Preoperative Predictors of Coexistent Papillary Thyroid Carcinoma in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

Muhammet KOCABAŞ , YUSUF ÖZTÜRK

  • Muhammet KOCABAŞ: Necmettin Erbakan University Faculty of Medicine
  • YUSUF ÖZTÜRK: Sakarya University, Faculty of Medicine
  • Year : 2026
  • Vol : 42
  • Issue : 1
  •  Page : 50-57
Objective: To evaluate the clinical, ultrasonographic, and cytological characteristics of noninvasive follicular thyroid neoplasm with papillary-like nuclear features
(NIFTP) and to identify preoperative factors associated with coexistent papillary thyroid carcinoma (PTC).
Materials and Methods: This retrospective study included a total of 115 patients histopathologically diagnosed with NIFTP after thyroidectomy. Demographic,
ultrasonographic, cytological, and pathological data were analyzed. Nodules were classified according to the European Thyroid Imaging and Reporting Data System
(EU-TIRADS) and the Bethesda cytology categories. The patients were divided into two groups: “NIFTP without coexistent PTC” and “NIFTP with coexistent PTC”.
Comparative and logistic regression analyses were performed to identify predictors of concomitant PTC.
Results: The mean age was 46.78±13.98 years, and 74.8% were female. The mean size of NIFTP nodules was 23.15±16.70 mm. According to the EU-TIRADS classification,
44.3% of nodules were category 3, 14.8% category 4, and 37.4% category 5. Cytology results were most frequently Bethesda I (27.0%), II (32.2%), and III (24.3%).
Coexistent PTC was identified in 33 patients (28.7%). In the results of univariate analysis, smaller nodule size (OR 0.956, 95% CI 0.924-0.990, p = 0.010) was significantly
associated with coexistent PTC, while EU-TIRADS category 5 (OR 2.288, 95% CI 1.002-5.228, p = 0.050) showed borderline significance. In multivariate analysis, only
smaller nodule size remained an independent predictor (OR 0.951, 95% CI 0.909-0.995, p = 0.030).
Conclusion: Smaller nodule size was found to independently predict coexistent PTC in NIFTP, whereas suspicious sonographic features such as solid composition,
presence of a halo, or high EU-TIRADS scores were not independent predictors. Careful evaluation of smaller nodules may improve preoperative risk stratification and
guide surgical decision-making.
Cite this Article As : Kocabas M, Ozturk Y. Preoperative Predictors of Coexistent Papillary Thyroid Carcinoma in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features. Selcuk Med J 2026;42(1): 50-57

Download Citation: Endnote/Zotero/Mendeley (RIS) RIS File

Download Citation: BibTeX BibTeX File

Conflict of interest : The authors declare that they have no conflict of interest.
This article is published under the CC BY-NC 4.0 license.
Selcuk Medical Journal
2026, Vol. 42 (1)
ISSN: 1017-6616
E-ISSN: 2149-8059
Received : , Accepted : , Published Online :

References

  1. 1. Nikiforov YE, Seethala RR, Tallini G, et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol. 2016;2(8):1023-1029. doi:10.1001/jamaoncol.2016.0386
  2. 2. Rosario PW, Mourão GF. Noninvasive 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
  3. 3. Nikiforov YE, Baloch ZW, Hodak SP, et al. Change in Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm With Papillarylike Nuclear Features. JAMA Oncol. 2018;4(8):1125-1126. doi:10.1001/jamaoncol.2018.1446
  4. 4. Chin PD, Zhu CY, Sajed DP, et al. Correlation of ThyroSeq Results with Surgical Histopathology in Cytologically Indeterminate Thyroid Nodules. Endocr Pathol. 2020;31(4):377-384. doi:10.1007/s12022-020-09641-2
  5. 5. Lubitz C. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: What is in a name?. Cancer Cytopathol. 2018;126(11):895-896. doi:10.1002/cncy.22065
  6. 6. Faquin WC, Wong LQ, Afrogheh AH, et al. 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):181-187. doi:10.1002/cncy.21631
  7. 7. Bongiovanni M, Giovanella L, Romanelli F, Trimboli P. Cytological Diagnoses Associated with Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features According to the Bethesda System for Reporting Thyroid Cytopathology: A Systematic Review and Meta-Analysis. Thyroid. 2019;29(2):222-228. doi:10.1089/thy.2018.0394
  8. 8. Hahn SY, Shin JH, Lim HK, et al. Preoperative differentiation between noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and non-NIFTP. Clin Endocrinol (Oxf). 2017;86(3):444-450. doi:10.1111/cen.13263
  9. 9. You SH, Lee KE, Yoo RE, et al. Prevention of total thyroidectomy in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) based on combined interpretation of ultrasonographic and cytopathologic results. Clin Endocrinol (Oxf). 2018;88(1):114-122. doi:10.1111/cen.13473
  10. 10. Seo JY, Park JH, Pyo JY, et al. A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea. J Pathol Transl Med. 2019;53(6):378-385. doi:10.4132/jptm.2019.09.18
  11. 11. Vignali P, Proietti A, Macerola E, et al. Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center. Cancers (Basel). 2022;14(2):420. Published 2022 Jan 14. doi:10.3390/cancers14020420
  12. 12. Song SJ, LiVolsi VA, Montone K, Baloch Z. Pre-operative features of non-invasive follicular thyroid neoplasms with papillary-like nuclear features: An analysis of their cytological, Gene Expression Classifier and sonographic findings. Cytopathology. 2017;28(6):488-494. doi:10.1111/cyt.12501
  13. 13. Canberk S, Montezuma D, Taştekin E, et al. "The other side of the coin": understanding noninvasive follicular tumor with papillary-like nuclear features in unifocal and multifocal settings. Hum Pathol. 2019;86:136-142. doi:10.1016/j.humpath.2018.10.040
  14. 14. Zajkowska K, Kopczyński J, Góźdź S, Kowalska A. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a problematic entity. Endocr Connect. 2020;9(3):R47-R58. doi:10.1530/EC-19-0566
  15. 15. Juhlin CC, Mete O, Baloch ZW. The 2022 WHO classification of thyroid tumors: novel concepts in nomenclature and grading. Endocr Relat Cancer. 2022;30(2):e220293. Published 2022 Dec 22. doi:10.1530/ERC-22-0293
  16. 16. Rossi ED, Faquin WC, Baloch Z, et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): Update and Diagnostic Considerations-a Review. Endocr Pathol. 2019;30(2):155-162. doi:10.1007/s12022-019-9574-7
  17. 17. Muñoz I, Solórzano M, Fuentes I, et al. Noninvasive Follicular Thyroid Neoplasia With Papillary-Like Nuclear Characteristics (NIFTP): Clinico-Pathological Analysis in a Chilean Centre. Clin Endocrinol (Oxf). Published online August 24, 2025. doi:10.1111/cen.70026
  18. 18. Tazeoglu D, Dag A, Esmer AC, Benli S, Arslan B, Arpaci RB. Is it Possible to Diagnose "Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features" Preoperatively?. Indian J Surg Oncol. 2023;14(2):368-375. doi:10.1007/s13193-022-01696-3
  19. 19. 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. doi:10.1038/modpathol.2016.65
  20. 20. Yang GCH, Fried KO. Pathologic basis of the sonographic differences between thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Ultrasonography. 2018;37(2):157-163. doi:10.14366/usg.17045
  21. 21. Kwon MR, Shin JH, Hahn SY, et al. Histogram analysis of greyscale sonograms to differentiate between the subtypes of follicular variant of papillary thyroid cancer. Clin Radiol. 2018;73(6):591.e1-591.e7. doi:10.1016/j.crad.2017.12.008
  22. 22. Kholová I, Haaga E, Ludvik J, et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile. Diagnostics (Basel). 2022;12(2):250. Published 2022 Jan 20. doi:10.3390/diagnostics12020250
  23. 23. Hekimsoy İ, Ertan Y, Serin G, et al. Comparison of ultrasound findings of papillary thyroid carcinoma subtypes based on the 2022 WHO classification of thyroid neoplasms. Front Endocrinol (Lausanne). 2024;15:1434787. Published 2024 Aug 14. doi:10.3389/fendo.2024.1434787
  24. 24. Liu R, Gao L, Xia Y, et al. Three ultrasound phenotypes of non-invasive follicular thyroid neoplasm with papillary-like nuclear features proposed for imaging-pathology analysis: single center experience. Gland Surg. 2021;10(1):307-318. doi:10.21037/gs-20-612
  25. 25. Leoncini A, Camponovo C, Gamarra E, et al. NIFTP-adjusted risk estimation of Bethesda thyroid cytology categories should consider the indication for FNA according to TIRADS. Endocrine. 2024;85(3):1261-1267. doi:10.1007/s12020-024-03800-9
  26. 26. Andrade de Almeida M, Canão P, Capela J, et al. Preoperative assessment of NIFTP clinicopathological characteristics and its impact on avoiding overtreatment. Langenbecks Arch Surg. 2025;410(1):204. Published 2025 Jul 1. doi:10.1007/s00423-025-03788-4
  27. 27. Canini V, Leni D, Pincelli AI, et al. Clinical-pathological issues in thyroid pathology: study on the routine application of NIFTP diagnostic criteria. Sci Rep. 2019;9(1):13179. Published 2019 Sep 12. doi:10.1038/s41598-019-49851-1
  28. 28. Fama F, Sindoni A, Cicciu M, et al. Preoperatively undiagnosed papillary thyroid carcinoma in patients thyroidectomized for benign multinodular goiter. Arch Endocrinol Metab. 2018;62(2):139-148. Published 2018 Apr 5. doi:10.20945/2359-3997000000017
  29. 29. Eloy C, Russ G, Suciu V, et al. Preoperative diagnosis of thyroid nodules: An integrated multidisciplinary approach. Cancer Cytopathol. 2022;130(5):320-325. doi:10.1002/cncy.22546