Curves comparing the survival of patients according to histological types. The difference between types was significant (P= .03).
Kowalski LP, Filho JG, Pinto CAL, Carvalho AL, de Camargo B. Long-term Survival Rates in Young Patients With Thyroid Carcinoma. Arch Otolaryngol Head Neck Surg. 2003;129(7):746-749. doi:10.1001/archotol.129.7.746
Copyright 2003 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2003
Thyroid carcinoma in patients younger than 18 years is rare. It is associated with a greater risk of metastases. However, the prognosis for these patients is better when compared with that of adults.
To present the experience of a single institution in the treatment of patients with thyroid carcinoma during childhood and adolescence.
Patients and Methods
Thirty-eight patients, ranging in age from 4 to 18 years, were diagnosed as having thyroid carcinoma. Pathologic types of carcinoma included 29 papillary, 4 follicular, 1 Hürthle cell, and 4 medullary cases.
Hypocalcemia was the main complication, being transitory in 9 patients (24%) and permanent in 6 patients (16%). Vocal cord palsy occurred in 2 patients (5%). Two patients (5%) had a surgical site infection. After a mean follow-up of 9.5 years (range, 1-40 years), 28 patients (74%) were alive and had no evidence of disease, 3 (8%) were alive and had recurrent disease, 4 (11%) died (2 of the disease and 2 of non–cancer-related causes), and 3 (8%) were lost to follow-up. The survival rates at 10 years for the patients with papillary, follicular, and medullary carcinoma were 93%, 100%, and 50%, respectively.
Thyroid carcinoma in patients younger than 18 years has a good prognosis even in the presence of neck or distant metastasis. Total thyroidectomy, associated with adjuvant radioactive iodine therapy and thyroidal suppression or not, is effective in patients with a well-differentiated thyroid carcinoma.
THYROID NODULES are less frequent in children than in adults.1,2 However, when present, they are more likely to be malignant.3- 6 The incidence of thyroid tumors has been increasing in various countries throughout the past few decades,7- 9 composing about 1% of all malignant neoplasias.10 The occurrence of thyroid carcinoma in those younger than 18 years is relatively rare (3%-6.3% of these cases).11- 13 The most frequent thyroid carcinoma in young people is the papillary carcinoma, predominantly found in adolescent girls. It is associated with a greater risk of lymph nodal metastases. However, the prognosis in these patients is better when compared with that of adults.12,14,15 On the other hand, the surgery used in the treatment of thyroid carcinoma in childhood is associated with a greater incidence of complications12,16; in addition, local and distant recurrences have been described, even after several years.16,17
This study evaluates the experience of a single institution in the treatment of patients with thyroid carcinoma in childhood and adolescence, analyzing the epidemiological factors, postoperative complications, and long-term survival.
Between September 14, 1961, and January 19, 2000, 40 patients, ranging in age from 4 to 18 years, with thyroid carcinoma were admitted for treatment at the Department of Head and Neck Surgery and Otorhinolaryngology, Centro de Tratamento e Pesquisa Hospital do Câncer A. C. Camargo. The pathologic diagnosis of all patients was reviewed and analyzed by a single pathologist (C.A.L.P.). Two patients were excluded because it was impossible to obtain material to perform the pathologic review. Among the 38 patients studied, 15 were boys (39%) and 23 were girls (61%). The patients with papillary carcinoma ranged in age from 4 to 18 years (mean, 13 years); those with follicular carcinoma, from 12 to 18 years (mean, 16 years); and those with medullary carcinoma, from 13 to 18 years (mean, 16 years).
Twenty-three patients (61%) reported the presence of a single nodule in the thyroid initially. The interval between the beginning of the signs and clinical symptoms and the definitive surgical treatment varied from 1 to 84 months (mean, 10 months). We did not find evidence of any patient with a history of radiotherapy in the head and neck region. Only 11 patients had not undergone previous surgical procedures. Of the 27 patients previously operated on, 6 had undergone a total thyroidectomy (1 with an adenectomy and 1 with a selective neck dissection), 8 had undergone a lobectomy (5 with an adenectomy), 4 had undergone a thyroid nodulectomy (1 with an adenectomy), and 9 had undergone a diagnostic adenectomy.
The evaluation during admission included a clinical history, a physical examination, routine laboratory testing, thorax radiography, and the determination of dosages of liothyronine sodium, levothyroxine sodium, and thyrotropin. Preoperative thyroid scintillography was performed in 21 patients (55%), and ultrasonography was performed in only 6 patients (16%). A fine-needle aspiration biopsy was performed in only 9 patients (24%). The patients' cancer was restaged retrospectively based on the 1997 International Union Against Cancer classification,17 according to the clinical data described, image examination results, the surgical report, and pathologic examination, as follows: 1, T1 N1a M0; 1, T1 N1b M0; 2, T2 N0 M0; 4, T2 N1a M0; 1, T2 N1b M0; 1, T2 N1b M1; 3, T3 N0 M0; 2, T3 N1a M0; 2, T3 N1b M0; 1, T4 N0 M0; 2, TX N0 M0; 1, TX N1a M0; 3, TX N1b M1; 13, TX NX M0; and 1, TX NX M1.
The surgical treatments used at the institution were 24 total thyroidectomies and 7 completions of total thyroidectomies. In 6 patients, the total thyroidectomy included the resection of adjacent structures (4 strap prethyroidal muscles, 1 trachea, and 1 recurrent laryngeal nerve). Another 6 patients had already undergone a total thyroidectomy, and 1 had undergone a lobectomy. An ipsilateral neck dissection was performed in 13 patients (8 radical neck dissections and 5 type III modified radical neck dissections). A bilateral neck dissection was performed in 8 patients (7 modified radical neck dissections and 1 lateral neck dissection). Paratracheal lymph node dissection was performed in 13 patients (4 ipsilateral and 9 bilateral dissections). The reviewed pathologic study showed papillary carcinoma in 29 patients (76%), follicular carcinoma in 4 patients (11%), Hürthle cell carcinoma in 1 patient (3%), and medullary carcinoma in 4 patients (11%) (percentages do not total 100 because of rounding).
Adjuvant therapy was used in 20 patients (53%). Trends in the indication of adjuvant therapy in the early part of this retrospective study were difficult to assess. Adjuvant radioactive iodine 131 (131I) was administered to 16 patients (42%), and postoperative external beam radiotherapy was used on 4 patients (11%) with an extrathyroidal extension. Hormonal reposition in a suppressive dose was administered in 34 patients (89%) with a differentiated carcinoma (papillary and follicular).
Actuarial survival calculations were made, using the Kaplan-Meier method and the Cox-Mantel test, to compare the differences in survival between the categories of the same variable. The association between the studied variables and the occurrence of complications was evaluated using the χ2 test or the Fisher exact test when applicable. P<.05 was considered significant.
Postoperative complications occurred in 19 patients (50%). Hypocalcemia was the main complication, being transitory in 9 patients (24%) and permanent in 6 (16%). Postoperative dysfunction of the recurrent laryngeal nerve occurred in 2 patients (5%). Two patients (5%) had a surgical site infection. There were no postoperative deaths. Despite the high incidence of complications in our series, we did not observe any significant correlations with sex, age, nodule size, previous surgery, type of thyroidectomy, and neck dissection or paratracheal lymph node dissection.
During the study period, 28 patients (74%) did not show recurrence of the disease. Local recurrence occurred in 4 patients (11%), regional in 3 patients (8%), distant in 2 patients (5%), and regional and distant in 1 patient (3%). The interval between initial treatment and recurrence ranged from 1 to 98 months (mean, 19.5 months). At the end of this study, after a mean follow-up of 9.5 years (range, 1-40 years), 28 patients (74%) were alive and had no evidence of disease, 3 (8%) were alive and had a recurrence, 2 (5%) were dead as a result of the disease, 2 (5%) were dead as a result of other causes, and 3 (8%) were lost to follow-up. Two patients had a second primary tumor during the study period (a lymphoma and a thymoma) (Table 1).
Overall actuarial survival at 10 and 20 years was 90%. No significant difference was shown between the categories for sex, age, nodule size, and tumor and nodal stages. Similarly, the presence or absence of a previous surgical procedure, the type of surgery, and adjuvant iodine therapy did not show any prognostic association (Table 2). The histological type was the only variable significantly associated with prognosis (P = .03). The survival rates at 10 years for the patients with papillary, follicular, and medullary carcinoma were 93%, 100%, and 50%, respectively (Figure 1).
Differentiated carcinomas of the thyroid are associated with an excellent prognosis in patients younger than 45 years.15 Similarly, series17- 19 that studied patients with thyroid carcinomas in childhood and adolescence, even in the presence of distant metastasis, showed a favorable long-term prognosis.
The presence of neck node metastases as an initial manifestation in patients with thyroid cancer is more common in children than in adults.12 However, in our series, the presence of a nodule in the thyroid was the main clinical manifestation, occurring in 23 patients (61%). Metastasis in the neck lymph nodes was shown as the initial manifestation in 9 patients (24%). Other studies13,16,20- 22 have shown an incidence of thyroid nodules at initial presentation ranging from 51% to 91%.
In our series, ultrasonography and 131I scintillography were performed in only 6 (16%) and 21 (55%) of the patients, respectively. The many diagnostic adenectomies previous to thyroidectomy suggest that thyroid nodules were not observed by the time of the first medical evaluation and, possibly, thyroid cancer was not considered among the diagnostic hypotheses. After the diagnosis of metastatic thyroid carcinoma, such patients underwent definitive treatment without further investigation, except for a thorax x-ray film. More recently, imaging studies2,23 have been used in the initial evaluation of the thyroid nodules, although they do not differentiate benign from malignant lesions.
Despite the evolution of the differential diagnosis of thyroid nodules with the introduction of fine-needle aspiration biopsy, frequently allowing the differential diagnosis between a benign and a malignant lesion, this examination has been little used in pediatric patients as a result of the technical difficulties and significant discomfort.6 In this series, a fine-needle aspiration biopsy was performed in only 9 patients (24%). Many patients underwent an adenectomy for the differential diagnosis of cervical adenopathies, but this procedure should certainly be discouraged because of the difficulty that occurs when the definitive surgical procedure is performed.
The evolution of surgical and anesthetic techniques has led to a significant reduction of the incidence of postoperative complications, so that thyroidectomy has become a procedure associated with a low morbidity and mortality. However, high postthyroidectomy complication rates in pediatric patients are described (range, 30%-82%).16,24 In our series, we noted postoperative complications in 19 patients (50%). Hypocalcemia was the most important of these complications (it was transitory in 9 patients [24%] and permanent in 6 [16%]), although we routinely identified the parathyroids (and recurrent laryngeal nerves) before performing the ligation of the inferior thyroid pedicles. An autotransplantation of the parathyroid in the sternocleidomastoid or anterior scalene muscles was performed during the past decade whenever there was vascular supply injury or the glands were accidentally removed. In the literature,11- 13,16,19,21,22 the incidence of permanent postthyroidectomy hypocalcemia in childhood and adolescence ranges from 8.1% to 24%. We did not observe any significant association between postoperative complications and sex, age, nodule size, previous surgery, type of thyroidectomy, and neck or paratracheal dissection. The main reason for this incidence is the difficulty in identifying the parathyroid, especially in smaller children, apart from the frequent necessity of performing paratracheal dissection because of the presence of metastatic lymph nodes. When these procedures are performed, the parathyroids, even when identified, may have significant ischemia. Lobectomy with isthmectomy is an acceptable alternative in adults younger than 45 years, and may reduce the risk of postoperative complications, mainly hypoparathyroidism. However, because of the high rates of multicentricity, this procedure is not acceptable for the population younger than 18 years. The acceptable alternative, for patients in whom the surgeon finds difficulty in identifying the parathyroids, is to perform a near-total thyroidectomy, followed by a therapeutic dose of 131I.12,16,25
The investigation of prognostic factors identifies patients with a high and low risk of recurrence and death caused by cancer. The prognosis for pediatric patients with a differentiated carcinoma is favorable, with less than 5% of deaths caused by cancer, according to various studies.16,25,26 In our study, we observed similar survival rates irrespective of sex, age, nodule size, tumor and node stages, presence or absence of previous surgical procedures, and adjuvant therapy. Although we did not observe significant differences in the prognosis of these patients after the use of adjuvant 131I therapy or radiation therapy, it might be because of the fact that the patients selected were at greatest risk of recurrence. Furthermore, a suppressive dose of levothyroxine sodium, used in most patients, possibly contributed toward the diminished rates of recurrence.
Medullary carcinomas are less frequent, result from mutations of the ret oncogene, arise in the calcitonin-producing parafollicular C cells, and may be part of the multiple endocrine neoplasia 2A or 2B syndrome. They are locally more aggressive tumors than differentiated carcinomas, and the frequency of neck and mediastinal lymph nodal metastasis may reach up to 50%.8 In this series, we noted the worst prognosis in children and adolescents with medullary carcinomas compared with those with well-differentiated carcinomas.
By analyzing the results, we may conclude that patients up to the age 18 years with thyroid carcinoma frequently have tumors in an advanced stage and have lymph nodal metastasis at initial presentation. Total thyroidectomy (despite the high rate of complications), associated with adjuvant radioactive iodine therapy and thyroidal suppression or not, is effective in the treatment of these patients.
Corresponding author and reprints: Luiz Paulo Kowalski, MD, PhD, Department of Head and Neck Surgery and Otorhinolaryngology, Centro de Tratamento e Pesquisa Hospital do Câncer A. C. Camargo, Rua Professor Antonio Prudente 211, 01509-900 São Paulo, Brazil (e-mail: email@example.com).
Accepted for publication November 21, 2002.
This study was presented at the annual meeting of the American Head and Neck Society, Boca Raton, Fla, May 11, 2002.