PMC8640956_01
Pathological results, radiological images, and PD-L1 assay of an esophageal squamous carcinoma patient with divergent MSI status between primary and metastatic lesions. (A) Histology of his primary and metastatic tumors. Magnification, x200. (B) Representative CT images associated with his clinical outcomes during the whole treatment. Outcomes were valuated according to RECIST 1.1 criteria. (C) IHC staining with anti-PD-L1 antibody (SP142). Magnification, x100.
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A biopsy sample of pathological diagnosis showed ESCC ( Figure 1A ). A computed tomography (CT) scan revealed obvious contrast-enhanced imaging of the upper esophagus with a thickening wall and narrowing lumen but without visible enlargement of the mediastinal lymph nodes ( Figure 1B ), and he was diagnosed with a T2N0M0, upper esophageal carcinoma. Unfortunately, no actionable alterations with strong evidence for targeted therapy were identified in his primary lesion, where the expression level of PD-L1 (SP142 staining) was 5% (CPS close to 6) and microsatellite stability (MSS) was present ( Figures 1C ,  2A ). Specifically, he received 3 cycles of paclitaxel liposome plus nedaplatin for 2 months followed by radical intensity-modulated radiotherapy (IMRT) (66 Gy at 2.2 Gy/session to the esophageal tumor) for 1 month until early July 2018 ( Figure 1B ). Nevertheless, the CT scan showed multiple enlarged lymph nodes of the right-side neck with suspected metastasis on June 25, 2018 ( Figure 1B ), which was verified by pathological diagnosis of a puncture biopsy of the right cervical mass ( Figure 1A ). Surprisingly, MSI-H along with dMMR ( Figures 2A, B ) was observed in his metastatic tumor with the soaring percentage (TPS 70%, CPS 75) of PD-L1 ( Figure 1C ). Gy at 2.2 Gy/session to the metastatic tumor) or single pembrolizumab treatment from July 2018 to March 2019 and exhibited sustained clinical response, regardless of primary or metastatic lesions ( Figure 1B ). Given the good response after adding pembrolizumab, this patient did not continue to undergo chemotherapy or radiotherapy but just maintained pembrolizumab (100 mg) monotherapy until June 2019 and achieved a complete response (CR) of both primary and metastatic tumors ( Figure 1B ). Subsequently, he stopped the above therapies in June 2019 and remained CR until the recent radiological evaluation in April 2021 ( Figure 1B ).
MSI status, MMR results, and immune phenotypes together with neoantigens in primary and metastatic lesions of this patient. (A) Detection results of five microsatellite sites by the MSI analysis system (Promega). (B) MMR results of MLH1, MSH2, MSH6, and PMS2 in metastasis. (C) Representative images of CK5/6 (cytokeratin 5/6), CD3, and CD8 shown by mIHC in primary and metastatic lesions. Nuclei (blue) were counterstained by DAPI. Magnification, x200. (D) Quantification results of mIHC from 15 random vision fields. (E) The number of predicted neoantigens in primary and metastatic tumors.
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Unfortunately, no actionable alterations with strong evidence for targeted therapy were identified in his primary lesion, where the expression level of PD-L1 (SP142 staining) was 5% (CPS close to 6) and microsatellite stability (MSS) was present ( Figures 1C ,  2A ). Surprisingly, MSI-H along with dMMR ( Figures 2A, B ) was observed in his metastatic tumor with the soaring percentage (TPS 70%, CPS 75) of PD-L1 ( Figure 1C ).