Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma

• Published in: Current issues in molecular biology Vol. 43; no. 3; pp. 2266 - 2275
• Main Authors: Pavlov, Vladislav, Snezhkina, Anastasiya, Kalinin, Dmitry, Golovyuk, Alexander, Kobelyatskaya, Anastasiya, Bakhtogarimov, Ildar, Volchenko, Nadezhda, Krasnov, George, Kudryavtseva, Anna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 17.12.2021; MDPI AG
• Subjects: Adult; Biomarkers, Tumor; Carotid Body - pathology; carotid paraganglioma; Case Report; Disease Progression; DNA Mutational Analysis; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Genetic Variation; Humans; Immunohistochemistry; metastasis; Mutation; Paraganglioma - diagnosis; Paraganglioma - genetics; Paraganglioma - therapy; recurrent tumor; SDHB; Succinate Dehydrogenase - genetics; Succinate Dehydrogenase - metabolism; TERT; whole-exome sequencing; recurrent tumor; TERT; metastasis; carotid paraganglioma; case report; SDHB; whole-exome sequencing
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb43030159

Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson's "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline mutation for metastatic CPGLs, as well as the potential prognostic value of the promoter mutation.