Tumor-specific prognosis of mutation-positive patients with head and neck paragangliomas

Genetic testing to identify succinate dehydrogenase (SDH) mutations in patients with head and neck paraganglioma (HNP) has been in clinical practice for more than a decade. However, the recurrence and metachronous tumor occurrence risks in surgically treated mutation-positive patients are not well studied.

Clinical and procedural details of consecutive patients who underwent excision for HNP from January 1996 to October 2016 were retrospectively reviewed. End points included recurrence, metachronous tumor detection, and mortality. Germline DNA was tested to identify mutations in SDHx genes. Patients were divided into three groups on the basis of genetic testing: group I, positive; group II, negative; and group III, unknown or offered but not tested.

HNP was diagnosed in 268 patients, 214 (147 female; mean age, 47 years) included in this study. Directed genetic testing was performed in 68; mutations were detected in SDH in 47 (69%), a majority SDHD. In group I, 47 patients had 64 procedures for 81 tumors (52 carotid body tumors [CBTs]); 17 (36%) were bilateral, 7 (15%) multiple, 3 (6%) functional, and 7 (15%) malignant. Residual tumor in 10 was significant in 2, managed by radiation therapy and reoperation. Local recurrence was detected in 12 patients (25%) at a median of 8 years; 11 metachronous mediastinal and retroperitoneal paragangliomas were detected in 8 (17%) at a median of 13 years. Systemic metastases occurred in five (10%). Six patients (13%) had more than one recurrence. In group II, 21 patients had 22 procedures for 23 tumors, 17 CBTs. Two (9%) were bilateral and two (9%) malignant. Excision was complete in all with no recurrence or systemic metastasis at last follow-up. For group III, 146 patients underwent 153 procedures for 156 tumors, 95 CBTs; 7 (5%) were bilateral, 2 (1%) multiple, 8 (5%) functional, and 1 (0.6%) malignant. Local recurrence was detected in nine (6%) at a median of 9 years and metachronous HNP in three (2%) at a median of 5 years. Systemic metastases occurred in two (1%). Mortality was 4% in group I and 3% in group III, none procedure or tumor related. Group I (mutation positive) had 10-year overall, recurrence-free, and metachronous tumor-free survival rates of 93%, 69.4%, and 73%, respectively, lower than the other groups (P < .001).

Bilateral, functional, malignant, recurrent, and metachronous tumors are more common in SDH mutation-positive patients with HNP. Overall survival in patients with HNP is high. Metachronous tumors or local recurrences occur late, and long-term follow-up is necessary.