BRAF V600

BRAF V600E and CTNNB1 mutation analysis is a valuable diagnostic tool for distinguishing RCC from CP. Given the potential for RCC to transform into PCP, the authors recommend BRAF V600E testing for all RCC cases. For BRAF V600E-positive cases, close monitoring of tumor progression or adjuvant therapies is advised.

Our work demonstrates that BET inhibition improves MAPK signaling blockade through profound epigenetic reprogramming of core transcription factor circuits. These findings provide a preclinical rationale for the evaluation of BET + BRAF + EGFR inhibition in patients with treatment-refractory BRAFV600E metastatic CRC (NCT06102902).

Outcomes following progression on chemotherapy and MAPK-targeted therapy with Encorafenib plus Cetuximab remain poor, highlighting an unmet need for effective later-line treatments. We discuss the mechanistic framework by which a subset of BRAFV600E-mutant MSS mCRC may respond to immune checkpoint inhibition through an inflamed immune microenvironment driven by constitutive MAPK signalling. This case illustrates the interplay between tumour-agnostic biomarkers such as TMB-high and tumour-specific context, and highlights the value of longitudinal genomic profiling, including ctDNA, to identify resistance mechanisms and guide treatment selection.

RCC was associated with a higher rate of dMMR and high-grade tumours, and a greater proportion of mucinous adenocarcinomas.

P1, N=6, Recruiting, Ipsen | Not yet recruiting --> Recruiting

Given her advanced age and frailty, she was treated with a first-line combination of pembrolizumab, dabrafenib, and trametinib. She achieved a radiographic complete response (CR) and has remained progression-free for over 26 months. This case highlights the potential synergy between MAPK pathway inhibition and immunotherapy, suggesting that even short-course targeted therapy may favorably remodel the tumor microenvironment to enable durable disease control in high-risk MSI-H/BRAF-mutant mCRC.

This case presents as a pitfall due to squamous differentiation in anaplastic thyroid carcinoma, which was initially misinterpreted as metastatic squamous cell carcinoma on fine needle aspiration (FNA) of the lymph node in the neck. Subsequent surgical resection reveals a unique rare occurrence of isolated anaplastic transformation of tall cell PTC in the metastatic lymph nodes, associated with the extremely rare co-occurrence of BRAF p.V600E and KRAS p.G12R mutations.

A high proportion of inconclusive results was observed, likely reflecting technical limitations related to the use of formalin-fixed, paraffin-embedded tissue. In conclusion, RET fusions were relatively uncommon in this Brazilian cohort but were enriched in younger patients, underscoring age-related differences in the molecular landscape of pediatric thyroid carcinoma and highlighting the need for larger, standardized multicenter studies.

P2, N=1, Terminated, University of Texas Southwestern Medical Center | N=52 --> 1 | Active, not recruiting --> Terminated; Sponsor decision to halt funding.

This review summarizes the key pathologic and molecular features associated with aggressive behavior in DTC, highlighting their diagnostic criteria, prognostic significance, and implications for clinical management. Comprehensive pathologic evaluation integrating morphologic and molecular findings remains essential for accurate risk stratification and multidisciplinary care of patients with thyroid carcinoma.

Treatment with combined BRAF and MEK inhibition (dabrafenib and trametinib) resulted in a clinical response. In addition to this index case, a literature review identified multiple additional SS harboring BRAF V600E, supporting its role as a recurrent, potentially targetable alteration in a small subset of SS. These findings highlight the value of comprehensive genomic profiling in SS, particularly in advanced or refractory cases, to identify rare but actionable molecular events that may expand therapeutic options.

These findings indicate that the targeted NGS 4-gene panel provides high diagnostic precision in distinguishing benign from malignant nodules. Its implementation offers a cost-effective, efficient molecular diagnostic strategy that may reduce unnecessary diagnostic procedures and facilitate optimized clinical management.