Aligning Cytology, Histopathology, and Surgical Choices: A 10 Year Review of Thyroid Nodule Management at the University Clinical Center of Kosovo

ORIGINAL ARTICLE
Rinё Limani, Shkelzen Reçica, Etnik Bajraktari, Zgjim Limani, Arbnora Shaqiri, Fisnik Kurshumliu, Labinota Kondirolli, Fatlinda Sadiku, Brikenё Blakaj Gashi, Drita Miftari Pazhari

 
For citation: Limani R, Reçica S, Bajraktari E, Limani Z, Shaqiri A, Kurshumliu F, Kondirolli L, Sadiku F, Gashi BB, Pazhari DM. Aligning Cytology, Histopathology, and Surgical Choices: A 10 Year Review of Thyroid Nodule Management at the University Clinical Center of Kosovo. International Journal of Biomedicine. 2025;15(2):325-332. doi:10.21103/Article15(2)_OA9
 
Originally published June 5, 2025
 

Abstract: 

Thyroid nodules are detected in up to 60% of individuals by high-resolution ultrasonography, yet only a small proportion prove malignant, with papillary thyroid carcinoma being the most common. Fine-needle aspiration cytology (FNAC) is the primary, minimally invasive, and cost-effective method to triage nodules for surgery. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) standardizes FNAC interpretation into six categories with associated malignancy risks. However, indeterminate categories Bethesda III (AUS/FLUS) and IV (follicular neoplasm/suspicious for follicular neoplasm) present diagnostic challenges, exhibiting malignancy rates from 5% to over 30%, influenced by institutional practices and follow-up protocols. Sampling technique, slide preparation, and diagnostic experience further affect consistency. In Kosovo, where molecular testing is yet largely unavailable, FNAC remains the sole preoperative tool. The rise in incidentally detected sub-centimeter nodules, many of them low-risk microcarcinomas, complicates management in settings where surveillance is unreliable, often leading to overtreatment. Although current guidelines now endorse active surveillance and adjunctive molecular markers for indeterminate lesions, these tests are cost-prohibitive in resource-limited regions. This study leverages the unique position of our academic center to conduct a 10-year retrospective analysis of over 1800 FNACs and 1000 surgical cases, aiming to validate local FNAC performance, refine risk stratification, and inform context-appropriate management pathways.

Keywords: 
thyroid nodule • risk stratification • fine-needle aspiration • histopathology • surgery
References: 
  1. Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, Paschke R, Valcavi R, Vitti P; AACE/ACE/AME Task Force on Thyroid Nodules. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE. Endocr Pract. 2016 May;22(5):622-39. doi: 10.4158/EP161208.GL. PMID: 27167915.
  2. 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 L. 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. PMID: 26462967; PMCID: PMC4739132.
  3. Ali SZ, Baloch ZW, Cochand-Priollet B, Schmitt FC, Vielh P, VanderLaan PA. The 2023 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2023 Sep;33(9):1039-1044. doi: 10.1089/thy.2023.0141. Epub 2023 Jul 8. PMID: 37427847.
  4. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 2012;56(4):333-9. doi: 10.1159/000339959. Epub 2012 Jul 25. PMID: 22846422.
  5. Hathi K, Rahmeh T, Munro V, Northrup V, Sherazi A, Chin CJ. Rate of malignancy for thyroid nodules with AUS/FLUS cytopathology in a tertiary care center - a retrospective cohort study. J Otolaryngol Head Neck Surg. 2021 Oct 11;50(1):58. doi: 10.1186/s40463-021-00530-0. PMID: 34635177; PMCID: PMC8504068.
  6. Kaya C, Bozkurt E, Türkyılmaz Mut D, Mihmanli M, Uludağ M. WHICH FACTORS ARE ASSOCIATED WITH MALIGNANCY IN THYROID NODULES CLASSIFIED AS BETHESDA CATEGORY 3 (AUS/FLUS) AND HOW DO THEY INFLUENCE THE PATIENT'S MANAGEMENT? Acta Endocrinol (Buchar). 2019 Oct-Dec;15(4):491-496. doi: 10.4183/aeb.2019.491. PMID: 32377247; PMCID: PMC7200114.
  7. Ito Y, Miyauchi A. Active surveillance of low-risk papillary thyroid microcarcinomas. Gland Surg. 2020 Oct;9(5):1663-1673. doi: 10.21037/gs-2019-catp-03. PMID: 33224844; PMCID: PMC7667125.
  8. Gordon AJ, Dublin JC, Patel E, Papazian M, Chow MS, Persky MJ, Jacobson AS, Patel KN, Suh I, Morris LGT, Givi B. American Thyroid Association Guidelines and National Trends in Management of Papillary Thyroid Carcinoma. JAMA Otolaryngol Head Neck Surg. 2022 Dec 1;148(12):1156-1163. doi: 10.1001/jamaoto.2022.3360. PMID: 36326739; PMCID: PMC9634599.
  9. Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011 Nov;96(11):3390-7. doi: 10.1210/jc.2011-1469. Epub 2011 Aug 31. PMID: 21880806; PMCID: PMC3205883.
  10. Steward DL, Carty SE, Sippel RS, Yang SP, Sosa JA, Sipos JA, Figge JJ, Mandel S, Haugen BR, Burman KD, Baloch ZW, Lloyd RV, Seethala RR, Gooding WE, Chiosea SI, Gomes-Lima C, Ferris RL, Folek JM, Khawaja RA, Kundra P, Loh KS, Marshall CB, Mayson S, McCoy KL, Nga ME, Ngiam KY, Nikiforova MN, Poehls JL, Ringel MD, Yang H, Yip L, Nikiforov YE. Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study. JAMA Oncol. 2019 Feb 1;5(2):204-212. doi: 10.1001/jamaoncol.2018.4616. Erratum in: JAMA Oncol. 2019 Feb 1;5(2):271. doi: 10.1001/jamaoncol.2018.6413. PMID: 30419129; PMCID: PMC6439562.
  11. Tessler FN, Middleton WD, Grant EG, Hoang JK, Berland LL, Teefey SA, Cronan JJ, Beland MD, Desser TS, Frates MC, Hammers LW, Hamper UM, Langer JE, Reading CC, Scoutt LM, Stavros AT. ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J Am Coll Radiol. 2017 May;14(5):587-595. doi: 10.1016/j.jacr.2017.01.046. Epub 2017 Apr 2. PMID: 28372962.
  12. Angelopoulos N, Goulis DG, Chrisogonidis I, Livadas S, Paparodis R, Androulakis I, Iakovou I. Diagnostic Performance of European and American College of Radiology Thyroid Imaging Reporting and Data System Classification Systems in Thyroid Nodules Over 20 mm in Diameter. Endocr Pract. 2025 Jan;31(1):72-79. doi: 10.1016/j.eprac.2024.10.004. Epub 2024 Oct 22. PMID: 39442878.
  13. Padmanabhan V, Marshall CB, Akdas Barkan G, Ghofrani M, Laser A, Tolgay Ocal I, David Sturgis C, Souers R, Kurtycz DF. Reproducibility of atypia of undetermined significance/follicular lesion of undetermined significance category using the bethesda system for reporting thyroid cytology when reviewing slides from different institutions: A study of interobserver variability among cytopathologists. Diagn Cytopathol. 2017 May;45(5):399-405. doi: 10.1002/dc.23681. Epub 2017 Feb 20. PMID: 28217980.
  14. Brito JP, Gionfriddo MR, Al Nofal A, Boehmer KR, Leppin AL, Reading C, Callstrom M, Elraiyah TA, Prokop LJ, Stan MN, Murad MH, Morris JC, Montori VM. The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab. 2014 Apr;99(4):1253-63. doi: 10.1210/jc.2013-2928. Epub 2013 Nov 25. PMID: 24276450; PMCID: PMC3973781.
  15. De Napoli L, Matrone A, Favilla K, Piaggi P, Galleri D, Ambrosini CE, Aghababyan A, Papini P, Valerio L, Viola D, Torregrossa L, Ugolini C, Proietti A, Basolo F, Miccoli P, Elisei R, Materazzi G. Role of Prophylactic Central Compartment Lymph Node Dissection on the Outcome Of Patients With Papillary Thyroid Carcinoma and Synchronous Ipsilateral Cervical Lymph Node Metastases. Endocr Pract. 2020 Aug;26(8):807-817. doi: 10.4158/EP-2019-0532. PMID: 33471672.
  16. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. JAMA. 2017 Apr 4;317(13):1338-1348. doi: 10.1001/jama.2017.2719. PMID: 28362912; PMCID: PMC8216772.
  17. 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. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol. 2016 Aug 1;2(8):1023-9. doi: 10.1001/jamaoncol.2016.0386. PMID: 27078145; PMCID: PMC5539411.
  18. Eissa MS, Sabry RM, Abdellateif MS. Evaluating the Diagnostic Role of ACR-TIRADS and Bethesda Classifications in Thyroid Nodules Highlighted by Cyto-Histopathological Studies. Exp Clin Endocrinol Diabetes. 2024 Nov;132(11):596-606. doi: 10.1055/a-2380-3674. Epub 2024 Aug 5. PMID: 39102864.
  19. Li C, Luo Y, Jiang Y, Li Q. Integrated intraoperative predictive model for malignancy risk assessment of thyroid nodules with atypia of undetermined significance cytology. Sci Rep. 2025 Jan 13;15(1):1860. doi: 10.1038/s41598-024-84716-2. PMID: 39805960; PMCID: PMC11730291.

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Received May 6, 2025.
Accepted June 1, 2025.
©2025 International Medical Research and Development Corporation.