ÖNEMI BELIRSIZ ATIPI/ÖNEMI BELIRSIZ FOLIKÜLER LEZYON VAKALARININ YÖNETIMINDE INFLAMATUAR PARAMETRELERIN ROLÜ

Yıl 2023, Cilt: 56 Sayı: 2, 131 - 135, 30.09.2023

Marlen Süleyman , Rıfat Bezirci

https://doi.org/10.20492/aeahtd.1342736

Öz

AMAÇ: Bu çalışma, biyopsi sonucu Önemi Belirsiz Atipi/Önemi Belirsiz Foliküler Lezyon (ÖBA/ÖBFL) olarak sınıflandırılan hastalarda hematolojik parametreler ve nötrofil-lenfosit oranı (NLO), platelet-lenfosit oranı (PLO), monosit-lenfosit oranı (MLO), sistemik immün-inflamasyon indeksi (Sİİ), sistemik inflamasyon yanıt indeksi (SİYİ) gibi ve belirteçlerin malignite riskini öngörü potansiyelini değerlendirmeyi amaçladı.

GEREÇ VE YÖNTEM: Bir Genel Cerrahi kliniğinde tiroidektomi yapılan toplam 188 hasta çalışmaya dahil edildi. Nötrofil sayısı, trombosit sayısı, lenfosit sayısı, monosit sayısı ve ortalama platelet hacmi (OPH) gibi hematolojik parametreler hastane veri tabanından toplandı. NLO, PLO, MLO, Sİİ ve SİYİ hesaplandı. İstatistiksel analizler SPSS v25 kullanılarak yapıldı.

BULGULAR: 38 hasta (%20,21) erkek ve 150 hasta (%79,79) kadındı. Ortalama yaş 48.6 (dağılım 23-79, SD ± 12,41 yıl) idi. Tiroidektomi örneklerinin histopatolojik incelemesinde 102 hastada (%54,3) benign, 86 hastada (%45,7) malign bulgular saptandı. Malign grubun yaş ortalaması 45,6 iken, benign grubun yaş ortalaması 51,1 idi (p = 0,02). Ortanca tümör boyutu malign grupta 17 mm, benign grupta ise 21 mm idi (p =0,042). Ortalama nötrofil sayısı sırasıyla benign grupta 4,29 ± 1,0 × 109/L ve malign grupta 4,69 ± 1,9 × 109/L idi (p = 0,031). NLO değerleri benign grup için 1.89 ve malign grup için 1,99 olarak hesaplanmıştır (p = 0.045). Sİİ değerleri malign grupta daha yüksek saptanmıştır, malign grupta medyan değer 584,11×109/L iken, benign grupta medyan değer 504,63×109/L'dir (p=0,037).
Çok değişkenli lojistik regresyon analizi, hem yaşın (odds oranı (OR) = 0,964; %95 güven aralığı (CI)= (0,939- 0,989); p = 0,05) hem de nötrofil sayısının OR = 1,598; %95 CI= (1,118- 2,285); p = 0,01) benign ve malign tiroid nodülleri arasındaki ayrım üzerinde önemli bir etkisi olduğunu göstermiştir.
SONUÇ: Yaş ve nötrofil sayısı malign tiroid nodülleri için bağımsız risk faktörleri olarak belirlenmiştir. Bethesda Kategori III tiroid nodülü olan hastalar arasında, 59,5 yaşın altında ve nötrofil sayısı 4,16 x 10^9/L'nin üzerinde olanlar tiroid malignitesi için artmış riske sahiptir.
Trombosit sayısı, monosit sayısı ve PLO, MLO ve SİYİ gibi enflamatuar parametreler Bethesda III nodüllerinde maligniteyi tespit etmek için yetersiz bulunmuştur. Bu grupta genç yaş, küçük nodül boyutu, yüksek nötrofil sayısı, NLO ve Sİİ malignite için risk faktörleri olarak tanımlanmıştır. Bu hastaların yönetiminde nodüllerin The Thyroid Imaging Reporting and Data System (TI-RADS) özellikleri de göz önünde bulundurulmalıdır.

Anahtar Kelimeler

Bethesda raporlama sistemi, Önemi belirsiz atipi/önemi belirsiz foliküler lezyonlar, nodüller, Tiroid kanseri, biyobelirteç

Destekleyen Kurum

Yok

Proje Numarası

-

The role of inflammatory parameters in the management of cases with atypia of undetermined significance/follicular lesions of undetermined significance

Öz

AIM: This study aimed to evaluate the potential of hematologic parameters and markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict the risk of malignancy in patients whose biopsy results were classified as Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS).
MATERIAL AND METHOD: A total of 188 patients who underwent thyroidectomy at a General Surgery clinic were included in the study. Hematological parameters, including neutrophil count, platelet count, lymphocyte count, monocyte count, and mean platelet volume (MPV) were collected from the hospital database. NLR, PLR, MLR, SII, and SIRI were calculated. Statistical analyses were performed using SPSS v25.
RESULTS: 38 patient (20.21%) were male and 150 patients (79.79 %) were female. The mean age was 48.6 (range 23-79, standard deviation (SD) ± 12.41years). Histopathological examination of the thyroidectomy specimens revealed benign findings in 102 patients (54.3%) and malignant findings in 86 patients (45.7%). The mean age of the malignant group was 45.6, while that of the benign group was 51.1 (p = 0.02). The median tumor size was 17 mm in the malignant group and 21 mm in the benign group (p =0.042). Mean neutrophil count were 4.29 ± 1.0 × 109/L in the benign group and 4.69 ± 1.9 × 109/L in malignant group, respectively (p = 0.031). NLR values were calculated as 1.89 for the benign group and 1.99 for the malignant group (p = 0.045). SII values were higher in the malignant group, with a median value of 584.11× 109/L in the malignant group, median value were 504.63× 109/L in the benign group (p=0.037).
Multivariate logistic regression analysis revealed that both age (odds ratio (OR) = 0.964; 95% confidence interval (CI)= (0.939 – 0.989); p = 0.05) and neutrophil count (odds ratio (OR) = 1.598; 95% confidence interval (CI)= (1.118 – 2.285); p = 0.01) had a significant impact on the differentiation between benign and malignant thyroid nodules.
CONCLUSION: Age and neutrophil count were identified as independent risk factors for malignant thyroid nodules. Among patients with Bethesda Category III thyroid nodules, those under 59.5 years of age and with a neutrophil count above 4.16 x 10^9/L have an increased risk for thyroid malignancy.
Platelet count, monocyte count, MPV and inflammatory parameters, such as PLR, MLR, and SIRI, were insufficient for detecting malignancy in Bethesda III nodules. In this group, young age, small nodule size, high neutrophil count, NLR, and SII were identified as risk factors for malignancy. The Thyroid Imaging Reporting and Data System (TI-RADS) characteristics of nodules should also be considered in the management of these patients.

Anahtar Kelimeler

Atypia of undetermined significance/follicular lesions of undetermined significance nodules, Thyroid cancer, biomarker

Proje Numarası

-

Kaynakça

• 1. Haugen BR, Alexander EK, Bible KC, 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.
• 2. 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(8):699-706.
• 3. Smith-Bindman R, Lebda P, Feldstein VA, et al. Risk of thyroid cancer based on thyroid ultrasound imaging characteristics: results of a population-based study. JAMA Intern Med. 2013;173(19):1788-96.
• 4. Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017;27(11):1341-6.
• 5. Ho AS, Sarti EE, Jain KS, et al. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid. 2014;24(5):832-9.
• 6. Turkyilmaz S, Ulusahin M, Celebi B, et al. Thyroid nodules classified as atypia or follicular lesions of undetermined significance deserve further research: Analysis of 305 surgically confirmed nodules. Cytopathology. 2017;28(5):391-399.
• 7. Hong SH, Lee H, Cho MS, Lee JE, Sung YA, Hong YS. Malignancy Risk and Related Factors of Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance in Thyroid Fine Needle Aspiration. Int J Endocrinol. 2018;2018:4521984.
• 8. Bernstein JM, Shah M, MacMillan C, Freeman JL. Institution-specific risk of papillary thyroid carcinoma in atypia/follicular lesion of undetermined significance. Head Neck. 2016;38 Suppl 1:E1210-5.
• 9. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493-503.
• 10. Guarino V, Castellone MD, Avilla E, Melillo RM. Thyroid cancer and inflammation. Mol Cell Endocrinol. 2010;321(1):94-102.
• 11. Cong R, Kong F, Ma J, Li Q, Wu Q, Ma X. Combination of preoperative neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio: a superior prognostic factor of endometrial cancer. BMC Cancer. 2020;20(1):464.
• 12. Ohsawa M, Hamai Y, Emi M, et al. Neutrophil-to-Lymphocyte Ratio as a Predictor of Postoperative Recurrence and Prognosis in Oesophageal Squamous Cell Carcinoma. Anticancer Res. 2022;42(3):1499-507.
• 13. Mellor KL, Powell A, Lewis WG. Systematic Review and Meta-Analysis of the Prognostic Significance of Neutrophil-Lymphocyte Ratio (NLR) After R0 Gastrectomy for Cancer. J Gastrointest Cancer. 2018;49(3):237-44.
• 14. Manatakis DK, Tseleni-Balafouta S, Tzelves L, et al. Diagnostic Accuracy of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Detecting Occult Papillary Thyroid Microcarcinomas in Benign Multinodular Goitres. J Thyroid Res. 2018;2018:3470429.
• 15. Geng Y, Shao Y, Zhu D, et al. Systemic Immune-Inflammation Index Predicts Prognosis of Patients with Esophageal Squamous Cell Carcinoma: A Propensity Score-matched Analysis. Sci Rep. 2016;6:39482.
• 16. Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-22.
• 17. Chen JH, Zhai ET, Yuan YJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017;23(34):6261-72.
• 18. Wang C, Jin S, Xu S, Cao S. High Systemic Immune-Inflammation Index (SII) Represents an Unfavorable Prognostic Factor for Small Cell Lung Cancer Treated with Etoposide and Platinum-Based Chemotherapy. Lung. 2020;198(2):405-14.
• 19. Zhang Z, Xia F, Wang W, Huang Y, Li X. The systemic immune-inflammation index-based model is an effective biomarker on predicting central lymph node metastasis in clinically nodal-negative papillary thyroid carcinoma. Gland Surg. 2021;10(4):1368-73.
• 20. Kars A, Sahin A, Kilic K, Sakat MS, Bilen A. Systemic immune inflammation index in differentiated thyroid cancers. Acta Otorhinolaryngol Ital. 2022;42(2):150-4.
• 21. Qi Q, Zhuang L, Shen Y, et al. A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy. Cancer. 2016;122(14):2158-67.
• 22. Zhou Q, Su S, You W, Wang T, Ren T, Zhu L. Systemic Inflammation Response Index as a Prognostic Marker in Cancer Patients: A Systematic Review and Meta-Analysis of 38 Cohorts. Dose Response. 2021;19(4):15593258211064744.
• 23. He P, Yang H, Lai Q, et al. The diagnostic value of blood cell-derived indexes in subacute thyroiditis patients with thyrotoxicosis: a retrospective study. Ann Transl Med. 2022;10(6):322.
• 24. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: A Cancer Journal for Clinicians. 2022;72(1):7-33.
• 25. 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;317(13):1338-48.
• 26. Chen W, Zheng R, Baade PD, Zhang S, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-32.
• 27. Agrawal S. Diagnostic accuracy and role of fine needle aspiration cytology in management of thyroid nodules. J Surg Oncol. 1995;58(3):168-72.
• 28. Bohacek L, Milas M, Mitchell J, Siperstein A, Berber E. Diagnostic accuracy of surgeon-performed ultrasound-guided fine-needle aspiration of thyroid nodules. Ann Surg Oncol. 2012;19(1):45-51.
• 29. Naim C, Karam R, Edde D. Ultrasound-guided fine-needle aspiration biopsy of the thyroid: methods to decrease the rate of unsatisfactory biopsies in the absence of an on-site pathologist. Can Assoc Radiol J. 2013;64(3):220-5.
• 30. Yoon JH, Lee HS, Kim EK, Moon HJ, Kwak JY. A nomogram for predicting malignancy in thyroid nodules diagnosed as atypia of undetermined significance/follicular lesions of undetermined significance on fine needle aspiration. Surgery. 2014;155(6):1006-13.
• 31. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6(1):149-63. 1.
• 32. Duymuş M. E. Diferansiye Tiroid Kanserli Hastalarda Preoperatif Nötrofil / Lenfosit Oranının Boyun Ultrasonografisi ve Patolojik Bulgularla İlişkisi. Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi. 2021; 54(2): 243-248.
• 33. Sit M, Aktas G, Erkol H, Yaman S, Keyif F, Savli H. Neutrophil to Lymphocyte Ratio is Useful in Differentiation of Malign and Benign Thyroid Nodules. P R Health Sci J. 2019 Mar;38(1):60-63.
• 34. McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev. 2013;39(5):534-40.
• 35. Bostan H, Sencar ME, Calapkulu M, et al. The predictive value of hematologic parameters in the risk of thyroid malignancy in cases with atypia/follicular lesion of undetermined significance. Eur Arch Otorhinolaryngol. 2022.
• 36. Ozmen S, Timur O, Calik I, et al. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) may be superior to C-reactive protein (CRP) for predicting the occurrence of differentiated thyroid cancer. Endocr Regul. 2017;51(3):131-6.
• 37. Bozan MB, Yazar FM, Kale İT, Yüzbaşıoğlu MF, Boran ÖF, Azak Bozan A. Delta Neutrophil Index and Neutrophil-to-Lymphocyte Ratio in the Differentiation of Thyroid Malignancy and Nodular Goiter. World J Surg. 2021;45(2):507-14.
• 38. Baldane S, Ipekci SH, Sozen M, Kebapcilar L. Mean platelet volume could be a possible biomarker for papillary thyroid carcinomas. Asian Pac J Cancer Prev. 2015;16(7):2671-4.
• 39. Machairas N, Kostakis ID, Prodromidou A, et al. Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions. Endocr Res. 2017;42(4):311-7.
• 40. Evranos Ogmen B, Aydin C, Kilinc I, Aksoy Altinboga A, Ersoy R, Cakir B. Can Repeat Biopsies Change the Prognoses of AUS/FLUS Nodule? Eur Thyroid J. 2020;9(2):92-8.