Lobectomy in follicular thyroid neoplasms' treatment

2012/2013 Cristiano Martins Antunes Lobectomy in follicular thyroid neoplasms' treatment março, 2013 Mestrado Integrado em Medicina Área: Cirurgia Geral Trabalho efetuado sob a Orientação de: Doutor António Taveira Gomes Trabalho organizado de acordo com as normas da revista: Journal of Surgical Research Cristiano Martins Antunes Lobectomy in follicular thyroid neoplasms’ treatment março, 2013 Dedicatória Ao meu orientador, Prof. Doutor António Taveira Gomes, e à Dra. Isabel Amendoeira A ti Susana pelo apoio e carinho incondicional À minha avó, mãe e irmão Acima de tudo, ao meu pai. 1 Lobectomy in follicular thyroid neoplasms’ treatment Antunes, Cristiano Martins1 (Degree in Basic Health Sciences; Medical student in an Integrated Master Degree in Medicine); Amendoeira, Isabel MD2,3; Taveira-Gomes, António, PhD1,4. From: 1Medicine Faculty of University of Porto, Porto; 2Pathological Anatomy department, Hospital de São João, Porto; 3Institute of Molecular Pathology and Immunology at the University of Porto (IPATIMUP); 4Surgery department, Hospital de São João, Porto. Categorization of manuscript - table of contents Oncology/Endocrine Address correspondence António Taveira Gomes, PhD Surgical department of Hospital de São João Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal Email: [email protected] Telephone: +351 919805853 Fax: +351 225513601 2 Abstract Background: The purpose of this study is to evaluate the suitability of lobectomy with isthmusectomy (LwI) in treatment of Follicular Thyroid Neoplasms (FTN), considering malignancy incidence and postoperative complications. Methods: 192 patients (165 females; 27 males) who underwent LwI for FTN from 01/2005 to 12/2007 were retrospectively evaluated: clinical and pathological features, surgical complications and five year outcome of the remnant lobe. Inclusion criteria were cytological Bethesda category III and IV or histological follicular architecture. Patients with metastatic follicular carcinoma or previous thyroid surgery were excluded. Results: Mean age was 48,68±14,93yrs. Overall malignancy occurred in 88 patients (45,83%) and 80 (41,67%) underwent thyroidectomy completion (TC), mainly by index lesion’s malignancy. Forty-one (21,35%) in LwI and 31 (38,75%) in TC specimens had associated malignancy, mainly papillary microcarcinomas. High preoperative Thyroid-Stimulating Hormone (TSH), histological multinodularity and, in cytology category IV, younger age, were significantly associated to malignancy. Permanent recurrent laryngeal nerve lesion occurred in 0,58% in Lwl and 1,52% in TC, and temporary dysphonia occurred in 9,25% and 6,06% (LwI and TC respectively). No LwI patients presented hypoparathyroidism and 3,03% in TC had temporary symptoms. In LwI, 36,70% developed hypothyroidism. Higher preoperative TSH was associated with hypothyroidism development. Conclusions: LwI was inappropriate in 40,10% patients with malignancy who required TC and 23,12% had no functional benefit because post-LwI hypothyroidism. Nodular relapse was reported in at least 23/113 LwI patients (20,35%). We propose total thyroidectomy for patients with FTN preoperative TSH higher than 2,16 mU/L and, in Bethesda category IV, less than 39,5yrs. Key words: thyroid gland, thyroidectomy, follicular neoplasm, thyroid neoplasms, thyroid adenoma, Follicular Thyroid Carcinomas, complications, Fine-Needle Aspiration Biopsy, thyroid lobectomy, hemithyroidectomy. 3 Introduction Thyroid differentiated cancer is the most common endocrine neoplasia and stands for 90% of thyroid cancers. Its incidence has increased in western world but its mortality has remained constant, suggesting a better diagnostic accuracy [1, 2]. Thyroid tumors present as nodular lesions which are highly prevalent. On physical examination, thyroid nodules are identified in 10% of patients and, by ultrasonography, there are reports of 67% [3]. However, only 5-30% of these are malignant [4]. With widespread use of Fine-Needle Aspiration Biopsy (FNAB), thyroid surgery for benign pathology has declined significantly. Despite a sensitivity of 83%, specificity of 92% and a accuracy of 95% [5], there is a “gray-zone” on FNAB which corresponds to Follicular Thyroid Neoplasms (FTN) whose uncertain nature requires histological evaluation [6]. FTN on FNAB can occur in nodular goiter, follicular adenoma (FA) as well as in well differentiated carcinomas (follicular carcinoma (FC) and follicular variant of papillary thyroid carcinoma (FVPTC)). The Bethesda System for reporting thyroid cytopathology has an implied risk of malignancy in category III of 5-15% and category IV of 15-30 % [7]. When FNAB revels a FTN, final diagnosis of FC depends on histological demonstration of capsular and/or vascular invasion; definitive diagnosis of FVPTC depends on a cytological evaluation with a better sample and/or histological diagnosis for nuclear atypia [8, 9]. Advances in molecular genetics have tried to define specific mutations for each FTN. RAS mutations and t(2,3) PAX8-PPAR-gama have been found in FTN however each mutation was found in the different FTN with similar frequencies [10, 11] and a study on genetic testing in indeterminate FNAB reported a sensitivity of 12%, specificity of 98%, a positive and negative predictive value of 38% and 65%, respectively [12]. So, despite several clinical, imaging and molecular features being associated with FTN nature, their role in therapeutic decision is yet limited, even when combined, which makes Lobectomy with Isthmusectomy (LwI) the most accurate diagnostic procedure. Preoperative characterization of FTN in a lesser invasive approach remains a challenge in endocrine pathology and a 4 significant controversy also remains in the definition of the best therapeutic approach [13, 14]. LwI is the minimal therapeutic procedure for patients with FTN, which has been accepted, since FTN are usually unifocal and malignancy risk is lesser than 30%. Patients who underwent LwI for FTN, had cancer in 19% and this procedure was considered adequate in 96% of patients [15], with comparable results to total thyroidectomy (TT) concerning recurrence and survival [16]. In more advanced neoplasms than T1N0M0, LwI had a 2,5-fold higher recurrence risk and 2,2-fold risk of death compared with TT [17], despite a lesser complications’ rate [18, 19]. TT has a higher risk of permanent hypoparathyroidism and recurrent laryngeal nerve palsy and all patients develop hypothyroidism requiring lifelong opotheraphy. In LwI, opotheraphy will be required in at least 10,9% of patients, with 1 out of 25 patients developing clinical hypothyroidism [20, 21]. LwI can cure patients with FA and minimally invasive FC. It has minimal risk of hypoparathyroidism and a lower morbidity than TT. Patients with FC (widely invasive or angioinvasive) or FVPTC, ultimately will need a thyroidectomy completion (TC). The aim of the present study is to evaluate the incidence of malignancy in patients with FTN who underwent LwI, morbidity of procedure, need for TC, late post-operative hypothyroidism and recurrent nodular disease. Patients and methods A retrospective study was carried out based on clinical files of patients who underwent LwI for FTN or follicular lesion of undetermined significance between January 2005 and December 2007 in Hospital de São João, Porto, Portugal, after approval by Ethical Commission Boarder. Inclusion criteria were lesions with cytological Bethesda category III and IV or histological FTN (FA, FC, FVPTC), independently of FNAB cytology. Patients with metastatic FC or previous thyroid surgery were excluded. All surgeries were performed in our center. FNAB diagnosis was made in our center and outside. The clinical, FNAB, 11 12. Moses W, Weng J, Sansano I, et al. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg 2010;34:2589. 13. Smith J, Cheifetz RE, Schneidereit N, Berean K, Thomson T. Can cytology accurately predict benign follicular nodules? Am J Surg 2005;189:592. 14. Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules. Ann Intern Med 2005;142:926. 15. Wiseman SM, Baliski C, Irvine R, et al. Hemithyroidectomy: the optimal initial surgical approach for individuals undergoing surgery for a cytological diagnosis of follicular neoplasm. Ann Surg Oncol 2006;13:425. 16. Shah JP, Loree TR, Dharker D, Strong EW. Lobectomy versus total thyroidectomy for differentiated carcinoma of the thyroid: a matched-pair analysis. Am J Surg 1993;166:331. 17. Loh KC, Greenspan FS, Gee L, Miller TR, Yeo PP. Pathological tumor-nodemetastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients. J Clin Endocrinol Metab 1997;82:3553. 18. Friedman M, Pacella BL, Jr. Total versus subtotal thyroidectomy. Arguments, approaches, and recommendations. Otolaryngol Clin North Am 1990;23:413. 19. Vaiman M, Nagibin A, Hagag P, Buyankin A, Olevson J, Shlamkovich N. Subtotal and near total versus total thyroidectomy for the management of multinodular goiter. World J Surg 2008;32:1546. 20. Su SY, Grodski S, Serpell JW. Hypothyroidism following hemithyroidectomy: a retrospective review. Ann Surg 2009;250:991. 21. Verloop H, Louwerens M, Schoones JW, Kievit J, Smit JW, Dekkers OM. Risk of hypothyroidism following hemithyroidectomy: systematic review and meta-analysis of prognostic studies. J Clin Endocrinol Metab 2012;97:2243. 22. Kim ES, Nam-Goong IS, Gong G, Hong SJ, Kim WB, Shong YK. Postoperative findings and risk for malignancy in thyroid nodules with cytological diagnosis of the so-called "follicular neoplasm". Korean J Intern Med 2003;18:94. 12 23. Baloch ZW, LiVolsi VA. Microcarcinoma of the thyroid. Adv Anat Pathol 2006;13:69. 24. Schlinkert RT, van Heerden JA, Goellner JR, et al. Factors that predict malignant thyroid lesions when fine-needle aspiration is "suspicious for follicular neoplasm". Mayo Clin Proc 1997;72:913. 25. Lee EK, Chung KW, Min HS, et al. Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. J Korean Med Sci 2012;27:1014. 26. Tuttle RM, Lemar H, Burch HB. Clinical features associated with an increased risk of thyroid malignancy in patients with follicular neoplasia by fine-needle aspiration. Thyroid 1998;8:377. 27. Gulcelik NE, Gulcelik MA, Kuru B. Risk of malignancy in patients with follicular neoplasm: predictive value of clinical and ultrasonographic features. Arch Otolaryngol Head Neck Surg 2008;134:1312. 28. Besic N, Sesek M, Peric B, Zgajnar J, Hocevar M. Predictive factors of carcinoma in 327 patients with follicular neoplasm of the thyroid. Med Sci Monit 2008;14:CR459. 29. Spanheimer PM, Sugg SL, Lal G, Howe JR, Weigel RJ. 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Table 1 – Pathological diagnosis LwI – Main histological diagnosis Index nodule Associated lesions Completion thyroidectomya n (%) n (%) n/N (%) Benignb 102 (53,13%) 36 (18,75%) 3/102 (2,94%)c WDTUMPd 2 (1,04%) - 0/2 (0%) Malign 88 (45,83%) 41 (21,35%) 77/88 (87,5%) Follicular carcinoma 3 (1,56%) - 3/3 (100%) Minimally invasive 1 Widely invasive 0 Angio-invasive 2 Hurthle cell follicular carcinoma 3 (1,56%) - 3/3 (100%) Minimally invasive 0 Widely invasive 0 Angio-invasive 3 Follicular variant papillary carcinoma 40 (20,83%) 6 (3,125%) 38/40 (95,00%)e Papillary carcinoma Hurthle cell variant 27 (14,07%) 3 (1,56%) 27/27 (100%) Classic papillary carcinoma 1 (0,52%) 2 (1,04%) 1/1 (100%) WDCNOSf 1 (0,52%) - 1/1 (100%) MicroFVPTC 12 (6,25%) - 4/12 (33,33%) Micro PTC Hurthle cells variant 1 (0,52%) - 0/1 (0,00%) Papillary microcarcinoma - 30 (15,625%) - Normal - 115 (59,90%) - a) According to index nodule histological diagnosis. b) Benign diagnosis – FA, FA with Hurthle cells, Hurthle cells adenoma, colloid nodule and Hashimoto thyroiditis. c) In 2 patients, TC was required by malignant associated lesion. d)Well Differentiated Tumor of Uncertain Malignant Potential e) One patient who did not underwent TC surgery had a FVPTC with 1,10 cm and associated benign adenomatous nodules. The other one had a solitary FVPTC with 1,00 cm. f) Well Differentiated Carcinoma Non Otherwise Specified. Table 2 – Cytological diagnosis (Bethesda Classification System for thyroid cytopathology) FNAB a N (%) Malignancy in histology N(%) I 9 (4,79%) - II 25 (13,30%) - III 26 (13,83%) 9 (34,61%) IV 105 (55,85%) 43 (40,95%) V 23 (12,23%) - Total 188 b a) Reclassification based on Bethesda classification system (FNAB I, II and V were included because histological exam revealed a FTN). b) In four patients FNAB was unknown. Table 3 - Surgical complications LwI complicationsa TC complicationsb Permanent RLNc lesion 1 (0,58%) Permanent RLN lesion 1 (1,52%) Temporary dysphonia 16 (9,25%) Temporary dysphonia 4 (6,06%) Hematoma/Hemorrhage 4 (2,31%) Temporary hypoparathyroidism 2 (3,03%) Abscess 1 (0,58%) No 59 (89,39%) Hypertrophic or keloid scar 2 (1,16%) Hypothyroidism 40 (23,12%)d No 113 (65,32%) a) Unknown in 19 patients. b) Unknown in 14 patients. c) RLN - Recurrent Laryngeal Nerve d) Isolated hypothyroidism occurred in 36 (20,81%) patients and 4 patients had another associated LwI complication (3 an acute and in 1 a late onset complication). Anexos