Ultraschall Med 2014; 35(1): 67-71
DOI: 10.1055/s-0033-1335857
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Potential Use of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Metastatic Superficial Lymph Nodes in Melanoma Patients

Möglicher Einsatz von kontrastverstärktem Ultraschall (CEUS) zum Nachweis metastatischer oberflächlicher Lymphknoten bei Melanom-Patienten?
L. Rubaltelli
1   Department of Medicine, Radiology, University of Padova
,
V. Beltrame
1   Department of Medicine, Radiology, University of Padova
,
E. Scagliori
2   Department of Radiology, Venetian Oncology Institute (IOV), IRCCS, Padova
,
E. Bezzon
2   Department of Radiology, Venetian Oncology Institute (IOV), IRCCS, Padova
,
A. C. Frigo
3   Department of Environmental Medicine and Public Health, University of Padova
,
M. Rastrelli
4   Melanoma and Sarcoma Unit, Veneto Institute of Oncology (IOV), IRCCS, Padova
,
R. Stramare
1   Department of Medicine, Radiology, University of Padova
› Author Affiliations
Further Information

Publication History

05 December 2012

14 May 2013

Publication Date:
16 July 2013 (online)

Abstract

Purpose: Malignant melanoma represents a significant and growing public health burden worldwide. Ultrasonography is the most useful diagnostic modality for regional lymph nodal staging. Because any focal areas of cortical lobulation or thickening-swelling should also be considered as a sign of metastases, we are going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign or malignant lymph nodes in patients with malignant melanoma based on blood stream patterns and investigate the diagnostic capability.

Patients and Methods: After the excision of cutaneous melanoma with positive excision margins but with negative sentinel lymph node, 540 patients underwent US of superficial lymph nodes. The inclusion criteria for CEUS consisted of both major signs (absence of the echogenic hilus, round shape, and peripheral capsular vascularity) and minor ones (the presence of focal cortical thickening). The diagnostic capability was evaluated by comparing the cytological findings with the enhancement pattern on CEUS. 

Results: US in combination with CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99. The likelihood ratios confirmed the good performance of the methods used.

Conclusion: CEUS increases the diagnostic accuracy of US in the differential diagnosis of benign and malignant LNs but it also allows us, when possible, to avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with a reduction in the number of false negatives and much earlier detection of nodal metastatic foci.

Zusammenfassung

Ziel: Das maligne Melanom stellt ein bedeutendes und weltweit zunehmendes Gesundheitsproblem dar. Die Sonografie ist die nützlichste diagnostische Methode für das Staging der regionären Lymphknoten. Da alle fokalen Areale einer kortikalen Lobulierung, Verdickung oder Schwellung als Zeichen einer Metastasierung angesehen werden sollten, berichten wir über den Nutzen der kontrastverstärkten Ultrasonografie (CEUS) zur Differentialdiagnose gutartiger und maligner Lymphknoten basierend auf den Perfusionsmustern und untersuchen die Diagnosekapazität.

Patienten und Methoden: Nach Entfernung der kutanen Melanome mit positiven Schnitträndern und negativen Wächterknoten wurde bei 540 Patienten eine Sonografie der oberflächlichen Lymphknoten durchgeführt. Die Einschlusskriterien für CEUS bestanden sowohl aus den Hauptzeichen (Fehlen des echoreichen Hilus, runde Form und periphere, kapsuläre Durchblutung) als auch aus einem Nebenzeichen (Auftreten einer Kortexverdickung). Die diagnostische Wertigkeit wurde durch den Vergleich der zytologischen Befunde mit den Perfusionsmustern der CEUS ermittelt.

Ergebnisse: Ultraschall in Kombination mit CEUS klassifizierte 534/540 Patienten korrekt. CEUS bestätigte bei Lymphknoten, die im B-Bild eine fokale Kortexverdickung aufwiesen, eine hohe Sensitivität (0,98) und Spezifität (0,99), darüber hinaus führte CEUS zu einer deutlich verbesserten diagnostischen Genauigkeit von 0,99. Der Likelihood-Ratio-Test bestätigte die gute Leistungsfähigkeit der angewandten Methoden.

Schlussfolgerung: CEUS erhöht die diagnostische Genauigkeit des US bei der Differentialdiagnose gutartiger und maligner Lymphknoten (LN), und erlaubt uns, gegebenenfalls unnötige invasive Eingriffe wie eine Feinnadelaspirationszytologie zu vermeiden. Darüber hinaus kann CEUS die Feinnadelaspirationszytologie bei einer hypoperfundierten fokalen Kortexverdickung stützen, indem diese die Anzahl falsch-negativer Befunde verringert und den wesentlich früheren Nachweis nodaler metastatischer Herde ermöglicht.

 
  • References

  • 1 Beddingfield 3rd FC. The melanoma epidemic: res ipsa loquitur. Oncologist 2003; 8: 459-465
  • 2 Voit C, Kron M, Schäfer G et al. Ultrasound-guided fine needle aspiration cytology prior to sentinel lymph node biopsy in melanoma patients. Ann Surg Oncol 2006; 13: 1682-1689
  • 3 Jemal A, Murray T, Samuels A et al. Cancer statistics, 2003. CA Cancer J Clin 2003; 53: 5-26
  • 4 Rigel DS. Epidemiology of melanoma. Semin Cutan Med Surg 2010; 29: 204-209
  • 5 Martinez S, Tseng WH, Young SE. Outcomes for lymph node-positive cutaneous melanoma over two decades. World J Surg 2011; 35: 1567-72
  • 6 Balch CM, Soong SJ, Gershenwald JE et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 19: 3622-3634
  • 7 Bafounta ML, Beauchet A, Chagnon S et al. Ultrasonography or palpation for detection of melanoma nodal invasion: a meta-analysis. Lancet Oncol 2004; 5: 673-680
  • 8 Uren RF, Howman-Giles R, Thompson JF et al. High-resolution ultrasound to diagnose melanoma metastases in patients with clinically palpable lymph nodes. Australas Radiol 1999; 43: 148-152
  • 9 Voit C, Mayer T, Proebstle TM et al. Ultrasound-guided fine-needle aspiration cytology in the early detection of melanoma metastases. Cancer 2000; 90: 186-193
  • 10 Xing Y, Bronstein Y, Ross MI et al. Contemporary diagnostic imaging modalities for the staging and surveillance of melanoma patients: a meta-analysis. J Natl Cancer Inst 2011; 103: 129-142
  • 11 Prayer L, Winkelbauer H, Gritzmann N et al. Sonography versus palpation in the detection of regional lymph-node metastases in patients with malignant melanoma. Eur J Cancer 1990; 26 (07) 827-30
  • 12 Ahuja A, Ying M. An overview of neck node sonography. Invest Radiol 2002; 37: 333-342
  • 13 Ying M, Ahuja A. Sonography of neck lymph nodes. Part I: normal lymph nodes. Clin Radiol 2003; 58: 351-358
  • 14 Ahuja A, Ying M. Sonography of neck lymph nodes. Part II: abnormal lymph nodes. Clin Radiol 2003; 58: 359-366
  • 15 Choi MY, Lee JW, Jang KJ. Distinction between benign and malignant causes of cervical, axillary, and inguinal lymphadenopathy: value of Doppler spectral waveform analysis. Am J Roentgenol Am J Roentgenol 1995; 165: 981-984
  • 16 Giovagnorio F, Caiazzo R, Avitto A. Evaluation of vascular patterns of cervical lymph nodes with power Doppler sonography. J Clin Ultrasound 1997; 25: 71-76
  • 17 Tschammler A, Ott G, Schang T et al. Lymphadenopathy: differentiation of benign from malignant disease-color Doppler US assessment of intranodal angioarchitecture. Radiology 1998; 208: 117-123
  • 18 Ahuja AT, Ying M, Ho SS et al. Distribution of intranodal vessels in differentiating benign from metastatic neck nodes. Clin Radiol 2001; 56: 197-201
  • 19 Stramare R, Tregnaghi A, Fittà C et al. High-sensitivity power Doppler imaging of normal superficial lymph nodes. J Clin Ultrasound 2004; 32: 273-276
  • 20 Abe H, Schmidt RA, Kulkarni K et al. Axillary lymph nodes suspicious for breast cancer metastasis: sampling with US-guided 14-gauge core-needle biopsy-clinical experience in 100 patients. Radiology 2009; 250: 41-49
  • 21 Bedi DG, Krishnamurthy R, Krishnamurthy S et al. Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer: in vitro sonographic study. Am J Roentgenol Am J Roentgenol 2008; 191: 646-652
  • 22 Bossuyt PM, Reitsma JB, Bruns DE et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD Initiative. Radiology 2003; 226: 24-28
  • 23 Simel DL, Samsa GP, Matchar DB. Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol 1991; 44: 763-770
  • 24 Karim-Kos HE, de Vries E, Soerjomataram I et al. Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 2008; 44: 1345-1389
  • 25 Coory M, Baade P, Aitken J et al. Trends for in situ and invasive melanoma in Queensland, Australia, 1982–2002. Cancer Causes Control 2006; 17: 21-27
  • 26 Machet L, Nemeth-Normand F, Giraudeau B et al. Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients. Br J Dermatol 2005; 152: 66-70
  • 27 Schafer-Hesterberg G, Schoengen A, Sterry W et al. Use of ultrasound to early identify, diagnose and localize metastases in melanoma patients. Expert Rev Anticancer Ther 2007; 7: 1707-1716
  • 28 Rubaltelli L, Khadivi Y, Tregnaghi A et al. Evaluation of lymph node perfusion using continuous mode harmonic ultrasonography with a second-generation contrast agent. J Ultrasound Med 2004; 23: 829-836
  • 29 Rubaltelli L, Beltrame V, Tregnaghi A et al. Contrast-enhanced ultrasound for characterizing lymph nodes with focal cortical thickening in patients with cutaneous melanoma. Am J Roentgenol Am J Roentgenol 2011; 196: W8-W12
  • 30 Piscaglia F, Nolsøe C, Dietrich CF et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall in Med 2012; 33: 33-59