Investigator
Catholic University Of Korea
Integrative Genomic and Clinicopathologic Characterization of Pure Primary Ovarian Large Cell Neuroendocrine Carcinoma: A Case Report and Molecular Insight
Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by platinum-based chemotherapy. Histopathologic and immunohistochemical analyses confirmed the diagnosis. Next-generation sequencing (NGS) revealed a pathogenic BRCA2 frameshift mutation (c.7177dupA), an ATM nonsense mutation, and Tier II mutations in TP53 and PTEN. The tumor exhibited homologous recombination deficiency (HRD), microsatellite instability-high (MSI-H), and an exceptionally high tumor mutational burden (TMB) of 277.49 mutations/Mb. These molecular alterations closely resemble those observed in high-grade neuroendocrine carcinomas of cervical and endometrial origin, suggesting a convergent genomic profile across gynecologic neuroendocrine carcinomas (NECs). Our findings underscore the potential of comprehensive genomic profiling in rare tumors such as ovarian LCNEC to refine diagnosis and identify candidates for biomarker-driven therapies, including PARP inhibitors and immune checkpoint inhibitors. This case supports the integration of molecular diagnostics into clinical practice and highlights the need for prospective studies incorporating molecular stratification to inform treatment strategies for rare and aggressive neuroendocrine tumors.
Tumour budding in pretreatment cervical biopsies: a prognosticator for personalised therapy in the era of precision oncology
Aims Tumour budding (TB) is a noteworthy morphologic indicator for tumour microenvironment (TME) especially because it is detectable with routine haematoxylin and eosin (H&E) staining. Its prognostic relevance has been demonstrated across various cancers, but its significance in pretreatment biopsy specimens of cervical cancer is unknown. This is the first study to investigate the prognostic value of TB in pretreatment cervical biopsy. Additional TME features identifiable with H&E such as cell nest size (CNS) were evaluated. Methods and results A retrospective review was conducted on the 2018 International Federation of Gynaecology and Obstetrics (FIGO) stage IIVA cervical cancer patients ( N = 182) who had completed standard treatment. In multivariate analysis, TB (hazard ratio [HR], 2.06) and CNS (HR, 2.16) independently predicted overall survival. While TB (AUC, 0.7065) slightly outperformed CNS (AUC, 0.6975) in discriminating overall survival, the combination of TB and CNS demonstrated the highest performance (AUC, 0.7192) in time‐dependent receiver operating characteristic analysis. Conclusions This study is the first to suggest TB in pretreatment biopsy specimens as a reliable morphologic prognosticator in cervical cancer. TME features may enhance precision oncology by offering insights into the individual tumour biology. The fact that these morphologic features are available from routine H&E slides, reserving immunohistochemistry or molecular analysis for indeterminate cases, is of particular value in low‐resource settings where the burden of cervical cancer is most significant.
