FINDINGS T2 MR (A) demonstrates innumerable subcenti-meter T2 bright structures in the liver parenchyma. These structures demonstrate corresponding T1 dark signal (B) and do not enhance at postcontrast imaging (C). Coronal MRCP slab image (D) also demonstrates these innumerable subcentimeter T2 bright cystic structures diffusely involving the right and left hepatic lobes.

DIFFERENTIAL DIAGNOSIS Liver cysts, metastases, micro-abscesses, von Meyenburg complexes.

DIAGNOSIS Cystic bile duct hamartomas (von Meyenburg complexes).

DISCUSSION The well-circumscribed morphology and homogeneous fluid bright signal (as bright as the CSF) in the above structures make liver cysts or von Meyenburg complexes the most likely etiology. Although metastases are often bright at T2 MR and areas of necrosis may appear fluid bright, the entire metastasis is usually not homogeneously fluid bright as in the above case. Similarly, the liquefied
portion of an abscess may demonstrate fluid bright signal but the entire abscess is usually not homogeneously fluid bright.

True hepatic cysts are thought to originate from ham-artomatous tissue and do not communicate with the biliary system. At histology, true hepatic cysts are lined by biliary type epithelium. Hepatic cysts are usually homogeneously dark at T1 MR, homogeneously bright at T2 MR, and do not enhance. Hepatic cysts may demonstrate intrinsic T1 bright signal if complicated by internal blood products.

There is some controversy as to whether hepatic cysts are all cystic bile duct hamartomas. Cystic bile duct hamartomas, also known as von Meyenburg complexes, are also cystic structures lined by biliary epithelium. It has been postulated that biliary hamartomas result from failure of involution of embryonic bile ducts. von Meyenburg complexes demonstrate homogeneously T1 dark signal, homogeneously T2 bright signal, and do not enhance. In other words, von Meyenburg complexes and cysts are indistinguishable at imaging and some authors believe that these structures are the same pathologic entity.

FINDINGS Numerous (>20) well-circumscribed T2 bright (A) and T1 dark (B) structures are present in the liver and replace more than 50% of the hepatic parenchyma. No enhancement was seen in these structures after administration of intravenous contrast material (C). The patient also has numerous renal cysts, best seen in the coronal T2-weighted image (D). Note that some of the renal and liver lesions contain intrinsic T1 bright material reflecting small-volume blood products or proteinaceous debris (D). Numerous non-enhancing structures are also present at contrast-enhanced CT (E). Ultrasound (F) demonstrates anechoic structures with increased through transmission and no internal blood flow.

DIFFERENTIAL DIAGNOSIS Abscesses, cystic liver metastases, polycystic liver disease.

DIAGNOSIS Polycystic liver disease associated with autosomal-dominant polycystic kidney disease (ADPCKD).

DISCUSSION Polycystic liver disease most commonly occurs in association with ADPCKD but may also occur in isolation due to a separate genetic mutation that results in autosomal-dominant polycystic liver disease. Polycystic liver disease occurs in approximately 30% to 70% of patients with ADPCKD due to mutations on chromosomes 4 and 16. The genetic mutations that result in isolated autosomal-dominant polycystic liver disease have been isolated to chromosomes 6 and 19.

The cysts in polycystic liver disease are bile duct hamartomas that are lined with biliary epithelium but have no connection to the biliary system. Over time, the epithelial lining secretes fluid and the cysts progressively enlarge.

Most patients with polycystic liver disease are asymptomatic, and liver function tests are usually normal. However, a minority of patients will develop massive hepatomegaly and secondary symptoms of abdominal pain, distention, and early satiety or dyspnea due to mass effect from the massively enlarged liver. Rarely, liver cysts may hemorrhage or become infected.

At MR, the cysts associated with polycystic liver disease appear as well-circumscribed T2 bright structures. T1 signal will vary depending on cyst content. Cysts are usually dark on T1-weighted imaging but may demonstrate intrinsic T1 bright signal if they contain blood products or proteinaceous debris. If a cyst becomes infected, it may demonstrate perilesional edema and rim and perilesional enhancement. At CT, polycystic liver disease appears as multiple well-circumscribed and nonenhancing cysts. At ultrasound, cysts associated with polycystic liver disease appear as anechoic (black) structures with increased through transmission and no internal blood flow.

Abscesses are not as homogeneous in signal intensity, may demonstrate adjacent edema, and often demonstrate abnormal enhancement such as internal septations or peripheral enhancement. Cystic liver metastases usually can be distinguished from polycystic liver disease as cystic metastases usually have a soft-tissue component and will demonstrate areas of enhancement after administration of intravenous contrast material.

FINDINGS T2-weighted MR (A) and T2-weighted MR with fat saturation (B) demonstrate numerous 2- to 4-mm cystic structures along the central intrahepatic biliary system. This finding is confirmed in the True FISP image (C) as well as at magnetic resonance cholangiopancreatography (MRCP) (D).

DIFFERENTIAL DIAGNOSIS Peribiliary cysts.

DIAGNOSIS Peribiliary cysts.

DISCUSSION Peribiliary cysts are thought to form when periductal glands become obstructed as a result of inflammation. Given the increased frequency of peribiliary cysts in patients with severe liver disease, portal hypertension, and portal vein occlusion, it has been hypothesized that elevated portal vein pressures may trigger the inciting inflammatory process. These cysts are usually asymptomatic though cases where large peribiliary cysts resulted in biliary obstruction have been described.

Peribiliary cysts can be detected as small cystic structures along the central intrahepatic biliary system at ultrasound, CT, or MR. At ultrasound, these structures may be difficult to identify but when visible appear hypo- to anechoic with increased through transmission and no internal blood flow. At CT and MR, these structures appear as nonenhancing fluid attenuation and fluid signal structures. At MR, these structures are most readily seen at T2-weighted imaging.

In one series of 12 patients, peribiliary cysts ranged in size from 0.3 to 2.5 cm. The most common morphology of peribiliary cysts is multiple adjacent round cysts with the appearance of beads on a string. When small, these peribiliary cysts may mimic periportal edema. Less commonly,
peribiliary cysts appear as dilated tubular structures that are difficult to distinguish from dilated bile ducts.

FINDINGS Axial (A) and coronal (B) T2-weighted MR images demonstrate a 19-cm T2 bright structure in the right hepatic lobe. The lesion demonstrates low signal at T1-weighted MR (C) and does not enhance after administration of intravenous contrast material (D). A small amount of layering T2 dark and T1 bright debris is present (A, C). Note the additional similar appearing but smaller lesion in the inferior right hepatic lobe (C).

DIFFERENTIAL DIAGNOSIS Abscess, biliary cystadenoma, hepatic cyst, hydatid cyst.

DIAGNOSIS Hepatic cyst.

DISCUSSION The above lesion is a unilocular cystic structure with a small amount of internal debris and no enhancing component. Abscesses are usually not as well defined and homogeneous as they often demonstrate enhancing septations and adjacent edema. Biliary cystadenomas are multilocular cystic masses. Hydatid cysts usually contain internal daughter cysts and may demonstrate wall calcification at CT.

The etiology of liver cysts is unknown. It has been postulated that these cystic structures are hamartomas that do not develop a normal connection to the biliary tree. These cysts are lined by epithelium that can secrete fluid and result in cyst enlargement.

Hepatic cysts are usually asymptomatic and no treatment is required. When large, these cysts may produce symptoms due to mass effect such as early satiety (if mass effect on the stomach) and shortness of breath (if diaphragm elevation).

FINDINGS Axial T2-weighted MR without (A) and with (B) fat saturation and coronal T2-weighted MR without fat saturation (C) demonstrate a 9-cm structure in the left hepatic lobe containing rounded areas of T2 bright signal abnormality with linear areas of internal T1 and T2 dark signal and no more than minimal adjacent inflammatory changes. T1-weighted MR (D) demonstrates the mass to be of lower signal than the adjacent hepatic parenchyma. Axial (E) and coronal (F) postcontrast MR demonstrate numerous rounded nonenhancing areas of fluid interspersed between irregular areas of enhancement and debris (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Abscess, biliary cystadenocarcinoma, intrahepatic cholangiocarcinoma.

DIAGNOSIS Abscess.

DISCUSSION Liver abscesses may result from a variety of conditions including gastrointestinal infection with resultant portal vein seeding or systemic sepsis. Patients who have undergone a bilioenteric anastomosis also are at increased risk for liver abscess due to cholangitis. Clinical presentation is highly variable with some patients presenting with fever and right-sided abdominal pain and other patients presenting with more vague abdominal pain.

At CT, ultrasound, and MR, liver abscesses have a varied appearance. Multiple abscesses may be visible scattered throughout the entire liver or a more focal area of infection may be visible. Individual abscesses may appear as unilocular or multilocular.

At CT, abscesses appear as multiple randomly distributed lesions or as clustered areas of hypoenhancing tissue or fluid. These structures have more ill-defined margins than simple liver cysts. At CT, abscesses may demonstrate a thick rim and enhancing internal septations. At ultrasound, small abscesses may appear as hypoechoic masses that can be difficult to distinguish from solid masses. As abscesses enlarge, mobile debris may be visible at ultrasound which is a clue to the diagnosis.

At MR, abscesses usually demonstrate T2 bright signal reflecting their fluid component. T2 signal may vary from mildly bright to fluid bright depending on the nature of the fluid component. Additionally, T2-weighted images with fat saturation may demonstrate bright signal, indicating edema within the adjacent liver or perihepatic fat. T1 signal intensity varies depending on the amount of fluid versus cellular debris present. Postcontrast images often demonstrate enhancing internal septations and rim-enhancing tissue.

FINDINGS Precontrast T1-weighted MR (A) demonstrates several ill-defined, low-signal lesions in the right hepatic lobe that are bright on T2-weighted imaging (B). Note also associated capsular retraction about the lesions. Arterial phase imaging with Gd-BOPTA (MultiHance; Bracco Diagnostics, Milan, Italy) demonstrates peripheral rim and perilesional enhancement (C) with subtle increase in enhancement of the most posterior lesion in the venous phase images (D).

DIFFERENTIAL DIAGNOSIS Hepatic epithelioid hemangio-endothelioma, metastatic disease, multifocal hepatocellular cancer, “pseudocirrhosis” reflecting treated metastatic disease.

DIAGNOSIS Hepatic epithelioid hemangioendothelioma.

DISCUSSION Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin. These tumors are often (>80%) multifocal and coalesce over time. Tumors may be peripheral in location with overlying capsular retraction. Lesions demonstrate peripheral rim enhancement and perilesional enhancement. Pulmonary nodules are the most common location for extrahepatic disease followed by nodal, omental, and mesenteric masses.

When imaging features are suggestive of epithelioid hemangioendothelioma, biopsy is needed to confirm the diagnosis. These tumors are often initially misdiagnosed at histology and immunostaining for endothelial markers is required to make the diagnosis. Therefore, mentioning epithelioid hemangioendothelioma in the imaging differential diagnosis can aid the pathologist in making the correct histologic diagnosis. Patients may present with vague symptoms of abdominal discomfort, weight loss, or be asymptomatic. If untreated, lesions usually enlarge and coalesce resulting in liver failure.

The capsular retraction associated with individual liver lesions seen in the present case can also be seen in the setting of treated metastatic disease. This “pseudocirrhosis” appearance has been described, for example, with treated breast cancer metastases. The patient in this case did not have a history of known cancer. The lesions in this case are difficult to distinguish from metastatic disease in general, though the overlying capsular retraction is somewhat atypical for untreated metastatic disease.

Unlike the present case, hepatocellular carcinomas are classically hyperenhancing (not rim enhancing) in the arterial phase and show washout often with a capsule or pseudo-capsule in delayed images. The nodular morphology of the liver in this case is due to focal areas of capsular retraction overlying individual liver lesions. Uninvolved portions of the liver (e.g., left hepatic lobe in the above images) have a normal morphology.

FINDINGS Grayscale ultrasound (A) demonstrates an approximately 4.5-cm hyperechoic lesion in the right hepatic lobe. Color Doppler image (B) demonstrates no definite internal blood flow. Increased through transmission is seen in A and B.

T2-weighted MR demonstrates an ovoid, well-circumscribed homogeneously bright lesion in the right hepatic lobe (C). Arterial phase image (D) acquired 20 seconds after administration of intravenous contrast material demonstrates peripheral, discontinuous nodular enhancement. Venous phase image (E) (acquired 70 seconds after administration of intravenous contrast material) and 3-minute delayed image (F) demonstrate progressive central filling of the lesion (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Hemangioma, hepatocellular adenoma, hepatocellular carcinoma.

DIAGNOSIS Hemangioma.

Hemangiomas are common tumors occurring in up to 20% of adults and are multiple in up to 40% of patients. These tumors are usually asymptomatic and do not require treatment. In rare cases in which large hemangiomas result in discomfort or are complicated by bleeding, they may be resected.

Histologically, hemangiomas are composed of multiple vascular channels of various sizes and sparse connective tissue. Blood supply is peripheral. Blood then fills in centrally as it makes its way through these dilated vascular channels. Large hemangiomas may contain a fibrous central scar.

At contrast-enhanced cross-sectional imaging (CT or MR), classic hemangiomas demonstrate peripheral discontinuous nodular enhancement with centripetal fill-in. This peripheral nodular enhancement is usually discontinuous and sometimes appears “cloud-like.” The areas of peripheral nodular enhancement are often as bright as the blood pool as in the above case.

At T2-weighted MR, classic hemangiomas are homogeneously bright and may be nearly as bright as the cerebrospinal fluid (CSF). At T2-weighted imaging, hemangiomas and hepatic cysts can appear very similar but can be distinguished in postcontrast imaging based on the classic enhancement pattern of hemangiomas shown above and the absence of hepatic cyst enhancement.

At ultrasound, hemangiomas sometimes appear hyperechoic with increased through transmission and sometimes appear hypoechoic. However, malignant tumors also can appear hyperechoic at ultrasound. CT or MR should be recommended to further characterize indeterminate liver lesions identified at ultrasound. The blood flow in hemangiomas is usually too slow to be detectable at color Doppler or power Doppler ultrasound. If blood flow is detected at ultrasound, the lesion in question is most likely not a hemangioma.

FINDINGS An approximately 3.5-cm well-circumscribed lesion is present at the junction of segments 4A and 4B. This lesion demonstrates signal loss at out-of-phase imaging (B) compared with the in-phase imaging (A) indicating the presence of fat. The lesion is faintly bright at T2-weighted MR (C) and is low signal at T1 precontrast MR (D). At dynamic imaging, the lesion hyperenhances in the arterial phase (E) and washes out in the delayed phase (3-minute delayed) images (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Hemangioma, hepatocellular adenoma, hepatocellular carcinoma.

DIAGNOSIS Hepatocellular adenoma.

DISCUSSION Hepatic adenomas are a benign proliferation of hepatocytes, usually in an otherwise normal liver. Adenomas are relatively rare tumors but occur with increased frequency in women taking oral contraceptive pills, patients with glycogen storage disease, and individuals using anabolic steroids. Adenomas may decrease in size with cessation of oral contraceptive or anabolic steroid use.

At histology, adenomas are characterized by sheets of hepatocytes separated by dilated sinusoids. These dilated, thin-walled sinusoids are perfused by arterial blood pressure from peripheral feeding vessels. Adenomas have minimal supporting connective tissue. As a result of their unique blood supply and lack of supporting connective tissue, adenomas are at increased risk for bleeding. When bleeding does occur, it may spread into the abdominal cavity and be life-threatening as these lesions usually do not have a complete capsule.

Adenoma cells contain large amounts of lipid which is detectable by the loss of signal at out-of-phase imaging. Adenomas are usually mildly hyperintense at T2-weighted imaging though not nearly as bright as hepatic cysts and classic hemangiomas. T1 precontrast signal intensity varies from low signal to high signal with intrinsic T1 bright signal indicating fat or blood products.

At postcontrast imaging, adenomas hyperenhance in the arterial phase and then become isointense to liver or washout at delayed phase imaging. Adenomas are usually sharply marginated, but only a minority of adenomas have a capsule. Calcifications are uncommon but may occur in areas of old hemorrhage or necrosis.

Adenomas may be difficult to distinguish from hepatocellular cancer based on imaging. It is important to note that adenomas typically occur in otherwise normal livers, whereas hepatocellular cancers usually occur in patients with findings of chronic liver disease (e.g., a nodular liver with fibrosis). Adenomas have a low rate of malignant transformation.

Primarily due to their risk of bleeding and also because of a possible low rate of malignant transformation, adenomas are often treated. Treatment options include surgical resection and embolization.

FINDINGS Axial T2-weighted (A), T1-weighted precontrast (B), T1-weighted arterial phase (C), T1-weighted portal venous phase (D), and T1-weighted delayed phase (E) MR images through the upper abdomen demonstrate a 6-cm, lobulated left hepatic lobe lesion. A T2 bright central scar is visible (A). The lesion hyperenhances in the late arterial phase (C, 20-second delay), but is “stealth” or isointense to the surrounding liver parenchyma at T2-weighted (A), T1-weighted precontrast (B), venous phase (D, 70-second delay), and delayed (E, 3-minute delay) images. Delayed enhancement of the central scar is visible (E) (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]). Color Doppler ultrasound image (F) demonstrates a hypoechoic mass with a central blood vessel.

DIFFERENTIAL DIAGNOSIS Focal nodular hyperplasia (FNH), hepatocellular adenoma, hepatocellular carcinoma, hemangioma, hypervascular metastasis.

DIAGNOSIS FNH.

DISCUSSION FNH is a benign hepatic tumor and is the second most common liver tumor following hemangioma. FNH is usually asymptomatic and has no malignant potential. Though the etiology of FNH is uncertain, a vascular malformation or vascular injury has been posited as the underlying event leading to the development of FNH.

At gross pathology, malformed vascular structures are visible within the central scar. Lobules of hepatic parenchyma surround the central scar and are separated by radiating fibrous bands. FNH does not have a capsule.

At MR imaging, FNH is most commonly iso- or mildly hyperintense on T2-weighted images and iso- or mildly hypointense on T1-weighted precontrast images. The central scar is frequently bright on T2-weighted images due to the presence of blood vessels, myxomatous elements, and biliary ductules. FNH avidly and homogeneously enhances in the arterial phase and becomes more isointense in the portal venous phase. The fibrous component of the central scar frequently demonstrates delayed contrast uptake. At 1- to 3-hour delayed images performed after administration of Gd-BOPTA, FNH appears iso- to hyperintense to the surrounding liver in more than 96% of cases.

At CT imaging, FNH is most commonly iso- to hypoattenuating relative to the surrounding liver at precontrast imaging, avidly and homogeneously enhances in the arterial phase, and becomes more “stealth” or isoattenuating to the surrounding liver in the portal venous phase. As with MR, the fibrous component of the central scar may demonstrate delayed contrast uptake.

Ultrasound imaging features of FNH are nonspecific. At ultrasound, FNH is usually hypoechoic and may demonstrate a central blood vessel.

FINDINGS Axial T1-weighted precontrast (A) and postcontrast arterial phase (B) images demonstrate a T1 dark, hyperenhancing lesion in segment 4A. No signal loss was seen in out-of-phase images to suggest fat within the lesion (not shown). T2-weighted image (C) demonstrates intrinsic T2 bright signal in the lesion (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]). Octreotide scan (D) demonstrates focal uptake of the radiopharmaceutical within the segment 4A lesion as well as in the region of the duodenum.

DIFFERENTIAL DIAGNOSIS BASED ON MAGNETIC RESONANCE IMAGES FNH, hemangioma, hepatocellular adenoma, hepatocellular carcinoma, hypervascular metastasis (e.g., primary neuroendocrine tumor, thyroid cancer, renal cell carcinoma, melanoma, and some breast cancers).

DIAGNOSIS Metastatic neuroendocrine tumor.

DISCUSSION The differential diagnosis of a hypervascular liver lesion includes metastatic disease from a hypervascular primary malignancy, hepatocellular carcinoma, hepatocellular adenoma, and FNH. Hemangiomas are also hyperenhancing lesions but classically demonstrate peripheral discontinuous nodular enhancement with central fill-in unlike the lesion in this case which is more homogeneously enhancing in the arterial phase.

Hepatocellular carcinoma would be unusual in a patient without a cirrhotic/nodular morphology of the liver. A history of oral contraceptive use and fat within the lesion (which this lesion did not have) would be more suggestive of hepatocellular adenoma. FNH would be expected to be more “stealth” or isointense on T1- and T2-weighted images.

This patient ultimately underwent a nuclear medicine octreotide scan that was positive for neuroendocrine tumor. A multilobulated duodenal bulb mass was seen at esophagoduodenoscopy and was determined to be the site of primary malignancy.

FINDINGS In- (A) and out-of-phase (B) images demonstrate a 3.5-cm mass (arrows) in the segment 4a liver that loses signal in the out-of-phase images indicating that the mass contains intracellular lipid. The mass is T2 bright (C), hyperenhances in the arterial phase (D), and washes out with a capsule (E) in the delayed phase images. At color Doppler ultrasound, the mass is hyperechoic and heterogeneous. No discrete blood vessels could be identified in the mass at color Doppler ultrasound. This mass was new when compared with an MR from 6 months prior (not shown). Incidentally noted in the T2-weighted image is a 1.2-cm T2 bright structure (C) that had imaging features compatible with a hemangioma at postcontrast imaging (not shown) (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]). Color Doppler ultrasound (F) demonstrates a corresponding echogenic mass.

DIFFERENTIAL DIAGNOSIS FNH, hemangioma, hepatocellular adenoma, hepatocellular carcinoma, metastasis from a hypervascular primary malignancy.

DIAGNOSIS Hepatocellular carcinoma.

DISCUSSION The differential diagnosis of a hyperenhancing hepatic mass is given above. Hemangioma can be eliminated from the list as the above-described mass does not demonstrate the classic peripheral discontinuous nodular enhancement with fill-in nor the T2 fluid bright signal seen with hemangiomas. FNH can be eliminated as the mass is not “stealth” in the T2-weighted image. Both hepatocellular adenoma and hepatocellular carcinoma may contain visible intracellular lipid though the patient demographics are usually quite different. Hepatic adenomas are rare tumors occurring usually in young women taking oral contraceptive pills, individuals with a glycogen storage disease, or individuals using anabolic steroids. Hepatocellular carcinomas tend to occur in patients with chronic liver disease like this patient.

Hepatocellular cancers are often bright at T2-weighted imaging. Fat-containing hepatocellular cancers will lose signal at out-of-phase imaging. About 80% to 90% of hepatocellular carcinomas are hypervascular and hyperenhance relative to the adjacent hepatic parenchyma in the arterial phase of imaging. About 10% to 20% of hepatocellular carcinomas are relatively hypoenhancing at arterial phase imaging. Hepatocellular carcinomas demonstrate a capsule at histologic evaluation in 65% to 82% of cases, and washout with a capsule is often seen at imaging.

FINDINGS Noncontrast T1-weighted MR (A) demonstrates a well-circumscribed 4.5-cm lesion in the segment 4 liver. T2-weighted MR (B) demonstrates corresponding T2 bright signal. This mass hyperenhances in the arterial phase (C) and washes out in the 3-minute delayed image (D). Comparing the in-phase (E) and out-of-phase image (F), small subtle areas of signal loss are seen in the out-of-phase image indicating a small fat component. Additionally, there is mild global signal loss in the out-of-phase image indicating mild diffuse hepatic steatosis (contrast agent: Gd-BOPTA [Multi- Hance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Hepatocellular adenoma, hepatocellular cancer, dysplastic nodule.

DIAGNOSIS Hepatocellular cancer.

DISCUSSION This tumor demonstrates the classic findings of hepatocellular cancer: arterial phase hyperenhancement, washout with a capsule at delayed phase imaging, T2 bright signal abnormality, and internal fat. Hepatic adenoma could have a very similar appearance. However, hepatocellular carcinoma is more likely in the above case given that the background liver exhibits early changes of chronic liver disease including a slightly nodular morphology and also linear areas of delayed reticular hyperenhancement (not well seen in the above images) indicating mild fibrosis.

A dysplastic nodule may show T2 bright signal abnormality and arterial hyperenhancement but should not demonstrate washout with a capsule at delayed imaging. Once washout is present, the lesion has progressed to hepatocellular cancer.

The above patient tested negative for hepatitis B and hepatitis C. This patient underwent a left hepatectomy as it was thought that she would have sufficient remaining liver parenchyma following surgery. Additionally, given that this patient’s liver synthetic function was normal, she likely would not have qualified for a liver transplant based on Model for End-Stage Liver Disease (MELD) score, even given exception points for the presence of tumor.

FINDINGS Arterial phase T1 postcontrast MR (A) demonstrates a 1.8-cm hyperenhancing lesion in the segment 8/4A liver. This lesion washes out with peripheral rim enhancement in the 3-minute delayed image (B). No definite T2 correlate is seen in T2-weighted images with and without fat saturation (C, D). No signal loss is seen in this lesion in the out-of-phase (F) as compared with the in-phase (E) image to indicate fat. The patient’s liver is small and nodular indicating changes of chronic liver disease. Small-volume ascites is present (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Dysplastic nodule, hepatocellular cancer, perfusional abnormality.

DIAGNOSIS Hepatocellular cancer.

DISCUSSION According to the Organ Procurement and Transplantation Network (OPTN) consensus panel (convened 2008, adopted 2011), lesions ≥1 and <2 cm can be diagnosed at MR as hepatocellular cancers if they demonstrate late arterial phase hyperenhancement, washout in more delayed images, and peripheral rim enhancement (capsule or pseudocapsule). The above 1.8-cm lesion therefore satisfies OPTN criteria for hepatocellular cancer as it hyperenhances in the late arterial phase and washes out with a capsule in the 3-minute delayed image.

Additionally, other criteria that can be used to diagnose hepatocellular cancer at MR according to OPTN include growth by ≥50% on serial scans ≤6 months apart and hyperenhancement in the late arterial phase for lesions that are ≥1 or <2 cm. For lesions ≥2 and ≤5 cm, hyperenhancement in the late arterial phase and either washout during later phases, or peripheral rim enhancement, or growth by ≥50% on scans ≤6 months apart is diagnostic of hepatocellular cancer.

Corresponding T2 bright signal abnormality and signal loss at out-of-phase imaging (indicating intravoxel fat) also may be seen in hepatocellular cancers. However, these latter two findings are not requirements to diagnose hepatocellular cancer at MR according to the OPTN.

Dysplastic nodules may hyperenhance in the late arterial phase and may demonstrate a T2 correlate but do not demonstrate washout in delayed images. Perfusional abnormalities generally demonstrate a geographic or triangular morphology rather than a round shape. Perfusional abnormalities are usually visible in the arterial phase but do not have correlates in the other series.

Available transplant livers go to the most ill patients as defined by the MELD score. MELD scores range from 6 to 40 with higher scores indicating more severely ill individuals. The MELD score is calculated based on creatinine, total bilirubin, and INR. When a donor liver becomes available, it usually goes to the matching recipient in a given region with the highest MELD score.

In 1996, a group from Milan, Italy (see Question 1), reported that liver transplant was an effective treatment for cirrhotic patients with small, unresectable hepatocellular cancers. Patients with hepatocellular cancers that fall within Milan criteria are given MELD exception points and begin with a MELD score of 22 rather than 6.

FINDINGS T1 precontrast MR (A) demonstrates a subcentimeter area of low signal in the segment 5 liver adjacent to the gallbladder fossa. A larger rounded area of T2 bright signal abnormality is seen in this location (B). This lesion hyper-enhances in the arterial phase images (C) but does not wash out at delayed phase imaging (D). Note also morphologic features of chronic liver disease with a somewhat small, nodular liver and widening of the gallbladder fossa (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Dysplastic nodule, hepatocellular cancer, perfusional abnormality.

DIAGNOSIS Dysplastic nodule.

DISCUSSION In the United States, approximately 80% to 90% of hepatocellular cancers occur in patients with cirrhosis. Hepatitis C infection is the most common cause of cirrhosis in North America and Europe, whereas hepatitis B infection is the most common cause of cirrhosis in Africa and Asia. Alcohol is the third leading cause of cirrhosis worldwide.

The liver responds to injury by regenerating. When subjected to prolonged injury (e.g., chronic viral hepatitis), innumerable regenerative nodules may form. It has been proposed that the development of hepatocellular cancer is often the end result of a process that begins with regenerative nodules which may progress to dysplastic nodules, and then may progress to hepatocellular cancer.

Diagnostic criteria for dysplastic nodules include hyper-enhancement at arterial phase imaging, sometimes with a T2 signal abnormality, but with no definite washout at delayed phase imaging. Arterial hyperenhancement with washout at delayed imaging is diagnostic of hepatocellular cancer. Additional features including T2 bright signal abnormality and internal fat are also supportive of a diagnosis of hepatocellular cancer but are not visible in every case.

A dysplastic nodule can be distinguished from a perfusional abnormality based on identification of a correlative area of signal abnormality in the T1 precontrast or T2-weighted images. Perfusional abnormalities are usually only visible in the arterial phase images without a correlate in the other series. Also, perfusional abnormalities often have a geographic rather than a rounded morphology. Many, though not all, perfusional abnormalities also occur in a subcapsular location.

The clinical management of nodules diagnosed as dysplastic nodules varies greatly when compared with those diagnosed as hepatocellular cancers at imaging. Perhaps because of lack of standardization in the imaging features used to diagnose a dysplastic nodule, the appropriate management of dysplastic nodules is a source of controversy in the literature. For example, recent guidelines from the American Association of Liver Disease do not recommend more aggressive screening of patients with dysplastic nodules. And the United Network for Organ Sharing (UNOS) does not require the reporting of dysplastic nodules at pretransplant imaging. However, high-volume transplant and imaging centers have observed a number of dysplastic nodules transition into hepatocellular cancers and recommend short-interval follow-up (e.g., 3-month MR) for patients with dysplastic nodules.

By comparison, hepatocellular cancers diagnosed at imaging usually prompt aggressive management ranging from resection in patients with small tumors and no known chronic liver disease, to liver transplant in patients with small, unresectable tumors and cirrhosis, to locoregional therapies such as chemoembolization in patients with unresectable hepatocellular cancer that does not meet criteria for liver transplant.

FINDINGS Arterial phase image (A) demonstrates no suspicious liver lesions. However, at portal venous phase (not shown) and 3-minute delayed imaging (B) a 7-mm area of low signal is visible in the lateral segment left hepatic lobe. No correlate is visible in the T1 precontrast (C) or T2-weighted image (D). Comparing out-of-phase (E) and in-phase (F) images, a corresponding area of signal loss is visible in the in-phase image.

DIFFERENTIAL DIAGNOSIS Hepatocellular carcinoma, metastasis, siderotic nodule.

DIAGNOSIS Siderotic nodule.

DISCUSSION Siderotic nodules are iron-containing nodules. The key to making the correct diagnosis in this case is identifying the corresponding area of signal loss in the in-phase MR image. If in-phase images are acquired with a longer TE than out-of-phase images, susceptibility artifacts will “bloom” or look darker/bigger in the in-phase images. Susceptibility artifacts can be caused by a variety of substances including iron, air, and surgical clips and other postoperative changes. Identification of a corresponding area of signal loss in the in-phase image confirms the presence of a siderotic nodule.

Classic hepatocellular cancers “wash out” or appear of lower signal than the surrounding hepatic parenchyma at delayed phase imaging and could look similar to this siderotic nodule in the delayed phase image. However, a corresponding area of arterial hyperenhancement is usually necessary to confidently diagnose hepatocellular cancer at initial presentation. Other findings that are supportive of a diagnosis of hepatocellular cancer but are not visible in every case include a corresponding T2 bright signal abnormality and signal loss at out-of-phase imaging indicating the presence of fat.

A metastasis could have an identical appearance in the portal venous phase and delayed phase images. Therefore, evaluation of the in- and out-of-phase images is key to avoid mistakenly diagnosing a siderotic nodule as a metastasis. Likewise, assessing for signal loss at out-of-phase imaging is key to avoid the pitfall of mistakenly diagnosing focal fat deposition as a metastasis. Areas of focal fat will lose signal at out-of-phase imaging.

FINDINGS Ultrasound (A) was initially performed. A parvus tardus waveform with delayed upstroke and low-peak systolic velocity was noted in all hepatic arterial structures (A). Patient then underwent contrast-enhanced MR (B) that demonstrated occlusion of the hepatic artery approximately 1.5 cm beyond its origin. Confirmatory arteriogram (C) demonstrates hepatic artery occlusion approximately 1.5 cm beyond its origin. Note opacification of the splenic artery, renal arteries, superior mesenteric artery, and inferior mesenteric artery but no opacification of the hepatic artery.

DIFFERENTIAL DIAGNOSIS Hepatic artery occlusion.

DIAGNOSIS Hepatic artery occlusion.

DISCUSSION When evaluating a patient who has undergone liver transplant, evaluation of the patency of vascular structures is critical. As the hepatic artery provides the only supply to the intrahepatic biliary system, hepatic artery stenosis or thrombosis can result in biliary ischemia. If the arterial stenosis or thrombosis is not corrected, biliary ischemia can result in multiple nonanastomotic stenoses visible at imaging and ultimately be a cause of graft failure. When searching for the hepatic artery, remember that the donor hepatic artery may be anastomosed to the recipient hepatic artery or directly to the aorta via an interposition graft.

Liver transplants require anastomoses of the hepatic artery, portal vein, common bile duct, and inferior vena cava. In general, complications of liver transplant visible at imaging include vascular complications, biliary complications, and other complications. Vascular complications include stenosis or thrombosis at any of the three vascular anastomoses (hepatic artery, portal vein, or inferior vena cava). Pseudoaneurysms may also form at anastomotic sites or within the liver parenchymal as a complication of biopsy or other intervention. Biliary complications include anastomotic narrowing, bile leak, and cholangitis. Other complications include hematoma, abscess, recurrent hepatitis, recurrent malignancy, and post transplant lymphoproliferative disorder (PTLD).

The major indication for liver transplant is end-stage liver disease that will be cured by the procedure. Etiologies of end-stage liver disease that may warrant transplant are numerous and include viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis, liver malignancies (e.g., hepatocellular cancer and epithelioid hemangioendothelioma), metabolic liver diseases (e.g., Wilson disease, hereditary hemochromatosis, glycogen storage disease, and α1-antitrypsin deficiency), vascular diseases of the liver (e.g., Budd-Chiari syndrome), cholestatic liver diseases (e.g., primary biliary cirrhosis and PSC), and miscellaneous causes (e.g., hepatic trauma).

Contraindications for liver transplant include active substance abuse. No strict age cutoff exists though some centers will not transplant patients older than 60 years and other centers will not transplant patients older than 70 years.

FINDINGS Grayscale ultrasound (A) demonstrates a small and nodular liver. Note the large amount of anechoic material surrounding the liver in keeping with ascites. Blood flow is detected in the main portal vein with power Doppler (B). T1- (C) and T2-weighted (D) MR also demonstrate a small and nodular liver with ascites as well as splenomegaly. (Evaluating signal intensity of the CSF is the most reliable way to determine if a sequence is T1- or T2-weighted. CSF is dark in T1-weighted images and is bright in T2-weighted images.)

DIFFERENTIAL DIAGNOSIS Hepatic cirrhosis with portal hypertension.

DIAGNOSIS Hepatic cirrhosis with portal hypertension.

DISCUSSION Cirrhosis is defined as liver disease characterized by hepatocyte damage and fibrosis. Cirrhosis is the seventh leading cause of disease-related death in the United States. Etiologies of cirrhosis include hepatitis C, hepatitis B, alcohol, and non-alcoholic fatty liver disease (NAFLD).

In early cirrhosis, liver morphology will appear normal at imaging. As cirrhosis progresses, a nodular hepatic contour is visible at imaging. Relative hypertrophy of the caudate lobe and of the lateral segment left hepatic lobe is also a morphologic feature of cirrhosis seen at imaging. Fissural widening, widening of the gallbladder fossa, and widening of the periportal space are also morphologic changes of cirrhosis.

As cirrhosis progresses, hepatic fibrosis results in increased pressure in the portal venous system, a condition known as portal hypertension. Findings seen in patients with portal hypertension include ascites, splenomegaly, and development of large collateral vessels. Large collateral vessels (also known as varices) form as a way for blood to return to the heart while bypassing the high-pressure hepatic portal venous system. Varices may form in a variety of locations, including around the esophagus, stomach, umbilicus, retroperitoneum, mesentery, rectum, and abdominal wall. Splenorenal shunts and hemorrhoids may also develop as collateral pathways in patients with portal hypertension.

As patients with cirrhosis are at increased risk for hepatocellular cancer, consideration should be given to hepatocellular cancer screening in patients with findings of chronic liver disease. Whether performed with CT or MR, arterial phase, venous phase, and delayed phase images are required for accurate hepatocellular cancer screening.

FINDINGS T1-weighted MR (A) demonstrates a small, nodular liver in keeping with changes of advanced chronic liver disease. Notice also the geographic area of low signal with linear margins involving primarily segments 4A and 8 near the inferior vena cava. T2-weighted MR demonstrates corresponding T2 bright signal abnormality in segments 4A (B) and 8 (not shown). Dynamic contrast-enhanced MR demonstrates this area to be hypoenhancing relative to adjacent hepatic parenchyma in the arterial phase (C) of enhancement, hyperenhancing in the portal venous phase (D), and extremely hyperenhancing in the 3-minute delayed image (E) (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]). Non-contrast CT (F) demonstrates a corresponding area of low attenuation.

DIFFERENTIAL DIAGNOSIS Confluent hepatic fibrosis.

DIAGNOSIS Confluent hepatic fibrosis.

DISCUSSION Hepatic fibrosis occurs in response to liver injury such as chronic inflammation due to hepatitis. Liver fibrosis is histologically defined as the deposition of substances including collagen and proteoglycans in the extracellular matrix.

The phrase “confluent fibrosis” refers to large, mass-like areas of fibrosis. Confluent fibrosis most commonly involves the anterior segment right hepatic lobe and medial segment left hepatic lobe.

At MR, areas of fibrosis usually demonstrate low T1 signal and high T2 signal due to the presence of water within areas of fibrosis. Areas of fibrosis exhibit delayed hyperenhancement at both CT and MR due to accumulation of gadolinium in the extracellular compartment. Areas of fibrosis can be thought of as hanging on to contrast material while contrast material washes out from the remainder of the liver. Delayed hyperenhancement in areas of confluent hepatic fibrosis is usually relatively homogeneous.

Confluent hepatic fibrosis can be distinguished from a neoplasm by its geographic morphology often with linear borders, associated capsular retraction, relatively homogeneous delayed hyperenhancement, and progressive volume loss over time.

FINDINGS T1- (A) and T2-weighted (B) MR images demonstrate a T1 dark mass in the right hepatic lobe with intermediate- to-bright, heterogeneous T2 signal. Postcontrast MR images in the arterial (C) and portal venous (D) phase as well as 3-minute delayed (E) MR image demonstrate progressive enhancement of the mass (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Hemangioma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma.

DIAGNOSIS Intrahepatic cholangiocarcinoma.

DISCUSSION Cholangiocarcinoma is the second most common primary liver cancer following hepatocellular carcinoma. Cholangiocarcinomas are categorized based on location as extrahepatic, intrahepatic hilar, and intrahepatic peripheral.

At MR and CT imaging, intrahepatic cholangiocarcinomas demonstrate progressive enhancement at delayed imaging as seen in this case due to their fibrous nature. Progressive enhancement at delayed image is thought to reflect contrast material diffusing into the tumor interstitium.

By comparison, hepatocellular carcinomas classically demonstrate hyperenhancement in the arterial phase and washout at delayed imaging. An additional helpful discriminator is that cholangiocarcinomas tend to constrict adjacent vessels, whereas hepatocellular carcinomas more commonly invade adjacent vessels. Also, intrahepatic cholangiocarcinomas are often associated with more peripheral biliary ductal dilatation, whereas hepatocellular carcinomas are not. Hemangiomas demonstrate discontinuous peripheral nodular enhancement with gradual more central filling at delayed imaging.

FINDINGS Grayscale ultrasound image (A) demonstrates two heterogeneous, primarily hypoechoic masses in the right hepatic lobe. Color Doppler image (B) demonstrates blood flow within the posterior mass and also in the anterior mass (not shown). The masses are hypermetabolic at positron emission tomography CT imaging (C). T2-weighted MR (D) demonstrates two corresponding T2 bright areas of signal abnormality in the right hepatic lobe. The masses are dark in the T1 precontrast images (E) and hypoenhance at venous phase MR (F) (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy]).

DIFFERENTIAL DIAGNOSIS Abscesses, metastatic disease, lymphoma.

DIAGNOSIS Lymphoma (secondary, non-Hodgkin).

DISCUSSION Primary hepatic lymphoma is rare, accounting for less than 1% of extranodal primary lymphomas and approximately 1% of primary hepatic tumors. Primary hepatic lymphoma most commonly occurs in immunocompromised patients.

Secondary hepatic lymphoma is more common than primary hepatic lymphoma. Secondary lymphoma occurs in up to 50% of patients with non-Hodgkin lymphoma and up to 20% of patients with Hodgkin lymphoma. Secondary lymphoma is more commonly multifocal or diffusely infiltrating rather than a solitary lesion. Secondary lymphoma is usually found in patients with widespread lymphoma.

At ultrasound, hepatic lymphoma is usually hypoechoic to anechoic. At CT, hepatic lymphoma is usually hypoattenuating. At MR, hepatic lymphoma may be dark or bright on T2-weighted images, is usually dark on T1-weighted images, and is usually hypoenhancing.

FINDINGS Color Doppler ultrasound demonstrates heterogeneous hepatic parenchyma (A) and patent transplant vasculature (not shown). Patient next underwent MR imaging to better evaluate the liver parenchyma. T2-weighted MR (B) demonstrates innumerable 1- to 2-cm T2 bright liver lesions that are T1 dark (C) and hypoenhancing (D) (contrast agent: Gd-BOPTA [MultiHance; Bracco Diagnostics, Milan, Italy)].

DIFFERENTIAL DIAGNOSIS Abscesses, post-transplant lymphoproliferative disorder (PTLD), metastatic disease.

DIAGNOSIS PTLD.

DISCUSSION PTLD occurs as a complication of organ transplantation due to immunosuppression. A majority of cases appear to be related to Epstein-Barr virus. PTLD is a general term that describes a spectrum of illnesses. At the milder end of the spectrum, some patients will manifest an acute mononucleosis-type illness. At the more severe end of the spectrum, patients develop a monoclonal proliferation of lymphoid cells that meet diagnostic criteria for lymphoma. Liver biopsy was performed in the above patient, and pathology revealed B-cell lymphoma.

PTLD is uncommon occurring in approximately 1% to 2% of liver transplant patients. PTLD is slightly more common in other solid organ transplant patients (e.g., kidney and lung) and occurs in up to a third of patients who undergo bowel transplant or multiple organ transplants.

Of patients who develop PTLD, a majority of patients will develop PTLD in the first year after transplant when immunosuppression is most intense. At imaging, patients with PTLD may present with solid organ lesions or lymphadenopathy
with extranodal disease being more common. PTLD preferentially involves the transplanted organ. Central nervous system and gastrointestinal tract involvement also may occur. The mainstay of treatment of PTLD is cessation or decrease in immunosuppressive medications.

Abscesses could have a similar appearance at imaging, though fever and elevated white blood cell count would be expected. Diffuse metastatic disease could have a similar appearance. Tissue sampling is usually required to make the diagnosis of PTLD.

FINDINGS Axial T1-weighted in-phase and out-of-phase images (A, B) through the upper abdomen demonstrate signal loss in the liver and spleen in the in-phase image. (The out-of-phase image can be identified based on the presence of the chemical shift artifact of the second kind, also known as the “India ink” artifact. This artifact occurs because the resonance frequencies of fat and water differ such that at TEs of approximately 2.3 ms at 1.5 T, fat and water protons are out-of-phase [imagine vectors pointing in opposite directions] and cancel each other out. A black line is seen at fat-water interfaces as a result of this cancellation in voxels that contain equal parts of fat and water.)

DIFFERENTIAL DIAGNOSIS Diffuse fat deposition, diffuse iron deposition.

DIAGNOSIS Diffuse iron deposition.

DISCUSSION Diffuse iron deposition is indicated by the signal loss in the liver and spleen seen in the in-phase image. This signal loss occurs because susceptibility artifacts due to iron increase with longer TEs, and the TE of the in-phase image (4.99 ms) is longer than the TE of the out-of phase image (2.33 ms).

FINDINGS Axial T1-weighted in-phase (A) and out-of-phase (B) images through the upper abdomen demonstrate signal loss in the liver in the out-of-phase image. (The out-of- phase image can be identified based on the presence of the chemical shift artifact of the second kind, also known as the “India ink” artifact. This artifact occurs because the resonance frequencies of fat and water differ such that at an echo time [TE] of approximately 2.2 ms at 1.5 T, fat and water protons are out-of-phase [imagine vectors pointing in opposite directions] and cancel each other out. A black line is seen at fat-water interfaces as a result of this signal cancellation in voxels that contain equal parts of fat and water.)

DIFFERENTIAL DIAGNOSIS Diffuse hepatic fat deposition, diffuse hepatic iron deposition.

DIAGNOSIS Diffuse hepatic fat deposition.

DISCUSSION Diffuse fat deposition is indicated by the signal loss in the liver seen in the out-of-phase image. Hepatic steatosis may result from a number of causes, including excessive alcohol consumption, obesity, insulin resistance, and steroid use. Nonalcoholic fatty liver disease (NAFLD) is a general term that encompasses both fatty liver (hepatic steatosis) and nonalcoholic steatohepatitis (NASH).

NASH is characterized by hepatic fat deposition with associated inflammation and can progress to fibrosis. NASH is an increasingly common etiology of chronic liver disease and cirrhosis in the United States. Individuals with hepatic steatosis may be asymptomatic or may have right upper quadrant pain or elevated liver function tests.

At cross-sectional imaging, hepatic inflammation manifests as heterogeneous arterial phase enhancement. Hepatic fibrosis is visible as reticular areas of increased enhancement at delayed postcontrast imaging.

FINDINGS Grayscale ultrasound (A) demonstrates an echogenic liver with a geographic hypoechoic area along the porta hepatis. No definite blood flow is visible in this area at color Doppler imaging (B). In-phase (C) and out-of-phase (D) MR demonstrate diffuse hepatic signal loss in the out-of-phase image with the exception of the hepatic parenchyma around the porta hepatis.

DIFFERENTIAL DIAGNOSIS Hepatic steatosis with fat sparing; hepatic steatosis with focal fat deposition.