Maarten van Leeuwen, Joost Nederend and Robin Smithuis Liver Incidentalomas What to do with incidentally found lesions in the liver? Maarten van Leeuwen, Joost Nederend and Robin Smithuis Radiology department of the University Medical Centre of Utrecht, the Leiden University and the Rijnland hospital, Leiderdorp, the Netherlands

With the increasing use of multidetector CT small hepatic lesions are frequently depicted. In many cases the pathological nature of these incidentally found liver lesions or incidentalomas is not known.  This results in a diagnostic problem, which is initiated by radiology so radiologists should take responsibility in correctly categorizing these lesions as to their clinical significance. 

In this article we will discuss the management of two different type of incidentally found liver lesions: Lesions that are too small to characterise (TSTC lesions) in asymptomatic individuals and in patients with a known malignancy. Hypervascular lesions

TSTC (too small to characterize lesions)

We see multiple hypodense lesions We see multiple hypodense lesions.  We cannot diagnose them with certainty as: cysts: water-density, sharp demarcation hemangiomas: slowly progressive peripheral nodular enhancement of arterial density malignant lesions: inhomogeneous, irregular demarcation, peripheral enhancement less than arterial density

TSTCs in patients without a known malignancy

TSTCs in patients with a primary malignancy

The percentage of malignancy depended much on the known primary tumor. Most metastases were found in patients with breast cancer. This is in accordance with the observation that breast metastases usually present as multiple small lesions, while liver metastases of colorectal cancer and lymphoma usually present as a solitary or a few larger masses.

Role of size and borders in risk of malignancy of TSTC

TSTCs in breast carcinoma

Conclusion In a patient without a known malignancy these small hypodense lesions, as a rule, should be considered as benign. In a patient with a known malignancy a single TSTC lesion can also be assumed to be benign. Even multiple TSTCs in these patients are mostly benign, especially when they are small, sharply defined and hypodens. In these latter cases you should not be too defensive!  Don't dictate 'we can't rule out metastases'.

In patients with breast cancer and no known liver metastases at presentation, these TSTC lesions have no positive predictive value for the development of liver metastases in the long term.

Incidental hypervascular lesions

Incidental hypervascular lesions are also very common findings in liver imaging. It is important to differentiate between 'touch' and 'don't touch' lesions. Benign 'don't touch' hypervascular tumors include hemangioma, FNH and small adenomas. 'Touch' lesions include large adenomas (more than 5 cm) and malignant tumors like Hepatocelular carcinoma (HCC), Fibrolamellar carcinoma (FLHCC) and metastases. 

Enhancement in Hemangioma A hemangioma is a slowly perfused vascular space.  So the timing and amount of enhancement will follow, but lag behind the arterial system.  Hemangiomas less than 1 cm frequently demonstrate immediate homogenous enhancement, isodense to the aorta. Hemangiomas larger than 1cm generally show slow centripetal spread of nodular enhancement, slowly decreasing in density. 

Enhancement in arterial phase is almost isodense to the aorta, and, as contrast diffuses toward the center of the lesion, the level of enhancement lowers slowly, and in the late phase is still hyperdense compared to the vascular spaces.

Enhancement in 'capillary blush‘ The typical, slowly perfused vascular space enhancement of a hemangioma has to be differentiated from the 'capillary blush' due to an abundant capillary network which characterizes FNH, adenoma, HCC and hypervascular metastases. 

As capillaries are surrounded by tissue the overall enhancement will be less dense compared to the enhancement of the vascular spaces in hemangioma.  Hence, in capillary blush, the enhancement occurs slightly later compared to the aorta and is less dense than the aorta. 

'Capillary blush' in FNH. Notice early enhancement, but not as bright as in hemangioma. In venous and delayed phase the enhancement is almost isodense to the liver.

Hemangiomas on dynamic MR will show the same enhancement characteristics as on contrast-enhanced CT.

The advantage of MR over CT is its higher sensitivity to contrast as will be shown in the next case. an atypical, apparently hypovascular lesion on CT, possibly metastasis.

Same case on dynamic MR.  Notice how MR depicts the nodular, peripheral, slowly progressing enhancement (blue curved arrow) which CT failed to depict.

Small hemangioma atypical on US, showing typical enhancement of small hemangioma on CT

Once we have excluded hemangiomas, our main goal is to determine whether a hypervascular lesion is a FNH, which is the most prevalent hypervascular solid lesion, or whether it is a lesion which needs further management like adenoma, HCC, FLHCC or hypervascular metastases.  For this purpose we have to look for morphologic features like inhomogeneity and presence of capsule, scar, calcification or fat.

Focal Nodular Hyperplasia (FNH) Histologically, FNH is not a tumor and consists of benign-appearing hepatocytes occurring in a liver that is otherwise normal (i.e. no cirrhosis). At late arterial phase, FNH typically presents with a bright homogeneous enhancement, but less intense than the aorta with a hypodense central scar.

At portal phase, FNH is often iso-attenuating to the normal liver and may be difficult to deliniate. Delayed phase often shows hyperattenuation of the central scar and septa due to late opacification of the fibrotic components. No calcifications, inhomogeneity or capsule should be seen in FNH.

Two adjacent hypervascular lesions with homogeneous enhancement in arterial phase and hypodense central scars in arterial and venous phase, which enhance in the equilibrium phase.

A typical FNH on MR. Slightly hypointense on T1WI and slightly hyperintense on T2WI.  The scar is somewhat hyperintense on T2. The enhancement is as we expect with 'capillary blush' with a scar that enhances late in the equilibrium phase.

Adenoma An adenoma is regularly characterized by bleeding, fat or peliosis. Regularly adenomas present with bleeding. In the 'out of phase' image there is signal loss indicating that the lesion contains fat, which is very suggestive for adenoma.

In the arterial phase there are two hypervascular lesions, somewhat less dense than we would expect in FNH.  Both lesions demonstrate a halo of a capsule, which should not be apparent in FNH.  Unlike in FNH, the enhancement is inhomogeneous and in the portovenous and equilibrium phase the lesions are not isodens to the liver.

On US a liver mass was seen and free fluid surrounding the liver On US a liver mass was seen and free fluid surrounding the liver. This is a typical presentation of an adenoma. On portal phase CT, the lesion is hypointense with haemorrhage adjacent to the lesion, extending subcapsularly.

The enhancement is due to a capillary blush, most intense in the arterial phase with apparent wash-out in portal and equilibrium phase, due to greater enhancement of the surrounding parenchyma. In the 'out of phase' image there is signal loss indicating that the lesion contains fat, which is very suggestive for adenoma. 

Hepatocellular carcinoma (HCC) Concerning the diagnosis of HCC, there is one thing to remember: 'Every hypervascular lesion in a cirrhotic liver is HCC until proven otherwise' . The inhomogeneous enhancement and the partial capsule are helpful for the diagnosis HCC.

a cirrhotic liver with irregular margins (arrows), suggesting that the hypervascular lesion is a HCC.  The inhomogeneous enhancement and the partial capsule

Fibrolamellar HCC When we encounter lobulated hypervascular masses in the liver, an important diagnosis that you don't want to miss is a fibrolamellar hepatocellular carcinoma (FLHCC). This particular form of HCC may mimic FNH on imaging. Like FNH, FLHCC also is a hypervascular, lobulated mass with a central scar . 

Both FNH and FLHCC appear in normal liver, unlike HCC that is most frequently seen in a cirrhotic liver. In distinction to FNH, FLHCC is inhomogeneous, large (> 5 cm), frequently has calcifications (>70%), a blunt central scar and usually there is lymphadenopathy. Calcifications in FNH are so uncommon that it should make you consider another diagnosis like FLHCC.

A pathologic specimen of FLHCC and FNH A pathologic specimen of FLHCC and FNH. At first glance they look very similar. However when you look carefully you will notice the more lamellar and heterogeneous structure of FLHCC compared to the homogeneous appearance of FNH.

A left-lobe fibrolamellar HCC in a 19-year-old man. A A left-lobe fibrolamellar HCC in a 19-year-old man.  A. Non-enhanced transverse CT scan shows calcification (curved arrow) within the hypoattenuating tumor (straight arrows).  B. Hepatic arterial contrast-enhanced transverse CT scan shows heterogeneous hypervascularity within the tumor (arrows).  C. Ten-minute delayed transverse CT scan demonstrates subtle areas of hyperattenuation that represent fibrous tissue within the central scar, radiating septa, and capsule (open arrows).   D. Transverse T2-weighted MR image (5,000/105) also demonstrates the central scar and septa (open arrow).

Hypervascular metastases Characteristics of hypervascular metastases are: A hypervascular primary tumor like endocrine tumors (thyroid, carcinoid), renal cell tumors and some breast carcinomas. Often coexisting hypo- and hypervascular metastases. Larger lesions are often inhomogeneous due to central necrosis.

Differential diagnosis of Hypervascular lesions Work up In the workup of incidentally found hypervascular lesions, we first have to decide whether the lesion is a hemangioma, because these are the most common lesions and usually have specific imaging findings. 

If not, we have to find out whether it is an FNH. For this differentiation we have to look at differences in enhancement pattern and differences in morphology like presence of a capsule, scar, calcification and inhomogeneity. Hypervascular lesions most often can be characterized, even when small.  FNH and hemangiomas need no further investigation or treatment. 

The preferred modality to characterize incidentalomas is MR, as it is better for lesion characterization and incidentalomas often occur in young females, where radiation burden should be minimized. If HCC or FLHCC is considered further investigation is always needed.

Differential diagnosis