Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies

Abstract

Background

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent.

Methods

Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field.

Objective

The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

This is a preview of subscription content, access via your institution.

Fig. 1

Abbreviations

PTMC:

Papillary thyroid microcarcinoma

DTC:

Differentiated thyroid cancer

Tg:

Thyroglobulin

TgAb:

Anti-thyroglobulin antibodies

rhTSH:

Recombinant human TSH

WBS:

Whole-body scan

RAI:

Radioactive iodine

US:

Ultrasound

FNA(C):

Fine-needle aspiration (cytology)

CCND:

Central compartment neck dissection

LID:

Low-iodine diet

MTA:

Maximum tolerated activity (of radioiodine)

CN0:

No clinical evidence of lymph nodes

References

  1. 1.

    Haugen BR, Alexander EK, Bible KC 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. https://doi.org/10.1089/thy.2015.0020

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, Rago T et al (2013) 2013 European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J. 2(3):147–159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. 3.

    Nardi F, Basolo F, Crescenzi A, Fadda G, Frasoldati A, Orlandi F, Palombini L, Papini E, Zini M, Pontecorvi A, Vitti P (2014) Italian consensus for the classification and reporting of thyroid cytology. J Endocrinol Investig 37(6):593–599. https://doi.org/10.1007/s40618-014-0062-0

    Article  Google Scholar 

  4. 4.

    Ali SZ, Cibas ES (eds) (2010) The Bethesda system for reporting thyroid cytopathology: definitions, criteria and explanatory notes. Springer, New York

    Google Scholar 

  5. 5.

    Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard Ba G, Gilbert J, Harrison B, Johnson SJ, Giles TE, Moss L, Lewington V, Newbold K, Taylor J, Thakker RV, Watkinson J, Williams GR, British Thyroid Association (2014) Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf) 81(Suppl 1):1–122

    Article  CAS  Google Scholar 

  6. 6.

    Yeh MW, Bauer AJ, Bernet VA et al (2015) American thyroid association statement on preoperative imaging for thyroid cancer surgery. Thyroid 25:3–13

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Wu LM, Gu HY, Qu XH, Zheng J, Zhang W, Yin Y, Xu JR (2012) The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma: a meta-analysis. Eur J Radiol 81(8):1798–1805

    Article  PubMed  Google Scholar 

  8. 8.

    Tufano RP, Clayman G, Heller KS, Inabnet WB, Kebebew E, Shaha A, Steward DL, Tuttle RM (2015) American thyroid association surgical affairs committee writing task force management of recurrent/persistent nodal disease in patients with differentiated thyroid cancer: a critical review of the risks and benefits of surgical intervention versus active surveillance. Thyroid 25(1):15–27

    Article  PubMed  Google Scholar 

  9. 9.

    Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS, Sturgeon C (2007) Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246:375–381

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Matsuzu K, Sugino K, Masudo K, Nagahama M, Kitagawa W, Shibuya H, Ohkuwa K, Uruno T, Suzuki A, Magoshi S, Akaishi J, Masaki C, Kawano M, Suganuma N, Rino Y, Masuda M, Kameyama K, Takami H, Ito K (2014) Thyroid lobectomy for papillary thyroid cancer: long-term follow-up study of 1,088 cases. World J Surg 38:68–79

    Article  PubMed  Google Scholar 

  11. 11.

    Adam MA, Pura J, Gu L, Dinan MA, Tyler DS, Reed SD, Scheri R, Roman SA, Sosa JA (2014) Extent of surgery for papillary thyroid cancer is not associated with survival: an analysis of 61,775 patients. Ann Surg 260:601–605

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Ito Y, Miyauchi A, Inoue H, Fukushima M, Kihara M, Higashiyama T, Tomoda C, Takamura Y, Kobayashi K, Miya A (2010) An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 4(1):28

    Article  Google Scholar 

  13. 13.

    Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, El-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA (2016) Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2:1023–1029

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Glockzin G, Hornung M, Kienle K et al (2012) Completion thyroidectomy: effect of timing on clinical complications and oncologic outcome in patients with differentiated thyroid cancer. World J Surg 36:1168–1173

    Article  PubMed  Google Scholar 

  15. 15.

    Hartl DM, Mamelle E, Borget I, Leboulleux S, Mirghani H, Schlumberger M (2013) Influence of prophylactic neck dissection on rate of retreatment for papillary thyroid carcinoma. World J Surg 37:1951–1958

    Article  PubMed  Google Scholar 

  16. 16.

    Viola D, Materazzi G, Valerio L, Molinaro E, Agate L, Faviana P, Seccia V, Sensi E, Romei C, Piaggi P, Torregrossa L, Sellari-Franceschini S, Basolo F, Vitti P, Elisei R, Miccoli P (2015) Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab 100:1316–1324

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Qu N, Zhang L, Ji QH, Chen JY, Zhu YX, Cao YM, Shen Q (2015) Risk factors for central compartment lymph node metastasis in papillary thyroid microcarcinoma: a meta-analysis. World J Surg 39:2459–2470

    Article  PubMed  Google Scholar 

  18. 18.

    Raffaelli M, De Crea C, Sessa L, Fadda G, Bellantone C, Lombardi CP (2015) Ipsilateral central neck dissection plus frozen section examination versus prophylactic bilateral central neck dissection in cN0 papillary thyroid carcinoma. Ann Surg Oncol 22:2032–2308

    Article  Google Scholar 

  19. 19.

    Collini P, Sampietro G, Pilotti S (2004) Extensive vascular invasion is a marker of risk of relapse in encapsulated non-Hürthle cell follicular carcinoma of the thyroid gland: a clinicopathological study of 18 consecutive cases from a single institution with a 11-year median follow-up. Histopathology 44:35–39

    Article  PubMed  CAS  Google Scholar 

  20. 20.

    Mahul B, Amin SE, Greene FL, Schilsky RL, Byrd DR, Gaspar LE, Washington MK, Gershenwald JE, Compton CC, Hess KR (2017) In: Brierley JD, Gospodarowicz MK, Wittekind C (eds) 2016 AJCC 8th Edition Cancer Staging Manual. Springer International Publishing AG, Cham, Switzerland.Edition). Wiley Blackwell, Oxford

  21. 21.

    Ganly I, Ibrahimpasic T, Rivera M et al (2012) Prognostic implication of papillary thyroid carcinoma with tall cell features. Mod Pathol 25:144A

    Google Scholar 

  22. 22.

    Dettmer MS, Schmitt A, Steinert H, Moch H, Komminoth P, Perren A (2012) Tall cell variant of papillary thyroid carcinoma- how many tall cells are needed? Mod Pathol 25:143

    Google Scholar 

  23. 23.

    Morris LG, Shaha AR, Tuttle RM, Sikora AG, Ganly I (2010) Tall-cell variant of papillary thyroid carcinoma: a matched-pair analysis of survival. Thyroid 20:153–158

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. 25.

    Nikiforov YE, Erickson LA, Nikiforova MN, Caudill CM, Lloyd RV (2001) Solid variant of papillary thyroid carcinoma: incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior. Am J Sur Pathol 25:1478–1484

    Article  CAS  Google Scholar 

  26. 26.

    Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J (2007) Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 31:1256–1264

    Article  PubMed  Google Scholar 

  27. 27.

    Asioli S, Erickson LA, Righi A, Jin L, Volante M, Jenkins S, Papotti M, Bussolati G, Lloyd RV (2010) Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression. Mod Pathol 23:1269–1278

    Article  PubMed  Google Scholar 

  28. 28.

    Regalbuto C, Malandrino P, Tumminia A, Le Moli R, Vigneri R, Pezzino V (2011) A diffuse sclerosing variant of papillary th thyroid carcinoma: clinical and pathologic features and outcomes of 34 consecutive cases. Thyroid 21:383–389

    Article  PubMed  Google Scholar 

  29. 29.

    Lam AK, Lo CY (2006) Diffuse sclerosing variant of papillary carcinoma of the thyroid: a 35-year comparative study at a single institution. Ann Surg Oncol 13:176–181

    Article  PubMed  Google Scholar 

  30. 30.

    Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A (2004) A novel classification system for patients with PTC: addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow-up period. Surgery 135:139–148

    Article  PubMed  Google Scholar 

  31. 31.

    Lamartina L, Durante C et al (2015) Low risk differentiated thyroid cancer and radioiodine remnant ablation: a systematic review of the literature. J Clin Endocrinol Metab 100:1748–1761

    Article  PubMed  CAS  Google Scholar 

  32. 32.

    Pacini F et al (2016) Recommendations for post-surgical thyroid ablation in differentiated thyroid cancer: a 2015 position statement of the Italian Society of Endocrinology. J Endocrinol Investig 39:341–347

    Article  CAS  Google Scholar 

  33. 33.

    Castagna MG et al (2016) Reappraisal of the indication for radioiodine thyroid ablation in differentiated thyroid cancer patients. J Endocrinol Invest 39:1087–1094

    Article  PubMed  CAS  Google Scholar 

  34. 34.

    Ruel E, Thomas S et al (2015) Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer. J Clin Endocrinol Metab 100:1529–1536

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. 35.

    Pacini F, Ladenson PW et al (2006) Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab 91:926–932

    Article  PubMed  CAS  Google Scholar 

  36. 36.

    Schlumberger M, Catargi B et al (2012) Strategies of radioiodine ablation in patients with low-risk thyoid cancer. NEJM 366:1663–1673

    Article  PubMed  CAS  Google Scholar 

  37. 37.

    Mallick U, Harmer C et al (2012) Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. NEJM 366:1674–1685

    Article  PubMed  CAS  Google Scholar 

  38. 38.

    Molinaro E, Giani C et al (2013) Patients with differentiated thyroid cancer who underwent radioiodine thyroid remnant ablation with low-activity 131I after either recombinant human TSH or thyroid hormone therapy withdrawal showed the same outcome after a 10-year follow-up. J Clin Endocrinol Metab 98:2693–2700

    Article  PubMed  CAS  Google Scholar 

  39. 39.

    Verburg FA, Mader U et al (2014) Long term survival in DTC is worse after low-activity initial post-surgical I-131 therapy in both high and low risk patients. J Clin Endocrinol Metab 99:4487–4496

    Article  PubMed  CAS  Google Scholar 

  40. 40.

    Castagna MG, Cevenini G et al (2013) Post-surgical thyroid ablation with low or high radioiodine activities results in similar outcomes in intermediate risk differentiated thyroid cancer patients. Eur J Endocrinol 169:23–29

    Article  PubMed  CAS  Google Scholar 

  41. 41.

    Tala Jury HP, Castagna MG, Fioravanti C, Cipri C, Brianzoni E, Pacini F (2010) Lack of association between urinary iodine excretion and successful thyroid ablation in thyroid cancer patients. J Clin Endocrinol Metab 95:230–237

    Article  PubMed  CAS  Google Scholar 

  42. 42.

    American Thyroid Association Taskforce On Radioiodine Safety, Sisson JC, Freitas J, McDougall IR, Dauer LT, Hurley JR, Brierley JD, Edinboro CH, Rosenthal D, Thomas MJ, Wexler JA, Asamoah E, Avram AM, Milas M, Greenlee C (2011) Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I: practice recommendations of the American Thyroid Association. Thyroid 21(4):335–346

    Article  Google Scholar 

  43. 43.

    International Commission on Radiological Protection (2004) Release of patients after therapy with unsealed radionuclides. Ann ICRP 34(2):v–vi, 1–79

    Article  Google Scholar 

  44. 44.

    Raccomandazioni per la dimissione dei pazienti a seguito di terapia medico nucleare con 131I. http://www.fisicamedica.it/2014_07_01_Raccomandazioni_dimissione_pazienti_131I.pdf

  45. 45.

    Brassard M, Borget I, Edet-Sanson A, Giraudet AL, Mundler O, Toubeau M, Bonichon F, Borson-Chazot F, Leenhardt L, Schvartz C, Dejax C, Brenot-Rossi I, Toubert ME, Torlontano M, Benhamou E, Schlumberger M, THYRDIAG Working Group (2011) Long-term follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients. J Clin Endocrinol Metab 2011 96:1352–1359

    Article  CAS  Google Scholar 

  46. 46.

    Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y, Takamura Y, Higashiyama T, Fukushima M, Kihara M, Inoue H, Tomoda C, Yabuta T, Masuoka H (2011) Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid 21:707–716

    Article  PubMed  Google Scholar 

  47. 47.

    Durante C, Montesano T, Attard M, Torlontano M, Monzani F, Costante G, Meringolo D, Ferdeghini M, Tumino S, Lamartina L, Paciaroni A, Massa M, Giacomelli L, Ronga G, Filetti S, PTC Study Group (2012) Long-term surveillance of papillary thyroid cancer patients who do not undergo post-operative radioiodine remnant ablation: is there a role for serum thyroglobulin measurement. J Clin Endocrinol Metab 2012 97:2748–2753

    Article  CAS  Google Scholar 

  48. 48.

    Durante C, Montesano T, Torlontano M, Attard M, Monzani F, Tumino S, Costante G, Meringolo D, Bruno R, Trulli F, Massa M, Maniglia A, D’Apollo R, Giacomelli L, Ronga G, Filetti S, PTC Study Group (2013) Papillary thyroid cancer: time course of recurrences during postsurgery surveillance. J Clin Endocrinol Metab 2013 98:636–642

    Article  CAS  Google Scholar 

  49. 49.

    Castagna MG, Tala Jury HP, Cipri C, Belardini V, Fioravanti C, Pasqui L, Sestini F, Theodoropoulou A, Pacini F (2011) The use of ultrasensitive thyroglobulin assays reduces but does not abolish the need for TSH stimulation in patients with differentiated thyroid carcinoma. J Endocrinol Investig 34:e219–e223

    CAS  Google Scholar 

  50. 50.

    Torlontano M, Crocetti U, Augello G, D’Aloiso L, Bonfitto N, Varraso A, Dicembrino F, Modoni S, Frusciante V, Di GA, Bruno R, Filetti S, Trischitta V (2006) Comparative evaluation of recombinant human thyrotropin-stimulated thyroglobulin levels, 131I whole body scintigraphy, and neck ultrasonography in the follow-up of patients with papillary thyroid microcarcinoma who have not undergone radioiodine therapy. J Clin Endocrinol Metab 2006 91:60–63

    Article  CAS  Google Scholar 

  51. 51.

    Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A (2010) Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid 20:1341–1349

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. 52.

    Vaisman F, Tala H, Grewal R, Tuttle RM (2011) In differentiated thyroid cancer, an incomplete structural reponse to therapy is associated with significantly worse clinical outcomes than only an incomplete thyroglobulin response. Thyroid 21:1317–1322

    Article  PubMed  CAS  Google Scholar 

  53. 53.

    Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M (2006) Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 91:2892–2899

    Article  PubMed  CAS  Google Scholar 

  54. 54.

    Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, Tuttle RM, Drucker W, Larson SM (2006) Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-d-glucose-positron emission tomography scanning. J Clin Endocrinol Metab 91:498–505

    Article  PubMed  CAS  Google Scholar 

  55. 55.

    Vaisman F, Momesso D, Bulzico DA, Pessoa CH, da Cruz MD, Dias F, Corbo R, Vaisman M, Tuttle RM (2013) Thyroid lobectomy is associated with excellent clinical outcomes in properly selected differentiated thyroid cancer patients with primary tumors greater than 1 cm. J Thyroid Res 2013:398194. https://doi.org/10.1155/2013/398194

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    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(7):2692–2700

    Article  PubMed  CAS  Google Scholar 

  57. 57.

    Freudenberg LS, Jentzen W, Petrich T, Frömke C, Marlowe RJ, Heusner T, Brandau W, Knapp WH, Bockisch A (2010) Lesion dose in differentiated thyroid carcinoma metastases after rhTSH or thyroid hormone withdrawal: 124I PET/CT dosimetric comparisons. Eur J Nucl Med Mol Imaging 37:2267–2276

    Article  PubMed  CAS  Google Scholar 

  58. 58.

    Potzi C, Moameni A, Karanikas G, Preitfellner J, Becherer A, Pirich C, Dudczak R (2006) Comparison of iodine uptake in tumour and nontumour tissue under thyroid hormone deprivation and with recombinant human thyrotropin in thyroid cancer patients. Clin Endocrinol (Oxf) 2006 65:519–523

    Article  CAS  Google Scholar 

  59. 59.

    Rani D, Kaisar S, Awasare S, Kamaldeep P, Abhyankar A, Basu S (2014) Examining recombinant human TSH primed 131I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol. Eur J Nucl Med Mol Imaging 41:1767–1780

    Article  PubMed  CAS  Google Scholar 

  60. 60.

    Tala H, Robbins R, Fagin JA, Larson SM, Tuttle RM (2011) Five-year survival is similar in thyroid cancer patients with distant metastases prepared for radioactive iodine therapy with either thyroid hormone withdrawal or recombinant human TSH. J Clin Endocrinol Metab 96:2105–2111

    Article  PubMed  CAS  Google Scholar 

  61. 61.

    Van Nostrand D, Atkins F, Yeganeh F, Acio E, Bursaw R, Wartofsky L (2002) Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. Thyroid 12:121–134

    Article  PubMed  Google Scholar 

  62. 62.

    Deandreis D, Rubino C, Tala H, Leboulleux S, Terroir M, Baudin E, Larson S, Fagin JA, Schlumberger M, Tuttle RM (2017) Comparison of empiric versus whole-body/-blood clearance dosimetry-based approach to radioactive iodine treatment in patients with metastases from differentiated thyroid cancer. J Nucl Med 58:717–722

    Article  PubMed  CAS  Google Scholar 

  63. 63.

    Pacini F, Lippi F, Formica N, Elisei R, Anelli S, Ceccarelli C, Pinchera A (1987) Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J Nucl Med 28:1888–1891

    PubMed  CAS  Google Scholar 

  64. 64.

    Padovani RP, Robenshtok E, Brokinn M, Tuttle RM (2012) Even without additional therapy, serum thyroglobulin concentrations often decline for years after total thyroidectomy and radioactive remnant ablation in patients with differentiated thyroid cancer. Thyroid 22:778–783

    Article  PubMed  CAS  Google Scholar 

  65. 65.

    Clement SC, Peeters RP, Ronckers CM et al (2015) Intermediate and long-term adverse effects of radioiodine therapy for differentiated thyroid carcinoma—a systematic review. Cancer Treat Rev 41:925–934

    Article  PubMed  CAS  Google Scholar 

  66. 66.

    Dingle IF, Mishoe AE, Nguyen SA et al (2013) Salivary morbidity and quality of life following radioactive iodine for well-differentiated thyroid cancer. Otolaryngol Head Neck Surg 148:746–752

    Article  PubMed  Google Scholar 

  67. 67.

    Canale D, Ceccarelli C, Caglieresi C et al (2015) Effects of radioiodine treatment for differentiated thyroid cancer on testis function. Clin Endocrinol (Oxf) 82:295–299

    Article  CAS  Google Scholar 

  68. 68.

    Wu JX, Young S, Ro K et al (2015) Reproductive outcomes and nononcologic complications after radioactive iodine ablation for well differentiated thyroid cancer. Thyroid 25:133–138

    Article  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Khang AR, Cho SW, Choi HS et al (2015) The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative (131) I dose over 37 GBq. Clin Endocrinol (Oxf) 23:220–227

    Google Scholar 

  70. 70.

    Sgouros G, Kolbert KS, Sheikh A, Pentlow KS, Mun EF, Barth A, Robbins RJ, Larson SM (2004) Patient-specific dosimetry for 131I thyroid cancer therapy using 124I PET and 3-dimensional-internal dosimetry (3D-ID) software. J Nucl Med 45:1366–1372

    PubMed  CAS  Google Scholar 

  71. 71.

    Brose MS, Nutting CM, Jarzab B et al (2014) Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384:319–328

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. 72.

    Schlumberger M, Tahara M, Wirth LJ et al (2015) Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372:621–630

    Article  PubMed  CAS  Google Scholar 

  73. 73.

    Abadin SS, Kaplan EL, Angelos P (2010) Malpractice litigation after thyroid surgery: the role of recurrent laryngeal nerve injuries, 1989–2009. Surgery 148(4):718–722

    Article  PubMed  Google Scholar 

  74. 74.

    Polistena A, Di Lorenzo P, Sanguinetti A, Buccelli C, Conzo G, Conti A, Niola M, Avenia N (2016) Medicolegal implications of surgical errors and complications in neck surgery: a review based on the Italian current legislation. Open Med 2016 11:298–306

    Google Scholar 

  75. 75.

    Randolph GW, Duh QY, Heller KS, LiVolsi VA, Mandel SJ, Steward DL, Tufano RP, Tuttle RM (2012) The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid 22:1144–1152

    Article  PubMed  Google Scholar 

  76. 76.

    Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl DM, Bidart JM, Travagli JP, Schlumberger M (2005) Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab 90:5723–5729

    Article  PubMed  CAS  Google Scholar 

  77. 77.

    Lango M, Flieder D, Arrangoiz R, Veloski C, Yu JQ, Li T, Burtness B, Mehra R, Galloway T, Ridge JA (2013) Extranodal extension of metastatic papillary thyroid carcinoma: correlation with biochemical endpoints, nodal persistence, and systemic disease progression. Thyroid 23:1099–1105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to F. Pacini.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to disclose.

Ethical approval

This study complies with ethical standard of research. It does not involve data or treatment of human being nor animals.

Informed consent

For this type of study informed consent is not required.

Additional information

Joint statements of six Italian societies: The Italian Thyroid Association (AIT), the Medical Endocrinology Association (AME), the Italian Society of Endocrinology (SIE), the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN), the Italian Society of Unified Endocrine Surgery (SIUEC) and the Italian Society of Anatomic Pathology and Diagnostic Cytology (SIAPEC).

Appendix 1: Reporting form for thyroid tumors

Appendix 1: Reporting form for thyroid tumors

Gross description (macroscopic)

Thyroid

  • Weight (size)

  • Multinodularity/uninodularity

  • Macroscopic appearance of the nodule:

    • diameter

    • homogeneous/heterogeneous

    • tumor color

    • expansive margins/infiltrative margins

    • presence/absence of a capsule

    • solid/colloid

    • cystic-hemorrhagic regression

    • calcifications (pattern and location).

  • Site

    • right lobe

    • left lobe

    • isthmus

    • pyramidal lobe

  • Distance from thyroid capsule/surgical margins

Lymph nodes

  • Site

  • Size of the specimen

  • Gross features of the largest nodes.

Microscopic examination

Thyroid nodule

  • Capsule (present/absent)

  • Structure (colloid/sclerotic/solid)

  • Histotype

    • NIFT-P

    • Papillary

      • Classical variant

      • Follicular variant

    • Follicular

      • Minimally invasive

      • Widely invasive

    • Oncocytic

    • Poorly differentiated (insular)

    • Anaplastic

    • Medullary

    • Thyroid lymphoma

    • Secondary tumors

  • Aggressive variants of PTC:

    • hobnail (report the presence)

    • tall cells (more than 10%)

    • solid (percentage value)

    • columnar cell (more than 10%)

    • diffuse sclerosing (report the presence)

  • Capsular invasion (tumor capsule/thyroid capsule)

  • Vascular invasion (no. of vessels: 4 or more) [19]

  • Minimal muscular invasion (strap muscles)

  • Extrathyroidal invasion (subcutaneous soft tissues, larynx, trachea, esophagus, recurrent laryngeal nerve, pre-vertebral fascia, neck muscles, large vessels) [20]

  • Immunohistochemistry and molecular analysis (if performed).

Lymph nodes

  • Total number

  • Number of metastatic nodes

  • Size of the largest metastatic area within the node, micro- (< 2 mm) or macrometastases Presence of extranodal invasion [75,76,77].

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pacini, F., Basolo, F., Bellantone, R. et al. Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. J Endocrinol Invest 41, 849–876 (2018). https://doi.org/10.1007/s40618-018-0884-2

Download citation

Keywords

  • Thyroid nodules
  • Thyroid cancer
  • Thyroid surgery
  • Radioiodine