RAS-Mutant Follicular Thyroid Tumors: A Continuous Challenge for Pathologists.

Publisher: Humana Press Country of Publication: United States NLM ID: 9009288 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0097 (Electronic) Linking ISSN: 10463976 NLM ISO Abbreviation: Endocr Pathol Subsets: MEDLINE

Publication: Totowa, NJ : Humana Press
Original Publication: Cambridge, MA : Blackwell Scientific Publications, [1990-

Thyroid Neoplasms*/pathology ; Thyroid Neoplasms*/genetics ; Thyroid Neoplasms*/diagnosis ; Adenocarcinoma, Follicular*/pathology ; Adenocarcinoma, Follicular*/genetics ; Adenocarcinoma, Follicular*/diagnosis ; Mutation*; Humans

The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of "high-grade" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Baloch ZW, Livolsi VA. Follicular-patterned lesions of the thyroid: the bane of the pathologist. Am J Clin Pathol. 2002;117 (1):143-50. (PMID: 11789719)
Tallini G, Tuttle RM, Ghossein RA. The History of the Follicular Variant of Papillary Thyroid Carcinoma. The Journal of clinical endocrinology and metabolism. 2017;102 (1):15-22. (PMID: 27732333)
Karnoub AE, Weinberg RA. Ras oncogenes: split personalities. Nature reviews Molecular cell biology. 2008;9(7):517-31. (PMID: 185680403915522)
Wood KW, Sarnecki C, Roberts TM, Blenis J. ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK. Cell. 1992;68(6):1041-50. (PMID: 1312393)
Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, et al. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 1994;370(6490):527-32. (PMID: 8052307)
McGrath JP, Capon DJ, Goeddel DV, Levinson AD. Comparative biochemical properties of normal and activated human RAS p21 protein. Nature. 1984;310(5979):644-9. (PMID: 6147754)
Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specific Pattern of ras Oncogene Mutations in Follicular Thyroid Tumors. The Journal of Clinical Endocrinology & Metabolism. 2003;88(6):2745-52.
Lemoine NR, Mayall ES, Wyllie FS, Farr CJ, Hughes D, Padua RA, et al. Activated ras Oncogenes in Human Thyroid Cancers. Cancer Research. 1988;48(16):4459-63. (PMID: 3293774)
Lemoine N, Mayall E, Wyllie F, Williams ED, Goyns M, Stringer B, et al. High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene. 1989;4(2):159-64. (PMID: 2648253)
Gire V, Wynford-Thomas D. RAS oncogene activation induces proliferation in normal human thyroid epithelial cells without loss of differentiation. Oncogene. 2000;19:737. (PMID: 10698491)
Miller KA, Yeager N, Baker K, Liao XH, Refetoff S, Di Cristofano A. Oncogenic Kras requires simultaneous PI3K signaling to induce ERK activation and transform thyroid epithelial cells in vivo. Cancer Res. 2009;69(8):3689-94. (PMID: 193518162669852)
Hernandez-Prera JC, Valderrabano P, Creed JH, de la Iglesia JV, Slebos RJC, Centeno BA, et al. Molecular Determinants of Thyroid Nodules with Indeterminate Cytology and RAS Mutations. Thyroid. 2021;31(1):36-49. (PMID: 326899097864115)
Suarez H, Du Villard J, Caillou Ba, Schlumberger M, Tubiana M, Parmentier C, et al. Detection of activated ras oncogenes in human thyroid carcinomas. Oncogene. 1988;2(4):403.
Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE. Prevalence of Ras mutations in thyroid neoplasia. Clin Endocrinol (Oxf). 1999;50(4):529-35. (PMID: 10468914)
Gupta N, Dasyam AK, Carty SE, Nikiforova MN, Ohori NP, Armstrong M, et al. RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers. The Journal of clinical endocrinology and metabolism. 2013;98(5):E914-22. (PMID: 235397345393462)
Rivera M, Ricarte-Filho J, Knauf J, Shaha A, Tuttle M, Fagin JA, et al. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol. 2010;23(9):1191-200. (PMID: 205262884573468)
Park JY, Kim WY, Hwang TS, Lee SS, Kim H, Han HS, et al. BRAF and RAS mutations in follicular variants of papillary thyroid carcinoma. Endocr Pathol. 2013;24(2):69-76. (PMID: 23625203)
Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-90.
Elsheikh TM, Asa SL, Chan JK, DeLellis RA, Heffess CS, LiVolsi VA, et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 2008;130(5):736-44. (PMID: 18854266)
Lloyd RV, Erickson LA, Casey MB, Lam KY, Lohse CM, Asa SL, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004;28(10):1336-40. (PMID: 15371949)
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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 : official journal of the American Thyroid Association. 2016;26(1):1-133. (PMID: 26462967)
Cibas ES, Ali SZ. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009;132(5):658-65. (PMID: 19846805)
Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017;27(11):1341-6. (PMID: 29091573)
Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta cytologica. 2012;56(4):333-9. (PMID: 22846422)
Roth MY, Witt RL, Steward DL. Molecular testing for thyroid nodules: Review and current state. Cancer. 2018;124(5):888-98. (PMID: 29278433)
Valderrabano P, Khazai L, Leon ME, Thompson ZJ, Ma Z, Chung CH, et al. Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology. Endocrine-related cancer. 2017;24(3):127-36. (PMID: 281046807771306)
Guan H, Toraldo G, Cerda S, Godley FA, Rao SR, McAneny D, et al. Utilities of RAS Mutations in Preoperative Fine Needle Biopsies for Decision Making for Thyroid Nodule Management: Results from a Single-Center Prospective Cohort. Thyroid. 2020;30(4):536-47. (PMID: 31996097)
Valderrabano P, Khazai L, Thompson ZJ, Leon ME, Otto KJ, Hallanger-Johnson JE, et al. Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules. Head Neck. 2018;40(8):1812-23. (PMID: 296247867771319)
Medici M, Kwong N, Angell TE, Marqusee E, Kim MI, Frates MC, et al. The variable phenotype and low-risk nature of RAS-positive thyroid nodules. BMC Med. 2015;13:184-.
Steward DL, Carty SE, Sippel RS, Yang SP, Sosa JA, Sipos JA, et al. Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study. JAMA Oncol. 2019;5(2):204-12. (PMID: 30419129)
Marcadis AR, Valderrabano P, Ho AS, Tepe J, Swartzwelder CE, Byrd S, et al. Interinstitutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules. Surgery. 2019;165(1):17-24. (PMID: 30360906)
An JH, Song KH, Kim SK, Park KS, Yoo YB, Yang JH, et al. RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2015;82(5):760-6. (PMID: 25109485)
Medici M, Kwong N, Angell TE, Marqusee E, Kim MI, Frates MC, et al. The variable phenotype and low-risk nature of RAS-positive thyroid nodules. BMC Med. 2015;13:184. (PMID: 262531024528713)
Nabhan F, Porter K, Lupo MA, Randolph GW, Patel KN, Kloos RT. Heterogeneity in Positive Predictive Value of RAS Mutations in Cytologically Indeterminate Thyroid Nodules. Thyroid. 2018;28(6):729-38. (PMID: 29665745)
Goldner WS, Angell TE, McAdoo SL, Babiarz J, Sadow PM, Nabhan FA, et al. Molecular Variants and Their Risks for Malignancy in Cytologically Indeterminate Thyroid Nodules. Thyroid. 2019;29(11):1594-605. (PMID: 314690536864764)
Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocrine-related cancer. 2013;20(4):603-10. (PMID: 237662373782569)
Bell RJ, Rube HT, Xavier-Magalhães A, Costa BM, Mancini A, Song JS, et al. Understanding TERT Promoter Mutations: A Common Path to Immortality. Mol Cancer Res. 2016;14(4):315-23. (PMID: 269414074852159)
Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nature Reviews Genetics. 2005;6(8):611-22. (PMID: 16136653)
Liu R, Xing M. Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy. Endocrine-related cancer. 2014;21(5):825-30. (PMID: 251215514175020)
Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120(23):3627-34. (PMID: 25209362)
Howell GM, Hodak SP, Yip L. RAS mutations in thyroid cancer. Oncologist. 2013;18(8):926-32. (PMID: 238737203755930)
Fukahori M, Yoshida A, Hayashi H, Yoshihara M, Matsukuma S, Sakuma Y, et al. The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012;22(7):683-9. (PMID: 22650231)
Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW, 2nd, Tallini G, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. The Journal of clinical endocrinology and metabolism. 2003;88(5):2318-26. (PMID: 12727991)
Karunamurthy A, Panebianco F, S JH, Vorhauer J, Nikiforova MN, Chiosea S, et al. Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules. Endocrine-related cancer. 2016;23(4):295–301.
Morariu EM, McCoy KL, Chiosea SI, Nikitski AV, Manroa P, Nikiforova MN, et al. Clinicopathologic Characteristics of Thyroid Nodules Positive for the THADA-IGF2BP3 Fusion on Preoperative Molecular Analysis. Thyroid. 2021;31(8):1212-8. (PMID: 33487086)
Bae JS, Jung SH, Hirokawa M, Bychkov A, Miyauchi A, Lee S, et al. High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid. Endocr Pathol. 2021;32(3):336-46. (PMID: 34313965)
Bongiovanni M, Sykiotis GP, La Rosa S, Bisig B, Trimech M, Missiaglia E, et al. Macrofollicular Variant of Follicular Thyroid Carcinoma: A Rare Underappreciated Pitfall in the Diagnosis of Thyroid Carcinoma. Thyroid. 2020;30(1):72-80. (PMID: 31701808)
Ardito G, Fadda G, Revelli L, Modugno P, Lucci C, Ardito F, et al. Follicular adenoma of the thyroid gland with extensive bone metaplasia. J Exp Clin Cancer Res. 2001;20(3):443-5. (PMID: 11718227)
Vergilio J, Baloch ZW, LiVolsi VA. Spindle cell metaplasia of the thyroid arising in association with papillary carcinoma and follicular adenoma. Am J Clin Pathol. 2002;117(2):199-204. (PMID: 11863215)
Doerfler WR, Nikitski AV, Morariu EM, Ohori NP, Chiosea SI, Landau MS, et al. Molecular alterations in Hürthle cell nodules and preoperative cancer risk. Endocrine-related cancer. 2021;28(5):301-9. (PMID: 33792557)
Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, 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):1023-9. (PMID: 270781455539411)
Erickson LA, Jin L, Wollan PC, Thompson GB, van Heerden J, Lloyd RV. Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors. Mod Pathol. 1998;11(2):169-74. (PMID: 9504687)
Hellgren LS, Stenman A, Paulsson JO, Höög A, Larsson C, Zedenius J, et al. Prognostic Utility of the Ki-67 Labeling Index in Follicular Thyroid Tumors: a 20-Year Experience from a Tertiary Thyroid Center. Endocr Pathol. 2022;33(2):231-42. (PMID: 353052399135869)
William A. Meissner and Shields Warren. Tumors of the thyroid gland. 1968;45.
Ye L, Zhou X, Huang F, Wang W, Qi Y, Xu H, et al. The genetic landscape of benign thyroid nodules revealed by whole exome and transcriptome sequencing. Nature Communications. 2017;8(1):15533. (PMID: 285809395465355)
Apel RL, Ezzat S, Bapat BV, Pan N, LiVolsi VA, Asa SL. Clonality of thyroid nodules in sporadic goiter. Diagn Mol Pathol. 1995;4(2):113-21. (PMID: 7551291)
Kopp P, Kimura ET, Aeschimann S, Oestreicher M, Tobler A, Fey MF, et al. Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters. The Journal of clinical endocrinology and metabolism. 1994;79(1):134-9. (PMID: 7517946)
Barletta JA, Mete O, Erickson LA, Kakudo K, Kondo T, Livolsi VA, et al. Thyroid follicular nodular disease. WHO Classification of Tumours Editorial Board Endocrine and neuroendocrine tumours [Internet]. 5th Edition ed. Lyon (France): International Agency for Research on Cancer; 2022.
Paulson VA, Shivdasani P, Angell TE, Cibas ES, Krane JF, Lindeman NI, et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Accounts for More Than Half of "Carcinomas" Harboring RAS Mutations. Thyroid. 2017;27(4):506-11. (PMID: 28114855)
Chu YH, Sadow PM. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Diagnostic updates and molecular advances. Semin Diagn Pathol. 2020;37(5):213-8. (PMID: 326466138329747)
Liu J, Singh B, Tallini G, Carlson DL, Katabi N, Shaha A, et al. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer. 2006;107(6):1255-64. (PMID: 16900519)
Rivera M, Tuttle RM, Patel S, Shaha A, Shah JP, Ghossein RA. Encapsulated papillary thyroid carcinoma: a clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes (histologic growth pattern). Thyroid. 2009;19(2):119-27. (PMID: 19191744)
Piana S, Frasoldati A, Di Felice E, Gardini G, Tallini G, Rosai J. Encapsulated well-differentiated follicular-patterned thyroid carcinomas do not play a significant role in the fatality rates from thyroid carcinoma. Am J Surg Pathol. 2010;34(6):868-72. (PMID: 20463572)
Thompson LD. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: a name change to noninvasive follicular thyroid neoplasm with papillary-like nuclear features would help prevent overtreatment. Modern Pathology. 2016;29(7):698-707. (PMID: 27102347)
Rosario PW, Mourão GF, Nunes MB, Nunes MS, Calsolari MR. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Endocrine-related cancer. 2016;23(12):893-7. (PMID: 27660403)
Xu B, Tallini G, Scognamiglio T, Roman BR, Tuttle RM, Ghossein RA. Outcome of large noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Thyroid. 2017;27(4):512-7. (PMID: 281361395385447)
Nikiforov YE, Baloch ZW, Hodak SP, Giordano TJ, Lloyd RV, Seethala RR, et al. Change in Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm With Papillarylike Nuclear Features. JAMA Oncol. 2018;4(8):1125-6. (PMID: 299023146584712)
Cho U, Mete O, Kim M-H, Bae JS, Jung CK. Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Modern Pathology. 2017;30(6):810-25. (PMID: 28281551)
Kim MJ, Won JK, Jung KC, Kim JH, Cho SW, Park DJ, et al. Clinical Characteristics of Subtypes of Follicular Variant Papillary Thyroid Carcinoma. Thyroid. 2018;28(3):311-8. (PMID: 29343212)
Lee SE, Hwang TS, Choi YL, Kim WY, Han HS, Lim SD, et al. Molecular Profiling of Papillary Thyroid Carcinoma in Korea with a High Prevalence of BRAF(V600E) Mutation. Thyroid. 2017;27(6):802-10. (PMID: 28293988)
Xu B, Serrette R, Tuttle RM, Alzumaili B, Ganly I, Katabi N, et al. How Many Papillae in Conventional Papillary Carcinoma? A Clinical Evidence-Based Pathology Study of 235 Unifocal Encapsulated Papillary Thyroid Carcinomas, with Emphasis on the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features. Thyroid. 2019;29(12):1792-803. (PMID: 314524536918873)
Seethala RR, Baloch ZW, Barletta JA, Khanafshar E, Mete O, Sadow PM, et al. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2018;31(1):39–55.
Chen DW, Rob FI, Mukherjee R, Giordano TJ, Haymart MR, Banerjee M. Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features. The Journal of clinical endocrinology and metabolism. 2022;107(10):e4072-e7. (PMID: 359180649516041)
Rana C, Bychkov A. NIFTP Statistics-Now You See It, Now You Don't. The Journal of clinical endocrinology and metabolism. 2022;108(1):e5-e6. (PMID: 36181476)
Thompson LDR, Poller DN, Kakudo K, Burchette R, Nikiforov YE, Seethala RR. An International Interobserver Variability Reporting of the Nuclear Scoring Criteria to Diagnose Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: a Validation Study. Endocr Pathol. 2018;29(3):242-9. (PMID: 29508145)
Liu Z, Bychkov A, Jung CK, Hirokawa M, Sui S, Hong S, et al. Interobserver and intraobserver variation in the morphological evaluation of noninvasive follicular thyroid neoplasm with papillary-like nuclear features in Asian practice. Pathol Int. 2019;69(4):202-10. (PMID: 30811774)
Vanzati A, Mercalli F, Rosai J. The “Sprinkling” Sign in the Follicular Variant of Papillary Thyroid Carcinoma: A Clue to the Recognition of This Entity. Archives of Pathology & Laboratory Medicine. 2013;137(12):1707-9.
Vickery ALJ. Thyroid papillary carcinoma: Pathological and philosophical controversies. The American Journal of Surgical Pathology. 1983;7(8):797-807. (PMID: 6660352)
Ghossein R, Kakudo K, Sadow P, Bongiovanni M, Jung C, Katoh R. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features. WHO Classification of Tumours Editorial Board Endocrine and neuroendocrine tumours [Internet]. WHO classification of tumours series, 5th ed.; vol. 10. Lyon (France): International Agency for Research on Cancer; 2022.
Barletta J, Fadda G, Kakudo K, Kondo T, LiVolsi V, Asa S, et al. Follicular thyroid carcinoma. WHO Classification of Tumours Editorial Board Endocrine and neuroendocrine tumours [Internet]. WHO classification of tumours series, 5th ed.; vol. 10. Lyon (France): International Agency for Research on Cancer; 2022.
Saliba M, Katabi N, Dogan S, Xu B, Ghossein RA. NRAS Q61R immunohistochemical staining in thyroid pathology: sensitivity, specificity and utility. Histopathology. 2021;79(4):650-60. (PMID: 339604378458224)
Oishi N, Kondo T, Vuong HG, Nakazawa T, Mochizuki K, Kasai K, et al. Immunohistochemical detection of NRAS(Q61R) protein in follicular-patterned thyroid tumors. Hum Pathol. 2016;53:51-7. (PMID: 26980032)
Crescenzi A, Fulciniti F, Bongiovanni M, Giovanella L, Trimboli P. Detecting N-RAS Q61R Mutated Thyroid Neoplasias by Immunohistochemistry. Endocr Pathol. 2017;28(1):71-4. (PMID: 28064410)
Kim M, Jeon S, Jung CK. Preoperative Risk Stratification of Follicular-patterned Thyroid Lesions on Core Needle Biopsy by Histologic Subtyping and RAS Variant-specific Immunohistochemistry. Endocrine Pathology. 2023;34(2):247-56. (PMID: 37040004)
Johnson DN, Sadow PM. Exploration of BRAFV600E as a diagnostic adjuvant in the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Hum Pathol. 2018;82:32-8. (PMID: 30146440)
Jiang XS, Harrison GP, Datto MB. Young Investigator Challenge: Molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Cancer Cytopathol. 2016;124(12):893-900. (PMID: 27893191)
Xu B, Viswanathan K, Zhang L, Edmund LN, Ganly O, Tuttle RM, et al. The solid variant of papillary thyroid carcinoma: a multi-institutional retrospective study. Histopathology. 2022;81(2):171-82. (PMID: 35474588)
Williams ED. Guest Editorial: Two Proposals Regarding the Terminology of Thyroid Tumors. Int J Surg Pathol. 2000;8(3):181-3. (PMID: 11493987)
Baser H, Topaloglu O, Tam AA, Alkan A, Kilicarslan A, Ersoy R, et al. Comparing Clinicopathologic and Radiographic Findings Between TT-UMP, Classical, and Non-Encapsulated Follicular Variants of Papillary Thyroid Carcinomas. Endocr Pathol. 2016;27(3):233-42. (PMID: 27256097)
Rivera M, Ricarte-Filho J, Patel S, Tuttle M, Shaha A, Shah JP, et al. Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): a clinicopathologic and molecular study. Hum Pathol. 2010;41(2):172-80. (PMID: 19913280)
Bongiovanni M, Mazzucchelli L, Giovanella L, Frattini M, Pusztaszeri M. Well-differentiated follicular patterned tumors of the thyroid with high-grade features can metastasize in the absence of capsular or vascular invasion: report of a case. Int J Surg Pathol. 2014;22(8):749-56. (PMID: 24788527)
Thompson LDR. High Grade Differentiated Follicular Cell-Derived Thyroid Carcinoma Versus Poorly Differentiated Thyroid Carcinoma: A Clinicopathologic Analysis of 41 Cases. Endocr Pathol. 2023;34(2):234-46. (PMID: 37195480)
Tallini G, LiVolsi V, Bongiovanni M, Jung C, Katoh R. Thyroid tumours of uncertain malignant potential. WHO Classification of Tumours Editorial Board Endocrine and neuroendocrine tumours [Internet]. WHO classification of tumours series, 5th ed.; vol. 10. Lyon (France) International Agency for Research on Cancer; 2022.
Guerrero D, Valderrabano P, Tarasova V, McIver B, Wenig B, Hernandez-Prera J, editors. Clinical Significance of TERT Promoter and TP53 Mutations in Thyroid Nodules with Indeterminate Cytology. LABORATORY INVESTIGATION; 2020: NATURE PUBLISHING GROUP 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013–1917 USA.
Topf MC, Wang ZX, Tuluc M, Pribitkin EA. TERT, HRAS, and EIF1AX Mutations in a Patient with Follicular Adenoma. Thyroid. 2018;28(6):815-7. (PMID: 29669480)
Wang N, Liu T, Sofiadis A, Juhlin CC, Zedenius J, Höög A, et al. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA. Cancer. 2014;120(19):2965-79. (PMID: 24898513)
Sobrinho-Simões M, Eloy C, Magalhães J, Lobo C, Amaro T. Follicular thyroid carcinoma. Mod Pathol. 2011;24 Suppl 2:S10-8. (PMID: 21455197)
Cracolici V, Kadri S, Ritterhouse LL, Segal JP, Wanjari P, Cipriani NA. Clinicopathologic and Molecular Features of Metastatic Follicular Thyroid Carcinoma in Patients Presenting With a Thyroid Nodule Versus a Distant Metastasis. Am J Surg Pathol. 2019;43(4):514-22. (PMID: 30557173)
Oh HS, Kim SJ, Song E, Lee YM, Sung TY, Kim WG, et al. Modified Transverse-Vertical Gross Examination: a Better Method for the Detection of Definite Capsular Invasion in Encapsulated Follicular-Patterned Thyroid Neoplasms. Endocr Pathol. 2019;30(2):106-12. (PMID: 30661168)
van Heerden JA, Hay ID, Goellner JR, Salomao D, Ebersold JR, Bergstralh EJ, et al. Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy. Surgery. 1992;112(6):1130–6; discussion 6–8.
Mete O, Asa SL. Pathological definition and clinical significance of vascular invasion in thyroid carcinomas of follicular epithelial derivation. Mod Pathol. 2011;24(12):1545-52. (PMID: 21804527)
Mete O, Asa S, Baloch Z, Erickson L, Ezzat S, Rotstein L, et al. Protocol for the examination of specimens from patients with carcinomas of the thyroid gland. College of American Pathologists. 2023 Version: 4.4.0.0.
Cracolici V, Parilla M, Henriksen KJ, Cipriani NA. An Evaluation of CD61 Immunohistochemistry in Identification of Vascular Invasion in Follicular Thyroid Neoplasms. Head Neck Pathol. 2020;14(2):399-405. (PMID: 31218593)
Asa SL, Erickson LA, Mete O. The Next Steps for Endocrine Pathology. Endocr Pathol. 2022;33(1):228-30. (PMID: 35226347)
O'Neill CJ, Vaughan L, Learoyd DL, Sidhu SB, Delbridge LW, Sywak MS. Management of follicular thyroid carcinoma should be individualised based on degree of capsular and vascular invasion. Eur J Surg Oncol. 2011;37(2):181-5. (PMID: 21144693)
Network NCC. Thyroid Cancer (Version 2.2024) [Available from: https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf .
Lang W, Choritz H, Hundeshagen H. Risk factors in follicular thyroid carcinomas. A retrospective follow-up study covering a 14-year period with emphasis on morphological findings. Am J Surg Pathol. 1986;10(4):246–55.
Xu B, Wang L, Tuttle RM, Ganly I, Ghossein R. Prognostic impact of extent of vascular invasion in low-grade encapsulated follicular cell-derived thyroid carcinomas: a clinicopathologic study of 276 cases. Hum Pathol. 2015;46(12):1789-98. (PMID: 264826054981341)
Yamazaki H, Katoh R, Sugino K, Matsuzu K, Masaki C, Akaishi J, et al. Encapsulated Angioinvasive Follicular Thyroid Carcinoma: Prognostic Impact of the Extent of Vascular Invasion. Ann Surg Oncol. 2022.
Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, et al. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol. 2022;33(1):27-63. (PMID: 35288841)
Tallini G, Lam A, Kondo T, Piana S, Asa S, Barletta J. High-grade follicular cell-derived non-anaplastic thyroid carcinoma. WHO Classification of Tumours Editorial Board Endocrine and neuroendocrine tumours [Internet]. WHO classification of tumours series, 5th ed.; vol. 10. Lyon (France): International Agency for Research on Cancer; 2022.
Stojanov IJ, Mete O, Asa SL. Obstacles to Tumor Capsule Assessment in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP). Endocr Pathol. 2023;34(4):484-6. (PMID: 37979079)

Keywords: RAS / RAS-like mutations; RAS-BRAFV600E dichotomy; Follicular nodular disease; Follicular thyroid adenoma; Follicular thyroid carcinoma; Invasive encapsulated variant of papillary thyroid carcinoma; NIFTP; Thyroid nodule

Date Created: 20240618 Date Completed: 20240910 Latest Revision: 20240910

20240911

10.1007/s12022-024-09812-5

38888731