The Role of CD56, HBME-1, and CK19 Immunohistochemical Markers in the differential Diagnosing of Thyroid Neoplasms
Main Article Content
Keywords
Papillary Thyroid Carcinoma, Follicular adenoma, Follicular Thyroid Carcinoma, Follicular patterned neoplasm.
Abstract
Background: The diagnosis of thyroid neoplasms is steadily increasing due to the widespread use of sensitive diagnostic techniques. While histopathologic evaluation using Hematoxylin and Eosin (H&E) staining is considered the "gold standard," it often faces challenges due to morphological overlap between benign and malignant follicular patterned lesions. This led to diagnostic uncertainties, underscoring the need for Immunohistochemistry (IHC) as a valuable adjunct. This study aims to evaluate the expression of IHC markers, Hector Battifora Mesothelial Cell-1 (HBME-1), Cluster of Differentiate (CD56 also known as Neural Cell Adhesion Molecule) and Cytokeratin-19 (CK19), in follicular patterned neoplasms of thyroid to aid in the diagnosis of malignant thyroid neoplasms
Methodology: The study was a descriptive analysis and it included 60 thyroidectomy specimens diagnosed as neoplastic by histopathology were studied after satisfying the inclusion and exclusion criteria. The IHC results were interpreted semi-quantitatively. Statistical analysis was performed using Chi-square test and Fisher’s-exact tests. P-value of <0.05 was considered as significant. Sensitivity and specificity for each marker and their combination in diagnosis were calculated.
Results: Among the sixty cases, 31.67% were benign neoplasms, and 68.33% were malignant. Loss of CD56 expression was noted in 75.68% of malignant cases. The specificity of CD56, HBME-1, and CK19 in identifying malignant neoplasms was 84.21%, 84.21%, and 89.47%, respectively. The accuracy of CD56 and CK19 in diagnosing follicular variant papillary thyroid carcinoma (FVPTC) from follicular adenoma (FA) was 79.31% and 93.10%, respectively. The specificity of CK19 in distinguishing FVPTC from FA was 89.47%. The specificity of CD56, CK19, and HBME-1 in diagnosing follicular thyroid carcinoma (FTC) from FA was 84.21%, 85%, and 84.21%, respectively.
Conclusions: Our study highlights the diagnostic utility of CD56, CK19, and HBME-1 in thyroid neoplasms incorporating these markers into routine diagnostic panels can significantly enhance the accuracy and reliability of thyroid malignancy assessments.
References
2. Sathishkumar K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for 2022 & projection for 2025: result from National Cancer Registry Programme, India. Indian Journal of Medical Research. 2022 Oct 1;156(4&5):598-607.
3. Canberk S, Gunes P, Onenerk M, Erkan M, Kilinc E, Kocak Gursan N, et al. New Concept of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma and Its Impact on the Bethesda System for Reporting Thyroid Cytopathology: A Single-Institute Experience. Acta Cytol 2016; 60: 198-204.
4. Fletcher CDM, editor. Fletcher Diagnostic Histopathology of Tumors. 5th ed., Philadelphia, PA: Elsevier Saunders; 2021. p. 1244-5.
5. Alves VA, Kakudo K, LiVolsi V, Lloyd RV, Nikiforov YE, Nose V, Papotti M, Thompson LD. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): achieving better agreement by refining diagnostic criteria. Clinics. 2018 May 21;73:e576.
6. LiVolsi VA, Baloch ZW. Follicular-patterned tumors of the thyroid: the battle of benign vs. malignant vs. so-called uncertain. Endocrine pathology. 2011 Dec; 22:184-9.
7. Nechifor-Boila A, Borda A, Sassolas G, Hafdi-Nejjari Z, Borson-Chazot F, Lifante JC, Sturm N, Lavérriere MH, Berger N, Decaussin-Petrucci M. Immunohistochemical markers in the diagnosis of papillary thyroid carcinomas: The promising role of combined immunostaining using HBME-1 and CD56. Pathology-Research and Practice 2013;209(9):585-592.
8. Barut F, Onak Kandemir N, Bektas S, Bahadir B, Keser S, Ozdamar SO. Universal markers of thyroid malignancies: galectin-3, HBME-1, and cytokeratin-19. Endocrine pathology 2010 Jun;21:80-9.
9. El Demellawy D, Nasr A, Alowami S. Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid. Diagnostic pathology. 2008 Dec;3:1-2.
10. Muthusamy S, Azhar Sha S, Abdullah Suhaimi SN, Kassim N, Mahasin M, Mohd Saleh MF, et al. CD56 expression in benign and malignant thyroid lesions. Malays J Pathol 2018;40:111-9.
11. Slaoui M, Bauchet AL, Fiette L. Tissue sampling and processing for histopathology evaluation. Drug safety evaluation: Methods and protocols. 2017:101-14.
12. Lloyd RV, Osamura RY, Kloppel G, Rosai J. (eds) WHO Classification of Tumours of Endocrine Organs. 4th ed. (IARC, 2017).
13. Calangiu CM, Simionescu CE, Stepan AE, Cernea D, Zăvoi RE, Mărgăritescu C. The expression of CK19, vimentin, and E-cadherin in differentiated thyroid carcinomas. Rom J Morphol Embryol 2014; 55:919-25.
14. Sharma, R, Verma N, Kaushal V, Sharma DR, Sharma D. Diagnostic accuracy of fine-needle aspiration cytology of thyroid gland lesions: A study of 200 cases in Himalayan belt. JJOCR & Therapeutics 2017.13, 451.
15. Mehrotra D, Anita A, Andola SK, Patil AG. Thyroid cytology evaluation based on the Bethesda system with clinico-morphological correlation. Ann of Pathol and Lab Med 2016;3(4):A347-355.
16. Renuka IV, Saila Bala G, Aparna C, Kumari R, Sumalatha K. The bethesda system for reporting thyroid cytopathology: interpretation and guidelines in surgical treatment. Indian J Otolaryngol Head Neck Surg. 2012 Dec;64(4):305-11. doi: 10.1007/s12070-011-0289-4.
17. Yang X, Hu Y, Shi H, Zhang C, Wang Z, Liu X, et al. The diagnostic value of TROP-2, SLP-2, and CD56 expression in papillary thyroid carcinoma. Eur Arch Otorhinolaryngol 2018; 275:2127-34.
18. Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol2001;14:338-42.
19. Palo S, Biligi DS. Differential diagnostic significance of HBME-1, CK19, and S100 in various thyroid lesions. Malays J Pathol2017; 39:55-67
20. Priyadarshini P, Patro MK, Das PK. Diagnostic role of immunohistochemical markers CK19 and CD56 in thyroid neoplasms. MGM Journal of Medical Sciences. 2023 Apr 1;10(2):176-83.
21. Tastekin E, Keskin E, Can N, Canberk S, Mut A, Erdogan E, et al. CD56, CD57, HBME1, CK19, Galectin-3, and p63 immunohistochemical stains in differentiating diagnosis of thyroid benign/malign lesions and NIFTP. Pol J Pathol 2019;70:286-94.
22. Dunđerović D, Lipkovski JM, Boričic I, Soldatović I, Božic V, Cvejić D, et al. Defining the value of CD56, CK19, Galectin 3, and HBME-1 in the diagnosis of follicular cell-derived thyroid lesions with a systematic review of the literature. Diagn Pathol 2015;10:196.
23. Abouhashem NS, Talaat SM. Diagnostic utility of CK19 and CD56 in differentiating thyroid papillary carcinoma from its mimics. Pathol Res Pract 2017;213:509-17.
24. Huang L, Wang X, Huang X, Gui H, Li Y, Chen Q, et al. Diagnostic significance of CK19, galectin-3, CD56, TPO, and Ki67 expression and BRAF mutation in papillary thyroid carcinoma. Oncol Lett 2018;15:4269-77.
25. Pyo JS, Kim DH, Yang J. Diagnostic value of CD56 immunohistochemistry in thyroid lesions. The International journal of biological markers. 2018 May;33(2):161-7.
26. Cho H, Kim JY, Oh YL. Diagnostic value of HBME‐1, CK19, Galectin 3, and CD56 in the subtypes of follicular variant of papillary thyroid carcinoma. Pathology International. 2018 Nov;68(11):605-13.
27. Sahoo S, Hoda SA, Rossi J, DeLellis RA. Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: A note of caution. Am J Clin Pathol 2001;116:696-702.
28. Dağlar Aday A, Demir H, Öztürk T. Utility of Immunohistochemistry Markers CK19, Gal-3, HBME-1 and Their Combinations for Differential Diagnosis of Thyroid Diseases. Indian Journal of Surgery. 2023 Oct;85(5):1203-11.
29. Nasr MR, Mukhopadhyay S. Papillary Thyroid Carcinoma: Use of HBME1 and CK19 as Diagnostic Markers. Methods of Cancer Diagnosis, Therapy, and Prognosis: General Overviews, Head and Neck Cancer and Thyroid Cancer. 2010:379-85.
30. El-Mahdy MM, Mabrouk SH, El-Din ZS, Ghazal FA, Mohamed HH. Diagnostic value of HBME-1 and CK19 expression in papillary thyroid carcinoma, well-differentiated tumours of uncertain malignant potential, and benign thyroid nodules. Egyptian Journal of Pathology. 2011 Dec 1;31(2):68-74.