PMC10443589_01
(A-D) Prior to treatment, computed tomography (CT) revealed lesions around the pancreas, liver, and lymph nodes located in the cardiophrenic angle. (E-H) CT revealed that lesions around the pancreas and lymph nodes reduced in size whereas the lesions proximal to the liver remained constant despite four cycles of immunotherapy and chemotherapy (IC). (I,J) CT revealed lymph nodes present even after mesohepatectomy and regional lymph node resection. (K,L) CT showed further enlargement of the lymph nodes in the cardiophrenic angle and paraesophageal region despite two cycles of IC. (M,N) CT revealed shrinkage of lymph nodes after stereotactic ablative radiotherapy. (A,B) and (E,F) The red arrow indicates lesions around the pancreas. (C,G) The red arrow indicates the lesion in the liver. (D,H) The red arrow indicates the lymph nodes in the cardiophrenic angle. (I,K,M) The red arrow indicates the lymph nodes located in the cardiophrenic angle. (J,L,N) The red arrow indicates the paraesophageal lymph nodes.
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F1
Multiple metastatic lesions were also detected in the lymph nodes located in the cardiophrenic angle, hepatic hilar region, and peripancreatic region (Figures 1A-D). H). However, a slight enlargement of the liver lesion was noted during the CT scan (Figure 1G). The lymph node in the cardiophrenic angle was difficult to remove due to its proximity to vascular structures (Figures 1I, J). The postoperative CT scan showed lymph node involvement in the cardiophrenic angle and paraesophageal region (Figures 1I, J). However, the CT showed further 34% enlargement of the lymph nodes after two cycles of IC treatment, which demonstrated progressive disease (PD) (Figures 1K, L). After two cycles, a partial response was achieved (Figures 1M, N).
The diagnosis of lymphoepithelioma-like intrahepatic cholangiocarcinoma was pathologically verified with the expression of programmed death-ligand 1 (PD-L1), PD-1, and CD8+T cells (x200 magnification). (A) Hematoxylin and eosin staining (x200) revealed columnar tumor cells with atypical nuclei that proliferated in a cord-like or glandular tubular pattern. The tumor cells were surrounded by collagen fibers, dense lymphocytic infiltration, and lymphoid follicles. (B) The brown cells in EBER-ISHx200 magnification images are the cells harboring Epstein-Barr virus (EBV) infection (EBV-encoded small RNA in situ hybridization, EBER-ISH). Representative examples showing immunohistochemical staining of samples that are PD-L1-positive in tumor cells (PD-1+ TCs, (C), PD-1-positive in tumor cells [PD-1+ TCs, (D)], and positive for CD8+T cells [CD8+T, (E)].
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F2
A core needle biopsy of the liver was performed, and the histology was consistent with LEL-ICC (Figure 2A). TTF-1, ALK-1, CDX2, WT-1, and CD34. The tumor tissues were positive for EBV-encoded RNA in situ hybridization (Figure 2B). IHC revealed that the tumor tissue had a combined positive score of 20 and a tumor proportion score of 18% (Figures 2C, D). T cells had infiltrated the tumor cells (Figure 2E). The TIME was examined using multiplex immunohistochemical staining and quantitative analysis (Table 1), but no gene mutations were identified.
Schematic representation of the anti-tumor therapy process. First-line treatment consisted of gemcitabine (1,000 mg/m2, d1, d8, q3w) plus cisplatin (25 mg/m2, d1, d8, q3w) and camrelizumab (200 mg, d1, q3w). Subsequently, the surgery was performed. After the surgery, the lymph nodes enlarged; the patient was readministered with GP plus camrelizumab. After two cycles, the tumor further enlarged. The patient was administered with the stereotactic ablative radiotherapy (SABR) combined with camrelizumab and GP (ICSABR), and achieved response after two cycles.
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F3
After multidisciplinary consultation, a combination regimen of gemcitabine (1,000 mg/m2, d1, d8, q3w) plus cisplatin (25 mg/m2, d1, d8, q3w) (GP) and camrelizumab (200 mg, d1, q3w) was administered on June 2021 (Figure 3).