case_images: PMC11092541_01
case_images: Illustration of MDM2-amplified InS with RECIST 1.1 objective response to anti-PD-1-based therapy. (a) and (b) Baseline CT scans of a 34-year-old patient (Case 1) diagnosed with metastatic InS to the bones, lungs (yellow circle), and lymph nodes (red arrowhead) - November 2022. (c) and (d) Evidence of uPR (-30.8%) following three cycles of pembrolizumab 200 mg q3w - January 2023. (e) and (f) Baseline CT scans of a 40-year-old patient (Case 2) diagnosed with metastatic InS to the lungs (yellow circle) and bones - May 2023. (g) and (h) Evidence of PR (-51.7%) following two cycles of pembrolizumab 200 mg q3w - June 2023. (i) Baseline CT scan of a -50-year-old patient (Case 3) diagnosed with metastatic InS to the bones and adrenal glands (red arrowhead) - December 2021. (j) Evidence of PR (-41.6%) following eight cycles of pembrolizumab 200 mg q3w plus investigational compound - May 2022.. InS, intimal sarcoma; MSI, microsatellite instability; PR, partial response; uPR, unconfirmed partial response.
case_images: 10.1177_17588359241250158-fig1.jpg
case_images: PMC11092541_03_10.1177_17588359241250158-fig1.jpg
case_images: fig1-17588359241250158
case_images: Delta -41.6%, Figure 1(i)-(j)], remaining on treatment with excellent tolerance for a total of 12 months (18 cycles). Due to clear PD in December 2022, we switched his systemic therapy to gemcitabine and docetaxel.
case_images: PMC11092541_02
case_images: Illustration of MDM2-amplified InS with RECIST 1.1 objective response to anti-PD-1-based therapy. (a) and (b) Baseline CT scans of a 34-year-old patient (Case 1) diagnosed with metastatic InS to the bones, lungs (yellow circle), and lymph nodes (red arrowhead) - November 2022. (c) and (d) Evidence of uPR (-30.8%) following three cycles of pembrolizumab 200 mg q3w - January 2023. (e) and (f) Baseline CT scans of a 40-year-old patient (Case 2) diagnosed with metastatic InS to the lungs (yellow circle) and bones - May 2023. (g) and (h) Evidence of PR (-51.7%) following two cycles of pembrolizumab 200 mg q3w - June 2023. (i) Baseline CT scan of a -50-year-old patient (Case 3) diagnosed with metastatic InS to the bones and adrenal glands (red arrowhead) - December 2021. (j) Evidence of PR (-41.6%) following eight cycles of pembrolizumab 200 mg q3w plus investigational compound - May 2022.. InS, intimal sarcoma; MSI, microsatellite instability; PR, partial response; uPR, unconfirmed partial response.
case_images: 10.1177_17588359241250158-fig1.jpg
case_images: PMC11092541_03_10.1177_17588359241250158-fig1.jpg
case_images: fig1-17588359241250158
case_images: Delta -41.6%, Figure 1(i)-(j)], remaining on treatment with excellent tolerance for a total of 12 months (18 cycles). Due to clear PD in December 2022, we switched his systemic therapy to gemcitabine and docetaxel.
case_images: Illustration of peritumoral lymphoid aggregates in a specimen of lung metastasectomy (case #2). (a) Microscopic assessment of case #2 pulmonary wedge resection specimen disclosing a high-grade spindle cell neoplasm (yellow arrow) with lymphoid aggregates at the tumor periphery (white dashed circle). Hematoxylin/eosin, 5x. (b) Hematoxylin/eosin, 10x. (c) CD20-positive immunostaining disclosing predominance of B-cell population in the center of a peritumoral lymphoid aggregate. (d) CD3-positive immunostaining disclosing abundant T-cell population across the entire peritumoral area, overlapping with B cells in its center.
case_images: 10.1177_17588359241250158-fig2.jpg
case_images: PMC11092541_02_10.1177_17588359241250158-fig2.jpg
case_images: fig2-17588359241250158
case_images: CD20+ lymphocytes [Figure 2(c)] admixed with numerous CD4+/CD8+ T cells [Figure 2(d)], as well as alveolar and intratumoral macrophages; the PD-L1 CPS staining was 7%; this specimen was also tested using the NGS Illumina TSO500 assay (Table 1), displaying amplifications in CDK4 (CN = 6) and MDM2 (CN = 35), 5.5 muts/Mb, absence of MSI status, but no sequence variants/fusions identified. Collectively, these findings suggest the presence of tertiary lymphoid structures (TLS) which may explain this patient's response to pembrolizumab.
case_images: PMC11092541_03
case_images: Illustration of MDM2-amplified InS with RECIST 1.1 objective response to anti-PD-1-based therapy. (a) and (b) Baseline CT scans of a 34-year-old patient (Case 1) diagnosed with metastatic InS to the bones, lungs (yellow circle), and lymph nodes (red arrowhead) - November 2022. (c) and (d) Evidence of uPR (-30.8%) following three cycles of pembrolizumab 200 mg q3w - January 2023. (e) and (f) Baseline CT scans of a 40-year-old patient (Case 2) diagnosed with metastatic InS to the lungs (yellow circle) and bones - May 2023. (g) and (h) Evidence of PR (-51.7%) following two cycles of pembrolizumab 200 mg q3w - June 2023. (i) Baseline CT scan of a -50-year-old patient (Case 3) diagnosed with metastatic InS to the bones and adrenal glands (red arrowhead) - December 2021. (j) Evidence of PR (-41.6%) following eight cycles of pembrolizumab 200 mg q3w plus investigational compound - May 2022.. InS, intimal sarcoma; MSI, microsatellite instability; PR, partial response; uPR, unconfirmed partial response.
case_images: 10.1177_17588359241250158-fig1.jpg
case_images: PMC11092541_03_10.1177_17588359241250158-fig1.jpg
case_images: fig1-17588359241250158
case_images: Delta -41.6%, Figure 1(i)-(j)], remaining on treatment with excellent tolerance for a total of 12 months (18 cycles). Due to clear PD in December 2022, we switched his systemic therapy to gemcitabine and docetaxel.