PMC9359099_01
Representative CT and MRI scans showing different disease stages and local ablative therapy during the disease course. (A) MRI (T2) of July 2017. White arrow points toward intrahepatic cholangiocarcinoma in segment V/VIII at first presentation. (B) MRI (T2) of October 2018 revealing a singular hepatic metastasis (white arrow). (C) Second intrahepatic recurrence of CCA (white arrow) diagnosed by MRI (T2) in February 2020. (D) CT-guided microwave ablation of this second hepatic metastasis in February 2020. (E) CT (portal venous phase) showing central necrotic lymph node metastases (red circles) in October 2020, before initiating olaparib/pembrolizumab combination therapy. (F) In July 2021, CT scan (portal venous phase) shows partial and complete remission of lymph node metastases after about 9 months of treatment with olaparib and pembrolizumab.
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CT as well as MRI scan revealed a 35 mm x 45 mm mass forming lesion in liver segment V/VIII without signs of thoracoabdominal metastasis (see Figure 1A). In October 2018, after 6 months of stable remission, a solitary hepatic metastasis (see Figure 1B), histologically confirmed by biopsy (see Figure 3), was diagnosed. CT of the abdomen revealed peritoneal metastasis with ascites as well as lymph node metastasis in November 2020 (see Figure 1E). Ca 125 reached 323 U/ml, consistent with radiological findings (see Figure 2). First radiological imaging in January 2021 already showed no signs of CCA recurrence, consistent with complete remission (see Figure 1F). Supplementary Figure 1).
Diagram of development of Ca 125 in U/ml over time after primary hemihepatectomy during the disease course and under multimodal therapy. Red arrows are labeled with therapeutic events. Black arrow heads indicate time of recurrence as diagnosed by imaging.
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CEA (0.7 ng/ml) and Ca 19-9 (<2 U/ml) were low and remained within the normal range during the entire disease course, whereas Ca 125 was slightly elevated (53.3 U/ml, ULN 35 U/ml) (see Figure 2). CT of the abdomen revealed peritoneal metastasis with ascites as well as lymph node metastasis in November 2020 (see Figure 1E). Ca 125 reached 323 U/ml, consistent with radiological findings (see Figure 2). Ca 125 decreased shortly after initiation of olaparib/pembrolizumab and has remained within normal range throughout since March 2021 (see Figure 2).
Liver biopsy (x20 magnification) of second hepatic metastasis in February 2020 shows infiltrates of atypical glandular proliferates in hematoxylin and eosin staining (A), which were positive for CK7 (B). Immunohistochemistry staining shows weak to moderate membranous expression of PDL1 in about 50% of the tumor cells and in about 20% of surrounding immune cells (C).
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In October 2018, after 6 months of stable remission, a solitary hepatic metastasis (see Figure 1B), histologically confirmed by biopsy (see Figure 3), was diagnosed. Figure 3C). Furthermore, the tumor tissue showed Her2neu overexpression with a FISH ratio >=2.