Conventional and contrast-enhanced ultrasound of scleroring angiomatoid nodular transformation of the spleen

Abstract

Sclerosing angiomatoid nodular transformation (SANT) is an uncommon non-tumorous disease of the spleen. The low morbidity and non-specific clinical symptoms of SANT might cause a misdiagnosis. The present study reported a case of a 31-year-old female with a SANT of the spleen. Findings on clinical manifestations and examinations, especially on contrast-enhanced ultrasound (CEUS), were carefully analyzed, and relevant literatures have also been reviewed.

Keywords

Scleroring angiomatoid nodular transformation spleen contrast-enhanced ultrasound

1 Introduction

Sclerosing angiomatoid nodular transformation (SANT) is an uncommon non-tumorous disease of the spleen. It was originally recognized and named by Martel and co-workers [1] in 2004. The main pathology features of the SANT are multiple angiomatoid nodular, along with normal splenic vascular markers in the angiomatoid nodules. SANT are often detected by health examination occasionally, because the majority of patients may be symptomless [2, 3]. Imaging modalities, such as ultrasound (US) and computed tomography (CT), are used to help diagnosing this disease in the spleen, but this disease is easily mixed up with a malignant tumor of the spleen [4, 5]. To further confirm the diagnosis of the SANT of the spleen, pathological and histochemical examinations are most essential. As a result, splenectomy is at the same time diagnostic and curative treatment for patients with SANT of the spleen [6].

At present, imaging findings of SANT of the spleen are widely described on conventional US, CT and magnetic resonance imaging (MRI) [7, 8]. However, only a few reports applied contrast-enhanced ultrasound (CEUS) in the diagnosis of SANT [9 –12]. According to guidelines by European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), CEUS facilitates identification of focal spleen lesions [13]. In this article, we report a case of a female patient with SANT of the spleen on various imaging examinations, especially on CEUS. The basic characteristics of SANT are discussed through literature review.

2 A case report

A 31-year-old female patient with a history of splenic space-occupying lesion (SOL) was referred to a follow-up US examination. The splenic SOL was firstly found by abdominal US during her health examination three years ago. Then, the patient was referred for contrast-enhanced magnetic resonance imaging (CEMRI) examinations, which showed a SOL in the spleen (about 3.8 cm in diameter). Clinician considered it a high probability of a splenic hemangioma at that time. The patient was asymptomatic and chose follow-up. Abdominal US follow-up at this time showed that the size of the splenic SOL significantly increased to 8.0 cm. Laboratory examination showed elevated C-reactive protein (CRP) (49.40 mg/L; reference limit:<8.20 mg/L), slightly decreased prealbumin (126 mg/L; reference range: 180-350 mg/L), slightly decreased albumin (34.9 mg/L; reference range: 40-55 mg/L). Serum tumor markers and hepatitis markers were in the normal level. As the pretreatment examinations for surgical treatment, she underwent contrast-enhanced computed tomography (CECT) and CEUS examinations. Findings on imaging and associated literatures were reviewed as shown below.

2.1 Imaging findings

2.1.1 CEMRI

The MR examinations three years ago were performed using Magnetom^® Trio Tim 3.0 MRI (Siemens AG, Munich, Germany). The contrast agent was administrated by means of a bolus injection of Gd-DTPA with a total dose of 30 ml. CEMRI showed a well-defined and lobulated SOL, which was about 3.8 cm in diameter, on the upper part of the spleen. The SOL showed homogeneous iso-intense on T1-weighted images, and slightly hypo-intense on T2-weighted images with patchy hypo-intense inside the lesion. Besides, no hyper-intense signal was observed on diffusion weighted imaging (DWI). The lesion appeared significant nodular enhancement at the periphery of the lesion during the arterial phase and spoke-wheel enhancement inside the lesion during the venous phase. The contrast agent was gradually filled in the delayed phase (Fig. 1). In general, the lesion showed a pattern of centripetal enhancement.

Fig. 1

MRI and CEMRI findings showed a SOL of the spleen. (a) T1-weighted image: a well-defined and homogeneous iso-intense SOL (white arrow) is found in the spleen (3.8 cm in diameter). (b) T2-weighted image: the lesion (white arrow) is slightly hypo-intense with patchy hypo-intense inside. (c) DWI: no high signal is found in the SOL (white arrow). (d) Arterial phase on dynamic CEMRI: the lesion (white arrow) appears significant nodular enhancement at the periphery. (e) Venous phase on dynamic CEMRI: spoke-wheel-like enhancement is seen inside the lesion (white arrow). (f) Delayed phase on dynamic CEMRI: the contrast agent is gradually filled. MRI: magnetic resonance imaging; CEMRI: contrast-enhanced magnetic resonance imaging. SOL: space-occupying lesion; DWI: diffusion weighted imaging.

2.1.2 CECT

The CT examinations before surgery were accomplished using a 64-slice CT scanner (Aquilion 64, Toshiba, Otawara, Japan). The contrast agent of iodixanol was administrated with a total dose of 100 ml and an injection rate of 2.5 ml/s. On unenhanced CT, a quasi-circular SOL (size: 7.8×6.0×8.0 cm) was found in the spleen, with slightly lower density and a slightly poorly defined boundary. The SOL was heterogenous with an average CT value of about 38 HU. After injecting contrast agent, the lesion showed nodular and septum-like enhancement at the periphery of the lesion during the arterial phase. In the venous phase and the delayed phase, there was an enlarged enhancement but not entire enhancement (Fig. 2). As a result, the lesion was suspicious of a splenic hemangioma.

Fig. 2

Unenhanced CT and CECT findings. (a) Unenhanced CT: the lesion of the spleen is quasi-circular with a slightly lower density and a slightly poorly defined boundary (size: 7.8×6.0×8.0 cm). (b) Arterial phase on dynamic CECT: nodular and septum-like enhancement is seen at the periphery of the lesion (white arrow). (c) Venous phase and (d) delayed phase on dynamic CECT: an enlarged but incomplete enhancement of the lesion (white arrow) is shown. CT: computed tomography; CECT: contrast-enhanced computed tomography.

2.1.3 Conventional US

Conventional US were performed using a GE LOGIQ E9 scanner (GE Healthcare, Milwaukee, WI, USA) with a 1–5 MHz curvilinear abdominal transducer. Gray-scale US showed a hypoechoic SOL (size: 8.0 cm×7.8 cm) in the enlarged spleen, with slightly irregular shape and well-defined margin. The SOL was heterogeneous, with short linear hyperechoic septa inside and posterior acoustic shadowing. Color Doppler US showed that the spleen vein is displaced by the compression of the lesion, and sparse blood flow signals were found inside the lesion (Fig. 3). The resistance index (RI) was 0.56 on pulsed wave (PW) Doppler US.

Fig. 3

US patterns of the spleen and appearance of the lesion during surgery. (a) Gray-scale US: a hypoechoic lesion (white arrow), with slightly irregular shape and well-defined margin is found in the spleen (size: 8.0 cm×7.8 cm). In addition, short linear hyperechoic septa is seen inside the lesion, along with posterior acoustic shadowing. (b) Color Doppler US: the displaced spleen vein (white arrow) and sparse blood flow signals are found inside the lesion. (c) Arterial phase (23 sec) and (d) Venous phase (99 sec) on CEUS: concentric hypo-enhancement is seen in comparison with the splenic parenchyma. (e) Delayed phase (183 sec) on CEUS: the lesion (white arrow) demonstrates remarkable hypo-enhancement. (f) Appearance of the lesion in laparoscopic surgery: the lesion is wine with the size of 8.0×7.8×6.0 cm (white arrow). Angiomatoid nodules are seen on its surface. US: ultrasound; CEUS: contrast-enhanced ultrasound.

2.1.4 CEUS

CEUS was performed with the same scanner and transducer by the same radiologist. The contrast agent (SonoVue, Bracco, Milan, Italy) was administrated by means of a bolus injection with a total dose of 1.5 ml. Then, 5 ml of saline solution was immediately followed. The lesion was firstly enhanced in 8 s after injecting contrast agent, with peripheral nodular enhancement. Afterwords, the range of enhancement expanded rapidly from the periphery to the center, reaching full enhancement at 11 s after contrast agent administration. The lesion is hypo-enhanced in comparison with the splenic parenchyma during the arterial phase and the venous phase. The shape and margin of the lesion on CEUS were clearer comparing to conventional US. However, the lesion showed remarkable hypo-enhancement in the delayed phase (Fig. 3). The initial diagnosis was inconclusive. Even though the lesion showed a pattern of centripetal enhancement in the early arterial phase, contrast agent washed out significantly in the delayed phase. Furthermore, the size of the lesion increased remarkably in the last three years, indicating the probability of malignant tumor of the spleen needs to be vigilant.

2.2 Pathological findings

Ultimately, laparoscopic splenectomy was performed for treatment. In appearance, the lesion tissue (size: 8.0×7.8×6.0 cm) was gray-red, in medium texture, along with angiomatoid nodules (Fig. 3f). Immunohistochemistry results of the specimen were shown as follows: CK-P(+), CK8/18(-), CD31(+), CD34(+), ERG(+), F8(+), S-100(-), P53(+), LCA(+), Ki-67(3% +) and EBER(-). Combining imaging, appearance, immunohistochemical findings and no medical history of other tumors, the lesion was considered as SANT of the spleen.

3 Discussions

SANT is a very uncommon non-tumorous entity of the spleen. At present, only a few cases of SANT of the spleen were reported in the literatures [3, 14]. Depending on a systematic review, SANT of the spleen occurs slightly more in females than in males (52.1% vs. 47.9%) [3]. More than half patients were incidentally discovered with SANT of the spleen during health examination [3]. Patients usually have no symptoms, but may go through abdominal discomfort, splenomegaly, acute abdomen, fever or vomiting [2]. The etiology of SANT of the spleen is unknown so far, which may be related to systemic inflammatory response and infection of Epstein-Barr virus [15 –17]. Some scholars believe the entity may be secondary to tissue hematoma caused by circulatory disorders or trauma, and then appears nodular transformation [1].

Generally, the diagnosis of SANT relies on pathology. On the gross pathology, most lesions are solitary, with good circumscription. The lesion shows a nodular and hemorrhagic appearance with dense fibrotic septa. Immunohistochemical results show peculiar heterogeneous immunostaining profile for vascular markers. The angiomatoid nodules of SANT consist of 3 distinct immunophenotypes: cord capillaries (CD34 + /CD8-/CD31+), sinusoids (CD34-/CD8 + /CD31+), and small veins (CD34-/CD8-/CD31+) [1]. However, SANT sometimes mimics a malignant tumor or metastatic tumor due to its nodular and vascular features and rapid growth [18, 19]. Splenectomy is both diagnostic and curative treatment for managing this entity [20]. Besides, previous study reported that endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed great value on diagnosing SANT [21].

Imaging examinations are vital for SANT diagnosis, because there are nearly no classical clinical symptoms and serum tumor markers of the patient. SANT of the spleen appears as a solid, single, oval or lobular, and well-defined lesion with a fibrous scar and occasional calcification on CT and MRI images. On unenhanced CT and MRI, it is difficult to differentiate between SANTs of the spleen and hemangiomas. The enhancement pattern of SANT of the spleen on CT/MRI shows a peripheral nodular enhancement and then progressive and centripetal nature, which is similar to that of hemangioma. Delayed enhancement of central fibrous scar is an important feature for diagnosing SANT [22]. Besides, multifarious comorbidities, such as liver cysts, renal cysts, solid tumor, etc. may accompany with SANT of the spleen [23].

On conventional gray-scale US, SANT of the spleen typically presents as a heterogeneous and hypoechoic lesion, which has a relatively regular shape [10]. In this case, the lesion was heterogeneous hypoechoic and irregular. It should be noted that there were short linear or flaky hyperechonic regions inside the lesion with posterior acoustic shadowing, which is consistent with the case of Menozzi et al. [12]. We speculated that the US feature corresponded to fibroclerotic tissue of the lesion. On color Doppler US, it usually presents sparse or no blood flow signals inside the lesion.

As for CEUS, it has potential of discriminating between benign and malignant disease of the spleen. In a single-center study by Lerchbaumer et al., CEUS correctly differentiated the benign and malignant focal splenic lesions with the accuracy of 98% [24]. Malignant tumors usually show early enhancement in the arterial phase and washout in the late phase on CEUS [25]. Besides, internal perfusion, heterogeneous enhancement, punctate enhancement and necrotic regions are also highly suggestive of malignancy [26]. Splenic benign tumors such as vascular tumors often show persistent late phase enhancement [13]. However, in this case, the CEUS patterns were not like typical common tumors of the spleen. The present case manifested peripheral nodular enhancement with rapid centripetal enhancement. The enhancement declined gradually during the venous phase and washed out in the delayed phase. Previous studies suggested that CEUS could provide morphologic information for diagnosing SANT of the spleen. However, the data is still limited [9–12 , 18]. To our knowledge, there are five studies using CEUS to diagnose SANT of the spleen (Table 1). Among the six cases reported in the previous studies, three of them demonstrated the spoke-wheel-like enhancement pattern, which means the enhancement begins from the periphery to the center of the lesion along with some “spoke wheel” pattern arterial vessels in the center. Similarly in the present case, the lesion showed the spoke-wheel-like enhancement pattern in the early arterial phase.

Table 1

Contrast-enhanced ultrasound findings in 7 patients with sclerosing angiomatoid nodular transformation of the spleen

Studies	Contrast agent	Size (cm)	Conventional US	CEUS
Gutzeit et al. [9]	Sonovue	8×6	Isoechogenicity with a hypoechoic rim, poorly-demarcated	Spoke-wheel-like enhancement
Cao et al. [10]	Sonovue	4.2×3.7	Hypoechoic, well-demarcated	NA
		5.2×3.6	Heterogeneous hypoechoic, unclear margin	Diffuse and homogeneous enhancement
		7.0×6.2	Hypoechoic, well-demarcated	Diffuse and lobular enhancement, 1-2 s later than the splenic parenchyma
Watanabe et al. [11]	Sonazoid	3.2×2.7	Hypoechoic, well-demarcated	Spoke-wheel-like enhancement, weaker than the splenic parenchyma
Menozzi et al. [12]	Sonovue	7.0 in diameter	Isoechoic, well-defined margin, posterior acoustic shadowing in the center	Spoke wheel pattern in the early arterial phase, slightly hypo-enhancement
Demirci et al. [18]	Sonovue	2.0 in diameter	Hypoechoic, blurred boundaries	Accentuated nodule-like enrichment of the boundaries in the arterial phase

US: ultrasound; CEUS: contrast-enhanced ultrasound; NA: not available.

Notably, SANT of the spleen should be differentiated from splenic lymphoma and splenic metastases, which are the most common malignant tumors of the spleen. Firstly, patients with splenic lymphomas and metastatic tumors may present with a medical history of enlarged lymph nodes or primary malignant tumor, and may have abnormal tumor markers in laboratory examinations [27]. In terms of imaging features, lymphomas tend to be multifocal hypoechoic lesions on US rather than solitary nodule. CEUS shows a fast in and fast out pattern, i.e., isoenhancement in the arterial phase and early washout [28]. The imaging features of splenic metastases, on the other hand, are associated with the primary tumor. Generally, the lesions are well-defined without posterior acoustic shadowing on US and show a marked venous phase washout on CEUS [9, 26].

In conclusion, we should be aware that a splenic SOL might represent a SANT in spite of its rareness. Imaging examinations are critical for the diagnosis. On gray-scale US, short linear or flaky hyperechonic regions inside the lesion and posterior acoustic shadowing might provide worthy clues for the diagnosis of SANT of the spleen. Furthermore, peripheral nodular enhancement, rapidly centripetal enhancement, and hypo-enhancement on CEUS highly suggests the probability of this rare entity. In the future, studies with large sample size will be needed to investigate the diagnostic accuracy of CEUS for SANT of the spleen.

Footnotes

Acknowledgment

This work was supported in part by the Shanghai Hospital Development Center (Grant SHDC12020117), National Natural Science Foundation of China (Grants 81927801, 82072092, 81901753 and 82001816), Fundamental Research Funds for the Central Universities (Grant 22120190213), Shanghai Municipal Health Commission (Grants 2019LJ21 and SHSLCZDZK03502), Science and Technology Commission of Shanghai Municipality (Grants 19441903200 and 19DZ2251100).

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