Reclassification as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): A retrospective review in a single institution and outcome study
Reclassification as NIFTP
Keywords:Noninvasive follicular thyroid neoplasm with papillary-like nuclear features, Thyroid cancer, Follicular thyroid neoplasm, Incidence, Outcome
Background/Aim: Since non-invasive follicular thyroid neoplasm (NIFTP) was first defined in 2016, past overtreatment status, impact for the risk of malignancy, and incidence of NIFTP have been the subject of study. Retrospective cohort studies have been published and present widely varying results in different geographic regions. This study aimed to reclassify follicular variants of papillary thyroid carcinoma (FVPTC) cases diagnosed in a single center using the defined stringent NIFTP criteria and to determine incidence, clinicopathological features, and survival of NIFTP cases.
Methods: This retrospective cohort study was conducted in a single center and consisted of patients with diagnosed follicular variant papillary thyroid carcinoma in thyroidectomy/thyroid lobectomy specimens between 2014 and 2021. Reports of FVPTC cases between 2014 and 2018 were evaluated by two experienced pathologists to identify candidates for NIFTP. Archived glass slides of the potential NIFTP cases were retrieved and reviewed independently by two pathologists.
Results: Between 2014 and 2021, 84 patients who underwent surgery were diagnosed with FVPTC. Reports of 49 patients diagnosed before 2018 were re-evaluated by two pathologists, and 20 cases were identified as candidates for NIFTP. After blind evaluation of pathology slides, five cases (10%) were diagnosed as NIFTP according to the criteria established before 2016, and two cases between 2016 and August 2018 were still diagnosed as NIFTP. Fourteen patients were diagnosed with NIFTP between 2014 and 2021. The median follow-up of the NIFTP patients was 4.3 years, and no recurrence and/or metastasis was reported.
Conclusion: NIFTP represents 7.6% of the papillary thyroid carcinoma (PTC) cases in our cohort, which is higher than the incidence rate in our country. The follow-up results of our cases were uneventful considering the indolent nature of NIFTP, but we had high thyroidectomy rates. Due to the concomitant PTC, multifocality, and uncertainties in the follow-up routine, we think it would be appropriate for these patients to remain in active follow-up.
Cramer JD, Fu P, Harth KC, Margevicius S, Wilhelm SM. Analysis of the rising incidence of thyroid cancer using the Surveillance, Epidemiology and End Results national cancer data registry. Surgery. 2010;148(6):1147-52. doi: 10.1016/j.surg.2010.10.016. DOI: https://doi.org/10.1016/j.surg.2010.10.016
Rosaí J, Zampi G, Carcangiu ML. Papillary carcinoma of the thyroid. A discussion of its several morphologic expressions, with particular emphasis on the follicular variant. Am J Surg Pathol. 1983;7(8):809-17. DOI: https://doi.org/10.1097/00000478-198307080-00010
LiVolsi VA. Papillary thyroid carcinoma: an update. Mod Pathol. 2011;24 (Suppl 2):S1-9. doi: 10.1038/modpathol.2010.129. DOI: https://doi.org/10.1038/modpathol.2010.129
Yu XM, Schneider DF, Leverson G, Chen H, Sippel RS. Follicular variant of papillary thyroid carcinoma is a unique clinical entity: a population-based study of 10,740 cases. Thyroid. 2013;23(10):1263-8. doi: 10.1089/thy.2012.0453. DOI: https://doi.org/10.1089/thy.2012.0453
Giani C, Torregrossa L, Piaggi P, Matrone A, Viola D, Molinaro E, et al. Outcome of classical (CVPTC) and follicular (FVPTC) variants of papillary thyroid cancer: 15 years of follow-up. Endocrine. 2020;68(3):607-16. doi: 10.1007/s12020-020-02229-0. DOI: https://doi.org/10.1007/s12020-020-02229-0
Liu J, Singh B, Tallini G, Carlson DL, Katabi N, Shaha A, et al. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer. 2006;107:1255–64. DOI: https://doi.org/10.1002/cncr.22138
Szpak-Ulczok S, Pfeifer A, Rusinek D, Oczko-Wojciechowska M, Kowalska M, Tyszkiewicz T, et al. Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma-Do They Exist? Int J Mol Sci. 2020;21(13):4629. doi: 10.3390/ijms21134629. DOI: https://doi.org/10.3390/ijms21134629
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;23:1191–2000. DOI: https://doi.org/10.1038/modpathol.2010.112
Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncology. 2016;2:1023–9. doi: 10.1001/jamaoncol.2016.0386. DOI: https://doi.org/10.1001/jamaoncol.2016.0386
Rosario PW, Mourão GF. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): a review for clinicians. Endocr Relat Cancer. 2019;26(5):R259-R266. doi:10.1530/ERC-19-0048. DOI: https://doi.org/10.1530/ERC-19-0048
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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. 2016;26(1):1-133. doi: 10.1089/thy.2015.0020. DOI: https://doi.org/10.1089/thy.2015.0020
Cho U, Mete O, Kim MH, 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(6):810-25. doi: 10.1038/modpathol.2017.9.
Parente DN, Kluijfhout WP, Bongers PJ, Verzijl R, Devon KM, Rotstein LE, et al. Clinical Safety of Renaming Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: Is NIFTP Truly Benign? World J Surg. 2018;42(2):321-6. doi: 10.1007/s00268-017-4182-5. DOI: https://doi.org/10.1007/s00268-017-4182-5
Canberk S, Montezuma D, Taştekin E, Grangeia D, Demirhas MP, Akbas M, et al. "The other side of the coin": understanding non-invasive follicular tumor with papillary-like nuclear features in unifocal and multifocal settings. Hum Pathol. 2019;86:136-42. doi: 10.1016/j.humpath.2018.10.040. DOI: https://doi.org/10.1016/j.humpath.2018.10.040
Nikiforov YE, Baloch ZW, Hodak SP, Giordano TJ, Lloyd RV, Seethala RR, et al. Change in Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm With Papillarylike Nuclear Features. JAMA Oncol. 2018;4(8):1125-6. doi: 10.1001/jamaoncol.2018.1446. DOI: https://doi.org/10.1001/jamaoncol.2018.1446
Lloyd RF, Osamura RY, Klöppel G, Rosai J, eds. WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon, France: IARC; 2017.
Mainthia R, Wachtel H, Chen Y, Mort E, Parangi S, Sadow PM, et al. Evaluating the projected surgical impact of reclassifying non-invasive encapsulated follicular variant of papillary thyroid cancer as non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Surgery. 2018;163(1):60-5. doi: 10.1016/j.surg.2017.04.037. DOI: https://doi.org/10.1016/j.surg.2017.04.037
Karaagac M, Sarigoz T, Ertan T, Topuz O. Evaluation of the Bethesda System and the ACR TIRADS in an Endemic Goiter Region. Endocr Res. 2020;45(4):226-32. doi: 10.1080/07435800.2020.1799226. DOI: https://doi.org/10.1080/07435800.2020.1799226
Haugen BR, Sawka AM, Alexander EK, Bible KC, Caturegli P, Doherty GM, et al. American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features. Thyroid. 2017;27(4):481-3. doi: 10.1089/thy.2016.0628. DOI: https://doi.org/10.1089/thy.2016.0628
Kluijfhout WP, Pasternak JD, Lim J, Kwon JS, Vriens MR, Clark OH, et al. Frequency of High-Risk Characteristics Requiring Total Thyroidectomy for 1-4 cm Well-Differentiated Thyroid Cancer. Thyroid. 2016;26(6):820-4. doi: 10.1089/thy.2015.0495. DOI: https://doi.org/10.1089/thy.2015.0495
Canini V, Leni D, Pincelli AI, Scardilli M, Garancini M, Villa C, et al. Clinical-pathological issues in thyroid pathology: study on the routine application of NIFTP diagnostic criteria. Sci Rep. 2019;9(1):13179. doi: 10.1038/s41598-019-49851-1. DOI: https://doi.org/10.1038/s41598-019-49851-1
Turan G, Özkara SK. Pathological findings of the retrospective diagnosis of NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) in 84 cases from Turkey and systematic review. Ann Diagn Pathol. 2021;53:151764. doi: 10.1016/j.anndiagpath.2021.151764. DOI: https://doi.org/10.1016/j.anndiagpath.2021.151764
Kiernan CM, Weiss VL, Mehrad M, Ely K, Baregamian N, Solórzano CC. New terminology-noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) and its effect on the rate of malignancy at a single institution. Surgery. 2018;163(1):55-9. doi: 10.1016/j.surg.2017.04.041. DOI: https://doi.org/10.1016/j.surg.2017.04.041
Kim TH, Lee M, Kwon AY, Choe JH, Kim JH, Kim JS, et al. Molecular genotyping of the non-invasive encapsulated follicular variant of papillary thyroid carcinoma. Histopathology. 2018;72(4):648-61. doi: 10.1111/his.13401. DOI: https://doi.org/10.1111/his.13401
Cho U, Mete O, Kim MH, 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(6):810-25. doi: 10.1038/modpathol.2017.9. DOI: https://doi.org/10.1038/modpathol.2017.9
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;29(3):276-88. doi: 10.1007/s12022-018-9519-6. DOI: https://doi.org/10.1007/s12022-018-9519-6
Wong KS, Strickland KC, Angell TE, Nehs MA, Alexander EK, Cibas ES, et al. The Flip Side of NIFTP: an Increase in Rates of Unfavorable Histologic Parameters in the Remainder of Papillary Thyroid Carcinomas. Endocr Pathol. 2017;28(2):171-6. doi: 10.1007/s12022-017-9476-5. DOI: https://doi.org/10.1007/s12022-017-9476-5
Agrawal N, Abbott CE, Liu C, Kang S, Tipton L, Patel K, et al. Non-invasive follicular tumor with papillary-like nuclear features: not a tempest in a teapot. Endocr Pract. 2017;23(4):451-7. doi: 10.4158/EP161632.OR. DOI: https://doi.org/10.4158/EP161632.OR
Chung R, Guan H, Ponchiardi C, Cerda S, Marwaha N, Yilmaz OH, et al. Non-invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Epidemiology and Long-Term Outcomes in a Strictly Defined Cohort. Thyroid. 2021;31(1):68-75. doi: 10.1089/thy.2019.0616. Epub 2020 Jul 23. DOI: https://doi.org/10.1089/thy.2019.0616
Rana C, Vuong HG, Nguyen TQ, Nguyen HC, Jung CK, Kakudo K, et al. The Incidence of Non-invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification. Thyroid. 2021;31(10):1502-13. doi: 10.1089/thy.2021.0158. DOI: https://doi.org/10.1089/thy.2021.0158
Celik M, Bulbul BY, Can N, Ayturk S, Tastekin E, Sezer A, et al. Comparison of clinicopathological features in patients with non-invasive follicular thyroid neoplasm with papillary-like nuclear features and follicular variant papillary thyroid cancer. Pol Arch Intern Med. 2020;130(2):100-5. doi: 10.20452/pamw.15120. DOI: https://doi.org/10.20452/pamw.15120
Taskin HE, Karatas A. Is there a relationship between patient age, tumor multifocality, and capsular invasion in papillary thyroid carcinoma? Retrospective evaluation of pathology specimens. J Surg Med. 2022;6(2):168-72. doi: https://doi.org/10.28982/josam.1061503. DOI: https://doi.org/10.28982/josam.1061503
Likhterov I, Osorio M, Moubayed SP, Hernandez-Prera JC, Rhodes R, Urken ML. The Ethical Implications of the Reclassification of Noninvasive Follicular Variant Papillary Thyroid Carcinoma. Thyroid. 2016;26(9):1167-72. doi: 10.1089/thy.2016.0212. DOI: https://doi.org/10.1089/thy.2016.0212
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