PMC10154565_01
Baseline PET-CT imaging and pathologic results. (A) High uptake of fluorodeoxyglucose (FDG) in enlarged retroperitoneal lymph nodes and (B) peripancreatic lesions below the caudate lobe of the liver. (C) Coronal view showed multiple hypermetabolic lesions in the abdominal cavity. (D) Hematoxylin and eosin staining on hepatopancreatic lesions under endoscopic ultrasound showed poorly differentiated carcinoma. (E) The Dako PD-L1 22C3 assay immunohistochemistry assay for PD-L1 expression revealed that the tumor proportion score (TPS) was 35%. Scale bar = 100mum.
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Further endoscopic ultrasound was performed to puncture the hypoechoic mass in the hepatopancreatic space and the pathology indicated poorly differentiated carcinoma ( Figure 1D ). To help identify the primary lesion, the patient underwent a positron emission tomography-CT (PET-CT) examination ( Figure 1 ). The top three predictions were gastric/esophagus cancer (62.5), colorectal cancer (9.4), and ovarian cancer (6.3), which indicated the most likely site was gastric/esophagus cancer (62.5,  Figure 2B ). The Dako PD-L1 22C3 assay immunohistochemistry assay for PD-L1 expression revealed a tumor proportion score of 35% ( Figure 1E ). Finally, we identified the top 9 enriched GO terms as shown in  Supplementary Figure S1 .
Summary of histopathological and molecular pathological information. (A) Pathological and immunohistochemical (IHC) results. (B) 90-gene tumor tissue traceability expression assay results. The maximum similarity score for tumor tissue traceability was 100. (C) Gene expression profile of tissue specimens analyzed by NGS. VAF, variant alle frequency. NGS, Next Generation Sequencing.
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AFP were negative. As summarized in  Figure 2A , the final pathological diagnosis was a metastatic poorly differentiated carcinoma, combined with an immunohistochemical predisposition to digestive system origin. The top three predictions were gastric/esophagus cancer (62.5), colorectal cancer (9.4), and ovarian cancer (6.3), which indicated the most likely site was gastric/esophagus cancer (62.5,  Figure 2B ). The Dako PD-L1 22C3 assay immunohistochemistry assay for PD-L1 expression revealed a tumor proportion score of 35% ( Figure 1E ). The summary results are listed in  Figure 2C . Given the presence of negative predictive biomarkers for immunotherapy, including adenomatous polyposis coli (APC) c.646C>T mutation at exon 7 and janus kinase 1 (JAK1) c.425del mutation at exon5, the patient is at risk of disease hyper-progression if given immunotherapy alone ( Figure 2C ).
The patient's clinical course schedule. Computed tomography scans of abdominal lesions at baseline (upper line) and after treatment (middle line) with nivolumab plus carboplatin and albumin-bound nanoparticle paclitaxel for six cycles and nivolumab maintenance. This case introduced an MDT workup with imaging, IHC series, tissue-of-origin assay, and NGS-based GEP. Immunochemotherapy incorporating TMB, PD-L1 status and GEP data benefited this patient with long-lasting response.
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After six cycles of combination therapy, CT imaging indicated complete remission ( Figure 3 ).