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Peer-reviewedCC BY 4.0Frontiers in Oncology

Case Report: Metachronous multiple primary neoplasms in a carrier of germline MSH2 c.958dupA Lynch syndrome

  • Liqiong Wang1,2
  • Ping Li3
  • Duanlin Hu1
  • Xiaozhong Wang1
  • Zhiyuan Xu4
4 affiliations
  1. 1Department of Gynecology, The University of Hong Kong-Shenzhen Hospital (HKU-SZH)
  2. 2Shenzhen Clinical Research Center for Rare Diseases
  3. 3Department of Pathology, The University of Hong Kong-Shenzhen Hospital
  4. 4Department of Oncology Medical Center, The University of Hong Kong-Shenzhen Hospital
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Abstract

Introduction: Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, conferring elevated risks of colorectal, endometrial, gastric, ovarian and other malignancies. We report a 38-year-old woman with a germline MSH2 c.958dupA (p.Thr320Asnfs*13) pathogenic frameshift mutation who developed metachronous multiple primary neoplasms affecting four organ systems over eight years.

Case description: She presented with abnormal uterine bleeding and was diagnosed with endometrioid endometrial adenocarcinoma (FIGO grade 3, stage IA, pT1a N0 M0) at age 38, receiving comprehensive surgical staging followed by vaginal brachytherapy. MMR immunohistochemistry showed loss of MSH2 and MSH6 protein expression with retained MLH1 and PMS2 and positive internal control, confirming dMMR consistent with the germline MSH2 variant. Eight months later, chest CT detected a right upper lobe lesion; wedge resection confirmed minimally invasive adenocarcinoma (MIA, pT1mi N0 M0, stage IA1). The tumour measured 0.8 cm with negative margins. ARMS-PCR detected an EGFR exon 19 deletion (19-DEL); other hotspot mutations were negative. Exploratory markers were assessed but did not guide management. Elastic fibre staining supported the MIA diagnosis. Serial esophagogastroduodenoscopy (2019–2021) documented gastric low-grade intraepithelial neoplasia (LGIN); endoscopic submucosal dissection (2023) achieved curative resection of high-grade gastric intraepithelial neoplasia (HGIN). In April 2026, colonoscopy detected >10 flat micro-polyps (0.2–0.3 cm) in the rectosigmoid colon with NICE type 1 features, treated with argon plasma coagulation without histological sampling; their nature remains undetermined. No recurrence occurred during eight years of follow-up.

Conclusion: This case illustrates the clinical and biological heterogeneity of neoplasms in a germline MSH2 carrier. The endometrial carcinoma was confirmed dMMR by immunohistochemistry, consistent with the germline MSH2 variant, and classified as Lynch-associated. The gastric precursor lesion was possibly Lynch-associated. The pulmonary MIA was compatible with a sporadic EGFR -driven origin, although a Lynch-associated contribution could not be excluded. Colorectal micro-polyps were of undetermined histological nature. Management should be individualized, and each lesion assessed on its own histology, molecular profile and tissue availability.

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Cite

BibTeXRIS
BibTeX
@article{wang2026case,
  title = {{Case Report: Metachronous multiple primary neoplasms in a carrier of germline MSH2 c.958dupA Lynch syndrome}},
  author = {Liqiong Wang and Ping Li and Duanlin Hu and Xiaozhong Wang and Zhiyuan Xu},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1958351},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1958351/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Case Report: Metachronous multiple primary neoplasms in a carrier of germline MSH2 c.958dupA Lynch syndrome
AU  - Liqiong Wang
AU  - Ping Li
AU  - Duanlin Hu
AU  - Xiaozhong Wang
AU  - Zhiyuan Xu
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1958351
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1958351/full
AB  - Introduction: Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, conferring elevated risks of colorectal, endometrial, gastric, ovarian and other malignancies. We report a 38-year-old woman with a germline MSH2 c.958dupA (p.Thr320Asnfs*13) pathogenic frameshift mutation who developed metachronous multiple primary neoplasms affecting four organ systems over eight years.  Case description: She presented with abnormal uterine bleeding and was diagnosed with endometrioid endometrial adenocarcinoma (FIGO grade 3, stage IA, pT1a N0 M0) at age 38, receiving comprehensive surgical staging followed by vaginal brachytherapy. MMR immunohistochemistry showed loss of MSH2 and MSH6 protein expression with retained MLH1 and PMS2 and positive internal control, confirming dMMR consistent with the germline MSH2 variant. Eight months later, chest CT detected a right upper lobe lesion; wedge resection confirmed minimally invasive adenocarcinoma (MIA, pT1mi N0 M0, stage IA1). The tumour measured 0.8 cm with negative margins. ARMS-PCR detected an EGFR exon 19 deletion (19-DEL); other hotspot mutations were negative. Exploratory markers were assessed but did not guide management. Elastic fibre staining supported the MIA diagnosis. Serial esophagogastroduodenoscopy (2019–2021) documented gastric low-grade intraepithelial neoplasia (LGIN); endoscopic submucosal dissection (2023) achieved curative resection of high-grade gastric intraepithelial neoplasia (HGIN). In April 2026, colonoscopy detected >10 flat micro-polyps (0.2–0.3 cm) in the rectosigmoid colon with NICE type 1 features, treated with argon plasma coagulation without histological sampling; their nature remains undetermined. No recurrence occurred during eight years of follow-up.  Conclusion: This case illustrates the clinical and biological heterogeneity of neoplasms in a germline MSH2 carrier. The endometrial carcinoma was confirmed dMMR by immunohistochemistry, consistent with the germline MSH2 variant, and classified as Lynch-associated. The gastric precursor lesion was possibly Lynch-associated. The pulmonary MIA was compatible with a sporadic EGFR -driven origin, although a Lynch-associated contribution could not be excluded. Colorectal micro-polyps were of undetermined histological nature. Management should be individualized, and each lesion assessed on its own histology, molecular profile and tissue availability.
SN  - 2234-943X
ER  -