Classic Variant Papillary Thyroid Carcinoma in Graves’ Disease and Multinodular Goiter Backgrounds: A Propensity Score-Matched Comparison

Yıl 2026, Cilt: 9 Sayı: 1, 209 - 213, 17.03.2026

Kubilay Dalcı , Burak Aydoğan

https://izlik.org/JA43GS36EG

Öz

ABSTRACT
Objective: There are conflicting data in the literature regarding the prognosis and aggressiveness of papillary thyroid carcinoma arising in the background of Graves’ disease. This study aimed to compare the histopathologic features of incidentally discovered classic variant papillary thyroid carcinomas in Graves’ disease and multinodular goiter backgrounds using propensity score matching.
Material and Methods: Patients who underwent total thyroidectomy for benign indications and were found to have classic variant papillary thyroid carcinoma on histopathologic examination at Çukurova University Balcalı Hospital between 2015 and 2025 were retrospectively evaluated. Graves’ disease diagnosis was established based on the criteria of at least 2 years of antithyroid drug use, TSH receptor antibody positivity, and presence of clinical/radiologic ophthalmopathy. Groups were balanced by propensity score matching at a 1:3 ratio for age and sex. Histopathologic aggressiveness parameters were compared using non-parametric tests.
Results: A total of 44 patients with incidentally discovered classic variant papillary thyroid carcinoma following thyroidectomy for benign indications were categorized into Graves’ disease (n=11) and multinodular goiter (n=33) groups.After matching, standardized mean difference of <0.10 was achieved for all covariates. Median tumor size was significantly smaller in the Graves’ disease group compared to the multinodular goiter group (6.0 mm vs 10.0 mm, p=0.007). While lymphatic invasion was not detected in any patient in the Graves’ disease group, it was observed at a rate of 33.3% in the multinodular goiter group (p=0.041). Extrathyroidal extension, perineural invasion, and vascular invasion rates were found to be lower in the Graves’ disease group. No recurrence was observed in any patient during a median 44-month follow-up.
Conclusion: Classic variant papillary thyroid carcinomas arising in the background of Graves’ disease demonstrate smaller size and less invasive features compared to those arising in multinodular goiter background. These findings suggest that the autoimmune microenvironment in Graves’ disease may have a potential protective effect on tumor invasiveness.

Anahtar Kelimeler

Graves’ disease , multinodular goiter , papillary thyroid carcinoma , classic variant , propensity score matching , lymphatic invasion

Graves Hastalığı ve Multinodüler Guatr Zemininde Gelişen Klasik Varyant Papiller Tiroid Karsinomu: Eğilim Skoru Eşleştirilmiş Karşılaştırma

https://izlik.org/JA43GS36EG

Öz

ÖZET
Amaç: Graves hastalığı zemininde gelişen papiller tiroid karsinomu olgularının prognozu ve agresifliği konusunda literatürde çelişkili veriler mevcuttur. Bu çalışmada, Graves hastalığı ve multinodüler guatr zemininde insidental olarak saptanan klasik varyant papiller tiroid karsinomlarının histopatolojik özelliklerinin eğilim skoru eşleştirmesi yöntemiyle karşılaştırılması amaçlanmıştır.
Gereç ve Yöntem: 2015-2025 yılları arasında Çukurova Üniversitesi Balcalı Hastanesi’nde benign endikasyonlarla total tiroidektomi uygulanan ve histopatolojik incelemede klasik varyant papiller tiroid karsinomu saptanan hastalar retrospektif olarak değerlendirildi. Graves hastalığı tanısı; en az 2 yıl antitiroid ilaç kullanımı, TSH reseptör antikor pozitifliği ve klinik/radyolojik oftalmopati varlığı kriterleriyle konuldu. Gruplar yaş ve cinsiyet açısından 1:3 oranında eğilim skoru eşleştirmesi ile dengelendi. Histopatolojik agresivite parametreleri non-parametrik testlerle karşılaştırıldı.
Bulgular: Benign endikasyonlarla tiroidektomi sonrası insidental olarak saptanan klasik varyant papiller tiroid karsinomu tanısı alan toplam 44 hasta, Graves hastalığı (n=11) ve multinodüler guatr (n=33) gruplarına ayrıldı. Eşleştirme sonrası tüm kovaryantlar için standardize ortalama farkı <0.10 olarak sağlandı. Graves hastalığı grubunda median tümör boyutu multinodüler guatr grubuna göre anlamlı derecede daha küçüktü (6.0 mm vs 10.0 mm, p=0.007). Lenfatik invazyon Graves hastalığı grubunda hiç saptanmazken, multinodüler guatr grubunda %33.3 oranında izlendi (p=0.041). Ekstratiroidal yayılım, perinöral invazyon ve vasküler invazyon oranları Graves hastalığı grubunda daha düşük bulundu. Median 44 aylık takipte hiçbir hastada nüks gözlenmedi.
Sonuç: Graves hastalığı zemininde gelişen klasik varyant papiller tiroid karsinomlar, multinodüler guatr zemininde gelişenlere kıyasla daha küçük boyutlu ve daha az invaziv özellik göstermektedir. Bu bulgular, Graves hastalığındaki otoimmün mikroçevrenin tümör invazivitesi üzerinde potansiyel koruyucu etkisi olabileceğini düşündürmektedir.

Anahtar Kelimeler

Graves hastalığı , multinodüler guatr , papiller tiroid karsinomu , klasik varyant , eğilim skoru eşleştirmesi , lenfatik invazyon

Kaynakça

• Zhou J, Wang WR, Zhang HF, et al. Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype. Front Endocrinol (Lausanne). 2023;14:1138100. Crossref
• Tez M. Letter to “the Prevalence of Incidental Thyroid Carcinoma in Patients Who Underwent Thyroidectomy for Multinodular Goiter”. Indian J Surg. 2018;80(1):103. Crossref
• May Mohammed Saleem AlQaraghuli ARA. The prevalence of micro papillary thyroid carcinoma and its correlation with age, gender and the histological background. World J Adv Healthc Res. 2022;6(11):1-4. Belfiore A, Russo D, Vigneri R, Filetti S. Graves' disease, thyroid nodules and thyroid cancer. Clin Endocrinol (Oxf). 2001;55(6):711-718. Crossref
• Yildirim Simsir I, Cetinkalp S, Kabalak T. Review of Factors Contributing to Nodular Goiter and Thyroid Carcinoma. Med Princ Pract. 2020;29(1):1-5. Crossref
• Kwon H, Moon BI. Prognosis of papillary thyroid cancer in patients with Graves' disease: a propensity score-matched analysis. World J Surg Oncol. 2020;18(1):266. Crossref
• Pellegriti G, Mannarino C, Russo M, et al. Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease. J Clin Endocrinol Metab. 2013;98(3):1014-1021. Crossref
• Mekraksakit P, Rattanawong P, Karnchanasorn R, et al. Prognosis of differentiated thyroid carcinoma in patients with Graves disease: A systematic review and meta-analysis. Endocr Pract. 2019;25(12):1323-1337. Crossref
• an Z, Teng W. Prognosis of differentiated thyroid cancer in patients with Graves' disease: a meta-analysis. Thyroid Res. 2025;18(1):51. Crossref
• Yano Y, Shibuya H, Kitagawa W, et al. Recent outcome of Graves' disease patients with papillary thyroid cancer. Eur J Endocrinol. 2007;157(3):325-329. Crossref
• Gopinath C, Crow H, Panthi S, Bantis L, Burman KD, Choudhary C. Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves' disease. J Clin Transl Endocrinol. 2023;33:100321. Crossref
• Jaume JC. Thyroid Cancer—The Tumor Immune Microenvironment (TIME) over Time and Space. Cancers (Basel). 2025;17(5):794. Crossref
• Nguyen VPT, Kurohama H, Akazawa Y, et al. Associations of clinicopathologic features and mutation status with lateral lymph node metastasis as a predictor of disease-free survival in papillary thyroid carcinoma. Pathol Res Pract. 2025;269:155951. Crossref
• Güden İ, Karatas I, Iscan Y, et al. Comparison of clinical and histopathological characteristics of differentiated thyroid cancers in euthyroid nodular goiter and Graves' disease. Endocr Connect. 2025;14(8). Crossref
• Abidin Sayiner Z, Yatkin Keles Y, Ozturk S, Akarsu E. An Analytical Comparison of Papillary Thyroid Carcinoma Patients Manifested with or without Graves' Disease. Sisli Etfal Hastan Tip Bul. 2024;58(3):354-358. Crossref
• Yuen HY, Wong KT, Ahuja AT. Sonography of diffuse thyroid disease. Australas J Ultrasound Med. 2016;19(1):13-29. Crossref
• González-Sánchez-Migallón E, Flores-Pastor B, Pérez-Guarinos CV, et al. Incidental versus non-incidental thyroid carcinoma: Clinical presentation, surgical management and prognosis. Endocrinol Nutr. 2016;63(9):475-481. Crossref
• Song Y, Fu L, Wang P, et al. Effect of Graves' disease on the prognosis of differentiated thyroid carcinoma: a meta-analysis. Endocrine. 2020;67(3):516-525. Crossref
• Mohan U, Sunny SP, Mendonca P, Kuriakose MA, Kannan S, Suresh A. Systematic Review and Meta-Analysis to Identify the Immunocytochemical Markers Effective in Delineating Benign from Malignant Thyroid Lesions in FNAC Samples. Endocr Pathol. 2022;33(2):243-256. Crossref
• de Matos LL, Del Giglio AB, Matsubayashi CO, de Lima Farah M, Del Giglio A, da Silva Pinhal MA. Expression of CK-19, galectin-3 and HBME-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol. 2012;7:97. Crossref