1.  INTRODUCTION

Primary hepatic lymphoma (PHL)

PHL is very rare, accounting for less than 1% of all non-Hodgkin lymphomas. To be classified as the primary form, the disease should be confined to the liver and regional lymph nodes, and according to some authors, the diagnosis of PHL also requires the absence of distant disease within six months after the diagnosis.

It is usually diagnosed in the 4th-5th decade and shows a male predominance.

Many etiologic factors have been proposed in the pathophysiology of PHL such as prolonged immunosuppression (including HIV), EBV, as well as hepatitis B and C.

Frequently it manifests as an oligosymptomatic disease, but clinical symptoms including right upper abdominal pain, hepatomegaly and systemic symptoms such as weight loss, fever and night sweats may be seen in up to 50% of cases.

Secondary hepatic lymphoma (SHL)

Secondary hepatic involvement is relatively common in the setting of lymphoma and it is by far the predominant subtype and the one the majority of radiologists are familiarized with. It indicates advanced disease and poorer outcome ratings.

Patients usually present with hepatosplenomegaly and generalized lymphadenopathy on examination and systemic symptoms such as fever, night sweats, and weight loss.

The most common extranodal site of involvement by non-Hodgkin lymphoma is the gastrointestinal tract and nearly half of these patients develop secondary hepatic disease.

2.  IMAGING FINDINGS

Imaging techniques:

Hepatic lymphoma has a wide range of imaging presentations, typically being evaluated on CT, MRI and PET/TC.

• On US, the lesion is normally well defined and hypoechoic or anechoic.
• On CT, the lesion is usually homogeneously hypodense (Fig. 3). Areas of hemorrhage, necrosis and cystic degeneration may occasionally be seen. Calcification and biliary dilatation, on the other hand, are uncommon. Capsule retraction of peripheric lesions is not uncommon after treatment.
• On MRI, lesions tend to show hypointense or isointense signals on T1-weighted imaging (T1WI) and hyperintense signals on T2-weighted imaging (T2WI) and typically show prominent restricted diffusion on DWI (Fig. 3). Although such lesions typically show a homogenous signal, necrosis or hemorrhage if present can cause some heterogeneity.
• On contrast-enhanced CT/MR, most hepatic lymphomas show minimal enhancement after the intravenous administration of a contrast agent. However, as described below, there might be different patterns of enhancement.
• On FDG-PET/CT, typically show avid hypermetabolism (Fig. 5, Fig. 9).

Morphological appearances and patterns of disease:

Although the imaging findings of PHL and SHL may overlap, some features can facilitate diagnostic discrimination: Fig. 1

- PHL: is commonly seen as a solitary mass, either presenting an infiltrative, expansive or exophytic growing pattern. If multiple, there may be a dominant lesion which also tends to be more heterogeneous.

- SHL: as opposed to PHL, the most frequent presentation tends to be multiple and homogeneous lesions and it has a more diffuse pattern of growth. A dominant mass is uncommon.

As either PHL or SHL can manifest as any of these patterns of growth, there are going to be discussed in the same classification, with their respective main differentials.

Fig. 2  illustrates the different patterns of disease seen in hepatic lymphoma. Lymphomatous involvement of the liver can manifest on imaging as solitary or multiple nodular patterns, diffuse infiltration, periportal soft tissue mass, etc.  A combination of these patterns can be seen in the same patient.

1.  Solitary discrete lesion:

This is the most common presentation of PHL on imaging, seen in approximately 60 % of cases. SHL, on the other hand, manifests in this manner in only about 10 % of cases. 

As mentioned earlier, hepatic lymphoma tends to be hypovascular on CT / MRI scans and typically shows the vessel penetration sign (Fig. 3), which means vascular encasement without thrombosis. Occasionally, a central scar may be seen. 

A “target-like” appearance (Fig. 4) also has been described in lesions where there is a peripheric rim enhancement with a central non-enhancing area. This feature is more common in PHL.

These characteristics apply to the multinodular pattern as well.

2.  Multifocal lesions:

Multifocal lesions or diffuse infiltration are the most common patterns of liver involvement in SHL, seen in up to 90% of cases, whereas this pattern is seen in about 35% of cases of PHL.

Lesions in SHL tend to be homogenous in density and size (Fig. 11). On the other hand, in the multifocal pattern in PHL lesions tend to be more heterogeneous and there is usually a dominant mass.

As mentioned previously, the enhancement patterns of the individual lesions in multinodular lymphoma are essentially similar to those described above for the solitary mass-forming and infiltrating varieties of lymphoma.

3.  Diffuse Infiltration and/or hepatomegaly:

Infiltration of tumor cells into the portal tracts as well as sinusoids is one of the most common patterns of hepatic involvement in cases of SHL. It´s rare in PHL, and when present it implies poor prognosis.

There are no specific imaging features, and the only sign of hepatic involvement is a diffuse enlargement of the liver (Fig. 13). 

In these cases, FDG-PET/CT is helpful by demonstrating diffuse FDG uptake in the enlarged liver and spleen with systemic FDG-avid lymphadenopathy.

4.  Periportal infiltrative growth:

This is an uncommon condition with few cases reported in the literature. It manifests as a periportal soft-tissue mass and is seen in both primary and secondary forms of hepatic lymphoma. Central biliary dilatation may occur due to compression of the main branches of the hepatic duct (Fig. 14).

The mass is usually hypoechoic in US and hypovascular on post-contrast TC / MRI. On MRI it also shows hypointense or isointense signal on T1WI and hyperintense signal on T2WI, and typically shows markedly restricted diffusion on DWI.

3. DIFFERENTIAL DIAGNOSIS

Fig. 17 summarises the main differential diagnosis in each pattern of disease. Physical examination and clinical and analytical settings are very important to suggest hepatic lymphoma as the main diagnosis. 

Solitary discrete lesion: pyogenic abscess (Fig. 18), hepatocellular carcinoma (HCC, Fig. 19), intrahepatic mass-forming or infiltrative cholangiocarcinoma (CC), focal nodular hyperplasia or focal steatosis.

Multifocal lesions: infectious disease (multifocal pyogenic or fungal abscesses), hypovascular metastatic liver disease (gastrointestinal tract, pancreatic adenocarcinomas… Fig. 21), malignant tumors including intrahepatic origin (primary multifocal CC (Fig. 20) or HCC) and granulomatous diseases (tuberculosis and sarcoidosis).

Diffuse Infiltration and/or hepatomegaly: acute hepatitis (Fig. 22) and diffuse steatosis (Fig. 23).

Periportal disease: periportal edema (Fig. 24), periductal cholangiocarcinoma (Fig. 25) and biliary dilatation( Fig. 26).