1992, The British Journal of Radiology, 65, 977-982
Sonography in thyroid carcinoma in children By tCristian J. Garcia, MD, Alan Daneman, MD, BCh, FRCPC, Kieran McHugh, MB, FRCR, *Helen Chan, MD and *Denis Daneman, MB, BCh, FRCPC Department of Radiology and the *Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8 {Received 7 January 1992 and in revised form 14 May 1992, accepted 3 June 1992) Keywords: Carcinoma, Children, Sonography, Thyroid Abstract. This paper reviews the clinical, sonographic and pathological findings of 20 children with thyroid carcinoma in an attempt to determine the value and limitations of sonography in thyroid neoplasms in this age group. Although sonography is an excellent technique for the evaluation of thyroid disorders and masses, certain limitations must be kept in mind. Microscopic foci of tumour might be missed and sonography cannot predictably differentiate benign from malignant disease. Previous radiation exposure should increase the level of suspicion for malignancy.
In children thyroid carcinoma is uncommon and constitutes 1-1.5% of all malignancies (Miller, 1985; Desjardins et al, 1988). Although sonography has been successfully used to study thyroid and extrathyroid neck masses in children (Friedmann et al, 1983; Sherman et al, 1985), its value and limitations in paediatric thyroid neoplasms have not been assessed. During the past 13 years, 40 children with thyroid carcinoma were treated at our institution and sonography was performed pre-operatively in 20 of them. This report correlates the data for these 20 patients. Material and methods
We reviewed the clinical, sonographic and pathological findings of 20 patients diagnosed as having thyroid carcinoma at the Hospital for Sick Children, Toronto, between 1977 and 1990: 10 girls and 10 boys, whose age at the time of diagnosis ranged from 6.3 to 19 years (mean =13.1 years). The sonographic examinations were performed with the patient in the supine position with a pillow under the shoulders and the neck hyperextended. No patient preparation or sedation was used. The thyroid lesions were considered hyper-, iso- or hypoechoic relative to the normal thyroid gland, echo-free or of mixed echogenicity. Six patients also had pre-operative computed tomography (CT) of the neck and 17 had at least one preoperative radionuclide thyroid scan (technetium-99m pertechnetate and/or iodine-131 scans). All patients had a chest radiograph and eight had chest CT pre-operatively. 19 patients were treated surgically with total or partial thyroidectomy and in one patient the diagnosis Address correspondence to Dr Alan Daneman, Radiologist-in-Chief, Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada. fPresent address: Departamento de Radiologia, Hospital Clinico Universidad Catolica de Chile, Marcoleta 347, Santiago, Chile, South America.
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of metastatic medullary thyroid carcinoma was made by a cervical node biopsy. Histology was available from all patients. Results
17 patients presented with an asymptomatic mass or thyroid nodule that had been present for up to two years; in three of these it was an incidental finding during routine examination. The neck mass was felt to be thyroid in origin in 14 cases and only one had multiple palpable thyroid nodules. One patient presented with hoarseness and cough and a mass was found. Two patients with known multiple endocrine neoplasia (MEN) syndrome Type lib had raised serum calcitonin levels; one of these did not have a palpable neck mass. All patients were clinically and biochemically euthyroid at the time of presentation. Five patients also had cervical lymphadenopathy. Seven patients had a history of neck or chest radiation, between two and 16 years previously, for Hodgkin's lymphoma, leukaemia, Ewing's sarcoma, metastatic Wilms' tumour or abdominal neuroblastoma. 19 patients were treated with total or partial thyroid resection. Post-operatively, ablative doses of radioactive iodine and/or L-thyroxine suppression were utilized. Histology Histology revealed papillary carcinoma in 12 cases (two with mixed papillary-follicular features), follicular carcinoma in six, and medullary carcinoma in two. The thyroid carcinoma was unicentric in 10 cases (follicular carcinoma 6, papillary carcinoma 4); in four of these it co-existed with one or two benign nodules (adenoma or colloid nodule). The carcinoma was multifocal in the other 10 (papillary carcinoma 8, medullary carcinoma 2). Of the 10 multifocal carcinomas, seven were bilateral in the gland and three unilateral. Identification of lesions on sonography
Sonography identified a single thyroid nodule or mass in 12 patients (Fig. 1) and two or more nodules in seven (Fig. 2). In one patient with medullary carcinoma and 977
C. J. Garcia, A. Daneman, K. McHugh, H. Chan and D. Danemat
Figure 1. Transverse sonogram of the thyroid in a 12-year-old girl shows a large, unicentric mass (arrows) in the right lobe. The mass has a mixed echogenicity with an echo-free periphery and echogenic centre. The trachea (T) is displaced to the left and the left lobe (t) is normal. Diagnosis: unicentric follicular carcinoma.
without a palpable thyroid mass, no definite thyroid nodules were detected and only a hyperechoic linear density was noted in the right lobe. In one patient with metastatic bilateral multifocal papillary carcinoma, contralateral involvement was suspected but the findings were equivocal. Sonography failed to detect carcinomatous involvement of the contralateral lobe in five of the seven cases with histologically proven multifocal bilateral carcinoma and in six of these the contralateral tumour foci were microscopic on histological examination (Fig. 3). Sonography also failed to detect a second 1 cm tumour nodule in the isthmus in a case of metastatic papillary carcinoma and a 0.5 cm nodule in a case of bilateral multifocal medullary carcinomas. In one patient who presented with a neck mass and extensive cervical lymphadenopathy, a metastatic lymph node was mistaken for a thyroid nodule on ultrasound examination: in this case the thyroid was small but diffusely infiltrated by a papillary carcinoma. In the three cases of unilateral multifocal involvement, sonography detected a single nodule: in two of these multiplicity was determined by multiple microscopic tumour foci.
Figure 3. Transverse sonogram of the thyroid in a 7-year-old girl shows a slightly hypoechoic, well defined nodule in the left lobe (large arrows) surrounded by a hypoechoic rim or halo (small arrows). This was shown to be a papillary carcinoma. The trachea (T) has been displaced towards the right and the right lobe of the thyroid (t) appears normal. However multiple microscopic tumour foci were noted histologically on the right.
Appearance of lesions on sonography The malignant lesions had an ill-defined margin in eight cases (Fig. 4) and were relatively well defined in 11 (Figs 1, 3). In the four patients in whom a unicentric carcinoma co-existed with benign nodules, the margins of the benign nodules were well defined in three and slightly ill-defined in one (Fig. 2). The size of the lesions varied from 1.5 to 4.5 cm in maximum diameter and the echogenicity was variable (Figs 1-4). The lesions were hyperechoic in six cases,
Figure 2. Multinodular thyroid gland in a 19-year-old boy with a history of chest and abdominal radiation 16 years previously because of pulmonary metastases from Wilms' tumour, (a) Longitudinal sonogram of the right lobe of the thyroid shows a relatively well defined nodule (arrows) of mixed echogenicity with multiple echo-free areas, shown to be a unicentric follicular carcinoma, (b) Longitudinal sonogram of the left lobe shows a smaller hypoechoic nodule (arrows) that was shown histologically to be an adenoma.
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Sonography in thyroid carcinoma in children
Figure 4. Longitudinal sonogram of the left lobe of the thyroid in a 16-year-old girl shows marked enlargement of the lobe (arrows) and a diffuse, ill-defined inhomogenous echo pattern. This was shown histologically to be a multifocal, unilateral papillary carcinoma.
hypoechoic in five, and isoechoic in three. In five cases the lesions were of mixed echogenicity with some echofree cystic areas, and in one case the echo pattern was inhomogenous. In none of the cases was a completely echo-free lesion noted. A halo or hypoechoic rim surrounding the nodule was present in four cases of bilateral multifocal papillary carcinoma. Calcified nodules were detected bilaterally in one case of multifocal medullary carcinoma and in one multifocal papillary carcinoma. The benign lesions also had variable echogenicity (hyperechoic 2 (one with halo), hypoechoic 1, echo-free 1)-
Figure 5. Computed tomograph (after intravenous contrast medium enhancement) of the upper chest in a 7-year-old girl with a mixed papillary-follicular carcinoma. The scan shows a mass of low attenuation (arrows) extending from the lower part of the thyroid through the thoracic inlet into the upper mediastinum on the left. The mass lies anterolateral to the trachea (T).
sonography. In one patient, CT identified extension of the tumour into the thoracic inlet (Fig. 5) and in two extensive adenopathy was noted. In two patients, lung metastases were detected on chest radiography and chest CT at the time of presentation and in one of these (medullary carcinoma) the lung metastases were calcified. This latter patient also had bony, hepatic and retroperitoneal metastases. The chest radiograph and/or chest CT were negative in all the other cases.
Discussion , Thyroid carcinoma may occur at any age and approximately 5-10% of cases occur in patients younger than 21 years (Zohar et al, 1986; Desjardins Radionuclide scans et al, 1988; Ceccarelli et al, 1988; Zimmerman et al, 15 of the radionuclude studies were considered 1988). It accounts for approximately 1.5% of all paediaabnormal and demonstrated a single "cold" lesion in tric cancers and 5% of malignancies involving the head nine patients, multiple cold lesions in three, single "hot" and neck in children (Miller, 1985; Desjardins et al, lesions in two and both cold and hot lesions in one. In 1988). Although in most series it is at least twice as two cases (medullary carcinoma 1, papillary carcinoma common in girls as in boys (Joppich et al, 1983; 1) the radionuclide study was normal. Desjardins et al, 1988; Ceccarelli et al, 1988; Zimmerman et al, 1988), we found no difference in sex distribution. Although thyroid carcinoma tends to be Other diagnostic modalities employed Six patients had computed tomography (CT) of the more advanced both locally and systemically at the time neck and in four of these the thyroid mass or masses of the diagnosis in children than in adults, the prognosis were easily identified. In the fifth it was difficult to is better in patients younger than 21 years than in older identify the thyroid mass separately from the adjacent people (Joppich et al, 1983; Zohar et al, 1986; extensive cervical lymphadenopathy. In the sixth patient Zimmerman et al, 1988). This is based on an excellent (medullary carcinoma) the gland was extremely small response in children to surgical treatment, followed by and CT, like sonography, failed to document a thyroid ablation of the thyroid remnant by radioactive iodine and thyroid suppression with L-thyroxine. mass. The thyroid masses showed low or patchy attenuaMetastatic involvement of the cervical lymph nodes tion. In one case of medullary carcinoma, calcified has been reported to be the most common presenting nodules were noted that had been demonstrated by symptom of thyroid carcinoma in children and may be Vol. 65, No. 779
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C. J. Garcia, A. Daneman, K. McHugh, H. Chan and D. Daneman
present in 30-90% of cases at the time of diagnosis (Reiter et al, 1981; Zohar et al, 1986; Desjardins et al, 1988; Zimmerman et al, 1988). In our series only seven cases (35%) had cervical lymphadenopathy at the time of presentation, but six of them also had thyroid nodules. However, a painless thyroid nodule or mass without associated symptoms may also be the first sign (Sherman et al, 1985) occurring in the majority of our cases (60%). Less frequently they metastasize to the lungs and occasionally to bone and other structures. Approximately 6-14% present with lung metastases at the time of diagnosis (Hopwood et al, 1976; Ceccarelli et al, 1988; Zimmerman et al, 1988), as occurred in two of our patients (10%). Most children with thyroid carcinoma are euthyroid although rarely they may present with hyperthyroidism (Kirkland et al, 1973; Hopwood et al, 1976). There is a significant association between thyroid neoplasms and previous exposure to ionizing radiation to the head and neck (Hagler et al, 1966; Refetoffet al, 1975; Cerletty et al, 1978; Walsh et al, 1978; Fleming et al, 1985), with a latency period that may be as long as 25 years (Miller, 1985; Zohar et al, 1986). This predisposing factor has been reported in 20-50% of children with thyroid carcinoma (Segal et al, 1985; Zohar et al, 1986) and occurred in 35% of our patients. However, the number of cases of thyroid malignancy related to radiation might increase with the improved survival of childhood malignancies in general. It has been reported that the incidence of malignancy in multinodular glands is lower (1-7%) than that in solitary nodules (10-25%) (Brown, 1981; Miller, 1985). However, according to McCall et al (quoted by Austin, 1982) there is no significant difference between the incidence of carcinoma in multinodular goitre and in that of solitary cold nodules after exclusion of those patients with factors which predispose to neoplasia (e.g. history of radiation exposure, multiple endocrine neoplasia syndrome). In a review of 16 cases with multinodular gland in children at our institution, we found four (25%) to be associated with carcinoma, three of whom had had neck radiation. In general a history of previous radiation, rapid enlargement of a thyroid nodule, cervical lymphadenopathy and hoarseness are all suggestive of malignancy (Reiter et al, 1981). Histologically the most common types are the well differentiated pure or mixed papillary and follicular carcinomas (90% in our series). Medullary carcinoma (10%) is far less frequent and anaplastic carcinomas are extremely rare in children (McCook et al, 1982; Miller, 1985; Zohar et al, 1986). Papillary or mixed papillary follicular carcinomas are frequently multicentric and bilateral and it is unclear whether they represent metastases or multifocal origin of the neoplasm (Reiter et al, 1981; Desjardins et al, 1988), and this is in accordance with our series. Multifocal thyroid carcinoma is more commonly associated with radiation (Cerletty et al, 1978; Walsh et al, 1978; Fleming et al, 1985) but often the lesions are less than 1 cm in size (Hagler et al, 1966). 980
In our series, all patients with a history of irradiation had multiple thyroid nodules, because of multifocal carcinoma in three cases and associated benign lesions in four (adenomas in two and a colloid nodule in two) (Fig. 2). Benign and malignant lesions may therefore coexist following radiation, as previously reported. (Hagler et al, 1966; Austin, 1982). Medullary thyroid carcinoma accounts for approximately 3.5-10% of all thyroid cancers at all ages (McCook et al, 1982) and occurs most commonly between the ages of 30 and 60. Although rarely diagnosed before 10 years, it has been reported even during the second year of life (Stjerholm et al, 1980), but C-cell hyperplasia is more likely to be seen in younger patients (Graze et al, 1978; Stjerholm et al, 1980; Jones & Sisson, 1983; Desjardins et al, 1988). The lesion most commonly occurs sporadically (80-90%) but may occur in families as a component of the multiple endocrine neoplasia II (MEN-II) syndrome (20%) (McCook et al, 1982; Desjardins et al, 1988). In the latter it is commonly associated with adrenal phaeochromocytoma and hyperplasia of the parathyroid glands (MEN-IIa). MEN-IIb is a less common form and consists of elements of MEN-IIa together with features of marfanoid habitus, mucosal neuromas and intestinal ganglioneuromatosis (McCook et al, 1982; Desjardins et al, 1988). This neoplasm is always associated with raised serum calcitonin levels (McCook et al, 1982; Jones & Sisson, 1983) which may be detected in screening studies performed because of the presence of other clinical features of the syndrome or of a neck mass (McCook et al, 1982; Desjardins et al, 1988). The thyroid lesions may be bilateral in approximately 20% of sporadic cases and 90% of those lesions associated with MEN II syndromes (Graze et al, 1978; McCook et al, 1982; Jones & Sisson, 1983) and was present in our two patients with MEN lib. Thyroid sonography has been used mainly in adults to differentiate solid from cystic lesions, solitary from multifocal lesions and thyroid from extrathyroidal lesions (Sackler et al, 1977; Scheible et al, 1979; Simeone et al, 1982; Walker et al, 1985). High resolution equipment allows detection of nodules as small as 2-3 mm (Sackler et al, 1977; Walker et al, 1985). Although sonographic criteria for the differentiation of benign and malignant nodules have been described (Propper et al, 1980; Simeone et al, 1982), these are not entirely reliable (Sackler et al, 1977; Propper et al, 1980; Hung et al, 1982). Poor definition of the margin of a nodule is more commonly seen in malignant lesions (Fig. 4). A halo or echo-free rim around the thyroid nodule has been described particularly in relation to benign nodules (Scheible et al, 1979) but has also been seen in some malignant nodules (Sackler et al, 1977; Propper et al, 1980), as was noted in four of our cases of carcinoma (Fig. 3). This sign should therefore be considered non-specific and not useful in the differentiation of benign from malignant disease. Purely cystic lesions of the thyroid are generally considered to be benign (Becker et al, 1980), with an inciThe British Journal of Radiology, November 1992
Sonography in thyroid carcinoma in children
dence of malignancy of about 2% in cysts less than 3 cm in diameter (Hayles et al, 1956; Allen et al, 1979; Hammer et al, 1982). Most cysts however result from necrosis or degeneration of benign nodules, usually adenomas, adenomatous nodules or colloid cysts (Becker et al, 1980). In our present series four malignant thyroid nodules presented with a mixed echogenicity 'with echo-free or cystic areas (Figs 1, 2), but none as a pure cyst. The ability of sonography to differentiate purely cystic lesions from those that are echogenic or of mixed echogenicity is a distinct advantage over thyroid scintigraphy. On sonography, thyroid carcinomas may have a heterogenous echo pattern but are more often less echogenic than the rest of the gland, with ill-defined margins (Scheible et al, 1979; Simeone et al, 1982), but may appear well circumscribed. In our series, the echogenicity of the nodules was variable, as were the margins (Figs 1-4). This finding of non-specific echo patterns in carcinoma strongly suggests that sonographic features should be correlated with the clinical findings. Sonography is more sensitive than clinical examination or thyroid scintigraphy in the detection of additional nodules. However, it may be difficult to define separate additional nodules with sonography when they are very numerous, when they are located in the isthmus and the gland is not enlarged or when there is associated extensive lymphadenopathy as occurred in two of our patients. Sonography has also been reported to have a higher sensitivity and specificity than clinical examination in the detection of local recurrence after thyroidectomy (Simeone et al, 1987). On radionuclide study thyroid carcinomas are usually "cold" (non-functioning) but rarely may be "hot" (functioning) as was found in three of our patients. Purely cystic lesions (on sonography) are very unlikely to be malignant and also are usually "cold" on radionuclide studies. The functional information obtained on a radionuclide scan is therefore likely to be quite limited in terms of differentiating benign and malignant nodules. Primary and metastatic medullary carcinomas tend to calcify and this can be detected on plain films, sonography or CT (Wallace et al, 1970; Pearson et al, 1973; McCook et al, 1982; Schwerk et al, 1985). Lung metastases (20%), bony metastases (17%), liver metastases (20%) and a fibronodular interstitial pattern in both lungs (Wallace et al, 1970; McCook et al, 1982) may occur, as noted in one patient of our series. On sonography hypoechoic nodules with calcification have been described (Schwerk et al, 1985) and this was seen in one of our patients. Sonography has thus been recommended in the screening of members of families affected by medullary carcinoma. Radionuclide studies are not useful since the tumour does not arise from the follicular cells. However, bone and liver scintigraphy are very useful for the detection of metastatic disease (McCook et al, 1982). Although thyroid carcinoma has been found in association with Hashimoto's thyroiditis (Mauras et al, Vol. 65, No. 779
1985; Desjardins et al, 1988), we did not see this association in the present series. In the presence of large thyroid masses and/or extensive cervical lymphadenopathy, CT proved to be more useful than sonography in the delineation of the extent of the mass, particularly into the thoracic inlet and mediastinum (Fig. 5) and for the differentiation of the primary thyroid lesion from the lymphadenopathy. We feel that cervical CT (and/or magnetic resonance imaging) is specifically indicated in those unusual cases of large thyroid masses and/or extensive lymphadenopathy. Sonography is therefore an excellent technique for the evaluation of thyroid disorders in children, especially for the study of thyroid nodules and masses, and has been shown in adults to be extremely valuable for the documentation of local recurrence following thyroidectomy (Simeone et al, 1987). However, certain limitations should be kept in mind. Sonography cannot detect very small microscopic foci of malignancy (but continuing technical advances with equipment providing greater spatial resolution should improve its ability to do so). Furthermore, sonography cannot predictably differentiate benign from malignant disease and the findings must be correlated with the clinical features and histology. Although sonography can delineate the exact location of thyroid nodules and masses and their relationship to adjacent structures in the vast majority of cases, it might be difficult to achieve this in the presence of an unusually large mass or in association with extensive cervical lymphadenopathy. We therefore recommend thyroid sonography in children with single or multiple thyroid nodules. Cystic nodules which are completely echo-free on sonography are highly unlikely to be malignant. The incidence of malignancy is markedly increased in those nodules that have a varying degree of echogenicity or are of mixed echogenicity on sonography. Furthermore, an illdefined margin to the nodule is suggestive of a more aggressive lesion. A history of previous irradiation exposure should also increase the level of suspicion for malignancy. References ALLEN, F. H.,
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The British Journal of Radiology, November 1992
Sonography in thyroid carcinoma in children By tCristian J. Garcia, MD, Alan Daneman, MD, BCh, FRCPC, Kieran McHugh, MB, FRCR, *Helen Chan, MD and *Denis Daneman, MB, BCh, FRCPC Department of Radiology and the *Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8 {Received 7 January 1992 and in revised form 14 May 1992, accepted 3 June 1992) Keywords: Carcinoma, Children, Sonography, Thyroid Abstract. This paper reviews the clinical, sonographic and pathological findings of 20 children with thyroid carcinoma in an attempt to determine the value and limitations of sonography in thyroid neoplasms in this age group. Although sonography is an excellent technique for the evaluation of thyroid disorders and masses, certain limitations must be kept in mind. Microscopic foci of tumour might be missed and sonography cannot predictably differentiate benign from malignant disease. Previous radiation exposure should increase the level of suspicion for malignancy.
In children thyroid carcinoma is uncommon and constitutes 1-1.5% of all malignancies (Miller, 1985; Desjardins et al, 1988). Although sonography has been successfully used to study thyroid and extrathyroid neck masses in children (Friedmann et al, 1983; Sherman et al, 1985), its value and limitations in paediatric thyroid neoplasms have not been assessed. During the past 13 years, 40 children with thyroid carcinoma were treated at our institution and sonography was performed pre-operatively in 20 of them. This report correlates the data for these 20 patients. Material and methods
We reviewed the clinical, sonographic and pathological findings of 20 patients diagnosed as having thyroid carcinoma at the Hospital for Sick Children, Toronto, between 1977 and 1990: 10 girls and 10 boys, whose age at the time of diagnosis ranged from 6.3 to 19 years (mean =13.1 years). The sonographic examinations were performed with the patient in the supine position with a pillow under the shoulders and the neck hyperextended. No patient preparation or sedation was used. The thyroid lesions were considered hyper-, iso- or hypoechoic relative to the normal thyroid gland, echo-free or of mixed echogenicity. Six patients also had pre-operative computed tomography (CT) of the neck and 17 had at least one preoperative radionuclide thyroid scan (technetium-99m pertechnetate and/or iodine-131 scans). All patients had a chest radiograph and eight had chest CT pre-operatively. 19 patients were treated surgically with total or partial thyroidectomy and in one patient the diagnosis Address correspondence to Dr Alan Daneman, Radiologist-in-Chief, Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada. fPresent address: Departamento de Radiologia, Hospital Clinico Universidad Catolica de Chile, Marcoleta 347, Santiago, Chile, South America.
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of metastatic medullary thyroid carcinoma was made by a cervical node biopsy. Histology was available from all patients. Results
17 patients presented with an asymptomatic mass or thyroid nodule that had been present for up to two years; in three of these it was an incidental finding during routine examination. The neck mass was felt to be thyroid in origin in 14 cases and only one had multiple palpable thyroid nodules. One patient presented with hoarseness and cough and a mass was found. Two patients with known multiple endocrine neoplasia (MEN) syndrome Type lib had raised serum calcitonin levels; one of these did not have a palpable neck mass. All patients were clinically and biochemically euthyroid at the time of presentation. Five patients also had cervical lymphadenopathy. Seven patients had a history of neck or chest radiation, between two and 16 years previously, for Hodgkin's lymphoma, leukaemia, Ewing's sarcoma, metastatic Wilms' tumour or abdominal neuroblastoma. 19 patients were treated with total or partial thyroid resection. Post-operatively, ablative doses of radioactive iodine and/or L-thyroxine suppression were utilized. Histology Histology revealed papillary carcinoma in 12 cases (two with mixed papillary-follicular features), follicular carcinoma in six, and medullary carcinoma in two. The thyroid carcinoma was unicentric in 10 cases (follicular carcinoma 6, papillary carcinoma 4); in four of these it co-existed with one or two benign nodules (adenoma or colloid nodule). The carcinoma was multifocal in the other 10 (papillary carcinoma 8, medullary carcinoma 2). Of the 10 multifocal carcinomas, seven were bilateral in the gland and three unilateral. Identification of lesions on sonography
Sonography identified a single thyroid nodule or mass in 12 patients (Fig. 1) and two or more nodules in seven (Fig. 2). In one patient with medullary carcinoma and 977
C. J. Garcia, A. Daneman, K. McHugh, H. Chan and D. Danemat
Figure 1. Transverse sonogram of the thyroid in a 12-year-old girl shows a large, unicentric mass (arrows) in the right lobe. The mass has a mixed echogenicity with an echo-free periphery and echogenic centre. The trachea (T) is displaced to the left and the left lobe (t) is normal. Diagnosis: unicentric follicular carcinoma.
without a palpable thyroid mass, no definite thyroid nodules were detected and only a hyperechoic linear density was noted in the right lobe. In one patient with metastatic bilateral multifocal papillary carcinoma, contralateral involvement was suspected but the findings were equivocal. Sonography failed to detect carcinomatous involvement of the contralateral lobe in five of the seven cases with histologically proven multifocal bilateral carcinoma and in six of these the contralateral tumour foci were microscopic on histological examination (Fig. 3). Sonography also failed to detect a second 1 cm tumour nodule in the isthmus in a case of metastatic papillary carcinoma and a 0.5 cm nodule in a case of bilateral multifocal medullary carcinomas. In one patient who presented with a neck mass and extensive cervical lymphadenopathy, a metastatic lymph node was mistaken for a thyroid nodule on ultrasound examination: in this case the thyroid was small but diffusely infiltrated by a papillary carcinoma. In the three cases of unilateral multifocal involvement, sonography detected a single nodule: in two of these multiplicity was determined by multiple microscopic tumour foci.
Figure 3. Transverse sonogram of the thyroid in a 7-year-old girl shows a slightly hypoechoic, well defined nodule in the left lobe (large arrows) surrounded by a hypoechoic rim or halo (small arrows). This was shown to be a papillary carcinoma. The trachea (T) has been displaced towards the right and the right lobe of the thyroid (t) appears normal. However multiple microscopic tumour foci were noted histologically on the right.
Appearance of lesions on sonography The malignant lesions had an ill-defined margin in eight cases (Fig. 4) and were relatively well defined in 11 (Figs 1, 3). In the four patients in whom a unicentric carcinoma co-existed with benign nodules, the margins of the benign nodules were well defined in three and slightly ill-defined in one (Fig. 2). The size of the lesions varied from 1.5 to 4.5 cm in maximum diameter and the echogenicity was variable (Figs 1-4). The lesions were hyperechoic in six cases,
Figure 2. Multinodular thyroid gland in a 19-year-old boy with a history of chest and abdominal radiation 16 years previously because of pulmonary metastases from Wilms' tumour, (a) Longitudinal sonogram of the right lobe of the thyroid shows a relatively well defined nodule (arrows) of mixed echogenicity with multiple echo-free areas, shown to be a unicentric follicular carcinoma, (b) Longitudinal sonogram of the left lobe shows a smaller hypoechoic nodule (arrows) that was shown histologically to be an adenoma.
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Sonography in thyroid carcinoma in children
Figure 4. Longitudinal sonogram of the left lobe of the thyroid in a 16-year-old girl shows marked enlargement of the lobe (arrows) and a diffuse, ill-defined inhomogenous echo pattern. This was shown histologically to be a multifocal, unilateral papillary carcinoma.
hypoechoic in five, and isoechoic in three. In five cases the lesions were of mixed echogenicity with some echofree cystic areas, and in one case the echo pattern was inhomogenous. In none of the cases was a completely echo-free lesion noted. A halo or hypoechoic rim surrounding the nodule was present in four cases of bilateral multifocal papillary carcinoma. Calcified nodules were detected bilaterally in one case of multifocal medullary carcinoma and in one multifocal papillary carcinoma. The benign lesions also had variable echogenicity (hyperechoic 2 (one with halo), hypoechoic 1, echo-free 1)-
Figure 5. Computed tomograph (after intravenous contrast medium enhancement) of the upper chest in a 7-year-old girl with a mixed papillary-follicular carcinoma. The scan shows a mass of low attenuation (arrows) extending from the lower part of the thyroid through the thoracic inlet into the upper mediastinum on the left. The mass lies anterolateral to the trachea (T).
sonography. In one patient, CT identified extension of the tumour into the thoracic inlet (Fig. 5) and in two extensive adenopathy was noted. In two patients, lung metastases were detected on chest radiography and chest CT at the time of presentation and in one of these (medullary carcinoma) the lung metastases were calcified. This latter patient also had bony, hepatic and retroperitoneal metastases. The chest radiograph and/or chest CT were negative in all the other cases.
Discussion , Thyroid carcinoma may occur at any age and approximately 5-10% of cases occur in patients younger than 21 years (Zohar et al, 1986; Desjardins Radionuclide scans et al, 1988; Ceccarelli et al, 1988; Zimmerman et al, 15 of the radionuclude studies were considered 1988). It accounts for approximately 1.5% of all paediaabnormal and demonstrated a single "cold" lesion in tric cancers and 5% of malignancies involving the head nine patients, multiple cold lesions in three, single "hot" and neck in children (Miller, 1985; Desjardins et al, lesions in two and both cold and hot lesions in one. In 1988). Although in most series it is at least twice as two cases (medullary carcinoma 1, papillary carcinoma common in girls as in boys (Joppich et al, 1983; 1) the radionuclide study was normal. Desjardins et al, 1988; Ceccarelli et al, 1988; Zimmerman et al, 1988), we found no difference in sex distribution. Although thyroid carcinoma tends to be Other diagnostic modalities employed Six patients had computed tomography (CT) of the more advanced both locally and systemically at the time neck and in four of these the thyroid mass or masses of the diagnosis in children than in adults, the prognosis were easily identified. In the fifth it was difficult to is better in patients younger than 21 years than in older identify the thyroid mass separately from the adjacent people (Joppich et al, 1983; Zohar et al, 1986; extensive cervical lymphadenopathy. In the sixth patient Zimmerman et al, 1988). This is based on an excellent (medullary carcinoma) the gland was extremely small response in children to surgical treatment, followed by and CT, like sonography, failed to document a thyroid ablation of the thyroid remnant by radioactive iodine and thyroid suppression with L-thyroxine. mass. The thyroid masses showed low or patchy attenuaMetastatic involvement of the cervical lymph nodes tion. In one case of medullary carcinoma, calcified has been reported to be the most common presenting nodules were noted that had been demonstrated by symptom of thyroid carcinoma in children and may be Vol. 65, No. 779
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C. J. Garcia, A. Daneman, K. McHugh, H. Chan and D. Daneman
present in 30-90% of cases at the time of diagnosis (Reiter et al, 1981; Zohar et al, 1986; Desjardins et al, 1988; Zimmerman et al, 1988). In our series only seven cases (35%) had cervical lymphadenopathy at the time of presentation, but six of them also had thyroid nodules. However, a painless thyroid nodule or mass without associated symptoms may also be the first sign (Sherman et al, 1985) occurring in the majority of our cases (60%). Less frequently they metastasize to the lungs and occasionally to bone and other structures. Approximately 6-14% present with lung metastases at the time of diagnosis (Hopwood et al, 1976; Ceccarelli et al, 1988; Zimmerman et al, 1988), as occurred in two of our patients (10%). Most children with thyroid carcinoma are euthyroid although rarely they may present with hyperthyroidism (Kirkland et al, 1973; Hopwood et al, 1976). There is a significant association between thyroid neoplasms and previous exposure to ionizing radiation to the head and neck (Hagler et al, 1966; Refetoffet al, 1975; Cerletty et al, 1978; Walsh et al, 1978; Fleming et al, 1985), with a latency period that may be as long as 25 years (Miller, 1985; Zohar et al, 1986). This predisposing factor has been reported in 20-50% of children with thyroid carcinoma (Segal et al, 1985; Zohar et al, 1986) and occurred in 35% of our patients. However, the number of cases of thyroid malignancy related to radiation might increase with the improved survival of childhood malignancies in general. It has been reported that the incidence of malignancy in multinodular glands is lower (1-7%) than that in solitary nodules (10-25%) (Brown, 1981; Miller, 1985). However, according to McCall et al (quoted by Austin, 1982) there is no significant difference between the incidence of carcinoma in multinodular goitre and in that of solitary cold nodules after exclusion of those patients with factors which predispose to neoplasia (e.g. history of radiation exposure, multiple endocrine neoplasia syndrome). In a review of 16 cases with multinodular gland in children at our institution, we found four (25%) to be associated with carcinoma, three of whom had had neck radiation. In general a history of previous radiation, rapid enlargement of a thyroid nodule, cervical lymphadenopathy and hoarseness are all suggestive of malignancy (Reiter et al, 1981). Histologically the most common types are the well differentiated pure or mixed papillary and follicular carcinomas (90% in our series). Medullary carcinoma (10%) is far less frequent and anaplastic carcinomas are extremely rare in children (McCook et al, 1982; Miller, 1985; Zohar et al, 1986). Papillary or mixed papillary follicular carcinomas are frequently multicentric and bilateral and it is unclear whether they represent metastases or multifocal origin of the neoplasm (Reiter et al, 1981; Desjardins et al, 1988), and this is in accordance with our series. Multifocal thyroid carcinoma is more commonly associated with radiation (Cerletty et al, 1978; Walsh et al, 1978; Fleming et al, 1985) but often the lesions are less than 1 cm in size (Hagler et al, 1966). 980
In our series, all patients with a history of irradiation had multiple thyroid nodules, because of multifocal carcinoma in three cases and associated benign lesions in four (adenomas in two and a colloid nodule in two) (Fig. 2). Benign and malignant lesions may therefore coexist following radiation, as previously reported. (Hagler et al, 1966; Austin, 1982). Medullary thyroid carcinoma accounts for approximately 3.5-10% of all thyroid cancers at all ages (McCook et al, 1982) and occurs most commonly between the ages of 30 and 60. Although rarely diagnosed before 10 years, it has been reported even during the second year of life (Stjerholm et al, 1980), but C-cell hyperplasia is more likely to be seen in younger patients (Graze et al, 1978; Stjerholm et al, 1980; Jones & Sisson, 1983; Desjardins et al, 1988). The lesion most commonly occurs sporadically (80-90%) but may occur in families as a component of the multiple endocrine neoplasia II (MEN-II) syndrome (20%) (McCook et al, 1982; Desjardins et al, 1988). In the latter it is commonly associated with adrenal phaeochromocytoma and hyperplasia of the parathyroid glands (MEN-IIa). MEN-IIb is a less common form and consists of elements of MEN-IIa together with features of marfanoid habitus, mucosal neuromas and intestinal ganglioneuromatosis (McCook et al, 1982; Desjardins et al, 1988). This neoplasm is always associated with raised serum calcitonin levels (McCook et al, 1982; Jones & Sisson, 1983) which may be detected in screening studies performed because of the presence of other clinical features of the syndrome or of a neck mass (McCook et al, 1982; Desjardins et al, 1988). The thyroid lesions may be bilateral in approximately 20% of sporadic cases and 90% of those lesions associated with MEN II syndromes (Graze et al, 1978; McCook et al, 1982; Jones & Sisson, 1983) and was present in our two patients with MEN lib. Thyroid sonography has been used mainly in adults to differentiate solid from cystic lesions, solitary from multifocal lesions and thyroid from extrathyroidal lesions (Sackler et al, 1977; Scheible et al, 1979; Simeone et al, 1982; Walker et al, 1985). High resolution equipment allows detection of nodules as small as 2-3 mm (Sackler et al, 1977; Walker et al, 1985). Although sonographic criteria for the differentiation of benign and malignant nodules have been described (Propper et al, 1980; Simeone et al, 1982), these are not entirely reliable (Sackler et al, 1977; Propper et al, 1980; Hung et al, 1982). Poor definition of the margin of a nodule is more commonly seen in malignant lesions (Fig. 4). A halo or echo-free rim around the thyroid nodule has been described particularly in relation to benign nodules (Scheible et al, 1979) but has also been seen in some malignant nodules (Sackler et al, 1977; Propper et al, 1980), as was noted in four of our cases of carcinoma (Fig. 3). This sign should therefore be considered non-specific and not useful in the differentiation of benign from malignant disease. Purely cystic lesions of the thyroid are generally considered to be benign (Becker et al, 1980), with an inciThe British Journal of Radiology, November 1992
Sonography in thyroid carcinoma in children
dence of malignancy of about 2% in cysts less than 3 cm in diameter (Hayles et al, 1956; Allen et al, 1979; Hammer et al, 1982). Most cysts however result from necrosis or degeneration of benign nodules, usually adenomas, adenomatous nodules or colloid cysts (Becker et al, 1980). In our present series four malignant thyroid nodules presented with a mixed echogenicity 'with echo-free or cystic areas (Figs 1, 2), but none as a pure cyst. The ability of sonography to differentiate purely cystic lesions from those that are echogenic or of mixed echogenicity is a distinct advantage over thyroid scintigraphy. On sonography, thyroid carcinomas may have a heterogenous echo pattern but are more often less echogenic than the rest of the gland, with ill-defined margins (Scheible et al, 1979; Simeone et al, 1982), but may appear well circumscribed. In our series, the echogenicity of the nodules was variable, as were the margins (Figs 1-4). This finding of non-specific echo patterns in carcinoma strongly suggests that sonographic features should be correlated with the clinical findings. Sonography is more sensitive than clinical examination or thyroid scintigraphy in the detection of additional nodules. However, it may be difficult to define separate additional nodules with sonography when they are very numerous, when they are located in the isthmus and the gland is not enlarged or when there is associated extensive lymphadenopathy as occurred in two of our patients. Sonography has also been reported to have a higher sensitivity and specificity than clinical examination in the detection of local recurrence after thyroidectomy (Simeone et al, 1987). On radionuclide study thyroid carcinomas are usually "cold" (non-functioning) but rarely may be "hot" (functioning) as was found in three of our patients. Purely cystic lesions (on sonography) are very unlikely to be malignant and also are usually "cold" on radionuclide studies. The functional information obtained on a radionuclide scan is therefore likely to be quite limited in terms of differentiating benign and malignant nodules. Primary and metastatic medullary carcinomas tend to calcify and this can be detected on plain films, sonography or CT (Wallace et al, 1970; Pearson et al, 1973; McCook et al, 1982; Schwerk et al, 1985). Lung metastases (20%), bony metastases (17%), liver metastases (20%) and a fibronodular interstitial pattern in both lungs (Wallace et al, 1970; McCook et al, 1982) may occur, as noted in one patient of our series. On sonography hypoechoic nodules with calcification have been described (Schwerk et al, 1985) and this was seen in one of our patients. Sonography has thus been recommended in the screening of members of families affected by medullary carcinoma. Radionuclide studies are not useful since the tumour does not arise from the follicular cells. However, bone and liver scintigraphy are very useful for the detection of metastatic disease (McCook et al, 1982). Although thyroid carcinoma has been found in association with Hashimoto's thyroiditis (Mauras et al, Vol. 65, No. 779
1985; Desjardins et al, 1988), we did not see this association in the present series. In the presence of large thyroid masses and/or extensive cervical lymphadenopathy, CT proved to be more useful than sonography in the delineation of the extent of the mass, particularly into the thoracic inlet and mediastinum (Fig. 5) and for the differentiation of the primary thyroid lesion from the lymphadenopathy. We feel that cervical CT (and/or magnetic resonance imaging) is specifically indicated in those unusual cases of large thyroid masses and/or extensive lymphadenopathy. Sonography is therefore an excellent technique for the evaluation of thyroid disorders in children, especially for the study of thyroid nodules and masses, and has been shown in adults to be extremely valuable for the documentation of local recurrence following thyroidectomy (Simeone et al, 1987). However, certain limitations should be kept in mind. Sonography cannot detect very small microscopic foci of malignancy (but continuing technical advances with equipment providing greater spatial resolution should improve its ability to do so). Furthermore, sonography cannot predictably differentiate benign from malignant disease and the findings must be correlated with the clinical features and histology. Although sonography can delineate the exact location of thyroid nodules and masses and their relationship to adjacent structures in the vast majority of cases, it might be difficult to achieve this in the presence of an unusually large mass or in association with extensive cervical lymphadenopathy. We therefore recommend thyroid sonography in children with single or multiple thyroid nodules. Cystic nodules which are completely echo-free on sonography are highly unlikely to be malignant. The incidence of malignancy is markedly increased in those nodules that have a varying degree of echogenicity or are of mixed echogenicity on sonography. Furthermore, an illdefined margin to the nodule is suggestive of a more aggressive lesion. A history of previous irradiation exposure should also increase the level of suspicion for malignancy. References ALLEN, F. H.,
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