FH (Fumarate Hydratase)

The FH VUS p.Lys414Glu has been reported in patients with HLRCC features but additional evidence is needed to support an interpretation of pathogenicity. Here we show that p.Lys414Glu is completely inactive, supporting a classification of pathogenic and providing critical evidence for clinical care and surveillance of patients with germline FH p.Lys414Glu.

The tumor showed intense FDG uptake with SUVmax of 14, which may be due a metabolic shift to aerobic glycolysis of the tumor caused by loss-of-function mutations of fumarate hydratase gene. This case indicates that fumarate hydratase gene mutation may be a possible factor for increased FDG uptake in uterine leiomyomas.

Therapeutic advances are reshaping the management of nccRCC, with IO/TKI regimens and histology-specific therapies showing promise. Continued integration of molecular classification, rare subtype-specific trials, and international collaboration will be essential to establish evidence-based treatment standards for this diverse and understudied population.

Altogether, this study characterizes the clinicopathological features of large cohort of bladder LMs, highlighting unrecognized morphologic features, including cases with massive necrosis. Our findings suggest that bladder LMs differ pathogenetically from their uterine counterparts, with a more limited role for hormone receptor signaling and distinct genetic alterations.

She subsequently received bevacizumab and erlotinib and achieved a favorable response. This case illustrates the practical challenges faced in treating fumarate hydratase-deficient renal cell carcinoma, including the lack of established systemic treatment guidelines and management of treatment-related adverse events. It highlights the value of integrating radiotherapy during interruptions in systemic therapy and the importance of multidisciplinary collaboration in this rare tumor.

This case highlights potential links to the pathophysiology of how HLRCC-associated renal cell cancers may arise from FH-deficient leiomyomas around a decade later. Leaving the excision site open after complete excision of this leiomyoma with FH-deficient morphology may decrease the risk of developing renal cell carcinoma.

HLRCC requires a high index of clinical suspicion for early diagnosis and appropriate oncological management. Its detection in primary care optimizes referral, follow-up, and family screening through an interdisciplinary approach.

P1, N=1314, Recruiting, Exelixis | Active, not recruiting --> Recruiting

Here we report 3 cases of diffuse glioma with succinate dehydrogenase deficiency that show many similarities with isocitrate dehydrogenase-mutant gliomas. We propose that succinate dehydrogenase deficiency with accumulation of the oncometabolite succinate can promote gliomagenesis in a similar manner as seen in isocitrate dehydrogenase-mutant and fumarate hydratase-deficient gliomas, and we discuss the proposed mechanisms that may lead to tumor formation.

Overall, metabolic RCC recognition in Italy is primarily morphology-driven but constrained by uneven access to confirmatory IHC, particularly 2SC, and to molecular assays. The findings argue for harmonized diagnostic algorithms, regional reference laboratory networks, and routine involvement of molecular tumor boards, supported by targeted educational initiatives (including curated digital slide repositories), to standardize practice and improve patient pathways from morphologic suspicion to genetic counselling and tailored surveillance.

Although IVL is a rare histologically benign tumour, it exhibits the capacity to infiltrate cardiac chambers and pulmonary vasculature. Therefore, early diagnosis via imaging techniques, precise assessment of the extent of intravenous leiomyoma involvement, complete lesion resection and perioperative administration of anti-oestrogen medications are pivotal for enhancing patient prognosis. Additionally, for cases with atypical nuclei or high Ki-67 levels, multidisciplinary collaboration is required to personalised treatment.