Surgery after combination therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody in sarcomatoid hepatocellular carcinoma: case report and literature review

Abstract

Introduction: Although surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable.

Case presentation: A 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free.

Conclusion: Combined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.

Keywords: anti-PD-1 antibody; anti-angiogenic therapy; combination therapy; sarcomatoid hepatocellular carcinoma; surgery.

Figure 1

Representative computed tomography images showing changes in the tumor throughout the treatment period prior to surgery. (A) perihepatic tumor with blurred edges in the right liver at initial diagnosis. (B) extrahepatic tumor growth (with a blurred boundary) covering the upper pole of the right kidney, 2 months after transcatheter arterial chemoembolization. (C) stable tumor size and clear boundary after treatment with tyrosine kinase inhibitors and anti-PD-1 antibodies for 6 months.

Figure 2

Hematoxylin-eosin staining of needle puncture biopsy and resected specimens. (A) original magnification of 100× and 400× in puncture biopsy specimen. (B) original magnification of 100× and 400× in resected specimen.

Figure 3

Surgical field and resected specimen. (A) surgical field after resection of the tumor. The white arrow shows the section of the right liver, the blue arrow indicates the sutured and repaired right diaphragm, and the yellow arrow shows the naked upper pole of the right kidney after resection of the perirenal fat sac. (B) resected specimen of the right liver. (C) resected specimen of the right diaphragm and tissues around the upper pole of the right kidney.

Figure 4

Timeline of treatment course.

Figure 5

Immunohistochemistry of spindle cells in the resected specimen (A–C) show positivity for CK, CK19, and β-catenin. (D) shows Ki-67 positivity in approximately 40% of cells.