SNN is a rare non-neoplastic lesion of the liver, which was first reported by Shepherd in 1983[3]. Until now, the pathogenesis of SNN was not clear, with several theories in the literature as follows [4, 5]: (1) central necrosis of hepatic hemangioma after sclerosis; (2) formation and progression of certain benign lesions after trauma in the liver; (3) parasitic infection; (4) malignant tumor of the digestive tract at the same time, which may lead to coagulative necrosis of liver due to allergic reaction.
SNN often occurs in patients aged between 60 to 70 years, but it had also been reported to occur between the ages of 30 to 40 years, with more males being affected than females [6]. Most patients showed no clinical symptoms, and SNN lesions were found occasionally during physical examination, postmortem examination, or operation [7]. The pathological features of SNN include nodular coagulation necrosis, and presence of a complete fibrous capsule around the lesion, with the infiltration of inflammatory cells in the capsule (mainly eosinophil cells and lymphocytes), and no vascular tissue in the lesion [4, 8].
It had been reported that the SNN lesions could reduce or disappear after conservative treatment. So, if SNN is highly suspected, surgical resection should be avoided [9, 10]. Therefore, a correct diagnosis before the operation is crucial.
There are no specific clinical symptoms and laboratory tests for the diagnosis of SNN [4, 11]. SNN often presents as hypo-echoic nodules on the conventional US, which lacks specificity, and thus makes it difficult to make a qualitative diagnosis. [12–14]. Color Doppler US has some limitations in the detection of the micro-vessels in the lesions, and puncture biopsy or surgical resection are the ultimate diagnostic methods and gold standard for SNN detection [15].
With the development of CEUS, the process of internal and peripheral blood perfusion can be dynamically observed in real time, which could effectively improve the accuracy of SNN diagnosis and reduce unnecessary biopsy or surgical trauma [16, 17].
In this study, 11 patients (11 / 24) showed no enhancement in the three phases, which was similar to the report by Wang Y et al [18]. However, in our study, 13 patients (13 / 24) showed peripheral thin rim-like enhancement in the arterial phase, which could easily be misdiagnosed as a malignant tumor such as metastatic hepatic carcinoma (MHC). However, the inner wall of the lesions enhancement ring was clear and sharp, and demonstrated iso-enhancement in the portal and delayed phases, which differed from the obviously decreased enhancement ring of the MHC lesion in the portal phase [2, 8]. Peripheral thin rim-like enhancement in the arterial phase suggested micro-vessel distribution around the lesions of the SNN. HE staining showed that the edges of the lesions were hyperplastic fibrous tissue and inflammatory response bands caused by infiltrated inflammatory cells. This might be the pathological basis of the peripheral thin rim-like enhancement observed in the arterial phase [4]. Some lesions showed septum-like enhancement, which might be related to fibrous tissue separation following multi-lesion fusion. Internal septum-like enhancement may be one of the characteristics of multi-lesion fusion. There was a significant difference in lesion size between the two enhancement patterns: the lesions which showed a peripheral thin rim-like enhancement were larger than those without enhancement. This suggested that the lesions were in different pathologic stage: those without enhancement might be at the end-stage and tended to atrophy. The lesions with peripheral thin rim-like enhancement might be at the relatively early stage and maintain the peripheral vessel distribution.
Previous literature has shown that presence of a marked peripheral rim-like enhancement with internal hypo-intensity on a longer MRI (a delayed time of 1–2 hours) was helpful in the diagnosis of SNN [19]. The contrast agent used during an MRI is different from that used during a CEUS. The ultrasonic contrast agent is a blood-pool imaging agent, which does not diffuse to the intercellular space and does not show delayed enhancement. The MRI contrast agent is an extracellular contrast agent, which can diffuse to the extracellular space. Because the contrast medium diffuses slowly between blood vessels and the fibrous tissue, the peripheral rim-like enhancement of the lesions is observed 1–2 hours after injection of the contrast agent. The interval is relatively long, making it unsuitable for routine clinical examination. SNN shows specific manifestations at the early stage of CEUS, which could reduce the examination time and gave better repeatability, thus making CEUS more suitable for clinical use.
SNN with peripheral rim-like enhancement in the arterial phase should especially be distinguished from MHC. Previous studies had reported that when MHC lesions appeared to be necrotic, it could present peripheral rim-like enhancement in the arterial phase with the interior of the lesion showing no enhancement in the three phases [20–22]. However, there was a significant difference in the thickness of the enhancement ring in the arterial phase between MHC and SNN. The enhancement rings of the MHC were thicker than that of the SNN [23]. Besides, the enhancement ring of the MHC was infiltrated by malignant tissue, and the contrast agent was washed out during the portal phase and demonstrated hypo-enhancement. Therefore, the hypoechoic area became larger in the delayed phase. However, the enhancement ring of the SNN was a thin fibrous capsule without obviously being washed out in the delayed phase; therefore, the hypoechoic area showed no significant change compared the arterial phase [24].
The peripheral rim-like enhancement observed on the CEUS can also be detected in some cases of intrahepatic cholangiocarcinoma (ICC). However, the enhancement ring in ICC is unevenly thicker with an irregular shape, and the interior of the lesion has a contrast agent filling. Clinical characteristics and specific laboratory examinations are also helpful for the differential diagnosis of SNN [25–27].
When an abscess with liquefied and necrotic tissue is formed, a peripheral rim-like enhancement is observed in the arterial phase, but honeycomb enhancement of the internal part can help with the differentiation [28–30].
Hepatic alveolar echinococcosis (HAE) is also a rare parasitic disease with a long incubation period and lack of specific clinical symptoms; therefore it is difficult to diagnose at the early stage [31]. HAE generally presents with an irregular solitary solid mass with no capsule, and most lesions have an unclear boundary and heterogenous internal echo with no blood flow signal detected [32, 33]. There is no contrast media filling in lesions during all the three phases in HAE, which can help distinguish HAE from the non-enhanced SNN. The combination of contact history in the epidemic area and specific laboratory examination could be helpful for a differential diagnosis [34, 35]. In addition, interventional procedures such as liver tumor ablation could also show no enhancement in the three phases, so the diagnosis of SNN should also consider the patient's history [19].
One case of this study relapsed 4 years after surgery, which has not been previously reported. The lesions showed no enhancement in all three phases during both CEUS examinations between four years. Therefore, although SNN is a benign lesion, there is a possibility of recurrence. Such patients who choose conservative treatment require attention and should be closely followed up.
This study was the first to report two types of enhancement patterns observed in SNN, and a case of relapse, which has not been reported in the literature. However, some limitations should also be noted, as this study was a retrospective study and with a relatively small number of cases. A larder sample size and prospective study is required for further investigation.