Perivascular epithelioid cell tumors (PEComas), rare mesenchymal neoplasms with heterogeneous behavior, are molecularly characterized by TSC2 inactivation driving mammalian target of rapamycin (mTOR) pathway activation. We present a typical case of a 63-year-old female with metastatic high-grade PEComa featuring a TSC2 mutation (68.57% VAF) and elevated tumor mutational burden (19.7 mut/Mb), manifesting as peritoneal carcinomatosis and pulmonary metastases. Everolimus therapy following multidisciplinary assessment induced a radiologically confirmed partial response within 4.5 months with sustained clinical benefit. This outcome validates mTOR inhibition in TSC2-mutated PEComas and underscores the imperative of molecular profiling in mesenchymal tumor management. The significant mutational burden suggests potential immunotherapy responsiveness, informing future combination strategies. These findings emphasize molecularly guided precision approaches in rare malignancies and warrant systematic exploration of therapeutic sequencing and resistance mechanisms in mTOR-driven tumors.

Background: Retroperitoneal liposarcoma (RPLS) is known for its propensity for local recurrence and short survival time. We aimed to identify a credible and specific prognostic biomarker for RPLS. Methods: Cases from The Cancer Genome Atlas (TCGA) sarcoma dataset were included as the training group. Co-expression modules were constructed using weighted gene co-expression network analysis (WGCNA) to explore associations between modules and survival. Survival analysis of hub genes was performed using the Kaplan–Meier method. In addition, independent external validation was performed on a cohort of 135 Chinese RPLS patients from the REtroperitoneal SArcoma Registry (RESAR) study (NCT03838718). Results: A total of 19 co-expression modules were constructed based on the expression levels of 26,497 RNAs in the TCGA cohort. Among these modules, the green module exhibited a positive correlation with overall survival (OS, p = 0.10) and disease-free survival (DFS, p = 0.06). Gene set enrichment analysis showed that the green module was associated with endocytosis and soft-tissue sarcomas. Survival analysis demonstrated that NINJ1, a hub gene within the green module, was positively associated with OS (p = 0.019) in the TCGA cohort. Moreover, in the validation cohort, patients with higher NINJ1 expression levels displayed a higher probability of survival for both OS (p = 0.023) and DFS (p = 0.012). Multivariable Cox analysis further confirmed the independent prognostic significance of NINJ1. Conclusions: We here provide a foundation for the establishment of a consensus prognostic biomarker for RPLS, which should not only facilitate medical treatment but also guide the development of novel targeted drugs.

Introduction Dedifferentiated liposarcoma (DDLPS) is a rare and aggressive subtype of soft tissue sarcoma, characterized by limited treatment options and poor prognosis. Despite surgical resection being the only potentially curative treatment for localized DDLPS, the recurrence rate remains high, and systemic chemotherapy, typically anthracycline-based, shows limited efficacy in advanced stages. While immune checkpoint inhibitors (ICIs) have shown promise in various sarcoma subtypes, including DDLPS, their role as a first-line treatment remains unclear. Methods We conducted a systematic meta-analysis to evaluate the efficacy of ICIs in treating patients with DDLPS. A total of 25 studies encompassing 245 patients were included. Data on overall response rate (ORR), progression-free survival, and grade III–V treatment-related adverse events were analyzed. We assessed treatment efficacy based on the line of therapy and treatment regimens, including ICI monotherapy, dual ICI therapy, and ICI combinations with other modalities. Results The pooled ORR for all ICI-based treatments was 7%. First-line ICI therapy yielded a significantly higher ORR of 22%, compared to 4% in later-line treatment. The combination of ICI with anthracyclines demonstrated the highest ORR of 52%. In contrast, ICI regimens combined with trabectedin or other agents showed limited efficacy. Sensitivity analysis confirmed the stability of results, and publication bias was not detected. Conclusion This meta-analysis supports the potential role of ICIs, particularly in combination with anthracyclines, as a first-line therapeutic strategy for DDLPS. These results provide a foundation for future prospective studies aimed at optimizing immunotherapy approaches for this rare and challenging malignancy.

Dedifferentiated liposarcoma (DDLPS), a rare disease with limited research, exhibits resistance to radiotherapy and chemotherapy. Few reports have analyzed

The first recurring message is that operative quality begins before the incision. Zheng et al. developed an ultrasonography-based model and simplified score to distinguish retroperitoneal ganglioneuroma from schwannoma in 74 patients. Optimism-corrected areas under the curve were 0.930 and 0.917, respectively, but the authors appropriately called for external validation and recalibration before routine use. In a cohort of 28 adults with primary retroperitoneal lymphangioma, Li et al. described characteristic multiloculated cystic imaging features, complete resection in all patients, and no recurrence or disease-specific death during a median follow-up of 76 months. Yang et al. similarly showed how pathology can resolve the marked clinical heterogeneity of pelvic solitary fibrous tumors: three patients underwent individualized open, robot-assisted, or laparoscopic R0 resection, with nuclear STAT6 supporting diagnosis. These series are small, but they illustrate how imaging, operative anatomy, and pathology should be interpreted as one continuous diagnostic process.Moving beyond pairwise discrimination, Feng et al. developed REMIND, an end-to-end deep learning model for contrast-enhanced computed tomography, using data from 12 Chinese centers. The model was trained in 606 patients, externally validated in 736, and prospectively evaluated in 188; it combined seven-class diagnosis with tumor segmentation and, in a reader study, achieved a top-1 accuracy comparable to senior radiologists while improving the performance of less-experienced readers (1). This work suggests that artificial intelligence may become a useful decision-support layer for rare, heterogeneous retroperitoneal neoplasms. Before such systems influence biopsy or operative strategy, however, their calibration, failure modes, and transportability should be tested prospectively in other populations and clinical workflows.Complex anatomy also benefits from explicit reconstruction. In a case of ganglioneuroma involving an ectopic inferior vena cava, Xu et al. used three-dimensional reconstruction to plan robot-assisted resection. Such tools should not be treated as decorative imaging. Their value lies in defining displacement, encasement, collateral pathways, and the likely need for vascular control before committing to an approach.Several reports show why apparent natural history or an unusual syndrome must not replace tissue diagnosis. Spontaneous radiological regression did not exclude malignancy in a Bosniak IV cystic renal lesion, which proved to be clear cell renal cell carcinoma after partial nephrectomy. In an adolescent with a large renal mass and a pathogenic TSC2 variant, malignant perivascular epithelioid cell tumor was distinguished from angiomyolipoma only after histopathological and molecular assessment. Adult pelvic fibrosarcoma presenting with bowel obstruction required an exclusionary pathological workup, while refractory mucocutaneous disease in a patient with retroperitoneal dedifferentiated liposarcoma was ultimately recognized as paraneoplastic pemphigus.The limits of inference from isolated PEComa cases are clarified by the TARPSWG study of Mor et al., which included 77 patients with primary extra-visceral retroperitoneal or abdominopelvic PEComas from 13 centers. Among 59 patients treated with curative intent, 24 recurred; outcomes differed by histological subtype, with PEComa not otherwise specified showing the highest recurrence and mortality, sclerosing PEComa an intermediate course, and angiomyolipoma predominantly indolent behavior (2). This pattern supports expert pathology review, biopsy-informed classification, and subtype-adapted surveillance rather than risk assessment based on tumor size alone. Together with the cases in this collection, it argues for early multidisciplinary review whenever symptoms, imaging, pathology, and presumed biology do not align.The second message is not maximal surgery, but appropriately scaled surgery. For dedifferentiated liposarcoma with true colonic infiltration, tumor resection with right hemicolectomy addressed contiguous disease and achieved short-term control. For advanced low-grade serous ovarian carcinoma extending to the iliac vessels and paraspinal region, coordinated gynecologic, orthopedic, plastic, and gastrointestinal surgery enabled R0 resection, femoral vein repair, and flap reconstruction. The proposed "Four Surgical Limits" frameworkanatomical, oncological, functional, and interdisciplinary -offers a useful language for determining when apparent technical limits can be crossed safely.The same principle applies to severe benign disease. A giant uterine leiomyoma complicated by pleural and ascitic effusions, venous thromboembolism, hernia, and pelvic organ prolapse was treated through staged stabilization followed by tumor resection. Conversely, intravenous leiomyomatosis extending through the inferior vena cava into the right atrium demonstrated that even successful en bloc removal does not end perioperative risk; postoperative pulmonary embolism demanded rapid recognition and treatment. These reports emphasize that resectability is not simply an anatomical label. It is a team judgment that includes physiological reserve, thrombotic risk, reconstructive options, and rescue capacity.Quantifying that risk may make perioperative planning more transparent. In 319 patients undergoing resection of primary retroperitoneal sarcoma, Zhuang et al. developed an internally validated morbidity nomogram incorporating age, tumor burden and location, operative time, the number and weighted score of resected organs, estimated blood loss, and packed red-cell transfusion. The model had a concordance index of 0.795 (95% confidence interval 0.746-0.844) (3). It offers a structured basis for risk stratification, counselling, and postoperative vigilance, but several inputs become known only during surgery. A clinically mature pathway will therefore need separately...