The renaming of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed by a group of experts in 2016 to prevent overtreatment of indolent, low-risk thyroid cancers. The aim of this study was to estimate the incidence and outcome for patients meeting the NIFTP criteria in a well-defined geographic region. Our cohort consisted of 134 patients with papillary thyroid carcinoma from the Region of Southern Denmark (RSD), 2007 to 2011. Patients were retrieved from the Danish Thyroid Cancer (DATHYRCA) Database. All potential NIFTP cases were reviewed by a thyroid pathologist. We identified no cases meeting all diagnostic criteria, but one probable NIFTP case from 2007 to 2011. The patient was treated according to the national guidelines and is alive and recurrence-free after 106 months of follow-up. Molecular testing showed KRAS mutation. In a population based set up the incidence rate of NIFTP is very low.
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Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7.
Londero SC, Krogdahl A, Bastholt L, Overgaard J, Pedersen HB, Frisch T, Bentzen J, Pedersen PU, Christiansen P, Godballe C. Papillary thyroid carcinoma in Denmark 1996–2008: an investigation of changes in incidence. Cancer Epidemiol. 2013;37:e1–6. https://doi.org/10.1016/j.canep.2012.10.011.
Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA Jr, Sigurdson AJ, Nikiforov YE. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab. 2014;99(2):E276–85. https://doi.org/10.1210/jc.2013-2503.
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, Nose V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2016;2(8):1023–9. https://doi.org/10.1001/jamaoncol.2016.0386.
Hodak S, Tuttle RM, Maytal G, Nikiforov YE, Randolph G. Changing the cancer diagnosis: the case of follicular variant of papillary thyroid cancer - Primum Non Nocere and NIFTP. Thyroid. 2016;26:869–71. https://doi.org/10.1089/thy.2016.0205.
Lloyd RVOR, Klöppel GK, Rosai J. (2017) WHO Classification of Tumours of Endocrine Organs. World Health Organization Classification of Tumours; tenth volume, 4th edition edn. Lyon, France: International Agency for Research on Cancer (IARC).
Chan JKC. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002;117(1):16–8. https://doi.org/10.1309/P7QL-16KQ-QLF4-XW0M.
Lloyd RV, Erickson LA, Casey MB, Lam KY, Lohse CM, Asa SL, Chan JKC, DeLellis RA, Harach HR, Kakudo K, LiVolsi VA, Rosai J, Sebo TJ, Sobrinho-Simoes M, Wenig BM, Lae ME. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004;28(10):1336–40. https://doi.org/10.1097/01.pas.0000135519.34847.f6.
Elsheikh TM, Asa SL, Chan JKC, DeLellis RA, Heffess CS, LiVolsi VA, Wenig BM. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 2008;130(5):736–44. https://doi.org/10.1309/AJCPKP2QUVN4RCCP.
Johnson DN, Furtado LV, Long BC, Zhen CJ, Wurst M, Mujacic I, Kadri S, Segal JP, Antic T, Cipriani NA. Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) are genetically and biologically similar to adenomatous nodules and distinct from papillary thyroid carcinomas with extensive follicular growth. Arch Pathol Lab Med. 2018. https://doi.org/10.5858/arpa.2017-0118-OA.
Thompson LDR, Poller DN, Kakudo K, Burchette R, Nikiforov YE, Seethala RR. An international interobserver variability reporting of the nuclear scoring criteria to diagnose noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a validation study. Endocr Pathol. 2018. https://doi.org/10.1007/s12022-018-9520-0.
Lloyd RV, Asa SL, LiVolsi VA, Sadow PM, Tischler AS, Ghossein RA, Tuttle RM, Nikiforov YE. The evolving diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Hum Pathol. 2018;74:1–4. https://doi.org/10.1016/j.humpath.2017.12.027.
Rosario PW. Long-term outcomes of patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) ≥4 cm treated without radioactive iodine. Endocr Pathol. 2017;28(4):367–8. https://doi.org/10.1007/s12022-017-9493-4.
Jaconi M, Manzoni M, Pincelli AI, Giardini V, Scardilli M, Smith A, Fellegara G, Pagni F. The impact of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature terminology in the routine diagnosis of thyroid tumours. Cytopathology. 2017;28(6):495–502. https://doi.org/10.1111/cyt.12459.
Parente DN, Kluijfhout WP, Bongers PJ, Verzijl R, Devon KM, Rotstein LE, Goldstein DP, Asa SL, Mete O, Pasternak JD. Clinical safety of renaming encapsulated follicular variant of papillary thyroid carcinoma: is NIFTP truly benign? World J Surg. 2017. https://doi.org/10.1007/s00268-017-4182-5.
Bychkov A, Jung CK, Liu Z, Kakudo K. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features in asian practice: perspectives for surgical pathology and cytopathology. Endocr Pathol. 2018. https://doi.org/10.1007/s12022-018-9519-6.
Londero SC, Mathiesen JS, Krogdahl A, Bastholt L, Overgaard J, Bentsen J, Hahn CH, Schytte S, Pedersen HB, Christiansen P, Godballe C, Study from the Danish Thyroid Cancer G. Completeness and validity in a national clinical thyroid cancer database: DATHYRCA. Cancer Epidemiol. 2014;38(5):633–7. https://doi.org/10.1016/j.canep.2014.07.009.
Baloch ZW, Harrell RM, Brett EM, Randolph G, Garber JR. American association of clinical endocrinologists and American college of endocrinology disease state commentary: managing thyroid tumors diagnosed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Endocr Pract. 2017;23(9):1153–8. https://doi.org/10.4158/EP171940.DSCR.
StatBank Denmark Available online at http://www.statbank.dk.
DAHANCA. (2005) Guidelines for behandling af Thyreoideacancer i Danmark. 2018.
Bjerregaard B, Larsen OB. The Danish pathology register. Scand J Public Health. 2011;39(7 Suppl):72–4. https://doi.org/10.1177/1403494810393563.
Faquin WC, Wong LQ, Afrogheh AH, Ali SZ, Bishop JA, Bongiovanni M, Pusztaszeri MP, VandenBussche CJ, Gourmaud J, Vaickus LJ, Baloch ZW. Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology. Cancer Cytopathol. 2016;124(3):181–7. https://doi.org/10.1002/cncy.21631.
Canberk S, Gunes P, Onenerk M, Erkan M, Kilinc E, Kocak Gursan N, Kilicoglu GZ. New concept of the encapsulated follicular variant of papillary thyroid carcinoma and its impact on the Bethesda system for reporting thyroid cytopathology: a single-institute experience. Acta Cytol. 2016;60(3):198–204. https://doi.org/10.1159/000447990.
Strickland KC, Howitt BE, Marqusee E, Alexander EK, Cibas ES, Krane JF, Barletta JA. The impact of noninvasive follicular variant of papillary thyroid carcinoma on rates of malignancy for fine-needle aspiration diagnostic categories. Thyroid. 2015;25(9):987–92. https://doi.org/10.1089/thy.2014.0612.
Thompson LD. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: a name change to noninvasive follicular thyroid neoplasm with papillary-like nuclear features would help prevent overtreatment. Mod Pathol. 2016;29(7):698–707. https://doi.org/10.1038/modpathol.2016.65.
Mainthia R, Wachtel H, Chen Y, Mort E, Parangi S, Sadow PM, Lubitz CC. Evaluating the projected surgical impact of reclassifying noninvasive encapsulated follicular variant of papillary thyroid cancer as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Surgery. 2018;163(1):60–5. https://doi.org/10.1016/j.surg.2017.04.037.
Poller DN, Johnson SJ, Stephenson TJ. Diagnosis of NIFTP in the UK. J Basic Clin Med. 2017;6(1):63–4.
Seethala RR, Baloch ZW, Barletta JA, Khanafshar E, Mete O, Sadow PM, LiVolsi VA, Nikiforov YE, Tallini G, Thompson LDR. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists. Mod Pathol. 2017. https://doi.org/10.1038/modpathol.2017.130.
Cibas ES, Baloch ZW, Fellegara G, LiVolsi VA, Raab SS, Rosai J, Diggans J, Friedman L, Kennedy GC, Kloos RT, Lanman RB, Mandel SJ, Sindy N, Steward DL, Zeiger MA, Haugen BR, Alexander EK. A prospective assessment defining the limitations of thyroid nodule pathologic evaluation. Ann Intern Med. 2013;159(5):325–32. https://doi.org/10.7326/0003-4819-159-5-201309030-00006.
Zhao L, Dias-Santagata D, Sadow PM, Faquin WC. Cytological, molecular, and clinical features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features versus invasive forms of follicular variant of papillary thyroid carcinoma. Cancer Cytopathol. 2017;125(5):323–31. https://doi.org/10.1002/cncy.21839.
Rivera M, Ricarte-Filho J, Knauf J, Shaha A, Tuttle M, Fagin JA, Ghossein RA. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol. 2010;23(9):1191–200. https://doi.org/10.1038/modpathol.2010.112.
Cho U, Mete O, Kim M-H, Bae JS, Jung CK. Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Mod Pathol. 2017;30:810. https://doi.org/10.1038/modpathol.2017.9.
We thank the Odense University Hospital, DAHANCA, Hans Skouby fond, and Kong Christian den Tiendes Fond.
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Reinke, R.H., Larsen, S.R., Mathiesen, J.S. et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features is Rare: A Population Based Study of Incidence. Head and Neck Pathol 14, 144–149 (2020). https://doi.org/10.1007/s12105-019-01032-2
- Follicular variant of papillary thyroid carcinoma