title: Metastatic pheochromocytoma: does the size and age matter?
abstract: BACKGROUND
  Pheochromocytomas are tumours arising from chromaffin tissue located in the adrenal medulla associated with typical symptoms and signs which may occasionally develop metastases, which are defined as the presence of tumour cells at sites where these cells are not found. This retrospective analysis was focused on clinical, genetic and histopathologic characteristics of primary metastatic versus primary benign pheochromocytomas.
  
  
  METHODS
  We identified 41 subjects with metastatic pheochromocytoma and 108 subjects with apparently benign pheochromocytoma. We assessed dimension and biochemical profile of the primary tumour, age at presentation and time to develop metastases.
  
  
  RESULTS
  Subjects with metastatic pheochromocytoma presented at a significantly younger age (41·4 ± 14·7 vs. 50·2 ± 13·7 years; P < 0·001) with larger primary tumours (8·38 ± 3·27 vs. 6·18 ± 2·75 cm; P < 0·001) and secreted more frequently norepinephrine (95·1% vs. 83·3%; P = 0·046) compared to subjects with apparently benign pheochromocytomas. No significant differences were found in the incidence of genetic mutations in both groups of subjects (25·7% in the metastatic group and 14·7% in the benign group; P = 0·13). From available histopathologic markers of potential malignancy, only necrosis occurred more frequently in subjects with metastatic pheochromocytoma (27·6% vs. 0%; P < 0·001). The median time to develop metastases was 3·6 years with the longest interval 24 years.
  
  
  CONCLUSIONS
  In conclusion, regardless of a genetic background, the size of a primary pheochromocytoma and age of its first presentation are two independent risk factors associated with the development of metastatic disease.
authors.affiliation: 3rd Department of Medicine, Department of Endocrinology and Metabolism, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Zelinka
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Musil
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Dušková
authors.forename: Deborah
authors.initials: D
authors.lastname: Burton
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Dragana
authors.initials: D
authors.lastname: Milosevic
authors.forename: Jiří
authors.initials: J
authors.lastname: Widimský
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000367:Age Factors; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D009638:Norepinephrine; D004837:Epinephrine