A Case of Fibrolamellar Hepatocellular Carcinoma in Which Tumor Control Was Achieved by Re-Administering Atezolizumab and Bevacizumab

Abstract

Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) clinically occurs in young people aged 20-30 years, who often have a normal liver background. We propose a treatment for such cases in which a combination therapy of atezolizumab and bevacizumab is followed by sandwiching radiation therapy to release tumor antigens and then re-administering the combination therapy of atezolizumab and bevacizumab (ABC conversion therapy).

Case: The patient is a 15-year-old girl. On April 18, 2022, she noticed skin yellowing and visited her local doctor. Computed tomography (CT) revealed a large mass in the right lobe of the liver and bile duct obstruction due to the tumor. She also had a nodule on her chest that appeared to be a metastatic tumor and was referred to Kinki University Hospital in April 2023. She was suspected to have FL-HCC based on contrast-enhanced ultrasound and CT scan results. There were findings suggestive of lung metastasis; however, she underwent a right hepatic lobectomy on May 17, 2023, considering the risk of liver failure and intra-abdominal bleeding due to the large liver tumor. A CT scan conducted on July 25, 2022, showing increased lung metastases, and she started atezolizumab/bevacizumab combination treatment on October 20, 2022. On March 15, 2023, multiple lung metastases and new intrahepatic lesions appeared, which was diagnosed as progressive disease (PD), and lenvatinib was discontinued. On November 17, 2023, radiation therapy (25 Gy/5 Fr) was administered to the lung and intrahepatic lesions to release tumor antigens, and on November 27, 2023, atezolizumab and bevacizumab combination treatment was resumed to control the tumor.

Conclusion: Combination therapy with atezolizumab, bevacizumab, and radiation therapy may be an option for the treatment of FL-HCC.

Keywords: atezolizumab; bevacizumab; combination therapy; fibrolamellar hepatocellular carcinoma; radiation therapy.

FIGURE 1

Contrast CT examination after referral. (a) Plain CT revealed a mass with a major diameter of 107 mm in the right lobe of the liver, with a slightly lower absorption than the liver parenchyma. Calcification is observed inside the tumor (arrow). Dilation of the left intrahepatic bile duct is observed (arrow). (b) In the arterial phase, most masses show heterogeneous deep staining, but the masses on the hepatic portal side show gradually increasing dark staining. The margin of the tumor is multilobed. (c) Staining persists even in the portal venous phase. (d) Staining persists even in the equilibrium phase. In addition, a nodule suspected of metastasis is observed in the left lung (data not shown).

FIGURE 2

Contrast‐enhanced abdominal ultrasound examination after referral. (a) In the arterial‐dominated phase, it is extracted as a hypervascular mass, with some axle‐shaped blood vessel structures also observed (arrow). (b) In the Kupffer phase, it is extracted as a defect image.

FIGURE 3

EOB‐MRI examination after introduction. (a) On plain MRI (T2WI), the mass exhibits a slightly lower density than the liver parenchyma. (b) In the arterial phase, most masses show heterogeneous deep staining; however, the masses on the hepatic portal side show gradually increasing dark staining. The tumor margin is multilobed. (c) Staining persists even during the portal venous phase. (d) In the hepatocyte phase, the mass exhibits decreased uptake of EOB.

FIGURE 4

MRCP examination after referral. Owing to the mass displacement in the right lobe of the liver, the hilar bile duct is narrowed, and the left and right intrahepatic bile ducts are dilated (arrows).

FIGURE 5

Macroscopic findings of resected specimen. The long axis is approximately 13 cm, and macroscopically, it appeared as a multinodular, fused, and solid tumor with lobulated margins. It also has coatings in certain areas. No evident central scarring was observed.

FIGURE 6

Histopathological findings. (a) H&E staining (magnification ×10) and (b) H&E staining (magnification ×20) shows atypical cells with round nuclei with clear nucleoli and abundant eosinophilic cells. Thick hyalinized fiber bundles are embedded in these atypical cells in a layered manner, and tumor cells proliferate as cables or small masses. (c) H&E staining (magnification ×10) and (d) H&E staining (magnification ×20) shows small vacuoles (pale bodies) exhibiting a sand grain‐like inclusion structure within the cytoplasmic bodies of tumor cells (arrows). The final pathological diagnosis was fibrolamellar carcinoma of the liver, Va1, Vv0, Vp0, b0, sm‐(4 mm), with positive lymph node metastasis.

FIGURE 7

Immunohistology findings. (a) Immunostaining shows positive HepPar1 findings (magnification ×10). (b) Immunostaining also showed positive findings for CK7 (magnification ×10).

FIGURE 8

Plain chest CT scan and PET‐CT scan 1 year and 5 months after referral. (a) Plain chest CT showing a mass with a mild FGD accumulation near the right hilum (arrow). (b) Plain chest CT showing an enlarged nodule in the left lung at the time of presentation (arrow). (c) PET‐CT reveals a mass with a mild FGD accumulation near the right hilum (arrow). (d) PET‐CT showing peritoneal dissemination (arrow).

FIGURE 9

Simple chest CT examination after radiation therapy. (a) The tumor near the right lung hilum did not increase after treatment. (b) The mass in the left lung did not increase after treatment.

FIGURE 10

Clinical course of liver function. (a) Changes in AST, ALT, ALP, and ɤGTP. (b) Changes in T‐bil and PT.