No somatic mutations were found in exons 2, 3, and 4 of the SDHD gene in any of the evaluated PGLs. The absence of mutations in the evaluated SDHD gene subunits suggests the involvement of other genetic factors or pathways in the development of these tumors, warranting further investigation in this field.

Subsequently, whole exome sequencing (WES) test identified a pathogenic frameshift variant in the SDHD gene, strongly suggestive of PPGL1. This study highlights the importance of considering atypical symptoms in diagnosing rare pediatric pheochromocytoma/paraganglioma tumors and underscores the value of genetic testing in identifying underlying genetic causes, thereby facilitating personalized management of the condition.

All PGLs remained stable and asymptomatic at 22-month follow-up imaging. TPGL should be considered in the differential diagnosis of a hypervascular TN in patients with SDHx-related pheochromocytoma-PGL syndromes and when such lesions with indeterminate cytology are encountered in patients with no known history of SDHx-mutation or syndrome.

An SDHD mutation variant was shared amongst unrelated patients but no founder-effect was established. Our findings confirmed that the pattern of SDHD mutation distribution amongst HNPGLs in Czech Republic differs from most studies worldwide.

68 Ga-DOTATATE PET/CT showed a significantly superior per lesion detection rate compared to all other functional and anatomical imaging modalities and may be the preferred functional imaging modality to evaluate SDHD -related PPGLs. Furthermore, owing to the 68 Ga-DOTATATE avidity of PPGLs in these patients, cold somatostatin analog and/or peptide receptor radionuclide therapy ( 177 Lu/ 90 Y/ 225 Ac/ 212 Pb-DOTATATE) can be considered as one of the therapeutic options. *Clinical Relevance/Application: 68 Ga-DOTATATE avidity and superiority allows for not only diagnostic evaluation but therapy as well realizing its true “theranostics” application in SDHD -related PPGLs.

Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4 T cells >43.90% in situ was associated with reduced recurrence-free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression, and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.

These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.

The reason for TRD of SDHB and SDHD PVs is unknown but we hypothesize a survival advantage selected during early embryogenesis. The existence of TRD for SDHB and SDHD has implications for reproductive counselling, and further research into the heterozygote state.

Further verifying the gene and protein expression levels of SDHs, we found that the tissues were consistent with the bioinformatics analysis. Our study analyzed the expression and prognostic value of SDHs in COAD, explored the pathway mechanisms involved, and the immune cell correlations, indicating that SDHs might be biomarkers for COAD patients.

Abdominal nonfunctional PGLs are associated with SDHB mutation, and SDHB staining should be performed as a screening.

This is the first study to report a lower likelihood of corporal tumors for patients with head and neck paragangliomas with SDH mutations positive for P81L. Larger studies are needed to determine if head and neck paraganglioma patients with P81L qualify for less intensive imaging surveillance to screen for second primary paragangliomas outside the head and neck.