Intrahepatic Cholangiocarcinoma with BRCA Mutation Achieved Pathological Complete Response after Neoadjuvant Gemcitabine, Cisplatin, and S-1 Therapy: A Case Report

Abstract

Introduction: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant cancer for which surgery is the only curative treatment. The prognosis of ICC is extremely poor, especially in cases of lymph node metastasis (LNM), owing to the high postoperative recurrence rate. Herein, we present a case of advanced ICC with a breast cancer susceptibility gene-2 (BRCA2) mutation, treated with preoperative chemotherapy, including cisplatin, followed by surgery, in which we achieved a pathologic complete response.

Case presentation: A 52-year-old woman was referred to our hospital and was subsequently diagnosed with bilateral breast cancer. Computed tomography (CT) and magnetic resonance imaging incidentally detected a liver tumor in the hilar region and lymph node enlargement in the hepatoduodenal ligament. A 19 mm tumor was observed in the area surrounded by the right and left branches of the portal vein and an abnormal portal branch of segment 7. Positron emission tomography-CT showed fluorodeoxyglucose uptake in the liver tumor, hepatoduodenal ligament lymph nodes, and bilateral breasts. A tumor biopsy showed a papillary tumor, and ICC was suspected. As ICC with LNM has a poor prognosis, neoadjuvant chemotherapy was planned. Genetic testing using a blood sample revealed a BRCA2 mutation, indicating the patient would benefit from chemotherapy, particularly cisplatin. The patient received a chemotherapy regimen comprised of gemcitabine, cisplatin, and S-1 (GCS), and after 7 courses, her carbohydrate antigen 19-9 level decreased from 2433 to 15 U/mL. CT showed that the tumor had shrunk and the LNMs were indistinct. The patient was referred to our department for curative surgery, which included a left hepatectomy, caudate lobectomy, hepatoduodenal ligament lymph node dissection, bile duct resection, and choledocojejunostomy. The postoperative course was generally uneventful, and the patient was discharged on postoperative day 18. Pathological examination of the resected specimen revealed an absence of malignant cells. At 24 months postoperative, there was no evidence of recurrence.

Conclusions: We encountered a patient with advanced ICC with a BRCA2 mutation, which was successfully treated with preoperative GCS therapy followed by surgical resection, and a pathologic complete response was achieved. GCS therapy, therefore, appears promising as neoadjuvant chemotherapy for the treatment of ICC.

Keywords: BRCA; GCS therapy; complete response; intrahepatic cholangiocarcinoma; neoadjuvant.

Fig. 1. Enhanced CT and 3D reconstruction images before chemotherapy. (A) A 19 mm low-density tumor (arrow) is seen at the origin of the right and left branches of the portal vein and the abnormal P7. (B) A 12 mm contrast-enhanced lymph node (dotted arrow) is observed in the hepatoduodenal ligament. (C) An abnormal portal branch of segment 7 (arrow) branches from the umbilical portion of the portal vein and runs dorsal to the middle hepatic vein (dotted arrow) and the right hepatic vein (arrowhead). The portal vein is shown in pink, and the hepatic vein is shown in light blue. Tumors are shown in red and lymph node metastases are shown in green.

CT, computed tomography

Fig. 2. Magnetic resonance imaging findings before chemotherapy. (A, B) On diffusion-weighted images, both the liver tumor (arrow) and enlarged lymph nodes (dotted arrow) show diffusion restriction.

Fig. 3. Positron emission tomography-CT findings before chemotherapy. (A, B) FDG uptake (SUV_max = 10.5) is observed in liver tumors (arrow). The lymph nodes (dotted arrow) also show high FDG uptake (SUV_max = 5.8).

FDG, fluorodeoxyglucose; SUV, standard uptake value

Fig. 4. Pathological findings of biopsy and resected specimens. (A) Tumor biopsy specimen showing atypical cells with papillary growth that cannot be ruled out as stromal invasion. Left panel: 40× magnification view, right panel: 200× magnification. (B) Resected liver specimen showing a scar around the left hepatic bile duct with mucous lakes. No residual carcinoma was observed. Left panel: 20× magnification, right panel: 200× magnification. (C) Resected lymph node specimen showing a scar with mucus lakes. No residual carcinoma was observed. Left panel: 20× magnification, right panel: 200× magnification.

Fig. 5. Enhanced CT findings after chemotherapy. (A, B) Both the liver tumor (arrow) and lymph nodes (dotted arrow) shrank but did not disappear.

CT, computed tomography