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Should familial disease be considered as a negative prognostic factor in micropapillary thyroid carcinoma?

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Abstract

Purpose

An increased aggressiveness of familial papillary thyroid carcinoma (FPTC) compared with sporadic form has been reported. On the contrary, the biological behavior of familial microPTC (FmPTC) is still debated. To assess if familial diseases should be considered as a negative prognostic factor in mPTC, the clinical presentation and outcome of FmPTC and sporadic mPTC (SmPTC) were compared.

Methods

We retrospectively analyzed 291 mPTC (SmPTC n = 248, FmPTC n = 43) patients followed for a median follow-up of 8.3 years. FmPTC was defined as the presence of PTC in two or more first-degree relatives, after excluding hereditary syndromes associated with PTC.

Results

FmPTC patients had more frequently bilateral tumor (32.6% versus 16.5%, p = 0.01) and lymph node metastases at diagnosis (30.2% versus 14.9%, p = 0.02). At the first follow-up, FmPTC patients had a higher rate of structural disease and a lower rate of remission compared to SmPTC (p = 0.01). Also in a multivariate model, using a “CHAID tree-building algorithm”, familial disease correlated with a worse clinical presentation and outcome of mPTC patients. Familial disease was associated with a higher rate of intermediate risk patients in non incidental mPTC and with a higher rate of structural incomplete response in mPTC without lymph node metastases (p = 0.01).

Conclusions

Like in macroPTC, the familial form of the diseases has been shown to be a negative prognostic factor also in mPTC, therefore, it should be highly regarded in the management of mPTC patients.

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References

  1. Hedinger C, Williams E (1988) Sobin L histologic types of thyroid tumours in World Health Organization histological classification of tumors, 2nd edn. Springer, New York, pp 9–10

    Book  Google Scholar 

  2. Davies L, Welch HG (2014) Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 140:317–322

    Article  PubMed  Google Scholar 

  3. Vaccarella S, Dal Maso L, Laversanne M, Bray F, Plummer M, Franceschi S (2015) The impact of diagnostic changes on the rise in thyroid cancer incidence: a population-based study in selected high-resource countries. Thyroid 25:1127–1136

    Article  PubMed  Google Scholar 

  4. Brito JP, Morris JC, Montori VM (2013) Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours. BMJ 347:f4706

    Article  PubMed  Google Scholar 

  5. Mazeh H, Sippel RS (2013) Familial nonmedullary thyroid cancer. Thyroid 23:1049–1056

    Article  PubMed  Google Scholar 

  6. Cantara S, Marzocchi C, Castagna MG, Pacini F (2017) HABP2 G534E variation in familial non-medullary thyroid cancer: an Italian series. J Endocrinol Invest 40:557–560

    Article  CAS  PubMed  Google Scholar 

  7. Moses W, Weng J, Kebebew E (2011) Prevalence, clinicopathologic features, and somatic genetic mutation profile in familial versus sporadic nonmedullary thyroid cancer. Thyroid 21:367–371

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ito Y, Kakudo K, Hirokawa M, Fukushima M, Yabuta T, Tomoda C, Inoue H, Kihara M, Higashiyama T, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Miyauchi A (2009) Biological behavior and prognosis of familial papillary thyroid carcinoma. Surgery 145:100–105

    Article  PubMed  Google Scholar 

  9. Capezzone M, Marchisotta S, Cantara S, Busonero G, Brilli L, Pazaitou-Panayiotou K, Carli AF, Caruso G, Toti P, Capitani S, Pammolli A, Pacini F (2008) Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity. Endocr Relat Cancer 15:1075–1081

    Article  CAS  PubMed  Google Scholar 

  10. Park YJ, Ahn HY, Choi HS, Kim KW, Park DJ, Cho BY (2012) The long-term outcomes of the second generation of familial nonmedullary thyroid carcinoma are more aggressive than sporadic cases. Thyroid 22:356–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pinto AE, Silva GL, Henrique R, MenezesTeixeira MR, Leite V, Cavaco BM (2013) Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour. Eur J Endocrinol 21:321–327

    Google Scholar 

  12. Pitoia F, Cross G, Salvai ME, Abelleira E, Niepomniszcze H (2011) Patients with familial non-medullary thyroid cancer have an outcome similar to that of patients with sporadic papillary thyroid tumors. Arq Bras Endocrinol Metabol 55:219–223

    Article  PubMed  Google Scholar 

  13. Bernet V (2010) Approach to the patient with incidental papillary microcarcinoma. J Clin Endocrinol Metab 95:3586–3592

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  15. Gui CY, Qiu SL, Peng ZH, Wang M (2018) Clinical and pathologic predictors of central lymph node metastasis in papillary thyroid microcarcinoma: a retrospective cohort study. J Endocrinol Invest 41:403–409

    Article  CAS  PubMed  Google Scholar 

  16. Lupoli G, Vitale G, Caraglia M, Fittipaldi MR, Abbruzzese A, Tagliaferri P, Bianco AR (1999) Familial papillary thyroid microcarcinoma: a new clinical entity. Lancet 353:637–639

    Article  CAS  PubMed  Google Scholar 

  17. Fernández-Real JM, Ricart W (1999) Familial papillary thyroid microcarcinoma. Lancet 353:1973–1974

    Article  PubMed  Google Scholar 

  18. Lee CR, Park S, Kang SW, Lee J, Jeong JJ, Nam KH, Chung WY, Park CS (2017) Is familial papillary thyroid microcarcinoma more aggressive than sporadic form? Ann Surg Treat Res 92:129–135

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pellegriti G, Scollo C, Lumera G, Regalbuto C, Vigneri R, Belfiore A (2004) Clinical behavior and outcome of papillary thyroid cancers smaller than 1.5 cm in diameter: study of 299 cases. J Clin Endocrinol Metab 89:3713–3720

    Article  CAS  PubMed  Google Scholar 

  20. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214

  21. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 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

    Article  PubMed  PubMed Central  Google Scholar 

  22. Momesso DP, Vaisman F, Yang SP, Bulzico DA, Corbo R, Vaisman M, Tuttle RM (2016) Dynamic risk stratification in patients with differentiated thyroid cancer treated without radioactive iodine. J Clin Endocrinol Metab 101:2692–2700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Leboulleux S, Tuttle RM, Pacini F, Schlumberger M (2016) Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? Lancet Diabetes Endocrinol 4:933–942

    Article  PubMed  Google Scholar 

  24. Nickel B, Brito JP, Barratt A, Jordan S, Moynihan R, McCaffery K (2017) Clinicians’ views on management and terminology for papillary thyroid microcarcinoma: a qualitative study. Thyroid 27:661–667

    Article  PubMed  Google Scholar 

  25. Pacini F, Basolo F, Bellantone R, Boni G, Cannizzaro MA, De Palma M, Durante C, Elisei R, Fadda G, Frasoldati A, Fugazzola L, Guglielmi R, Lombardi CP, Miccoli P, Papini E, Pellegriti G, Pezzullo L, Pontecorvi A, Salvatori M, Seregni E, Vitti P (2018) Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. J Endocrinol Invest 41:849–876

    Article  CAS  PubMed  Google Scholar 

  26. Davies L (2016) Overdiagnosis of thyroid cancer. BMJ 355:i6312

    Article  PubMed  Google Scholar 

  27. Mazeh H, Benavidez J, Poehls JL, Youngwirth L, Chen H, Sippel RS (2012) In patients with thyroid cancer of follicular cell origin, a family history of nonmedullary thyroid cancer in one first-degree relative is associated with more aggressive disease. Thyroid 22:3–8

    Article  PubMed  Google Scholar 

  28. Uchino S, Noguchi S, Kawamoto H, Yamashita H, Watanabe S, Yamashita H, Shuto S (2002) Familial nonmedullary thyroid carcinoma characterized by multifocality and a high recurrence rate in a large study population. World J Surg 26:897–902

    Article  PubMed  Google Scholar 

  29. Tavarelli M, Russo M, Terranova R, Scollo C, Spadaro A, Sapuppo G, Malandrino P, Masucci R, Squatrito S, Pellegriti G (2015) Familial non-medullary thyroid cancer represents an independent risk factor for increased cancer aggressiveness: a retrospective analysis of 74 families. Front Endocrinol (Lausanne) 6:117

    Article  Google Scholar 

  30. Wang X, Cheng W, Li J, Su A, Wei T, Liu F, Zhu J (2015) Endocrine tumours: familial nonmedullary thyroid carcinoma is a more aggressive disease: a systematic review and meta-analysis. Eur J Endocrinol 172:R253–R262

    Article  CAS  PubMed  Google Scholar 

  31. Cao J, Chen C, Chen C, Wang QL, Ge MH (2016) Clinicopathological features and prognosis of familial papillary thyroid carcinoma–a large-scale, matched, case-control study. Clin Endocrinol 84:598–606

    Article  Google Scholar 

  32. Castagna MG, Forleo R, Maino F, Fralassi N, Barbato F, Palmitesta P, Pilli T, Capezzone M, Brilli L, Ciuoli C, Cantara S, Formichi C, Pacini F (2018) Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor. J Endocrinol Invest 41:1029–1035

    Article  CAS  PubMed  Google Scholar 

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Funding

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

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Authors and Affiliations

  1. Section of Endocrinology and Metabolism, Department of Medical, Surgical and Neurological Sciences, University of Siena, Policlinico Santa Maria alle Scotte, Viale Bracci 1, 53100, Siena, Italy

    M. Capezzone, C. Secchi, N. Fralassi, S. Cantara, L. Brilli, C. Ciuoli, T. Pilli, F. Maino, R. Forleo, F. Pacini & M. G. Castagna

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  1. M. Capezzone
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  2. C. Secchi
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  3. N. Fralassi
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  4. S. Cantara
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  5. L. Brilli
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  6. C. Ciuoli
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  7. T. Pilli
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  8. F. Maino
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  9. R. Forleo
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  10. F. Pacini
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  11. M. G. Castagna
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Correspondence to M. G. Castagna.

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Capezzone, M., Secchi, C., Fralassi, N. et al. Should familial disease be considered as a negative prognostic factor in micropapillary thyroid carcinoma?. J Endocrinol Invest 42, 1205–1213 (2019). https://doi.org/10.1007/s40618-019-01039-0

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