Real-time contrast enhanced ultrasound imaging of focal splenic lesions

European Journal of Radiology 83 (2014) 646–653

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Real-time contrast enhanced ultrasound imaging of focal splenic lesions Wei Li a , GuangJian Liu a,∗ , Wei Wang a , Zhu Wang a , Yang Huang a , ZuoFeng Xu a , XiaoYan Xie a , MingDe Lu a,b a Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-Sen University, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China b Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

a r t i c l e

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Article history: Received 6 November 2013 Received in revised form 11 January 2014 Accepted 13 January 2014 Keywords: Focal splenic lesion Ultrasound Contrast agent

a b s t r a c t Objective: To investigate the imaging features of focal splenic lesions (FSLs) on contrast-enhanced ultrasound (CEUS). Methods: Thirty two patients with FSLs proved by pathology were retrospectively analyzed. CEUS was performed using intravenous bolus injection of 2.4 ml sulfur hexafluoride-filled microbubble contrast agent and real time scanning. There were hemangioma (n = 7), lymphoma (n = 8), true cyst (n = 3), infarction (n = 4), hematolymphangioma (n = 2), metastasis tumor (n = 2), and one for each of the following entities extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans’ cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma. Results: Among 21 benign lesions, 4 infarctions and 3 cysts presented non-enhancement throughout CEUS scanning, and the other 14 lesions displayed various enhancement levels with 6 (42.9%) hyperenhancement, 2 (14.3%) iso-enhancement and 6 (42.9%) hypo-enhancement in arterial phase and 11 (78.6%) hypo-enhancement, 1 (7.1%) iso-enhancement and 2 (14.3%) hyper-enhancement in late phase, respectively. The enhancement pattern included 9 (64.3%) homogeneous, 4 (28.6%) heterogeneous and 1 (7.1%) rim-like enhancement. As for the malignant FSLs, all the lesions became completely or extensively hypo-enhancement during the late phase no matter their vascularity during arterial phase. Conclusions: The CEUS features reported in this series may enrich the knowledge for CEUS characterization of FSLs. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Focal splenic lesions (FSLs) are rare compared with liver, kidney and other abdominal parenchymal organs, but show a wide variety of pathologies. Vascular neoplasms of the spleen constitute the majority of primary FSLs, with benign vascular tumors such as hemangioma, hamartoma, lymphangioma, and malignant ones mainly of angiosarcoma [1]. As to the secondary splenic tumors, lymphoma and metastasis are dominate, where spleen may be involved in 30–40% of patients with systemic lymphoma [2,3], and metastasis in 1% of advanced visceral malignancy [4]. Although these tumors are rare, improvement for characterization of FSLs

∗ Corresponding author at: Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-Sen University, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China. Tel.: +86 20 87765183; fax: +86 20 87765183. E-mail address: [email protected] (G. Liu). 0720-048X/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2014.01.011

is extremely important in order to avoid unnecessary splenectomy and conserve the important immunological function of spleen in clinical practice. Most of the FSLs are found incidentally in asymptomatic patients by imaging evaluation. Characterization of FSLs also relies on imaging evaluation in clinical practice. Ultrasound (US) is the most popular imaging modality for screening and preliminary diagnosis of lesions from multiple parenchymal organs. But differentiation between benign and malignant FSLs is still challenging for US, since baseline gray scale US only had moderate accuracy around 50% [5], and color Doppler US provided limit information for the diagnosis [6–9]. Contrast-enhanced ultrasound (CEUS) has shown good performance in detection and characterization of focal liver lesions [10–13] and has been strongly recommended by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) in clinical practice [14–17]. However, the CEUS features of FSLs were still not extensively investigated, and the literatures concerning the CEUS findings of FSLs were mainly based on limited

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Table 1 The basic characteristics of 32 patients with focal splenic lesions. Entity

n

Male/female

Age (year)

Diameter (cm)

Solitary/multiple

Pathologic examination method, biopsy/surgery

Hemangioma Lymphoma Infarction Cyst Hematolymphangioma Langerhans’ cell histiocytosis Metastasis tumor Myxofibrosarcoma Inflammatory pseudotumor Extramedullary hemopoiesis Tuberculosis Hamartoma

7 8 4 3 2 1 2 1 1 1 1 1

3/4 5/3 2/2 2/1 0/2 0/1 2/0 0/1 1/0 1/0 0/1 1/0

39.4 ± 10.8 (27–56) 54.9 ± 11.3 (40–77) 47.3 ± 18.0 (29–65) 20.7 ± 2.5 (18–23) 24.3 ± 8.1 (15–29) 37 53 ± 21.2 (38–68) 55 39 62 55 52

4.9 ± 3.1 (1.2–9.0) 7.5 ± 3.3 (1.4–11.6) 5.5 ± 2.7 (2.7–8.9) 14.9 ± 13.9 (2.4–30.0) 3.1 ± 4.9 (1.1–4.2) 6.6 3.8 ± 0.4 (3.5–4.0) 17.0 6.0 4.6 1.7 4.3

6/1 1/7 4/0 3/0 1/1 1/0 1/1 1/0 1/0 1/0 1/0 1/0

3/4 4/4 3/1 0/3 0/2 0/1 0/2 0/1 0/1 1/0 0/1 0/1

Note: Values are mean ± SD (range).

cases with only part of lesions confirmed by histological diagnosis and showed some variable results. Furthermore, the CEUS findings of malignant and some benign FSLs may partially overlap which limited its performance for characterization. Therefore, the recommended uses and indications from EFSUMB are only for characterization of splenic parenchymal inhomogeneity or suspected lesions on conventional US; to confirm suspected splenic infarction; to characterize suspected accessory spleens or splenosis; and to detect splenic malignant lesions in oncologic patients when CT and/or MRI and PET are contraindicated or inconclusive [18,19]. This report describes our experience using CEUS to evaluate patients with a variety of FSLs. Here we present the imaging findings of pathologically proved FSLs on CEUS, in order to provide more knowledge of the enhancement features of FSLs which may be helpful for differential diagnoses in clinical practice. 2. Materials and methods

2.2. Examination technique All baseline US and CEUS examinations were performed by two radiologists with at least five years’ experiences on CEUS. The details of US equipment and settings of contrast specific imaging used in the present study were listed in Table 2. The size, location, echogenicity, and margin on baseline US together with the internal blood flow signals on color Doppler US were recorded. The contrast specific imaging was initiated to perform the real time CEUS examination. The most identifiable lesion on baseline US was selected as the targeted lesion for CEUS evaluation. A bolus injection of 2.4 ml of sulfur hexafluoride microbubble contrast agent (SonoVue® ; Bracco, Milan, Italy) was administered intravenously via a 20 G cannula in the antecubital vein, followed by a flush of 5 ml of saline solution immediately. The target lesion and surrounding spleen parenchyma were observed continuously for at least 3 min. All the images of CEUS were stored on the hard disk of the scanner in DICOM format.

2.1. Patients We retrospectively reviewed the images of 32 patients with FSLs who underwent CEUS examinations for characterization in our hospital from August 2005 to December 2012. There were 17 male and 15 female patients with mean age ± SD of 43.5 ± 13.4 years old (range from 15 to 77 years). The basic characteristics of these 32 patients were shown in Table 1. All the diagnoses were confirmed by pathologic examinations with specimens obtained from surgery (n = 21) or biopsy (n = 11). Biopsy was performed under US guidance using a core tissue biopsy system with 18 G needle (Bard MAGNUM® , AZ, USA). There were 7 hemangiomas, 8 lymphomas, 3 true cysts, 4 infarctions, 2 hematolymphangiomas, 2 metastatic tumors, and extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans’ cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma each in 1.

2.3. Image analysis All of the images were retrospectively reviewed by another two experienced radiologists on CEUS and were not involved in the scanning and blinded to the clinical and laboratorial information, histopathology results, and other imaging findings. Disagreements over the imaging findings were solved by consensus of the reviewers. The reviewers determined the diameters and echogenicity of the lesions on baseline US and evaluated the enhancement level and pattern in different phases of CEUS imaging. The enhancement levels of FSLs were classified as hyper-enhancement, iso-enhancement, hypoenhancement and non-enhancement compared with the surrounding spleen parenchyma; the contrast distribution was divided as

Table 2 Ultrasound equipment and contrast specific modes. Ultrasound equipment, manufacturer

Contrast specific imaging technique

Transducer

Mechanical index

Pre contrast SSD ␣10; Aloka, Tokyo, Japan

Extended PHD

Acuson Sequoia 512; Siemens, Mountain View, CA Aplio SSA-770A; Toshiba, Tokyo, Japan Aplio 500; Toshiba, Tokyo, Japan

Contrast pulse sequencing (CPS) Pulse subtraction-contrast harmonic imaging (PS-CHI) Pulse subtraction-contrast harmonic imaging (PS-CHI)

Convex array (model UST-9130), 2–6 MHz Vector array (model 4V1), 1–4 MHz Convex array (model PVT-375BT), 1.9–6.0 MHz Convex array (model PVT-375 BT), 1.9–6.0 MHz

Post contrast

0.60–1.10

0.06–0.20

1.40–1.90

0.15–0.21

0.40–1.10

0.06–0.10

0.40–1.10

0.06–0.10

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Fig. 1. Hemangioma. A well-defined hyper-echoic lesion (arrows) in the spleen with 1.6 cm in diameter on baseline US (A), heterogeneous hypo-enhancement in arterial phase (B, 22 s) and distinct hypo-enhancement in late phase (C, 123 s).

homogeneous, heterogeneous and peripheral rim-like enhancement. The phases of CEUS were defined as arterial phase (5–30 s) and late phase (60–300 s) after the contrast agent injection.

3. Results 3.1. Hemangioma On baseline US, 3 hemangiomas were hyper-echoic (42.9%), 3 hypo-echoic (42.9%) and 1 mixed echogenicity (14.3%). The majority of the lesions (6/7, 85.7%) were round with well-defined borders and without blood flow signals on color Doppler US. On CEUS, 4 (57.2%) showed hypo-enhancement in both arterial and late phase (Fig. 1); one (14.3%) presented iso-enhancement in arterial phase with slow wash-out in late phase. The other two (28.6%) lesions showed homogeneous or heterogeneous hyperenhancement in arterial phase with one washed out to be iso-enhancement and another one sustained hyper-enhancement in late phase (Fig. 2).

3.2. Lymphoma On baseline US, there were 7 (87.5%) patients presented diffused lesions and one with solitary lesion. As to the echogenicity, 5 (62.5%) of the lesions were hypo-echoic and the other 3 (37.5%) were mixed echogenicity. Half of the lymphomas showed sharp border and the other half were poorly defined in margin. On CEUS, the lesions showed hyper-enhancement, isoenhancement and hypo-enhancement in arterial phase were 4 (50%), 1 (12.5%) and 3 (37.5%), respectively. All the lesions presented contrast washout in late phase (Fig. 3). As for the enhancement pattern, 4 (50%) were heterogeneous, 3 (37.5%) were peripheral rim-like, and only 1 was homogeneous. 3.3. Infarction On baseline US, all lesions were hypo-echoic in wedge shape with poorly defined border and without blood flow signals on color Doppler US. On CEUS, all lesions showed wedge-shaped nonenhancement throughout examination with clear delineation of the border (Fig. 4).

Fig. 2. Hemangioma. A poorly defined iso-echoic lesion (arrows) in the spleen with 9.0 cm in diameter on baseline US (A), heterogeneous hyper-enhancement in arterial phase (B, 19 s) and sustained hyper-enhancement in late phase (C, 158 s). Contrast-enhanced CT scan correlated well with CEUS (D and E).

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Fig. 3. Lymphoma. A poorly defined mix-echoic lesion (arrows) in spleen with 11.1 cm in diameter on baseline US (A), heterogeneous hyper-enhancement in arterial phase (B, 14 s) and hypo-enhancement in late phase (C, 161 s).

3.4. Cyst

3.7. Other rare FSLs

On baseline US, all three cysts were anechoic, round in shape with well-defined border with one showed multiple internal separation. On CEUS, the wall and internal separation showed slight hyper-enhancement during the arterial phase, and the cystic part of the lesions presented non-enhancement throughout the vascular and late phase (Fig. 5).

On baseline imaging, one patient presented multiple lesions and the other with solitary lesion. Both cases were hypo-echoic and round in shape with well-defined margin. During arterial phase of CEUS, the solitary lesion showed heterogeneous hyper-enhancement, and the multiple lesions presented homogeneous hypo-enhancement. All the lesions showed clear contrast washout in late phase (Fig. 6).

The following FSLs are rare with only one case of each presented in our series, which included extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans’ cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma. On baseline US, all these lesions were round with well-defined margin. Langerhans’ cell histiocytosis, hamartoma and tuberculosis were hypo-echoic, extramedullary hemopoiesis showed hyperechoic, while inflammatory pseudotumor and myxofibrosarcoma presented mixed echogenicity. On CEUS, Langerhans’ cell histiocytosis, myxofibrosarcoma and extramedullary hemopoiesis (Fig. 8) showed hypo-enhancement, while inflammatory pseudotumor, hamartoma (Fig. 9) and tuberculosis (Fig. 10) were hyper-enhanced in arterial phase. Except the hamartoma sustained hyper-enhancement, all the other lesions showed contrast washout in late phase. The imaging characteristics of the lesions on CEUS examination are summarized in Table 3.

3.6. Metastatic tumor

4. Discussion

One splenic metastasis was from hepatocellular carcinoma and the other one from combined hepatocellular carcinoma and cholangiocarcinoma in our series. On baseline imaging, one case was multiple lesions and the other one was solitary lesion. All the metastatic tumors were hypo-echoic and round in shape with welldefined margin. During arterial phase of CEUS, the case with solitary lesion showed homogeneous hyper-enhancement, while the case with multiple lesions presented homogeneous hypo-enhancement. All the lesions washed out to be hypo-enhancement in the late phase (Fig. 7).

A great variety of FSLs may be incidentally found using imaging studies during clinical practice, which are challenging for the diagnosis. Timely characterization of FSLs can provide important information for a rational treatment decision. Since the imaging findings of FSLs are usually non-specific, precise non-invasive diagnosis could hardly be made. Even when typical imaging findings presented, many benign FSLs need long term follow-up and malignant ones require biopsy or splenectomy for confirmation of the diagnosis. Spleen resection may lead to the loss of the important immunological organ. Although the accuracy of US-guided percutaneous biopsy was reported high (84.9–92.0%) [20–22],

3.5. Hematolymphangioma

Fig. 4. Infarction. A poorly defined hypo-echoic lesion (arrows) in spleen with 6.2 cm in diameter on baseline US (A), non-enhancement in arterial phase (B, 11 s), and CECT shows wedge-shaped non-enhancement with clear delineation of the border (C).

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Fig. 5. Cyst. A poorly defined hypo-echoic lesion (arrows) in spleen with 12.5 cm in diameter on baseline US (A), and non-enhancement within the cyst, while the wall and internal separation shows slight hyper-enhancement in the arterial phase (B, 20 s).

Fig. 6. Hematolymphangioma. A well-defined hyper-echoic lesion (arrows) in spleen with 4.1 cm in diameter and lack of blood supply on color Doppler flow image (A), and hypo-enhancement in late phase (B, 80 s).

Fig. 7. Metastasis. A well-defined hypo-echoic lesion (arrows) in spleen with 4.0 cm in diameter on baseline US (A), homogeneous hyper-enhancement in arterial phase image (B, 18 s) and hypo-enhancement in late phase (C, 60 s).

complications like hemorrhage were also relatively high (1.3–3.8%) and may result in splenectomy or death [23–25]. To obtain a precise diagnosis of FSLs merely depending on the imaging findings on baseline and color Doppler US is extremely difficult. The application of second-generation microbubble contrast agents provides US the ability to visualize micro-perfusion of tissue with high temporal and spatial resolution in many organs, and the enhancement features of lesions are very helpful for characterization. CEUS has greatly improved the diagnostic performance of US, especially in the field of focal liver lesions which has been comparable to CECT [13]. The applications of CEUS in diagnosis of

FSLs were also reported in different studies based on different reference standard and has been included in the EFSUMB Guidelines for non-hepatic applications. Benign FSLs usually present nonenhancement or rapid wash-in in arterial phase with sustaining enhancement during late phase, while malignant FSLs often present rapid and marked wash-out in late phase no matter their appearance of arterial phase. However, the CEUS findings of malignant and some benign FSLs may overlap, where some hemangiomas, hamartomas and other uncommon lesions may show contrast wash-out in late phase and confuse with the malignant pattern [18,19]. Therefore, we presented our preliminary experiences on CEUS findings

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Fig. 8. Extramedullary hemopoiesis. A well-defined hyper-echoic lesion (arrows) located in hilus of spleen with 4.6 cm in diameter on baseline image (A), heterogeneous hypo-enhancement in arterial phase (B, 23 s) and hypo-enhancement in late phase (C, 90 s).

Fig. 9. Hamartoma. A well-defined hypo-echoic lesion (arrows) in spleen with 4.3 cm in diameter on baseline image (A), rich blood supply is shown on power Doppler image (B), homogenous hyper-enhancement in arterial phase (C, 18 s) and sustained hyper-enhancement in late phase (D, 180 s).

Fig. 10. Tuberculosis. A well-defined hypo-echoic lesion (arrows) in hilus of spleen with 1.7 cm in diameter on baseline image (A), homogeneous hyper-enhancement in arterial phase (B, 11 s) and hypo-enhancement in late phase (C, 72 s).

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Table 3 Enhancement level of lesions in different vascular phases (n = 32). Enhancement level

Hemangioma Lymphoma Infarction Cyst Hematolymphangioma Langerhans’ cell histiocytosis Metastasis tumor Myxofibrosarcoma Inflammatory pseudotumor Extramedullary hemopoiesis Tuberculosis Hamartoma

Arterial phase

Late phase

Hyper

Iso

Hypo

Non

Hyper

Iso

Hypo

Non

2 (28.6) 3 (37.5) 0 1 (33.3) 1 (50) 0

1 (14.3) 1 (12.5) 0 0 0 0

4 (57.1) 4 (50.0) 0 0 1 (50) 1 (100)

0 0 4 (100) 2 (66.7) 0 0

1 (14.3) 1 (12.5) 0 0 0 0

1(14.3) 0 0 0 0 0

5 (71.4) 7 (87.5) 0 1 (33.3) 2 (100) 1 (100)

0 0 4 (100) 2 (66.7) 0 0

1 (50.0) 0 1 (100)

0 0 0

1 (50.0) 1 (100) 0

0 0 0

0 0 0

0 0 0

2 (100) 1 (100) 1 (100)

0 0 0

0

1 (100)

0

0

0

0

1 (100)

0

1 (100) 1 (100)

0 0

0 0

0 0

0 1 (100)

0 0

1 (100) 0

0 0

Note: Data are numbers of lesions; data in parentheses are percentages.

of a wide variety of FSLs which were all proved by pathological examination, in order to broad the knowledge of CEUS features of FSLs. In our study, 32 patients including 21 benign and 11 malignant lesions were examined with CEUS. Among 21 benign lesions, 4 infarctions and 3 cysts presented non-enhancement throughout the CEUS examination, while the other 14 lesions displayed various enhancement levels and patterns. As for the malignant FSLs, all the lesions became completely or extensively hypo-enhancement during the late phase no matter their vascularity during arterial phase. Hemangiomas are the most common primary benign neoplasms of the spleen, which are usually asymptomatic and discovered incidentally [1]. Although spontaneous splenic rupture is rare, it may present acute clinical symptoms and result in emergency surgery [26]. Splenic hemangiomas have varied radiological appearances depending on the capillary or cavernous components of the hemangioma [27]. The smaller hemangiomas usually show homogeneous echogenicity on US, while the larger ones may present a more complex appearance due to development of thrombosis, infarction and pseudo cystic degeneration. The popular enhancement pattern of splenic hemangioma on CEUS was reported to be iso-enhancement in all phases or peripheral globular enhancement followed by progressive centripetal fill-in and persistent retention of contrast on the delayed phase. Cavernous hemangiomas typically show heterogeneous enhancement due to presence of cystic non-enhancing areas within the lesion. In the present study, none of hemangiomas presented the peripheral globular enhancement which was different from the literature. Ramani et al. [28] also reported that splenic hemangiomas do not have well-defined peripheral nodules that coalesce over time. This characteristic is thought to reflect the differences in vascular supply to the background organ rather than inherent differences which is different from hepatic hemangiomas. Based on our findings in these limited cases, CEUS could only provide few information for characterization of splenic hemangioma. Taibbi et al. [29] pointed out that further technique as CT and MRI might be mandatory for characterization of splenic hemangioma. And regular follow up is necessary once the diagnosis of hemangioma established. Hamartoma is another vascular tumor which had a characteristic arteriographic pattern with irregular dilated tortuous vessels on angiography [30]. In our case, the hamartoma lesion was markedly enhanced on CEUS which coincided with previous reports [30–33] that hamartoma may present a marked lasting enhancement in both phases.

For benign FSLs, CEUS may help to draw conclusive diagnosis of infarctions and cysts, which appear complete non-enhancement throughout CEUS procedure. But for some hemangioma, hamartoma and other relatively rare benign FSLs, such as inflammatory pseudotumor, extramedullary hemopoiesis, hematolymphangioma and tuberculosis, CEUS may present similar imaging findings with malignant tumors [18,19]. In this situation, further imaging studies and biopsy may be necessary for definitive diagnosis. Lymphomas have been described radiologically for four different patterns of splenic involvement, which were diffuse infiltration; small, focal or miliary nodules; multiple large nodular lesions; and bulky solid masses. Literature reported that lymphoma nodules and masses were lack of blood supply and hypo-enhancement on CECT and CEUS. In our series, most lymphomas were hypo-echoic or mixed-echoic with multiple lesions. And all the lymphomas showed hypo-enhancement in late phase, which was the same as the literature report [34], but displayed varied appearance in arterial phase as being hyper-, iso- or hypo-enhancing relative to normal spleen. Metastatic tumors of the spleen are relatively uncommon and secondary to lack of afferent lymphatic [4]. Most splenic metastasis tumors were from bronchogenic carcinomas, osteosarcomas, soft tissue sarcomas and renal cell carcinomas [35]. The sonographic appearances of splenic metastasis are variable and mostly appear to be hypo-echoic. Cystic or necrotic degeneration is usually seen in metastasis from melanoma and the lesions appear as unilocular or multilocular cystic lesions with septations. Splenic metastases typically enhance slightly followed by rapid washout which was similar to lymphoma [36,37]. Therefore, it is impossible to differentiate lymphoma from metastases on CEUS appearance alone. In our report, one metastasis was from hepatocellular carcinoma and the other from combined hepatocellular carcinoma and cholangiocarcinoma [38]. The former case showed homogeneous hyper-enhancement and the latter one was hypo-enhanced in arterial phase. Both lesions appeared to be rapid wash-out pattern in late phase. The other rare malignant tumors which included Langerhans’ cell histiocytosis and myxofibrosarcoma were described each one case in our data, showing consistently hypo-enhancement throughout the arterial and late phase of CEUS. Although all the malignant splenic tumors presented contrast washout in the late phase which agree with the general rule for malignant liver tumors on CEUS, it is still lack of specific features to differentiate from benign splenic ones.

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The main limitation of current study was small number of cases, especially for the rare FSLs. What’s more, SonoVue may produce spleen enhancement much longer than liver, usually more than 5 min. The reason might be specific accumulate of microbubbles in the reticuloendothelial system or sinusoids [39,40]. The absence of reticuloendothelial cells in the splenic tumors may result in differences in contrast enhancement between the lesions and the normal splenic parenchyma. In our and other previous studies, the lesions and spleen parenchyma were always scanned for about 5 min. Therefore, whether to extend the scan time until spleen specific phase may provide useful information for differentiation between benign and malignant FSLs should be future investigated.

[13]

[14]

[15]

[16]

5. Conclusions [17]

In summary, benign FSLs may present various features on CEUS except infarction and cystic lesions which always show non-enhancement. Some rare benign FSLs like inflammatory pseudotumor, hematolymphangioma, extramedullary hemopoiesis and tuberculosis may have similar appearance with malignant ones on CEUS. While malignant FSLs used to display rapid and distinct contrast wash-out in late phase no matter the enhancement level in arterial phase. Although our findings may enrich the knowledge of CEUS features of FSLs, CEUS could only help to draw conclusive diagnosis for infarction and cystic lesions and provide limited information for characterization of some FSLs. Therefore, CT or MRI should still be recommended for non-invasive characterization of FSLs when CEUS fails, and regular follow up or biopsy may be necessary for conclusive diagnosis. Financial support

[18]

[19]

[20] [21]

[22]

[23] [24]

[25] [26]

This study was supported by National Nature Science Foundation of China (Nos. 30901384, 81301238 and 81271576).

[27]

Conflicts of interest

[28]

There are no conflicts of interest to declare. References [1] Abbott RM, Levy AD, Aguilera NS, Gorospe L, Thompson WM. From the archives of the AFIP: primary vascular neoplasms of the spleen: radiologic–pathologic correlation. Radiographics 2004;24(4):1137–63. [2] Castellino RA. The non-Hodgkin lymphomas: practical concepts for the diagnostic radiologist. Radiology 1991;178(2):315–21. [3] Castellino RA. Hodgkin disease: practical concepts for the diagnostic radiologist. Radiology 1986;159(2):305–10. [4] Lam KY, Tang V. Metastatic tumors to the spleen: a 25-year clinicopathologic study. Arch Pathol Lab Med 2000;124(4):526–30. [5] Guibaud L. Sonography of the pediatric abdomen: pancreas and spleen. J Radiol 2001;82(6 Pt 2):755–63. [6] Stang A, Keles H, Hentschke S, et al. Differentiation of benign from malignant focal splenic lesions using sulfur hexafluoride-filled microbubble contrastenhanced pulse-inversion sonography. Am J Roentgenol 2009;193(3):709–21. [7] Urrutia M, Mergo PJ, Ros LH, Torres GM, Ros PR. Cystic masses of the spleen: radiologic–pathologic correlation. Radiographics 1996;16(1):107–29. [8] Benter T, Kluhs L, Teichgraber U. Sonography of the spleen. J Ultrasound Med 2011;30(9):1281–93. [9] Bhasin A, Gulati MS, Kashyap R. Value of power Doppler sonography in the evaluation of torsion in a wandering spleen. J Clin Ultrasound 2001;29(1): 60–1. [10] D’Onofrio M, Martone E, Faccioli N, Zamboni G, Malago R, Mucelli RP. Focal liver lesions: sinusoidal phase of CEUS. Abdom Imaging 2006;31(5):529–36. [11] Strobel D, Bernatik T, Blank W, et al. Diagnostic accuracy of CEUS in the differential diagnosis of small (
[29]

[30]

[31] [32]

[33]

[34] [35]

[36]

[37]

[38]

[39]

[40]

653

Trial): CEUS vs. MRI – a prospective comparison in 269 patients. Ultraschall Med 2010;31(5):492–9. Seitz K, Strobel D, Bernatik T, et al. Contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions – prospective comparison in clinical practice: CEUS vs. CT (DEGUM multicenter trial). Parts of this manuscript were presented at the Ultrasound Dreilandertreffen 2008, Davos. Ultraschall Med 2009;30(4):383–9. Claudon M, Dietrich CF, Choi BI, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver – update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall Med 2013;34(1):11–29. Claudon M, Cosgrove D, Albrecht T, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) – update 2008. Ultraschall Med 2008;29(1):28–44. Dietrich CF, Cui XW, Boozari B, Hocke M, Ignee A. Contrast-enhanced ultrasound (CEUS) in the diagnostic algorithm of hepatocellular and cholangiocellular carcinoma, comments on the AASLD guidelines. Ultraschall Med 2012;33(Suppl. 1):S57–66. Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. J Hepatol 2012;57(4):930–2. Sidhu PS, Choi BI, Nielsen MB. The EFSUMB guidelines on the non-hepatic clinical applications of contrast enhanced ultrasound (CEUS): a new dawn for the escalating use of this ubiquitous technique. Ultraschall Med 2012;33(1):5–7. 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 Med 2012;33(1):33–59. Friedlander MA, Wei XJ, Iyengar P, Moreira AL. Diagnostic pitfalls in fine needle aspiration biopsy of the spleen. Diagn Cytopathol 2008;36(2):69–75. McInnes MD, Kielar AZ, Macdonald DB. Percutaneous image-guided biopsy of the spleen: systematic review and meta-analysis of the complication rate and diagnostic accuracy. Radiology 2011;260(3):699–708. Liang P, Gao Y, Wang Y, Yu X, Yu D, Dong B. US-guided percutaneous needle biopsy of the spleen using 18-gauge versus 21-gauge needles. J Clin Ultrasound 2007;35(9):477–82. Cai Y, Liu X. Feasibility and safety of minilaparoscopy-guided spleen biopsy. Surg Endosc 2013;27(9):3499. Gomez-Rubio M, Lopez-Cano A, Rendon P, et al. Safety and diagnostic accuracy of percutaneous ultrasound-guided biopsy of the spleen: a multicenter study. J Clin Ultrasound 2009;37(8):445–50. O’Malley ME, Wood BJ, Boland GW, Mueller PR. Percutaneous imaging-guided biopsy of the spleen. Am J Roentgenol 1999;172(3):661–5. Laseter T, McReynolds T. Spontaneous splenic rupture. Mil Med 2004;169(8):673–4. Gorg C, Gorg K, Bert T, Barth P. Colour Doppler ultrasound patterns and clinical follow-up of incidentally found hypoechoic, vascular tumours of the spleen: evidence for a benign tumour. Br J Radiol 2006;79(940):319–25. Ramani M, Reinhold C, Semelka RC, et al. Splenic hemangiomas and hamartomas: MR imaging characteristics of 28 lesions. Radiology 1997;202(1):166–72. Taibbi A, Bartolotta TV, Matranga D, Midiri M, Lagalla R. Splenic hemangiomas: contrast-enhanced sonographic findings. J Ultrasound Med 2012;31(4):543–53. Chou YH, Chiou HJ, Tiu CM, Chiou SY, Hsia CY, Tsay SH. Splenic hamartoma: presentation on contrast-enhanced sonography. J Clin Ultrasound 2004;32(8):425–8. Yu RS, Zhang SZ, Hua JM. Imaging findings of splenic hamartoma. World J Gastroenterol 2004;10(17):2613–5. Wang JH, Ma XL, Ren FY, et al. Multi-modality imaging findings of splenic hamartoma: a report of nine cases and review of the literature. Abdom Imaging 2013;38(1):154–62. Nakanishi S, Shiraki K, Yamamoto K, et al. Basket pattern blood flow signals discovered in a case of splenic hamartoma by power Doppler ultrasonography. World J Gastroenterol 2005;11(33):5235–8. Yu X, Yu J, Liang P, Liu F. Real-time contrast-enhanced ultrasound in diagnosing of focal spleen lesions. Eur J Radiol 2012;81(3):430–6. Comperat E, Bardier-Dupas A, Camparo P, Capron F, Charlotte F. Splenic metastases: clinicopathologic presentation, differential diagnosis, and pathogenesis. Arch Pathol Lab Med 2007;131(6):965–9. Sutherland T, Temple F, Galvin A, Hennessy O. Contrast-enhanced ultrasound of the spleen: an introduction and pictorial essay. Insights Imaging 2011;2(5):515–24. Neesse A, Huth J, Kunsch S, et al. Contrast-enhanced ultrasound pattern of splenic metastases – a retrospective study in 32 patients. Ultraschall Med 2010;31(3):264–9. Huang Y, Liu GJ, Lu MD, Liao B. Gallbladder metastatic combined hepatocellular carcinoma and cholangiocarcinoma without primary intrahepatic tumor. Dig Dis Sci 2013;58(9):2733–5. Yanagisawa K, Moriyasu F, Miyahara T, Yuki M, Iijima H. Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol 2007;33(2):318–25. Lim AK, Patel N, Eckersley RJ, Taylor-Robinson SD, Cosgrove DO, Blomley MJ. Evidence for spleen-specific uptake of a microbubble contrast agent: a quantitative study in healthy volunteers. Radiology 2004;231(3):785–8.