Endocrine Abstracts

Paragangliomas (PGL) and pheochromocytomas (PHEO) are rare neuroendocrine tumors with an estimated prevalence of 1:6500 and 1:2500, respectively. Although most PGL/PHEO are benign, approximately 10% of PHEOs and 15-35% of PGLs have metastatic disease, which it is main cause of death, with 6 years of median survival. Objective: To characterize the metastatic PHEOs and PGLs from a single center. Methods: Retrospective analysis of clinical records of patients with metastatic PHEO or PGL diagnosed from 2000 to 2022. Results: We identified 23 patients, 52.2% male, median age at diagnosis was 38 years (Δ8-77) and at metastasis diagnosis 40 years (Δ12-77). The median follow-up was 4 years (Δ0-17). A total of 8 PHEOs and 23 PGLs (30.4% multifocal) were identified. PGLs were located in the head and neck (n=8, 35%), abdomen (n=8, 35%) and mediastinum (n=7, 30%). The median tumor size was 50mm (Δ 20-160mm). The most frequent complaints were hypertension (39.1%), tachycardia (17.4%), hyperhidrosis and headache (13%); 13% were asymptomatic. A functional profile was detected in 56.5%. The majority of primary tumors (n=19, 82.6%) underwent surgery. Regarding germline mutations, 43.5% had a mutation in SDHB gene, 4.3% in the SDHD; in 52.2% mutations were not detected. Bone was the main site of secondary deposits (n=17, 73.9%), followed by lymph nodes (n=16, 69.2%), liver (n=8, 34.8%), lung (n=6, 26.1%) and kidneys (n=1, 4.3%). Multifocal metastases were identified in 13 patients (56.5%). Metastases were present at diagnosis in 6 cases (26.1%). Metastases-directed therapies were radiotherapy in 60.9% (n=14), ¹³¹I-MIBG in 26.1% (n=6), surgery in 21.7% (n=5), chemotherapy in 21.7% (n=5), tyrosine kinase inhibitors (TKI) in 17.4% (n=4), peptide receptor radionuclide therapy (PRRT) in 17.4% (n=4) and chemoembolization in 8.7% (n=2). Multimodality approaches were used in 47.8% (n=11). Surgery obtained a remission rate of 80%. After radiotherapy 50% had disease progression, 30% stability, 5% partial response and 5% remission. PRRT achieved 50% of disease stability and 50% of progression. After chemotherapy 80% progressed and 20% showed partial response. All the patients progressed after ¹³¹I-MIBG, TKI and chemoembolization. Median estimate survival from diagnosis was 14 years and from metastases diagnosis was 11 years, with 39.1% death rate.

Discussion: Metastases location is similar to what is described in the literature. Metastatic disease treatment is challenging due to the low response rate of approved treatments, with the surgical approach offering the best remission rate.