Table 1

Succinate-deficient tumours associated with SDHA PGV (SDHA-associated/on-target tumours)

Tumour typeStrength of association
Wild-type GIST+++
Renal cancer†+
Pituitary adenoma‡Rare
  • *For PPGL it is assumed that PGV in other PPGL predisposition genes have been excluded. The National Test Directory now indicates that this testing should include FH, MAX, MEN1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127 and VHL including analysis for CNVs (National Test Directory indication R223 Inherited phaeochromocytoma and PGL.17

  • †For renal cancer, histopathological examination for characteristic features and immunohistochemistry can be helpful in assessing dSDH status.26 SDHB expression is lost in most dSDH tumours with a germline SDHA, SDHB, SDHC or SDHD pathogenic variant. Limitation to the utility of SDHB IHC include interobserver variation, false-negative results (presence of SDHB on IHC where a germline variant exists may be more common for SDHA-mutated tumours) and equivocal SDHB staining patterns in the presence of germline or somatic VHL inactivation.11 SDHA IHC can reveal loss of SDHA expression in SDHA-mutated tumours but is less widely available than SDHB IHC.

  • ‡For neuroblastoma and pituitary adenoma, immunohistochemical evidence of SDH deficiency should be sought and other causes excluded before an SDHA variant is considered causal.

  • GIST, gastrointestinal stromal tumour; IHC, immunohistochemistry; PGL, paraganglioma; PGV, pathogenic germline variant; PPGL, phaeochromocytoma and paraganglioma.