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Pulmonary Artery Intimal Sarcoma in a Patient with Lynch Syndrome: Response to an Immune Checkpoint Inhibitor

Pulmonary Artery Intimal Sarcoma in a Patient with Lynch Syndrome: Response to an Immune... Intimal sarcoma is an extremely rare mesenchymal tumor arising in the great vessels. To date, intimal sarcoma has not been reported in patients with Lynch syndrome (LS), even though this syndrome lacks DNA mismatch repair ability genetically and is prone to various malignancies. This patient was diagnosed with LS by the Revised Amsterdam Criteria II, and she suffered from intimal sarcoma in the left pulmonary artery. She had a germline missense variant of PMS2 (c.1399G>A, pV467I) which is classified as a variant of unknown significance. In her intimal sarcoma, PMS2 expression was decreased. Additionally, it exhibited microsatellite instability and a high tumor mutational burden (69 mutations/Mb) which are features of mismatch repair deficiency, although PMS2 (c.1399G>A, pV467I) missense is a variant of unknown significance. The metastatic lesions of intimal sarcoma in this patient responded heterogeneously to pembrolizumab, an immune checkpoint inhibitor. Cytotoxic agents and radiation were also effective for some metastatic lesions, but some lesions, including her liver metastases, were resistant. The hypermutable nature of the LS genotype might acquire resistance to an immune checkpoint inhibitor and other cytotoxic agents such as occurred with her liver metastases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncology Karger

Pulmonary Artery Intimal Sarcoma in a Patient with Lynch Syndrome: Response to an Immune Checkpoint Inhibitor

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Publisher
Karger
Copyright
© 2023 The Author(s). Published by S. Karger AG, Basel
eISSN
1662-6575
DOI
10.1159/000528682
Publisher site
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Abstract

Intimal sarcoma is an extremely rare mesenchymal tumor arising in the great vessels. To date, intimal sarcoma has not been reported in patients with Lynch syndrome (LS), even though this syndrome lacks DNA mismatch repair ability genetically and is prone to various malignancies. This patient was diagnosed with LS by the Revised Amsterdam Criteria II, and she suffered from intimal sarcoma in the left pulmonary artery. She had a germline missense variant of PMS2 (c.1399G>A, pV467I) which is classified as a variant of unknown significance. In her intimal sarcoma, PMS2 expression was decreased. Additionally, it exhibited microsatellite instability and a high tumor mutational burden (69 mutations/Mb) which are features of mismatch repair deficiency, although PMS2 (c.1399G>A, pV467I) missense is a variant of unknown significance. The metastatic lesions of intimal sarcoma in this patient responded heterogeneously to pembrolizumab, an immune checkpoint inhibitor. Cytotoxic agents and radiation were also effective for some metastatic lesions, but some lesions, including her liver metastases, were resistant. The hypermutable nature of the LS genotype might acquire resistance to an immune checkpoint inhibitor and other cytotoxic agents such as occurred with her liver metastases.

Journal

Case Reports in Oncology – Karger

Published: Jan 1, 2023

Keywords: Lynch syndrome; Immune checkpoint inhibitor; Intimal sarcoma

References

  • Mutations associated with HNPCC predisposition: update of ICG-HNPCC/INSiGHT mutation database
    Peltomäki, P; Vasen, H
  • Extracolonic manifestations of Lynch syndrome
    Bansidhar, BJ
  • A novel Lynch syndrome pedigree bearing germline MSH2 missense mutation c.1808A>T (Asp603Val)
    Sekine, R; Shimazu, K; Nakano, D; Yamaguchi, T; Suzuki, Y; Fukuda, K
  • Cardiac intimal sarcoma with PDGFR beta mutation and co-amplification of PDGFR alpha and MDM2: an autopsy case analyzed by whole-exome sequencing
    Ito, Y; Maeda, D; Yoshida, M; Yoshida, A; Kudo-Asabe, Y; Nanjyo, H
  • Assay complementarity to overcome false-negative testing for microsatellite nstability/mismatch repair deficiency: a pembrolizumab-sensitive intimal sarcoma
    Henick, BS; Ingham, M; Shirazi, M; Marboe, C; Turk, A; Hsiao, S
  • Sarcomas associated with hereditary nonpolyposis colorectal cancer: broad anatomical and morphological spectrum
    Nilbert, M; Therkildsen, C; Nissen, A; Akerman, M; Bernstein, I
  • Comprehensive mutation analysis of PMS2 in a large cohort of probands suspected of Lynch syndrome or constitutional mismatch repair deficiency syndrome
    van der Klift, HM; Mensenkamp, AR; Drost, M; Bik, EC; Vos, YJ; Gille, HJJP
  • Isolated loss of PMS2 immunohistochemical expression is frequently caused by heterogenous MLH1 promoter hypermethylation in Lynch Syndrome screening for endometrial cancer patients. full text links
    Kato, A; Sato, N; Sugawara, T; Takahashi, K; Kito, M; Makino, K
  • Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort
    Rosty, C; Clendenning, M; Walsh, MD; Eriksen, SV; Southey, MC; Winship, IM
  • Detection of point mutations of the Axin1 gene in colorectal cancers
    Jin, L-H; Shao, Q-J; Luo, W; Ye, Z-Y; Li, Q; Lin, S-C
  • BARD1 mystery: tumor suppressors are cancer susceptibility genes
    Hawsawi, YM; Shams, A; Theyab, A; Abdali, WA; Hussien, NA; Alatwi, HE
  • Cancer risks associated with germline PALB2 pathogenic variants: an international study of 524 families
    Yang, X; Leslie, G; Doroszuk, A; Schneider, S; Allen, J; Decker, B
  • Functional interrogation of Lynch syndrome-associated MSH2 missense variants via CRSPR-Cas9 gene editing in human embryonic stem cells
    Rath, A; Mishra, A; Ferreira, VD; Hu, C; Omerza, G; Kelly, K
  • Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study
    Marabelle, A; Fakih, M; Lopez, J; Shah, M; Shapira-Frommer, R; Nakagawaetal, K
  • Acquired resistance to immune checkpoint inhibitors
    Schoenfeld, AJ; Hellmann, MD
  • PD-1 blockade in tumors with mismatch-repair deficiency
    Le, DT; Uram, JN; Wang, H; Bartlett, BR; Kemberling, H; Eyring, AD
  • An update on immune checkpoint therapy for the treatment of Lynch syndrome
    Therkildsen, C; Jensen, LH; Rasmussen, M; Bernstein, I
  • Acquired resistance to immunotherapy in MMR-D pancreatic cancer
    Hu, ZI; Hellmann, MD; Wolchok, JD; Vyas, M; Shia, J; Stadler, ZK