World J Surg (2010) 34:1254–1260 DOI 10.1007/s00268-010-0391-x
Diagnostic Utility of Fine-Needle Aspiration Cytology in Pediatric Differentiated Thyroid Cancer Anna E. Bargren • Goswin Y. Meyer-Rochow Mark S. Sywak • Leigh W. Delbridge • Herbert Chen • Stan B. Sidhu
•
Published online: 21 January 2010 Ó Socie´te´ Internationale de Chirurgie 2010
Abstract Background Pediatric patients present with thyroid nodules less often than adults, but the rate of malignancy is much higher. This study was designed to determine the ability of fine-needle aspiration cytology (FNA) to diagnose accurately and facilitate management of thyroid neoplasms in pediatric patients. Methods A retrospective study revealed 110 patients \19 years old who had undergone thyroid surgery and FNA biopsy at two academic institutions over the last 28 years. FNA sensitivity for diagnosing papillary thyroid cancer (PC) and follicular neoplasm (FN) was investigated. Results Of 110 patients who presented for surgery, 27 had PC and 33 had a FN: 4 follicular carcinomas (FCs) and 29 follicular adenomas (FAs). Among the PCs patients, the FNA results were as follows: 1 (4%) nondiagnostic, 6 (22%) atypical, 2 (7%) benign, and 18 (67%) malignant lesions. The sensitivity of a malignant FNA was 90% for diagnosing a PC. Sensitivity of an atypical FNA was 75% for FCs and 69% for FAs, giving an overall FN sensitivity of 70%. Of the atypical FNA readings, 60% had confirmed histological atypical features, and 19% were malignant. In
A. E. Bargren H. Chen (&) Section of Endocrine Surgery, Department of Surgery, H4/722 Clinical Science Center, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792, USA e-mail:
[email protected] A. E. Bargren e-mail:
[email protected] G. Y. Meyer-Rochow M. S. Sywak L. W. Delbridge S. B. Sidhu Endocrine Surgical Unit, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, Australia
123
95% of the malignant FNA reports, final histology confirmed PC, resulting in a positive predictive value of 95%. Conclusions FNA biopsy can reliably diagnose malignancy in pediatric thyroid patients and should be used as a standard technique to indicate surgical treatment. Atypical or suspicious FNA results do not predict cancer effectively, confirming the current accepted practice for adults that diagnostic excision is required to exclude malignancy in pediatric patients.
Introduction Thyroid cancer accounts for 1–3% of all malignancies in the adult population [1–3]. Patients usually present with a thyroid nodule, which is biopsied using fine-needle aspiration (FNA) to obtain a cytologic diagnosis prior to definitive surgical management. Palpable thyroid nodules are present in an estimated 3–7% of adults [4]. With advanced screening techniques such as ultrasonography (US), thyroid nodules can be detected in 13–50% of the adult population [4–7]. Approximately 5% of thyroid nodules are malignant [8–10]. With early diagnosis and appropriate surgical and radioiodine treatment, the mortality rate from thyroid cancer is less than 1% [2, 11]. Papillary thyroid cancer (PC) is the most common subtype, representing 80–90% of all thyroid cancers [1, 2]. Palpable thyroid nodules are less common in children and adolescents, with an incidence of 1.5% [12]. However, the rate of malignancy among pediatric thyroid nodules is approximately 16%, about three times that of adults [13, 14]. Pediatric patients also have a much greater incidence of lymph node metastasis (40–80%) and distant metastasis (25%) when compared to that in adults [6, 15–24]. Differentiated thyroid cancer (DTC) is the most common type
World J Surg (2010) 34:1254–1260
of thyroid malignancy in children and encompasses both papillary (80–95%) and follicular (5–15%) carcinomas [17, 19, 21, 22, 25, 26]. The incidence of multifocal tumors varies among studies, ranging from 20 to 55% [17, 18, 21, 23]. Neither size nor number of nodules has been shown to be predictive of malignancy [4, 9, 27]. Whereas younger patients present with more extensively metastatic tumors, overall thyroid cancer rates are higher in older children, comprising 1% of all cancers in patients \15 years of age and 7% in patients 15–19 years of age [11, 21]. As in adults, pediatric thyroid cancer is also more common in girls (62–75%) than in boys (15–38%) [17, 19, 22, 24, 28]. Within DTC, the sex ratio varies with age, peaking at puberty (14–16 years old) [2, 19]. Other risk factors for thyroid cancer in the pediatric population include familial disease and radiation exposure [4]. Although pediatric thyroid cancer patients present with a more advanced stage of disease than adults, they have a better overall prognosis for survival, with 5- and 10-year survival rates of 99.5 and 98.5%, respectively [2, 17, 21]. The American Association of Clinical Endocrinologists/ Associazione Medici Endocrinologi Task Force guidelines recommend that any thyroid nodule [ 1 cm, or a suspicious nodule \ 1 cm, should undergo FNA cytology [4, 6]. FNA is an accurate diagnostic test for detecting thyroid malignancy and can greatly help physicians and surgeons establish an effective management strategy [4–6, 9, 29, 30]. The use of FNA for the diagnosis of thyroid nodules has been studied extensively in adults and is widely acknowledged as a safe, cost-effective, reliable test. FNA has been demonstrated to have a mean sensitivity of 83% (range 65– 98%) and mean specificity of 92% (range 72–100%) [4, 9, 27, 30–34]. False-negative FNA results vary from 1 to 11%; however, this number differs greatly among laboratories and is heavily dependent on the experience of the cytologist [4, 9, 31]. FNA use has increased cancer yield at surgery up to 50% [9]. In the past, the low incidence of pediatric thyroid cancer has led to only a few FNA studies, and they have reported inconsistent results [26, 35]. Concerns over FNA use in the pediatric population include complications resulting from small neck size and the need for restraints or heavy sedation during the procedure [29]. When FNA is performed, however, most children are being diagnosed and treated in a manner similar to adults [36, 37]. Although there is no clear consensus on the reporting of thyroid FNA results, they are generally divided into four diagnostic categories: nondiagnostic, benign, atypical, and malignant. A diagnostic FNA result is defined as having six groups of cells containing at least 10 cells each, which allows interpretation of characteristics that are indicative of a specific cancer or thyroid condition. Past studies have shown that a nondiagnostic or inadequate FNA result
1255
occurs in 10% to 20% of FNA tests [4, 9, 26, 30, 35, 38– 41]. Benign FNA results can indicate a cyst, colloid nodule, multinodular goiter, lymphocytic thyroiditis, or other benign thyroid pathology. Atypical FNA results can present a diagnostic challenge, as they can include a variety of both benign and malignant nodules. Samples grouped in this category are determined to be ‘‘atypical’’ or ‘‘suspicious’’ but are not diagnostic owing to poorly defined criteria. Hu¨rthle cell and follicular neoplasms (follicular adenomas and follicular carcinomas) cannot be accurately classified as malignant or benign by FNA. The cytologic result is, instead, designated an ‘‘atypical neoplasm,’’ with adenoma or carcinoma clarified upon surgical pathology. Of atypical FNA results, 20–50% are malignant in adult populations, with the pediatric rate closer to 50% [9, 14, 34, 42]. Because of the high incidence of cancerous nodules, surgery of all atypical nodules is recommended in adults as well as children [9, 14]. Malignant results include all other forms of thyroid cancer. Most subtypes of PC can be readily identified by FNA cytology characteristics, which include increased cellularity, cells organized in sheets or papillary cell groups, and nuclear differences such as intracellular holes and grooves [9]. Current treatment recommendations for pediatric thyroid cancer include total thyroidectomy, lymph node dissection, and radioiodine treatment [21, 23, 25, 43–45]. Because residual disease is discovered in up to 33% of pediatric patients who undergo less than total thyroidectomy and lymph node dissection—which necessitates completion surgery in 15–25% of these patients—an aggressive primary procedure is suggested to lower the risk of disease recurrence [17, 18, 20, 23, 25, 46]. Initial bilateral central (level VI) compartment lymph node dissection has been shown to reduce the need for repeat surgery from 20.6 to 7.2% [18]. Total thyroidectomy also allows the use of follow-up radioiodine imaging and thyroglobulin measures for detecting disease recurrence. With high rates of metastasis and unknown multifocality in the pediatric population, total thyroidectomy is now recommended regardless of tumor size or the increased risk of morbidity incurred by radical surgery [17, 20]. This study was designed to determine the ability of FNA to diagnose accurately and facilitate management of thyroid neoplasms in pediatric patients.
Materials and methods Data collection A retrospective review of 497 patients \ 19 years old who had thyroid surgery between June 1980 and June 2008 at
123
1256
World J Surg (2010) 34:1254–1260
the University of Wisconsin Hospital and Clinics (United States) and the University of Sydney Endocrine Surgical Unit (Australia) was performed. Among these subjects, 110 surgical patients also had undergone FNA biopsy of a thyroid nodule within a year prior to surgery. [Of note, it is standard practice at both institutions to perform FNA under US guidance; however, prior to the mid-1990s records were not available as to whether US was being used on all or selected patients.] This cohort of 110 patients was used for all subsequent analysis. All FNA biopsy and final histology results were reviewed. For the purposes of statistical analysis, FNA cytology results were categorized as nondiagnostic, benign, malignant, or atypical. Patients who had an incidental thyroid cancer identified postoperatively on surgical histology were eliminated from the cohort, as the FNA did not target this focus.
(48/110) were atypical, and 17% (19/110) were malignant. PC and FN were the most common final diagnoses. Other pathology included goiter, Hashimoto’s thyroiditis, Hu¨rthle cell neoplasm, Grave’s disease, and benign colloid nodule. Patient demographics of the entire cohort are summarized in Table 1, and FNA results are shown in Table 2.
Groupings
Malignant FNA
Analysis based on tumor type—papillary thyroid cancer (PC) or follicular neoplasm (FN)—patient age, year of surgery and thyroid nodule size was performed. Age was split into categories of \15 years and 15–19 years in accordance with a number of similar studies. Date of surgery was classified by 10-year increments, including 1980– 1989, 1990–1999, and 2000–2008. Thyroid nodule size groups were \1 cm, 1–3 cm, and [3 cm.
There were 19 malignant cytology results and of these, 18 patients (95%) were diagnosed with PC. The remaining false positive patient was diagnosed with a goiter upon surgical histology. The PPV for a malignant FNA was 95% for PC and 0% for FC. Surgical treatment of patients who
Statistical definitions
Atypical FNA Of 48 atypical FNA results, 64% were confirmed to have atypical features (either malignant or benign) upon final histologic diagnosis. Of the atypical FNAs, 19% were malignant including 3 FCs (6%) and 6 PCs (13%). Altogether, 23% of these patients underwent total thyroidectomy; the remaining 77% had less aggressive surgery, such as lobectomy or isthmus removal.
Table 1 Patient demographics Parameter
No.
%
Age (years)
Pediatric patients with a final diagnosis of PC or FN were analyzed with this system based on their initial FNA readings. In the PC group, benign FNA readings were considered false-negative results, and malignant FNAs were true-positive results. In the FN group, an atypical FNA report was considered a true-positive result for both follicular adenoma (FA) and follicular carcinoma (FC) as the designation of follicular ‘‘carcinoma’’ can only be established upon final surgical pathology by the presence of capsular invasion, whereas a benign FNA result was considered falsely negative. False-positives were defined as cases diagnosed as malignant by cytology but that were revealed to be benign upon final histology. FNA sensitivity for PC and FN detection was determined using these definitions of true-positive and false-negative. The positive predictive value (PPV) of atypical and malignant FNA readings from the 110-patient cohort was also established.
Results Of the FNA cohort presenting for surgery, 9% (10/110) were nondiagnostic, 30% (33/110) were benign, 44%
123
Average
14.6
Range
5–19
\15
43
39
15–19
65
59
Male
20
18
Female
90
82
1980–1989
26
24
1990–1999 2000–2008
33 51
30 46
Gender
Date of surgery
Table 2 Fine-needle aspiration results Parameter
No.
%
Total FNAs
110
100
FNA result Nondiagnostic
10
9
Benign
33
30
Atypical Malignant
48 19
44 17
FNA fine-needle aspiration
World J Surg (2010) 34:1254–1260
had a malignant FNA consisted of 95% total thyroidectomy, and 5% lobectomy.
1257 Table 3 Patients with papillary thyroid cancer and FNA cytology Parameter
No. %
FNA
Sensitivity
ND B
A M
Papillary thyroid cancer PC statistical definition
Of the pediatric patient cohort, 25% (27/110) had a surgical diagnosis of PC. In all, 4 lobectomies (15%) and 23 thyroidectomies (85%) were performed. There were 18 cases (63%) of lymph node metastasis. Five patients (19%) with PC had a history of previous neck irradiation: four to treat lymphoma and one for medulloblastoma. One patient (4%) had a nondiagnostic FNA result, and 26 (96%) had diagnostic FNAs, which were subclassified as 2 benign (7%), 18 malignant (67%), and 6 atypical (22%). The FNA sensitivity for the diagnosis of PC was 90% in pediatric patients. There were 20 girls (74%) and 7 boys (26%). The average age at the time of surgery was 14.9 years (range 5– 18 years). There were 7 patients \15 years old and 20 patients 15–19 years old. These age groups had FNA sensitivities for PC of 86 and 92%, respectively. PC nodules were \1 cm in 3 patients (12%), between 1 and 3 cm in 11 patients (42%) and [3 cm in 6 patients (19%). The average nodule was 2.2 cm (range 0.2–5.0 cm). The smaller two nodule size groups had a sensitivity of 100%, and nodules [ 3 cm had a sensitivity of 83%. Nine patients had multinodular disease (45%) compared to 11 patients who had a single nodule (55%). Their sensitivities were 100 and 89%, respectively. Four patients underwent FNA and surgery for PCs during the 1980–1989 period, 5 during 1990–1999, and 18 during 2000–2008. The sensitivities for FNA during those intervals were 50%, 100%, and 93%, respectively (Table 3). Follicular neoplasm Of the 110 patients, 33 (31%) had FN, of which 4 were FC (12%) and 29 were FA (88%). In all, 26 lobectomies (79%) and 4 total thyroidectomies (12%) were performed. Of the four patients with FC, there were one benign (25%) and three atypical (75%) FNA results. The sensitivity of a malignant FNA result to detect FC was 0%, whereas the sensitivity of an atypical result for FC detection was 75%. The 29 FA patients had FNA results consisting of 3 nondiagnostic (10%), 8 benign (28%), and 18 atypical (62%). The sensitivity of an atypical FNA was 69% for FA. The overall sensitivity of an atypical FNA to detect FN in pediatric surgery patients was 70%. There were 29 girls (88%) and 4 boys (12%) with FN. In all, 16 patients (48%) were \15 years old and had an FNA sensitivity of 54% for FN; and 17 patients (52%) were 15–18 years old with an
PC patients
– 27
100 1
FN –
TP
2
18
6
0.90
Patient demographics Age \15
7
26 0
1
0
6
0.86
15–18
20
74 1
1
6
12
0.92
Gender Male
7
26
20
74
Female Date of surgery 1980–1989
4
15 1
1
1
1
0.50
1990–1999
5
19 0
0
1
4
1.00
2000–2008
18
67 0
1
4
13
0.93
Disease characteristics Nodule size \1.0 cm 1.0–2.9 cm
3
11 0
0
0
3
1.00
11
41 0
0
3
8
1.00
[3.0 cm
6
22 0
1
0
5
0.83
NA
7
26 1
1
3
2
0.67
11
41 0
1
2
8
0.89
9 7
33 0 26
0
1
8
1.00
# nodules 1 [1 NA
PC papillary thyroid cancer, ND non-diagnostic, B benign, A atypical, M malignant, NA not available
FNA sensitivity of 76%. The average age at the time of surgery was 14.2 years (range 5.0–18.8 years). Of the 33 FN patients with FNA, 29 had information available on the thyroid nodule size. The average nodule size was 2.4 cm (range 1.0–7.5 cm). Altogether, 21 nodules were 1–3 cm, and 8 were [3 cm. The two groups had an FNA sensitivity for FN detection of 72 and 50%, respectively (Tables 4, 5). Ten operations (30%) took place during the 1980–1989 period, 11 (33%) during 1990–1999, and 12 (36%) during 2000–2008. The FNA sensitivities for those intervals were 75, 70, and 58%, respectively.
Discussion In adult patients with thyroid nodules, FNA has been proven to be an efficient, safe, reliable method for diagnosis. Although thyroid nodules are less common in pediatric patients, the rate of malignancy is much higher than in adults [13, 14]. The lack of studies and low incidence of pediatric thyroid cancer have limited conclusive evidence
123
1258
World J Surg (2010) 34:1254–1260
Table 4 Patients with a follicular neoplasm and FNA cytology Parameter
No. %
FNA
Sensitivity
ND B FN statistical definition
–
A
M
FN TP TP
FN patients
33
100 3
9
21
0
0.70
FA
29
88 3
8
18
0
0.69
FC
4
12 0
1
3
0
0.75
16 17
48 3 52 0
6 4
7 13
0 0
0.54 0.76
Patient demographics Age \15 15–18 Gender Male
4
12
29
88
1980–1989
10
30 2
2
6
0
0.75
1990–1999
11
33 1
3
7
0
0.70
2000–2008
12
36 0
5
7
0
0.58
Female Date of surgery
Disease characteristics Nodule size (cm) \1.0 cm
0
0 0
0
0
0
1–3 cm
21
64 3
5
13
0
0.72
[3 cm
8
24 0
4
4
0
0.50
NA
4
12 0
0
4
0
1.00
ND non-diagnostic, B benign, A atypical, M malignant, NA not available Table 5 Diagnostic sensitivity of FNA Type
Sensitivity
PC
0.90
FN
0.70
FA
0.69
FC
0.75
PC papillary thyroid cancer, FN follicular nodule, FA follicular adenoma, FC follicular carcinoma
on the reliability of FNA biopsy in this population [26, 35]. Sensitivity values range from 60 to 100%, with some studies having as few as 12 patients in a cohort [14, 26, 29, 36, 47]. The demographics of the patient cohort in our study resembled characteristics seen in other pediatric studies [11, 17, 19, 21, 22, 24–26, 28]. Among the children and adolescents requiring thyroid surgery, there were more girls (82%) than boys (18%). The incidence of PC increased with age, with most (74%) being 15–19 years old. Also notable was the fact that 19% of patients with PC had prior exposure to neck irradiation. In our study, 9% of the FNA procedures were nondiagnostic. Nondiagnostic results may be due to a sampling
123
error, high cystic fluid concentration, or incorrect pathologist interpretation. Studies have shown that a highly experienced cytopathologist is recommended to reduce the number of nondiagnostic FNAs [48, 49]. It is also suggested that a nodule be aspirated at three or four different sites and that several nodules be aspirated in patients with multinodular disease [9, 38]. Many FNAs are now guided by US (US-FNA), which decreases the number of nondiagnostic results by providing clear visualization of the inserted needle and reducing the risk of cystic fluid contamination. US-FNA is especially useful for examining small and nonpalpable nodules [31, 32, 50, 51]. Of the children and adolescents in our study who underwent an FNA biopsy for a suspicious thyroid nodule, 90% had a diagnostic result. This number is comparable to that in the adult population, which has been reported to have an 87% rate of diagnostic results [4, 9, 30, 39, 41]. Our study demonstrated that pediatric patients who are diagnosed with PC by an FNA biopsy have a 90% chance of confirmed PC upon final histology. This suggests that FNA is a highly diagnostic tool in children and adolescents with PC, capable of facilitating the appropriate primary surgical procedure. Our results also show a 63% chance of lymph node metastasis in pediatric PC patients, supporting the argument for prophylactic central lymph node clearance or therapeutic clearance of involved lymph node regions along with total thyroidectomy [21, 23, 25, 43–45, 52]. Pediatric thyroid nodules that were diagnosed as atypical on FNA had a 60% chance of having atypical cellular features verified upon final histology. There was a 19% chance of malignancy (13% PC, 6% FC). Other studies cite up to 50% pediatric malignancy in atypical FNA results [14], whereas our study more closely reflects the adult value of 20% [9, 34]. This suggests that more cancerous cases were correctly identified as malignant by FNA, a narrower category than atypical. As expected, FNA was not a reliable diagnostic test for distinguishing FC from FA. Because atypical FNA results were accepted as correct for both FC and FA patients, a malignant FNA would be needed to discern a nodule with FC. None of the FC cases in our study were detected as malignant by FNA as FC is defined by capsular invasion, a feature that can only be detected upon final histology. With 70% sensitivity of an atypical result and a 19% risk of malignancy, all pediatric patients with an atypical FNA result should undergo surgery for a confirmative diagnosis and appropriate management. Limitations of FNA include the inability to diagnose incidentalomas. Although studies demonstrate that FNA accuracy is not limited by the size of a nodule [38, 53], it is impossible to target an incidentaloma with biopsy because, by definition, these nodules are undetected by palpation or
World J Surg (2010) 34:1254–1260
US, being discovered only upon final surgical histology. Concerns are also present with FNA use in multifocal tumors, which occur in 20–50% of pediatric patients [17, 18, 21, 23]. This correlated with our study, in which 41% of patients with PC had multiple nodules. If the dominant nodule is the only focus aspirated, the cancer cells may be missed as neither size nor number of nodules are predictive of malignancy [6]. Three patients with malignancy (two PCs, one FC) had a false-negative benign FNA diagnosis. The patient with PC underwent FNA and surgery in 1980, at a time with FNA had been established as a diagnostic technique for only a few years. Unfortunately, these cytology slides have been discarded and could not be reexamined. In addition to standard errors experienced with FNA biopsy mentioned previously, this false-negative test may have been the result of hand-guided FNA biopsy or pathologist inexperience. The remaining PC and FC patient files were also examined; however, no specific explanation could be determined for this error outside of the standard FNA limitations. The results of this study support that FNA biopsy should be used in all pediatric patients with suspicious thyroid nodules, regardless of age or sedation requirements. Among the 110 pediatric patients, 27 (25%) had a malignant nodule that was identified as malignant or suspicious by FNA biopsy. Without a reliable biopsy, these patients would have required an initial diagnostic hemithyroidectomy and subsequently a second procedure for completion thyroidectomy after histologic confirmation of malignancy. Accurate FNA results can prevent sequential surgeries, ensuring that the cancer is appropriately managed with the primary procedure and thereby reducing the surgical and anesthetic risks and discomfort of a second surgical procedure. An atypical FNA result does not accurately predict cancer and cannot distinguish between FA and FC; however, there remains a 19% risk of malignancy, indicating that all patients with an atypical biopsy result require diagnostic thyroid resection. FNA biopsy is a highly accurate preoperative diagnostic test for the detection of PC, reliably allowing surgeons to plan definitive surgery in pediatric patients with PC and eliminate the need for a diagnostic primary surgery. The results of this study are comparable with those of adult FNA studies and demonstrate that pediatric patients should follow a similar diagnostic course, including the use of FNA as an indication of thyroid nodule malignancy. Acknowledgments The authors thank Pamela Edhouse, University of Sydney Endocrine Surgical Department, Royal North Shore Hospital, St. Leonards, NSW, Australia, for her assistance with patient data acquisition.
1259
References 1. Schlumberger M (2007) Papillary and follicular thyroid carcinoma. Ann Endocrinol (Paris) 68:120–128 2. Parisi MT, Mankoff D (2007) Differentiated pediatric thyroid cancer: correlates with adult disease, controversies in treatment. Semin Nucl Med 37:340–356 3. Skinner MA (2001) Cancer of the thyroid gland in infants and children. Semin Pediatr Surg 10:119–126 4. AACE/AME Task Force on Thyroid Nodules (2006) American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 12:63–102 5. Castro MR, Gharib H (2003) Thyroid fine-needle aspiration biopsy: progress, practice, and pitfalls. Endocr Pract 9:128–136 6. Cooper DS, Doherty GM, Haugen BR et al (2006) Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16:109–142 7. Mortensen JD, Woolner LB, Bennett WA (1955) Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 15:1270–1280 8. Belfiore A, La Rosa GL (2001) Fine-needle aspiration biopsy of the thyroid. Endocrinol Metab Clin North Am 30:361–400 9. Gharib H, Papini E (2007) Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin North Am 36:707–735 vi 10. Tan GH, Gharib H (1997) Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 126:226–231 11. Ries L, Melbert D, Krapcho M et al (2008) SEER cancer statistics review. National Cancer Institute, Bethesda, MD 12. Wartofsky L (2000) The thyroid nodule. In: Wartofsky L (ed) Thyroid cancer: a comprehensive guide to clinical management. Humana Press, Totowa, NJ, pp 3–7 13. Halac I, Zimmerman D (2005) Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am 34:725–744 x 14. Raab SS, Silverman JF, Elsheikh TM et al (1995) Pediatric thyroid nodules: disease demographics and clinical management as determined by fine needle aspiration biopsy. Pediatrics 95:46–49 15. Luster M, Lassmann M, Freudenberg LS et al (2007) Thyroid cancer in childhood: management strategy, including dosimetry and long-term results. Hormones (Athens) 6:269–278 16. De Keyser LF, Van Herle AJ (1985) Differentiated thyroid cancer in children. Head Neck Surg 8:100–114 17. Demidchik YE, Demidchik EP, Reiners C et al (2006) Comprehensive clinical assessment of 740 cases of surgically treated thyroid cancer in children of Belarus. Ann Surg 243:525–532 18. Dinauer CA, Breuer C, Rivkees SA (2008) Differentiated thyroid cancer in children: diagnosis and management. Curr Opin Oncol 20:59–65 19. Farahati J, Bucsky P, Parlowsky T et al (1997) Characteristics of differentiated thyroid carcinoma in children and adolescents with respect to age, gender, and histology. Cancer 80:2156–2162 20. Feinmesser R, Lubin E, Segal K et al (1997) Carcinoma of the thyroid in children: a review. J Pediatr Endocrinol Metab 10:561–568 21. Grigsby PW, Gal-or A, Michalski JM et al (2002) Childhood and adolescent thyroid carcinoma. Cancer 95:724–729 22. La Quaglia MP, Black T, Holcomb GW 3rd et al (2000) 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 35:955– 959; discussion 960
123
1260 23. Spinelli C, Bertocchini A, Antonelli A et al (2004) Surgical therapy of the thyroid papillary carcinoma in children: experience with 56 patients \ or = 16 years old. J Pediatr Surg 39:1500– 1505 24. Newman KD, Black T, Heller G et al (1998) 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 227:533–541 25. Demidchik I, Kontratovich VA (2003) Repeat surgery for recurrent thyroid cancer in children. Vopr Onkol 49:366–369 26. Hosler GA, Clark I, Zakowski MF et al (2006) Cytopathologic analysis of thyroid lesions in the pediatric population. Diagn Cytopathol 34:101–105 27. Leenhardt L, Hejblum G, Franc B et al (1999) Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules. J Clin Endocrinol Metab 84:24–28 28. Hung W (1999) Solitary thyroid nodules in 93 children and adolescents: a 35-years experience. Horm Res 52:15–18 29. Lugo-Vicente H, Ortiz VN, Irizarry H et al (1998) Pediatric thyroid nodules: management in the era of fine needle aspiration. J Pediatr Surg 33:1302–1305 30. Yang J, Schnadig V, Logrono R et al (2007) Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer 111:306–315 31. Carmeci C, Jeffrey RB, McDougall IR et al (1998) Ultrasoundguided fine-needle aspiration biopsy of thyroid masses. Thyroid 8:283–289 32. Danese D, Sciacchitano S, Farsetti A et al (1998) Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules. Thyroid 8:15–21 33. Furlan JC, Bedard YC, Rosen IB (2005) Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease. Can J Surg 48:12–18 34. Mandell DL, Genden EM, Mechanick JI et al (2001) Diagnostic accuracy of fine-needle aspiration and frozen section in nodular thyroid disease. Otolaryngol Head Neck Surg 124:531–536 35. Gharib H, Zimmerman D, Goellner JR et al (1995) Fine-needle aspiration biopsy: use in diagnosis and management of pediatric thyroid diseases. Endocr Pract 1:9–13 36. Arda IS, Yildirim S, Demirhan B et al (2001) Fine needle aspiration biopsy of thyroid nodules. Arch Dis Child 85:313–317 37. Corrias A, Einaudi S, Chiorboli E et al (2001) Accuracy of fine needle aspiration biopsy of thyroid nodules in detecting malignancy in childhood: comparison with conventional clinical, laboratory, and imaging approaches. J Clin Endocrinol Metab 86:4644–4648 38. Alexander EK, Heering JP, Benson CB et al (2002) Assessment of nondiagnostic ultrasound-guided fine needle aspirations of thyroid nodules. J Clin Endocrinol Metab 87:4924–4927
123
World J Surg (2010) 34:1254–1260 39. Gharib H (1997) Changing concepts in the diagnosis and management of thyroid nodules. Endocrinol Metab Clin North Am 26:777–800 40. McHenry CR, Walfish PG, Rosen IB (1993) Non-diagnostic fine needle aspiration biopsy: a dilemma in management of nodular thyroid disease. Am Surg 59:415–419 41. Schmidt T, Riggs MW, Speights VO Jr (1997) Significance of nondiagnostic fine-needle aspiration of the thyroid. South Med J 90:1183–1186 42. Brooks AD, Shaha AR, DuMornay W et al (2001) Role of fineneedle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors. Ann Surg Oncol 8:92–100 43. Delbridge L (2003) Total thyroidectomy: the evolution of surgical technique. ANZ J Surg 73:761–768 44. Handkiewicz-Junak D, Wloch J, Roskosz J et al (2007) Total thyroidectomy and adjuvant radioiodine treatment independently decrease locoregional recurrence risk in childhood and adolescent differentiated thyroid cancer. J Nucl Med 8:879–888 45. Savio R, Gosnell J, Palazzo FF et al (2005) The role of a more extensive surgical approach in the initial multimodality management of papillary thyroid cancer in children. J Pediatr Surg 40:1696–1700 46. Handkiewicz-Junak D, Wloch J, Czarniecka A et al (2006) Completion total thyroidectomy in children with differentiated thyroid cancer. Endokrynol Pol 57:356–361 47. Amrikachi M, Ponder TB, Wheeler TM et al (2005) Thyroid fineneedle aspiration biopsy in children and adolescents: experience with 218 aspirates. Diagn Cytopathol 32:189–192 48. Florentine BD, Staymates B, Rabadi M et al (2006) The reliability of fine-needle aspiration biopsy as the initial diagnostic procedure for palpable masses: a 4-year experience of 730 patients from a community hospital-based outpatient aspiration biopsy clinic. Cancer 107:406–416 49. Ljung BM, Drejet A, Chiampi N et al (2001) Diagnostic accuracy of fine-needle aspiration biopsy is determined by physician training in sampling technique. Cancer 93:263–268 50. Izquierdo R, Arekat MR, Knudson PE et al (2006) Comparison of palpation-guided versus ultrasound-guided fine-needle aspiration biopsies of thyroid nodules in an outpatient endocrinology practice. Endocr Pract 12:609–614 51. Kim SJ, Kim EK, Park CS et al (2003) Ultrasound-guided fineneedle aspiration biopsy in nonpalpable thyroid nodules: is it useful in infracentimetric nodules? Yonsei Med J 44:635–640 52. Sywak M, Cornford L, Roach P et al (2006) Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery 140:1000–1005 discussion 1005–1007 53. Accurso A, Rocco N, Palumbo A et al (2005) Usefulness of ultrasound-guided fine-needle aspiration cytology in the diagnosis of non-palpable small thyroid nodules. Tumori 91:355–357
