Vascular pattern analysis for the prediction of clinical behaviour in pheochromocytomas and paragangliomas

Lindsey Oudijk, Francien van Nederveen, Cécile Badoual, Frédérique Tissier, Arthur S Tischler, Marcel Smid, José Gaal, Charlotte Lepoutre-Lussey, Anne-Paule Gimenez-Roqueplo, Winand N M Dinjens, Esther Korpershoek, Ronald de Krijger, Judith Favier, Lindsey Oudijk, Francien van Nederveen, Cécile Badoual, Frédérique Tissier, Arthur S Tischler, Marcel Smid, José Gaal, Charlotte Lepoutre-Lussey, Anne-Paule Gimenez-Roqueplo, Winand N M Dinjens, Esther Korpershoek, Ronald de Krijger, Judith Favier

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Vascular architecture in PCC/PGLs.
Fig 1. Vascular architecture in PCC/PGLs.
Immunostaining of blood vessels with anti-CD34 reveals a homogenously distributed vascular pattern in benign tumors (A, D), while malignant tumors display irregularity (B) and vascular structures forming arcs (C), networks (E) and parallels (F). All panels are at the same magnification. Scale bar = 100μm.

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