Encapsulated follicular thyroid tumors of uncertain malignant potential in the new international histological classification

The new fourth edition of the WHO classification of tumors of endocrine organs published by the International agency for research of cancer (IARC) in 2017 as the previous third edition of 2004 pays substantial attention to the thyroid gland tumors. Experts revised criteria of malignancy in category of encapsulated non-invasive follicular thyroid neopasm with papillary-like nuclear features. The previous edition classified these tumors as malignant follicular variant of papillary thyroid carcinoma (PTC). The new edition considers their behavior status as borderline or tumors of uncertain malignant potential. An estimation of malignancy of follicular thyroid tumors is impossible in preoperative cytological smears due to unknown cytological markers of malignancy and in 10% tumors after surgery due to equivocal histological features of capsular/vascular invasion and/or doubtful PTC-like nuclear features. Criteria of non-invasive follicular thyroid neoplasm with papillary-like nuclear features as well as criteria of two classification categories of follicular and well differentiated tumors of uncertain malignant potential (UMP) are presented in this paper. A special attention is paid to diagnostic significance of invasive growth as a basic feature of malignancy. In connection with the revised criteria of international classification we discuss an importance of adequate histological examination and influence of new borderline categories on surgical treatment of encapsulated follicular thyroid tumors in the paper.

1. Lloyd RV, Osamura RY, Klöppel G, Rosai J, editors. WHO Classification of Tumours of Endocrine Organs. Lyon: IARC; 2017.

2. Rosai J, Carcangiu ML, DeLellis RA. Atlas of Tumor Pathology: Tumors of the Thyroid Gland. Washington: Armed Forces Institute of Pathology; 1992.

3. Williams ED. Guest editorial: two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol. 2000;8(3):181-183. doi: 10.1177/106689690000800304.

4. DeLellis RA, Lloyd RV, Hertz PU, Eng C, editors. WHO Classification of Tumours; Pathology and Genetics of Tumours of Endocrine Organs. Lyon: IARC; 2004.

5. Nikiforov YE, Seethala RR, Tallini G, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2016;2(8):1023-1029. doi: 10.1001/jamaoncol.2016.0386.

6. LiVolsi VA, Baloch ZW. The many faces of follicular variant of papillary thyroid carcinoma. Pathol Case Rev. 2009;14(6):214-218. doi: 10.1097/PCR.0b013e3181c75e9b.

7. Lindsay S. Carcinoma of thyroid gland: a clinical and pathological study of 239 patients at the University of California Hospital. Springfield: Charles C. Thomas; 1960.

8. Chem KT, Rosai J. Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases. Am J Surg Pathol. 1977;1(2):123-130.

9. Kakudo K, Bai Y, Liu Z, et al. Classification of thyroid follicular cell tumors: with special reference to borderline lesions. Endocr J. 2012;59(1):1-12. doi: 10.1507/endocrj.EJ11-0184.

10. Arora N, Scognamiglio T, Zhu B, Fahey TJ, 3rd. Do benign thyroid nodules have malignant potential? An evidence-based review. World J Surg. 2008;32(7):1237-1246. doi: 10.1007/s00268-008-9484-1.

11. Papotti M, Rodriguez J, De Pompa R, et al. Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol. 2005;18(4):541-546. doi: 10.1038/modpathol.3800321.

12. Prasad ML, Pellegata NS, Huang Y, et al. Galectin-3, fibronectin-1, CITED-1, HBME-1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol. 2005;18(1):48-57. doi: 10.1038/modpathol.3800235.

13. Fischer S, Asa SL. Application of immunohistochemistry to thyroid neoplasms. Arch Pathol Lab Med. 2008;132(3):359-372. doi: 10.1043/1543-2165(2008)132[359:AOITTN]2.0.CO;2.

14. Scognamiglio T, Hyjek E, Kao J, Chen Y-T. Diagnostic usefulness of HBME1, Galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol. 2006;126(5): 700-708. doi: 10.1309/044v86jn2w3cn5yb.

15. Abrosimov AY, Dvinskikh NY, Sidorin AV. Cells of benign and borderline thyroid tumor express malignancy markers. Bull Exp Biol Med. 2016;160(5):698-701. doi: 10.1007/s10517-016-3253-1.