FH (Fumarate Hydratase)

The recent developments and acquired knowledge on newer renal entities with eosinophilic cytoplasm opened insights into the clinical, pathological, immunohistochemical, molecular, epidemiological aspects, and the prognosis of these entities. We emphasize the role of routine morphology, aided by appropriate and select immunohistochemistry, as essential keys for diagnosing eosinophilic renal tumours.

Although they account for only about 5% of RCC, they are clinically significant due to distinctive biology, frequent diagnostic pitfalls, and therapeutic implications. Many pathology laboratories lack immediate access to fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to confirm MDRC; this review emphasizes morphologic recognition and immunohistochemical surrogates, followed by rational triage for ancillary testing when available.

FH overexpression restored the effects of TRIM47. Collectively, the observations demonstrate that TRIM47 accelerates the progression of ICC by interacting with FH and ubiquitinating FH, indicating that TRIM47/FH axis may be potential target for ICC treatment.

Eosinophilic globules, staghorn-like vessels and diffuse nuclear atypia have been shown to have high diagnostic value and could be considered morphologic indicators of dFH-LMs. The substantial interobserver reproducibility of eosinophilic globules makes this feature particularly promising for routine clinical practice.

Currently, molecular analyses guide treatment decisions in advanced cases following discussions in molecular tumour boards. Therefore, the classification of subtypes, together with their specific molecular alterations and signalling pathways, is gaining importance not only for targeted systemic therapy but also for the identification of patients with a hereditary tumour syndrome.The task of pathologists is to identify new tumour entities and genetically inherited tumour forms in order to ensure the best possible clinical care for patients.

However, it can be difficult to identify malignant tumors in a polycystic kidney using imaging alone, and pathological confirmation by biopsy is often required. The present report highlights the usefulness of performing needle biopsy for suspected masses using the same method that is used by nephrologists for kidney biopsy in cases in which determining the lesion nature from imaging alone is difficult and in hydratase-deficient renal cell carcinoma arising in acquired cystic kidney disease as a dialysis-associated renal carcinoma.

Other metabolic regulators, such as hypoxia-inducible factor 1-alpha (HIF-1α), mammalian target of rapamycin (mTOR), and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), may also sustain the fibrotic phenotype through coupling signaling that drives ECM production to metabolic programming. Overall, the proposed metabolic perspective of uterine fibroid pathogenesis invites further exploration of mechanistic investigation in uterine-specific models and therapeutic targeting through larger cohort studies.

FH-deficient RCC has a high risk of metastasis and recurrence, requiring strict follow-up. Although definitive diagnosis relies on immunohistochemistry, imaging features-such as mixed cystic-solid morphology, hemorrhagic cysts, and, compared with clear cell RCC, lower enhancement, restricted diffusion, and higher FDG uptake-may serve as important diagnostic clues that facilitate accurate pathological diagnosis and management.

The patient was treated with immunization and targeted therapy (Sunitinib and Tislelizumab injection) and subsequently received a robotic radical nephrectomy. Patients with similar conditions might initially present gynecology for uterine fibroids, easily ignored due to their rarity, missing the time window for diagnosing and treating RCC. This case underscores the need for early genetic screening in patients with recurrent uterine leiomyomas suggestive of FH deficiency.

Functional experiments demonstrated that radioresistant ESCC cells (KYSE410R) exhibited elevated OXPHOS activity, which is reversed by targeting TCA cycle enzymes (CPI-613 (Devimistat), fumarate hydratase-IN-1 (FH-IN-1), etc.) or Oxidative phosphorylation (OXPHOS) inhibitors (IACS-010759, Rotenone, etc.). Clinically, high Amphiregulin/Epiregulin (AREG/EREG) levels correlated with nCRT resistance and poor prognosis. Collectively, the CEBPB/AREG/EREG axis drives radioresistance by reprogramming OXPHOS, suggesting inhibition of this pathway or OXPHOS itself as a promising strategy to enhance ESCC therapeutic responses.