PMID- 33682326
OWN - NLM
STAT- Publisher
LR  - 20210308
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Linking)
DP  - 2021 Mar 7
TI  - Pseudohypoxic pheochromocytomas and paragangliomas dominate in children.
PG  - e28981
LID - 10.1002/pbc.28981 [doi]
AB  - 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) Wnt-altered. 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 
      diagnosed PPGLs will open new avenues for personalized diagnosis, treatment, and 
      surveillance.
CI  - © 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.
FAU - Redlich, Antje
AU  - Redlich A
AUID- ORCID: 0000-0002-1732-1869
AD  - Pediatric Oncology Department, Otto von Guericke University Children's Hospital, 
      Magdeburg, Germany.
FAU - Pamporaki, Christina
AU  - Pamporaki C
AD  - Department of Medicine III, University Hospital Carl Gustav Carus, Technische 
      Universität Dresden, Dresden, Germany.
FAU - Lessel, Lienhard
AU  - Lessel L
AD  - Pediatric Oncology Department, Otto von Guericke University Children's Hospital, 
      Magdeburg, Germany.
FAU - Frühwald, Michael C
AU  - Frühwald MC
AD  - Paediatric and Adolescent Medicine, University Medical Center, Augsburg, Germany.
FAU - Vorwerk, Peter
AU  - Vorwerk P
AD  - Pediatric Oncology Department, Otto von Guericke University Children's Hospital, 
      Magdeburg, Germany.
FAU - Kuhlen, Michaela
AU  - Kuhlen M
AUID- ORCID: 0000-0003-4577-0503
AD  - Paediatric and Adolescent Medicine, University Medical Center, Augsburg, Germany.
LA  - eng
GR  - Deutsche Kinderkrebsstiftung/
PT  - Journal Article
DEP - 20210307
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
SB  - IM
OTO - NOTNLM
OT  - children
OT  - germline mutations
OT  - paraganglioma
OT  - pheochromocytoma
OT  - pseudohypoxic
EDAT- 2021/03/09 06:00
MHDA- 2021/03/09 06:00
CRDT- 2021/03/08 06:03
PHST- 2020/12/12 00:00 [received]
PHST- 2021/02/09 00:00 [revised]
PHST- 2021/02/10 00:00 [accepted]
PHST- 2021/03/08 06:03 [entrez]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
AID - 10.1002/pbc.28981 [doi]
PST - aheadofprint
SO  - Pediatr Blood Cancer. 2021 Mar 7:e28981. doi: 10.1002/pbc.28981.