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Case Reports
. 2025 Mar 25;56(1):86.
doi: 10.1007/s12029-025-01203-1.

Microsatellite Stable Colorectal Tumours in Patients with Lynch Syndrome: A Case Report and Systematic Review Analysing Clinical Features and Implications for Immunotherapy

Fani Kapoulitsa  1 , Davide Mauri  1 , Konstantinos K Tsilidis  2   3 , Konstantinos Katsanos  4 , Eleni Timotheadou  5 , Maria Smaragdi Vlachou  1 , Konstantinos Kamposioras  6   7
Affiliations
Case Reports

Microsatellite Stable Colorectal Tumours in Patients with Lynch Syndrome: A Case Report and Systematic Review Analysing Clinical Features and Implications for Immunotherapy

Fani Kapoulitsa et al. J Gastrointest Cancer. .

Abstract

Purpose: Lynch syndrome is an autosomal dominant genetic disorder associated with early-onset colorectal cancer (CRC), endometrial cancer and other malignancies. This condition is defined by deficient DNA mismatch repair and high microsatellite instability (dMMR/MSI-high), exhibiting a substantial response to immunotherapy. However, microsatellite-stable (MSS) tumours may infrequently occur in individuals with Lynch syndrome. Our aim was to evaluate the efficacy of immunotherapy in patients with Lynch Syndrome and dMMR/MSS colorectal cancer.

Methods: A systematic review of the literature in medical databases, major related conferences and relevant oncology journals was conducted to identify the available evidence. Medical records from the Medical and Clinical Oncology Department of the University Hospital of Ioannina were also reviewed.

Results: Four cases of MSS colorectal cancer associated with Lynch syndrome and MSH6 germline mutation were identified. Three of these four patients were treated with immune checkpoint inhibitors. Two patients with metastatic disease experienced disease progression, but one patient who received neoadjuvant immunotherapy achieved a partial response. All four patients were diagnosed with colorectal cancer in ages younger than 52 (16-51 years old).

Conclusion: MSS CRC tumours in patients with Lynch syndrome is an infrequent phenomenon and under-represented in the literature. The limited efficacy of immune checkpoint inhibitors is highlighted in this rare subset of patients.

Keywords: DMMR/MSS; DNA mismatch repair (MMR); Immune checkpoint inhibitors (ICI); Lynch Syndrome; Microsatellite stability (MSS).

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate and Publish: The authors declare that this research is performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its subsequent amendments. Institutional Review Board (IRB) approval was granted. The subject involved gave their informed consent prior to the inclusion in this case series and provided informed consent for publication. Disclosure: This manuscript has not been published elsewhere in any language, nor is it under consideration for publication by another journal. Competing Interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart. A systematic review of literature for patients with Lynch syndrome and dMMR/MSS colorectal cancer
See this image and copyright information in PMC

References

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