Tumor marker pseudoprogression and immune-related cholangitis during conversion therapy for massive hepatocellular carcinoma: a case report

Abstract

Cases with massive (diameter ≥10 cm) hepatocellular carcinomas (HCCs) are uncommon and typically have poor outcomes; however, conversion therapy offers a beacon of hope for remission in patients with massive unresectable HCCs. Recently, immune checkpoint inhibitors (ICIs) have been used in combination with other treatment modalities to improve the response rates to conversion therapies, yet the safety and generalizability of this combination have not been extensively validated. Herein, we report a man with a chief complaint of abdominal pain who was diagnosed with massive unresectable HCC. Notably, the patient successfully underwent curative surgery after quadruple conversion therapy using tislelizumab (an ICI), lenvatinib, transarterial chemoembolization, and hepatic arterial infusion chemotherapy directed by a multidisciplinary team. With a complete response achieved, this case demonstrated the major potential of this combination regimen for HCC, and the remarkable efficacy was also reflected by substantial reductions in both alpha-fetoprotein and des-gamma-carboxy prothrombin overall. Nevertheless, transient increases in both biomarkers (tumor marker pseudoprogression) were observed within the first three weeks after initiating ICI treatment. Furthermore, the patient developed a biliary stricture, which resolved after discontinuing the ICI and was ultimately assessed as an immune-related adverse event. Therefore, in the context of combination therapy, further evaluation of the robustness of tumor markers is warranted, and it is crucial for clinicians to be mindful of potential immune-related adverse events.

Keywords: case report; conversion therapy; hepatocellular carcinoma; immune checkpoint inhibitor; immune-related adverse event; pseudoprogression; tislelizumab; tumor marker.

Figure 1

Timeline of clinical treatment and assessment. (A) Serial scans along the treatment timeline with red dotted circle depicting the dominant tumor lesion. Contrast-enhanced scans were obtained in the arterial phase, and no intratumoral arterial enhancement remained in the liver on day 155 from baseline. (B) Line graph showing changes in tumor markers during conversion therapy. Baseline DCP value above the upper limit of detection, 30,000 mAU/mL, is truncated to 30,000 mAU/mL. CE-CT, contrast-enhanced computed tomography; CE-MRI, contrast-enhanced magnetic resonance imaging; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy.

Figure 2

Line graph showing changes in liver enzymes and total bilirubin during conversion therapy. TACE, transarterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy.

Figure 3

Radiologic scans of the common bile duct before and after conversion therapy. (A, B) Coronal multiplanar reconstruction of contrast-enhanced computed tomography images displaying the pretreatment (baseline) diameter of the middle-lower (A) and upper (B) portions of the common bile duct. (C, D) Magnetic resonance cholangiopancreatography images revealing (C) stricture of the middle-lower portion of the common bile duct and (D) dilatation of the upper biliary region on day 155 from baseline. ▸◂, duct diameter as measured by imaging.

Figure 4

Hematoxylin and eosin staining of resected tumor and common bile duct biopsy tissues. (A, B) Histopathological examination of the resected tumor showing (A) large areas of necrosis in the center of the mass and (B) intrahepatic biliary hyperplasia and fibrosis in the surrounding hepatic tissues. (C–F) Common bile duct biopsy revealing (C, D) hyperplasia of the biliary epithelium and (E, F) severe inflammatory cell infiltration and fibrosis of the bile duct wall. Original magnification, 50× (A–C, E) or 200× (D, F).