Multifocality in patients treated for papillary Thyroid Carcinoma: a preliminary analysis of related risk factors.

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Paolo Del Rio
Tommaso Loderer
Mario Giuffrida
Federico Cozzani
Matteo Rossini
Deborah Bonfili
Elena Bonati


thyroid carcinoma, multifocality, thyroidectomy, lobectomy, Bethesda.



Multifocality is usually detected afterwards surgery for papillary thyroid cancer (PTC) and has been reported in 18-87% of PTC.


This is a retrospective single-center study involving a series of 238 patients that underwent thyroidectomy or lobectomy after preoperative fine needle aspiration (FNA) diagnosis of Thyr 5 or Thyr 6, according to Bethesda classification, from January 2015 to December 2019 at the General Surgery Unit of the University - Hospital of Parma. We divided patients into two main groups: patients with multifocal papillary thyroid cancer at postoperative diagnosis and patients with unifocal papillary thyroid cancer. The aim of the study is to identify demographic or preoperative radiological risk factors for the presence of multifocal PTC and to verify the presence of cyto-histological features of greater aggressiveness in multifocal tumors than in unifocal ones.


Out of our sample, 176 patients were females (73,9%) and 62 males (26,1%) with a mean age of 50,45 ±14,41. Preoperative cytological diagnosis resulted Thyr 5 in 47 cases (19,7%) and Thyr 6 in 191 cases (80,3%). Multifocal cancer was reported in 35,8% of the females and in 32,3% of the males. Older age was significatively related to the presence of multifocal papillary carcinoma (p<0.05). Preoperative bilateral thyroid nodules were associated with a higher finding of multifocal disease at histological examination (p<0.05). The presence of multifocal disease was related with a higher soft tissue invasion at the histological specimen (p<0.05).  Tumor size was not related to multifocal PTC in our study.


Older age of patient and preoperative bilateral thyroid nodules are significantly associated to multifocal thyroid cancer. In add to this, multifocal disease is related to higher finding of perithyroidal tissue invasion at histological exam. In case of predictive factors for multifocal PTC, surgeons should take total/near-total thyroidectomy always into consideration.


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1) Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R.. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013;2013:965212. doi: 10.1155/2013/965212. Epub 2013 May 7
2) Del Rio P, Montana Montana C, Mingardi G, Piva G, Sianesi M, Corcione L.D. ) Thyroid micro-carcinoma: only a diagnostic epidemic? Minerva Endocrinol. 2017 Sep;42(3):203-212. doi: 10.23736/S0391-1977.16.02483-4. Epub 2016 Sep 2
3) Cibas ES, Ali SZ.Cibas ES, et al The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017 Nov;27(11):1341-1346. doi: 10.1089/thy.2017.0500.
4) G Fadda 1 , F Basolo, A Bondi, G Bussolati, A Crescenzi, O Nappi, F Nardi, M Papotti, G Taddei, L Palombini Cytological classification of thyroid nodules. Proposal of the SIAPEC-IAP Italian Consensus Working Group, SIAPEC-IAP Italian Consensus Working Group Pathologica . 2010 Oct;102(5):405-8.
5) NCCN clinical practice guidelines in oncology. THyroid Carcinoma 2(2014)
6) Del Rio P, Montana Montana C, Cozzani F, Rossini M, Loderer T, Dall'Aglio E, Cataldo S, Marina M, Graziano C. Is there a correlation between thyroiditis and thyroid cancer? Endocrine. 2019 Dec;66(3):538-541. doi: 10.1007/s12020-019-01935-8. Epub 2019 Apr 19.Endocrine. 2019. PMID: 31004335
7) L. Davies, H.G. Welch Current thyroid cancer trends in the United States JAMA Otolaryngol Head Neck Surg, 140 (2014), pp. 317-322 PMID:24557566
8) M.R. Castro, H. Gharib. Continuing controversies in the management of thyroid nodules. Ann Intern Med, 142 (2005), pp. 926-931PMID:15941700
9) Ceresini G, Corcione L, Michiara M, Sgargi P, Teresi G, Gilli A, Usberti E, Silini E, Ceda GP Thyroid cancer incidence by histological type and related variants in a mildly iodine-deficient area of Northern Italy, 1998 to 2009. Cancer. 2012 Nov 15;118(22):5473-80. doi: 10.1002/cncr.27591. Epub 2012 Apr 19.Cancer. 2012. PMID: 22517468
10) 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 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. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020
11) 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 PItalian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. J Endocrinol Invest. 2018 Jul;41(7):849-876. doi: 10.1007/s40618-018-0884-2. Epub 2018 May 4.J Endocrinol Invest. 2018. PMID: 29729004
12) Iacobone M, Jansson S, Barczyński M, Goretzki P Multifocal papillary thyroid carcinoma--a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. 2014 Feb;399(2):141-54. doi: 10.1007/s00423-013-1145-7. Epub 2013 Nov 22.Langenbecks Arch Surg. 2014. PMID: 24263684
13) S. Xue, P. Wang, J. Liu, G. Chen Total thyroidectomy may be more reasonable as initial surgery in unilateral multifocal papillary thyroid microcarcinoma: a single-center experience World J Surg Oncol, 15 (1) (2017), p. 62 PMID: 28302162
14) A.L. Mitchell, A. Gandhi, D. Scott-Coombes, P. Perros. Management of thyroid cancer: United Kingdom National multidisciplinary guidelines. J Laryngol Otol, 130 (Suppl. S2) (2016), pp. 150-160)
15) Unalp HR, Erbil Y, Akguner T, et al. Does near total thyroidectomy offer advantage over total thyroidectomy in terms of postoperative hypocalcemia? Int J Surg 2009;7:120-5.
16) Feng JW, Qu Z, Qin AC, Pan H, Ye J, Jiang Y. Significance of multifocality in papillary thyroid carcinoma. Eur J Surg Oncol. 2020 Oct;46(10 Pt A):1820-1828. doi: 10.1016/j.ejso.2020.06.015. Epub 2020 Jun 19. PMID: 32732090.
17) N. Vorasubin, C. Nguyen, M. Wang Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: a meta-analysis Ear Nose Throat J, 95 (2) (2016), pp. 73-77
18) Gur EO, Karaisli S, Haciyanli S, Kamer E, Genc H, Atahan K, Haciyanli M. Multifocality related factors in papillary thyroid carcinoma. Asian J Surg. 2019 Jan;42(1):297-302. doi: 10.1016/j.asjsur.2018.05.004. Epub 2018 Jul 4. PMID: 30585170.
19) Ritter A, Mizrachi A, Bachar G, et al. Detecting Recurrence Following Lobectomy for Thyroid Cancer: Role of Thyroglobulin and Thyroglobulin Antibodies. J Clin Endocrinol Metab 2020;105:dgaa152.
20) Haigh PI, Urbach DR, Rotstein LE. Extent of thyroidectomy is not a major determinant of survival in lower high-risk papillary thyroid cancer. Ann Surg Oncol 2005;12:81-9.
21) Bilimoria KY, Bentrem DJ, Ko CY, et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 2007;246:375-81.
22) Patel KN, Yip L, Lubitz CC, Grubbs EG, Miller BS, Shen W, Angelos P, Chen H, Doherty GM, Fahey TJ 3rd, Kebebew E, Livolsi VA, Perrier ND, Sipos JA, Sosa JA, Steward D, Tufano RP, McHenry CR, Carty SE. The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg. 2020 Mar;271(3):e21-e93. doi: 10.1097/SLA.0000000000003580.
23) Del Rio P, Viani L, Montana CM, Cozzani F, Sianesi M. Minimally invasive thyroidectomy: a ten years experience. Gland Surg. 2016 Jun;5(3):295-9. doi: 10.21037/gs.2016.01.04.
24) Miccoli P, Fregoli L, Rossi L, Papini P, Ambrosini CE, Bakkar S, De Napoli L, Aghababyan A, Matteucci V, Materazzi Minimally invasive video-assisted thyroidectomy (MIVAT). G.Miccoli P, et al. Gland Surg. 2020 Jan;9(Suppl 1):S1-S5. doi: 10.21037/gs.2019.12.05
25) Dionigi G, Dralle H, Materazzi G, Kim HY, Miccoli P.Happy 20th birthday to minimally invasive video-assisted thyroidectomy! J Endocrinol Invest. 2020 Mar;43(3):385-388. doi: 10.1007/s40618-019-01119-1. Epub 2019 Sep 25
26) Janlu Song, Ting Yan , Wangwang Qiu,Youben Fan, Zhili Yang. Clinical analysis of risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: a retrospective study of 3686 patients. Cancer Management and research 2020;12,2523-2530.
27) Limberg J, Ullmann TM, Stefanova D, Buicko JL, Finnerty BM, Zarnegar R, Fahey TJ 3rd, Beninato T Does Aggressive Variant Histology Without Invasive Features Predict Overall Survival in Papillary Thyroid Cancer?: A National Cancer Database Analysis. Ann Surg. 2019 Oct 9. doi: 10.1097/SLA.0000000000003632. Online ahead of print
28) Yuan J, Li J, Chen X, Lin X, Du J, Zhao G, Chen Z, Wu Z Identification of risk factors of central lymph node metastasis and evaluation of the effect of prophylactic central neck dissection on migration of staging and risk stratification in patients with clinically node-negative papillary thyroid microcarcinoma. Bull Cancer. 2017 Jun;104(6):516-523. doi: 10.1016/j.bulcan.2017.03.005. Epub 2017 May 2.
29) Geron Y, Benbassat C, Shteinshneider M, Or K, Markus E, Hirsch D, Levy S, Ziv-Baran T, Muallem-Kalmovich L. Multifocality Is not an Independent Prognostic Factor in Papillary Thyroid Cancer: A Propensity Score-Matching Analysis. Thyroid. 2019 Apr;29(4):513-522. doi: 10.1089/thy.2018.0547. Epub 2019 Mar 15. PMID: 30799769.
30) Harries V.,Wang Y.L., McGill M.,Xu B.,Tuttle M.,Wong J.R., Shaha AR.,Shah JP.,Ghossein R.,Patel S.G., Ganly I. Sshould multifocality be an indiction for completion thyroidectomy in papillary thyroid carcinoma? Surgery 167 (2020)10-17.
31) Sun R, Zhang H, Liu K, Fan J, Li G, Song X, Li C. Clinicopathologic Predictive Factors of Cervical Lymph Node Metastasis in Differentiated Thyroid Cancer. Acta Otorrinolaringol Esp. 2018 May-Jun;69(3):149-155. doi: 10.1016/j.otorri.2017.06.002. Epub 2017 Nov 20

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