Metastatic risk factors in pheochromocytoma/paraganglioma

Author:

Rebrova D. V.1ORCID,Loginova O. I.1ORCID,Vorobyev S. L.2ORCID,Vorokhobina N. V.3ORCID,Kozorezova E. S.2ORCID,Indeykin F. A.2ORCID,Savelyeva T. V.1ORCID,Sleptsov I. V.1ORCID,Chernikov R. A.1ORCID,Fedorov E. A.1ORCID,Semenov A. A.1ORCID,Chinchuk I. K.1ORCID,Shikhmagomedov Sh. Sh.1ORCID,Alekseev M. A.1ORCID,Krasnov L. M.1ORCID,Rusakov V. F.1ORCID

Affiliation:

1. Saint Petersburg State University, Saint Petersburg State University Hospital

2. National Clinical Center of Morphological Diagnostic

3. North-Western State Medical University n.a. I.I. Mechnikov

Abstract

Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and «non-metastatic». Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15–20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.

Publisher

Endocrinology Research Centre

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