Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma

Version 1 : Received: 14 March 2024 / Approved: 14 March 2024 / Online: 14 March 2024 (13:01:14 CET)

A peer-reviewed article of this Preprint also exists.

Milinkovic, M.; Soldatovic, I.; Zivaljevic, V.; Bozic, V.; Zivotic, M.; Tatic, S.; Dundjerovic, D. Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma. Diagnostics 2024, 14, 849. Milinkovic, M.; Soldatovic, I.; Zivaljevic, V.; Bozic, V.; Zivotic, M.; Tatic, S.; Dundjerovic, D. Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma. Diagnostics 2024, 14, 849.

Abstract

A Challenging task in routine practice is finding distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, SDHB expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS<4) and 54 potentially malignant (PASS ≥4). We found no notable difference between intratumoral MVD and potentially malignant behavior. Group of potentially malignant tumors are significantly larger in size, have lower intratumoral MVD, and decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1,02 and 1,22 respectively). Most tumors maintains SDHB expression, only 6 cases (5,2%) showed a loss of expression (4 of them in PASS<4 group and 2 in PASS≥4). PASS score is easy available for assessment, and complemented with markers of biological behavior completes risk stratification algorithm. Size is directly related with PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Keywords

Angiogenesis; Pheochomocytoma; Paraganglioma; CD105; ERG; PASS; Ki67; S100, SDHB

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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