Clinicopathological, immunophenotypic and genetic studies of mediastinal paragangliomas†

Ying Han R. Hsu, Jorge Torres-Mora, Benjamin R. Kipp, William R. Sukov, Sarah M. Jenkins, Jesse S. Voss, Emily G. Barr Fritcher, Hartzell V. Schaff, Stephen D. Cassivi, Anja C. Roden

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS: Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS: Twenty-four patients with mediastinal paraganglioma (7 men, 29.2%) had a median age of 45.5 years (19.8-72.2). Twenty-one (87.5%) paragangliomas were completely resected. Six (of 24, 25.0%) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8%) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26%) patients in 10% (n = 2) and 1% (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4%) cases. ATRX expression was lost in 11 (of 23, 47.8%) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8-14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS: Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.

Original languageEnglish (US)
Pages (from-to)867-875
Number of pages9
JournalEuropean journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
Volume56
Issue number5
DOIs
StatePublished - Nov 1 2019

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Paraganglioma
Mutation
Succinate Dehydrogenase
Multiple Endocrine Neoplasia
Germ-Line Mutation
Mediastinum
Neoplasms
Immunohistochemistry
Neoplasm Metastasis
Ligands
Morbidity
Mortality

Keywords

  • Mediastinum
  • Paraganglioma
  • Succinate dehydrogenase mutation

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Clinicopathological, immunophenotypic and genetic studies of mediastinal paragangliomas†. / Hsu, Ying Han R.; Torres-Mora, Jorge; Kipp, Benjamin R.; Sukov, William R.; Jenkins, Sarah M.; Voss, Jesse S.; Barr Fritcher, Emily G.; Schaff, Hartzell V.; Cassivi, Stephen D.; Roden, Anja C.

In: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Vol. 56, No. 5, 01.11.2019, p. 867-875.

Research output: Contribution to journalArticle

Hsu, Ying Han R. ; Torres-Mora, Jorge ; Kipp, Benjamin R. ; Sukov, William R. ; Jenkins, Sarah M. ; Voss, Jesse S. ; Barr Fritcher, Emily G. ; Schaff, Hartzell V. ; Cassivi, Stephen D. ; Roden, Anja C. / Clinicopathological, immunophenotypic and genetic studies of mediastinal paragangliomas†. In: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2019 ; Vol. 56, No. 5. pp. 867-875.
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abstract = "OBJECTIVES: Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS: Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS: Twenty-four patients with mediastinal paraganglioma (7 men, 29.2{\%}) had a median age of 45.5 years (19.8-72.2). Twenty-one (87.5{\%}) paragangliomas were completely resected. Six (of 24, 25.0{\%}) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8{\%}) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26{\%}) patients in 10{\%} (n = 2) and 1{\%} (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4{\%}) cases. ATRX expression was lost in 11 (of 23, 47.8{\%}) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8-14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS: Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.",
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T1 - Clinicopathological, immunophenotypic and genetic studies of mediastinal paragangliomas†

AU - Hsu, Ying Han R.

AU - Torres-Mora, Jorge

AU - Kipp, Benjamin R.

AU - Sukov, William R.

AU - Jenkins, Sarah M.

AU - Voss, Jesse S.

AU - Barr Fritcher, Emily G.

AU - Schaff, Hartzell V.

AU - Cassivi, Stephen D.

AU - Roden, Anja C.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - OBJECTIVES: Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS: Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS: Twenty-four patients with mediastinal paraganglioma (7 men, 29.2%) had a median age of 45.5 years (19.8-72.2). Twenty-one (87.5%) paragangliomas were completely resected. Six (of 24, 25.0%) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8%) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26%) patients in 10% (n = 2) and 1% (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4%) cases. ATRX expression was lost in 11 (of 23, 47.8%) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8-14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS: Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.

AB - OBJECTIVES: Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS: Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS: Twenty-four patients with mediastinal paraganglioma (7 men, 29.2%) had a median age of 45.5 years (19.8-72.2). Twenty-one (87.5%) paragangliomas were completely resected. Six (of 24, 25.0%) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8%) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26%) patients in 10% (n = 2) and 1% (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4%) cases. ATRX expression was lost in 11 (of 23, 47.8%) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8-14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS: Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.

KW - Mediastinum

KW - Paraganglioma

KW - Succinate dehydrogenase mutation

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