Ali S Alzahrani1,2, Meshael Alswailem3, Yosra Moria4, Ayman Aldeheshi5, Hindi Al-Hindi5. 1. Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. aliz@kfshrc.edu.sa. 2. Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. aliz@kfshrc.edu.sa. 3. Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. 4. Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. 5. Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Abstract
CONTEXT: SDHB p.R90X germline mutation is the most common genetic alteration in our patients with familial or apparently sporadic pheochromocytoma/paraganglioma (PPGL). OBJECTIVE: To analyze the clinical and pathological characteristics, response to therapy, and outcome of patients with SDHB p.R90X-associated PPGL and describe the clinical phenotypic variability in the patients carrying this mutation. METHODS: We reviewed the clinical and pathological characteristics and analyzed the phenotypic variability of all 13 patients that have SDHB p.R90X mutation-associated PPGL. RESULTS: Thirteen patients (five females and eight males). The median age at diagnosis was 23 years (range 8-43). Although the mutation was the same, there was significant phenotypic variability between patients and even within the same family. Four patients (30.8%) had a family history of PPGL and six patients (46%) had distant metastasis. Surgery of the primary tumor was performed in 11 patients (84.6%). Two patients had inoperable PPGL. Patients with metastasis received different combinations of chemotherapy, Lu177 radiotherapy, multikinase inhibitors, and external irradiation. Only five patients (38.5%) were in remission at a follow-up duration of 4-9 years. The other patients either died due to their disease progression (four patients, 30.8%) or continue to have progressive disease (two patients, 15.4%) or recurrence (one patient, 7.7%). Patients with distant metastasis were older, had larger primary tumors, were more likely to have a family history of PPGL and had a worse outcome. CONCLUSION: SDHB p.R90X mutation-associated PPGL have significant phenotypic variability and are associated with a high risk of distant metastasis and mortality.
CONTEXT: SDHB p.R90X germline mutation is the most common genetic alteration in our patients with familial or apparently sporadic pheochromocytoma/paraganglioma (PPGL). OBJECTIVE: To analyze the clinical and pathological characteristics, response to therapy, and outcome of patients with SDHB p.R90X-associated PPGL and describe the clinical phenotypic variability in the patients carrying this mutation. METHODS: We reviewed the clinical and pathological characteristics and analyzed the phenotypic variability of all 13 patients that have SDHB p.R90X mutation-associated PPGL. RESULTS: Thirteen patients (five females and eight males). The median age at diagnosis was 23 years (range 8-43). Although the mutation was the same, there was significant phenotypic variability between patients and even within the same family. Four patients (30.8%) had a family history of PPGL and six patients (46%) had distant metastasis. Surgery of the primary tumor was performed in 11 patients (84.6%). Two patients had inoperable PPGL. Patients with metastasis received different combinations of chemotherapy, Lu177 radiotherapy, multikinase inhibitors, and external irradiation. Only five patients (38.5%) were in remission at a follow-up duration of 4-9 years. The other patients either died due to their disease progression (four patients, 30.8%) or continue to have progressive disease (two patients, 15.4%) or recurrence (one patient, 7.7%). Patients with distant metastasis were older, had larger primary tumors, were more likely to have a family history of PPGL and had a worse outcome. CONCLUSION: SDHB p.R90X mutation-associated PPGL have significant phenotypic variability and are associated with a high risk of distant metastasis and mortality.
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Authors: Lauren Fishbein; Ignaty Leshchiner; Vonn Walter; Ludmila Danilova; A Gordon Robertson; Amy R Johnson; Tara M Lichtenberg; Bradley A Murray; Hans K Ghayee; Tobias Else; Shiyun Ling; Stuart R Jefferys; Aguirre A de Cubas; Brandon Wenz; Esther Korpershoek; Antonio L Amelio; Liza Makowski; W Kimryn Rathmell; Anne-Paule Gimenez-Roqueplo; Thomas J Giordano; Sylvia L Asa; Arthur S Tischler; Karel Pacak; Katherine L Nathanson; Matthew D Wilkerson Journal: Cancer Cell Date: 2017-02-02 Impact factor: 31.743
Authors: Shatha Albattal; Meshael Alswailem; Yosra Moria; Hindi Al-Hindi; Majed Dasouki; Mohamed Abouelhoda; Hala Aba Alkhail; Entissar Alsuhaibani; Ali S Alzahrani Journal: Oncotarget Date: 2019-10-15