Background: Hürthle cell (HC) neoplasms are rare among pediatric thyroid cancers. HC adenomas (HCA) are typically benign and localized unilaterally without recurrence, and they are thus treated by hemithyroidectomy. HC carcinomas (HCC) can be bilateral and are more aggressive, necessitating total thyroidectomy. Diagnosis relies upon surgical histopathology demonstrating invasion for classification as HCC or lack of invasion in HCA, since fine needle aspiration fails to differentiate between the two. Methods: We report a case of a 14-year-old adolescent female with bilateral HCA. She had an initial left hemithyroidectomy for a large nodule measuring 2 × 1.5 × 1.2 cm3 in the left lobe, while smaller subcentimeter nodules remained under surveillance in the right. One year later, a nodule in the right lobe doubled in size, necessitating a right hemithyroidectomy which also revealed HCA. Conclusion: To our knowledge, this is the first reported case of bilateral HCA in pediatrics. It highlights the importance of close surveillance of persistent small nodules, even in patients with previously documented benign lesions such as HCA, which are typically thought to be unilateral and localized. Both HCA and HCC remain unpredictable in behavior, and treatment of HCA should be individualized.

Keywords:
Hürthle cell adenoma, Hürthle cell carcinoma, Atypical Hürthle cell adenoma, Bilateral Hürthle cell adenoma, Adolescent
1.
Corrias A, Mussa A, Baronio F, Arrigo T, Salerno M, Segni M, Vigone MC, Gastaldi R, Zirilli G, Tuli G, Beccaria L, Iughetti L, Einaudi S, Weber G, De Luca F, Cassio A; Study Group for Thyroid Diseases of Italian Society for Pediatric Endocrinology and Diabetology: Diagnostic features of thyroid nodules in pediatrics. Arch Pediatr Adolesc Med 2010;164:714-719.
2.
Niedziela M: Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 2006;13:427-453.
3.
Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A, Pinchera A: The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab 1999;84:561-566.
4.
Haugen BRM, Alexander EK, Bible KC, Doherty G, Mandel SJ, Nikiforov YE, Pacini F, Randolph G, Sawka A, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward D, Tuttle RMM, Wartofsky L: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016;26:1-133.
5.
Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, Dinauer CA, Hamilton J, Hay ID, Luster M, Parisi MT, Rachmiel M, Thompson GB, Yamashita S, American Thyroid Association Guidelines Task Force: Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2015;25:716-759.
6.
Gupta A, Ly S, Castroneves LA, Frates MC, Benson CB, Feldman HA, Wassner AJ, Smith JR, Marqusee E, Alexander EK, Barletta J, Doubilet PM, Peters HE, Webb S, Modi BP, Paltiel HJ, Kozakewich H, Cibas ES, Moore FD Jr, Shamberger RC, Larsen PR, Huang SA: A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults. J Clin Endocrinol Metab 2013;98:3238-3245.
7.
Arici C, Erdogan O, Altunbas H, Boz A, Melikoglu M, Karayalcin B, Karpuzoglu T: Differentiated thyroid carcinoma in children and adolescents. Clinical characteristics, treatment and outcome of 15 patients. Horm Res 2002;57:153-156.
8.
Waguespack SG, Francis G: Initial management and follow-up of differentiated thyroid cancer in children. J Natl Compr Canc Netw 2010;8:1289-1300.
9.
Hung W, Sarlis NJ: Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid 2002;12:683-702.
10.
Wasvary H, Czako P, Poulik J, Lucas R: Unilateral lobectomy for Hürthle cell adenoma. Am Surg 1998;64:729-732; discussion 732-733.
11.
Stojadinovic A, Ghossein RA, Hoos A, Urist MJ, Spiro RH, Shah JP, Brennan MF, Shaha AR, Singh B: Hürthle cell carcinoma: a critical histopathologic appraisal. J Clin Oncol 2001;19:2616-2625.
12.
Asa SL: My approach to oncocytic tumours of the thyroid. J Clin Pathol 2004;57:225-232.
13.
Cannon J: The significance of Hürthle cells in thyroid disease. Oncologist 2011;16:1380-1387.
14.
Kushchayeva Y, Duh QY, Kebebew E, Clark OH: Prognostic indications for Hürthle cell cancer. World J Surg 2004;28:1266-1270.
15.
Chindris AM, Casler JD, Bernet VJ, Rivera M, Thomas C, Kachergus JM, Necela BM, Hay ID, Westphal SA, Grant CS, Thompson GB, Schlinkert RT, Thompson EA, Smallridge RC: Clinical and molecular features of Hürthle cell carcinoma of the thyroid. J Clin Endocrinol Metab 2015;100:55-62.
16.
Montone KT, Baloch ZW, LiVolsi VA: The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 2008;132:1241-1250.
17.
McLeod MK, Thompson NW: Hürthle cell neoplasms of the thyroid. Otolaryngol Clin North Am 1990;23:441-452.
18.
Pu RT, Yang J, Wasserman PG, Bhuiya T, Griffith KA, Michael CW: Does Hürthle cell lesion/neoplasm predict malignancy more than follicular lesion/neoplasm on thyroid fine-needle aspiration? Diagn Cytopathol 2006;34:330-334.
19.
Sierk AE, Askin FB, Reddick RL, Thomas CG Jr: Pediatric thyroid cancer. Pediatr Pathol 1990;10:877-893.
20.
DeLellis RA, Lloyd RV, Heitz PU: Pathology and Genetics of Tumors of Endocrine Organs. World Health Organization Classification of Tumors. Lyon, IARC Press, 2004.
21.
Heerden V: Total thyroidectomy for Hürthle cell neoplasm of the thyroid. Arch Surg 1983;118:532.
22.
Azadian A, Rosen IB, Walfish PG, Asa SL: Management considerations in Hürthle cell carcinoma. Surgery 1995;118:711-714; discussion 714-715.
23.
Lopez-Penabad L, Chiu AC, Hoff AO, Schultz P, Gaztambide S, Ordonez NG, Sherman SI: Prognostic factors in patients with Hürthle cell neoplasms of the thyroid. Cancer 2003;97:1186-1194.
24.
Chen H, Nicol TL, Zeiger MA, Dooley WC, Ladenson PW, Cooper DS, Ringel M, Parkerson S, Allo M, Udelsman R: Hürthle cell neoplasms of the thyroid: are there factors predictive of malignancy? Ann Surg 1998;227:542-546.
25.
Rosen IB, Luk S, Katz I: Hürthle cell tumor behavior: dilemma and resolution. Surgery 1985;98:777-783.
26.
Zhang YW, Greenblatt DY, Repplinger D, Bargren A, Adler JT, Sippel RS, Chen H: Older age and larger tumor size predict malignancy in Hürthle cell neoplasms of the thyroid. Ann Surg Oncol 2008;15:2842-2846.
27.
Sippel RS, Elaraj DM, Khanafshar E, Zarnegar R, Kebebew E, Duh QY, Clark OH: Tumor size predicts malignant potential in Hürthle cell neoplasms of the thyroid. World J Surg 2008;32:702-707.
28.
Taneri F, Tekin E, Salman B, Anadol AZ, Ersoy E, Poyraz A, Onuk E: Huerthle cell neoplasms of the thyroid: predicting malignant potential. Endocr Regul 2000;34:19-21.
29.
Chao TC, Lin JD, Chen MF: Surgical treatment of Hürthle cell tumors of the thyroid. World J Surg 2005;29:164-168.
30.
Melck A, Bugis S, Baliski C, Irvine R, Anderson DW, Wilkins G, Zhang H, Wiseman SM: Hemithyroidectomy: the preferred initial surgical approach for management of Hürthle cell neoplasm. Am J Surg 2006;191:593-597.
31.
Gosain AK, Clark OH: Hürthle cell neoplasms. Malignant potential. Arch Surg 1984;119:515-519.
32.
Thompson NW, Dunn EL, Batsakis JG, Nishiyama RH: Hürthle cell lesions of the thyroid gland. Surg Gynecol Obstet 1974;139:555-560.
33.
Sugino K, Ito K, Mimura T, Kameyama K, Iwasaki H, Ito K: Hürthle cell tumor of the thyroid: analysis of 188 cases. World J Surg 2001;25:1160-1163.
34.
Lyshchik A, Drozd V, Demidchik Y, Reiners C: Diagnosis of thyroid cancer in children: value of gray-scale and power doppler US. Radiology 2005;235:604-613.
35.
McHenry CR, Huh ES, Machekano RN: Is nodule size an independent predictor of thyroid malignancy? Surgery 2008;144:1062-1068; discussion 1068-1069.
36.
Drozd VM, Lushchik ML, Polyanskaya ON, Fridman MV, Demidchik YE, Lyshchik AP, Biko J, Reiners C, Shibata Y, Saenko VA, Yamashita S: The usual ultrasonographic features of thyroid cancer are less frequent in small tumors that develop after a long latent period after the Chernobyl radiation release accident. Thyroid 2009;19:725-734.
37.
Mussa A, Salerno MC, Bona G, Wasniewska M, Segni M, Cassio A, Vigone MC, Gastaldi R, Iughetti L, Santanera A, Capalbo D, Matarazzo P, De Luca F, Weber G, Corrias A: Serum thyrotropin concentration in children with isolated thyroid nodules. J Pediatr 2013;163:1465-1470.
38.
Kim EK, Park CS, Chung WY, Oh KK, Kim DI, Lee JT, Yoo HS: New sonographic criteria for recommending fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. AJR Am J Roentgenol 2002;178:687-691.
39.
Lew JI, Rodgers SE, Solorzano CC: Developments in the use of ultrasound for thyroid cancer. Curr Opin Oncol 2010;22:11-16.
40.
Lew JI, Solorzano CC: Use of ultrasound in the management of thyroid cancer. Oncologist 2010;15:253-258.
41.
Pisanu A, Sias L, Uccheddu A: Factors predicting malignancy of Hürthle cell tumors of the thyroid: influence on surgical treatment. World J Surg 2004;28:761-765.
42.
Maizlin ZV, Wiseman SM, Vora P, Kirby JM, Mason AC, Filipenko D, Brown JA: Hürthle cell neoplasms of the thyroid: sonographic appearance and histologic characteristics. J Ultrasound Med 2008;27:751-757; quiz 759.
43.
Corrias A, Einaudi S, Chiorboli E, Weber G, Crino A, Andreo M, Cesaretti G, de Sanctis L, Messina MF, Segni M, Cicchetti M, Vigone M, Pasquino AM, Spera S, de Luca F, Mussa GC, Bona G: Accuracy of fine needle aspiration biopsy of thyroid nodules in detecting malignancy in childhood: comparison with conventional clinical, laboratory, and imaging approaches. J Clin Endocrinol Metab 2001;86:4644-4648.
44.
Alaedeen DI, Khiyami A, McHenry CR: Fine-needle aspiration biopsy specimen with a predominance of Hürthle cells: a dilemma in the management of nodular thyroid disease. Surgery 2005;138:650-656; discussion 656-657.
45.
Layfield LJ, Cibas ES, Baloch Z: Thyroid fine needle aspiration cytology: a review of the National Cancer Institute state of the science symposium. Cytopathology 2010;21:75-85.
46.
McHenry CR, Thomas SR, Slusarczyk SJ, Khiyami A: Follicular or Hürthle cell neoplasm of the thyroid: can clinical factors be used to predict carcinoma and determine extent of thyroidectomy? Surgery 1999;126:798-802; discussion 802-804.
47.
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.
48.
Hocevar M, Auersperg M: Role of serum thyroglobulin in the pre-operative evaluation of follicular thyroid tumours. Eur J Surg Oncol 1998;24:553-557.
49.
Strazisar B, Petric R, Sesek M, Zgajnar J, Hocevar M, Besic N: Predictive factors of carcinoma in 279 patients with Hürthle cell neoplasm of the thyroid gland. J Surg Oncol 2010;101:582-586.
50.
Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W, European Thyroid Cancer Taskforce: European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006;154:787-803.
51.
Chiappetta G, Toti P, Cetta F, Giuliano A, Pentimalli F, Amendola I, Lazzi S, Monaco M, Mazzuchelli L, Tosi P, Santoro M, Fusco A: The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hürthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions. J Clin Endocrinol Metab 2002;87:364-369.
52.
Maxwell EL, Palme CE, Freeman J: Hürthle cell tumors: applying molecular markers to define a new management algorithm. Arch Otolaryngol Head Neck Surg 2006;132:54-58.
53.
Donatini G, Beaulieu A, Castagnet M, Kraimps JL, Levillain P, Fromont G: Thyroid Hürthle cell tumors: research of potential markers of malignancy. J Endocrinol Invest 2016;39:153-158.
54.
Nascimento MC, Bisi H, Alves VA, Longatto-Filho A, Kanamura CT, Medeiros-Neto G: Differential reactivity for galectin-3 in Hürthle cell adenomas and carcinomas. Endocr Pathol 2001;12:275-279.
55.
Cerutti JM, Oler G, Delcelo R, Gerardt R, Michaluart P Jr, de Souza SJ, Galante PA, Huang P, Riggins GJ: PVALB, a new Hürthle adenoma diagnostic marker identified through gene expression. J Clin Endocrinol Metab 2011;96:E151-E160.
56.
Guadagni S, Francavilla S, Agnifili A, De Bernardinis G, Mariani G, Carboni M: Hürthle cell adenoma of the thyroid: in 32 consecutive cases. J R Coll Surg Edinb 1996;41:246-249.
57.
Gundry SR, Burney RE, Thompson NW, Lloyd R: Total thyroidectomy for Hürthle cell neoplasm of the thyroid. Arch Surg 1983;118:529-532.
58.
Kundel A, Thompson GB, Richards ML, Qiu LX, Cai Y, Schwenk FW, Lteif AN, Pittock ST, Kumar S, Tebben PJ, Hay ID, Grant CS: Pediatric endocrine surgery: a 20-year experience at the Mayo Clinic. J Clin Endocrinol Metab 2014;99:399-406.
59.
Herrera MF, Hay ID, Wu PS, Goellner JR, Ryan JJ, Ebersold JR, Bergstralh EJ, Grant CS: Hurthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biologic behavior. World J Surg 1992;16:669-674; discussion 774-775.
60.
Arganini M, Behar R, Wu TC, Straus F 2nd, McCormick M, DeGroot LJ, Kaplan EL: Hürthle cell tumors: a twenty-five-year experience. Surgery 1986;100:1108-1115.
61.
Grant CS, Barr D, Goellner JR, Hay ID: Benign Hürthle cell tumors of the thyroid: a diagnosis to be trusted? World J Surg 1988;12:488-495.
62.
Ristevska N, Stojanoski S, and Gjorceva DP: Appearance of Hürthle cell carcinoma soon after surgical extirpation of Hürthle cell adenoma and follicular adenoma of the thyroid gland. Radiol Oncol 2015;49:26-31.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.