Clinical, genetic, radiological characteristics and management of mediastinal paragangliomas: a literature review and case series.

in Endocrine-related cancer by Mark Quinn, Yasmine Kemkem, Gemma White, Phil Touska, Dimitra Christodoulou, Audrey Jacques, Louise Breen, Barbara McGowan, Mamta Joshi, Fahim Ul Hassan, Karen Harrison-Phipps, Johnathan Hubbard, Rupert Obholzer, Louise Izatt, Paul Carroll, Anand Velusamy

TLDR

  • A literature review and analysis of 18 cases of mediastinal paragangliomas found that most cases were associated with a pathogenic germline variant and that (68Ga)-DOTATATE PET CT is highly effective in detecting disease.

Abstract

Paragangliomas (PGLs) are neuroendocrine tumours (NETs) that arise from neural crest derived cells. Up to 40% of cases occur due to the presence of a pathogenic germline variant (PGV) in a known gene. Mediastinal PGLs are rare but are being diagnosed with increasing frequency. Treatment generally involves surgery but is complicated in mediastinal PGLs due to their anatomy. Here we will perform a literature review and discuss our experience with 18 such cases. Cases were identified via the Guy's and St Thomas' NHS Foundation Trust NET multidisciplinary team database. Tumours ranged in size from 0.6cx0.6cm to 6.8cmx4.9cm. 72.2% were associated with a PGV of SDHB or SDHD. 22.2% developed metastatic disease but it was only possible to attribute 50% of these to a mediastinal primary. (68Ga)-DOTATATE PET CT demonstrated 100% sensitivity. Literature review identified 233 cases. A PGV was reported in 81% of cases with metastatic disease in approximately 39.2%. It was not possible to confirm that all cases of metastatic disease were secondary to a mediastinal primary. Our experience confirms the high rate of mediastinal PGLs arising in the presence of a PGV. The lower rate of metastatic disease in our cohort (11.1%) likely represents earlier diagnosis thanks to the application of screening protocols and the increased sensitivity of (68Ga)-DOTATATE PET CT. With this increased sensitivity we have diagnosed small mediastinal PGLs which were not evident on alternative imaging modalities. In the absence of growth or catecholamine secretion, the need to intervene on these is unclear.

Overview

  • The study aims to investigate the characteristics and management of mediastinal paragangliomas (PGLs), a rare type of neuroendocrine tumor.
  • The study includes a literature review and analysis of 18 cases of mediastinal PGLs diagnosed at Guy's and St Thomas' NHS Foundation Trust.
  • The study examines the role of pathogenic germline variants (PGVs) in the development of mediastinal PGLs and the effectiveness of (68Ga)-DOTATATE PET CT in detecting disease.

Comparative Analysis & Findings

  • The study found that 72.2% of mediastinal PGLs were associated with a PGV in the SDHB or SDHD genes, and 22.2% developed metastatic disease.
  • The study's findings confirm the high rate of mediastinal PGLs arising in the presence of a PGV, and the lower rate of metastatic disease in the cohort is likely due to earlier diagnosis and increased sensitivity of (68Ga)-DOTATATE PET CT.
  • The study highlights the importance of (68Ga)-DOTATATE PET CT in detecting mediastinal PGLs, with 100% sensitivity in detecting disease.

Implications and Future Directions

  • The study's findings have implications for the management of mediastinal PGLs, with earlier diagnosis and intervention possible thanks to the increased sensitivity of (68Ga)-DOTATATE PET CT.
  • Further research is needed to determine the optimal approach to managing small mediastinal PGLs that do not exhibit growth or catecholamine secretion, and to investigate the role of PGVs in the development of mediastinal PGLs.
  • The study's findings highlight the importance of multidisciplinary teams and the use of PET CT in the diagnosis and management of PGLs.
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