Clinical Report: Undifferentiated Pleomorphic Sarcoma in Lynch Syndrome

Overview

This report presents a case of undifferentiated pleomorphic sarcoma (UPS) in a patient with Lynch syndrome (LS) carrying a germline MLH1 mutation. The findings suggest that UPS may be an uncommon extracolonic manifestation of LS, emphasizing the need for molecular testing in atypical sarcomas.

Background

Undifferentiated pleomorphic sarcoma is a rare and aggressive soft tissue sarcoma, typically found in the extremities. Lynch syndrome is a hereditary cancer syndrome primarily associated with colorectal cancer but may also involve other malignancies. Recent evidence indicates that sarcomas, including UPS, may represent rare extracolonic manifestations of Lynch syndrome, warranting further investigation.

Data Highlights

No numerical data or trial data presented in the article.

Key Findings

• The patient had a germline MLH1 c.2171T>A mutation and developed synchronous malignancies including colorectal cancer, cholangiocarcinoma, and retroperitoneal UPS.
• Molecular testing revealed mismatch repair deficiency (dMMR) in two of the malignancies, confirming the diagnosis of Lynch syndrome.
• Undifferentiated pleomorphic sarcoma may represent a rare extracolonic manifestation of Lynch syndrome.
• Comprehensive molecular testing, including MSI and germline variant analysis, is crucial in diagnosing atypical LS-associated tumors.
• Prior studies have shown that sarcomas in LS patients often exhibit dMMR or MSI-H status.

Clinical Implications

Healthcare professionals should consider the possibility of undifferentiated pleomorphic sarcoma in patients with Lynch syndrome, particularly those with atypical presentations. Molecular testing for mismatch repair deficiency should be included in the diagnostic evaluation of such cases to guide treatment strategies.

Conclusion

This case underscores the importance of recognizing undifferentiated pleomorphic sarcoma as a potential manifestation of Lynch syndrome and highlights the need for molecular testing in the management of these patients.

References

1. BJS, British Journal of Surgery, 2023 -- Risks of Metachronous Colorectal Cancer Following Extended or Segmental Resection in Lynch Syndrome Patients with MLH1, MSH2, and MSH6
2. The ASCO Post, 2013 -- Women with Lynch Syndrome and Endometrial Cancer Are at Increased Risk of Other Cancers
3. NCCN Guidelines® Insights, 2025 -- Soft Tissue Sarcoma, Version 1.2025
4. Acta Neuropathologica — Somatic mosaicism of SOX10 indel mutations is associated with a specific variant of segmental schwannomatosis
5. Blood Cancer Journal — Multi-Omics Analysis of Three Hematological Cancers in a Patient Identifies Their Origin from Clonal Hematopoietic Stem Cells
6. NCCN Guidelines® Insights - Soft Tissue Sarcoma, Version 1.2025 | NCCN Continuing Education
7. ARCHIVED Hereditary Cancer Testing 2024-06-30 (updated 2025-01-01) to 2025-03-22 | Carelon Clinical Guidelines and Pathways
8. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication | FDA