High Resolution Sonographic Detection of Axillary Lymph Node Metastases in Breast Cancer

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1 High Resolution Sonographic Detection of Axillary Lymph Node Metastases in Breast Cancer Wei Tse Yang, MBBS, FRCR, Anil Ahuja, MBBS, DMRD, MD (Born), FRCR, Alice Tang, MBBS, FRCR, Michael Suen, MBBCh, BAO (N.U.I.), MRC Path, Walter King, FRCS Can, FRCS (Edin), FACS, Constantine Metreweli, MA, MBBChir (Cantab), FRCP, MRCS, DMRD, FRCR Axillary lymph node status is crucial in the evaluation of prognosis and in treatment planning of breast cancer. High resolution real time sonographic scans of the breast and both axillae were performed on 4 patients with breast carcinoma, all of whom had axillary lymph node dissection and histologic assessment. The sensitivity of high-resolution ultrasonography in the detection of axillary nodal metastases was 84.%, with a specificity of 9. %, accuracy of 92. %, positive predictive value of 94.9%, and negative predictive value 90.%. Ultrasonography of the axilla provides good information on anatomy and pathology and may have a potential role in the prognostic work-up of patients who are not surgical candidates. KEY WORDS: Ultrasonography; Axilla, lymph nodes; Breast cancer; Metastases, breast cancer. I tis well recognized that axillary nodal status is the primary prognostic factor in breast cancer. Reports in the literature indicate that current preoperative assessment methods are inadequate.t-4 The aim of this study was to determine the detection rate for axillary lymph node metastases in breast cancer using high-resolution ultrasonography. PATIENTS AND METHODS One hundred and fourteen consecutive women with newly diagnosed breast cancer (40 stage Tl, 66 stage T2, five stage T3, and three stage T4) were prospectively studied by clinical examination, breast ultrasonography, and x-ray mammography. All had Received August, 995, from the Departments of Diagnostic Radiology and Organ Imaging (W. T. Y ~ A.A., A.T., C.M.), Cellular Anatomy and Pathology (M.S.), and Surgery (W.K.), The Chinese University of Hong Kong, Hong Kong. Revised manuscript accepted for publication November 22, 995. Address correspondence and reprint requests to Wei Tse Yang, MBBS, FRCR, Department of Radiology, Prince of Wales Hospital, Shiltin, N.T., Hong Kong. axillary lymph node dissection and histologic evaluation. The minimum number of involved nodes was six, with 0 co of patients showing more than 0 lymph nodes with metastases at dissection. The mean age was 54.8 years (range, 20 to 88 years). All scans were performed with real-time using a dynamic 0.5 MHz linear probe (HOI Ultramark 9, ATL, Bothell, WA) or 0 MHz linear array probe (VST Masters Series, Diasonics, Santa Clara, CA). Careful search for adenopathy was made along the axilla in longitudinal and transverse planes using the axillary vessels as a landmark. Nodes were defined as normal or abnormal on the basis of published criteria. 5,6 We defined a normal axillary lymph node on ultrasonograms as an ovoid hypoechoic C-shaped rim of lymphoid tissue (usually to 2 mm thick) around a central echogenic fatty hilum. An abnormal lymph node was rounded and hypoechoic, with or without associated eccentric cortical hypertrophy and obliteration of the fatty hilum.5 A further criterion of abnormality in this study was eccentric cortical hypertrophy (Fig. ). Size was not used as a criterion for metastatic nodes in this 996 by the American Institute of Ultrasound in Medicine J Ultrasound Med 6:24-246, /96/$3.50

2 242 AXILLARY LYMPH NODE METASTASES IN BREAST CANCER J Ultrasound Med 6:24-246, 996 Table 2: Axillary Lymph Node Involvemen t According to Tumor Size ( T Staging) Tumor Stage T (< 2 em) T2 (2-5 em) T~ (> 5 em) T4 (skin involvement) Figure Transverse ultrasonogram of the axilla shows eccentric cortical hypertrophy of a lymph node ( ~ lwrt whitr nrmws), which show(_>d metastatic carcinoma from the breast on fineneedle aspiration biopsy. Adjacent normi"'l lymph node is seen (/aug whitr nrmws). RESULTS Axillary dissection revealed metastases in 44 of 4 patients (38.9%). The ultrasonographic results are presented in Table. A total of 56 nodes were sonographically positive, compared with 326 histologically positive nodes. Seven false negative resu lts were found on ultrasonography, with a maximum of three histologically involved lymph nodes in these patients. Two false positive cases were diagnosed on ultrasonography, which turned out to be reactive hyperplasia on histologic examination. TabJe 2 shows the correlation between lymph node involvement and tumor size. The histologically positive and negative cases according to ultrasonographic findings are given in Tables 3 and 4. No axillary lymph node metastases were detected by mammogra phy or clinical examination that were missed by ultrasonography, as all seven sonographically fa lse negative cases also were missed by mammography and clinical examination. In 3 patients with axillary masses Table : Correlation Between Ultrasonography and Histology Number of Patients Sonogra phic fi ndings Nega tive Tot0l Negative Total B Nu mber of Patients wjth Lymph Node Involvement 8/ 40 30/ 66 3/ 5 3/ or axillary lymph nodes that were suggestive of metastases clinically and mammographically, ultrasonography showed normal axillary lymph nodes in six and no visible or abnormal axillary nodes in seven. One patient whose lymph nodes were clinically and mammographically suspected of being metastatic showed sonographic findings suggestive of obliteration of central fatty hilum, but this subsequently was found to be reactive hyperplasia (Fig. 2). Another patient, whose initial clinical presentation was a malignant right breast mass and a 5 em right axillary mass (thought to be axillary nodal metastasis clinically and mammographically), was shown to have two focal breast masses on ultrasonography, the second in the tail of the right breast (Fig. 3). Multifocal carcinoma was confirmed at mastectomy, and axillary nodal dissection was nega tive. The comparison between ultrasonography, mammography, and clinical examination is given in Table 5. The sonographic morphology of abnormal axillary nodes detected in this study are shown in Table 6. DISCUSSION The importance of axillary lymph node status has resulted in the development and exploration of many methods of preoperative detection of axillary nodal metastases. Approximately 50% of patients with palpable breast cancer have axillary lymph node metastases at presentation.,8 The prevalence of axillary nodal involvement in breast cancer is 40 to 0% and has been shown to be related to tumor size.9 The risk for a positive node is said to be 30% if the primary tumor is larger than em, and 5% if the primary tumor is less than em. In patients with T3 cancer, up to 60% will have axillary nodal metastases at presentation. Complete axillary node dissection with meticulous histopathologic search is the most accurate method of evaluation of the axilla, and this procedure is performed to determine the risk of systemic disease, for treatment planning and overall prognosis.

3 J Ultrasound Med 6:24-246, 996 Table 3: Histologically Proved Cases with Lymph Node Metastases ---- Ultrasonography No. Negative Total 3 44 Mammography Negative YANG ET AL 9 26 Clinical Negative Nonetheless, the 40% reported prevalence of axillary deposits in patients treated by mastectomy is believed by Steele to be a gross underestimation.jo lere is, however, evidence to the contrary that occult micrometastases do not prejudice survival In this study, mammography had a sensitivity of 40.9% and specificity of 80.0%, which was significantly lower than that for ultrasonography. This may be due to the difficult technique in examining the axilla and the limitations in mammographic resolution and depiction of lymph node morphology. Mammographically, a normal lymph node is seen as a rimlike structure with a fatty center surrounded by lymphoid tissue, whereas a metastatic node most frequently shows increased attenuation, with occasionally an irregular shape and rarely visible microcalcifications within.l2,3 Our results agree with those of earlier studies that ultrasonography is superior to palpation and mamfigure 2 Transverse ultrasonogram shows an axillary lymph node of less than em with findings suggestive of partial obliteration of the central fatty hilum (wlitc arrows). Axillary dissection revealed reactive hyperplasia with no evidence of metastases. Table 4: Histologically Proved Cases Without Lymph Node Metastases Ultrasonography No. Negative Total 68 0 Mammography Clinical Negative Negative mography in the detection of axillary nodal metastases. The sensitivity of high-resolution ultrasonography in this study (84.%) is higher than that reported by Pamilo and coworkerst3 (2.2%) and Bruneton and colleaguest4 (2.%). This improvement from previous studies in the 980s may be due to several factors, including more advanced technology and better defined criteria of normal and abnormal axillary lymph nodes on ultrasonography. Additional criteria for abnormal lymph nodes in this study included the morphology-e.g., obliteration of central fatty hilum (Fig. 4) and eccentric cortical hypertrophy (Fig. ). In previous studies,t3,t4 the presence of dark hypoechoic nodes (Figs. 5, 6) larger than 5 mm was the main criterion for abnormality. The specificity of ultrasonography in the detection of axillary metastases was 9. % and the accuracy was 92. %. However, although ultrasonography can depict an abnormal node well, it is not a reliable predictor of histologic nature, and currently it cannot always differentiate reactive or inflammatory conditions from malignant causes. Two false-positive cases were later found to be reactive hyperplasia on histologic examination (Fig. 2). Sonographically guided fine-needle sampling may increase reliability in such situations.3.5 The sensitivity of 84.% marks an improvement from previous studies, which ideally will encourage more sonographic studies of the axilla with the aim of detecting lymph node metastases and ultimately reducing the need for surgical exploration. The remaining 6% of false-negative cases include Table 5: Comparison of Ultrasonography, Mammography, and Clinical Evaluation in the Detection of Axillary Lymph Node Metastases in Breast Cancer Sensitivity Specificity Accuracy PPV NPV Ultrnsonography Mammography Clinical Evaluation 84.'i'o 9. % 92. % 94.9% 90.% 40.9% 80.0% 64.9% 56.3% 68.3% 34.'lo.% 60.5% 48.4% 65.% PPV, predictive value; NPV, Negative predictive value.

4 244 AXILLARY LYMPH NODE METASTASES IN BREAST CANCER Table 6: Abnormal Axillary Lymph Nodes on Ultrasonography (n = 39) Sonograpbic Morphology Rounded and hypoechoic Obliteration of fatty hilum Eccentric cortical hypertrophy (> 2 mm thickness) Number 32 0" 2 Five patients also showed rounded and hy poechoic lymph nodes. A J Ultrasound Med 6:24-246, 996 those cases with microscopic deposits (i.e., no macroscopically enlarged nodes). Although we believe this is likely to be beyond current ultrasound beam resolution and will be for some time, the results suggest that ultrasonography is a worthwhile technique on which to concentrate to further improve differentiation of reactive from malignant lymph nodes. In conclusion, the relatively high positive and negative predictive values of ultrasonography in detecting metastatic axillary nodes from breast cancer (94.9% and 90.%, respectively) suggest that it has a potential role in the prognostic work-up of patients who are not surgical candidates (because of either large tumors or poor physical condition), and also in situations in which breast conserving therapy or primary radiation therapy is an option. It js also useful for assessment after inadequate axillary dissection and for follow-up of the nontreated axilla, which has a much higher rate of recurrence.4 Figa re 3 A, Cranio-oblique mammogram shows a malignant appt.'i"'lri ng right breast lesion and a second malignant appear ing right axillary mass (arrows) thought to represent axillary nodal metastases. B, Ultrasonogram of the same patient shows the axillary mass was actually in the tail of the breast, demonstrating simililr morphology ilnd echotexture to the primary breilst lt.>sion (not shown). The diilgnosis of multifocill breilst carcinoma wils confi rmed at surgery. Axlllilry nodal d issection WilS negative.

5 J Ultrasound Med 6:24-246, 996 YANG ET AL 245 Figure 4 Obliteration of part of central fatty hilum (wflifearrows) in a patient with axillary metastases. REFERENCES. March DE, Wechsler RJ, Kurtz AB, et al; Cf-pathologic correlation of axillary lymph nodes in breast carcinoma. J Comput Assist Tomogr 5:440,99 2. Kalisher L: Xeroradiography of axillary lymph disease. Radiology :6, Kendall BE, Arthur JF, Patey DH: Lymphangiography in carcinoma of the breast: A comparison of clinical, radiological, and pathological findings in axillary lymph nodes. Cancer 6:233, Osborne MP, Payne JH, Richardson VJ, et al: Tile preoperative detection of axillary lymph node metastases in breast cancer by isotopic imaging. Br J Surg 0:4, 983 Yang WT, Ahuja A, Tang A, et al: Ultrasonographic demonstration of normal axillary lymph nodes - a learning curve. J Ultrasound Med 4:823, 995 Marchal G, Oyen R, Verschakelen J, et al: Sonographic appearance of normal lymph nodes. J Ultrasound Med 4:4, Henderson IC, Canellos GP: Cancer of the breast: The last decade. N Engl J Med 362:, Walsh JS, Dixon JM, Chetty U, et al: Colour Doppler studies of axillary node metastases in breast carcinoma. Clin Radiol49:89, Carter CL, Allen C, Henson DE: Relation of tumour size, lymph node status, and survival in 24,40 breast cancer cases. Cancer 63:8, Steele RJC: The axillary lymph nodes in breast cancer: Seven years on. J R Coli Surg Edinb 28:282, 983. Fisher ER, Swanmidoss S, Le CH, et al: Detection and significance of occult axillary metastases in patients with invasive breast cancer. Cancer 42:2025, Bjurstam NG: Radiography of the female breast and axilla. Acta Radio) Diagn Suppl35:0, 98 8 Figure 5 A, Ultrasonogram shows two matted, rounded, hypoechoic axillary lymph nodes with metastatic carcino rna. Note the obliterated fatty hilum in one node (wflite arrow). 8, Corresponding cranio-oblique mammogram shows the abnormal dense axillary nodes (arrows) and the primary breast malignancy.

6 246 AXILLARY LYMPH NODE METASTASES IN BREAST CANCER J Ultrasound Med 6:24-246, Pamilo M, Soiva M, Lwast E; Real time ultrasound, axil lary mammography and clinical examination in the detection of axillary lymph node metastases in breast cancer patients. J Ultrasound Med 8;5, Bruneton JN, Caramella E, Hery M, et al: Axilary lymph node metastases in breast cancer: Preoperative detection with US. Radiology 58:325, Fomage 8, Sneige N, Faroux MJ, et al: Sonographic appearance and ultrasound guided fine-needle aspiration biopsy of breast carcinomas smaller than cmj. J Ultrasound Med 9:559, 990 B Figure 6 A, Ultrasonogram of the axia demonstrates two rounded hypoechoic nodules highly suggestive of malig nancy. These were confirmed to be metastases til surgery. 8, Corresponding mammogram shows part of the abnormally dense axillary nodes (arrows).