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Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases

RATIONALE: Paragangliomas (PGLs) are rare neuroendocrine tumors that are strongly influenced by genetics, and succinate dehydrogenase-deficient PGLs appear to constitute one of the most important categories. Interestingly, somatic PGLs only possess genomic alterations involving the SDHB and SDHD sub...

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Autores principales: Huang, Yen-Chun, Chang, Hsiao-Huang, Chen, Ming-Huang, Huang, Kuo-Hung, Li, Anna Fen-Yau, Lin, Chien-Hsing, Shyr, Yi-Ming, Fang, Wen-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544306/
https://www.ncbi.nlm.nih.gov/pubmed/33031286
http://dx.doi.org/10.1097/MD.0000000000022497
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author Huang, Yen-Chun
Chang, Hsiao-Huang
Chen, Ming-Huang
Huang, Kuo-Hung
Li, Anna Fen-Yau
Lin, Chien-Hsing
Shyr, Yi-Ming
Fang, Wen-Liang
author_facet Huang, Yen-Chun
Chang, Hsiao-Huang
Chen, Ming-Huang
Huang, Kuo-Hung
Li, Anna Fen-Yau
Lin, Chien-Hsing
Shyr, Yi-Ming
Fang, Wen-Liang
author_sort Huang, Yen-Chun
collection PubMed
description RATIONALE: Paragangliomas (PGLs) are rare neuroendocrine tumors that are strongly influenced by genetics, and succinate dehydrogenase-deficient PGLs appear to constitute one of the most important categories. Interestingly, somatic PGLs only possess genomic alterations involving the SDHB and SDHD subunits, and no SDHA alterations have been described. Here, we are presenting the clinical and genetic analyses of 2 cases with the first somatic SDHA variant identified in PGLs. PATIENT CONCERNS: Here, we reported 2 family members with the diagnosis of PGL. Patient 1 is a 55-year-old woman with a functionally perigastric PGL that co-occurred with a gastric gastrointestinal stromal tumor (GIST), and patient 2 is a 43-year-old woman with a nonfunctionally pericardial PGL, who was the younger sister of the first patient. DIAGNOSES: Imaging surveys of the 2 cases depicted the presence of a perigastric and a pericardial mass, respectively. A diagnosis of paragangliomas was established by immunohistochemistry (IHC). INTERVENTIONS: Both patients underwent single-stage resection of the lesion after preoperative oral α-adrenoceptor therapy for 2 weeks. We later performed comprehensive genomic profiling on the tumor samples, including PGL and GIST from patient 1 and PGL from patient 2, and searched for novel actionable mutations, including in all succinate dehydrogenase subunits, as the IHC results were negative for SDHB. OUTCOMES: Both patients had an uneventful recovery after surgery and the sequencing showed a novel somatic variant in the SDHA gene on chromosome 5q11 (c.1945_1946delTT). Regular follow-up with biochemical testing and image studies showed no evidence of recurrence after a year for patient 1 and 6 years for patient 2. LESSONS: PGLs often lead to considerable diagnostic difficulty due to their multiple anatomical locations and variable symptoms, as presented by our cases. The comprehensive use of images and plasma/urine catecholamine measurement can aid the diagnosis of PGLs. In addition, our findings also demonstrate the usefulness and importance of genetic analysis of SDHA mutations in patients exhibiting SDHB IHC-negative PGL. Additional studies utilizing comprehensive genomic profiling are needed to identify the group of PGLs harboring this SDHA genomic alteration.
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spelling pubmed-75443062020-10-30 Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases Huang, Yen-Chun Chang, Hsiao-Huang Chen, Ming-Huang Huang, Kuo-Hung Li, Anna Fen-Yau Lin, Chien-Hsing Shyr, Yi-Ming Fang, Wen-Liang Medicine (Baltimore) 5700 RATIONALE: Paragangliomas (PGLs) are rare neuroendocrine tumors that are strongly influenced by genetics, and succinate dehydrogenase-deficient PGLs appear to constitute one of the most important categories. Interestingly, somatic PGLs only possess genomic alterations involving the SDHB and SDHD subunits, and no SDHA alterations have been described. Here, we are presenting the clinical and genetic analyses of 2 cases with the first somatic SDHA variant identified in PGLs. PATIENT CONCERNS: Here, we reported 2 family members with the diagnosis of PGL. Patient 1 is a 55-year-old woman with a functionally perigastric PGL that co-occurred with a gastric gastrointestinal stromal tumor (GIST), and patient 2 is a 43-year-old woman with a nonfunctionally pericardial PGL, who was the younger sister of the first patient. DIAGNOSES: Imaging surveys of the 2 cases depicted the presence of a perigastric and a pericardial mass, respectively. A diagnosis of paragangliomas was established by immunohistochemistry (IHC). INTERVENTIONS: Both patients underwent single-stage resection of the lesion after preoperative oral α-adrenoceptor therapy for 2 weeks. We later performed comprehensive genomic profiling on the tumor samples, including PGL and GIST from patient 1 and PGL from patient 2, and searched for novel actionable mutations, including in all succinate dehydrogenase subunits, as the IHC results were negative for SDHB. OUTCOMES: Both patients had an uneventful recovery after surgery and the sequencing showed a novel somatic variant in the SDHA gene on chromosome 5q11 (c.1945_1946delTT). Regular follow-up with biochemical testing and image studies showed no evidence of recurrence after a year for patient 1 and 6 years for patient 2. LESSONS: PGLs often lead to considerable diagnostic difficulty due to their multiple anatomical locations and variable symptoms, as presented by our cases. The comprehensive use of images and plasma/urine catecholamine measurement can aid the diagnosis of PGLs. In addition, our findings also demonstrate the usefulness and importance of genetic analysis of SDHA mutations in patients exhibiting SDHB IHC-negative PGL. Additional studies utilizing comprehensive genomic profiling are needed to identify the group of PGLs harboring this SDHA genomic alteration. Lippincott Williams & Wilkins 2020-10-09 /pmc/articles/PMC7544306/ /pubmed/33031286 http://dx.doi.org/10.1097/MD.0000000000022497 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/)
spellingShingle 5700
Huang, Yen-Chun
Chang, Hsiao-Huang
Chen, Ming-Huang
Huang, Kuo-Hung
Li, Anna Fen-Yau
Lin, Chien-Hsing
Shyr, Yi-Ming
Fang, Wen-Liang
Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases
title Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases
title_full Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases
title_fullStr Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases
title_full_unstemmed Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases
title_short Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases
title_sort somatic sdha mutations in paragangliomas in siblings: case report of 2 cases
topic 5700
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544306/
https://www.ncbi.nlm.nih.gov/pubmed/33031286
http://dx.doi.org/10.1097/MD.0000000000022497
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