Pheochromocytoma-paraganglioma due to germline SDHB mutation in children are common

Abstract

Introduction Pheochromoctyoma-paraganglioma syndrome (PHEO-PGL) due to SDH germline mutation is easily identified by loss of SDHB by immunohistochemistry. Pham et al . showed a 16% (5/30) prevalence of SDH mutation in a retrospective review of the Mayo clinic involving thirty patients (1975-2005). Aim Ascertain the prevalence of PHEO-PGL due to SDHB germline mutations in a local paediatric population by using IHC. Method 14 patients were ascertained from the pathology database with pheochromocytoma and or paraganglioma, SDHA and SDHB IHC was performed on FFPE blocks. Results Three patients had SDHB germline mutations, three had VHL mutation and eight had no genetic studies performed. Of the 14 patients, four had multiple tumours and of these, three showed loss of SDHB staining. All three patients with loss of SDHB by IHC had genetically confirmed germline mutations of SDHB. A novel observation was that three patients with VHL syndrome showed a characteristic weak granular cytoplasmic staining, a pattern distinct from SDHB loss and normal controls. Discussion (1) We found the prevalence of SDH germline mutations was 28% in children with PHEO-PGL, which is higher than historically identified. (2) In patients with multiple tumours the prevalence was 75% (3/4 patients). (3) We found a distinctive weak granular positive cytoplasmic SDHB staining pattern in tumours with VHL germline mutations.