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DOI: 10.1055/s-0032-1313113
False Negative Results in Axillary Lymph Nodes by Ultrasonography and Ultrasonography-Guided Fine-Needle Aspiration in Patients with Invasive Ductal Carcinoma
Falsch negative Ergebnisse der Untersuchung der axillären Lymphknoten mittels Sonografie und ultraschallgestützter Feinnadelpunktion bei Patienten mit invasiv-duktalem KarzinomPublikationsverlauf
17. April 2012
05. Juli 2012
Publikationsdatum:
20. Dezember 2012 (online)
![](https://www.thieme-connect.de/media/ultraschall/201306/lookinside/thumbnails/10.1055-s-0032-1313113-1.jpg)
Abstract
Purpose: For preoperative evaluation of ALN status using various methods, axillary US and subsequent US-FNA targeting the LNs suspicious for metastasis are the most widely used methods. The purpose of our study was to assess the rate of false-negative results at preoperative ultrasonography (US) and ultrasonography guided fine needle aspiration (US-FNA) of axillary lymph nodes (ALNs) in breast cancer patients and the number of false-negative lymph nodes, and to evaluate factors related to ALN false negative results in US and/or US-FNA in patients diagnosed with invasive ductal carcinoma.
Materials and Methods: Among 317 patients who underwent surgery for invasive ductal carcinoma during 2009 in Severance hospital, 237 patients had no reported ALN metastasis on preoperative US-FNA and US. We retrospectively reviewed the subsequent surgical pathology and clinicopathologic findings and assessed the rate of false-negative results from US and US-FNA of ALN and the number of false-negative lymph node. We performed univariate analysis and multivariate logistic regression analysis to evaluate the relationships between variable clinicopathologic factors (T-stage, position of ALN, hormone receptors, histologic grade, lymphovascular invasion (LVI) and performance of FNA) and cytologic results (false-negative result; FNALN and true negative result; TNALN) from US and/or US-FNA of ALN.
Results: The rate of false-negative results was 42.4 % (59/139) in both US and US-FNA of ALN but among them, 57.6 % (34/59) showed only one metastatic ALN. Breast cancer with FNALN on US and US-FNA was significantly related to positive estrogen receptor (p = 0.003), positive progesterone receptor (p = 0.001), and the presence of LVI (p = 0.004) in univariate analysis. In multivariate analysis, high T stages (≥ T2, odds ratio (OR) 4.007, p = 0.004) and LVI (OR 7.951, p = 0.001) showed significant correlation with FNALN on US and US-FNA.
Conclusion: More than half of patients with FNALN showed only one metastatic ALN. LVI and high T-stages were the most important factors attributed to FNALN on US and US-FNA in patients with invasive ductal carcinoma.
Zusammenfassung
Ziel: Für die präoperative Bewertung des axillären Lymphknoten(ALK-)Status mit verschiedenen Methoden sind die axilläre Sonografie und die darauf folgende Fokussierung der für Metastasen verdächtigen Lymphknoten mittels ultraschallgestützter Feinnadelpunktion (US-FNP) die am häufigsten eingesetzten Methoden. Das Ziel unserer Studie war es, die Rate an falsch negativen Ergebnissen beim präoperativen Ultraschall (US) und bei der ultraschallgestützten Feinnadelpunktion der axillären Lymphknoten bei Patienten mit Mammakarzinom zu berechnen und die Anzahl der falsch negativen Lymphknoten und der Faktoren zu bewerten, die mit den ALK falsch negativen Ergebnissen im US und/oder der US-FNP bei Patienten mit invasiv-duktalem Karzinom in Verbindung stehen.
Material und Methoden: Von den 317 Patientinnen, bei denen im Jahre 2009 im Severance Hospital aufgrund eines invasiv-duktalen Karzinoms eine Operation vorgenommen wurde, hatten 237 Patienten aufgrund der präoperativen US-FNP und des US keine ALK-Metastasen. Wir überprüften retrospektiv die darauffolgende chirurgische Pathologie und die klinisch-pathologischen Befunde und bestimmten die Rate der falsch negativen ALK-Ergebnisse in US und US-FNP und die Anzahl der falsch negativen Lymphknoten. Wir führten eine univariante Analyse und multivariante logistische Regressionsanalyse durch, um die Verhältnisse zwischen den verschiedenen klinisch-pathologischen Faktoren (T-Stadium, Lage der ALK, Hormonrezeptoren, histologische Graduierung, lymphovaskuläre Invasion [LVI] und Durchführung der FNP) und zytologischen Befunden (falsch negatives Ergebnis; FNALK und echt negatives Ergebnis; TNALK) in Bezug US und/oder US-FNP des ALK zu bewerten.
Ergebnisse: Die Rate an falsch negativen Ergebnissen betrug 42,4 % (59/139) sowohl im US als auch der US-FNP der ALK, aber davon zeigten 57,6 % (34/59) nur eine ALK-Metastase. Mammakarzinome mit FNALK im US und der US-FNP zeigten in der univarianten Analyse eine signifikante Korrelation zum positiven Östrogen-Rezeptor (p = 0,003), positiven Progesteron-Rezeptor (p = 0,001), und dem Vorliegen einer LVI (p = 0,004). Bei der multivarianten Analyse zeigten hohe T-Stadien (≥ T2, Odds Ratio [OR] 4,007, p = 0,004) und eine LVI (OR 7,951, p = 0,001) eine signifikante Korrelation zu FNALK im US und der US-FNP.
Schlussfolgerung: Mehr als die Hälfte der Patienten mit FNALK wiesen nur eine ALK-Metastase auf. LVI und hohe T-Stadien waren die wichtigsten Faktoren im Zusammenhang mit FNALK im US und der US-FNP bei Patienten mit invasiv-duktalem Karzinom.
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References
- 1 Wilking N, Rutqvist LE, Carstensen J et al. Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Stockholm Breast Cancer Study Group. Acta Oncol 1992; 31: 29-35
- 2 Bryan RM, Mercer RJ, Bennett RC et al. Prognostic factors in breast cancer and the development of a prognostic index. Br J Surg 1986; 73: 267-271
- 3 Fisher B, Bauer M, Wickerham DL et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 1983; 52: 1551-1557
- 4 Goyal A, Newcombe RG, Chhabra A et al. Morbidity in breast cancer patients with sentinel node metastases undergoing delayed axillary lymph node dissection (ALND) compared with immediate ALND. Ann Surg Oncol 2008; 15: 262-267
- 5 Veronesi U, Paganelli G, Galimberti V et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997; 349: 1864-1867
- 6 Purushotham AD, Upponi S, Klevesath MB et al. Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol 2005; 23: 4312-4321
- 7 Fraile M, Rull M, Julian FJ et al. Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: an approach to its validity. Ann Oncol 2000; 11: 701-705
- 8 Meng Y, Ward S, Cooper K et al. Cost-effectiveness of MRI and PET imaging for the evaluation of axillary lymph node metastases in early stage breast cancer. Eur J Surg Oncol 2011; 37: 40-46
- 9 Vaidya JS, Vyas JJ, Thakur MH et al. Role of ultrasonography to detect axillary node involvement in operable breast cancer. Eur J Surg Oncol 1996; 22: 140-143
- 10 Abe H, Schmidt RA, Sennett CA et al. US-guided core needle biopsy of axillary lymph nodes in patients with breast cancer: why and how to do it. Radiographics 2007; 27: S91-S99
- 11 de Freitas Jr R, Costa MV, Schneider SV et al. Accuracy of ultrasound and clinical examination in the diagnosis of axillary lymph node metastases in breast cancer. Eur J Surg Oncol 1991; 17: 240-244
- 12 Koehler KE, Ohlinger R. Sensitivity and specificity of preoperative ultrasonography for diagnosing nodal metastases in patients with breast cancer. Ultraschall in Med 2011; 32: 393-399
- 13 Krishnamurthy S, Sneige N, Bedi DG et al. Role of ultrasound-guided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma. Cancer 2002; 95: 982-988
- 14 Bonnema J, van Geel AN, van Ooijen B et al. Ultrasound-guided aspiration biopsy for detection of nonpalpable axillary node metastases in breast cancer patients: new diagnostic method. World J Surg 1997; 21: 270-274
- 15 de Kanter AY, van Eijck CH, van Geel AN et al. Multicentre study of ultrasonographically guided axillary node biopsy in patients with breast cancer. Br J Surg 1999; 86: 1459-1462
- 16 Bedrosian I, Bedi D, Kuerer HM et al. Impact of clinicopathological factors on sensitivity of axillary ultrasonography in the detection of axillary nodal metastases in patients with breast cancer. Ann Surg Oncol 2003; 10: 1025-1030
- 17 Deurloo EE, Tanis PJ, Gilhuijs KG et al. Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer. Eur J Cancer 2003; 39: 1068-1073
- 18 van Rijk MC, Deurloo EE, Nieweg OE et al. Ultrasonography and fine-needle aspiration cytology can spare breast cancer patients unnecessary sentinel lymph node biopsyUltrasonography and fine-needle aspiration cytology. Ann Surg Oncol 2006; 13: 31-35
- 19 Tinnemans JG, Wobbes T, Holland R et al. Treatment and survival of female patients with nonpalpable breast carcinoma. Ann Surg 1989; 209: 249-253
- 20 Silverstein MJ, Skinner KA, Lomis TJ. Predicting axillary nodal positivity in 2282 patients with breast carcinoma. World J Surg 2001; 25: 767-772
- 21 Kambouris AA. Axillary node metastases in relation to size and location of breast cancers: analysis of 147 patients. Am Surg 1996; 62: 519-524
- 22 Fein DA, Fowble BL, Hanlon AL et al. Identification of women with T1-T2 breast cancer at low risk of positive axillary nodes. J Surg Oncol 1997; 65: 34-39
- 23 Lee JH, Kim SH, Suh YJ et al. Predictors of Axillary Lymph Node Metastases (ALNM) in a Korean Population with T1-2 Breast Carcinoma: Triple Negative Breast Cancer has a High Incidence of ALNM Irrespective of the Tumor Size. Cancer Res Treat 2010; 42: 30-36
- 24 Boughey JC, Middleton LP, Harker L et al. Utility of ultrasound and fine-needle aspiration biopsy of the axilla in the assessment of invasive lobular carcinoma of the breast. Am J Surg 2007; 194: 450-455
- 25 Neal CH, Daly CP, Nees AV et al. Can preoperative axillary US help exclude N2 and N3 metastatic breast cancer?. Radiology 2010; 257: 335-341
- 26 Moore A, Hester M, Nam MW et al. Distinct lymph nodal sonographic characteristics in breast cancer patients at high risk for axillary metastases correlate with the final axillary stage. Br J Radiol 2008; 81: 630-636
- 27 Holwitt DM, Swatske ME, Gillanders WE et al. Scientific Presentation Award: The combination of axillary ultrasound and ultrasound-guided biopsy is an accurate predictor of axillary stage in clinically node-negative breast cancer patients. Am J Surg 2008; 196: 477-482
- 28 Yang WT, Chang J, Metreweli C. Patients with breast cancer: differences in color Doppler flow and gray-scale US features of benign and malignant axillary lymph nodes. Radiology 2000; 215: 568-573
- 29 Topal U, Punar S, Tasdelen I et al. Role of ultrasound-guided core needle biopsy of axillary lymph nodes in the initial staging of breast carcinoma. Eur J Radiol 2005; 56: 382-385
- 30 Moon HJ, Kim MJ, Kim EK et al. US surveillance of regional lymph node recurrence after breast cancer surgery. Radiology 2009; 252: 673-681
- 31 Edge SB, Byrd DR, Compton CC et al. AJCC cancer staging manual. 7th ed. New York, NY: Springer; 2010
- 32 Wolff AC, Hammond ME, Schwartz JN et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007; 25: 118-145
- 33 Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 1957; 11: 359-377
- 34 Rosen PP, Oberman HA, Hart WR et al. Tumors of the breast: based on the proceedings of the 53rd Annual Anatomic Pathology Slide Seminar of the American Society of Clinical Pathologists, October 29 and 30, 1987, Sheraton New Orleans Hotel, New Orleans, Louisiana. Chicago: ASCP Press; 1988
- 35 Genta F, Zanon E, Camanni M et al. Cost/accuracy ratio analysis in breast cancer patients undergoing ultrasound-guided fine-needle aspiration cytology, sentinel node biopsy, and frozen section of node. World J Surg 2007; 31: 1155-1163
- 36 Baruah BP, Goyal A, Young P et al. Axillary node staging by ultrasonography and fine-needle aspiration cytology in patients with breast cancer. Br J Surg 2010; 97: 680-683
- 37 Kuenen-Boumeester V, Menke-Pluymers M, de Kanter AY et al. Ultrasound-guided fine needle aspiration cytology of axillary lymph nodes in breast cancer patients. A preoperative staging procedure. Eur J Cancer 2003; 39: 170-174
- 38 Swinson C, Ravichandran D, Nayagam M et al. Ultrasound and fine needle aspiration cytology of the axilla in the pre-operative identification of axillary nodal involvement in breast cancer. Eur J Surg Oncol 2009; 35: 1152-1157
- 39 Brancato B, Zappa M, Bricolo D et al. Role of ultrasound-guided fine needle cytology of axillary lymph nodes in breast carcinoma staging. Radiol Med 2004; 108: 345-355
- 40 Gruber I, Hahn M, Fehm T et al. Relevance and Methods of Interventional Breast Sonography in Preoperative Axillary Lymph Node Staging. Ultraschall in Med 2011;
- 41 Bear HD. Completion axillary lymph node dissection for breast cancer: immediate versus delayed versus none. J Clin Oncol 2008; 26: 3483-3484
- 42 Grube BJ, Giuliano AE. Observation of the breast cancer patient with a tumor-positive sentinel node: implications of the ACOSOG Z0011 trial. Semin Surg Oncol 2001; 20: 230-237
- 43 Olson Jr JA, McCall LM, Beitsch P et al. Impact of immediate versus delayed axillary node dissection on surgical outcomes in breast cancer patients with positive sentinel nodes: results from American College of Surgeons Oncology Group Trials Z0010 and Z0011. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2008; 26: 3530-3535
- 44 Meretoja TJ, Vironen JH, Heikkila PS et al. Outcome of selected breast cancer patients with micrometastasis or isolated tumor cells in sentinel node biopsy and no completion axillary lymph node dissection. J Surg Oncol 102: 215-219
- 45 Maaskant-Braat AJ, van de Poll-Franse LV, Voogd AC et al. Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study. Breast cancer research and treatment 2011; 127: 195-203
- 46 Reed J, Rosman M, Verbanac KM et al. Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study. J Am Coll Surg 2009; 208: 333-340
- 47 Bernier J. Do we really need to undergo any axillary treatment after sentinel node biopsy in patients with early breast cancer and micrometastasis?. Breast 2011; 20: 385-388
- 48 Koelliker SL, Chung MA, Mainiero MB et al. Axillary lymph nodes: US-guided fine-needle aspiration for initial staging of breast cancer – correlation with primary tumor size. Radiology 2008; 246: 81-89
- 49 Somasundar P, Gass J, Steinhoff M et al. Role of ultrasound-guided axillary fine-needle aspiration in the management of invasive breast cancer. Am J Surg 2006; 192: 458-461
- 50 Onitilo AA, Engel JM, Greenlee RT et al. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 2009; 7: 4-13
- 51 Jonjic N, Mustac E, Dekanic A et al. Predicting sentinel lymph node metastases in infiltrating breast carcinoma with vascular invasion. Int J Surg Pathol 2006; 14: 306-311
- 52 Bevilacqua J, Cody 3rd H, MacDonald KA et al. A prospective validated model for predicting axillary node metastases based on 2,000 sentinel node procedures: the role of tumour location [corrected]. Eur J Surg Oncol 2002; 28: 490-500
- 53 Colleoni M, Rotmensz N, Maisonneuve P et al. Prognostic role of the extent of peritumoral vascular invasion in operable breast cancer. Ann Oncol 2007; 18: 1632-1640
- 54 Hayes BD, Feeley L, Quinn CM et al. Axillary fine needle aspiration cytology for pre-operative staging of patients with screen-detected invasive breast carcinoma. J Clin Pathol 2011; 64: 338-342
- 55 Ciatto S, Brancato B, Risso G et al. Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a triage test in breast cancer staging. Breast Cancer Res Treat 2007; 103: 85-91
- 56 Alkuwari E, Auger M. Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients: a study of 115 cases with cytologic-histologic correlation. Cancer 2008; 114: 89-93
- 57 Altomare V, Guerriero G, Carino R et al. Axillary lymph node echo-guided fine-needle aspiration cytology enables breast cancer patients to avoid a sentinel lymph node biopsy. Preliminary experience and a review of the literature. Surg Today 2007; 37: 735-739
- 58 Zakaria S, Pantvaidya G, Reynolds CA et al. Sentinel node positive breast cancer patients who do not undergo axillary dissection: are they different?. Surgery 2008; 143: 641-647
- 59 Leidenius MH, Vironen JH, Riihela MS et al. The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases. Eur J Surg Oncol 2005; 31: 13-18
- 60 Feu J, Tresserra F, Grases PJ et al. Ultrasonographic findings for in vitro detection of metastatic breast cancer in axillary lymph nodes. J Ultrasound Med 1999; 18: 727-728
- 61 Rao R, Lilley L, Andrews V et al. Axillary staging by percutaneous biopsy: sensitivity of fine-needle aspiration versus core needle biopsy. Ann Surg Oncol 2009; 16: 1170-1175
- 62 Taylor K, O’Keeffe S, Britton PD et al. Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: a pilot study. Clin Radiol 2011; 66: 1064-1071
- 63 Kim MJ, Park BW, Lim JB et al. Axillary lymph node metastasis: CA-15-3 and carcinoembryonic antigen concentrations in fine-needle aspirates for preoperative diagnosis in patients with breast cancer. Radiology 254: 691-697