Morphological and immunohistochemical evaluation of interface lesions between chronic lymphocytic thyroiditis and papillary thyroid cancers

Yıl 2022, Cilt: 5 Sayı: 2, 552 - 557, 15.03.2022

Pınar Celepli , İrem Bigat , Salih Celepli , Sema Hücümenoğlu

https://doi.org/10.32322/jhsm.1052732

Öz

Objective: To evaluate the expression of papillary thyroid carcinoma-associated tumor markers in reactive and dysplastic changes showing papillary thyroid carcinoma-like nuclear features in chronic lymphocytic thyroiditis cases.
Material and Method: In this study, we retrospectively analyzed 84 cases diagnosed with chronic lymphocytic thyroiditis based on the analysis of thyroidectomy specimens in our center over the last five years. We classified them as normal, reactive and dysplastic changes and performed an immunohistochemical analysis using HBME-1, Galectin-3, Cytokeratin 19, and Cyclin D1.
Results: The mean age of the patients was 45.5 years, and 68 were female and 16 were male. According to the morphological features, 42.9% of the were classified to have normal morphology, 44.0% reactive atypia, and 13.1% follicular epithelial dysplasia (FED). Of the chronic lymphocytic thyroiditis cases, 42.9% were associated with malignancy, with the most common accompanying malignancy being papillary thyroid cancer (36.9%). Immunohistochemically: for HBME-1, FED (72.7%) was higher (p<0.05) than normal and reactive atypia (0.0%); for Galectin-3, FED (63.6%) was higher (p<0.05) than normal and reactive atypia (0.0%); for Cytokeratin 19, Reactive atypia (75.7%) and FED (90.9%) were higher than normal (44.4%); and for Cyclin-D1, Reactive atypia (62.2%) and FED (81.8%) were higher than normal (33.3%).
Conclusions: We consider that reactive and dysplastic changes including papillary thyroid carcinoma-like nuclear changes may support preneoplastic changes in terms of morphology and immunoprofile in chronic lymphocytic thyroiditis cases.

Anahtar Kelimeler

Thyroid cancer, follicular epithelial dysplasia, chronic lymphocytic thyroiditis

Kaynakça

• Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2018, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2018/, based on November 2020 SEER data submission, posted to the SEER web site, 2021. Access date: 12.10.2021.
• Canberk S. Precursor and borderline lesions of the thyroid (indolent lesions of epithelial origin): from theory to practice. Gland Surg 2020; 9: 1724-34. 
• Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. 9th Edition. Ellsevier Health sciences 2020.
• Jankovic B, Le KT, Hershman JM. Clinical review: Hashimoto’s thyroiditis and papillary thyroid carcinoma: is there a correlation? J Clin Endocrinol Metab 2013; 98: 474–82.
• Chui MH, Cassol CA, Asa SL, Mete O. Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis. Virchows Arch 2013; 462: 557–63.
• Paunovic I, Isic T, Havelka M, Tatic S, Cvejic D, Savin S. Combined immunohistochemistry for thyroid peroxidase, galectin-3, CK19 and HBME-1 in differential diagnosis of thyroid tumors. Apmis 2012; 120: 368–79. 
• de Matos PS, Ferreira AP, de Oliveira FF, Assumpcao LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 2005; 47: 391–401.
• Temmim L, Ebraheem AK, Baker H, Sinowatz F. Cyclin D1 protein expression in human thyroid gland and thyroid cancer. Anat Histol Embryol 2006; 35: 125-9.
• Virchow R. Die Krankhaften Geschwulste. Aetologie der neoplastichen Geschwulste/Pathogenie der neoplastischen Geschwulste. Verlag von August Hirschwald, Berlin 1863.
• Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 2007; 121: 2373–80.
• Noureldine SI, Tufano RP. Association of Hashimoto's thyroiditis and thyroid cancer. Curr Opin Oncol 2015; 27: 21-5.
• Pusztaszeri MP, Faquin WC, Sadow PM. Tumor-associated inflammatory cells in thyroid carcinomas. Surg Pathol Clin 2014; 7: 501-14.
• Guarino V, Castellone MD, Avilla E, Melillo RM. Thyroid cancer and inflammation. Mol Cell Endocrinol 2010; 321: 94-102.
• Boi F, Pani F, Mariotti S. Thyroid autoimmunity and thyroid cancer: review focused on cytological studies. Eur Thyroid J 2017; 6: 178-86.
• Ehlers M, Schott M. Hashimoto's thyroiditis and papillary thyroid cancer: are they immunologically linked? Trends Endocrinol Metab 2014; 25: 656-64.
• Nicolson NG, Brown TC, Korah R, Carling T. Immune cell infiltrate-associated dysregulation of DNA repair machinery may predispose to papillary thyroid carcinogenesis. Surgery 2020; 167: 66–72.
• Kholová I, Kalfert D, Lintusaari J, Rajakorpi E, Ludviková M. Follicular epithelial dysplasia as hashimoto thyroiditis‑related atypia: a series of 91 specimens. Endocrine Pathology 2021; 32: 368–74.
• Berho M, Suster S. Clear nuclear changes in Hashimoto's thyroiditis. A clinicopathologic study of 12 cases. Ann Clin Lab Sci 1995; 25: 513-21.
• Di Pasquale M, Rothstein JL, Palazzo JP. Pathologic features of Hashimoto's-associated papillary thyroid carcinomas. Hum Pathol 2001; 32: 24-30.
• Ma H, Yan J, Zhang C, et al. Expression of papillary thyroid carcinoma-associated molecular markers and their significance in follicular epithelial dysplasia with papillary thyroid carcinoma-like nuclear alterations in Hashimoto's thyroiditis. Int J Clin Exp Pathol 2014; 7: 7999-8007.
• Prasad ML, Huang Y, Pellegata NS, de la Chapelle A, Kloos RT. Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC. Histopathology 2004; 45: 39-46.
• Nasr MR, Mukhopadhyay S, Zhang S, Katzenstein AL. Absence of the BRAF mutation in HBME1+ and CK19+ atypical cell clusters in Hashimoto thyroiditis: supportive evidence against preneoplastic change. Am J Clin Pathol 2009; 132: 906–12.
• Arif S, Blanes A, Diaz-Cano SJ. Hashimoto’s thyroiditis shares features with early papillary thyroid carcinoma. Histopathology 2002; 41: 357–62.
• Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 2014; 159: 676–90.
• Jung CK, Little MP, Lubin JH, et al. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab 2014; 99: E276-85.
• Muzza M, Degl'Innocenti D, Colombo C, et al. The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies. Clin Endocrinol (Oxf) 2010; 72: 702-8.
• Kang DY, Kim KH, Kim JM, et al. High prevalence of RET, RAS, and ERK expression in Hashimoto's thyroiditis and in papillary thyroid carcinoma in the Korean population. Thyroid 2007; 17: 1031-8.
• Sargent R, LiVolsi V, Murphy J, Mantha G, Hunt JL. BRAF mutation is unusual in chronic lymphocytic thyroiditis-associated papillary thyroid carcinomas and absent in non-neoplastic nuclear atypia of thyroiditis. Endocr Pathol 2006; 17: 235–41.