Open AccessMON-202 Germline SDHB Exon 1 Deletion Is Associated with Absence of 131I-metaiodobenzylguanidine (MIBG) Uptake in Malignant Paragangliomas
Author(s) -
Janaina Petenuci,
Gustavo F C Fagundes,
Flavia Tedesco Motta,
Aurea Luiza F. Magalhães,
André Vicente Guimarães,
A. Benedetti,
Ana Caroline F Afonso,
Maria Adelaide Albergaria Pereira,
George Barbério Coura-Filho,
Maria Cláudia Nogueira Zerbini,
Sheila Aparecida Coelho Siqueira,
Victor Srougi,
Fábio Y Tanno,
José L Chambô,
Marcela S. S. Ferrari,
João Batista de Andrade Neto,
Ana Claudia Latrônico,
Ana O. Hoff,
Berenice Bilharinho Mendonça,
Maria Candida Barisson Villares Fragoso,
Madson Q. Almeida
Publication year - 2020
Publication title -
journal of the endocrine society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.046
H-Index - 20
ISSN - 2472-1972
DOI - 10.1210/jendso/bvaa046.1135
Subject(s) - sdhb , germline mutation , exon , germline , paraganglioma , medicine , cancer research , metastasis , mutation , pheochromocytoma , pathology , oncology , biology , cancer , genetics , gene
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.