Maternal pheochromocytoma and childbirth in Sweden 1973-2015: a population-based study on short and long-term outcome.

PURPOSE: Data guiding management of pheochromocytoma and paraganglioma (PPGL) in pregnant women is limited, and long-term effects on the child are unknown. The aim of this retrospective registry-based case-cohort study was to assess how maternal PPGL and treatment impacts maternal and fetal outcome, including long-term outcome for the child. The main outcomes were maternal and fetal mortality and morbidity at delivery and relative healthcare consumption in children born by mothers with PPGL during pregnancy. METHODS: The National Birth Register identified 4,390,869 pregnancies between 1973-2015. Data was crosslinked with three Swedish national registers to identify women diagnosed with pheochromocytoma or paraganglioma within one year before or after childbirth. Hospital records were reviewed and register data was collected for five age-matched controls for each child until age 18. RESULTS: 21 women and 23 children were identified (incidence 4.8/1.000.000 births/year), all women with adrenal pheochromocytomas (Pc). The majority (71%) were diagnosed post-partum. Nine women (43%) were hypertensive during pregnancy. Preterm delivery was more common in Pc patients compared to controls (30% vs 6%, p < 0.001). There was no maternal or fetal mortality. Timing of tumor removal did not affect gestational weight or APGAR scores. There was no observed difference in hospital admissions between children affected by maternal Pc and controls. CONCLUSION: Pc was commonly diagnosed after delivery and raised the risk of pre-term delivery, suggesting a need for an increased awareness of this diagnosis. However, reassuringly, there was no fetal or maternal mortality or any observed long-term impact on the children.

Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2α correlate to an aggressive tumor phenotype. We show that HIF-2α localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2α was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2α expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.