One genotype, many phenotypes: SDHB p.R90X mutation-associated paragangliomas.

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, Lu 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.