MON-202 Germline SDHB Exon 1 Deletion Is Associated with Absence of 131I-metaiodobenzylguanidine (MIBG) Uptake in Malignant Paragangliomas

• Published in: Journal of the Endocrine Society Vol. 4; no. Supplement_1
• Main Authors: Petenuci, Janaina, Fagundes, Gustavo Freitas Cardoso, Motta, Flavia Tedesco, Magalhães, Aurea Luiza F, Guimaraes, Augusto G, Benedetti, Anna Flavia Figueredo, Afonso, Ana Caroline F, Pereira, Maria Adelaide A, Coura-Filho, George B, Zerbini, Maria Claudia N, Siqueira, Sheila, Srougi, Victor, Tanno, Fabio Y, Chambo, Jose Luis, Ferrari, Marcela S S, Neto, Joao Evangelista Bezerra, Latronico, Ana Claudia, Hoff, Ana O, Mendonca, Berenice Bilharinho, Fragoso, Maria Candida B V, Almeida, Madson Q
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08-05-2020
• Subjects: Adrenal
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvaa046.1135

Abstract
Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells. More than 30% of patients with PPGLs have a hereditary predisposition. Malignancy in PPGLs is defined by the presence of local invasion or metastasis in nonchromaffin tissues. Germline SDHB mutations are found in approximately 40% of malignant PPGLs, mainly paragangliomas (PGLs). However, SDHB mutations are not a prognostic factor in malignant PPGLs. To date, no genotype-phenotype correlation has been reported in malignant PPGLs associated with SDHB mutations. Aim: To investigate clinical and imaging features of patients with malignant PGLs harboring germline SDHB exon 1 deletion or splicing site mutation. Methods: We retrospectively evaluated 22 unrelated individuals with malignant PPGLs. Six out of 22 (27%) malignant PPGLs harbored germline SDHB mutations. Three patients had SDHB exon 1 deletion and 3 splicing site mutation (2 with c.201-2A>G and one with c.423 + 1G>A). All SDHB defects were classified as likely pathogenic. Results: In the exon 1 deletion group, 2 patients had abdominal PGLs (one also had a neck PGL) and one had only head and neck PGLs. In the splicing site mutation group, all 3 patients had abdominal PGLs (one also had a neck PGL). Median age at diagnosis was 26 yrs (16 to 45) and 33 yrs (26 to 53) in the exon 1 deletion and splicing mutation groups, respectively. Two patients (one in each group) had metastasis at diagnosis. All 6 patients had bone metastasis, but liver and/or lung metastasis were more frequent in patients with SDHB exon 1 deletion (66 vs. 33%). Interestingly, metastasis from malignant PGLs harboring SDHB splicing site mutations were 131I-metaiodobenzylguanidine (MIBG) avid in all cases, whereas metastatic lesions from malignant PGLs harboring SDHB exon 1 deletion did not present any MIBG uptake on diagnostic imaging studies. Therefore, all 3 patients with SDHB exon 1 deletion were treated with chemotherapy (cyclophosphamide, vincristine and dacarbazine). In contrast, all 3 patients with splicing site mutations have been treated with MIBG therapy. Median follow-up was 87 months (8 to 360 months). Only one patient (exon 1deletion group) died because of disease progression. Conclusion: We first demonstrated here that germline SDHB exon 1 deletion is associated with absence of MIBG uptake in malignant PGLs. This finding needs to be confirmed in an expanded cohort of malignant PPGLs.