title: Vascular pattern analysis for the prediction of clinical behaviour in pheochromocytomas and paragangliomas.
abstract: Pheochromocytomas (PCCs) are neuroendocrine tumors arising from chromaffin cells of the adrenal medulla. Related tumors that arise from the paraganglia outside the adrenal medulla are called paragangliomas (PGLs). PCC/PGLs are usually benign, but approximately 17% of these tumors are malignant, as defined by the development of metastases. Currently, there are no generally accepted markers for identifying a primary PCC or PGL as malignant. In 2002, Favier et al. described the use of vascular architecture for the distinction between benign and malignant primary PCC/PGLs. The aim of this study was to validate the use of vascular pattern analysis as a test for malignancy in a large series of primary PCC/PGLs. Six independent observers scored a series of 184 genetically well-characterized PCCs and PGLs for the CD34 immunolabeled vascular pattern and these findings were correlated to the clinical outcome. Tumors were scored as malignant if an irregular vascular pattern was observed, including vascular arcs, parallels and networks, while tumors with a regular pattern of short straight capillaries were scored as benign. Mean sensitivity and specificity of vascular architecture, as a predictor of malignancy was 59.7% and 72.9%, respectively. There was significant agreement between the 6 observers (mean κ = 0.796). Mean sensitivity of vascular pattern analysis was higher in tumors >5 cm (63.2%) and in genotype cluster 2 tumors (100%). In conclusion, vascular pattern analysis cannot be used in a stand-alone manner as a prognostic tool for the distinction between benign and malignant PCC, but could be used as an indicator of malignancy and might be a useful tool in combination with other morphological characteristics.
authors: Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Lindsey
authors: L
authors: Oudijk
authors: Laboratory for Pathology, PAL Dordrecht, Dordrecht, the Netherlands.
authors: Francien
authors: F
authors: van Nederveen
authors: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75006 Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Département d'anatomo-pathologie, F-75015 Paris, France.
authors: Cécile
authors: C
authors: Badoual
authors: Department of Pathology, Pitié-Salpetrière Hospital, AP-HP, Pierre and Marie Curie University, Sorbonne Universities, Paris, France; INSERM U1016 CNRS UMR8104, Institut Cochin, Paris Descartes University, Sorbonne Paris Cité, France.
authors: Frédérique
authors: F
authors: Tissier
authors: Department of Pathology, Tufts University School of Medicine & Tufts Medical Center, Boston, Massachusetts, United States of America.
authors: Arthur S
authors: AS
authors: Tischler
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors: Marcel
authors: M
authors: Smid
authors: Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: José
authors: J
authors: Gaal
authors: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75006 Paris, France; INSERM, UMR970, Paris Cardiovascular Research Center, F-75015 Paris, France.
authors: Charlotte
authors: C
authors: Lepoutre-Lussey
authors: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75006 Paris, France; INSERM, UMR970, Paris Cardiovascular Research Center, F-75015 Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Service de Génétique, F-75015 Paris, France.
authors: Anne-Paule
authors: AP
authors: Gimenez-Roqueplo
authors: Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Winand N M
authors: WN
authors: Dinjens
authors: Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Esther
authors: E
authors: Korpershoek
authors: Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Pathology, Reinier de Graaf Hospital, Delft, the Netherlands.
authors: Ronald
authors: R
authors: de Krijger
authors: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75006 Paris, France; INSERM, UMR970, Paris Cardiovascular Research Center, F-75015 Paris, France.
authors: Judith
authors: J
authors: Favier
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000098:blood supply* / Q000473:pathology*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D010235:Paraganglioma / Q000098:blood supply* / Q000473:pathology*; D010673:Pheochromocytoma / Q000098:blood supply* / Q000473:pathology*; D011379:Prognosis; D055815:Young Adult