Incidentally Detected Splenic Lesions in Ultrasound: Does Contrast-Enhanced Ultrasonography Improve the Differentiation of Benign Hemangioma/Hamartoma from Malignant Lesions?

Zusammenfassung

Ziel: Ziele dieser Arbeit waren die Identifikation und die Validierung von unterschiedlichen tumorspezifischen Kontrastmittelmustern für die Differenzialdiagnose zwischen benignen vaskulären Neoplasien (Typ Hämangiom/Hamartom) und malignen Milzherden in der Kontrastmittelsonografie (CEUS).

Material und Methoden: 136 Milzläsionen (58 benigne vaskuläre Neoplasien, 78 maligne Läsionen) wurden jeweils in der B-Bild-Sonografie (US) und nachfolgend in der Kontrastmittelsonografie nach Sulfur-Hexafluoride-Injektion untersucht und dokumentiert. Zwei On-site-Reader analysierten das Kontrastmittelverhalten der Milzläsionen während der arteriellen und parenchymalen Phase. Mittels univariater und multivariater Analyse wurden tumorspezifische Kontrastmittelmuster, die signifikant mit einer der beiden Tumordiagnosen korreliert waren, identifiziert. Zwei geblindete Off-site-Reader benutzten diese tumorspezifischen Kontrastmittelmuster als Diagnosekriterien und stellten unabhängig voneinander anhand der Befunde der B-Bild-Sonografie und der Kontrastmittelsonografie eine Diagnose der Milzherde. Die diagnostische Treffsicherheit und Confidence (Az-Werte) sowie die Übereinstimmung der Off-site-Reader (қ-Werte) wurden kalkuliert. Referenzstandards waren Histopathologie oder CT und/oder MRI mit klinischem Verlauf.

Ergebnisse: In der multivariate Analyse waren arterielles Hyper- oder Isoenhancement unabhängige Prediktoren für eine benigne vaskuläre Neoplasie (Odds Ratio, 3,558; p < 0,0017). In der Subgruppe der iso- oder hypoechogenen Läsionen war arterielles Hyperenhancement praktisch beweisend für eine benigne vaskuläre Neoplasie (Odds Ratio, 21,333; p < 0,001). In der geblindeten Situation verbesserte sich die diagnostische Treffsicherheit und Confidence (Az-Werte) für beide Off-site Reader signifikant von 63,2 % und 70,6 % (0,785 und 0,818) in der B-Bild-Sonografie auf 87,5 % und 88,2 % (0,915 und 0,908) in der Kontrastmittelsonografie (p < 0,001). Die Interreaderübereinstimmung verbesserte sich ebenfalls (қ = 0,52 für B-Bild-Sonografie vs. қ = 0,88 nach Kontrastmittelsonografie).

Schlussfolgerung: Die Kontrastmittelsonografie verbessert die Differenzialdiagnose zwischen benigen vaskulären Neoplasien und malignen Tumoren in der Milz und scheint besonders hilfreich bei unklaren, zufällig im Ultraschall entdeckten hypoechogenen Milzherden.

Abstract

Purpose: The aim of the study was to identify and validate enhancing features for differentiating benign vascular neoplasms of the hemangioma/hamartoma type from malignant splenic lesions on contrast-enhanced ultrasonography (CEUS).

Materials and Methods: 136 splenic lesions (58 benign vascular neoplasms, 78 malignant) in 136 patients underwent baseline US and pulse-inversion CEUS after sulfur hexafluoride-filled microbubble injection. Two on-site readers assessed lesion enhancement features during arterial and parenchymal phase in consensus. Best predicting CEUS features for lesion diagnosis were identified through univariate and multivariate analyses. Two blinded off-site readers independently issued a confidence rating for lesion diagnosis in baseline US and CEUS using extracted diagnostic CEUS features. Diagnostic performance, receiver operating curves (Az-value), and interreader agreement were calculated. The reference standards were histopathology or CT and/or MR imaging with clinical follow-up. 

Results: Multivariate analysis outlined arterial hyperenhancement or isoenhancement to be an independent CEUS predictor of benign vascular neoplasms (odds ratio, 3.558; p < 0.0017). Within the subgroup of isoechoic or hypoechoic lesions, arterial hyperenhancement was virtually diagnostic for benign vascular neoplasm (odds ratio, 21.333; p < 0.001). The diagnostic accuracy and confidence (Az-value) of the two readers was 63.2 % and 70.6 % (0.785 and 0.818) for baseline US, which improved significantly to 87.5 % and 88.2 % (0.915 and 0.908) for CEUS (p < 0.001). Interreader agreement also increased with CEUS (қ = 0.88) compared to baseline US (қ = 0.52).

Conclusion: Sulfur hexafluoride-enhanced CEUS improves differentiation between benign vascular and malignant splenic tumors and may be especially useful in clinical scenarios in which the incidental hypoechoic splenic lesion is unclear on conventional US.

Key words

spleen - ultrasound - microbubbles - hemangioma - lymphoma

• References

• 1 Abbott RM, Levy AD, Aguliera NS et al. From the archives of the AFIP. Primary vascular neoplasms of the spleen: radiologic-pathologic correlation. Radiographics 2004; 24: 1137-1163
• 2 Robertson F, Leander P, Ekberg O. Radiology of the spleen. Eur Radiol 2001; 11: 80-95
• 3 Stang A, Keles H, Hentschke S et al. Differentiation of benign from malignant splenic lesions using sulfur hexafluoride-filled microbubble contrast-enhanced pulse-inversion sonography. AJR Am J Roentgenol 2009; 193: 709-721
• 4 Görg C, Bert T. Contrast-enhanced sonography of focal splenic lesions with a second-generation contrast agent. Ultraschall in Med 2005; 26: 470-477
• 5 Kamaya A, Weinstein S, Desser TS. Multiple lesions of the spleen: differential diagnosis of cystic and solid lesions. Semin Ultrasound CT MRI 2006; 27: 389-403
• 6 Wan YL, Cheung YC, Lui KW et al. Ultrasonographic finding and differentiation of benign and malignant focal splenic lesions. Postgrad Med J 2000; 76: 488-493
• 7 Bachmann C, Görg C. The value of B-mode and colour Doppler sonography in the diagnosis of focal splenic lesions. Ultraschall in Med 2004; 25: 444-447
• 8 Paterson A, Frush DP, Donnelly LF et al. A pattern-oriented approach to splenic imaging in infants and children. Radiographics 1999; 19: 1465-1485
• 9 Ferrozzi F, Bova D, Draghi F et al. CT findings in primary vascular tumors of the spleen. AJR Am J Roentgenol 1996; 166: 1097-1101
• 10 Rabushka LS, Kawashima A, Fishman EK. Imaging of the spleen: CT with supplemental MR examination. Radiographics 1994; 14: 307-332
• 11 Luna A, Ribes R, Caro P et al. MRI of focal splenic lesions without and with dynamic gadolinium enhancement. AJR Am J Roentgenol 2006; 186: 1533-1547
• 12 Elsayes KM, Narra VR, Mukundan G et al. MR imaging of the spleen: spectrum of abnormalities. Radiographics 2005; 25: 967-982
• 13 Ramani M, Reinhold C, Semelka RC et al. Splenic hemangiomas and hamatomas: MR imaging characteristics of 28 lesions. Radiology 1997; 202: 166-172
• 14 Strobel D, Seitz K, Blank W et al. Contrast-enhanced Ultrasound for the Characterization of focal Liver Lesions – Diagnostic Accuracy in Clinical Practice (DEGUM Multicenter Trial). Ultraschall in Med 2008; 29: 499-505
• 15 Strobel D, Seitz K, Blank W et al. Tumor-Specific Vascularization Pattern of Liver Metastasis, Hepatocellular Carcinoma, Hemangioma, Focal Nodular Hyperplasia in the Differential Diagnosis of 1349 Liver Lesions in Contrast-Enhanced Ultrasound (CEUS). Ultraschall in Med 2009; 30: 376-382
• 16 Mostbeck G. CEUS from a Radiological Standpoint: Dream and Reality. Ultraschall in Med 2009; 30: 125-127
• 17 Braun B. Focal Liver Processes: Better is the Enemy of Good: CEUS in the Fast Lane. Ultraschall in Med 2009; 30: 329-332
• 18 Seitz K. EFSUMB-Guidelines for CEUS are Directive and Effective. Ultraschall in Med 2010; 31: 225-227
• 19 Seitz K, Strobel D, Bernatik T et al. Contrast-Enhanced Ultrasound for the Characterization of Focal Liver Lesions – Prospective Comparison in Clinical Practice: CEUS vs. CT (DEGUM Multicenter Trial). Ultraschall in Med 2009; 30: 383-389
• 20 Seitz K, Bernatik T, Strobel D et al. Contrast-Enhanced Ultrasound (CEUS) for the Characterization of Focal Liver Lesions (DEGUM Multicenter Trial) – CEUS vs. MRI – a Prospective Comparison in 269 Patients. Ultraschall in Med 2010; 31: 492-499
• 21 Catalano O, Lobianco R, Sandomenico F et al. Real-time contrast-enhanced ultrasound of the spleen: examination technique and preliminary clinical experience. Radiol Med 2003; 106: 338-356
• 22 Catalano O, Sandomenico F, Matarazzo I et al. Contrast-enhanced sonography of the spleen. AJR Am J Roentgenol 2005; 184: 1150-1156
• 23 Catalano O, Sandomenico F, Vallone P et al. Contrast-enhanced sonography of the spleen. Semin Ultrasound CT MRI 2006; 27: 426-433
• 24 Peddu P, Shah M, Sidhu PS. Splenic abnormalities: a comparative review of ultrasound, microbubble-enhanced ultrasound and computed tomography. Clin Radiol 2004; 59: 777-792
• 25 Chiavaroli R, Pierfrancesco G, Tundo P. Characterization of nontraumatic focal splenic lesions using contrast-enhanced sonography. J Clin Ultrasound 2011; 39: 310-315
• 26 Yu X, Yu J, Liang P et al. Real-time contrast-enhanced ultrasound in diagnosing of focal spleen lesions. Eur J Radiol 25.01.2011; Epub ahead of print
• 27 von Herbay A, Barreiro AP, Ignee A et al. Contrast-enhanced ultrasonography with Sonovue: Differentiation between benign and malignant lesions of the spleen. J Ultrasound Med 2009; 28: 421-434
• 28 Görg C. The forgotten organ: contrast-enhanced sonography of the spleen. Eur J Radiol 2007; 64: 189-201
• 29 Görg C, Görg K, Bert T et al. Colour Doppler ultrasound patterns and clinical follow-up of incidentally found hypoechoic vascular tumors in the spleen: evidence for a benign tumor. Br J Radiol 2006; 79; 319-325
• 30 Bert T, Tebbe J, Görg C. What should be done with echoic splenic tumors incidentally found by ultrasound ?. Z Gastroenterol 2010; 48: 465-471
• 31 Chou YH, Chiou HJ, Tiu CM et al. Splenic hamartoma: presentation on contrast-enhanced sonography. J Clin Ultrasound 2004; 32: 425-428
• 32 McGahan JP, Horton S, Gercovich EO et al. Appearance of solid organ injury with contrast-enhanced sonography in blunt andominal trauma: preliminary experience. AJR Am J Roentgenol 2006; 187: 658-666
• 33 Seeger M, Fölsch UR. Diagnosis of acute splenic infarction by echo-enhanced ultrasound. Dtsch Med Wochenschr 2004; 129: 876-879
• 34 Görg C, Graef C, Bert T. Contrast-enhanced sonography for differential diagnosis of an inhomogeneous spleen of unknown cause in patients with pain in the left upper quadrant. J Ultrasound Med 2006; 25: 729-734
• 35 Perez-Grueso MJ, Repiso A, Gomez R et al. Splenic focal lesions as manifestation of sarcoidosis: characterization with contrast-enhanced sonography. J Clin Ultrasound 2007; 35: 405-408
• 36 Tafuto S, Catalano O, Barba G et al. Real-time contrast-enhanced specific ultrasound in staging and follow-up of splenic lymphomas. Front Biosci 2006; 11: 2224-2226
• 37 Picardi M, Soricelli A, Pane F et al. Contrast-enhanced harmonic compound US of the spleen to increase staging accuracy in patients with Hodgkin lymphoma: a prospective study. Radiology 2009; 251: 574-582
• 38 Neese A, Huth J, Kunsch S et al. Contrast-Enhanced Ultrasound Pattern of Splenic Metastases – a retrospective study in 32 patients. Ultraschall in Med 2010; 31: 264-269
• 39 Claudon M, Cosgrove D, Albrecht T et al. Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) – Update 2008. Ultraschall in Med 2008; 29: 28-44
• 40 Piscaglia F, Nolsoe 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 2011; 32, 26 August, epub ahead of print
• 41 Stang A, Keles H, Seydewitz C et al. Contrast agents in transabdominal ultrasonography: state of the art and perspectives. Dtsch Med Wochenschr 2006; 131: 1813-1818
• 42 Lim AK, Patel N, Eckersley RJ et al. Evidence for spleen-specific uptake of a microbubble contrast agent: a quantitative study in healthy volunteers. Radiology 2004; 231: 785-788
• 43 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristics curves: a nonparametric approach. Biometrics 1988; 44: 837-845
• 44 Hanley JA, McNeil BJ. A method of comparing areas under receiver operating characteristics curves derived from the same cases. Radiology 1983; 148: 839-843
• 45 Landis JR, Koch GG. The measurement of observer agreement for categorial data. Biometrics 1977; 33: 159-174
• 46 Wilson SR, Burns PN. Microbubble-enhanced US in body imaging: what role ?. Radiology 2010; 257: 24-39
• 47 Ros RP, Moser RP, Dachman AH et al. Hemangioma of the spleen: radiologic-pathologic correlation in ten cases. Radiology 1987; 162: 73-77
• 48 Kishikawa T, Numaguchi Y, Watanabe K et al. Angiographic diagnosis of benign and malignant splenic tumors. AJR Am J Roentgenol 1978; 130: 339-344
• 49 Rösch J. Tumours of the spleen: the value of selective arteriography. Clin Radiol 1966; 17: 183-190
• 50 Wexter L, Abrams ML. Hamartoma of the splee. Angiographic observation. AJR Am J Roentgenol 1964; 92: 1150-1155
• 51 Teates CD, Seale DC, Allen MS. Hamartoma of the spleen. AJR Am J Roentgenol 1972; 116: 419-422
• 52 Tada S, Shin M, Takashima T et al. Diffuse capillary hemangiomatosis of the spleen as a course of portal hypertension. Radiology 1972; 104: 63-64
• 53 Peronneau P, Lasau N, Leguerny L et al. Contrast Ultrasonography: Necessity of linear Data Processing for the Quantification of Tumor Vascularisation. Ultraschall in Med 2010; 31: 370-378