Safety of Biopsy in Phaeochromocytoma and Paraganglioma
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that can produce excess catecholamines such as adrenaline and noradrenaline. Because these hormones can trigger severe blood pressure spikes, dangerous heart rhythms, or other complications, biopsy has traditionally been discouraged when PPGL is suspected. This international multicentre study re-examined that long-standing caution by looking at real-world biopsy outcomes across multiple hospitals and countries.
Why biopsy has been controversial
Doctors often avoid biopsy in suspected PPGL because puncturing the tumor may release large amounts of catecholamines into the bloodstream. In theory, this can lead to hypertensive crisis, tachyarrhythmia, cardiogenic shock, stroke, or even death. In practice, however, the evidence behind the “do not biopsy” rule has mostly come from isolated case reports rather than large studies. That gap in evidence is what made this study important.
Biopsy may still be considered when a tissue diagnosis is needed to guide treatment, especially if a tumor is suspected to be metastatic, atypical, or another cancer remains in the differential diagnosis. But until now, the true frequency of serious complications was not well defined.
How the study was done
This retrospective cohort study included patients of any age with PPGLs who underwent either percutaneous core-needle biopsy or fine-needle aspiration at participating centres. Head and neck paragangliomas were excluded, since their clinical behavior and biopsy considerations differ from adrenal or other extra-adrenal PPGLs.
Between 1 September 1993 and 31 May 2025, 222 patients underwent 234 biopsies across 19 hospitals in 11 countries. The investigators collected standardized data, including biochemical evidence of catecholamine excess, use of alpha-adrenoceptor blockade before biopsy, biopsy type, lesion location, and complications.
The main outcome was biopsy-related mortality among procedures performed at participating centres. Secondary outcomes included serious catecholamine-related complications and serious non-catecholamine-related complications such as bleeding or infection.
Who was included
The study population included 110 women and 112 men. Among the 207 patients with available biochemical data, 139 had elevated epinephrine or norepinephrine, or their metabolites, meaning many tumors were hormonally active. Before 27 of 232 biopsies, patients received alpha-adrenoceptor blockade, a medication strategy sometimes used to reduce blood pressure instability from catecholamine release.
Importantly, not all biopsies were performed in the same clinical context. Some were done for suspected primary tumors, while many were performed on metastatic lesions. This distinction matters because metastatic lesions may behave differently from primary adrenal tumors and may sometimes be biopsied when the diagnosis is uncertain.
What the study found
Among 106 biopsies with available mortality data, one biopsy-related death occurred, corresponding to a mortality rate of 0.9% (95% CI 0.0–5.1). The death was due to biopsy-related infection rather than a catecholamine surge.
Serious catecholamine-related complications occurred after 4 of 233 biopsies, or 1.7% (95% CI 0.5–4.3). These included tachyarrhythmia, hypertensive crisis, and cardiogenic shock. While these events are clinically significant, they were uncommon.
Notably, no serious catecholamine-related complications were reported in several important subgroups: patients without catecholamine excess, patients who underwent fine-needle aspiration, and patients whose biopsied lesions were metastatic. This suggests that the risk may not be uniform across all PPGL cases and may depend on tumor biology, procedure type, and clinical setting.
Serious non-catecholamine-related complications were more frequent than catecholamine-related events. They occurred after 10 of 233 biopsies, or 4.3% (95% CI 2.1–7.8), and were mainly due to bleeding and infection. This finding is clinically important because it shows that while hormone-related risk exists, standard procedural risks may be just as relevant, or even more so, when considering biopsy.
What the results mean
The findings challenge the absolute avoidance of biopsy in all suspected or confirmed PPGLs. The study suggests that percutaneous biopsy can be performed with a low overall mortality rate and a relatively low rate of serious complications, especially when carefully selected patients are assessed in experienced centres.
At the same time, the results do not mean biopsy is risk-free. Serious events did occur, and the risk appeared higher in some settings than others. The study supports a more nuanced, individualized approach rather than a blanket prohibition. Before biopsy, clinicians should carefully assess whether the result will change management, whether biochemical testing suggests catecholamine excess, whether alpha-blockade is needed, and whether imaging or other diagnostic methods could provide the information without tissue sampling.
Clinical implications
For clinicians, this study provides a more evidence-based framework for decision-making. If PPGL is suspected, biochemical testing should usually be performed before any invasive procedure whenever possible. Cross-sectional imaging and functional imaging may also help characterize the lesion and determine whether biopsy is necessary.
If biopsy is considered essential, the procedure should ideally be done in a setting with expertise in endocrine tumors, interventional radiology, anesthesia support, and close hemodynamic monitoring. Preparedness for hypertensive crisis, arrhythmia, and bleeding or infection is important. Pre-procedure alpha-blockade may be appropriate in selected patients, although the study was not designed to determine which preparation strategy is best.
In patients with metastatic disease, where tissue confirmation may guide systemic therapy, this study suggests the risk of serious catecholamine-related complications may be lower than historically feared, especially for fine-needle aspiration or when catecholamine excess is absent. Even so, each case should be reviewed individually.
Limitations
As a retrospective study, the research depends on the quality and completeness of previously recorded data. Not every biopsy had complete information on complications, biochemical status, or pre-procedure management. In addition, the study reflects real-world practice across multiple centres, which is a strength, but also means that biopsy techniques and supportive care may have varied.
Another important limitation is that biopsies with fatal outcomes done outside participating centres may have been underrepresented, because such cases are less likely to be referred. For that reason, the true mortality risk could be somewhat higher or lower than observed. Still, the large sample size makes this the most informative study to date on the question.
Bottom line
This international study found that percutaneous biopsy of pheochromocytoma and paraganglioma was associated with a low mortality rate and a low rate of serious complications. Most complications were not related to catecholamine release. The results do not eliminate risk, but they do argue against a one-size-fits-all ban on biopsy. Instead, they support careful patient selection, individualized risk-benefit assessment, and management in experienced centres.
For patients and families, the key message is that biopsy decisions in PPGL should be made thoughtfully, after hormone testing and imaging review, and with a plan to manage blood pressure and other potential complications if the procedure is necessary.