Ultrasonographic Differentiation Between Metastatic and Benign Lymph Nodes in Patients With Papillary Thyroid Carcinoma

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1 Article Ultrasonographic Differentiation Between Metastatic and Benign Lymph Nodes in Patients With Papillary Thyroid Carcinoma Pedro Weslley Souza Rosário, PhD, Sérgio de Faria, MD, Luciano Bicalho, MD, Maria Flávia Gatti Alves, MD, Michelle Aparecida Ribeiro Borges, MD, Saulo Purisch, MD, Eduardo Lanza Padrão, MD, Leonardo Lamego Rezende, MD, Álvaro Luís Barroso, MD Objective. The purpose of this study was to evaluate the ultrasonographic characteristics of metastatic lymph nodes in patients with papillary thyroid carcinoma. Methods. The ultrasonographic characteristics of lymph nodes were analyzed in 112 consecutive patients who underwent thyroidectomy and lymph node dissection, with the diagnosis being confirmed by anatomopathologic examination. Results. A total of 198 lymph nodes were metastatic, and 152 were benign (normal or with nonspecific lymphadenitis). Minimum axial diameters of 7 mm for level II (upper internal jugular chain) and 6 mm for the rest of the neck were observed in 93% of metastatic lymph nodes, absence of an echogenic hilum in 88%, hyperechogenicity in relation to the adjacent muscles in 86%, a round shape in 80%, calcifications in 49.5%, and intranodal cystic necrosis in 20%. These ultrasonographic characteristics were observed in 17%, 10%, 4.5%, 29.5%, 0%, and 0% of benign lymph nodes, respectively. Conclusions. Even basic ultrasonographic characteristics (shape, echogenicity and echogenic hilum, calcifications, and intranodal cystic necrosis) help in the differentiation between metastatic and nonmetastatic lymph nodes in patients with papillary thyroid carcinoma. Key words: lymph nodes; papillary carcinoma; ultrasonography. Abbreviations FNAC, fine-needle aspiration cytologic examination; S/L, short axis/long axis Received April 25, 2005, from the Endocrinology Service, Santa Casa de Belo Horizonte, Minas Gerais, Brazil. Revision requested May 6, Revised manuscript accepted for publication May 26, Address correspondence to Pedro Weslley Souza Rosário, PhD, Centro de Estudos e Pesquisa da Clinica de Endocrinologia e Metabologia, Avenida Francisco Sales 1111, 5 Andar Ala D, Santa Efigênia, Belo Horizonte-MG, Brazil. pedrorosario@globo.com Approximately two thirds of recurrences of differentiated thyroid carcinoma occur in the neck region, most of them in the lymph nodes. 1 Ultrasonography is the most sensitive method for the detection of metastatic lymph nodes, 2 4 but other conditions might cause cervical lymphadenopathy, with differentiation being important so that patients do not unnecessarily undergo invasive methods or even surgery. This study evaluated the ultrasonographic characteristics of benign and metastatic cervical lymph nodes in patients with papillary thyroid carcinoma to contribute to the image-based differentiation of cervical lymphadenopathy in these patients by the American Institute of Ultrasound in Medicine J Ultrasound Med 2005; 24: /05/$3.50

2 Lymph Node Metastases in Papillary Carcinoma Materials and Methods In a prospective study, we analyzed the ultrasonographic characteristics of cervical lymph nodes, all with the diagnosis confirmed histologically after surgical removal, in 112 consecutive patients (80 women; mean age, 45.6 years; range, years) with thyroid papillary carcinoma who underwent thyroidectomy and lymph node dissection. The correlation between lymph nodes visualized by ultrasonography(before surgical removal) and the anatomopathologic result was analyzed in 350 lymph nodes, including 198 metastatic lymph nodes and 152 benign lymph nodes (normal or with nonspecific lymphadenitis, none of them with granulomatous disease or a specific inflammatory process). The study was approved by the Research Ethics Committee of our institution. Ultrasonography was performed with a linear multifrequency 7.5- to 10-MHz transducer, and the images were analyzed by an experienced professional. Results Minimum axial diameters of 7 mm for level II (upper internal jugular chain) and 6 mm for the rest of the neck 5 were observed in 184 (93%) of 198 metastatic lymph nodes and 26 (17%) of 152 benign lymph nodes. One hundred nineteen metastatic lymph nodes (60%) were located in the internal jugular chain, the chain considered characteristic of metastases from papillary carcinoma. 6 A change from an oval (short axis/long axis [S/L] ratio <0.5) 7,8 to round (S/L ratio 0.5) shape was observed in 160 metastatic lymph nodes (80%) and in 45 nonmalignant lymph nodes (29.5%). Hyperechogenicity in relation to the adjacent muscles was detected in 170 malignant lymph nodes (86%) and in only 7 benign lymph nodes (4.5%). Intranodal cystic necrosis was observed in 40 metastatic nodes (20%). Calcifications were present in 98 malignant lymph nodes (49.5%) and were peripheral in 85 (86.5%) of 98 lymph nodes. None of the normal or reactive lymph nodes showed calcifications or cystic necrosis. The absence of an echogenic hilum was observed in 174 malignant lymph nodes (88%) and in only 15 benign lymph nodes (10%); well-defined limits were noted in 115 metastatic lymph nodes (58%) and 115 nonmalignant lymph nodes (75.5%). Considering shape and echogenicity (hyperechogenicity and absence of an echogenic hilum), at least 2 of these characteristics were observed in all cases of metastatic lymph nodes without calcifications or intranodal cystic necrosis. Sensitivity, specificity, and positive and negative predictive values of the characteristics in the differentiation between metastatic and benign lymph nodes are presented in Table 1. Normal and metastatic lymph nodes in the neck are shown in Figures 1 3. Discussion With respect to size, minimum axial diameters of 7 mm for level II lymph nodes and 6 mm for the rest of the neck as proposed by van den Brekel et al 5 seem to be adequate for the distinction of lymph nodes with and without metastases, showing 93% sensitivity, 83% specificity, and 88.5% accuracy in this present series. The loca- Table 1. Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value of the Ultrasonographic Characteristics in the Differentiation Between Metastatic and Benign Lymph Nodes in Patients With Papillary Carcinoma Ultrasonographic Characteristic Sensitivity, n (%) Specificity, n (%) PPV, n (%) NPV, n (%) Accuracy, % Size* 184/198 (93) 126/152 (83) 184/210 (88) 126/140 (90) 89 S/L ratio /198 (80) 107/152 (70.5) 160/205 (78) 107/145 (74) 76 Hyperechogenicity in relation 170/198 (86) 145/152 (95.5) 170/177 (96) 145/173 (84) 90 to the adjacent muscles Absence of an echogenic hilum 174/198 (88) 137/152 (90) 174/189 (92) 137/161 (85) 89 Calcifications 98/198 (49.5) 152/152 (100) 98/98 (100) 152/252 (60) 71.5 Intranodal cystic necrosis 40/198 (20) 152/152 (100) 40/40 (100) 152/310 (49) 55 NPV indicates negative predictive value; and PPV, positive predictive value. *Minimum axial diameters of 7 mm for level II (upper internal jugular chain) and 6 mm for the rest of the neck J Ultrasound Med 2005; 24:

3 Rosário et al tion of altered lymph nodes also helps in the differential diagnosis, with location in the internal jugular chain being a characteristic of thyroid carcinoma metastases. 6 With respect to shape, lymph node rounding (S/L ratio 0.5) 7,8 is a common finding in metastatic lymph nodes, 7,9 11 as confirmed in this study, in which this characteristic showed 80% sensitivity. Hyperechogenicity in relation to the adjacent muscle also represents a relevant finding 7,12 typical of papillary carcinoma metastases 6 and was observed in this series in 86% of metastatic nodes, being rare in normal or reactive lymph nodes. Intranodal cystic necrosis, observed in 20% of metastatic nodes, has also been described in this type of metastasis. 7,12 Calcifications, rare in metastases of other tumors, are frequent characteristics of lymph nodes affected by papillary carcinoma, with their frequency ranging from 50% to 69% in other series, most of them being peripheral. 7,12 In this study, 49.5% of the metastatic nodes had calcifications. These last 2 characteristics (cystic necrosis and calcifications) were not observed in normal or reactive lymph nodes but may occasionally occur in lymph nodes after radiotherapy and in nodes affected by tuberculosis. 6,7,11 The absence of an echogenic hilum was detected in 88% of metastatic lymph nodes, with a positive predictive value of 92% and accuracy of 89%, in agreement with some studies showing that this characteristic is frequent in metastatic lymph nodes, 13 whereas others did not confirm this finding. 9 Thus, the use of these characteristics in the distinction of benign and malignant lymph nodes continues to be controversial. 6 The nodal border also has not been considered a relevant characteristic in the differentiation between malignant and benign cervical lymph nodes, 6 and 58% of the malignant lymph nodes analyzed here showed well-defined borders on ultrasonography. One method that is highly useful in the definition of the etiology of abnormal cervical lymph nodes is fine-needle aspiration cytologic examination (FNAC), which should preferentially be guided by ultrasonography in patients with papillary carcinoma because in these individuals metastatic lymph nodes may have cystic degeneration that can cause a false-negative FNAC result. Previous studies have shown the value of ultrasonographically guided FNAC, reporting 89% to 98% sensitivity, 95% to 98% specificity, and 95% to 97% accuracy. 14,15 Figure 1. Sonogram showing oval, hypoechoic normal cervical lymph nodes. Figure 2. Sonogram showing a round, hypoechoic metastatic node (left). Note the absence of an echogenic hilum. J Ultrasound Med 2005; 24:

4 Lymph Node Metastases in Papillary Carcinoma Figure 3. Sonogram of a hyperechoic metastatic node with intranodal cystic necrosis (left). We did not determine the vascularization characteristics of lymph nodes, although this finding is important in the differential diagnosis, with metastatic lymph nodes generally showing peripheral vascularization with or without central vascularization. 6,16,17 Vascular resistance, which is higher in metastatic lymph nodes, 16,17 may also contribute to this differentiation, but its value has been questioned. 18 In addition, metastatic lymph nodes in papillary carcinoma of the thyroid have low vascular resistance. 19 Better accuracy in the distinction between metastatic and nonmetastatic nodes seems to be obtained with the use of a contrast agent on power Doppler ultrasonography. 20,21 In addition, the detection of thyroglobulin in lymph node aspirates also shows high specificity 22 and might be particularly useful in cases of cystic lesions with negative cytologic findings. 23,24 We conclude that even basic ultrasonographic characteristics (shape, echogenicity, echogenic hilum, calcifications, and cystic necrosis) help in the differentiation of metastatic and nonmetastatic lymph nodes in patients with papillary carcinoma. References 1. Mazzaferri EL, Kloos R. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001; 86: Schlumberger M, Berg G, Cohen O, et al. Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 2004; 150: Rosario PS, Cardoso LD, Fagundes TA, Reis JS, Maia FF, Purisch S. Usefulness of radioiodine scanning in patients with moderate or high risk differentiated thyroid carcinoma in whom thyroglobulin after thyroxin withdrawal is undetectable after initial treatment. Arq Bras Endocrinol Metabol 2004; 48: Rosario PW, Fagundes TA, Maia FF, Messias-Franco ACH, Figueiredo MB, Purisch S. Ultrasonography in the diagnosis of cervical recurrence in patients with differentiated thyroid carcinoma. J Ultrasound Med 2004; 23: van den Brekel MW, Castelijns JA, Snow GB. The size of lymph nodes in the neck on sonograms as a radi J Ultrasound Med 2005; 24:

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