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Annals of Surgical Oncology 10:15-20 (2003)
© 2003 Society of Surgical Oncology

ORIGINAL ARTICLES

Surgical Experience in Children With Differentiated Thyroid Carcinoma

Jan Willem Haveman, MD, Karin M. van Tol, MD, Catrienus W. Rouwé, MD, Do A. Piers, MD, PhD and John T. M. Plukker, MD, PhD

From the Departments of Surgical Oncology (JWH, JTMP), Internal Medicine (KMVT), Paediatrics (CWR), and Nuclear Medicine (DAP), University Hospital Groningen, Groningen, The Netherlands.

Correspondence: Address correspondence and reprint requests to: J. T. M. Plukker, MD, PhD, Department of Surgical Oncology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands; Fax: 31-50-361-4873; E-mail: j.th.plukker{at}chir.azg.nl


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Background: The optimal surgical treatment in children with well-differentiated thyroid carcinoma remains an important point of discussion. In this study, we evaluated our surgical experience and reviewed the literature accordingly to identify the most adequate treatment.

Methods: We retrospectively analyzed 21 children, all under the age of 18 years at the time of diagnosis, with differentiated thyroid carcinoma (17 papillary, 3 follicular, and 1 Hürthle cell carcinoma). Total thyroidectomy was performed, followed by radioiodine therapy, as a part of the initial treatment in all patients. The results were compared with data from the literature.

Results: Eleven children (52%) who presented with cervical lymph node metastases were treated by a modified radical neck dissection. Pulmonary metastases were seen at diagnosis in three patients. Six patients developed temporary complications. During follow-up, with a median of 11 years (range, 2–26 years), two patients (10%) developed recurrences, and no patient died during this observation period. A literature search confirmed our experience of excellent results without an increase of complications in the more aggressively treated patients.

Conclusions: In children with differentiated thyroid cancer, treatment should consist of total thyroidectomy, followed by a modified radical neck dissection (when indicated) and iodine-131 ablation treatment. This aggressive approach seems to be justified because of the high incidence of nodal involvement and the low complication and recurrence rate after surgery.

Key Words: Differentiated thyroid carcinoma • Treatment • Surgery • Childhood


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Differentiated thyroid carcinoma is rare in childhood, comprising approximately 1% of all cancers diagnosed before the age of 18 years.1–4 Clinically these tumors behave differently compared with thyroid carcinoma in adults. Nodal involvement is frequently found at the first clinical presentation (35%–83%), and pulmonary metastases are detected relatively more often at the time of diagnosis (5%–16%).5–14 Furthermore, recurrence rates are usually higher compared with those in adults.15,16 The prognosis even in case of distant metastases is relatively good.17,18 The extent of surgical resection in children with these tumors remains controversial. Because of the low incidence and good prognosis of thyroid carcinoma in these children, prospective trials comparing different therapeutic approaches are not available. Because of low mortality and recurrence rates at short-term follow-up, a long observation time is necessary. For this reason, retrospective cohort studies remain valuable in comparing the results of different therapeutic regimens.

In this study, we report a single center’s experience with 21 cases of differentiated thyroid carcinoma in children under the age of 18 years at the time of diagnosis who were treated over the last 25 years. We analyzed retrospectively the efficacy of vigorous surgery followed by radioactive iodine ablation (RAI) and reviewed the literature with respect to the current most optimal treatment strategy.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
From October 1974 to September 1999, 21 children (14 girls and 7 boys) aged 7 to 17 years (median, 14 years) were treated at the University Hospital Groningen for differentiated thyroid carcinoma. Data were collected from clinical and pathological report after approval of our institutional ethical commission.

Patients were preoperatively staged by physical examination of the cervical region and chest x-rays. Total thyroidectomy was performed in all patients with pathologic proof of thyroid carcinoma. There were no patients with tumors <1 cm in which a hemithyroidectomy was indicated. Clinically suspected cervical nodes were confirmed by preoperative cytological or intraoperative frozen-section examination. In case of nodal metastases, a selective ipsilateral neck dissection was performed of regions II to V (according to Robbins),19 including nodes along the jugular chain, the tracheoesophageal grooves, and the posterior triangle of the neck. Approximately 4 weeks after the operation, a diagnostic iodine-131 (131I) whole-body scan (dosage of 131I: .5–1.0 mCi, depending on body weight) was performed to detect any abnormal uptake of radioiodine. Ablation with 30 to 150 mCi of 131I was then performed to destroy all remnants of functional thyroid tissue. Thereafter, thyroid hormone was given to suppress the thyroid-stimulating hormone secretion (thyroid-stimulating hormone target level: .03–.3 mµ/L). All patients were followed up regularly by serum thyroglobulin (Tg) measurements and diagnostic 131I whole-body scanning. In case of persistent or recurrent 131I uptake lesions, a repeated dose of 131I treatment was given. Recurrences were categorized as local in a previously resected thyroid bed; as nodal metastases in the neck, superior mediastinum, or both; and as distant metastases. We also reviewed the literature in MEDLINE. We analyzed single-center studies concerning patients under the age of 21 years with differentiated thyroid carcinoma. Some studies were not analyzed because of incomplete data or follow-up.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
Clinical Presentation
Patient characteristics are listed in Table 1. Before surgery, vocal cord function was normal in all patients. One patient had been exposed to external radiation (craniospinal) because of acute lymphatic leukemia 5 years before diagnosis. Twelve patients presented with a solitary thyroid nodule, six with clinically pathologic enlarged lymph nodes, and three with both thyroid and lymph node enlargement.


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  		TABLE 1. Patient characteristics
 
Surgical Procedure
In all patients, a total thyroidectomy was performed. Before 1985, seven patients with clinically suspicious solitary thyroid enlargement underwent a diagnostic hemithyroidectomy followed by total thyroidectomy after confirmation of cancer by frozen-section examination. In four patients, the definitive diagnosis could not be made during the same surgical procedure. In these patients, completion of total thyroidectomy was performed later.

From 1985, fine-needle aspiration biopsy was performed in case of solitary thyroid enlargement. When malignancy was proven cytologically, a total thyroidectomy was performed (n = 5).

Eleven patients (52%) underwent nodal dissection. Nine patients presented with suspected palpable cervical lymph nodes. After confirmation of metastatic thyroid carcinoma, all of these patients underwent a selective neck dissection of regions II to V. In two patients, pathologically enlarged jugular lymph nodes were removed during the operation, and frozen section confirmed malignancy. Therefore, an ipsilateral neck dissection was subsequently performed. In two patients, the recurrent laryngeal nerve was totally encircled by extrathyroidal tumor and could not be preserved.

Postoperative Complications
Six patients developed postoperative complications. Transient vocal cord dysfunction occurred in three patients (14%), and hypoparathyroidism was observed in two patients (10%). Fortunately, all patients recovered completely within 6 months. Both patients with postoperative parathyroid dysfunction had a large tumor with extrathyroidal extension, positive lymph nodes, and invasion of the upper mediastinum. In these patients, a lymph node dissection was performed. Transient Horner syndrome was seen in one patient (5%) after a selective cervical node dissection.

Histological Examination
Seventeen patients were diagnosed with papillary thyroid carcinoma, three with follicular thyroid carcinoma, and one with Hürthle cell thyroid carcinoma. Eleven patients (52%), all with papillary thyroid carcinoma, had proven lymph node metastases. Multifocality was seen in six patients (29%) and extrathyroidal invasion (T4) in eight patients (38%) (Table 2). Multifocality and extrathyroidal invasion was observed only in patients with papillary thyroid carcinoma.


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  		TABLE 2. Histological findings and tumor-node-metastasis (TNM) classification (UICC 1997)
 
Postoperative Screening
Three patients (14%), all with papillary thyroid carcinoma, showed pulmonary metastases on postoperative 131I whole-body scanning. All these patients were treated with high-dose 131I therapy, with cumulative doses of 150, 350, and 885 mCi. They are currently clinically and biochemically free of disease (2, 13, and 26 years, respectively; Table 3).


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  		TABLE 3. Clinical course of patients without recurrence
 
Follow-Up
Two patients (10%) with papillary thyroid carcinoma developed recurrences. These patients had a significant increase in serum Tg levels (Table 4). Segment resection of the right upper lobe was performed in one patient who developed pulmonary metastases 8 years after initial therapy. Surgical intervention was followed by repetitive doses of 131I (total 600 mCi). She is now >15 years free of disease. The other patient developed nodal involvement 6 years after the initial treatment. A selective neck dissection was performed, and she is now free of disease for >2 years (Table 4).


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  		TABLE 4. Clinical course of patients with recurrence
 
In all children, growth and development were not affected by the therapy, and their mental and physical performance was normal at the last follow-up. At a median follow-up of 11 years (range, 2–26 years), all patients were clinically and biochemically disease free, with undetectable Tg levels at the last follow-up (Tg-on, with thyroid hormone suppression dose). No patient died during the follow-up period.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
This study shows that total thyroidectomy, eventually combined with a modified radical neck dissection in clinical nodal involvement, followed by RAI ablation, leads to a low recurrence rate and excellent survival in children with differentiated thyroid cancer. Children are more likely to have nodal metastasis, but their overall prognosis is improved, hampering the assessment of treatment efficacy.

The discussion concerning the most adequate and safe surgical treatment in children and adolescents for differentiated thyroid carcinoma has continued for a long time. In our hospital, total thyroidectomy is performed in all patients except for those with papillary intrathyroidal tumors <1 cm in diameter, for which hemithyroidectomy is standard. Lymph node dissection is performed in case of macroscopic nodal involvement. Total thyroidectomy is always followed by ablation with 131I. Most investigators recommend total thyroidectomy as the best surgical intervention.10–12,14,20–22 In a recently performed multivariate analysis including 109 children, Jarzab et al.8 demonstrated a positive effect of total thyroidectomy and additional nodal dissection on disease-free survival. They also found that additional RAI ablation was associated with less recurrence. However, in a study by Newman et al.,23 the recurrence rate after total or subtotal thyroidectomy was identical to the results of limited resection, i.e., lobectomy. However, patients with more extensive disease were more frequently treated with total or subtotal thyroidectomy. These findings confound a direct comparative retrospective analysis of thyroid lobectomy with total or subtotal thyroidectomy. Others opt for a more conservative surgical approach, despite a high rate of recurrence in their non–radical-surgery patients (>30%).5,16,24 In patients with thyroid carcinoma confined to the thyroid gland without lymph node or detectable distant metastases, Welch Dinauer et al.25 found more local recurrences in patients treated with lobectomy compared with total or subtotal thyroidectomy. These observations underline the role of extensive surgery even in case of limited disease. Generally, the recurrence rate of 2% to 33% in the group with a more aggressive approach10–14 was lower, compared with the results in the less aggressively treated patients (Table 5; 15%–45%),5–8 whereas the complication rate does not seem to be higher in these patients, i.e., permanent hypoparathyroidism in 0% to 21% and laryngeal nerve palsy in 0% to 17% of the patients. Furthermore, Table 5 emphasizes the role of 131I postoperative ablation treatment, with fewer recurrences in the more aggressively treated patients.


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  		TABLE 5. Complications and recurrence rate of treatment in children with differentiated thyroid carcinoma: literature overview
 
There are several arguments in favor of total thyroidectomy. First, differentiated thyroid carcinoma is often bilateral and multifocal. In this study, histological examination revealed multifocality in 6 (29%) of 21 cases. When surgical intervention was limited to hemithyroidectomy alone, a recurrence with re-exploration was inevitable. Moreover, these reinterventions often lead to a higher rate of complication.10,14 Second, it permits 131I diagnostic scanning and treatment, because of the absence of normal thyroid tissue. Third, it allows the use of serum Tg as a sensitive marker of recurrence. Adequate monitoring of Tg is essential during follow-up, as was documented in two patients in this study. Arguments against total thyroidectomy are mainly based on the fear of high complication rates. Generally, groups in which treatment is limited to hemithyroidectomy do not experience fewer complications.20,22 In our study, we encountered postoperative complications in six patients; all were temporary. Transient laryngeal nerve injury was seen in only 3 (8%) of 40 nerves at risk. Two nerves could not be preserved, because they were totally encircled by tumor. After 1980, perineural dissection was performed to prevent laryngeal nerve transsection in such cases. Transient hypoparathyroidism was seen in two patients, and this is comparable with other studies.

Nodal involvement had no adverse effect on the long-term clinical outcome in our series. Despite the high incidence of lymph node metastases in children, there is no need for prophylactic neck dissection. In this study, cervical lymph nodes were involved in 11 (52%) of 21 patients. One patient developed lymph node metastases during the follow-up period and subsequently underwent a selective neck dissection. Surgeons who treat children with thyroid cancer should have experience with neck dissection.

Follow-up of children with differentiated thyroid carcinoma consists of regular Tg assays and eventually 131I total-body scanning. Detectable serum Tg levels during adequate suppressive levothyroxine treatment are an indication of persistent, recurrent, or metastatic disease. Positive diagnostic 131I whole-body scanning will allow treatment with high-dose 131I. However, in case of palpable or large tumor load, surgical resection should be augmented. In case of negative diagnostic 131I scanning and detectable serum Tg levels, empirical treatment with high-dose 131I can be started, but this is debatable. The use of whole-body positron emission tomography with 18F-fluorodeoxyglucose in case of negative 131I scans is also described.26,27


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
In differentiated thyroid carcinoma in children, total thyroidectomy and selective lymph node dissection (if indicated) is the treatment of choice. Surgery should be followed by 131I ablation therapy. To minimize the complication rate, experience is mandatory. Follow-up should be directed at detecting thyroid cancer tissue as soon as possible.


   Footnotes
 
This is a report of a single-center experience and review of the literature in children with well-differentiated thyroid carcinoma. An aggressive approach is associated with fewer recurrences and a lower complication rate.

Received for publication March 4, 2002. Accepted for publication August 16, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987; 102: 1088–95.[Medline]
  2. Samuel AM, Rajashekharrao B, Shah DH. Pulmonary metastases in children and adolescents with well- differentiated thyroid cancer. J Nucl Med 1998; 39: 1531–6.[Abstract/Free Full Text]
  3. Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 1993; 114: 1050–7.[Medline]
  4. McConahey WM, Hay ID, Woolner LB, van Heerden JA, Taylor WF. Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc 1986; 61: 978–96.[Medline]
  5. La Quaglia MP, Corbally MT, Heller G, Exelby PR, Brennan MF. Recurrence and morbidity in differentiated thyroid carcinoma in children. Surgery 1988; 104: 1149–56.[Medline]
  6. Robie DK, Welch Dinauer CA, Tuttle RM, et al. The impact of initial surgical management on outcome in young patients with differentiated thyroid cancer. J Pediatr Surg 1998; 33: 1134–8.[CrossRef][Medline]
  7. Alessandri AJ, Goddard KJ, Blair GK, Fryer CJ, Schultz KR. Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma. Med Pediatr Oncol 2000; 35: 41–6.[CrossRef][Medline]
  8. Jarzab B, Handkiewicz-Junak D, Wloch J, et al. Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children. Eur J Nucl Med 2000; 27: 833–41.[CrossRef][Medline]
  9. Welch Dinauer CA, Tuttle RM, Robie DK, et al. Clinical features associated with metastasis and recurrence of differentiated thyroid cancer in children, adolescents and young adults. Clin Endocrinol (Oxf) 1998; 49: 619–28.[CrossRef][Medline]
  10. Segal K, Shvero J, Stern Y, Mechlis S, Feinmesser R. Surgery of thyroid cancer in children and adolescents. Head Neck 1998; 20: 293–7.[Medline]
  11. Danese D, Gardini A, Farsetti A, Sciacchitano S, Andreoli M, Pontecorvi A. Thyroid carcinoma in children and adolescents. Eur J Pediatr 1997; 156: 190–4.[CrossRef][Medline]
  12. Hallwirth U, Flores J, Kaserer K, Niederle B. Differentiated thyroid cancer in children and adolescents: the importance of adequate surgery and review of literature. Eur J Pediatr Surg 1999; 9: 359–63.[Medline]
  13. Samuel AM, Sharma SM. Differentiated thyroid carcinomas in children and adolescents. Cancer 1991; 67: 2186–90.[Medline]
  14. Bingol-Kologlu M, Tanyel FC, Senocak ME, Buyukpamukcu N, Hicsonmez A. Surgical treatment of differentiated thyroid carcinoma in children. Eur J Pediatr Surg 2000; 10: 347–52.[Medline]
  15. Samaan NA, Schultz PN, Hickey RC, et al. The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients. J Clin Endocrinol Metab 1992; 75: 714–20.[Abstract]
  16. Zimmerman D, Hay ID, Gough IR, et al. Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades. Surgery 1988; 104: 1157–66.[Medline]
  17. Brink JS, van-Heerden JA, McIver B, et al. Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis. Surgery 2000; 128: 881–6.[Medline]
  18. La-Quaglia MP, Black T, Holcomb GW, et al. Differentiated thyroid cancer: clinical characteristics, treatment, and outcome in patients under 21 years of age who present with distant metastases. A report from the Surgical Discipline Committee of the Children’s Cancer Group. J Pediatr Surg 2000; 35: 955–9.[CrossRef][Medline]
  19. Robbins KT, Medina JE, Wolfe GT, Levine PA, Sessions RB, Pruet CW. Standardizing neck dissection terminology. Official report of the Academy’s Committee for Head and Neck Surgery and Oncology. Arch Otolaryngol Head Neck Surg 1991; 117: 601–5.[Abstract]
  20. Jocham A, Joppich I, Hecker W, Knorr D, Schwarz HP. Thyroid carcinoma in childhood: management and follow up of 11 cases. Eur J Pediatr 1994; 153: 17–22.[Medline]
  21. Harness JK, Thompson NW, McLeod MK, Pasieka JL, Fukuuchi A. Differentiated thyroid carcinoma in children and adolescents. World J Surg 1992; 16: 547–53.[Medline]
  22. Dottorini ME, Vignati A, Mazzucchelli L, Lomuscio G, Colombo L. Differentiated thyroid carcinoma in children and adolescents: a 37-year experience in 85 patients. J Nucl Med 1997; 38: 669–75.[Abstract/Free Full Text]
  23. Newman KD, Black T, Heller G, et al. Differentiated thyroid cancer: determinants of disease progression in patients < 21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children’s Cancer Group. Ann Surg 1998; 227: 533–41.[CrossRef][Medline]
  24. Desjardins JG, Bass J, Leboeuf G, et al. A twenty-year experience with thyroid carcinoma in children. J Pediatr Surg 1988; 23: 709–13.[CrossRef][Medline]
  25. Welch Dinauer CA, Tuttle RM, Robie DK, McClellan DR, Francis GL. Extensive surgery improves recurrence-free survival for children and young patients with class I papillary thyroid carcinoma. J Pediatr Surg 1999; 34: 1799–804.[CrossRef][Medline]
  26. van Tol KM, Jager PL, Dullaart RP, Links TP. Follow-up in patients with differentiated thyroid carcinoma with positive 18F-fluoro-2-deoxy-D-glucose-positron emission tomography results, elevated thyroglobulin levels, and negative high-dose 131I posttreatment whole body scans. J Clin Endocrinol Metab 2000; 85: 2082–3.[Free Full Text]
  27. Muros MA, Llamas EJ, Ramirez NA, et al. Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in differentiated thyroid carcinoma with negative radioiodine scans and elevated serum thyroglobulin levels. Am J Surg 2000; 179: 457–61.[CrossRef][Medline]



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