Neuroradiolog y / Head and Neck Imaging • Original Research Sohn et al. Ultrasound and FNAB of Lymph Node Metastasis

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Neuroradiology/Head and Neck Imaging Original Research

Yu-Mee Sohn1,2 Jin Young Kwak1 Eun-Kyung Kim1 Hee Jung Moon1 Soo Jin Kim1 Min Jung Kim1 Sohn YM, Kwak JY, Kim EK, Moon HJ, Kim SJ, Kim MJ

Keywords: fine-needle aspiration biopsy, lymph node metastasis, ultrasound DOI:10.2214/AJR.09.3128 Received June 3, 2009; accepted after revision July 2, 2009. 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, South Korea. Address correspondence to J. Y. Kwak ([email protected]). 2 Department of Radiology, Kyung Hee University Medical Center, Seoul, South Korea.

AJR 2010; 194:38–43 0361–803X/10/1941–38 © American Roentgen Ray Society

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Diagnostic Approach for Evaluation of Lymph Node Metastasis From Thyroid Cancer Using Ultrasound and Fine-Needle Aspiration Biopsy OBJECTIVE. The purpose of our study was to investigate ultrasound criteria to determine the most accurate criterion to differentiate metastatic from benign lymph nodes on ultrasound and to evaluate the frequency of metastasis according to the cytology results. MATERIALS AND METHODS. One hundred eighteen consecutive patients with thyroid malignancy underwent fine-needle biopsy of suspicious lymph nodes. We investigated the diagnostic performance of each ultrasound feature (loss of fatty hilum, presence of cystic change or calcification, hyperechogenicity, and round shape) and ultrasound criteria 1 and 2. We considered criterion 1 to be if one of the aforementioned malignant ultrasound findings was present and criterion 2 to be if one of the aforementioned malignant ultrasound findings, excluding the loss of fatty hilum, was present. Cytology results were divided into metastasis, macrophages without malignant cells, cell paucity, and negative for malignancy, and we evaluated the frequency of metastasis. RESULTS. There were 91 metastatic and 27 benign nodes. The area under the receiver operating characteristic curve value of criterion 2 was significantly higher than that of criterion 1. The frequency of metastasis was highest with a cytologic result of metastasis (95.8%), followed by macrophages without malignant cells (87.5%), cell paucity (71.4%), and negative for malignancy (34.4%). CONCLUSION. The most accurate ultrasound criterion to differentiate metastatic from benign lymph nodes was ultrasound criterion 2 (any suspicious ultrasound features except for loss of fatty hilum), and we should not neglect lymph nodes with suspicious ultrasound features, even if they do not contain malignant cells on cytology.

T

hyroid cancer often metastasizes to cervical lymph nodes, and early detection of metastasis is important for planning surgery and management of patients [1]. Ultrasound is the imaging method of choice for detecting and characterizing cervical lymph nodes in thyroid cancer and providing guidance for fineneedle aspiration biopsy (FNAB) [1]. Ultrasound and ultrasound-guided FNAB are the main diagnostic tools for detecting cervical metastasis of thyroid cancer by preoperative cytologic analysis and recurrence after thyroid surgery [2–5]. Numerous previous reports have described the ultrasound characteristics of metastatic lymph nodes of papillary thyroid cancer, such as the presence of calcification [1, 3, 5–10], cystic change [1, 3, 5–12], loss of an echogenic fatty hilum [3, 5–10, 13– 15], hyperechogenicity [3, 6, 8–10], round shape [3, 5–10, 13, 14], and abnormal vascu-

larity on color Doppler images [3, 6, 8, 9, 14]. Recent studies have shown excellent diagnostic performance using a combination of various ultrasound characteristics [3, 7–10]. However, loss of fatty hilum as a diagnostic ultrasound criterion of metastatic lymph nodes has been the subject of debate [16–19]. The cytology results of metastatic thyroid cancer in cervical lymph nodes displayed a higher frequency of foamy macrophages (38.5%) and cystic degeneration (44.7%), even though no malignant cells were found on cytology [20]. However, to the best of our knowledge, the frequency of metastasis according to each cytology result of lymph nodes has not been reported. Therefore, in this study we investigated the most accurate criteria to differentiate metastatic from benign lymph nodes on ultrasound and evaluated the frequency of metastasis according to the cytology results.

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Ultrasound and FNAB of Lymph Node Metastasis TABLE 1:  Aspirated Lymph Nodes in 118 Patients

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Levels of Aspirated Lymph Nodes

I



II



No. of Patients Initial Surgery (n = 70)

Postsurgery (n = 48) 1

4

8

III

31

14

IV

28

19



V

7

4



VI

Materials and Methods Patients The institutional review board approved this retrospective observational study and required neither patient approval nor patient informed consent for the review of images and records. Informed consent was obtained from all patients before FNAB. From January 2003 to December 2005, 135 consecutive patients at our institution underwent FNAB due to suspicious metastatic cervical lymph nodes of papillary thyroid carcinoma. During the study period, we considered a lymph node to be suspicious when it had one of following features: loss of fatty hilum, cystic change, calcification, hyperechogenicity (higher echogenicity than the surrounding muscles), and round shape (long to transverse diameter ratio < 1.5). Doppler ultrasound was not routinely performed. Eight lymph nodes in eight patients were excluded because there was no subsequent surgical excision or longterm imaging follow-up for at least 2 years. Nine patients also were excluded because ultrasound examinations were unavailable. Ultimately, 118 lymph nodes in 118 patients were included in this analysis. Forty-eight patients had already undergone surgery for thyroid papillary carcinoma, and the remaining 70 had no prior surgery for cytologically confirmed papillary carcinoma (Table 1).

2 calcification, hyperechogenicity (higher echogenicity than the surrounding muscles), and round shape (long to transverse diameter ratio < 1.5) (Figs. 1–3). The ultrasound results were grouped as positive (suspicious) and negative (benign), and lymph nodes were considered positive if one of the malignant sonographic findings was present on ultrasound (criterion 1) [1, 3, 5–10]. Lymph nodes were also considered positive if one of the malignant sonographic findings was present, excluding loss of fatty hilum (criterion 2), on ultrasound [16–19].

Preoperative Evaluation of Lymph Nodes At our institution, we performed ultrasoundguided FNAB on lymph nodes with suspicious ultrasound features. However, we did not perform ultrasound-guided FNAB on central lymph nodes with suspicious ultrasound features in patients who were scheduled for thyroidectomy because routine central lymph node dissections were performed at the time of thyroidectomy. Lymph nodes were considered suspicious during the study period when one of the suspicious ultrasound findings (loss of fatty hilum, calcifications, cystic change, hyperechogenicity, and round shape) was present. Ultrasound-guided FNAB was performed by one of three radiologists who had 4, 6, and 10 years of experience with thyroid imaging. They

were aware of the patients’ clinical histories. Ultrasound-guided FNAB was performed with a 23-gauge needle attached to a 20-mL disposable plastic syringe and aspirator. Materials obtained from FNAB were smeared on glass slides. All smears were placed in 95% alcohol for Papanicolau staining, and the remaining material was rinsed in saline to be processed as a cell block. The cytopathologist was not on site during the biopsy.

Cytopathologic Evaluation One of five cytopathologists interpreted the ultrasound-guided FNAB according to their schedules. They were blinded with respect to the ultrasound diagnosis. At our institution, cytology results were divided into one of the following four categories: metastasis, macrophages without malignant cells, cell paucity, and negative for malignancy. Metastasis was defined as positive for metastatic thyroid carcinoma [3], macrophages without malignant cells were reported when cytology showed foamy macrophages with no malignant cells [20], cell paucity was assigned in cases with insufficient material [3], and negative for malignancy included reactive lymph nodes or other benign lymphadenitis [3]. We used the initial cytologic report for the cytopathologic evaluations.

Surgical Protocol and Histopathologic Analyses When cytology results revealed malignant cells in lymph nodes, unilateral modified neck dissection was performed as the initial thyroid surgery. However, selective frozen sectioning was performed as the initial thyroid surgery in patients with lymph nodes with suspicious ultrasound features but no definite malignant cells on cytology. Selective dissection was performed in patients who had already undergone thyroid surgery. We evaluated the final results of aspirated lymph nodes in level-by-level analyses and compared them to pathology reports.

Imaging and Image Analyses Ultrasound evaluation of cervical lymph nodes was undertaken using a 7-15–MHz linear-array transducer (HDI 5000, Philips Healthcare) and 8-15–MHz linear-array transducer (Acuson Sequoia, Siemens Healthcare). Compound imaging was performed in all cases using the HDI 5000 machine, and lymph node sizes were measured along the longest diameter on transverse scans. Two radiologists with 2 and 8 years of experience with thyroid imaging retrospectively reviewed the thyroid ultrasound examinations in consensus. They had no knowledge of the clinical history or cytopathologic results of the patients while performing the consensus reading. Suspicious ultrasound features of lymph nodes were the following: loss of fatty hilum, cystic change,

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Fig. 1—37-year-old woman with level IV metastatic lymph node in left neck. Ultrasound image shows loss of fatty hilum, microcalcification, and hyperechogenicity in lymph node (arrows). Cytology results confirmed lymph node metastasis.

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Sohn et al.

Fig. 3—32-year-old woman with level II metastatic lymph nodes in left neck. Ultrasound image shows loss of fatty hilum and cystic change. Cytology results confirmed macrophages without malignant cells.

Fig. 2—56-year-old woman with level IV metastatic lymph nodes in right neck. Ultrasound image shows microcalcification (arrow), loss of fatty hilum, and round shape in lymph nodes (arrowheads). Cytology results confirmed lymph node metastasis.

Statistical Analyses

analysis was performed to compare the two ultrasound criteria to differentiate metastatic from benign lymph nodes. We evaluated the frequency of metastasis according to cytology results. Statistical significance was assumed when the p value was less than 0.05.

A reference standard was set by pathology results from lymph node dissections or long-term imaging follow-up for at least 2 years with no subsequent surgical excision. Categorical data were summarized using frequencies and percentages. The Student’s t test was used to determine differences between metastatic and benign lymph nodes according to age and lymph node size on ultrasound. The chi-square test was performed to evaluate the differences between benign and malignant groups by sex. Diagnostic performance, including sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV), was calculated according to the ultrasound findings. We also examined diagnostic performance by ultrasound grouping (criteria 1 and 2). The chisquare test or Fisher’s exact test was used to compare each ultrasound finding to standard results. Receiver operating characteristic (ROC) curve

Results This study included 23 men and 95 women with a mean age of 51 ± 13.4 years. The mean size of lymph nodes was 13.8 ± 8.5 mm. Pathologic confirmations were obtained from 115 patients. There were 91 malignant and 24 benign results on pathology. Three patients who did not undergo surgery had nodes that decreased in size during the long-term imaging follow-up duration of at least 2 years. Therefore, this study consisted of 91 malignant and 27 benign lymph nodes. There was no significant difference between metastatic and benign lymph nodes according to

age (p = 0.765) and sex (p = 0.071). The mean longest diameter of metastatic lymph nodes (14.5 mm ± 9 mm) was significantly larger than that of benign nodes (11.4 mm ± 5.8 mm) (p = 0.042). The diagnostic performance of each ultrasound finding in this study is shown in Table 2. Ultrasound criteria 1 and 2 as well as each suspicious ultrasound feature had statistical significance with metastasis. Most ultrasound features had high specificity and PPV but low sensitivity and NPV. However, loss of fatty hilum had the highest sensitivity and NPV but showed lower specificity than other ultrasound features. When each ultrasound feature and ultrasound criteria 1 and 2 were compared, criterion 2 had the highest accuracy. The area under the ROC curve value (0.83; 95% CI, 0.739–0.920] of criterion 2 was significantly higher than that (0.704; 95% CI, 0.609–0.798) of criterion 1 (p = 0.006) (Fig. 4).

TABLE 2:  Diagnostic Accuracy of Each Ultrasound Feature Ultrasound Feature

TP

TN

FP

Sensitivity (%)

FN

Specificity (%)

Accuracy (%)

PPV (%)

NPV (%)

Loss of fatty hilum

91

13

14

0

100 (91/91)

48 (13/27)

88 (104/118) 87 (91/105)

100 (13/13)

Cystic change

31

26

1

60



34 (31/91)

96 (26/27)

48 (57/118)

97 (31/32)



30 (26/86)

Presence of calcification

41

25

2

50



45 (41/91)

93 (25/27)

56 (66/118)

95 (41/43)



33 (25/75)

Hyperechogenicity

54

23

4

37



59 (54/91)



85 (23/27)

65 (77/118)

93 (54/58)



38 (23/60)

Round shape

50

24

3

41



55 (50/91)

89 (24/27)

63 (74/118)

94 (50/58)



37 (24/65)

Any suspicious ultrasound feature (criterion 1)

91

11

16

0

100 (91/91)



41 (11/27)

86 (102/118) 85 (91/107)

100 (11/11)

Any suspicious ultrasound feature, excluding loss of fatty hilum (criterion 2)

87

19

8

4





70 (19/27)

89 (106/118) 92 (87/95)



96 (87/91)

83 (19/23)

Note—Data in parentheses are number of cases. TP = true-positive, TN = true-negative, FP = false-positive, FN = false-negative, PPV = positive predictive value, NPV = negative predictive value.

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Ultrasound and FNAB of Lymph Node Metastasis 1.0

Sensitivity

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0.8 0.6 0.4 0.2 0

0

0.2

0.4 0.6 1 − Specificity

The frequency of metastasis was highest with a cytology reading of metastasis (68/71, 95.8%), followed by macrophages without malignant cells (7/8, 87.5%), cell paucity (5/7, 71.4%), and negative for malignancy (11/32, 34.4%). Discussion Ultrasound characteristics of metastatic lymph nodes of thyroid cancer have been reported by several investigators [1, 5, 6, 11]. Major ultrasound characteristics suggesting metastasis of thyroid cancer included the presence of calcification [1, 3, 5–10], cystic change [1, 3, 5–12], loss of echogenic fatty hilum [3, 5–10, 13–15], hyperechogenicity [3, 6, 8–10], round shape [3, 5–10, 13, 14], and abnormal vascularity [3, 6, 8, 9, 14]. The results of previous studies [5, 7–11] that examined diagnostic performance of each ultrasound characteristic are shown in Table 3. The frequency of metastasis was 62.0–100% in lymph nodes with absent hilum [5, 7–10], 19.0–80.0% in those with round shapes [7– 10], 58.0–86.0% in those with hyperechogenicity [8–10], 3.0–49.5% in those with calcification [5, 7–11], 13.2–70.0% in those with cystic change [5, 7, 9–11], and 47.0–47.6% in those with abnormal vascularity [8, 9]. Of these ultrasound characteristics, several studies have shown that calcification and cystic change have 100% specificity and PPV [10, 11] and that they are not observed in normal or reactive lymph nodes [10]. Calcifications in metastatic lymph nodes are shown in punctate microcalcifications on ultrasound, and these calcifications are laminated, calcified, spherical bodies on cytology that are called psammoma bodies [21]. Psammoma bodies were reported to be formed by calcification of intravascular tumor thrombi or infarcted tips of malignant papillae, and their presence is considered to be diagnostic of malignancy [22]. Some investigators have reported that cystic degeneration of lymph nodes was highly suggestive of metastasis in

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0.8

1.0

Fig. 4—Graph shows receiver operating characteristic curve of two ultrasound criteria to differentiate metastatic from benign lymph nodes. Area under ROC curve value (0.83) of criterion 2 (dashed line) was significantly higher than that of criterion 1 (0.704) (solid line).

thyroid cancer [1, 11, 23] and squamous cell carcinoma of the head and neck [23]. Thyroid papillary carcinoma most commonly showed cystic formation in lymph node metastasis, and the incidence of cystic change of lymph nodes in thyroid cancer was reported in 10–25% of cases [23]. This cystic change is the result of liquefaction necrosis [12] or spontaneous or postradiotherapeutic central breakdown of keratin, which gives the node a pseudocystic appearance [24]. Cystic changes are shown on ultrasound as small solitary cystic areas, multiple peripheral cystic areas, or almost complete replacement of the node by cystic formation [11]. Another study [12] reported that pure cystic change was mostly found in young adults. These ultrasound findings were explained by the increased aggressiveness of tumors at a young age, which caused extensive necrosis [24]. In the current study, cystic change also had high specificity and PPV as diagnostic ultrasound features. Several investigators revealed good results on preoperative staging when the criterion involving one suspicious finding was present on ultrasound [9, 17, 25, 26]. In this study, we evaluated diagnostic performance in the diagnosis of metastasis with combined ultrasound criteria (1 and 2) as well as suspicious ultrasound findings, such as loss of fatty hilum, calcification, cystic change, hyperechogenicity, and round shape. Most ultrasound features had high specificity and PPV but low sensitivity and NPV. However, loss of fatty hilum had the highest sensitivity and NPV but lower specificity than other ultrasound features. This result is consistent with previous reports [16–19] that loss of fatty hilum is not a definite criterion for differentiation between malignant and benign lymph nodes. When each ultrasound feature and ultrasound criteria 1 and 2 were compared, criterion 2 had the highest accuracy, with a significantly higher area under the curve value than criterion 1. The results correspond to those of previous studies that

loss of fatty hilum is not a specific ultrasound feature for malignancy [16–19]. Until now, malignant cells on cytology have been considered suggestive of metastasis, prompting surgical management. However, the frequency of metastasis has been reported rarely on other cytologic results of suspicious lymph nodes on ultrasound, to the best of our knowledge. Cytology results of metastatic thyroid cancer in cervical lymph nodes displayed a higher frequency of foamy macrophages (38.5%), even if no malignant cells were found on cytology [20, 23]. In this study, we categorized cytologic results as metastasis, presence of macrophages without malignant cells, cell paucity, and negative for malignancy. The inclusion of macrophages in this criterion was supported by a previous report [20]. The frequency of metastasis was the highest in lymph nodes with suspicious ultrasound features having malignant cells (95.8%), followed by macrophages without malignant cells (87.5%), cell paucity (71.4%), and negative for malignancy (34.4%). When metastatic lymph nodes were diagnosed on cytology, functional compartment en bloc dissection was preferred over selective dissection (“berry picking”) because of improved mortality [27–30]. However, we cannot neglect a lymph node with a suspicious ultrasound feature, even when it does not have malignant cells on cytology. A recent study [31] reported an effective method of preoperative ultrasound-guided tattooing using charcoal suspension for localizing nonpalpable cervical recurrent lymph nodes after thyroidectomy. This method can be applied to suspicious lymph nodes on ultrasound as a preoperative ultrasound marking for sampling with frozen sectioning and determining further surgical treatment. Therefore, we suggest that frozen sampling with preoperative ultrasound marking should be performed for pathologic confirmation of a lymph node with a suspicious ultrasound feature to prevent undertreatment of patients. In addition to FNAB, several studies [3, 4, 17, 32–34] have reported the detection of thyroglobulin (Tg) in FNAB washout fluid. FNAB-Tg identified metastasis and recurrence of the neck with excellent sensitivity and specificity, especially cystic metastatic lymph nodes, which can show a higher incidence of false-negative findings on cytology than metastatic lymph nodes without cystic change [3, 23, 32, 33]. Moreover, the FNABTg test and the combination of FNAB-Tg and

41

NA NA 87 48 100 97 96 34 95 93 45 93 85 59 94 89 118 This study

91

55

80

Note—PPV = positive predictive value, NA = not applicable.

78

NA

70.5

65.6

198

517

350

Kuna et al. [7]

Rosario et al. [10]

221

FNAB cytology have been shown to be more sensitive and accurate than FNAB cytology alone [3, 32, 34]. However, the current study was a retrospective study, and additional Tg data could not be obtained. The first limitation of the current study is that it is retrospective and included only patients who underwent ultrasound-guided FNAB and thyroid surgery or imaging follow-up for at least 2 years. Therefore, selection bias does exist. Second, the high percentage of included lymph nodes with metastasis with suspicious features on initial ultrasound resulted in incomplete examination of the most accurate criterion to differentiate malignant from benign lymph nodes. This was another form of selection bias. Third, abnormal vascularity of lymph nodes was not included, and inclusion was not possible because of the retrospective design. Fourth, we used the initial cytologic results of the lymph nodes. In the study period, five cytopathologists interpreted the FNAB slides at our institution. This was a limitation of the study because of the possibility of interobserver variability in cytologic interpretations. Fifth, we could not perform a node-by-node analysis of all lymph nodes and instead, a levelby-level analysis was performed. Lastly, the study included a relatively small number of patients. Further prospective study will be necessary to resolve these issues. In conclusion, the most accurate ultrasound criterion to differentiate metastatic from benign lymph nodes was ultrasound criterion 2 (any suspicious ultrasound features except loss of fatty hilum), and we should not neglect lymph nodes with suspicious ultrasound features, even if they do not contain malignant cells on cytology.

NA

NA

NA

NA

NA

NA

NA 92

NA NA

90 88

99.5 NA

100 100

NA 21.3

20 100

NA NA

100 49.5

5.4 NA

96

NA

95.5

NA

57.1

NA

86

NA

76.9

NA NA

52.6 75.0

64 21

71.4 31.6

100 77

100 100

61 92

26.3 100

78 63

100 31.6

92 NA NA

78.9

NA

80.2 21

53 91

45

Takashima et al. [5]

NA

NA

NA

78.9

NA NA

Park et al. [9]

23.8

66.7

42.9

97 99

NA

47 54

NA NA

54 72

NA NA

NA NA

NA 70

NA 100

NA NA

100 3

30 NA

83

NA NA NA NA NA

91 58 75 81 75

Kessler et al. [11]

20 63

Lyshchik et al. [8]

60 141

Study [Reference No.]

Short-to-Long Axis No. of Diameter Ratio > 0.5 Abnormal Echogenicity Calcification Cystic Change Absent Hilum Peripheral Vascularity Metastatic Lymph Sensitivity Specificity PPV Sensitivity Specificity PPV Sensitivity Specificity PPV Sensitivity Specificity PPV Sensitivity Specificity PPV Sensitivity Specificity PPV Nodes (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) Total No. of Lymph Nodes

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TABLE 3:  Previous Reports of Diagnostic Values According to Ultrasound Criteria to Differentiate Metastatic From Benign Lymph Nodes

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Sohn et al.

Acknowledgments The authors are grateful to Kyung Hwa Han, biostatistician, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Korea, for her help with the statistics in this study. References 1. Miseikyte-Kaubriene E, Trakymas M, Ulys A. Cystic lymph node metastasis in papillary thyroid carcinoma. Medicina (Kaunas) 2008; 44:455–459 2. Boland GW, Lee MJ, Mueller PR, Mayo-Smith W, Dawson SL, Simeone JF. Efficacy of sonographically guided biopsy of thyroid masses and cervical lymph nodes. AJR 1993; 161:1053–1056 3. Jeon SJ, Kim E, Park JS, et al. Diagnostic benefit of thyroglobulin measurement in fine-needle aspi-

ration for diagnosing metastatic cervical lymph nodes from papillary thyroid cancer: correlations with US features. Korean J Radiol 2009; 10:106– 111 4. Kim MJ, Kim EK, Kim BM, et al. Thyroglobulin measurement in fine-needle aspirate washouts: the criteria for neck node dissection for patients with thyroid cancer. Clin Endocrinol (Oxf) 2009; 70:145–151 5. Takashima S, Sone S, Nomura N, Tomiyama N, Kobayashi T, Nakamura H. Nonpalpable lymph nodes of the neck: assessment with US and USguided fine-needle aspiration biopsy. J Clin Ultrasound 1997; 25:283–292 6. Fish SA, Langer JE, Mandel SJ. Sonographic imaging of thyroid nodules and cervical lymph nodes. Endocrinol Metab Clin North Am 2008; 37:401–417, ix 7. Kuna SK, Bracic I, Tesic V, Kuna K, Herceg GH, Dodig D. Ultrasonographic differentiation of benign from malignant neck lymphadenopathy in thyroid cancer. J Ultrasound Med 2006; 25:1531– 1537; quiz 1538–1540 8. Lyshchik A, Higashi T, Asato R, et al. Cervical lymph node metastases: diagnosis at sonoelastography—initial experience. Radiology 2007; 243: 258–267 9. Park JS, Son KR, Na DG, Kim E, Kim S. Performance of preoperative sonographic staging of papillary thyroid carcinoma based on the sixth edition of the AJCC/UICC TNM classification system. AJR 2009; 192:66–72 10. Rosario PW, de Faria S, Bicalho L, et al. Ultrasonographic differentiation between metastatic and benign lymph nodes in patients with papillary thyroid carcinoma. J Ultrasound Med 2005; 24: 1385–1389 11. Kessler A, Rappaport Y, Blank A, Marmor S, Weiss J, Graif M. Cystic appearance of cervical lymph nodes is characteristic of metastatic papillary thyroid carcinoma. J Clin Ultrasound 2003; 31:21–25 12. Wunderbaldinger P, Harisinghani MG, Hahn PF, et al. Cystic lymph node metastases in papillary thyroid carcinoma. AJR 2002; 178:693–697 13. Ahuja A, Ying M, King A, Yuen HY. Lymph node hilus: gray scale and power Doppler sonography of cervical nodes. J Ultrasound Med 2001; 20: 987–992; quiz 994 14. Na DG, Lim HK, Byun HS, Kim HD, Ko YH, Baek JH. Differential diagnosis of cervical lymphadenopathy: usefulness of color Doppler sonography. AJR 1997; 168:1311–1316 15. Ying M, Ahuja A, Metreweli C. Diagnostic accuracy of sonographic criteria for evaluation of cervical lymphadenopathy. J Ultrasound Med 1998; 17:437–445 16. Ahuja A, Ying M. Sonography of neck lymph

AJR:194, January 2010

Downloaded from www.ajronline.org by 37.44.207.154 on 01/16/17 from IP address 37.44.207.154. Copyright ARRS. For personal use only; all rights reserved

Ultrasound and FNAB of Lymph Node Metastasis nodes. Part II. Abnormal lymph nodes. Clin Radiol 2003; 58:359–366 17. Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid 2008; 18:411–418 18. Tsunodo-Shimizu H, Saida Y. Ultrasonographic visibility of supraclavicular lymph nodes in normal subjects. J Ultrasound Med 1997; 16:481–483 19. Vassallo P, Wernecke K, Roos N, Peters PE. Differentiation of benign from malignant superficial lymphadenopathy: the role of high-resolution US. Radiology 1992; 183:215–220 20. Tseng FY, Hsiao YL, Chang TC. Cytologic features of metastatic papillary thyroid carcinoma in cervical lymph nodes. Acta Cytol 2002; 46:1043– 1048 21. Ahuja AT, Chow L, Chick W, King W, Metreweli C. Metastatic cervical nodes in papillary carcinoma of the thyroid: ultrasound and histological correlation. Clin Radiol 1995; 50:229–231 22. Ellison E, Lapuerta P, Martin SE. Psammoma bodies in fine-needle aspirates of the thyroid: predictive value for papillary carcinoma. Cancer

AJR:194, January 2010

1998; 84:169–175 23. Ustun M, Risberg B, Davidson B, Berner A. Cystic change in metastatic lymph nodes: a common diagnostic pitfall in fine-needle aspiration cytology. Diagn Cytopathol 2002; 27:387–392 24. Verge J, Guixa J, Alejo M, et al. Cervical cystic lymph node metastasis as first manifestation of occult papillary thyroid carcinoma: report of seven cases. Head Neck 1999; 21:370–374 25. Gonzalez HE, Cruz F, O’Brien A, et al. Impact of preoperative ultrasonographic staging of the neck in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2007; 133:1258–1262 26. Shimamoto K, Satake H, Sawaki A, Ishigaki T, Funahashi H, Imai T. Preoperative staging of thyroid papillary carcinoma with ultrasonography. Eur J Radiol 1998; 29:4–10 27. Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16:109–142 28. Goropoulos A, Karamoshos K, Christodoulou A, et al. Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma. World J Surg 2004; 28:1275–1281 29. Kupferman ME, Patterson M, Mandel SJ, LiVolsi

V, Weber RS. Patterns of lateral neck metastasis in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2004; 130:857–860 30. Wang TS, Dubner S, Sznyter LA, Heller KS. Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes. Arch Otolaryngol Head Neck Surg 2004; 130:110–113 31. Kang TW, Shin JH, Han BK, et al. Preoperative ultrasound-guided tattooing localization of recurrences after thyroidectomy: safety and effectiveness. Ann Surg Oncol 2009; 16:1655–1659 32. Cignarelli M, Ambrosi A, Marino A, et al. Diagnostic utility of thyroglobulin detection in fineneedle aspiration of cervical cystic metastatic lymph nodes from papillary thyroid cancer with negative cytology. Thyroid 2003; 13:1163–1167 33. Cunha N, Rodrigues F, Curado F, et al. Thyroglobulin detection in fine-needle aspirates of cervical lymph nodes: a technique for the diagnosis of metastatic differentiated thyroid cancer. Eur J Endocrinol 2007; 157:101–107 34. Frasoldati A, Toschi E, Zini M, et al. Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer. Thyroid 1999; 9: 105–111

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