Pheochromocytomas and paragangliomas in children: Data from the Italian Cooperative Study (TREP)

Virgone, Calogero; Andreetta, Marina; Avanzini, Stefano; Chiaravalli, Stefano; Pasquale, Deborah De; Crocoli, Alessandro; Inserra, Alessandro; D’Angelo, Paolo; Alaggio, Rita; Opocher, Giuseppe; Cecchetto, Giovanni; Ferrari, Andrea; Bisogno, Gianni; Dall’Igna, Patrizia

doi:10.1002/pbc.28332

Cited by 16 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is confirmed by our data. In the Tumori Rari in Etá Pediatrica (TREP) study, however, completeness of surgery showed no statistically significant differences in EFS 23 …”

Section: Discussionmentioning

confidence: 91%

“…In the Tumori Rari in Etá Pediatrica (TREP) study, however, completeness of surgery showed no statistically significant differences in EFS. 23 When applying the cluster approach [13][14][15]24 to our patients, most patients (96%) with known mutational context presented with PPGLs of the pseudohypoxia group (either VHL/EPAS1-or TCA cycle-related), whereas 50-60% of PPGLs in adults belong to the kinase signaling cluster. 15 A high prevalence of cluster 1 mutations in children was previously reported by Pamporaki et al 3 This has important implications for diagnosis, treatment, and surveillance in children as pseudohypoxic PPGLs are associated with a higher risk of subsequent PPGL events and metastatic disease.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Pseudohypoxic pheochromocytomas and paragangliomas dominate in children

Redlich

Pamporaki

Lessel

et al. 2021

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Objective: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that are associated with cancer predisposition syndromes in up to 80% of affected children. PPGLs can be divided into molecularly defined groups with comparable pathogenesis and biology: (1) pseudohypoxic, (2) kinase signaling, and (3) Wntaltered. Methods:We report the data of children and adolescents diagnosed with PPGL who have been registered with the German GPOH-MET registry since 1997.Results: By December 2019, a total of 88 patients with PPGL were reported.Pheochromocytoma occurred in 56%, paraganglioma in 35%, and synchronous PPGLs in 9.1%. A total of 16% of patients presented with lymph node (5.7%) and distant metastases (10%). Median follow-up was 4.2 years (range 0-17.1). Overall and disease-free survival (DFS) were 98.6% and 54.0%, respectively. Local relapses, metastases, and subsequent PPGLs occurred in 11%, 4.5%, and 15% of patients. Germline mutations were detected in 83% of patients (51% in VHL, 21% in SDHB, 7.8% in SDHD, and one patient each in RET and NF1). One patient was diagnosed with Pacak-Zhuang syndrome. A total of 96% of patients presented with PPGL of the pseudohypoxic subgroup (34% TCA cycle-related, 66% VHL/EPAS1-related). In multivariate analyses, extent of tumor resection was a significant prognostic factor for DFS. Conclusions:Most pediatric PPGLs belong to the pseudohypoxia subgroup, which is associated with a high risk of subsequent PPGL events and metastatic disease. Comprehensive molecular profiling of children and adolescents with newly diagnosedPPGLs will open new avenues for personalized diagnosis, treatment, and surveillance.

show abstract

“…This is confirmed by our data. In the Tumori Rari in Etá Pediatrica (TREP) study, however, completeness of surgery showed no statistically significant differences in EFS 23 …”

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 94%

Pseudohypoxic pheochromocytomas and paragangliomas dominate in children

Redlich

Pamporaki

Lessel

et al. 2021

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

“…In most cases, PPGLs are sporadic in pediatric population but they may also be part of more complex hereditary syndrome. In one study constituting of 50 patients with PPGL, 56% had pheochromocytoma and 44% had paraganglioma [92]. Complication of massive catecholamine secretion can include hypertensive crisis, cardiomyopathy, pancreatitis, seizure, stroke and even multiorgan failure and death [91].…”

Section: Ppgls In Children and Cardiovascular Complicationsmentioning

confidence: 99%

Cardiovascular Manifestations and Complications of Pheochromocytomas and Paragangliomas

Y‐Hassan

Falhammar

2020

JCM

View full text Add to dashboard Cite

Pheochromocytomas and paragangliomas (PPGLs) are rare neuro-endocrine tumors. The catecholamine surge causes paroxysmal or chronic secondary hypertension. PPGLs may present as hypertensive- or PPGL-crisis with severe life-threatening cardiac and cerebrovascular complications. PPGLs-induced cardiac manifestations have been reported with diagnoses as PPGLs-induced electrocardiogram (ECG) changes “mimicking acute myocardial infarction”, arrhythmias, myocarditis, acute coronary syndrome, dilated cardiomyopathy, and lately as takotsubo syndrome. Critical analysis of these reports reveals that most of these cardiac manifestations have certain features in common. They have a dramatic clinical presentation and are reversible if the disease is treated with appropriate medical therapy and surgical resection of the PPGL tumor. They may have the same repolarization ECG changes irrespective of the clinical cardiac diagnosis, usually associated with mild to moderate elevations of myocardial biomarkers as troponins and normal coronary arteries. The histopathological findings are usually focal or multifocal in the form hypercontracted sarcomeres and contraction band necrosis (myofibrillar degeneration) with subsequent secondary mononuclear cell infiltration. Evidences argue the PPGL caused surge of catecholamines triggers hyperactivation of the sympathetic nervous system with cardiac sympathetic nerve terminal disruption with norepinephrine spillover causing the cardiac complications. A comprehensive review of various reported cardiovascular manifestations and complications of PPGLs are presented.

show abstract

“…Because extra‐appendicular NETs may be part of a syndrome harbored by a germline mutation, even if less frequently than other neoplasms, 30 the diagnostic workup in children should include the genetic counseling, especially considering their rarity and the need of more precise epidemiologic data 31,32 …”

Section: Discussionmentioning

confidence: 99%

Extra‐appendicular neuroendocrine tumors: A report from the TREP project (2000‐2020)

Virgone

Ferrari

Chiaravalli

et al. 2021

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Background Extra‐appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking. Patients and Methods Patients with a diagnosis of extra‐appendicular NET registered on the Tumori Rari in Età Pediatrica ‐ Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients’ presentation, tumor features, treatment, and outcome were reviewed. Results Twenty‐seven patients with extra‐appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3‐year event‐free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5‐95% vs 33% 95% CI 5‐68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3‐year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow‐up, and one is alive with disease; five died, and five were lost to follow‐up. Conclusions Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease.

show abstract

Pheochromocytomas and paragangliomas in children: Data from the Italian Cooperative Study (TREP)

Cited by 16 publications

References 39 publications

Pseudohypoxic pheochromocytomas and paragangliomas dominate in children

Pseudohypoxic pheochromocytomas and paragangliomas dominate in children

Cardiovascular Manifestations and Complications of Pheochromocytomas and Paragangliomas

Extra‐appendicular neuroendocrine tumors: A report from the TREP project (2000‐2020)

Contact Info

Product

Resources

About