Oudijk Lindsey, van Nederveen Francien, Badoual Cécile, Tissier Frédérique, Tischler Arthur S, Smid Marcel, Gaal José, Lepoutre-Lussey Charlotte, Gimenez-Roqueplo Anne-Paule, Dinjens Winand N M, Korpershoek Esther, de Krijger Ronald, Favier Judith
Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Laboratory for Pathology, PAL Dordrecht, Dordrecht, the Netherlands.
PLoS One. 2015 Mar 20;10(3):e0121361. doi: 10.1371/journal.pone.0121361. eCollection 2015.
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.
嗜铬细胞瘤（PCCs）是起源于肾上腺髓质嗜铬细胞的神经内分泌肿瘤。起源于肾上腺髓质外副神经节的相关肿瘤称为副神经节瘤（PGLs）。PCC/PGLs通常为良性，但根据转移情况定义，这些肿瘤中约17%为恶性。目前，尚无普遍接受的用于识别原发性PCC或PGL为恶性的标志物。2002年，法维耶等人描述了利用血管结构区分良性和恶性原发性PCC/PGLs。本研究的目的是验证血管模式分析在一大系列原发性PCC/PGLs中作为恶性肿瘤检测方法的有效性。6名独立观察者对一系列184个基因特征明确的PCCs和PGLs的CD34免疫标记血管模式进行评分，并将这些结果与临床结果相关联。如果观察到不规则血管模式，包括血管弧、平行线和网络，则将肿瘤评为恶性，而具有短直毛细血管规则模式的肿瘤评为良性。作为恶性肿瘤预测指标的血管结构的平均敏感性和特异性分别为59.7%和72.9%。6名观察者之间存在显著一致性（平均κ=0.796）。血管模式分析的平均敏感性在直径>5 cm的肿瘤（63.2%）和基因型簇2的肿瘤（100%）中更高。总之，血管模式分析不能单独用作区分良性和恶性PCC的预后工具，但可作为恶性肿瘤的指标，并且可能是与其他形态学特征相结合的有用工具。
