Skip to main content
Log in

Hobnail Variant of Papillary Thyroid Carcinoma: a Literature Review

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Papillary thyroid carcinoma is the most common thyroid malignancy and it is usually associated with a good prognosis. However, recurrence, metastases, and cancer death may occur in 10 to 15% of patients with more aggressive types of papillary thyroid carcinoma, such as tall cell, columnar cell, solid variant, or the more recently described hobnail variant of papillary thyroid carcinoma. Papillary thyroid carcinoma with a prominent hobnail pattern is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. The hobnail variant of papillary thyroid carcinoma shows prominent hobnail features, which have also been referred to as micropapillary. The typical hobnail/micropapillary morphological features show loss of cellular polarity/cohesiveness and support an epithelial-mesenchymal transition as a possible mechanism of metastasis. BRAF p.V600E is the most common mutation in papillary thyroid carcinoma, including the hobnail variant; recent and continuing studies are focused on defining other molecular anomalies that may be useful for prognostic stratification and may provide therapeutic targets.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Asioli S, Erickson LA, Sebo TJ, Zhang J, Jin L, Thompson GB, Lloyd RV. Papillary thyroid carcinoma with prominent hobnail features: a new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of eight cases. Am J Surg Pathol 2010 34:44–52, 2010.

    Article  Google Scholar 

  2. Lloyd RV, Buehler D, Khanafshar E. Papillary thyroid carcinoma variants. Head Neck Pathol 5:51–56, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ashraf K, Nosé V. Pathology of thyroid gland. In: Lloyd RV (Ed.) Endocrine Pathology, 1st edn. New York: Springer, pp. 181–235, 2010.

  4. Lubitz CC, Sosa JA. The changing landscape of papillary thyroid cancer: epidemiology, management, and the implications for patients. Cancer 122: 3754–3759, 2016.

    Article  PubMed  Google Scholar 

  5. Asioli S, Erickson LA, Righi A, Lloyd RV. Papillary thyroid carcinoma with hobnail features: histopathologic criteria to predict aggressive behavior. Hum Pathol 44: 320–328, 2013.

    Article  PubMed  Google Scholar 

  6. Asioli S, Maletta F, Pagni F, Pacchioni D, Vanzati A, Mariani S, et al. Cytomorphologic and molecular features of hobnail variant of papillary thyroid carcinoma: case series and literature review. Diagn Cytopathol 42:78–84, 2014.

    Article  PubMed  Google Scholar 

  7. Nucera C. Evolution of resistance to thyroid cancer therapy. Aging (Albany NY) 8:1576–1577, 2016.

    Article  Google Scholar 

  8. Kakudo K, Tang W, Ito Y, Mori I, Nakamura Y, Miyauchi A. Papillary carcinoma of the thyroid in Japan: subclassification of common type and identification of low risk group. J Clin Pathol 57:1041–1046, 2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Motosugi U, Murata S-I, Nagata K, Yasuda M, Shimizu M. Thyroid papillary carcinoma with micropapillary and hobnail growth pattern: a histological variant with intermediate malignancy? Thyroid 19:535–537, 2009.

    Article  PubMed  Google Scholar 

  10. Eloy C. Newly described thyroid tumours and variants. Diagn Histopathol 22:179–183, 2016.

    Article  Google Scholar 

  11. Albores-Saavedra J. Papillary thyroid carcinoma with prominent hobnail features: a new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of 8 cases. Am J Surg Pathol 34: 913, 2010.

    Article  PubMed  Google Scholar 

  12. Rosai J, Albores-Saavedra J, Asioli S, Baloch ZW, Bogdanova T, Chen H, et al. Papillary thyroid carcinoma. In: Lloyd RV, Asa SL, Kloppel G, Rosai J. WHO classification of tumours of endocrine organs, 4th edition. Lyon: IARC Press, pp. 81–92, 2017.

    Google Scholar 

  13. Lino-Silva LS, Domínguez-Malagón HR, Caro-Sánchez CH, Salcedo-Hernández RA. Thyroid gland papillary carcinomas with “micropapillary pattern,” a recently recognized poor prognostic finding: clinicopathologic and survival analysis of 7 cases. Hum Pathol 43:1596–1600, 2012.

    Article  PubMed  Google Scholar 

  14. Lubitz CC, Economopoulos KP, Pawlak AC, Lynch K, Dias-Santagata D, Faquin WC, Sadow PM. Hobnail variant of papillary thyroid carcinoma: an institutional case series and molecular profile. Thyroid 24:958–965, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Amacher AM, Goyal B, Lewis JS Jr, El-Mofty SK, Chernock RD. Prevalence of a hobnail pattern in papillary, poorly differentiated, and anaplastic thyroid carcinoma: a possible manifestation of high-grade transformation. Am J Surg Pathol 39:260–265, 2015.

    Article  PubMed  Google Scholar 

  16. Lee YS, Kim Y, Jeon S, Bae JS, Jung SL, Jung CK. Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review. Int J Clin Exp Pathol 8:7988–7997, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ieni A, Barresi V, Cardia R, Licata L, Di Bari F, Benvenga S, Tuccari G. The micropapillary/hobnail variant of papillary thyroid carcinoma: a review of series described in the literature compared to a series from one southern Italy pathology institution. Rev Endocr Metab Disord 17:521–527, 2016.

    Article  CAS  PubMed  Google Scholar 

  18. Morandi L, Righi A, Maletta F, Rucci P, Pagni F, Gallo M, Rossi S, Caporali L, Sapino A, Lloyd RV, Asioli S. Somatic mutation profiling of hobnail variant of papillary thyroid carcinoma. Endocr Relat Cancer 24:107–117, 2017.

    Article  PubMed  Google Scholar 

  19. Teng L, Deng W, Lu J, Zhang J, Ren X, Duan H, et al. Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. Oncotarget 28:22023–22033, 2017.

    Google Scholar 

  20. Lilo MT, Bishop JA, Ali SZ. Hobnail variant of papillary thyroid carcinoma: a case with an unusual presentation. Diagn Cytopathol. 2017 Apr 16. https://doi.org/10.1002/dc.23723.

  21. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26:1-133, 2016.

    Google Scholar 

  22. Cassol CA, Asa SL. Molecular pathology of thyroid cancer. Diagn Histopathol 17:124–139, 2011.

    Article  Google Scholar 

  23. Perros P. Report of the thyroid cancer guidelines update group. In: British Thyroid Association & Royal College of Physicians (Ed.) Guidelines for the Management of Thyroid Cancer, 2nd edn. London: Royal College of Physicians, pp. 1–92, 2007.

  24. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 132:658–665, 2009.

    Article  PubMed  Google Scholar 

  25. Bellevicine C, Cozzolino I, Malapelle U, Zeppa P, Troncone G. Cytological and molecular features of papillary thyroid carcinoma with prominent hobnail features: a case report. Acta Cytol 56:560–564, 2012.

    Article  PubMed  Google Scholar 

  26. Lee SH, Jung CK, Bae JS, Jung SL, Choi YJ, Kang CS. Liquid-based cytology improves preoperative diagnostic accuracy of the tall cell variant of papillary thyroid carcinoma. Diagnostic Cytopathol 42:11–17, 2014.

    Article  Google Scholar 

  27. Lloyd RV, Erickson LA, Asioli S. In response. Am J Surg Pathol 34: 914, 2010.

    Article  Google Scholar 

  28. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:244–285, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nassar H, Pansare V, Zhang H, Che M, Sakr W, Ali-Fehmi R, Grignon D, et al. Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein. Mod Pathol 17:1045–1050, 2004.

    Article  CAS  PubMed  Google Scholar 

  30. Romei C, Elisei R. RET/PTC translocations and clinico-pathological features in human papillary thyroid carcinoma. Front Endocrinol (Lausanne). 11;3:54, 2012.

    CAS  Google Scholar 

  31. Abubaker J, Jehan Z, Bavi P, Sultana M, Al-Harbi S, Ibrahim M, Al-Nuaim A, et al. Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population. J Clin Endocrinol Metab 93:611–618, 2008.

    Article  CAS  PubMed  Google Scholar 

  32. Lui WO, Zeng L, Rehrmann V, Deshpande S, Tretiakova M, Kaplan EL, Leibiger I, et al. CREB3L2-PPARγ fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis. Cancer Res 68:7156–7164, 2008.

    Article  CAS  PubMed  Google Scholar 

  33. Santarpia L, El-Naggar AK, Cote GJ, Myers JN, Sherman SI.. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab 93:278–284, 2008.

    Article  CAS  PubMed  Google Scholar 

  34. Viola D, Valerio L, Molinaro E, Agate L, Bottici V, Biagini A, Lorusso L, et al. 2016. Treatment of advanced thyroid cancer with targeted therapies: ten years of experience. Endocr Relat Cancer, 23:R185–R205

    Article  CAS  PubMed  Google Scholar 

  35. Ciampi R, Nikiforov YE. Alterations of the BRAF gene in thyroid tumors. Endocr Pathol 16:163–171, 2005.

    Article  CAS  PubMed  Google Scholar 

  36. Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 309:1493–1501, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 99: E754–E765, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu Z, Kakudo K, Bai Y, Li Y, Ozaki T, Miyauchi A, Taniguchi E, et al. Loss of cellular polarity/cohesiveness in the invasive front of papillary thyroid carcinoma, a novel predictor for lymph node metastasis; possible morphological indicator of epithelial mesenchymal transition. J Clin Pathol 64:325–329, 2011.

    Article  PubMed  Google Scholar 

  39. Hardin H, Guo Z, Shan W, Montemayor-Garcia C, Asioli S, Yu X-M, Harrison AD, et al. The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p in papillary thyroid carcinoma progression. Am J Pathol 184:2342–2354, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Asioli S, Erickson LA, Righi A, Jin L, Volante M, Jenkins S, Papotti M, et al. Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression. Modern Pathol 23:1269–1278, 2010.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sofia Asioli.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ambrosi, F., Righi, A., Ricci, C. et al. Hobnail Variant of Papillary Thyroid Carcinoma: a Literature Review. Endocr Pathol 28, 293–301 (2017). https://doi.org/10.1007/s12022-017-9502-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-017-9502-7

Keywords

Navigation