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From the Archives of the AFIP

Fibrolamellar Carcinoma of the Liver: Radiologic-Pathologic Correlation

¹ Departments of Radiologic Pathology (J.K.M., P.T.R., G.N.B., N.K., P.R.R.)
² Hepatobiliary Pathology (Z.D.G.), Armed Forces Institute of Pathology, 14th and Alaska Sts, NW, Washington DC 20306
³ Department of Radiology, Okayama University, Japan (N.K.)
⁴ Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (P.R.R.)

	Abstract

Top Abstract INTRODUCTION CLINICAL FEATURES PATHOLOGIC FEATURES RADIOLOGIC FEATURES DIFFERENTIAL DIAGNOSIS BIOPSY FOR DIAGNOSIS PROGNOSIS AND TREATMENT References

 
Fibrolamellar carcinoma is a malignant hepatocellular tumor with distinct clinical and pathologic differences from hepatocellular carcinoma. It differs from hepatocellular carcinoma in demographics, condition of the affected liver, tumor markers, and prognosis. Fibrolamellar carcinoma characteristically manifests as a large hepatic mass in adolescents or young adults (without gender predominance). Cirrhosis; elevated -fetoprotein levels; and typical risk factors for hepatocellular carcinoma such as viral hepatitis, alcohol abuse, and metabolic disease are typically absent. Fibrolamellar carcinoma is characterized pathologically by cords of tumor cells surrounded by abundant collagenous fibrous tissue arranged in a parallel or lamellar distribution. Fibrotic lamellae often coalesce to form a central scar. Fibrolamellar carcinoma characteristically appears on radiologic images as a lobulated heterogeneous mass with a central scar in an otherwise normal liver. Radiologic evidence of cirrhosis, vascular invasion, or multifocal disease—findings typical of hepatocellular carcinoma—is uncommon in fibrolamellar carcinoma. Imaging features of fibrolamellar carcinoma overlap with those of other scar-producing lesions including focal nodular hyperplasia (FNH), hepatocellular adenoma and carcinoma, hemangioma, metastases, and cholangiocarcinoma. FNH, in particular, may simulate fibrolamellar carcinoma, since both have similar demographic and clinical characteristics. Because some believe that radiologic diagnosis of FNH is possible, it is important to understand the imaging appearance of fibrolamellar carcinoma to avoid misdiagnosing this malignant tumor as a FNH.

Index Terms: Liver neoplasms, 761.324 • Liver neoplasms, MR, 761.12141

	INTRODUCTION

Top Abstract INTRODUCTION CLINICAL FEATURES PATHOLOGIC FEATURES RADIOLOGIC FEATURES DIFFERENTIAL DIAGNOSIS BIOPSY FOR DIAGNOSIS PROGNOSIS AND TREATMENT References

 
Fibrolamellar carcinoma is an uncommon variant of hepatocellular carcinoma. Initially described by Edmonson in 1956 (1), fibrolamellar carcinoma was not appreciated as a specific subtype of hepatocellular carcinoma for 20 years and was variably referred to as hepatocellular carcinoma with laminar fibrosis, hepatocellular carcinoma with polygonal cell type and fibrous stroma, oncocytic hepatocellular carcinoma, eosinophilic hepatocellular carcinoma with lamellar fibrosis, and finally fibrolamellar carcinoma.

The clinical impact of establishing this diagnosis was not fully appreciated until 1980 when Craig et al (2) and Berman et al (3) simultaneously reported that patients with fibrolamellar carcinoma differed from those with hepatocellular carcinoma in age, presence of underlying liver disease, positivity of tumor markers, and prognosis. Although fibrolamellar carcinoma is relatively uncommon among total cases of hepatocellular carcinoma (2–5), it represents a considerable proportion of hepatocellular carcinoma cases in patients younger than 50 years of age with a noncirrhotic liver (4).

This article is based on a review of the literature and 58 cases of fibrolamellar carcinoma with cross-sectional imaging studies contained within the archives of the Armed Forces Institute of Pathology (AFIP) and collected between 1985 and 1998. A previous report from the AFIP described 17 cases of fibrolamellar carcinoma collected between 1956 and 1983 (6) and reviewed nine ultrasonographic (US), 10 computed tomographic (CT), but no magnetic resonance (MR) imaging studies. Since then, 58 cases of fibrolamellar carcinoma have been accessioned, with a total of 35 US, 54 CT, 14 MR imaging, and 11 scintigraphic studies. In this article, we examine the clinical, pathologic, and radiologic features of fibrolamellar carcinoma emphasizing modalities (MR imaging) and techniques (dynamic contrast enhancement) that were not discussed in the previous review. Understanding the pathologic basis of the imaging appearance of fibrolamellar carcinoma helps one to distinguish it from other liver neoplasms. The differential diagnosis, treatment options, and prognosis of fibrolamellar carcinoma are also discussed.

	CLINICAL FEATURES

Top Abstract INTRODUCTION CLINICAL FEATURES PATHOLOGIC FEATURES RADIOLOGIC FEATURES DIFFERENTIAL DIAGNOSIS BIOPSY FOR DIAGNOSIS PROGNOSIS AND TREATMENT References

 
Fibrolamellar carcinoma occurs predominantly in young adult patients, with an age range of 5–69 years (mean, 23 years). Most patients present in the 2nd or 3rd decade of life (2,3,5,6). Men and women are at equal risk for fibrolamellar carcinoma, in contrast with the strong male predilection associated with hepatocellular carcinoma and female predominance in focal nodular hyperplasia (FNH). Fibrolamellar carcinoma accounts for 1%–9% of cases of hepatocellular carcinoma overall (2–5); however, it may represent up to 35% of hepatocellular carcinomas in individuals under 50 years of age without underlying cirrhosis (4). Patients with fibrolamellar carcinoma typically do not have underlying liver disease, although occasionally hepatitis and cirrhosis may be present (<5% of cases) (2,7,8). In fact, cirrhosis and hepatitis are not believed to predispose patients to development of fibrolamellar carcinoma. No specific risk factors for fibrolamellar carcinoma have been identified. Compared with its prevalence in the United States, fibrolamellar carcinoma is less common in Europe (9) and rare in Japan and China (10). In the Far East, fibrolamellar carcinoma constitutes a significantly smaller percentage of hepatocellular malignancies, both because of a decreased prevalence of fibrolamellar carcinoma and an increased prevalence of hepatocellular carcinoma.

The clinical presentation of patients with fibrolamellar carcinoma is variable. These patients commonly have pain, hepatomegaly, palpable right upper quadrant abdominal mass, and cachexia (2,3), and symptoms are usually present for 3–12 months before diagnosis (6). Uncommon presenting signs and symptoms include metastatic disease, pain, and fever, which simulate a hepatic abscess; gynecomastia in men (11); or venous thrombosis (6).

Gynecomastia, which is rare in patients with fibrolamellar carcinoma, results from direct conversion of circulating androgens to estrogens by the enzyme aromatase, which is elaborated by the malignant hepatocytes of fibrolamellar carcinoma (11), rather than resulting from liver failure (alcoholic cirrhosis, in particular).

Jaundice is a rare sign, present in 5% of cases, that results from biliary compression caused by either direct tumor invasion or mass effect or by metastatic lymphadenopathy, rather than from functional liver failure (12).

Fibrolamellar carcinoma is not usually associated with serum hepatocellular tumor markers such as -fetoprotein. In patients with fibrolamellar carcinoma, levels of -fetoprotein are typically normal, unlike the frequently elevated levels found in patients with hepatocellular carcinoma (1,7). However, mild elevation of -fetoprotein levels (less than 200 ng/µL [200 µg/L]) may occur in up to 10% of patients with fibrolamellar carcinoma (7). Rarely, marked elevated levels of -fetoprotein (10,000 ng/µL [10,000 µg/L]), similar to those found in hepatocellular carcinoma, may be found in patients with fibrolamellar carcinoma (13).

Frequently, serum transaminase levels are mildly elevated (less than 100 IU/L), and rarely more marked elevation (100–400 IU/L) may occur (2). In rare cases, patients may have hepatitis B surface antigen, and, if they also have hepatitis and cirrhosis, the conditions are thought to be incidental and not causative of fibrolamellar carcinoma. Various other tumor markers may be present, including vitamin B12 binding capacity (14), neurotensin (15), and carcinoembryonic antigen. These tumor markers are neither sensitive nor specific for screening for or characterizing fibrolamellar carcinoma; however, they may be useful clinically to monitor response to treatment and possible recurrence (16).

	PATHOLOGIC FEATURES

Top Abstract INTRODUCTION CLINICAL FEATURES PATHOLOGIC FEATURES RADIOLOGIC FEATURES DIFFERENTIAL DIAGNOSIS BIOPSY FOR DIAGNOSIS PROGNOSIS AND TREATMENT References

 
Fibrolamellar carcinoma is usually a large, single, well-demarcated, lobulated, nonencapsulated intrahepatic mass. Cut tumor specimens are tan, brown, or brownish green with streaks of white fibrous tissue. Fibrous tissue infiltrates throughout the tumor and may separate the tumor into small "islands" or "compartments" (2,3,6). The fibrotic tissue may coalesce to form a scar, which is typically central. A central scar was reported in 20%–50% of cases (6,13) and seen in 60% of the 58 AFIP cases.

Although most commonly a solitary mass (80%–90% of cases), fibrolamellar carcinoma may appear less frequently as a mass with small peripheral satellite lesions (10%–15%), a bilobed mass (5%), and rarely as diffuse multifocal masses (less than 1%) (2,3,6). Lesions are characteristically intrahepatic, although some are pedunculated (20% of cases). Tumors average 13 cm in diameter, and most vary from 5 to 20 cm (2,3,6,17). Although the tumors are sharply marginated against the liver parenchyma, encapsulation of fibrolamellar carcinoma rarely occurs, unlike hepatocellular carcinoma, which is frequently encapsulated. Hemorrhage and necrosis, which manifest microscopically in one-third of cases, are grossly visible in only 10% of cases and, when present, are usually minor in degree (6). Rarely, massive necrosis and hemorrhage of fibrolamellar carcinoma have resulted in a multicystic appearance that simulates that of a cystic hepatic neoplasm (18).

The occasional brownish-green staining of fibrolamellar carcinoma is caused by bile pigment. These tumors may contain bile pigment because well-differentiated primary hepatocellular neoplasms retain the ability to absorb bilirubin from the blood but have a decreased ability to secrete bilirubin into the biliary system.

Fibrolamellar carcinoma consists of large eosinophilic, polygonal neoplastic cells arranged in sheets, cords, or trabeculae separated by parallel sheets of fibrous tissue (ie, lamellae). The cells are characteristically well differentiated, with mitoses being uncommon, and have granular-appearing cytoplasm and large nuclei with prominent nucleoli (Fig 1) (1–3). The granular cytoplasm results from numerous cytoplasmic mitochondria and resembles the mitochondria-laden oncocytes of oncocytomas, hence the previous descriptive name of oncocytic hepatocellular carcinoma. The lamellae consist of dense hypocellular and avascular connective tissue, predominantly collagen (Fig 1) (2,3,19). Collagen deposition and lamellae formation (fibrosis), if infiltrative, result in a compartmentalized appearance and, if coalescent, result in a central fibrous scar (Fig 1). Collagen deposition and fibrosis in fibrolamellar carcinoma are thought by some (20) to result from tumor secretion of transforming growth factor-ß and not ischemia or necrosis.

View larger version (165K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Histologic appearance of fibrolamellar carcinoma. (a) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) demonstrates nests of fibrolamellar malignant tumor cells (arrowhead) separated by fibrotic strands or lamellae (arrow). (b) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) shows more confluent fibrosis separating the malignant tumor cells. (c) High-power photomicrograph (original magnification, x280; hematoxylin-eosin stain) shows the granular (mitochondria-laden) appearance of the cytoplasm and large nuclei with prominent nucleoli (arrow). (d) High-power photomicrograph (original magnification, x160; Masson stain) demonstrates intense staining of lamellae, indicative of extensive collagen.

View larger version (167K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Histologic appearance of fibrolamellar carcinoma. (a) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) demonstrates nests of fibrolamellar malignant tumor cells (arrowhead) separated by fibrotic strands or lamellae (arrow). (b) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) shows more confluent fibrosis separating the malignant tumor cells. (c) High-power photomicrograph (original magnification, x280; hematoxylin-eosin stain) shows the granular (mitochondria-laden) appearance of the cytoplasm and large nuclei with prominent nucleoli (arrow). (d) High-power photomicrograph (original magnification, x160; Masson stain) demonstrates intense staining of lamellae, indicative of extensive collagen.

View larger version (165K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  Histologic appearance of fibrolamellar carcinoma. (a) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) demonstrates nests of fibrolamellar malignant tumor cells (arrowhead) separated by fibrotic strands or lamellae (arrow). (b) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) shows more confluent fibrosis separating the malignant tumor cells. (c) High-power photomicrograph (original magnification, x280; hematoxylin-eosin stain) shows the granular (mitochondria-laden) appearance of the cytoplasm and large nuclei with prominent nucleoli (arrow). (d) High-power photomicrograph (original magnification, x160; Masson stain) demonstrates intense staining of lamellae, indicative of extensive collagen.

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 1d.  Histologic appearance of fibrolamellar carcinoma. (a) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) demonstrates nests of fibrolamellar malignant tumor cells (arrowhead) separated by fibrotic strands or lamellae (arrow). (b) High-power photomicrograph (original magnification, x160; hematoxylin-eosin stain) shows more confluent fibrosis separating the malignant tumor cells. (c) High-power photomicrograph (original magnification, x280; hematoxylin-eosin stain) shows the granular (mitochondria-laden) appearance of the cytoplasm and large nuclei with prominent nucleoli (arrow). (d) High-power photomicrograph (original magnification, x160; Masson stain) demonstrates intense staining of lamellae, indicative of extensive collagen.

Calcification has been reported in 35%–55% of tumors (6,13,17,21). Calcifications usually are punctate, nodular, or stellate and are located within the scar. Rarely, calcifications may be linear and originate from the tumor parenchyma or capsule. Fibrosis from fibrolamellar carcinoma has been reported to involve the adjacent liver resulting in capsular retraction; however, capsular retraction is rare and was seen in less than 10% of the AFIP cases. Capsular retraction, although uncommon in any liver tumor, is characteristic of hepatic malignancy and has most frequently been associated with cholangiocarcinoma (22).

Vascular invasion (of the portal or hepatic vein) by fibrolamellar carcinoma is uncommon (6), occurring in less than 5% of the AFIP cases and those reported in the literature. This infrequency of vascular invasion is in direct contrast with the portal and hepatic vein invasion that commonly occurs in patients with hepatocellular carcinoma (23). Systemic venous thrombosis may result from direct invasion of the hepatic veins and inferior vena cava, direct mass effect on the inferior vena cava, or as part of a paraneoplastic process (Trousseau syndrome). Rarely, fibrolamellar carcinoma has directly invaded and occluded the hepatic veins, resulting in Budd-Chiari syndrome (24).

Fibrolamellar carcinoma may be advanced in up to 80% of patients at the time of presentation. Regional adenopathy occurs in 50%–70% of patients, and distant metastases occur less commonly (20%) (2,3,5,17). Fibrolamellar carcinoma–involved lymph nodes may be soft tissue, necrotic, or fibrotic (similar to the primary tumor).

The liver adjacent to fibrolamellar carcinoma may contain foci of nodular hyperplasia (25,26), which is thought to be a regenerative response of the liver to any injury or insult. Hypervascular tumors such as fibrolamellar carcinoma may cause a vascular "steal" (26) from the surrounding liver and lead to adjacent relative ischemia, which results in hepatic regeneration or nodular hyperplasia. Peritumoral nodular hyperplasia is not seen at radiologic examination but may inadvertently be sampled instead of the tumor during biopsy, resulting in a misdiagnosis of nodular hyperplasia or even FNH (16,26).

	RADIOLOGIC FEATURES

Top Abstract INTRODUCTION CLINICAL FEATURES PATHOLOGIC FEATURES RADIOLOGIC FEATURES DIFFERENTIAL DIAGNOSIS BIOPSY FOR DIAGNOSIS PROGNOSIS AND TREATMENT References

 
Radiographic Characteristics
Abdominal radiography is not helpful in the evaluation of patients with fibrolamellar carcinoma. However, occasionally fibrolamellar carcinoma may be initially detected as an enlarged liver, liver mass, or hepatic calcification (Fig 2). Calcifications, usually nodular or stellate and small in relation to the tumor, have been visualized in up to 40% of abdominal radiographs (6).

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Fibrolamellar carcinoma in a 20-year-old man who presented with abdominal pain. (a) Abdominal radiograph demonstrates an irregular, nodular calcification (black arrow) within a hepatic mass as well as a pulmonary metastasis (white arrow). (b) Gallium-67 citrate scan shows increased uptake in the hepatic mass.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Fibrolamellar carcinoma in a 20-year-old man who presented with abdominal pain. (a) Abdominal radiograph demonstrates an irregular, nodular calcification (black arrow) within a hepatic mass as well as a pulmonary metastasis (white arrow). (b) Gallium-67 citrate scan shows increased uptake in the hepatic mass.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Fibrolamellar carcinoma in a 34-year-old patient with elevated levels of transaminase. (a) US scan demonstrates a 15-cm echogenic intrahepatic mass with irregular margins and a hypoechoic rim. (b) On a contrast material–enhanced CT scan, the mass demonstrates linear, enhancing vessels that create "compartments" within the tumor. (c) Hepatic angiogram (arterial phase) demonstrates the large intrahepatic mass with tortuous, irregular vessels that compartmentalize the tumor. (d) Technetium-99m–labeled sulfur colloid scan displays a cold defect, which corresponds to the mass. (e) Photograph of the gross specimen shows the lobulated mass with a central scar that was not visualized on images.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Fibrolamellar carcinoma in a 34-year-old patient with elevated levels of transaminase. (a) US scan demonstrates a 15-cm echogenic intrahepatic mass with irregular margins and a hypoechoic rim. (b) On a contrast material–enhanced CT scan, the mass demonstrates linear, enhancing vessels that create "compartments" within the tumor. (c) Hepatic angiogram (arterial phase) demonstrates the large intrahepatic mass with tortuous, irregular vessels that compartmentalize the tumor. (d) Technetium-99m–labeled sulfur colloid scan displays a cold defect, which corresponds to the mass. (e) Photograph of the gross specimen shows the lobulated mass with a central scar that was not visualized on images.

View larger version (98K): [in this window] [in a new window] [Download PPT slide]   Figure 3c.  Fibrolamellar carcinoma in a 34-year-old patient with elevated levels of transaminase. (a) US scan demonstrates a 15-cm echogenic intrahepatic mass with irregular margins and a hypoechoic rim. (b) On a contrast material–enhanced CT scan, the mass demonstrates linear, enhancing vessels that create "compartments" within the tumor. (c) Hepatic angiogram (arterial phase) demonstrates the large intrahepatic mass with tortuous, irregular vessels that compartmentalize the tumor. (d) Technetium-99m–labeled sulfur colloid scan displays a cold defect, which corresponds to the mass. (e) Photograph of the gross specimen shows the lobulated mass with a central scar that was not visualized on images.

View larger version (65K): [in this window] [in a new window] [Download PPT slide]   Figure 3d.  Fibrolamellar carcinoma in a 34-year-old patient with elevated levels of transaminase. (a) US scan demonstrates a 15-cm echogenic intrahepatic mass with irregular margins and a hypoechoic rim. (b) On a contrast material–enhanced CT scan, the mass demonstrates linear, enhancing vessels that create "compartments" within the tumor. (c) Hepatic angiogram (arterial phase) demonstrates the large intrahepatic mass with tortuous, irregular vessels that compartmentalize the tumor. (d) Technetium-99m–labeled sulfur colloid scan displays a cold defect, which corresponds to the mass. (e) Photograph of the gross specimen shows the lobulated mass with a central scar that was not visualized on images.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 3e.  Fibrolamellar carcinoma in a 34-year-old patient with elevated levels of transaminase. (a) US scan demonstrates a 15-cm echogenic intrahepatic mass with irregular margins and a hypoechoic rim. (b) On a contrast material–enhanced CT scan, the mass demonstrates linear, enhancing vessels that create "compartments" within the tumor. (c) Hepatic angiogram (arterial phase) demonstrates the large intrahepatic mass with tortuous, irregular vessels that compartmentalize the tumor. (d) Technetium-99m–labeled sulfur colloid scan displays a cold defect, which corresponds to the mass. (e) Photograph of the gross specimen shows the lobulated mass with a central scar that was not visualized on images.

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Fibrolamellar carcinoma in a patient who presented with jaundice. (a) US scan shows a heterogeneous mass with a hyperechoic scar and shadowing from the calcification. (b) T2-weighted spin-echo MR image (repetition time msec/echo time msec = 2,216/80) demonstrates the hyperintense mass with a hypointense scar (arrow). Intrahepatic biliary dilatation adenopathy in the porta hepatis (not shown) was an incidental finding.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Fibrolamellar carcinoma in a patient who presented with jaundice. (a) US scan shows a heterogeneous mass with a hyperechoic scar and shadowing from the calcification. (b) T2-weighted spin-echo MR image (repetition time msec/echo time msec = 2,216/80) demonstrates the hyperintense mass with a hypointense scar (arrow). Intrahepatic biliary dilatation adenopathy in the porta hepatis (not shown) was an incidental finding.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Progressive homogeneity of fibrolamellar carcinoma at dynamic CT. (a) Nonenhanced CT scan shows a large low-attenuation mass. (b) Contrast-enhanced arterial-phase CT scan demonstrates irregular heterogeneous enhancement of the lesion and fails to show a scar. (c) Contrast-enhanced CT scan shows a 3.0-cm enlarged heterogeneous lymph node with central necrosis in the porta hepatis. (d) Contrast-enhanced equilibrium-phase CT scan shows that the tumor has become more homogeneous and has evidence of a central scar. (e) Photograph of the bivalved gross specimen demonstrates the lobulated tumor with a small, central, yellowish fibrous scar.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Progressive homogeneity of fibrolamellar carcinoma at dynamic CT. (a) Nonenhanced CT scan shows a large low-attenuation mass. (b) Contrast-enhanced arterial-phase CT scan demonstrates irregular heterogeneous enhancement of the lesion and fails to show a scar. (c) Contrast-enhanced CT scan shows a 3.0-cm enlarged heterogeneous lymph node with central necrosis in the porta hepatis. (d) Contrast-enhanced equilibrium-phase CT scan shows that the tumor has become more homogeneous and has evidence of a central scar. (e) Photograph of the bivalved gross specimen demonstrates the lobulated tumor with a small, central, yellowish fibrous scar.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Progressive homogeneity of fibrolamellar carcinoma at dynamic CT. (a) Nonenhanced CT scan shows a large low-attenuation mass. (b) Contrast-enhanced arterial-phase CT scan demonstrates irregular heterogeneous enhancement of the lesion and fails to show a scar. (c) Contrast-enhanced CT scan shows a 3.0-cm enlarged heterogeneous lymph node with central necrosis in the porta hepatis. (d) Contrast-enhanced equilibrium-phase CT scan shows that the tumor has become more homogeneous and has evidence of a central scar. (e) Photograph of the bivalved gross specimen demonstrates the lobulated tumor with a small, central, yellowish fibrous scar.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 5d.  Progressive homogeneity of fibrolamellar carcinoma at dynamic CT. (a) Nonenhanced CT scan shows a large low-attenuation mass. (b) Contrast-enhanced arterial-phase CT scan demonstrates irregular heterogeneous enhancement of the lesion and fails to show a scar. (c) Contrast-enhanced CT scan shows a 3.0-cm enlarged heterogeneous lymph node with central necrosis in the porta hepatis. (d) Contrast-enhanced equilibrium-phase CT scan shows that the tumor has become more homogeneous and has evidence of a central scar. (e) Photograph of the bivalved gross specimen demonstrates the lobulated tumor with a small, central, yellowish fibrous scar.

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 5e.  Progressive homogeneity of fibrolamellar carcinoma at dynamic CT. (a) Nonenhanced CT scan shows a large low-attenuation mass. (b) Contrast-enhanced arterial-phase CT scan demonstrates irregular heterogeneous enhancement of the lesion and fails to show a scar. (c) Contrast-enhanced CT scan shows a 3.0-cm enlarged heterogeneous lymph node with central necrosis in the porta hepatis. (d) Contrast-enhanced equilibrium-phase CT scan shows that the tumor has become more homogeneous and has evidence of a central scar. (e) Photograph of the bivalved gross specimen demonstrates the lobulated tumor with a small, central, yellowish fibrous scar.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Increasing homogeneity of fibrolamellar carcinoma and better scar visualization at delayed CT. (a) Nonenhanced CT scan demonstrates a low-attenuation mass with punctate calcifications within a central scar. (b) Contrast-enhanced arterial-phase CT scan shows initial heterogeneous enhancement of the mass. (c) Contrast-enhanced equilibrium-phase CT scan shows increasing homogeneity of the tumor with superior visualization of the scar (arrow).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Increasing homogeneity of fibrolamellar carcinoma and better scar visualization at delayed CT. (a) Nonenhanced CT scan demonstrates a low-attenuation mass with punctate calcifications within a central scar. (b) Contrast-enhanced arterial-phase CT scan shows initial heterogeneous enhancement of the mass. (c) Contrast-enhanced equilibrium-phase CT scan shows increasing homogeneity of the tumor with superior visualization of the scar (arrow).

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 6c.  Increasing homogeneity of fibrolamellar carcinoma and better scar visualization at delayed CT. (a) Nonenhanced CT scan demonstrates a low-attenuation mass with punctate calcifications within a central scar. (b) Contrast-enhanced arterial-phase CT scan shows initial heterogeneous enhancement of the mass. (c) Contrast-enhanced equilibrium-phase CT scan shows increasing homogeneity of the tumor with superior visualization of the scar (arrow).

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Delayed enhancement of the central scar in fibrolamellar carcinoma at delayed CT. (a) Contrast-enhanced CT scan demonstrates a heterogeneously enhancing mass with a low-attenuation central scar. (b) Delayed contrast-enhanced CT scan demonstrates delayed enhancement of the central scar (black arrow) and peripheral enhancement of the pseudocapsule (white arrow).

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Delayed enhancement of the central scar in fibrolamellar carcinoma at delayed CT. (a) Contrast-enhanced CT scan demonstrates a heterogeneously enhancing mass with a low-attenuation central scar. (b) Delayed contrast-enhanced CT scan demonstrates delayed enhancement of the central scar (black arrow) and peripheral enhancement of the pseudocapsule (white arrow).

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 8.  Fibrolamellar carcinoma with capsular retraction. Nonenhanced CT scan demonstrates a large mass with capsular retraction (arrow), which is an uncommon finding in malignant neoplasms.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Fibrolamellar carcinoma in a 23-year-old woman who presented with bilateral iliofemoral vein thrombosis. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) show a 6.5-cm heterogeneous mass in the right hepatic lobe and an enlarged lymph node adjacent and posterior to the pancreas. The lymph node contains a central scar (arrow in b) and is compressing the inferior vena cava. (c) Hepatic angiogram (obtained with a superior mesentery artery injection) shows the intrahepatic vascular mass replacing the right hepatic artery and the posterior pancreatic lymph node with an enlarged supplying artery and neovascularity (arrowhead). The narrowing of the proximal replaced right hepatic artery (arrow) was caused by mass effect of the adjacent tumor and not direct arterial invasion. (d) Photograph of the resected lymph node shows the tumor, which has replaced the normal tissue and contains a central scar of fibrosis.

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Fibrolamellar carcinoma in a 23-year-old woman who presented with bilateral iliofemoral vein thrombosis. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) show a 6.5-cm heterogeneous mass in the right hepatic lobe and an enlarged lymph node adjacent and posterior to the pancreas. The lymph node contains a central scar (arrow in b) and is compressing the inferior vena cava. (c) Hepatic angiogram (obtained with a superior mesentery artery injection) shows the intrahepatic vascular mass replacing the right hepatic artery and the posterior pancreatic lymph node with an enlarged supplying artery and neovascularity (arrowhead). The narrowing of the proximal replaced right hepatic artery (arrow) was caused by mass effect of the adjacent tumor and not direct arterial invasion. (d) Photograph of the resected lymph node shows the tumor, which has replaced the normal tissue and contains a central scar of fibrosis.

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Fibrolamellar carcinoma in a 23-year-old woman who presented with bilateral iliofemoral vein thrombosis. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) show a 6.5-cm heterogeneous mass in the right hepatic lobe and an enlarged lymph node adjacent and posterior to the pancreas. The lymph node contains a central scar (arrow in b) and is compressing the inferior vena cava. (c) Hepatic angiogram (obtained with a superior mesentery artery injection) shows the intrahepatic vascular mass replacing the right hepatic artery and the posterior pancreatic lymph node with an enlarged supplying artery and neovascularity (arrowhead). The narrowing of the proximal replaced right hepatic artery (arrow) was caused by mass effect of the adjacent tumor and not direct arterial invasion. (d) Photograph of the resected lymph node shows the tumor, which has replaced the normal tissue and contains a central scar of fibrosis.

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Fibrolamellar carcinoma in a 23-year-old woman who presented with bilateral iliofemoral vein thrombosis. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) show a 6.5-cm heterogeneous mass in the right hepatic lobe and an enlarged lymph node adjacent and posterior to the pancreas. The lymph node contains a central scar (arrow in b) and is compressing the inferior vena cava. (c) Hepatic angiogram (obtained with a superior mesentery artery injection) shows the intrahepatic vascular mass replacing the right hepatic artery and the posterior pancreatic lymph node with an enlarged supplying artery and neovascularity (arrowhead). The narrowing of the proximal replaced right hepatic artery (arrow) was caused by mass effect of the adjacent tumor and not direct arterial invasion. (d) Photograph of the resected lymph node shows the tumor, which has replaced the normal tissue and contains a central scar of fibrosis.

CT is ideal for staging fibrolamellar carcinoma. The tumor may spread by direct invasion, lymphatics, or blood vessels. Lymphadenopathy (50%–70% of cases), pulmonary metastases, direct organ invasion, or peritoneal implants may result (5,13,17). Metastases to the lymph nodes are most common and typically occur in the porta hepatis. Affected lymph nodes may be homogeneous or heterogeneous in attenuation. Heterogeneous lymph nodes reflect necrosis or fibrosis (Fig 5) (16). Fibrosis, if present, is similar pathologically to the primary fibrolamellar carcinoma, and the affected lymph node may contain a scar (Fig 9).

MR Imaging Characteristics
At MR imaging, fibrolamellar carcinoma most commonly appears as a large, lobulated mass. Among the 14 AFIP cases with MR imaging studies, 86% of the masses were hypointense relative to the liver on T1-weighted images and 14% were isointense. Lesions were usually homogeneous (80% of cases), with heterogeneity being less common (20%). On T2-weighted images, the mass was heterogeneous and hyperintense in the vast majority (85%) of cases and uncommonly isointense or homogeneous (15% of cases).

The fibrous scar, if present, is usually hypointense on all MR images, regardless of pulse sequence used (Figs 5, 9–11) (31,35). This widely described imaging feature has been used to discriminate between fibrolamellar carcinoma and FNH. However, in rare cases, fibrolamellar carcinoma may demonstrate a hyperintense scar on T2-weighted images, a finding that simulates the hyperintense scar characteristic of FNH (34,36). A central scar was seen in 12 of the 14 AFIP cases with MR imaging studies. In 10 cases, the scar was hypointense; in one case (previously reported in the literature [34]), the scar was hyperintense; and in the last case, the scar had heterogeneous signal intensity.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  Fibrolamellar carcinoma in a 22-year-old woman. (a) T1-weighted gradient-echo MR image (90/150, 4° flip angle) demonstrates a slightly hypointense mass with a central hypointense scar. (b) On the T2-weighted spin-echo MR image (3,800/90), the mass is hyperintense and the scar remains hypointense. (c, d) On gadolinium-enhanced T1-weighted gradient-echo images (90/150, 4° flip angle) obtained in early (c) and delayed (d) phases, the mass heterogeneously enhances during the early phase and becomes increasingly homogeneous in the late phase. (e) Photograph of the cut gross specimen shows the lobulated, well-demarcated mass with a central scar and visible bile staining.

View larger version (78K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  Fibrolamellar carcinoma in a 22-year-old woman. (a) T1-weighted gradient-echo MR image (90/150, 4° flip angle) demonstrates a slightly hypointense mass with a central hypointense scar. (b) On the T2-weighted spin-echo MR image (3,800/90), the mass is hyperintense and the scar remains hypointense. (c, d) On gadolinium-enhanced T1-weighted gradient-echo images (90/150, 4° flip angle) obtained in early (c) and delayed (d) phases, the mass heterogeneously enhances during the early phase and becomes increasingly homogeneous in the late phase. (e) Photograph of the cut gross specimen shows the lobulated, well-demarcated mass with a central scar and visible bile staining.

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 11c.  Fibrolamellar carcinoma in a 22-year-old woman. (a) T1-weighted gradient-echo MR image (90/150, 4° flip angle) demonstrates a slightly hypointense mass with a central hypointense scar. (b) On the T2-weighted spin-echo MR image (3,800/90), the mass is hyperintense and the scar remains hypointense. (c, d) On gadolinium-enhanced T1-weighted gradient-echo images (90/150, 4° flip angle) obtained in early (c) and delayed (d) phases, the mass heterogeneously enhances during the early phase and becomes increasingly homogeneous in the late phase. (e) Photograph of the cut gross specimen shows the lobulated, well-demarcated mass with a central scar and visible bile staining.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 11d.  Fibrolamellar carcinoma in a 22-year-old woman. (a) T1-weighted gradient-echo MR image (90/150, 4° flip angle) demonstrates a slightly hypointense mass with a central hypointense scar. (b) On the T2-weighted spin-echo MR image (3,800/90), the mass is hyperintense and the scar remains hypointense. (c, d) On gadolinium-enhanced T1-weighted gradient-echo images (90/150, 4° flip angle) obtained in early (c) and delayed (d) phases, the mass heterogeneously enhances during the early phase and becomes increasingly homogeneous in the late phase. (e) Photograph of the cut gross specimen shows the lobulated, well-demarcated mass with a central scar and visible bile staining.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 11e.  Fibrolamellar carcinoma in a 22-year-old woman. (a) T1-weighted gradient-echo MR image (90/150, 4° flip angle) demonstrates a slightly hypointense mass with a central hypointense scar. (b) On the T2-weighted spin-echo MR image (3,800/90), the mass is hyperintense and the scar remains hypointense. (c, d) On gadolinium-enhanced T1-weighted gradient-echo images (90/150, 4° flip angle) obtained in early (c) and delayed (d) phases, the mass heterogeneously enhances during the early phase and becomes increasingly homogeneous in the late phase. (e) Photograph of the cut gross specimen shows the lobulated, well-demarcated mass with a central scar and visible bile staining.

Fibrolamellar carcinoma, unlike many well-differentiated hepatocellular carcinomas or hepatocellular adenomas, has not been reported to accumulate substantial intracellular lipid or glycogen. Therefore, decreased signal intensity on opposed-phase images or increased signal intensity on T1-weighted images, which may occur with lipid-containing hepatic adenoma or hepatocellular carcinoma (37–39), would not be expected to occur. There were no cases of fibrolamellar carcinoma with pronounced hyperintensity on T1-weighted images among the 14 AFIP cases.

Experience with liver-specific contrast agents for MR imaging is limited. One class of these agents, super paramagnetic iron oxide (SPIO) particles, is cleared by the reticuloendothelial system, similar to the uptake of sulfur colloid by the liver and spleen in a nuclear medicine study (40). SPIO agents have been used to characterize liver lesions or, more commonly, to screen for liver metastases. If used to image the liver, SPIO agents permit lesions that possess substantial reticuloendothelial activity (such as FNH and occasionally hepatic adenoma) to be distinguished from those without (all other liver lesions) (41,42). Although, to our knowledge, experience with MR imaging–specific reticuloendothelial agents has not been reported specifically, fibrolamellar carcinoma would not be expected to enhance significantly, if at all, after SPIO administration. Absence of enhancement is helpful in distinguishing fibrolamellar carcinoma from FNH (41,42).

Angiographic Characteristics
Angiography has been used to define arterial and portal anatomy preoperatively, help confirm portal vein invasion, and occasionally display intrahepatic tumor not visualized by other means. However, angiography has limited value for diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma is hypervascular and demonstrates enlarged feeding (Figs 3, 9) arteries and a dense tumor blush. The central scar is avascular. Fibrous septa may be visualized extending from the periphery to the center of the tumor and surrounding a smaller portion of it, thus creating a compartmentalized appearance. Arteriovenous and arterioportal shunting are absent. The uncommon finding of portal vein thrombosis may be visualized if contrast agent is injected into the splenic or mesenteric artery (6).

Scintigraphic Characteristics
Scintigraphy may be helpful in narrowing the differential diagnosis for a liver mass. One scintigraphic study historically used to evaluate hepatic masses is Tc-99m–labeled sulfur colloid examination of the liver and spleen. Uptake of sulfur colloid (which is similar to that of SPIO agents in MR imaging) correlates with the reticuloendothelial activity of the liver, spleen, and bone marrow and depends on a significant number and normal activity of Kupffer cells. Because Kupffer cells are not present in fibrolamellar carcinomas in either substantial quantity or function, these tumors appear on Tc-99m–labeled sulfur colloid images as photopenic defects; this appearance was seen in all 11 AFIP cases with scintigraphic studies (Fig 3).

In rare cases, Ga-67 scintigraphy may be used to characterize a liver mass (or because clinical manifestations are suggestive of an abscess) and may reveal fibrolamellar carcinoma (Fig 2) (6). However, gallium uptake is not specific for fibrolamellar carcinoma, since other intrahepatic inflammatory processes or tumors (eg, lymphoma, hepatocellular carcinoma) may demonstrate increased activity (Fig 2).

Occasionally, scintigraphic studies performed with Tc-99m–labeled red blood cells may be used to evaluate an intrahepatic mass. On these images, fibrolamellar carcinoma may demonstrate increased activity during the arterial phase but will appear as a photopenic defect on delayed images (Fig 12). This appearance is opposite of that of hepatic hemangiomas, which initially appear as a photopenic defect but demonstrate increased activity on delayed images.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Fibrolamellar carcinoma in a 26-year-old patient. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) demonstrate an enhancing mass with a calcified, low-attenuation scar. Adjacent to the mass is a satellite lesion of fibrolamellar carcinoma (arrowhead in b). Within the anterior liver is a wedge-shaped defect (arrow in b) corresponding to focally increased arterial flow. The area of increased vascularity likely reflects subsegmental portal vein occlusion with compensatory increased arterial flow. This finding is not specific for malignant invasion. (c, d) On dynamic (c) and static (d) Tc-99m–labeled red blood cell images, the hypervascular mass has increased uptake during the dynamic phase but not during the delayed phase. This finding of early increased vascularity with washout is not consistent with a diagnosis of hepatic hemangioma.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Fibrolamellar carcinoma in a 26-year-old patient. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) demonstrate an enhancing mass with a calcified, low-attenuation scar. Adjacent to the mass is a satellite lesion of fibrolamellar carcinoma (arrowhead in b). Within the anterior liver is a wedge-shaped defect (arrow in b) corresponding to focally increased arterial flow. The area of increased vascularity likely reflects subsegmental portal vein occlusion with compensatory increased arterial flow. This finding is not specific for malignant invasion. (c, d) On dynamic (c) and static (d) Tc-99m–labeled red blood cell images, the hypervascular mass has increased uptake during the dynamic phase but not during the delayed phase. This finding of early increased vascularity with washout is not consistent with a diagnosis of hepatic hemangioma.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 12c.  Fibrolamellar carcinoma in a 26-year-old patient. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) demonstrate an enhancing mass with a calcified, low-attenuation scar. Adjacent to the mass is a satellite lesion of fibrolamellar carcinoma (arrowhead in b). Within the anterior liver is a wedge-shaped defect (arrow in b) corresponding to focally increased arterial flow. The area of increased vascularity likely reflects subsegmental portal vein occlusion with compensatory increased arterial flow. This finding is not specific for malignant invasion. (c, d) On dynamic (c) and static (d) Tc-99m–labeled red blood cell images, the hypervascular mass has increased uptake during the dynamic phase but not during the delayed phase. This finding of early increased vascularity with washout is not consistent with a diagnosis of hepatic hemangioma.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 12d.  Fibrolamellar carcinoma in a 26-year-old patient. (a, b) Contrast-enhanced CT scans (a obtained at a higher level than b) demonstrate an enhancing mass with a calcified, low-attenuation scar. Adjacent to the mass is a satellite lesion of fibrolamellar carcinoma (arrowhead in b). Within the anterior liver is a wedge-shaped defect (arrow in b) corresponding to focally increased arterial flow. The area of increased vascularity likely reflects subsegmental portal vein occlusion with compensatory increased arterial flow. This finding is not specific for malignant invasion. (c, d) On dynamic (c) and static (d) Tc-99m–labeled red blood cell images, the hypervascular mass has increased uptake during the dynamic phase but not during the delayed phase. This finding of early increased vascularity with washout is not consistent with a diagnosis of hepatic hemangioma.

	DIFFERENTIAL DIAGNOSIS

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Because of their clinical and imaging similarities, FNH is often confused for fibrolamellar carcinoma. FNH occurs most frequently in young and middle-aged women as a solitary lesion less than 5 cm in size. Calcification is uncommon, occurring in less than 2% of cases (43). FNH is usually isoattenuating or isointense relative to the liver on all CT and MR images, respectively, except for arterial-phase images, on which FNH appears with pronounced homogeneous enhancement (Fig 13). However, variations in attenuation and enhancement patterns or atypical imaging findings are present in up to 50% of patients with FNH (44). In the common clinical scenario in which dynamic CT demonstrates a mass with minimally atypical imaging findings suggestive of FNH (44), MR imaging or scintigraphy may be helpful for confirming the diagnosis (45,46). In addition, FNHs commonly have a scar (seen in 78% of cases at MR imaging [41]) that characteristically (72%–100% of cases) has high signal intensity on T2-weighted images (Fig 14) (42). The scar can occasionally be detected at US or CT, but it is most commonly seen and best characterized with MR imaging. The presence of a hyperintense scar is extremely useful for differentiating FNH from fibrolamellar carcinoma because the latter characteristically (although not invariably) possesses a hypointense scar.

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  FNH in a 10-year-old girl evaluated with multiphasic CT. (a) Color flow Doppler US scan (shown in black and white) shows a subtle isoechoic mass with prominent central vessels corresponding to a central scar. (b) Contrast-enhanced arterial-phase CT scan demonstrates the densely enhancing, 5-cm mass with a central scar. (c, d) Contrast-enhanced portal-phase (c) and delayed-phase (d) CT scans show washout of contrast material from the tumor with nonvisualization of the scar. (e) Tc-99m–labeled sulfur colloid scan demonstrates increased activity in the mass in comparison with the normal liver (arrow).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  FNH in a 10-year-old girl evaluated with multiphasic CT. (a) Color flow Doppler US scan (shown in black and white) shows a subtle isoechoic mass with prominent central vessels corresponding to a central scar. (b) Contrast-enhanced arterial-phase CT scan demonstrates the densely enhancing, 5-cm mass with a central scar. (c, d) Contrast-enhanced portal-phase (c) and delayed-phase (d) CT scans show washout of contrast material from the tumor with nonvisualization of the scar. (e) Tc-99m–labeled sulfur colloid scan demonstrates increased activity in the mass in comparison with the normal liver (arrow).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 13c.  FNH in a 10-year-old girl evaluated with multiphasic CT. (a) Color flow Doppler US scan (shown in black and white) shows a subtle isoechoic mass with prominent central vessels corresponding to a central scar. (b) Contrast-enhanced arterial-phase CT scan demonstrates the densely enhancing, 5-cm mass with a central scar. (c, d) Contrast-enhanced portal-phase (c) and delayed-phase (d) CT scans show washout of contrast material from the tumor with nonvisualization of the scar. (e) Tc-99m–labeled sulfur colloid scan demonstrates increased activity in the mass in comparison with the normal liver (arrow).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 13d.  FNH in a 10-year-old girl evaluated with multiphasic CT. (a) Color flow Doppler US scan (shown in black and white) shows a subtle isoechoic mass with prominent central vessels corresponding to a central scar. (b) Contrast-enhanced arterial-phase CT scan demonstrates the densely enhancing, 5-cm mass with a central scar. (c, d) Contrast-enhanced portal-phase (c) and delayed-phase (d) CT scans show washout of contrast material from the tumor with nonvisualization of the scar. (e) Tc-99m–labeled sulfur colloid scan demonstrates increased activity in the mass in comparison with the normal liver (arrow).

View larger version (84K): [in this window] [in a new window] [Download PPT slide]   Figure 13e.  FNH in a 10-year-old girl evaluated with multiphasic CT. (a) Color flow Doppler US scan (shown in black and white) shows a subtle isoechoic mass with prominent central vessels corresponding to a central scar. (b) Contrast-enhanced arterial-phase CT scan demonstrates the densely enhancing, 5-cm mass with a central scar. (c, d) Contrast-enhanced portal-phase (c) and delayed-phase (d) CT scans show washout of contrast material from the tumor with nonvisualization of the scar. (e) Tc-99m–labeled sulfur colloid scan demonstrates increased activity in the mass in comparison with the normal liver (arrow).

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.  FNH in a 68-year-old woman. (a) SPIO-enhanced T1-weighted spin-echo MR image (500/20) demonstrates a 5-cm mass that is predominantly isointense relative to the adjacent liver and that contains a hypointense scar (arrow). (b) On the T2-weighted spin-echo MR image (4,000/80), the mass remains similar in signal intensity, but the scar is now hyperintense (arrow). (c) SPIO-enhanced T2-weighted spin-echo (4,000/80) demonstrates uptake of SPIO and significant negative enhancement of focal areas (arrows).

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.  FNH in a 68-year-old woman. (a) SPIO-enhanced T1-weighted spin-echo MR image (500/20) demonstrates a 5-cm mass that is predominantly isointense relative to the adjacent liver and that contains a hypointense scar (arrow). (b) On the T2-weighted spin-echo MR image (4,000/80), the mass remains similar in signal intensity, but the scar is now hyperintense (arrow). (c) SPIO-enhanced T2-weighted spin-echo (4,000/80) demonstrates uptake of SPIO and significant negative enhancement of focal areas (arrows).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 14c.  FNH in a 68-year-old woman. (a) SPIO-enhanced T1-weighted spin-echo MR image (500/20) demonstrates a 5-cm mass that is predominantly isointense relative to the adjacent liver and that contains a hypointense scar (arrow). (b) On the T2-weighted spin-echo MR image (4,000/80), the mass remains similar in signal intensity, but the scar is now hyperintense (arrow). (c) SPIO-enhanced T2-weighted spin-echo (4,000/80) demonstrates uptake of SPIO and significant negative enhancement of focal areas (arrows).

	BIOPSY FOR DIAGNOSIS

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Fibrolamellar carcinoma is diagnosed pathologically by means of either resection or percutaneous biopsy. Use of percutaneous biopsy is beneficial if there is diagnostic uncertainty about the radiologic diagnosis. In these situations, confirmation of the diagnosis with percutaneous biopsy allows appropriate surgical treatment in cases of fibrolamellar carcinoma versus follow-up in cases of FNH, which requires no treatment.

For fibrolamellar carcinoma, the preferred technique for performing percutaneous biopsy is core biopsy, rather than fine-needle aspiration. In fine-needle aspiration, malignant hepatocytes may be aspirated without the characteristic fibrotic lamellae and therefore result in a diagnosis of hepatocellular carcinoma and not fibrolamellar carcinoma. Fibrolamellar carcinoma has been diagnosed by means of fine-needle aspiration, although the reliability of cytologic diagnosis is unknown (49). In the AFIP series, seven cases (subsequently proved to be fibrolamellar carcinoma) were submitted with results of fine-needle aspiration. In four cases, fibrolamellar carcinoma was diagnosed correctly as a hepatocellular malignancy, but in one case fibrolamellar carcinoma was misdiagnosed as melanoma. In the two remaining cases, results of fine-needle aspiration were nondiagnostic or "negative for malignancy."

Biopsies in which multiple core specimens are obtained are helpful because fibrolamellar carcinoma may contain areas with variable differentiation and cell types (hepatocellular carcinoma, neuroendocrine differentiation) (17). Biopsy specimens should be obtained "midsubstance," rather than from the periphery of the lesion because the hepatic parenchyma adjacent to fibrolamellar carcinoma may demonstrate nodular hyperplastic changes and simulate FNH. If only the area adjacent to the tumor is sampled, fibrolamellar carcinoma could be misdiagnosed as FNH (25,26).

Because of the hypervascularity of fibrolamellar carcinoma and the possibility of coincidental liver disease, caution must be used in the biopsy procedure. Biopsies performed through at least 1 cm of hepatic parenchyma are associated with minimal risk of significant hemorrhage (0.1% of cases) (49), although cutting needles or core biopsies are associated with a threefold increased risk of complications compared with fine-needle aspiration (50).

	PROGNOSIS AND TREATMENT

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Patients with fibrolamellar carcinoma have a better prognosis than those with hepatocellular carcinoma, and aggressive surgical resection or liver transplantation may be indicated, even in the presence of advanced lesions with limited metastatic disease (2,3,5,51,52).

Fibrolamellar carcinoma is treated by surgical resection of the hepatic mass. The majority of patients with fibrolamellar carcinoma (80%) will be treated with an attempt at curative resection (subtotal hepatectomy or liver transplantation) (17). The presence of advanced-stage disease, direct invasion of adjacent organs, lymphadenopathy, or limited metastasis does not preclude attempts at curative resection (5). The presence of extensive liver involvement precludes liver resection but is not a contraindication to liver transplantation. Involvement of the main portal vein or hepatic artery, however, is a contraindication to curative resection (5). In inoperable cases of fibrolamellar carcinoma, the patient may benefit from adjuvant chemotherapy (either systemic or intraarterial). In up to 50% of these cases, the tumors respond to chemotherapy, permitting an attempt at curative resection (53).

The most recent 5-year survival rate from a large surgical series for fibrolamellar carcinoma is 67% (5). The prognosis for fibrolamellar carcinoma is significantly better than that for hepatocellular carcinoma, for which only one-third of patients undergo curative resection and the reported 5-year survival rates vary from 0 to 25% (54).

Fibrolamellar carcinoma is frequently recurrent (Fig 15). Thus, follow-up imaging studies are needed to detect recurrent disease. Resection of recurrent lymphadenopathy and of recurrent local, limited metastatic disease prolongs survival and may be curative in a few patients (17).

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.  Fibrolamellar carcinoma that recurred 16 months after initial hepatic segmentectomy. (a) Contrast-enhanced CT scan shows an enhancing intrahepatic mass with low attenuation. (b) Photograph of partial hepatectomy specimen shows the recurrent fibrolamellar carcinoma with central fibrosis.

View larger version (81K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.  Fibrolamellar carcinoma that recurred 16 months after initial hepatic segmentectomy. (a) Contrast-enhanced CT scan shows an enhancing intrahepatic mass with low attenuation. (b) Photograph of partial hepatectomy specimen shows the recurrent fibrolamellar carcinoma with central fibrosis.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Fibrolamellar carcinoma invading the portal vein. (a) T2-weighted spin-echo MR image (4,000/14) shows a heterogeneous hyperintense mass with a hypointense scar. (b) T1-weighted spin-echo MR image (550/15) shows soft tissue expanding the right and left portal veins (arrows). Cavernous transformation is present, with signal voids from blood flow surrounding the left portal vein (arrowhead). (c) Contrast-enhanced CT scan demonstrates the calcified fibrolamellar carcinoma, but portal vein invasion is more difficult to detect (arrow).

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Fibrolamellar carcinoma invading the portal vein. (a) T2-weighted spin-echo MR image (4,000/14) shows a heterogeneous hyperintense mass with a hypointense scar. (b) T1-weighted spin-echo MR image (550/15) shows soft tissue expanding the right and left portal veins (arrows). Cavernous transformation is present, with signal voids from blood flow surrounding the left portal vein (arrowhead). (c) Contrast-enhanced CT scan demonstrates the calcified fibrolamellar carcinoma, but portal vein invasion is more difficult to detect (arrow).

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 10c.  Fibrolamellar carcinoma invading the portal vein. (a) T2-weighted spin-echo MR image (4,000/14) shows a heterogeneous hyperintense mass with a hypointense scar. (b) T1-weighted spin-echo MR image (550/15) shows soft tissue expanding the right and left portal veins (arrows). Cavernous transformation is present, with signal voids from blood flow surrounding the left portal vein (arrowhead). (c) Contrast-enhanced CT scan demonstrates the calcified fibrolamellar carcinoma, but portal vein invasion is more difficult to detect (arrow).

	Footnotes

 
Address reprint requests to J.K.M.

Abbreviations: AFIP = Armed Forces Institute of Pathology FNH = focal nodular hyperplasia SPIO = super paramagnetic iron oxide

CME FEATURE This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician's Recognition Award. To obtain credit, see the questionnaire on pp 472–480.

LEARNING OBJECTIVES After reading this article and taking the test, the reader will: • Be familiar with the spectrum of radiologic appearances of fibrolamellar carcinoma. • Understand the pathologic basis of the radiologic findings of fibrolamellar carcinoma. • Be familiar with the clinical and radiologic manifestations of fibrolamellar carcinoma compared with those of FNH, the tumor with which it is most commonly confused.

Received for publication October 23, 1998. Revision received November 4, 1998. December 10, 1998. Accepted for publication January 11, 1998.

	References

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