Artur Kowalik

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma

Vulvar squamous cell carcinoma (VSCC) originates from the progression of either a high-grade squamous intraepithelial lesion (HSIL) or differentiated-type vulvar intraepithelial neoplasia (dVIN), often in a background of lichen sclerosus (LS). The mechanisms leading to the progression of these premalignant lesions to VSCC are elusive. This study aims to identify pathogenic mutations implicated in VSCC development. Using next-generation sequencing, 38 HSIL, 19 dVIN, 20 LS, of which 10 were solitary lesions and 10 with adjacent VSCC, and 10 VSCC adjacent to LS, were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific). Pathogenic mutations of TP53 were the most common genetic alterations identified in 53% and 24% of dVIN and HSIL cases, respectively, followed by CDKN2A (p16) mutated in 42% and 0% of dVIN and HSIL, respectively. Seven (70%) and three (30%) of 10 cases of VSCC associated with LS carried TP53 and CDKN2A mutations, respectively, whereas neither solitary LS nor LS associated with VSCC cases harbored mutations in these genes. It appears that TP53 mutations are early events during VSCC carcinogenesis, being present in both HSIL and dVIN lesions. Our preliminary data do not support a genetic background for the notion of LS as the VSCC premalignant lesion.

Updated Guidelines for the Diagnosis and Treatment of Endometrial Carcinoma: The Polish Society of Gynecological Oncology (2025v)

In 2023, the Polish Society of Gynecologic Oncology (PSGO) published clinical recommendations for the diagnosis, treatment, and care of women with endometrial cancer (EC), developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. A 2025 update was initiated in response to new evidence, particularly regarding systemic therapies for metastatic, advanced, or recurrent EC, and the introduction of an updated FIGO classification. A targeted literature review identified relevant phase III clinical trials and systematic reviews, including RUBY, GY-018, AtTend, and DUO-E. These trials were critically assessed by an Expert Panel in accordance with the AGREE II methodology. Updated recommendations were formulated based on this evidence, with a comparative analysis of the old and new FIGO staging systems and visual updates to treatment pathways. Key changes include the addition of immunotherapy (I/O) plus chemotherapy (CHTH) as first-line treatment for all molecular subtypes of high-grade endometrioid and non-endometrioid carcinomas, replacing chemotherapy alone. For MMRp-positive cases, the 2025 version introduces the use of Olaparib alongside Durvalumab and CHTH. HER2-positive MMRp serous carcinoma remains eligible for trastuzumab in combination with CHTH. Second-line treatment guidance remains unchanged for patients who did not receive I/O plus CHTH initially. However, options for those previously treated with this combination are still under evaluation. This update ensures alignment with the latest international standards and reinforces evidence-based, personalized care for EC patients.