MLH1 (MutL homolog 1)

Lesion-specific molecular characterization combined with regional lymph node MMR phenotyping is critical for the precise management of SCRCs with discordant MMR status. This case provides a referable diagnostic workflow and surgical decision-making framework for this rare clinical scenario, supporting risk-adapted individualized therapy for molecularly heterogeneous colorectal cancer.

NY-ESO-1 expression was associated with response to nivolumab, while PD-L1 expression, particularly CPS, may provide clinically relevant prognostic information. Integrated assessment of tumor-related biomarkers and the host immune microenvironment may further improve patient stratification in ESCC.

The benefit-cost ratio (BCR) analysis demonstrated the greater cost-effectiveness of genetic testing compared to endoscopic surveillance to all relatives at risk. Although our cohort is clinically enriched and does not reflect the population prevalence of LS in Southern Thailand, these findings highlight the substantial LS burden within high-risk families and underscore the importance of incorporating genetic screening, counseling, and tailored surveillance strategies into clinical practice.

Post-operatively, she received six cycles of carboplatin, paclitaxel, and dostarlimab every three weeks, followed by maintenance dostarlimab. This case illustrates that aggressive multimodal therapy including immune checkpoint inhibition may achieve durable disease control in advanced-stage MMR-deficient uterine LCNEC. While the relative contributions of surgery, chemotherapy, radiation, and immunotherapy cannot be separated, the favorable outcome supports further investigation of immunotherapy in rare high-grade endometrial neuroendocrine carcinomas and underscores the importance of including these histologies in clinical trials.

Our study shows that MSI and neoantigen accumulation emerge during the evolution of precancerous lesions in LS. These findings support the clinical evaluation of Nous-209, a shared neoantigen vaccine, as an immunoprevention strategy for MSI-driven colorectal carcinogenesis, with important implications for cancer prevention research.

P=N/A, N=185, Terminated, Washington University School of Medicine | N=310 --> 185 | Trial completion date: Jan 2027 --> Mar 2026 | Recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Mar 2026; Loss of space for imaging

This exploratory analysis suggested a higher uptake of risk-reducing surgery at the safety-net hospital than at the university medical center. Understanding factors contributing to this difference will be critical to supporting gynecologic cancer risk management in Lynch syndrome.

MLH1 promoter methylation, MMR deficiency, and CDX2 are rare events in PTC and do not appear to influence PFS. Although infrequent, the expression of CDX2 is not exclusive to any PTC subtype.

In reporting these neoplasms, we highlight that signet ring cells occasionally occur in primary endometrial carcinomas of endometrioid-type and, although numbers are small, there appears to be an association with MMR deficiency. These tumors have a propensity for high-stage at presentation.

The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling.

Consequently, molecular testing revealed mismatch repair deficiency (dMMR) among two cancers, thereby confirming the diagnosis of LS. This case suggests that UPS may represent a rare extracolonic manifestation of LS and highlights the importance of considering MMR/MSI testing in sarcomas of uncertain origin, which may have implications for diagnosis and personalized treatment strategies, including the use of immune checkpoint inhibitors.

© 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland