Email this article 
Post a Comment Overview of Hurthle cell carcinoma of thyroid
Abstract - 428 PDF - 55Abstract
The clinical behaviour of Hurthle cell carcinoma (HCC) of the thyroid is variable and there are many controversies in the literature. Here, we summarize an up-to-date review of the literature on genetics, diagnosis (ultrasound scan, fine needle aspiration, frozen section, etc.), and management. At presentation, treatment decision should be made by a multidisciplinary board. Recurrent HCCs are seldom curable despite salvage treatments, which include radioactive iodine ablation, radiofrequency ablation, ethanol ablation, external radiotherapy, and systemic therapy. Further research is needed to develop more efficacious systemic treatments. Currently, lenvatinib, sunitinib, and sorafenib are available. The completed and ongoing clinical trials for HCC are summarized.
Keywords
Full Text:
PDFReferences
World Health Organization. Pathology and genetics of tumours of endocrine organs: 3rd ed. Llyod RV, Heitz PU, Eng C (eds). Lyon, France: IARC Press; 2004. p. x–x.
Bai S, Baloch ZW, Samulski TD, Montone KT, LiVolsi VA. Poorly differentiated oncocytic (Hürthle cell) follicular carcinoma: An institutional experience. Endocr Pathol 2015; 26(2): 164–169. doi: 10.1007/s12022-015-9367-6.
Kim WG, Kim TY, Kim TH, Jang HW, Jo YS, et al. Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: Retrospective analysis of Korean multicenter data. Korean J Intern Med 2014; 29(3): 325–333. doi: 10.3904/kjim.2014.29.3.325.
Shin DY, Jo YS. Clinical implications of follicular and Hurthle cell carcinoma in an iodine-sufficient area. Korean J Intern Med 2014; 29(3): 305–306. doi: 10.3904/kjim.2014.29.3.305.
Cipriani NA, Nagar S, Kaplan SP, White MG, Antic T, et al. Follicular thyroid carcinoma: How have histologic diagnoses changed in the last half-century and what are the prognostic implications? Thyroid 2015; 25(11): 1209–1216. doi: 10.1089/thy.2015.0297.
Eilers SG, LaPolice P, Mukunyadzi P, Kapur U, Wendel Spiczka A, et al. Thyroid fine-needle aspiration cytology: Performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data. Cancer Cytopathol 2014; 122(10): 745–750. doi: 10.1002/cncy.21440.
Renshaw AA, Gould EW. Impact of specific patterns on the sensitivity for follicular and Hurthle cell carcinoma in thyroid fine-needle aspiration. Cancer 2016; 124(10): 729–736. doi: 10.1002/cncy.21741.
Cibas ES, Ali SZ. The Bethesda System for reporting thyroid cytopathology. Thyroid 2009; 19(11): 1159–1165. doi: 10.1089/thy.2009.0274.
Ahmadi S, Stang M, Jiang XS, Sosa JA. Hurthle cell carcinoma: current perspectives. Onco Targets Ther 2016; 9: 6873-6884.
Xu B, Ghossein R. Evolution of the histologic classification of thyroid neoplasms and its impact on clinical management. Eur J Surg Oncol 2017 May 18. pii: S0748-7983(17)30478-X. doi: 10.1016/j.ejso.2017.05.002.
. Crippa S, Mazzucchelli L, Cibas ES, Ali SZ. The Bethesda System for reporting thyroid fine-needle aspiration specimens. Am J Clin Pathol 2010; 134(2): 343–344. doi: 10.1309/AJCPXM9WIRQ8JZBJ.
Boonyaarunnate T, Olson MT, Ali SZ. ‘Suspicious for a follicular neoplasm’ before and after the Bethesda System for Reporting Thyroid Cytopathology: Impact of standardized terminology. Acta Cytol 2013; 57(5): 455–463. doi: 10.1159/000351664.
Fischer AH, Clayton AC, Bentz JS, Wasserman PG, Henry MR, et al. Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: Analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Arch Pathol Lab Med 2013; 137(1): 26–31. doi: 10.5858/arpa.2012-0009-CP.
Mathur A, Najafian A, Schneider EB, Zeiger MA, Olson MT. Malignancy risk and reproducibility associated with atypia of undetermined significance on thyroid cytology. Surgery 2014; 156(6): 1471–1476. doi: 10.1016/j.surg.2014.08.026.
VandenBussche CJ, Adams C, Ali SZ, Olson MT. Cytotechnologist performance for screening Hürthle cell atypia in indeterminate thyroid fine-needle aspirates. Acta Cytol 2015; 59(5): 377–383. doi: 10.1159/000441939.
McKee S, Wu H, Wang X, Cramer H, Lin J, et al. Hürthle cell neoplasms diagnosed by fine needle aspiration are not associated with an increased risk of malignancy. Acta Cytol 2014; 58(3): 235–238. doi: 10.1159/000361073.
Ali SZ, Cibas ES. The Bethesda System for reporting thyroid cytopathology II. Acta Cytol 2016; 60(5): 397–398. doi: 10.1159/000451071.
Caleo A, Landolfi L, Vitale M, Di Crescenzo V, Vatrella A, et al. The diagnostic accuracy of fine-needle cytology of Hurthle cell lesions: A comprehensive cytological, clinical and ultrasonographic experience. Int J Surg 2016; 28(Suppl 1): S65–69. doi: 10.1016/j.ijsu.2015.12.049.
Ferris RL, Baloch Z, Bernet V, Chen A, Fahey TJ 3rd, et al. American Thyroid Association statement on surgical application of molecular profiling for thyroid nodules: Current impact on perioperative decision making. Thyroid 2015; 25(7): 760–768. doi: 10.1089/thy.2014.0502.
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, 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 2016; 26(1): 1–133. doi: 10.1089/thy.2015.0020.
Zakerkish M, Rajaei E, Dargahi M, Bahadoram M. A rare constellation of Hurthle cell thyroid carcinoma and parathyroid carcinoma. J Clin Diagn Res 2015; 9(12): OD08–OD10. doi: 10.7860/JCDR/2015/16540.6983.
Sinno S, Choucair M, Nasrallah M, Wadi L, Jabbour MN, et al. Activating BRAF mutations detected in mixed Hurthle cell carcinoma and multifocal papillary carcinoma of the thyroid gland: Report of an unusual case and review of the literature. Int J Surg Pathol 2016; 24(6): 519–524. doi: 10.1177/1066896916639377.
Sriphrapradang C, Sornmayura P, Chanplakorn N, Trachoo O, Sae-Chew P, et al. Fine-needle aspiration cytology of parathyroid carcinoma mimic Hürthle cell thyroid neoplasm. Case Rep Endocrinol 2014; 2014: 680876. doi: 10.1155/2014/680876.
Pathak KA, Klonisch T, Nason RW, Leslie WD. FDG-PET characteristics of Hürthle cell and follicular adenomas. Ann Nucl Med 2016; 30(7): 506–509. doi: 10.1007/s12149-016-1087-6.
Zandieh S, Pokieser W, Knoll P, Sonneck-Koenne C, Kudlacek M, et al. Oncocytic adenomas of thyroid-mimicking benign or metastatic disease on 18F-FDG-PET scan. Acta Radiol 2015; 56(6): 709–713. doi: 10.1177/0284185114537928.
Prestwich RJ, Viner S, Gerrard G, Patel CN, Scarsbrook AF. Increasing the yield of recombinant thyroid-stimulating hormone-stimulated 2-(18-fluoride)-flu-2-deoxy-ᴅ-glucose positron emission tomography-CT in patients with differentiated thyroid carcinoma. Br J Radiol 2012; 85(1018): e805–e813. doi: 10.1259/bjr/26733491.
Palaniswamy SS, Subramanyam P. Diagnostic utility of PET/CT in thyroid malignancies: An update. Ann Nucl Med 2013; 27(8): 681–693. doi: 10.1007/s12149-013-0740-6.
Petric R, Besic H, Besic N. Preoperative serum thyroglobulin concentration as a predictive factor of malignancy in small follicular and Hürthle cell neoplasms of the thyroid gland. World J Surg Oncol 2014; 12: 282. doi: 10.1186/1477-7819-12-282.
Arduc A, Dogan BA, Tuna MM, Tutuncu Y, Isik S, et al. Higher body mass index and larger waist circumference may be predictors of thyroid carcinoma in patients with Hurthle-cell lesion/neoplasm fine-needle aspiration diagnosis. Clin Endocrinol (Oxf) 2015; 83(3): 405–411. doi: 10.1111/cen.12628.
Ganly I, Ricarte Filho J, Eng S, Ghossein R, Morris LGT, et al. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy. J Clin Endocrinol Metab 2013; 98(5): E962–E972. doi: 10.1210/jc.2012-3539.
Dettori T, Frau DV, Lai ML, Mariotti S, Uccheddu A, et al. Aneuploidy in oncocytic lesions of the thyroid gland: Diffuse accumulation of mitochondria within the cell is associated with trisomy 7 and progressive numerical chromosomal alterations. Gene Chromosome Canc 2003; 38(1): 22–31. doi: 10.1002/gcc.10238.
Segev DL, Saji M, Phillips GS, Westra WH, Takiyama Y, et al. Polymerase chain reaction-based microsatellite polymorphism analysis of follicular and Hürthle cell neoplasms of the thyroid. J Clin Endocrinol Metab 1998; 83(6): 2036–2042. doi: 10.1210/jc.83.6.2036.
Catalogue of Somatic Mutations in Cancer (COSMIC). Hurthle carcinoma (UK) [Internet]. Wellcome Trust Sanger Institute [cited 2017 May 24]. Available from: http://cancer.sanger.ac.uk/cosmic/browse/tissue#in=t&sn=thyroid&ss=NS&hn=carcinoma&sh=Hurthle_cell_carcinoma.
Yoo SK, Lee S, Kim SJ, Jee HG, Kim BA, et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet 2016; 12(8): e1006239. doi: 10.1371/journal.pgen.1006239.
Santos JC, Bastos AU, Cerutti JM, Ribeiro ML. Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma. BMC Cancer 2013; 13: 79. doi: 10.1186/1471-2407-13-79.
Campo C, Köhler A, Figlioli G, Elisei R, Romei C, et al. Inherited variants in genes somatically mutated in thyroid cancer. PLoS One 2017; 12(4): e0174995. doi: 10.1371/journal.pone.0174995.
Nikolic A, Ristanovic M, Zivaljevic V, Rankov AD, Radojkovic D, et al. SMAD4 gene promoter mutations in patients with thyroid tumors. Exp Mol Pathol 2015; 99(1): 100–103. doi: 10.1016/j.yexmp.2015.06.005.
Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 2013; 13(3): 184–199. doi: 10.1038/nrc3431.
Carvalho S, Vítor AC, Sridhara SC, Martins FB, Raposo AC, et al. SETD2 is required for DNA double-strand break repair and activation of the p53-mediated checkpoint. Elife 2014; 3: e02482. doi: 10.7554/eLife.02482.
Vengoechea J, Carpenter L, Zárate YA. Papillary thyroid cancer in a patient with interstitial 6q25 deletion including ARID1B. Am J Med Genet A 2014; 164A(7): 1857–1859. doi: 10.1002/ajmg.a.36515.
Nasirden A, Saito T, Fukumura Y, Hara K, Akaike K. In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is associated with poor prognosis, in contrast to BRAF (V600E) mutation. Virchows Arch 2016; 469(6): 687–696. doi: 10.1007/s00428-016-2027-5.
Oliveira G, Polónia A, Cameselle-Teijeiro JM, Leitão D, Sapia S, et al. EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE). Virchows Arch 2017; 470(5): 517–525. doi: 10.1007/s00428-017-2095-1.
Mück F, Bracharz S, Marschalek R. DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex. Am J Blood Res 2016; 6(3): 28–45.
Lim JH, Jang S, Park CJ, Chi HS, Lee JO, et al. FISH analysis of MLL gene rearrangements: Detection of the concurrent loss or gain of the 3’ signal and its prognostic significance. Int J Lab Hematol 2014; 36(5): 571–579. doi: 10.1111/ijlh.12192.
Vargas C, Radziwill G, Krause G, Diehl A, Keller S, et al. Small-molecule inhibitors of AF6 PDZ-mediated protein-protein interactions. ChemMedChem. 2014; 9(7): 1458–1462. doi: 10.1002/cmdc.201300553.
Heasley LR, McMurray MA. Small molecule perturbations of septins. Methods Cell Biol 2016; 136: 311–319. doi: 10.1016/bs.mcb.2016.03.013.
Danecek P, Nellåker C, McIntyre RE, Buendia-Buendia JE, Bumpstead S, et al. High levels of RNA-editing site conservation amongst 15 laboratory mouse strains. Genome Biol 2012; 13(4): 26. doi: 10.1186/gb-2012-13-4-r26.
Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, 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): 3627–3634. doi: 10.1002/cncr.29038.
Kasaian K, Chindris AM, Wiseman SM, Mungall KL, Zeng T, et al. MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma. J Clin Endocrinol Metab 2015; 100(4): E611–E615. doi: 10.1210/jc.2014-3622.
Sugishita Y, Kammori M, Yamada O, Yamazaki K, Ito K, et al. Biological differential diagnosis of follicular thyroid tumor and Hürthle cell tumor on the basis of telomere length and hTERT expression. Ann Surg Oncol 2014; 21(7): 2318–2325. doi: 10.1245/s10434-014-3552-6.
Chindris AM, Casler JD, Bernet VJ, Rivera M, Thomas C, et al. Clinical and molecular features of Hürthle cell carcinoma of the thyroid. J Clin Endocrinol Metab 2015; 100(1): 55–62. doi: 10.1210/jc.2014-1634.
Landa I, Ganly I, Chan TA, Mitsutake N, Matsuse M, et al. Frequent somatic TERT promoter mutations in thyroid cancer: Higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab 2013; 98(9): E1562–E1566. doi: 10.1210/jc.2013-2383.
Barbacid M. Ras genes. Annu Rev Biochem. 1987; 56: 779–827. doi: 10.1146/annurev.bi.56.070187.004023.
Valerio L, Pieruzzi L, Giani C, Agate L, Bottici V, et al. Targeted therapy in thyroid cancer: State of the art. Clin Oncol (R Coll Radiol) 2017; 29(5): 316–324. doi: 10.1016/j.clon.2017.02.009.
Hou P, Liu D, Shan Y, Hu S, Studeman K, et al. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res 2007; 13(4): 1161–1170.
Genetics Home Reference. AKT1 gene (US) [Internet]. U.S. National Institutes of Health [Cited 2017 May 25]. Available from: https://ghr.nlm.nih.gov/gene/AKT1.
Krhin B, Goricar K, Gazic B, Dolzan V, Besic N. Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm: An association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma. Radiol Oncol 2016; 50(3): 289–296. doi: 10.1515/raon-2016-0031.
Petric R, Gazic B, Goricar K, Dolzan V, Dzodic R, et al. Expression of miRNA and occurrence of distant metastases in patients with Hürthle cell carcinoma. Int J Endocrinol 2016; 2016: 8945247. doi: 10.1155/2016/8945247.
National Comprehensive Cancer Network (US) [Internet]. NCCN Foundation [Cited 2017 June 1]. Available from: http://www.nccn.org.
Febrero B, Rodriguez JM, Parrilla P. Hurthle cell carcinoma with jugulo-subclavian venous thrombosis. Acta Otorrinolaringol Esp 2015; 66(2): 125–126. doi: 10.1016/j.otorri.2013.07.003.
Jillard CL, Youngwirth L, Scheri RP, Roman S, Sosa JA. Radioactive iodine treatment is associated with improved survival for patients with Hürthle cell carcinoma. Thyroid 2016; 26(7): 959–964. doi: 10.1089/thy.2016.0246.
Ahmadi S, Stang M, Jiang XS, Sosa JA. Hürthle cell carcinoma: Current perspectives. Onco Targets Ther 2016; 9: 6873–6884. doi: 10.2147/OTT.S119980.
ClinicalTrials.gov. Is ablative radio-iodine necessary for low risk differentiated thyroid cancer patients (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT01398085?term=hurthle+cell+thyroid+cancer&rank=5.
Zavitsanos P, Amdur RJ, Drew PA, Cusi K, Werning JW, et al. Favorable outcome of Hurthle cell carcinoma of the thyroid treated with total thyroidectomy, radioiodine, and selective use of external-beam radiotherapy. Am J Clin Oncol 2015; Feb 26. doi: 10.1097/COC.0000000000000180.
Besic N, Schwarzbartl-Pevec A, Vidergar-Kralj B, Crnic T, Gazic B, et al. Treatment and outcome of 32 patients with distant metastases of Hürthle cell thyroid carcinoma: A single-institution experience. BMC Cancer 2016; 16: 162. doi: 10.1186/s12885-016-2179-3.
Nagar S, Aschebrook-Kilfoy B, Kaplan EL, Angelos P, Grogan RH. Hurthle cell carcinoma: An update on survival over the last 35 years. Surgery 2013; 154(6): 1263–1271. doi: 10.1016/j.surg.2013.06.029.
Bikas A, Kundra P, Desale S, Mete M, O’Keefe K, et al. Phase 2 clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer. Eur J Endocrinol 2016; 174(3): 373–380. doi: 10.1530/EJE-15-0930.
Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: A randomised, double-blind, phase 3 trial. Lancet 2014; 384(9940): 319–328. doi: 10.1016/S0140-6736(14)60421-9.
ClinicalTrials.gov. Safety and efficacy of sorafenib in patients with advanced thyroid cancer: A phase II clinical study (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT02084732?term=hurthle+cell+thyroid+cancer&rank=9.
Mayo Clinic. Sorafenib tosylate with or without everolimus in treating patients with advanced, radioactive iodine refractory Hurthle cell thyroid cancer (US) [Internet]. Mayo Foundation for Medical Education and Research [cited 2017 March 25]. Available from: http://www.mayo.edu/research/clinical-trials/cls-20203467.
ClinicalTrials.gov. Combination of temsirolimus and sorafenib in the treatment of radioactive iodine refractory thyroid cancer (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT01025453?term=hurthle+cell+thyroid+cancer&rank=8.
ClinicalTrials.gov. Romidepsin in treating patients with recurrent and/or metastatic thyroid cancer that has not responded to radioactive iodine (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT00098813?term=hurthle+cell+thyroid+cancer&rank=6.
Sherman EJ, Su YB, Lyall A, Schöder H, Fury MG, et al. Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma. Thyroid 2013; 23(5): 593–599. doi: 10.1089/thy.2012.0393.
ClinicalTrials.gov. A phase 2, open-label study of AMG 706 to treat subjects with locally advanced or metastatic thyroid cancer (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT00121628?term=hurthle+cell+thyroid+cancer&rank=7.
ClinicalTrials.gov. Bortezomib in treating patients with metastatic thyroid cancer that did not respond to radioactive iodine therapy (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT00104871?term=hurthle+cell+thyroid+cancer&rank=10.
Sugino K, Kameyama K, Ito K, Nagahama M, Kitagawa W, et al. Does Hürthle cell carcinoma of the thyroid have a poorer prognosis than ordinary follicular thyroid carcinoma? Ann Surg Oncol 2013; 20(9): 2944–2950. doi: 10.1245/s10434-013-2965-y.
ClinicalTrials.gov. Studies on tumors of the thyroid (US) [Internet]. U.S. National Institutes of Health [cited 2017 March 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT00001160?term=hurthle+cell+thyroid+cancer&rank=3.
DOI: http://dx.doi.org/10.18282/amor.v3.i4.130
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
