Paragangliomas the Forgotten Neuroendocrine Neoplasms: A Retrospective Review of 237 Cases From 2 Centers in 2 Years

Abstract

Abstract Background: paragangliomas (PGN) (including adrenal PGN or pheochromocytomas) are uncommon neuroendocrine neoplasias. Their ubiquity and lack of uniform nomenclature has resulted in systematic sub-registry and limited resources for patients and clinicians. However, 40% of them are hereditary, 10–20% are hormonally active and 50% result in treatment-related complications. Objectives: to describe the clinical and biochemical characteristics of PGN in two referral centers in a 2-year period. Materials and Methods: a retrospective review of the files of patients evaluated in the Centro Medico Nacional Siglo XXI or the Instituto Nacional de Neurología y Neurocirugia between June 2018 and May 2020, even if diagnosis was prior to those dates. The search was performed using ICD-10 terms in the outpatient registries. Data is described using non-parametric statistics, including medians (interquartilic ranges, IQR). According to the reported incidences we expected to find 35 new cases per year in each hospital. Results: 237 patients, 86.4% female with a median age at diagnosis of 54 years (IQR 45–64) were found. The tumors were located in the head 23.9%, neck 63.3%, thorax 0.4%, adrenal in 11.1%, other sites in the abdomen 1.3%. The most common symptoms in head PGN were hypoacusia (85.2%) and cranial nerve palsies (39.3%), in the neck, a visible mass and pain (30.6%) while the “classic” catecholaminergic symptoms were more common in thoracic and abdominal tumors (>50%). Tumors were large or invasive in 50.1% of the cases and at least one hormone was above the upper limit of normal (ULN) in 40.6% of the 64 evaluated cases, mostly urinary dopamine (70% of cases tested, 1.1–2.1 ULN) and plasma and urine metanephrines (60% of cases tested, 1.1- 33.7 ULN and 50% cases, 1.1–22 ULN, respectively). Severe systolic hypertension was more frequent in male patients <30 years of age and 41.6% were candidates to genetic testing due to the tumor characteristics or patient history. Surgery was performed in 55.6%, radiotherapy in 25.2% and 12.1% are under surveillance or pending surgery, 7.1% were lost to follow up. Only 5 cases with metastasis were documented in 1215 patient-years of follow-up. Treatment-related complications were reported in 14.7% and persistence in 32.2%. Conclusions: despite the retrospective nature of the study and sub registry, we found more tumors than expected. The frequency of hormonal production was high, but it is likely related to patient selection bias (mostly symptomatic cases studied). Dopamine and metanephrines are useful in the evaluation of PGN. Endocrinologists should be aware of these common tumors and be part of the multidisciplinary team.