1 Introduction

Primary hepatic lymphoma (PHL) is defined as a lymphoma localized and limited to liver or perihepatic lymph nodes, with no evidence of distant lymph node enlargement, splenomegaly or splenic lesions, bone marrow or blood diseases for at least 6 months after the onset of liver tumor [1, 2]. PHL mainly affects middle-aged individuals with a male predominance and has nonspecific clinical symptoms. Its diagnosis and differential diagnosis mainly depend on radiology and pathology.

Previous studies of PHL in radiology mainly focused on describing the imaging manifestations of PHL using multimodal imaging approaches and comparing the differences between PHL and secondary hepatic lymphoma (SHL), as well as differential diagnosis with other common liver malignant tumors [3,4,5]. However, an accurate diagnosis of PHL by imaging approaches remains a challenge: misdiagnosis may be common and the definitive diagnosis can only be achieved through histopathologic examination of the biopsy or operative specimen [6]. PHL is a rare primary liver tumor with variable and non-specific imaging manifestations, but some features are found to be useful diagnostic clues in an appropriate clinical setting. The purpose of this study was to investigate and summarize the CT or MRI characteristics of PHL, which may contribute to its diagnosis and differentiation from other common liver tumors in daily clinical practice.

2 Methods

This study was approved by the Ethics Committee of our hospital. The requirement for informed consent was obtained from all participants. Sixteen patients with PHL proved by pathology were retrospectively collected from two hospitals in this study.

Of the 16 patients, 10 patients underwent abdominal or abdominal-pelvic contrast enhanced CT imaging, and 11 patients underwent abdominal contrast-enhanced MR scanning. Multiphase-enhanced CT images were obtained using different scanners, including Siemens Somatom Definition AS+ (Siemens, Forchheim, Germany), GE Discovery CT750 HD (GE Healthcare, Milwaukee, WI), and GE Revolution EVO. The CT imaging parameters were as follows: tube voltage, 120 kVp; auto tube current; reconstruction section thickness, 1.0–1.5 mm; field of view, 350 mm × 350 mm; matrix, 512 × 512. The volume of contrast medium was 1.2 mL/kg with an upper limit of 150 mL, a concentration of 300 mg/mL iodine through antecubital vein at the rate of 2.5 mL/s via a high-pressure syringe. MRI examinations were performed using different scanners, including 1.5T GE Signa Excite MR scanner (GE Healthcare, Milwaukee, WI), and 3.0T GE Discovery MR750 MR scanner. Unenhanced MRI consisted of axial in-phase and out-of-phase T1WI, axial fat-suppressed T2-weighted imaging (T2WI), coronal T2WI, and diffusion-weighted imaging (DWI). The apparent diffusion coefficient (ADC) map was generated from the DWIs and the ADC values were obtained by measuring the intensity of the map. Dynamic contrast-enhanced T1WI with fat-suppressed technique was performed in the axial, coronal and sagittal planes after administration of 0.4 mL/kg of gadolinium at a rate of 2 mL/s followed by an equal amount of normal saline bolus injection.

Clinical data were recorded, including patient age, sex, clinical presentation and laboratory test. The imaging features were reviewed by two abdominal radiologists (Z.Y.D and C.J.M) with 5 years and 7 years of experiences in hepatic imaging in consensus. The following characteristics were evaluated: the distribution (single lesion, multiple nodules or diffuse infiltrative type), growth appearance (i.e. biliary pass-through sign and vascular floating sign, present or absent), density or signal characteristics, target sign on T2WI (i.e. mildly hyperintense lesion with very hyperintense central necrosis, present or absent), central necrosis (present or absent), as well as the enhancement pattern of lesions including multinodular sign in the arterial phase, washout of contrast medium in the portal-venous or delayed phase, and pseudocapsule in the delayed phase. Biliary pass-through /vascular floating sign occurred as biliary/vascular encasement by the PHL without obstruction, occlusion and thrombosis. The double-ring sign was considered a new imaging feature, defined as the enhancement of peripheral pseudocapsule and inner wall of the central necrosis region in the delayed phase.

DWI and ADC maps were evaluated both qualitatively and quantitatively. For qualitative analysis, we considered signal restriction when lesions appeared hyperintense at high b-values (b, 1000 s/mm2) on DWI and hypointense on the ADC map, compared to the surrounding parenchyma. For quantitative analysis, circular regions of interest (ROIs) of at least 5 cm2 were drawn within the solid component of lesions, defined by definite enhancement on contrast-enhanced T1WIs. Meanwhile, ADC values were obtained by measuring equal sizes of ROIs in the surrounding parenchyma. At least three measurements were performed and averaged for each lesion. Student’s t-test was used for the statistical evaluation, and a P value of less than 0.05 was considered significant.

3 Results

This retrospective study enrolled 16 patients, which consisted of 7 women and 9 men, ranging from 27 to 86 years old with an average age of 62 years. Eleven patients had non-specific symptoms including right upper abdominal pain, malaise and nausea, whereas the others had no clinical symptoms. Seven patients had elevated lactate dehydrogenase (LDH) levels, six had irregular liver function tests. All patients were found abnormal in the beta-2-microglobulin test. Five patients had HBV and HCV-related chronic hepatitis (3/5 and 2/5, respectively). Characteristics of clinical and laboratory test were summarized in Table 1.

Table 1 Clinical information and the blood tests for 16 patients with PHL
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Results of multimodal imaging showed that lesions are confined to livers for all the patients without distant lymphadenopathy, splenomegaly or splenic lesions, etc. Of the 16 patients, 13 (13/16, 81%) had focal masses, 3 (3/16, 19%) had multiple nodules, and none had diffuse lesions (Figs. 1, 2). The lesions with vascular floating sign were found in 10 patients (10/16, 63%) and biliary pass-through sign were found in 6 patients (6/16, 37%) (Fig. 3). Lesions with necrosis were observed in 10 patients (10/16, 63%). Among 11 patients undergoing MR, the lesions presented target sign on T2WI were found in 5 patients (5/11, 45%). For signal intensity, all lesions were hypointense on T1WI compared to the liver and high signal intensity on T2WI, with low ADC values. The mean ADC value of the PHLs was 0.69 × 10–3 mm2/s (SD = 0.38), which was significantly lower than the mean ADC value of the background liver (1.21 × 10–3 mm2/s, SD = 0.19) (P < 0.05). On contrast-enhanced CT or MR images, PHLs had multinodular sign in the arterial phase in 10 patients (10/16, 63%), and presented washout of contrast medium in the portal-venous or delayed phase in 12 patients (12/16, 75%), pseudocapsule in the delayed phase in 15 patients (15/16, 94%), and double-ring sign in the delayed phase in 8 patients (8/16, 50%) (Fig. 4).

Fig. 1
figure 1

A 64-year-old man with primary hepatic lymphoma. Axial out-of-phase (a) and in-phase (b) T1-weighted images showed a hypointense signal tumor in the liver. c Axial fat-suppressed T2-weighted image revealed the mildly hyperintense signal tumor (black arrow) with central high signal necrosis (*), which presented a “target” appearance. d Diffusion-weighted MR image (b = 1000 s/mm2) showed the lesion as hyperintense relative to the liver with obviously low ADC values on e apparent diffusion coefficient map. Axial fat-suppressed T1-weighted images f before administration of contrast material and g in arterial phase, h portal-venous and i delayed phase after administration of contrast agent. In the arterial phase, the lesion had the multinodular sign (black arrow) with inhomogeneous enhancement. In the portal-venous phase, the mass continued to enhancement, and showed pseudocapsule (red arrow) and double-ring sign (red arrow and yellow arrow) in the delayed phase

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Fig. 2
figure 2

The same patient as in Fig. 1. a–d Fluorodeoxyglucose (FDG) PET/CT images showed the avidly hypermetabolic lesion. e Needle biopsy demonstrated primary diffuse large B-cell hepatic lymphoma

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Fig. 3
figure 3

PHL in a 71-year-old woman with upper abdominal malaise. a Axial fat-suppressed T2-weighted image showed a large, well-define, mildly high signal intense tumor (black arrow) with biliary (yellow arrow) and vascular (red arrow) floating sign. b–d multi-planar fat-suppressed post-contrast T1-weighted images displayed the enhanced tumor (black arrow) with a vascular floating sign (red arrow). e Biopsy demonstrated primary diffuse large B-cell hepatic lymphoma

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Fig. 4
figure 4

Primary diffuse large B-cell hepatic lymphoma in an 83-year-old man with fever and abnormal results on liver function tests. a Axial T2-weighted image showed a mildly hyperintense signal tumor in the liver with central high signal necrosis (*). b, c DWI (b = 1000 s/mm2) showed the tumor as hyperintense relative to the liver with obviously low ADC values. The same patient’s abdominal contrast enhanced CT images in d arterial phase, e portal-venous and f delayed phase. The mass showed pseudocapsule (red arrow) and double-ring sign (red arrow and yellow arrow) in delayed phase of CT

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Pathological examinations of the biopsy or excised specimens were undertaken on 16 patients, all of which were proven as the lymphoproliferative disorder confined to the liver. Among 10 patients with precise histological types, the predominant type is non-Hodgkin lymphoma (9/10, 90%), consisting of eight diffuse large B-cell lymphomas and one Burkitt lymphoma.

4 Discussion

PHL is a rare and poorly defined disease that accounts for less than 0.1% of all NHL [7, 8]. Up to now, its specific imaging manifestations have not been clearly described, but some features are useful diagnostic clues in an appropriate clinical setting. Our retrospective study demonstrates that its distinctive imaging characteristics including biliary/vascular floating sign, multinodular sign, washout in the portal phase, pseudo-capsule and double-ring sign in the delayed phase, may contribute to its diagnosis and differentiation. Furthermore, remarkably low ADC value, biliary/vascular floating sign, multinodular sign and double-ring sign in the delayed phase would be the most important characteristics to suspect PHL.

As a rare type of malignant tumor, PHL mainly affects middle-aged and elderly people with a male-to-female ratio of 2.3:1 [9]. The most common clinical presentation includes right upper abdominal pain, jaundice, weight loss, or first detection during physical examination. Most patients have high LDH levels, high beta-2 microglobulin levels and abnormal liver enzymes, although these may be normal [10]. In our study, the mean age and gender of patients with PHL is in line with previous literature, showing that the incidence of crowd of PHL are elderly men, especially the immunocompromised or viral-infected patients [11]. In the previous studies, LDH and beta-2 microglobulin levels were often elevated [2]. In our study, we observed that the LDH levels were noticeably elevated in 5 patients (5/16, 31%), and slightly elevated in one patient; in contrast, the elevated beta-2 microglobulin levels were more significant in all PHL patients. It has been reported that Non-Hodgkin lymphoma is the main histological subtype of PHL with a predominant immunophenotype of diffuse large B-cell lymphoma [3], which is consistent with the result of our study.

As a rare disease, few researches have reported the radiological manifestations of PHL, which is often mistaken as other space-occupying hepatic lesions, such as hepatocellular carcinoma and metastases. In our current study, PHL showed variable morphologic distribution and the focal-mass type was the main pattern, which is consistent with previous studies [4]. In unenhanced MRI, PHL was hypointense on T1WI and homogeneous/heterogeneous hyperintense on T2WI compared to adjacent hepatic parenchyma, as well as showed restricted diffusion on DWI with obviously low ADC values. The main reasons of PHL with a remarkable low ADC value could be high nuclear-to-cytoplasm ratio and high cellularity [12]. Our study demonstrated that PHL mainly presented heterogeneous enhancement. What’s more, a few typical imaging features of PHL were also observed, including biliary/vascular floating sign, multinodular sign in the arterial phase, washout of contrast medium in the portal-venous or delayed phase, pseudocapsule in the delayed phase, and double-ring sign in the delayed phase of the dynamic enhancement [5].

Compared to homogeneous secondary hepatic lymphoma, our study found that PHL mainly demonstrated heterogeneous high signal intensity, and usually had necrosis to some extent, which presented a “target” appearance with a central hyperintense region and a peripheral mildly high signal intensity rim on fat-suppressed T2WI [13]. After contrast agent administration, some PHLs showed part range slightly high density/signal regions in the arterial phase with washout of contrast medium in the portal-venous or delayed phase and pseudocapsule in the delayed phase, which may be easily misdiagnosed as hepatocellular carcinoma (HCC). For PHL, the mass usually encases the intra-hepatic bile duct or portal vein without invasion or compression, which is regarded as a biliary/vascular floating sign. By contrast, HCC usually shows vascular displacement or invasion, which can induce tumor thrombus in the portal vein [14]. Intrahepatic cholangiocarcinoma, another common liver tumor, may be easy to identify by growth pattern, density or signal intensity, degree of diffusion restriction and enhancement characteristics. In addition, although post-transplant lymphoproliferative disorder (PTLD) is a rare hematologic malignancy, the imaging differential with PHL also need to take into account. At CT and MR, when there is an ill-defined or well-defined mass in the liver with low density on CT and poorly enhanced after contrast medium administration, combined with serology, cultures, a clinical history of transplant and immunosuppression therapy, the possibility of PTLD may be raised.

In our study, we found and first proposed a distinctive imaging characteristic of PHL: double-ring sign in the delayed phase of contrast enhancement. The two hyper-enhanced rings are consisted of tumor pseudocapsule and line-like delay-enhanced margin of the central necrotic region in the delayed phase, respectively. The formation of pseudocapsule may be due to peritumoral fibrosis and bile duct reaction caused by tumor space-occupying effect, and the line-like enhanced margin of the central necrotic region is considered as new granulation tissue, which both present delayed enhancement after contrast agent administration [3]. This manifestation is a characteristic sign for diagnosis of PHL comparing with other hepatic diseases.

There were several limitations in our study. First, because of its retrospective analytic nature, our study was not blinded to the diagnosis. Secondly, as the cases were collected from different hospitals, the quality control of clinical information, laboratory tests and imaging data was lax. Finally, owing to the rarity of the tumor, this was a small sample study. Our findings need to be further verified.

5 Conclusions

PHL is a rare liver tumor and precise imaging diagnosis remains a challenge. When a hepatic space-occupying lesion with the following characteristic imaging signs in an elder patient: obviously low ADC value, biliary/vascular floating sign, multinodular sign in the arterial phase, washout of contrast medium in the portal-venous or delayed phase, pseudocapsule in the delayed phase, and double-ring sign in the delayed phase of the dynamic enhancement, PHL should be considered as a possible diagnosis. The management and prognosis of PHL are remarkably different from those other hepatic neoplasms. Its final diagnosis depends on histopathology.