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Papillary Microcarcinoma of the Thyroid: Clinical Characteristics and BRAFV600E Mutational Status of 977 Cases

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies. It is estimated that papillary thyroid microcarcinoma (PTMC) accounts for up to 30 % of all PTCs. The clinical significance of PTMC is still unclear, although it may be related to recurrence, distant metastasis, and mortality. The purpose of this study was to analyze the clinical characteristics and BRAFV600E mutational status of PTMCs in a Chinese population and to determine risk factors for poor prognosis.

Methods

We performed a retrospective review of 977 PTMC cases that underwent surgical resection from January 2001 to January 2010 at Tianjin Medical University Cancer Institute and Hospital.

Results

The mean size of 977 PTMCs was 5.2 (range, 2–10) mm. Multifocal tumors were seen in 323 patients. The majority of patients (692) had a T1 lesion, whereas 279 had T3 and 6 had T4a; 40.1 % patients had BRAFV600E mutation. The frequencies of extrathyroidal extension and lymph node metastasis were 29.2 and 23.4 %, respectively. Distant metastasis was present in 15 patients. Half of the patients (50.8 %) received a total thyroidectomy and others had a lobectomy.

Conclusions

The present study suggests that highly aggressive PTMCs may arise in a subset of patients with BRAFV600E mutation and tumors greater than 5 mm. Extrathyroidal invasion, lymph node metastases, and the type of surgical procedures were significantly associated with tumor recurrence. Although multivariate analysis showed that tumor recurrence was not associated with BRAFV600E mutation, it has not been shown that treating these patients more aggressively changes outcomes.

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References

  1. Udelsman R, Chen H. The current management of thyroid cancer. Adv Surg. 1999;33:1–27.

    Google Scholar 

  2. Lloyd R, De Lellis R, Heitz P, Eng C. World Health Organization classification of tumours: pathology and genetics of tumours of the endocrine organs. Lyon, France: IARC Press International Agency for Research on Cancer; 2004.

    Google Scholar 

  3. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi A, et al. An observational trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003;13:381–7.

    Article  PubMed  Google Scholar 

  4. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid-prognostic significance of lymph node metastasis and multifocality. Cancer. 2003;98:31–40.

    Article  PubMed  Google Scholar 

  5. Cappelli C, Castellano M, Braga M, Gandossi E, Pirola I, De Martino E, Agosti B, Agabiti Rosei E. Aggressiveness and outcome of papillary thyroid carcinoma (PTC) versus microcarcinoma (PMC): a mono-institutional experience. J Surg Oncol. 2007;95:555–60.

    Article  PubMed  CAS  Google Scholar 

  6. Leenhardt L, Grosclaude P, Che′rie′-Challine L. Thyroid Cancer Committee. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French thyroid cancer committee. Thyroid. 2004;14:1056–106.

    Article  PubMed  Google Scholar 

  7. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. J Am Med Assoc. 2006;295:2164–7.

    Article  CAS  Google Scholar 

  8. Lee X, Gao M, Ji Y, Yu Y, Feng Y, Li Y, Zhang Y, Cheng W, Zhao W. Analysis of differential BRAFV600E mutational status in high aggressive papillary thyroid microcarcinoma. Ann Surg Oncol. 2009;16:240–5.

    Article  PubMed  Google Scholar 

  9. Lin KD, Lin JD, Huang HS, Jeng LB, Ho YS. Skull metastasis with brain invasion from thyroid papillary microcarcinoma. J Formos Med Assoc. 1997;96:280–2.

    PubMed  CAS  Google Scholar 

  10. Liou M, Lin J, Chung M, Liau C, Hsueh C. Renal metastasis from papillary thyroid microcarcinoma. Acta Otolaryngol. 2005;125:438–42.

    Article  PubMed  CAS  Google Scholar 

  11. Arora N, Turbendian HK, Kato MA, Moo TA, Zarnegar R, Fahey TJ. Papillary thyroid carcinoma and microcarcinoma: is there a need to distinguish the two? Thyroid. 2009;19:473–7.

    Article  PubMed  Google Scholar 

  12. Moon HJ, Kim EK, Chung WY. Minimal extrathyroidal extension in patients with papillary thyroid microcarcinoma: is it a real prognostic factor? Ann Surg Oncol. 2011;18:1916–23.

    Article  PubMed  Google Scholar 

  13. Besic N, Pilko G, Petric R, Hocevar M, Zgajnar J. Papillary thyroid microcarcinoma: prognostic factors and treatment. J Surg Oncol. 2008;97:221–5.

    Article  PubMed  Google Scholar 

  14. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, Biddinger PW, Nikiforov YE. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006;30:216–22.

    Article  PubMed  Google Scholar 

  15. Namba H, Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, Ohtsuru A, Saenko VA, Kanematsu T, Yamashita S. Clinical implication of hot spot BRAF mutation,V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003;88:4393–7.

    Article  PubMed  CAS  Google Scholar 

  16. Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A, Santoro M, Fagin JA, Nikiforov YE. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas. J Clin Endocrinol Metab. 2003 88 5399–5404.

    Google Scholar 

  17. Puxeddu E, Moretti S, Elisei R, Romei C, Pascucci R, Martinelli M, Marino C, Avenia N, Rossi ED, Fadda G, Cavaliere A, Ribacchi R, Falorni A, Pontecorvi A, Pacini F, Pinchera A, Santeusanio F. BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas. J Clin Endocrinol Metab. 2004;89:2414–20.

    Article  PubMed  CAS  Google Scholar 

  18. Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res. 2003;63:4561–7.

    PubMed  CAS  Google Scholar 

  19. Kim KH, Kang DW, Kim SH, Seong IO, Kang DY. Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population. Yonsei Med J. 2004;45:818–21.

    PubMed  CAS  Google Scholar 

  20. Liu D, Liu Z, Condouris S, Xing M. BRAF V600E maintains proliferation, transformation, and tumorigenicity of BRAF-mutant papillary thyroid cancer cells. J Clin Endocrinol Metab. 2007;92:2264–71.

    Article  PubMed  CAS  Google Scholar 

  21. Kim EK, Park CS, Chung WY, Oh KK, Kim DI, Lee JT, Yoo HS. New sonographic criteria for recommending fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. AJR Am J Roentgenol. 2002;178:687–91.

    Article  PubMed  Google Scholar 

  22. Neuhold N, Schultheis A, Hermann M. Incidental papillary microcarcinoma of the thyroid-further evidence of a very low malignant potential: a retrospective clinicopathological study with up to 30 years of follow-up. Ann Surg Oncol. 2011;18:3430–6.

    Article  PubMed  Google Scholar 

  23. Rouxel A, Hejblum G, Bernier MO, Boelle PY, Menegaux F, Mansour G, Hoang C, Aurengo A, Leenhardt L. Prognostic factors associated with the survival of patients developing locoregional recurrences of differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2004;89:5362–8.

    Article  PubMed  CAS  Google Scholar 

  24. Hay ID, Hutchinson ME, Gonzales-Londosa T, et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery. 2008;144:908-88.

    Article  Google Scholar 

  25. Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J Surg. 2008;32:747–53.

    Article  PubMed  Google Scholar 

  26. Kasai N, Sakamoto A. New subgrouping of small thyroid carcinomas. Cancer. 1987;60:1767–70.

    Article  PubMed  CAS  Google Scholar 

  27. Edge SB, Compton CC, Byrd DR. AJCC cancer staging manual, 7th edition. New York: Springer; 2010.

    Google Scholar 

  28. Burgess JR, Tucker P. Incidence trends for papillary thyroid carcinoma and their correlation with thyroid surgery and thyroid fine-needle aspirate cytology. Thyroid. 2006;16:47–53.

    Article  PubMed  Google Scholar 

  29. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006;295:2164–7.

    Article  PubMed  CAS  Google Scholar 

  30. Leenhardt L, Grosclaude P, Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid. 2004;14:1056–60.

    Article  PubMed  Google Scholar 

  31. Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer. 2009;115(16):3801-7.

    Article  PubMed  Google Scholar 

  32. Grodski S, Brown T, Sidhu S, Gill A, Robinson B, Learoyd D, et al. Increased incidence of thyroid cancer is due to increased pathologic detection. Surgery. 2008;144:1038–43.

    Article  PubMed  Google Scholar 

  33. Nikiforov YE. Thyroid tumors: Classification and general considerations. In: Nikiforov YE, Biddinger PW, Thompson LDR, editors. Diagnostic pathology and molecular genetics of the thyroid. Philadelphia: Lippincott Williams & Wilkins; 2009:95–102.

    Google Scholar 

  34. Statistik Austria. Available: http://www.statistik.at/web_de/statistiken/gesundheit/krebserkrankungen/schilddruese/021796.html. Accessed 22 Aug 2010.

  35. Yamamoto Y, Maeda T, Izumi K, Otsuka H. Occult papillary carcinoma of the thyroid. A study of 408 autopsy cases. Cancer. 1990;65:1173–9.

    Article  PubMed  CAS  Google Scholar 

  36. Bramley MD, Harrison BJ. Papillary microcarcinoma of the thyroid gland. Br J Surg. 1996;83:1674–83.

    Article  PubMed  CAS  Google Scholar 

  37. Hay ID, Grant CS, van Heerden JA, et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112:1139-46.

    PubMed  CAS  Google Scholar 

  38. Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;237:399-407.

    PubMed  Google Scholar 

  39. Kwak JY, Kim EK, Kim MJ, et al. Papillary microcarcinoma of the thyroid: predicting factors of lateral neck node metastasis. Ann Surg Oncol. 2009;16:1348-55.

    Article  PubMed  Google Scholar 

  40. Friguglietti CU, Dutenhefner SE, Brandao LG, Kulcsar MA. Classification of papillar thyroid microcarcinoma according to the size and fine-needle aspiration cytology: behavior and therapeutic implications. Head Neck. 2011;33:696–701.

    Article  PubMed  Google Scholar 

  41. Miccoli P, Minuto MN, Ugolini C, Panicucci E, Berti P, Massi M, et al. Intrathyroidal differentiated thyroid carcinoma: tumor size-based surgical concepts. World J Surg. 2007;31:888–94.

    Article  PubMed  Google Scholar 

  42. Kwak JY, Kim E, Chung WY, Moon HJ, Kim MJ, Choi JR. Association of BRAFV600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology. 2009;253:854–60.

    Article  PubMed  Google Scholar 

  43. Howell GM, Carty SE, Armstrong MJ. Both BRAF V600E mutation and older age (> 65 years) are associated with recurrent papillary thyroid cancer. Ann Surg Oncol. 2011;5:19.

    Google Scholar 

  44. Zheng X, Xia T, Lin L, Gao S, Lee Y, Yu Y, Wei S, Gao M. BRAFV600E status and clinical characteristics in solitary and multiple papillary thyroid carcinoma: experience of 512 cases at a clinical center in China. World J Surg Oncol. 2012;10(1):104.

    Article  PubMed  Google Scholar 

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Acknowledgment

The authors thank Prof. Baocun Sun in Tianjin Medical University Cancer Institute and Hospital for providing materials, the members of Dr. Gao’s department for their assistance in the discussion, and Dr. Peirong Yu, Professor, Department of Plastic Surgery at the MD Anderson Cancer Center, Houston, TX, for scientific and language editing.

Conflict of interest

The authors declare that there is no conflict of interest for this study.

Funding

This research did not receive any specific grant from any funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Oncology Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China

    Xiangqian Zheng MD, PhD, Songfeng Wei MD, PhD, Yang Yu MD, PhD, Xinwei Yun MD & Ming Gao MD, PhD

  2. Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Oncology Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China

    Ying Han MD, PhD & Xiubao Ren MD, PhD

  3. Respiratory Department, Xiaolan Hospital Affiliated to Southern Medical University, Guangdong, People’s Republic of China

    Yancong Li MD

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  1. Xiangqian Zheng MD, PhD
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Correspondence to Ming Gao MD, PhD.

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Zheng, X., Wei, S., Han, Y. et al. Papillary Microcarcinoma of the Thyroid: Clinical Characteristics and BRAFV600E Mutational Status of 977 Cases. Ann Surg Oncol 20, 2266–2273 (2013). https://doi.org/10.1245/s10434-012-2851-z

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  • DOI: https://doi.org/10.1245/s10434-012-2851-z

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