Abstract
Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors often associated with mutations in SDHx genes. The immunohistochemistry of succinate dehydrogenase (SDH) subunits has been considered a useful instrument for the prediction of SDHx mutations in paragangliomas/pheochromocytomas. We compared the mutation status of SDHx genes with the immunohistochemical (IHC) staining of SDH subunits in CPGLs. To identify pathogenic/likely pathogenic variants in SDHx genes, exome sequencing data analysis among 42 CPGL patients was performed. IHC staining of SDH subunits was carried out for all CPGLs studied. We encountered SDHx variants in 38% (16/42) of the cases in SDHx genes. IHC showed negative (5/15) or weak diffuse (10/15) SDHB staining in most tumors with variants in any of SDHx (94%, 15/16). In SDHA-mutated CPGL, SDHA expression was completely absent and weak diffuse SDHB staining was detected. Positive immunoreactivity for all SDH subunits was found in one case with a variant in SDHD. Notably, CPGL samples without variants in SDHx also demonstrated negative (2/11) or weak diffuse (9/11) SDHB staining (42%, 11/26). Obtained results indicate that SDH immunohistochemistry does not fully reflect the presence of mutations in the genes; diagnostic effectiveness of this method was 71%. However, given the high sensitivity of SDHB immunohistochemistry, it could be used for initial identifications of patients potentially carrying SDHx mutations for recommendation of genetic testing.
Highlights
Carotid paraganglioma (CPGL) is a rare neuroendocrine tumor that arises from the carotid body
We evaluated the possibility of SDHA/SDHB immunostaining use to predict variants in any of the SDHx genes in CPGLs
succinate dehydrogenase (SDH) has a critical role in mitochondrial metabolism; disruption of the SDH complex leads to abnormal accumulation of succinate in the cytosol, reprogramming of the energy metabolism, increased ROS production, stabilization of hypoxia-inducible factors (HIFs), and altered gene expression [40]
Summary
Carotid paraganglioma (CPGL) is a rare neuroendocrine tumor that arises from the carotid body. CPGL represents more than half of all head and neck (HN) paragangliomas (PGLs) [1]. According to the WHO Classification of Head and Neck Tumors 2017, PGLs were reclassified from indeterminate to malignant tumors with variable potential of metastasis [2]. As CPGL associates with the carotid arteries and adjacent nerves, its resection is challenging. Potential surgical complications include stroke, the possibility of cerebrovascular accident, and neural dysfunction, which can manifest clinically as hoarseness, vocal change, aspiration, dysphagia, dysarthria, facial asymmetry, or shoulder weakness [3]. Radiotherapy and chemotherapy can be used for unresectable and metastatic tumors, as well as for bilateral CPGLs; surgery remains the primary form of treatment [4,5,6]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.