Peri-operative management, surgical outcome and prognostication in pheochromocytoma and paraganglioma

Abstract

Pheochromocytomas and paragangliomas (PPGL) are rare tumors originating from the adrenal medulla and paraganglionic tissue. Although mainly non-metastatic they can still be life threatening due to excretion of catecholamines and if untreated the development of chronic hypertension and severe cardiovascular events may occur. The only curative treatment is surgery, but this per se can increase the risk of excessive hormone excretion and it has long been recommended to treat patients with alpha-adrenoceptor blocking drugs (AAB) prior to surgery. However, increased incidental detection of smaller tumors and advances in surgical and anesthesiologic techniques has led us to question its necessity. Paper I of this thesis accounts for a prospective study in which ten patients with pheochromocytoma were operated without AAB. When compared to ten pre-treated controls we saw no significant differences in peri- or post-operative hemodynamics and the time spent in post-operative surveillance and hospital in total was shorter in the study group.

Pregnancy can also provoke hormone release and both maternal and fetal mortality has historically been up to 50% in cases with PPGL in pregnant women. There is no consensus regarding the best timing and strategy for tumor removal and whether there are any long-term effects on the offspring has not been previously studied. Paper II was a register based study on short and long-term outcome for mother and child in pregnancies complicated by PPGL in Sweden during 1973 - 2015. The perinatal outcome was favorable regardless of timing of diagnosis or treatment and there was no reported mortality. No long-term effects on the children were observed.

Furthermore, PPGLs lack the typical stigmata that differentiate malignant from benign in other tumors and better histopathological markers for distinguishing tumors prone to metastasize are sought for. In papers III and IV we investigated the correlation of several histopathological markers, genetic alterations, and clinical data in a total of 149 PPGL patients. We found high cytoplasmic HIF2α and negative SDHB staining to be more common in metastatic tumors.

In conclusion we find contemporary PPGL surgery to be safe, even in pregnant women, and our data support omitting AAB in most cases. HIF2α and SDHB are promising as prognostic markers in PPGL immunohistochemistry.