Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL)

Daniela Yone Veiga Iguchi; Sebastião Nunes Martins Filho; Iberê Cauduro Soares; Sheila Aparecida Coelho Siqueira; Venâncio Avancini Ferreira Alves; Aline Kawassaki Assato; Ji Hoon Yang; Madson Q Almeida; Maria Candida Barisson Villares Fragoso; Gustavo Freitas Cardoso Fagundes; Berenice B Mendonca; Delmar Muniz Lourenço Junior; Ana O Hoff; Luciana Audi Castroneves; Bruno Ferraz-de-Souza; Maria Lucia Cardillo Correa Giannella; Maria Adelaide Albergaria Pereira

doi:10.1210/jendso/bvae093

Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL)

J Endocr Soc. 2024 May 7;8(7):bvae093. doi: 10.1210/jendso/bvae093. eCollection 2024 May 23.

Authors

Daniela Yone Veiga Iguchi¹, Sebastião Nunes Martins Filho², Iberê Cauduro Soares³, Sheila Aparecida Coelho Siqueira⁴, Venâncio Avancini Ferreira Alves⁵, Aline Kawassaki Assato⁵, Ji Hoon Yang⁶, Madson Q Almeida⁷, Maria Candida Barisson Villares Fragoso^{8

9}, Gustavo Freitas Cardoso Fagundes⁷, Berenice B Mendonca¹⁰, Delmar Muniz Lourenço Junior⁷, Ana O Hoff⁹, Luciana Audi Castroneves⁹, Bruno Ferraz-de-Souza^{11

12}, Maria Lucia Cardillo Correa Giannella¹³, Maria Adelaide Albergaria Pereira¹

Affiliations

¹ Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
² Department of Laboratory Medicine and Pathology, University of Alberta, Alberta T6G 1C9, Canada.
³ Divisão de Anatomia Patológica, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil.
⁴ Divisão de Anatomia Patológica, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
⁵ Laboratório de Investigaçãoc Médica LIM/14, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.
⁶ Clínica de Endocrinologia, Hospital do Servidor Público Municipal de São Paulo, São Paulo 01532-000, Brazil.
⁷ Laboratório de Endocrinologia Molecular e Celular LIM/25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.
⁸ Laboratório de Hormônios e Genética Molecular LIM/42, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.
⁹ Divisão de Endocrinologia e Metabologia, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil.
¹⁰ Laboratório de Hormônios e Genética Molecular LIM/42, Laboratório de Sequenciamento em Larga Escala (SELA), Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.
¹¹ Laboratório de Endocrinologia Celular e Molecular LIM/25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo 01246-903, Brazil.
¹² School of Medicine, University of Notre Dame Australia, Fremantle WA 6160, Australia.
¹³ Laboratório de Carboidratos e Radioimunoensaio LIM/18, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.

Abstract

Context: Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease.

Objective: This work aimed to develop a prognostic score of metastatic potential in PGLs.

Methods: A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis ≥96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS).

Results: Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS.

Conclusion: The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk.

Keywords: GAPP; PASS; metastatic paraganglioma; non-metastatic paraganglioma; paraganglioma; pheochromocytoma.