TFE3 fusion

The fusion partner gene ZC3H4 is uncommon, and this is the third reported PEComa case. The fusion partner gene PRCC is often reported in TFE3-rearranged renal cell carcinoma, and this PEComa case is the second reported in the head and neck region. The initially reported cases with the fusion partner genes ZC3H4 and PRCC were categorized as malignant. These cases were discussed with a literature review.

Given the limited clinical experience with OFMT, multidisciplinary tumour boards are crucial for tailoring individualized treatment strategies. This study contributes to the growing body of literature on OFMT, providing a foundation for future research.

Upregulation of GSTP1 mediated by chimeric TFE3 promotes TFE3-tRCC progression by targeting JNK signaling pathway, which underscore the potential of GSTP1 as a promising therapeutic target for TFE3-tRCC.

TFE3-RCC ARID2 KO cells demonstrated heightened sensitivity to the ERBB3 inhibitor AZD8931 compared to their wild-type counterparts, exhibiting significantly reduced migration and proliferation rates. These findings suggest that the PRCC-TFE3-ARID2-ERBB3 axis plays a critical role in TFE3-RCC pathogenesis and highlights the potential of targeting ERBB3 in ARID2-deficient TFE3-RCC as a therapeutic strategy. This study provides new insights into the molecular mechanisms of TFE3-RCC and suggests avenues for precision treatment of this aggressive cancer.

Pharmacologic or genetic inhibition of mTOR signaling downregulates expression of the SFPQ-TFE3 fusion protein and rescues nephric lineage marker expression and transcriptional activity in vitro. These data provide evidence of a potential epithelial cell-of-origin for TFE3 -driven PEComas and highlight a reciprocal role for SFPQ-TFE3 and mTOR in driving lineage plasticity in the kidney, expanding our understanding of the pathogenesis of MiT/TFE-driven tumors.

We report VCP as a novel fusion partner in ASPS and PSPC1 as a novel TFE3 fusion partner in PEComa (detected in one PEComa). Future studies should shed light on the most appropriate terminological subtyping of these highly overlapping tumors.

These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.

P1, N=67, Terminated, Ikena Oncology | N=198 --> 67 | Trial completion date: Jun 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Aug 2024; Sponsor strategic reasons

Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS.

This case report highlights the importance of detailed diagnosis, prompt treatment, and close monitoring of patients with ASPS.

In conclusion, while radical surgical excision remains crucial for early-stage ASPS, the landscape for advanced cases is evolving with targeted therapies showing promising results. However, further randomized trials are necessary to broaden the treatment options available and to evaluate these new therapies against existing standard care regimens. This ongoing research is vital to improving outcomes for patients with ASPS and tailoring more effective treatment strategies.

Although the median follow-up time for our study was short (18 months, available in 7 cases), all cases pursued a benign clinical course, with no recurrences or metastases. Our study provides further characterization of this novel entity, supporting its wider recognition.