FH (Fumarate Hydratase)

Here, we report an HLRCC patient with stage III RCC who achieved a pathologic complete response following one cycle of dual immune checkpoint blockade with nivolumab and ipilimumab and remains disease-free 15 months later. This case extends findings from previous reports and suggests that dual checkpoint blockade may result in clinically meaningful activity in a subset of patients.

Our findings highlight the pronounced morphological heterogeneity of FHd RCC and the critical role of combined FH and 2SC immunohistochemistry for accurate diagnosis. FHd RCC should be recognized as a distinct, highly malignant renal neoplasm, warranting comprehensive histological, immunohistochemical, and genetic assessment, along with genetic counseling to identify potential hereditary background.

ICI rechallenge may offer favorable clinical benefit and acceptable safety in patients with metastatic nccRCC. Higher density of mature iTLSs correlated with the efficacy of ICI-rechallenge but warrants further validation.

FH-TPS-HLRCC is underdiagnosed and RCC risk is lower than earlier HLRCC estimates. Many individuals are identified through broad hereditary cancer gene panel testing and exhibit less obvious manifestations such as uterine leiomyomata. Adult RCC surveillance is warranted in FH-TPS-HLRCC, but the need for pediatric screening merits further study.

In contrast, a distinct set of agents, such as the combination of bevacizumab and erlotinib, is the principal systemic therapy consideration for FH-deficient RCC. Therefore, FH loss by IHC does not necessarily always indicate a pathogenic FH mutation. Further molecular studies are critical in determining the underlying pathogenic mutation.

A propagation of adenomyosis within the uterine blood vessels is a rare histological finding causing diagnostic difficulties as it resembles intravascular spreading of malignant neoplasm. Although this is not a tumor entity, it represents an important differential diagnosis in the oncopathological practice. The pathologist's knowledge about this phenomenon is crucial to avoid confusion with vascular dissemination of malignancy.

Future metabolic interventions targeting succination modification could significantly improve cancer therapies. This review offers a comprehensive overview of the role of protein succination modification in tumor metabolism and immune evasion, along with its potential clinical applications.

P2, N=28, Recruiting, Instituto do Cancer do Estado de São Paulo | Active, not recruiting --> Recruiting

A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

The c.1431_1433dupAAA variant was identified in the homozygous state in patients with mild intellectual disability and features overlapping with FMRD. Our findings suggest that all variants identified in FMRD patients require independent clinical evaluation for HLRCC association.