Somatic-only SDHD variant with tumor-specific loss of heterozygosity in metastatic carotid body tumor: a case report with review of literature
Abstract
Carotid body tumors (CBTs) are rare paragangliomas in which genetic predisposition, particularly pathogenic variants in succinate dehydrogenase (SDHx) genes, plays an important role in tumorigenesis. Previous genetic studies of CBTs have primarily focused on germline SDHx variants, whereas somatic alterations remain poorly characterized. Among SDHx genes, SDHB variants are known to be associated with a higher metastatic risk, while SDHD variants are generally linked to a lower metastatic rate. We report the case of a 41-year-old man who presented with a painless right-sided neck mass. Imaging studies demonstrated a hypervascular tumor located at the carotid bifurcation with circumferential encasement of the carotid artery. During surgery, the tumor was classified as a Shamblin type III CBT, and complete surgical resection with vascular reconstruction was performed. Histopathological examination confirmed paraganglioma with metastasis to a single cervical lymph node. Germline genetic testing did not reveal any pathogenic variants. However, comprehensive tumor genomic profiling identified a somatic SDHD c.304C>G (p.His102Asp) variant accompanied by tumor-specific loss of heterozygosity (LOH) and copy-number loss at the SDHD locus, findings compatible with biallelic SDHD inactivation. The patient remained free of recurrence during follow-up. To our knowledge, this represents the first reported case of metastatic CBT harboring a somatic-only SDHD variant with tumor-specific LOH. This case suggests that reliance on germline testing alone may underestimate the molecular drivers of CBT and highlights the potential clinical value of tumor-based genomic profiling for risk stratification and prognostic assessment.
Related
- PO012 | RECURRENT CENTRAL RETINAL VEIN THROMBOSIS IN A PATIENT WITH MILD HEMOPHILIA A AND HETEROZYGOSITY FOR THE PROTHROMBIN G20210A VARIANT
- Cell-type-resolved somatic variant discovery from bulk long-read sequencing
- Case Report: Coexpression of somatic EGFR, BRCA1, and BRCA2 mutations in metastatic non-small cell lung cancer
- Primary renal Ewing sarcoma with extensive metastatic disease at diagnosis: A case report and literature review
- CFTR variant-associated hereditary pancreatitis complicated by diabetes mellitus: a case report and literature review
BibTeX
@article{kasahara2026somaticonly,
title = {{Somatic-only SDHD variant with tumor-specific loss of heterozygosity in metastatic carotid body tumor: a case report with review of literature}},
author = {Ken Kasahara and Keisuke Yoshihama and Katsuyoshi Idei and Yuki Matsui and Takuya Mikoshiba and Takeyuki Kono and Mariko Sekimizu and Kohei Nakamura and Ippei Fukada and Takayuki Ueno and Katsuhiro Mizutani and Takenori Akiyama and Hideaki Obara and Hiroyuki Ozawa},
journal = {Endocrine Journal},
year = {2026},
month = sep,
doi = {10.1507/endocrj.ej26-0224},
url = {https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0224/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Somatic-only SDHD variant with tumor-specific loss of heterozygosity in metastatic carotid body tumor: a case report with review of literature
AU - Ken Kasahara
AU - Keisuke Yoshihama
AU - Katsuyoshi Idei
AU - Yuki Matsui
AU - Takuya Mikoshiba
AU - Takeyuki Kono
AU - Mariko Sekimizu
AU - Kohei Nakamura
AU - Ippei Fukada
AU - Takayuki Ueno
AU - Katsuhiro Mizutani
AU - Takenori Akiyama
AU - Hideaki Obara
AU - Hiroyuki Ozawa
PY - 2026
DA - 2026/09/11
JO - Endocrine Journal
DO - 10.1507/endocrj.ej26-0224
UR - https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0224/_article
AB - Carotid body tumors (CBTs) are rare paragangliomas in which genetic predisposition, particularly pathogenic variants in succinate dehydrogenase (SDHx) genes, plays an important role in tumorigenesis. Previous genetic studies of CBTs have primarily focused on germline SDHx variants, whereas somatic alterations remain poorly characterized. Among SDHx genes, SDHB variants are known to be associated with a higher metastatic risk, while SDHD variants are generally linked to a lower metastatic rate. We report the case of a 41-year-old man who presented with a painless right-sided neck mass. Imaging studies demonstrated a hypervascular tumor located at the carotid bifurcation with circumferential encasement of the carotid artery. During surgery, the tumor was classified as a Shamblin type III CBT, and complete surgical resection with vascular reconstruction was performed. Histopathological examination confirmed paraganglioma with metastasis to a single cervical lymph node. Germline genetic testing did not reveal any pathogenic variants. However, comprehensive tumor genomic profiling identified a somatic SDHD c.304C>G (p.His102Asp) variant accompanied by tumor-specific loss of heterozygosity (LOH) and copy-number loss at the SDHD locus, findings compatible with biallelic SDHD inactivation. The patient remained free of recurrence during follow-up. To our knowledge, this represents the first reported case of metastatic CBT harboring a somatic-only SDHD variant with tumor-specific LOH. This case suggests that reliance on germline testing alone may underestimate the molecular drivers of CBT and highlights the potential clinical value of tumor-based genomic profiling for risk stratification and prognostic assessment.
SN - 1348-4540
SN - 0918-8959
ER -