Neuroendocrine tumors (NETs) are complex cancers that can originate in various organs, including the ovaries. While primary ovarian NETs (PON) are uncommon, distinguishing them from neuroendocrine ovarian metastases (NOM) has posed a significant challenge for doctors and researchers alike. A recent study published in The Journal of Pathology: Clinical Research by NETRF Pilot Award recipient Hans Hofland, MD, PhD of Erasmus Medical Center in the Netherlands, provides valuable insights into the clinicopathological and epigenetic differences between these two tumor types. This research is crucial in improving diagnostic accuracy and ensuring appropriate treatment strategies for patients with ovarian NETs.
Key Findings from the Study
The study examined 88 patients diagnosed with ovarian NETs between 1991 and 2023. Of these, 71 cases were identified as NOM, meaning the tumors had spread from another location, while 17 cases were classified as PON, meaning the tumor originated in the ovary. By analyzing clinical data, immunohistochemical markers, and DNA methylation patterns, researchers discovered several distinguishing features:
- Lateralization Matters: PONs were found exclusively on one ovary (unilateral), whereas NOMs were often present in both ovaries (bilateral in 78% of cases).
- The Role of Teratomas: Over half of PONs (53%) were associated with teratomas—often benign tumors containing different types of tissues—while no NOMs were found with teratomatous components. If a neuroendocrine tumor is found within a teratoma, it is highly likely to be a primary ovarian tumor.
- Molecular Similarities with Midgut NETs: PONs that were not associated with teratomas (PON-T−) shared similar molecular profiles and genetic markers with midgut NETs, suggesting that some of these tumors might actually be undetected metastases rather than true primary ovarian tumors.
- Survival and Disease Progression: Patients with PON generally had a longer overall survival compared to those with NOM, emphasizing the importance of correctly identifying the tumor type for optimal treatment planning.
Why This Matters for Patients
The findings of this study are particularly relevant for patients with ovarian NETs because an accurate diagnosis can significantly impact treatment decisions. If a tumor is a primary ovarian NET, surgical removal of the ovary may be curative. However, if it is a metastasis from another site, a more aggressive and systemic approach, including further imaging and targeted therapies, may be necessary.
Moreover, this study reinforces the importance of thorough imaging studies to ensure that midgut NETs are not missed. This could lead to more effective long-term monitoring and treatment strategies for patients diagnosed with ovarian NETs.
The Future of Ovarian NET Research
This research underscores the need for continued investigation into the molecular characteristics of neuroendocrine tumors. Advances in DNA methylation profiling and immunohistochemistry provide new tools to differentiate between primary and metastatic NETs, ultimately helping doctors make more informed treatment decisions.
Dr. Hofland says “Ovarian NETs can originate within an ovarian teratoma, which is a tumor composed of very different tissues. Through molecular analyses of ovarian tumors, this study found that when an ovarian NET is not found within a teratoma, it is most likely a metastasis from a primary small bowel NET. This has important consequences for staging and management of these tumors. Furthermore, it opens up novel research questions about why these NET subtypes preferentially metastasize to the ovaries.”
At NETRF, we remain committed to supporting groundbreaking research that improves the lives of NET patients. We encourage patients, caregivers, and healthcare providers to stay informed and advocate for comprehensive diagnostic approaches when facing an ovarian NET diagnosis.
For more information on NETs originating in the gynecologic tract, listen to our NETWise podcast episode on Gynecologic NETs here.