TİROİD FOLİKÜLER NEOPLAZİSİNDE MALİGNİTE RİSKİNİ ARTTIRAN PREDİKTİF FAKTÖRLER

Öz

Giriş: Tiroid nodülü tespit edilen hastaların %22-42’si Bethesda kategori IV “Foliküler Neoplazi (FN)” tanısı almaktadır. Foliküler neoplazide önerilen tedavi yöntemi hemitiroidektomi (HT) olsa da hasta veya hastalığa ait bazı özellikler bu tedavi seçimin total tiroidektomi (TT) yönünde olmasına neden olmaktadır. Bu çalışmanın amacı FN tespit edilen ve cerrahi uygulanan hastalardaki klinik sonuçlarımızı değerlendirmek, patoloji sonucu malign gelen hastalarda prediktif risk faktörlerini belirlemektir. Gereç ve Yöntemler: Çalışmaya 364 hasta dahil edildi. İnce iğne aspirasyon biyopsi (İİAB) sonucu FN olan nodül “hedef nodül” olarak tanımlandı. Hastalar, hedef nodülde cerrahi sonrası malignite saptanmayan (Grup 1) ve saptanan (Grup 2) olarak iki gruba ayrıldı. İki grubun demografik, radyolojik ve klinik özellikleri belirlendi. Hastalara HT veya TT olarak iki ayrı tür cerrahi işlem uygulandı. Sonuç: Hasta sayısı, Grup 1’de 199 (%54,7), Grup 2’de 165 (%45,3) idi. Hastaların 138 (%37,9)’inde hedef nodül dışında insidental olarak malignite saptandı. Malignite riskini etkileyen faktörleri belirlemek amacı ile yapılan tek değişkenli lojistik regresyon analizi sonucunda 45 yaşın malignite için belirleyici bir kestirim değeri olabileceği gözlendi. 45 yaş altında malignite riski; 45 ve üzerindekilere göre daha fazla bulundu. Kadın hastaların 123’ünde (%42,7), erkek hastaların ise 42’isinde (%55,3) malignite görüldü. Ayrıca nodül boyutu 2 cm ve üzerinde olan hastalarda malignite riski artmaktaydı. Tartışma: FN olgularında erkek cinsiyette, 2 cm ve üzerinde olan nodüllerde, genç yaşlarda malignite riski artmaktadır. Bizim verilerimize göre FN’de malignite riski %45,3’tür. Ayrıca insidental tiroid kanseri oranı %37,9’dur. Bu oranların literatürdeki verilerden fazla olmasını bölgemizde tiroid kanser sıklığının fazla olmasına bağlamaktayız.

Anahtar Kelimeler

• Foliküler Neoplazi
• Nodül Boyutu
• Yaş
• Cinsiyet

Predictive Factors Increasing the Risk of Malignancy in Thyroid Follicular Neoplasia

Abstract

Introduction: 22-42% of patients with thyroid nodules are diagnosed as Bethesda category IV “Follicular Neoplasia (FN)”. The aim of this study is to evaluate our clinical results in patients with FN who underwent surgery and determine predictive risk factors in patients with malignant pathology results. Materials and Methods: 364 patients were included in the study. Fine needle aspirastion biopsy (FNAB) with a FN result was defined as a “target nodule”. Demographic, radiological and clinical characteristics of the two groups were determined. Two different types of surgical procedures were applied to the patients: HT or TT. Results: The number of patients was 199 (54.7%) in Group 1 and 165 (45.3%) in Group 2. Malignancy was incidentally detected in 138 patients (37.9%) outside the target nodule. The risk of malignancy was higher in those under 45 compared to those aged 45 and older. Malignancy was observed in 123 (42.7%) of female patients and 42 (55.3%) of male patients. Additionally, the risk of malignancy increased in patients with nodules measuring 2 cm or larger. Conclusion: In FN cases, the risk of malignancy increases in males, in nodules 2 cm and above, and in younger age groups. According to our data, the risk of malignancy in FN is 45.3%. Additionally, the rate of incidental thyroid cancer is 37.9%. We attribute the higher rates of these findings compared to literature to the increased frequency of thyroid cancer in our region.

Keywords

• follicular neoplasia
• nodule size
• thyroid nodule

Kaynakça

1. 1.Moon WJ, Jung SL, Lee JH, et al. Benign and malignant thyroid nodules: US differentiation multicenter retrospective study. Radiology, 2008; 247: 762-70. https://doi.org/10.1148/radiol.2473070944
2. 2.Tiroid Hastalıkları tanı ve tedavi klavuzu. TEMD, Tiroid Çalışma Grubu, 2020.
3. 3.Castro MR, Gharib H. Thyroid disorders. Thyroid nodules. In: Camacho PM, Gharib H, Sizemore GW. Evidence-based Endocrinology. Philadelphia: Lippincott Williamsand Wilkins Co, 2003:39-73.
4. 4.Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132:658-65. https://doi.org/10.1309/AJCPPHLWMI3JV4LA
5. 5.Syed ZA, Zubair WB, Beatrix CP, Fernando CS, Philippe V, Paul AV. The 2023 Bethesda System for reporting thyroid cytopathology. Thyroid. 2023; 33(9):1039-1044.
6. 6.Seiberling KA, Dutra JC, Gunn J. Ultrasound-guided fine needle aspiration biopsy of thyroid nodules performed in the office. Laryngoscope, 2008; 118:228-31. https://doi.org/10.1097/MLG.0b013e318157465d
7. 7.Mikosch P, Gallowitsch H, Kresnik E, et al. Value of ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in an endemic goitre area. Eur J Nucl Med, 2000; 27:62-9. https://doi.org/10.1007/PL00006664
8. 8.Goldstein RE, Netterville JL, Burkey B, et al. Implications of follicular neoplasms, atypia, and lesions suspicious for malignancy diagnosed by fine-needle aspiration of thyroid nodules. Ann Surg, 2002; 235:656. https://doi.org/10.1097/00000658-200205000-00007

9. 9.Smith J, Cheifetz RE, Schneidereit N, Berean K, Thomson T. Can cytology accurately predict benign follicular nodules? Am. J. Surg. 2005; 189(5):592-595. https://doi.org/10.1016/j.amjsurg.2005.01.028
10. 10.Vander JB, Gaston EA, Dawber TR. The significance of nontoxic thyroid nodules. Final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med, 1968; 69:537-40. https://doi.org/10.7326/0003-4819-69-3-537
11. 11.Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol, 1977; 7:481-93. https://doi.org/10.1111/j.1365-2265.1977.tb01340.x
12. 12.Tan GH, Gharib H. Thyroid incidentalomas: Management ap- proaches to nonpalpable nodules discovered incidentally on thy- roid imaging. Ann Intern Med, 1997; 126:226-31. https://doi.org/10.7326/0003-4819-126-3-199702010-00009
13. 13.Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest, 2009; 39:699-706. https://doi.org/10.1111/j.1365-2362.2009.02162.x
14. 14.Lin JD, Chao TC, Huang BY, et al. Thyroid cancer in the thyroid nodules evaluated by ultrasonography and fine- needle aspiration cytology. Thyroid, 2005; 15:708-17. https://doi.org/10.1089/thy.2005.15.708
15. 15.Wiest PW, Hartshorne MF, Inskip PD, et al. Thyroid palpation versus high resolution thyroid ultrasonography in the detection of nodules. J Ultrasound Med, 1998; 17:487-96. https://doi.org/10.7863/jum.1998.17.8.487
16. 16.Dal Maso L, Panato C, Franceshi S, Serraino D, Buzzoni C, Busco S, et al. The impact of overdiagnosis on thyroid cancer epidemic in Italy, 1998-2012. Eur J Cancer, 2018; 94:6-15. https://doi.org/10.1016/j.ejca.2018.01.083
17. 17.Horn-Ross PL, Lichtensztajn DY, Clarke CA, Dosiou C, Oakley- Girvan I, Reynolds P, et al. Continued rapid increase in thyroid cancer incidence in California: trends by patient, tumor and neighborhood characteristics. Cancer Epidemiol Biomarkers Prev, 2014; 23:1067-79. https://doi.org/10.1158/1055-9965.EPI-13-1089
18. 18.Hegedüs L. The thyroid nodule. N Engl J Med, 2004; 351:1764-71. https://doi.org/10.1056/NEJMcp031436
19. 19.Su DH, Liao KM, Hsiao YL, et al. Determining when to operate on patients with Hashimoto's thyroiditis with nodular lesions: the role of ultrasound-guided fineneedle aspiration cytology. Acta Cytol, 2004; 48:622-9. https://doi.org/10.1159/000326432
20. 20.Sclabas GM, Staerkel GA, Shapiro SE, et al. Fine- needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients. Am J Surg, 2003; 186:702-9. https://doi.org/10.1016/j.amjsurg.2003.08.015
21. 21.Wong LQ, Baloch ZW. Analysis of the bethesda system for reporting thyroid cytopathology and similar precursor thyroid cytopathology reporting schemes. Adv Anat Pathol, 2012; 19:313-19. https://doi.org/10.1097/PAP.0b013e3182666398
22. 22.Gulcelik NE, Gulcelik MA, Kuru B. Risk of malignancy in patients with follicular neoplasm: predictive value of clinical and ultrasonographic features. Arch Otolaryngol Head Neck Surg, 2008; 134:1312-1315. https://doi.org/10.1001/archotol.134.12.1312
23. 23.Jeong SH, Hong HS, Lee EH, Cha JG, Park JS, Kwak JJ. Outcome of thyroid nodules characterized as atypia of undeter- mined significance or follicular lesion of undetermined significance and correlation with Ultrasound features and BRAF(V600E) mutation analysis. AJR Am J Roentgenol, 2013; 201:854-860. https://doi.org/10.2214/AJR.12.9901
24. 24.McCoy KL, Jabbour N, Ogilvie JB, Ohori NP, Carty SE, Yim JH: The incidence of cancer and rate of false-negative cytology in thyroid nodules greater than or equal to 4 cm in size. Surgery 2007; 142:837-844. https://doi.org/10.1016/j.surg.2007.08.012
25. 25.Huğken BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 2016; 26(1):1-133. https://doi.org/10.1089/thy.2015.0020
26. 26.Kiernan CM, Solorzano CC. Bethesda Category III, IV and V. Thyroid Nodules Can nodule size help predict malignancy? J Am Coll Surg, 2017; 1072-7515. https://doi.org/10.1016/j.jamcollsurg.2017.02.002
27. 27.Lee SH, Baek JS, Lee JY, Lim JA, Cho SY, Lee TH, et al. Predictive factors of malignancy in thyroid nodules with a cytological diagnosis of follicular neoplasm. Endocr Pathol, 2013; 24:177-83. https://doi.org/10.1007/s12022-013-9263-x
28. 28.Kim K, Jung CK, Lim DJ, Bae JS, Kim JS. Clinical and pathologic features for predicting malignancy in thyroid follicular neoplasms. Gland Surg, 2021; 10(1):50-58. https://doi.org/10.21037/gs-20-500
29. 29.Grant EG. Thyroid Ultrasound Reporting Lexicon: White Paper of the ACR Thyroid Imaging, Reporting and Data System (TIRADS) Committee. Journal of the American College of Radiology, 2015; 12(12):1272-79. https://doi.org/10.1016/j.jacr.2015.07.011
30. 30.Najafian A, Olson MT, Schneider EB, Zeiger MA. Clinical Presentation of Patients with a Thyroid Follicular Neoplasm: Are there Preoperative Predictors of Malignancy? Ann Surg Oncol, 2015; 22:3007-3013. https://doi.org/10.1245/s10434-014-4324-z
31. 31.Sillery JC, Reading CC, Charboneau JW, Henrichsen TL, Hay ID, Mandrekar JN. Thyroid follicular carcinoma: sonographic features of 50 cases. AJR Am J Roentgenol, 2010; 194(1):44-54. https://doi.org/10.2214/AJR.09.3195
32. 32.Rago T, Di Coscio G, Basolo F, et al. Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients. Clin Endocrinol (Oxf), 2007; 66(1):13-20. https://doi.org/10.1111/j.1365-2265.2006.02677.x
33. 33.Raber W, Kaserer K, Niederle B, Vierhapper H. Risk factors for malignancy of thyroid nodules initially identified as follicular neoplasia by fine-needle aspiration: results of a prospective study of one hundred twenty patients. Thyroid, 2000; 10(8):709-12. https://doi.org/10.1089/10507250050137806
34. 34.Bongiovanni M, Spitale, A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta cytologica, 2012; 56(4):333-339. https://doi.org/10.1159/000339959
35. 35.Yim JH, Kim EY, Kim WG, et al. Postoperative findings of the cytological diagnosis of follicular neoplasm or Hürthle cell neoplasm and the risk of malignancy. Endocrinol Metabol, 2010; 25:316-20. https://doi.org/10.3803/EnM.2010.25.4.316
36. 36.Özdemir A, Uyan M, Kalcan S, Çolakoğlu MK, Pergel A. Malignancy rates and risk factors in Bethesda category IV thyroid nodules: Is lobectomy enough in an endemic region? J Exp Clin Med, 2022; 39(3):749-754. https://doi.org/10.52142/omujecm.39.3.30
37. 37.Conzo G, Giorgio CP, Gambardella C, et al. Controversies in the surgical management of thyroid follicular neoplasms. Retrospective analysis of 721 patients. International Journal of Surgery, 2014; 12:29-34. https://doi.org/10.1016/j.ijsu.2014.05.013
38. 38.Seong Hyeon Lee, Jeong Su Baek, et al. Predictive factors of malignancy in thyroid nodules with a cytological diagnosis of follicular neoplasm, Endocr. Pathol, 2013; 24(4):177-183. https://doi.org/10.1007/s12022-013-9263-x
39. 39.Kelman AS, Rathan A, Leibowitz J, et al. Thyroid cytology and the risk of malignancy in thyroid nodules: importance of nuclear atypia in indeterminate specimens. Thyroid, 2001; 11:271-7. https://doi.org/10.1089/105072501750159714
40. 40.Davis NL, Gordon M, Germann E, et al. Clinical parameters predictive of malignancy of thyroid follicular neoplasms. Am J Surg, 1991; 161:567-9. https://doi.org/10.1016/0002-9610(91)90901-O
41. 41.Schlinkert RT, Van Heerden JA, Goellner JR, et al. Factors that predict malignant thyroid lesions when fine-needle aspiration is "suspicious for follicular neoplasm." Mayo Clin Proc. 1997; 72(10):913-6. https://doi.org/10.1016/S0025-6196(11)63360-0
42. 42.Tuttle RM, Lemar H, Burch HB. Clinical features associated with an increased risk of thyroid malignancy in patients with follicular neoplasia by fine-needle aspiration. Thyroid, 1998; 8:377-83. https://doi.org/10.1089/thy.1998.8.377
43. 43.Yang GC, Goldberg JD, Ye PX. Risk of malignancy in follicular neoplasms without nuclear atypia: statistical analysis of 397 thyroidectomies. Endocr Pract, 2003; 9:510-6. https://doi.org/10.4158/EP.9.6.510
44. 44.Lee KH, Shin JH, Ko ES, Hahn SY, Kim JS, Kim JH, et al. Predictive factors of malignancy in patients with cytologically suspicious for Hurthle cell neoplasm of thyroid nodules. Int J Surg, 2013; 11:898-902. https://doi.org/10.1016/j.ijsu.2013.07.010
45. 45.Kamran SC, Marqusee E, Kim MI, Frates MC, Ritner J, Peters H, Benson CB, Doubilet PM, Cibas ES, Barletta J, Cho N, Gawande A, Ruan D, Moore FD, Jr., Pou K, Larsen PR and Alexander EK: Thyroid nodule size and prediction of cancer. J Clin Endocrinol Metab, 2013; 98:564-570. https://doi.org/10.1210/jc.2012-2968
46. 46.Ho TW, Shaheen AA, Dixon E, Harvey A. Utilization of thyroidectomy for benign disease in the United States: a 15-year population-based study. Am J Surg, 2011; 201:570-574. https://doi.org/10.1016/j.amjsurg.2010.12.006
47. 47.Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL and Tuttle RM: Revised American Thyroid Asso- ciation management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 2009; 19:1167-1214. https://doi.org/10.1089/thy.2009.0110
48. 48.Ibrahim YH, Mohammed SE, Deniwar A, Eldin S, et al. The impact of thyroid nodule size on the risk of malignancy in follicular neoplasm. Anticancer Res, 2015; 35(3):1635-9.
49. 49.Anil C, Goksel S, Gursoy A. Hashimoto's thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid, 2010; 20(6):601- 606. https://doi.org/10.1089/thy.2009.0450
50. 50.Konturek A, Barczyn ́ski M, Wierzchowski W, Stopa M, Nowak W. Coexistence of papillary thyroid cancer with Hashimotothyroiditis. Langenbecks Arch Surg, 2013; 398(3):389-394. https://doi.org/10.1007/s00423-012-1021-x
51. 51.Pu RT, Yang J, Wasserman PG, Bhuiya T, Griffith KA, Michael CW. Does Hurthle cell lesion/neoplasm predict malignancy more than follicular lesion/neoplasm on thyroid fine-needle aspiration? Diagn Cytopathol, 2006; 34(5):330-334. https://doi.org/10.1002/dc.20440
52. 52.Zhang Y, Dai J, Wu T, Yang N, Yin Z. The study of the coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. J Cancer Res Clin Oncol, 2014; 140(6):1021-1026. https://doi.org/10.1007/s00432-014-1629-z
53. 53.Kim TY, Kim WB, Song JY, et al. The BRAFV600E mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma. Clin Endocr, 2005; 63:588-93. https://doi.org/10.1111/j.1365-2265.2005.02389.x
54. 54.Fukushima T, Suzuki S, Mashiko M, et al. BRAF mutations in papillary carcinomas of the thyroid. Oncogene, 2003; 22:6455. https://doi.org/10.1038/sj.onc.1206739
55. 55.Cho U, Oh WJ, Bae JS, et al. Clinicopathological features of rare BRAF mutations in Korean thyroid cancer patients. J Korean Med Sci, 2014; 29:1054-60. https://doi.org/10.3346/jkms.2014.29.8.1054
56. 56.Liu RT, Hou CY, You HL, et al. Selective occurrence of ras mutations in benign and malignant thyroid follicular neoplasms in Taiwan. Thyroid, 2004; 14:616-21. https://doi.org/10.1089/1050725041692882
57. 57.Bae JS, Choi SK, Jeon S, et al. Impact of NRAS mutations on the diagnosis of follicular neoplasm of the thyroid. Int J Endocrinol, 2014; 1:289-834. https://doi.org/10.1155/2014/289834
58. 58.Parikh PP, Allan BJ, Lew JI. Surgeon-performed ultrasound predictors of malignancy in patients with Hurthle cell neoplasms of the thyroid. J Surg Res, 2013; 184:247-252. https://doi.org/10.1016/j.jss.2013.03.005
59. 59.Williams MD, Suliburk JW, Staerkel GA, Busaidy NL, Clayman GL, Evans DB, Perrier ND. Clinical significance of distinguishing between follicular lesion and follicular neoplasm in thyroid fine-needle aspiration biopsy. Ann Surg Oncol, 2009; 16:3146-3153. https://doi.org/10.1245/s10434-009-0666-3
60. 60.David E, Rosen IB, Bain J, James J, Kirsh JC. Management of the hot thyroid nodule. Am J Surg, 1995; 170(5):481-3. https://doi.org/10.1016/S0002-9610(99)80334-1
61. 61.Mc Henry CR, Raeburn C, Strickland T, Marty JJ. The utility of routine frozen section examination for intraoperative diagnosis of thyroid cancer, Am. J. Surg. 1996; 172(6):658-661. https://doi.org/10.1016/S0002-9610(96)00302-9