoma (Schmincke-Regaud). Pathol Res Pract. 1986;181(3):349–56. https://doi.org/10.1016/S0344-0338(86)80118-2.

    Article  CAS  PubMed  Google Scholar 

  8. Chen CL, Su IJ, Hsu MM, Hsu HC. Granulomatous nasopharyngeal carcinoma: with emphasis on difficulty in diagnosis and favorable outcome. Journal of the Formos Med Assoc = Taiwan yi zhi. 1991;90(4):353–6.

    CAS  PubMed  Google Scholar 

  9. Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology E-Book. Amsterdam: Elsevier Health Sciences; 2017.

    Google Scholar 

  10. Prathap K, Looi LM, Prasad U. Localized amyloidosis in nasopharyngeal carcinoma. Histopathology. 1984;8(1):27–34.

    Article  CAS  Google Scholar 

  11. Kamiyoshihara M, Hirai T, Kawashima O, Ishikawa S, Morishita Y. Sarcoid reactions in primary pulmonary carcinoma: report of seven cases. Oncol Rep. 1998;5(1):177–80.

    CAS  PubMed  Google Scholar 

  12. Diaz Del Arco C, Acenero MJ. Sarcoid reaction: a rare occurrence associated to colon adenocarcinoma (case report and literature review). J Gastrointest Oncol. 2016;7(4):E72–E7676. https://doi.org/10.21037/jgo.2016.03.07.

    Article  PubMed  PubMed Central  Google Scholar 

  13. O'Connell MJ, Schimpff SC, Kirschner RH, Abt AB, Wiernik PH. Epithelioid granulomas in Hodgkin disease. A favorable prognostic sign? JAMA. 1975;233(8):886–9.

    Article  CAS  Google Scholar 

  14. Sacks EL, Donaldson SS, Gordon J, Dorfman RF. Epithelioid granulomas associated with Hodgkin’s disease: clinical correlations in 55 previously untreated patients. Cancer. 1978;41(2):562–7.

    Article  CAS  Google Scholar 

  15. Brincker H. Sarcoid reactions and sarcoidosis in Hodgkin's disease and other malignant lymphomata. Br J Cancer. 1972;26(2):120–3.

    Article  CAS  Google Scholar 

  16. Brady G, MacArthur GJ, Farrell PJ. Epstein-Barr virus and Burkitt lymphoma. J Clin Pathol. 2007;60(12):1397–402. https://doi.org/10.1136/jcp.2007.047977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bickham K, Munz C, Tsang ML, Larsson M, Fonteneau JF, Bhardwaj N, et al. EBNA1-specific CD4+ T cells in healthy carriers of Epstein-Barr virus are primarily Th1 in function. J Clin Investig. 2001;107(1):121–30. https://doi.org/10.1172/JCI10209.

    Article  CAS  PubMed  Google Scholar 

  18. Finberg RW. Epstein-Barr virus-specific T cells for the management of Epstein-Barr virus lymphomas. Curr Opin Oncol. 2001;13(5):349–53.

    Article  CAS  Google Scholar 

  19. Munz C, Bickham KL, Subklewe M, Tsang ML, Chahroudi A, Kurilla MG, et al. Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med. 2000;191(10):1649–60.

    Article  CAS  Google Scholar 

  20. Leen A, Meij P, Redchenko I, Middeldorp J, Bloemena E, Rickinson A, et al. Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol. 2001;75(18):8649–59.

    Article  CAS  Google Scholar 

  21. Haralambieva E, Rosati S, van Noesel C, Boers E, van Marwijk KM, Schuuring E, et al. Florid granulomatous reaction in Epstein-Barr virus-positive nonendemic Burkitt lymphomas: report of four cases. Am J Surg Pathol. 2004;28(3):379–83.

    Article  Google Scholar 

  22. Frappier L. Role of EBNA1 in NPC tumourigenesis. Semin Cancer Biol. 2012;22(2):154–61. https://doi.org/10.1016/j.semcancer.2011.12.002.

    Article  CAS  PubMed  Google Scholar 

  23. Pavic M, Debourdeau P, Vacelet V, Rousset H. Sarcoidosis and sarcoid reactions in cancer. Rev Med Interne. 2008;29(1):39–45. https://doi.org/10.1016/j.revmed.2007.09.041.

    Article  CAS  PubMed  Google Scholar 

  24. Looi LM. The pattern of amyloidosis in a Malaysian patient population. Histopathology. 1991;18(2):133–41.

    Article  CAS  Google Scholar 

  25. Ueno T, Hoshii Y, Cui D, Kawano H, Gondo T, Takahashi M, et al. Immunohistochemical study of cytokeratins in amyloid deposits associated with squamous cell carcinoma and dysplasia in the oral cavity, pharynx and larynx. Pathol Int. 2003;53(5):265–9.

    Article  Google Scholar 

  26. Tsujikawa T, Kumar S, Borkar RN, Azimi V, Thibault G, Chang YH, et al. Quantitative multiplex immunohistochemistry reveals myeloid-inflamed tumor-immune complexity associated with poor prognosis. Cell Rep. 2017;19(1):203–17. https://doi.org/10.1016/j.celrep.2017.03.037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank all the members of the Cancer Center, Chang Gung Memorial Hospital, for their invaluable help.

Funding

This study was supported by a grant (MOST105-2628-B-182A-008-MY3) from the Ministry of Science & Technology and a grant (CMRPG2G0231) from Chang Gung Memorial Hospital, Keelung, Taiwan.

Author information

Author notes

  1. Yi-Chan Lee and Li-Yu Lee contributed equally as the first authors.

Authors and Affiliations

  1. Department of Otolaryngology—Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan

    Yi-Chan Lee

  2. Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Li-Yu Lee & Tseng-tong Kuo

  3. Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Ngan-Ming Tsang

  4. Department of Hematology-Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Cheng-Lung Hsu

  5. Department of Otolaryngology—Head and Neck Surgery, Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, Kwei-Shan, Taoyuan, 33305, Taiwan

    Li-Jen Hsin & Kai-Ping Chang

  6. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Yi-Chan Lee, Li-Yu Lee, Ngan-Ming Tsang, Cheng-Lung Hsu, Li-Jen Hsin & Kai-Ping Chang

Authors
  1. Yi-Chan Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li-Yu Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ngan-Ming Tsang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng-Lung Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Jen Hsin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tseng-tong Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kai-Ping Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YCL and LYL: Substantial contributions to the acquisition of data. Giving final approval of the version to be published. NMT: Analysis and interpretation of data. Giving final approval of the version to be published. CLH: Ensuring that questions related to the accuracy of the work are appropriately investigated and resolved. Giving final approval of the version to be published. LJH: Drafting and revising the manuscript critically. Giving final approval of the version to be published. TTK: Revising the manuscript for important intellectual content. Giving final approval of the version to be published. KPC: Substantial contributions to conception of the manuscript. Revising the manuscript critically for important intellectual content. Giving final approval of the version to be published.

Corresponding author

Correspondence to Kai-Ping Chang.

Ethics declarations

Conflict of interest

None declared.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, YC., Lee, LY., Tsang, NM. et al. Prognostic Significance of Granuloma and Amyloid Deposition in Nasopharyngeal Carcinoma. Head and Neck Pathol 15, 153–162 (2021). https://doi.org/10.1007/s12105-020-01194-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-020-01194-4

Keywords

Search

Navigation