Long-term prognosis of patients with pediatric pheochromocytoma

Abstract

A third of patients with paraganglial tumors, pheochromocytoma, and paraganglioma, carry germline mutations in one of the susceptibility genes, RET, VHL, NF1, SDHAF2, SDHA, SDHB, SDHC, SDHD, TMEM127, and MAX. Despite increasing importance, data for long-term prognosis are scarce in pediatric presentations. The European-American-PheochromocytomaParaganglioma-Registry, with a total of 2001 patients with confirmed paraganglial tumors, was the platform for this study. Molecular genetic and phenotypic classification and assessment of gene-specific long-term outcome with second and/or malignant paraganglial tumors and life expectancy were performed in patients diagnosed at !18 years. Of 177 eligible registrants, 80% had mutations, 49% VHL, 15% SDHB, 10% SDHD, 4% NF1, and one patient each in RET, SDHA, and SDHC. A second primary paraganglial tumor developed in

Genotype-phenotype correlation in paediatric pheochromocytoma and paraganglioma: a single centre experience from India

“…In our paediatric cohort, bilateral PCC and extra-adrenal PGL were seen in 23.33% and 30% respectively. Similar high rates of multiple (25%-55%), bilateral PCC (20%-34%) and extra-adrenal tumours (18%-54%) have been reported previously in children [11,12,[20][21][22][23][24][25] Frequency of germline mutations in our paediatric PCC/PGL patients was significantly higher than the adult counterparts. Most of the previous studies have reported similar findings with higher frequency of germline mutations in younger PCC/PGL patients [7][8][9][10].…”

“…The phenotypic findings of our paediatric cohort are similar to the larger series of paediatric PCC/PGL patients described in literature [11,12,[20][21][22][23][24][25]. In our paediatric cohort, bilateral PCC and extra-adrenal PGL were seen in 23.33% and 30% respectively.…”

“…Most data available on the genotype of paediatric PCC/ PGL is derived from the European-American-Pheochromocytoma-Paraganglioma-Registry (EAPPR, n = 171) which reports germline mutations in 81% of the cases whereas studies from Spain (n = 36) and the UK (n = 7) report genetic yields of 69% and 100%, respectively [11,12,22]. A study from Germany reported germline mutations in 59% of the children even in AS cases [10].…”

“…Biochemical phenotype, location and number of PCC/PGL, choice of nuclear imaging, mode of treatment, recurrence of PCC/PGL, potential for malignancy and most importantly, association with other tumours are determined by the underlying germline mutations [7][8][9][10][11][12][13][14][15][16]. The only large study available on genotype-phenotype correlation in children is from a registry including patients from various European-American countries and no such data in Indian paediatric PCC/PGL patients is available [12]. In a recent multicentric study (n = 150 among which 120 were from our centre), we reported genotype-phenotype correlation in Indian PCC/PGL patients [17].…”

Genotype–phenotype Correlation in Children with Pheochromocytoma and Paraganglioma

“…The heritability is highest (up to 80%) for PPGL diagnosed during childhood. 4 The PPGLs of various genetic backgrounds can be segregated by their transcription profile into two main clusters (cluster 1 and 2) that have helped to guide the wjoes discovery of novel susceptibility genes. Cluster 1 is enriched with genes that are associated with the hypoxic response, and cluster 2 contains tumors that activate kinase signaling and protein translation.…”