PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha)

In vivo, high glucose synergized with PKA activation to promote metastasis, whereas glycolysis inhibition blocked new metastases. Thus, HHEX-PRKAR2B-mediated PKA activation is a critical hub for PDAC progression, modulated by glucose and reinforcing glycolysis via HK2, revealing novel therapeutic targets for metabolic intervention.

Exploiting this 'death switch' offers a novel therapeutic framework through three principal strategies: (1) inducing pyroptosis to eliminate apoptosis-resistant cells, (2) utilizing pyroptosis-induced inflammation to enhance immune checkpoint inhibitor efficacy, and (3) developing targeted therapeutics that directly modulate these switch molecules. Although controlling pyroptosis-associated inflammation remains challenging, understanding and manipulating the apoptosis-to-pyroptosis transition provides an innovative approach to overcome drug resistance and develop more effective cancer treatments.

All cases highlight the absence of a consistent genotype-phenotype correlation in CNC, emphasizing the need for individualized management strategies. The findings underscore the complexity of diagnosing and treating CNC, particularly in pediatric populations, and call for further research into the underlying molecular mechanisms to develop more targeted therapies.

This case underscores the importance of periodically reassessing genetic variants, as reclassification can significantly impact patient management. It also highlights the clinical variability of CNC and the need to screen for CNC features in young patients with acromegaly. Further research is warranted to determine the value ofPRKAR1A testing in isolated GH- and GH/PRL-secreting PA.

These findings provide concrete molecular targets for antiangiogenic therapy and establish clinically actionable biomarkers for glioma patient stratification in the 3PM framework. The online version contains supplementary material available at 10.1007/s13167-025-00428-1.

MM arising within CGMN poses diagnostic and therapeutic challenges. While molecular and epigenomic profiling supports accurate classification and understanding of disease biology, the role of immunotherapy remains uncertain-marked by reduced efficacy and significant immune-related toxicity. A multidisciplinary approach is essential to guide management and improve outcomes in this rare pediatric malignancy.

MMNST should be considered when encountering suspicious peripheral nerve sheath lesions. Promptly performing appropriate biopsies and molecular testing is critical due to this condition's poor prognosis. https://thejns.org/doi/abs/10.3171/CASE25314.

To transition from pathologic description to clinical impact, future efforts must focus on validating diagnostic criteria in large, multi-institutional cohorts, integrating comprehensive molecular profiling to uncover therapeutic vulnerabilities, and establishing evidence-based management protocols. The pathologic recognition of STOX must be seamlessly connected to systematic genetic evaluation and long-term monitoring, fulfilling the translational imperative of this diagnosis.

Here, we show that IPA isoforms are a novel source of microproteins, and we reveal the novel paradigm of miP-5'UTR-IPA genes that produce both a canonical full-length mRNA and a microprotein-coding IPA isoform.

The majority of ILCHSCN demonstrate loss of expression of STK11, while LCCSCT shows retained expression. Our findings support that STK11 IHC is highly specific and moderately sensitive in distinguishing between these two tumours. The combination of STK11 and PRKAR1A IHC has even greater utility for distinguishing ILCHSCN and LCCSCT.

Although rare, OCM preferentially occurs in the sinonasal tract, and therefore may be encountered by head and neck pathologists. Given their predilection for young patients and overlapping morphologic features, OCM are easily misdiagnosed as other matrix-forming sinonasal tumors, especially nasal chondromesenchymal hamartoma. Immunohistochemical demonstration of PRKAR1A loss is valuable for confirming an OCM diagnosis, which should prompt clinical investigation for the possibility of Carney complex.

Given the limited epidemiological knowledge on MMNSTs, our study contributes to the literature by documenting a case of intra- and extraspinal, cervical MMNST without any of the previously known driver mutations or copy number changes. While the WHO 2021 classification designates these tumors as potentially malignant, our findings support existing reports that more benign courses can occur.