Not all ovarian cancer starts in the ovaries, and distinguishing the origin can be critical in determining prognosis, and quick and effective patient care. A team of pathologists reviewed dozens of cases to identify metastatic malignancies hiding in plain sight. We spoke with Lauren E Schwartz, corresponding author of this study, to learn more about this initiative.
What inspired this study?
This study was inspired by a difficult case involving a woman with an unknown cancer. Initial samples were inconclusive, but repeat sampling of the ovarian mass showed signet ring cells, which strongly suggested the tumor had spread from another site. Further testing confirmed the cancer had started in the stomach.
What makes these tumors hard to recognize as metastatic rather than primary ovarian cancers?
Metastatic ovarian tumors can be hard to diagnose because of what I call “pod bias” – pathologists often assume it’s a primary ovarian tumor, especially if there’s no clinical history. It’s important to stay open-minded and consider metastasis, particularly when the tumor has unusual features, affects both ovaries, or doesn’t look like a typical primary ovarian tumor.
What are the main features under the microscope that can help pathologists tell metastatic tumors apart from primary ovarian ones?
Histology is important, but the biggest clues for spotting metastatic tumors often come from the clinical history and gross exam. A known non-ovarian cancer, tumors in both ovaries, or smaller tumor size should raise concern for metastasis. Under the microscope, features like signet ring cells strongly suggest the cancer may have spread from the stomach or appendix. If a tumor doesn’t match common ovarian types like high-grade serous or endometrioid carcinoma, metastasis should be considered.
Which cancers most often spread to the ovaries? Are there any clues that help point to where the tumor started?
The most common cancers that spread to the ovaries come from the colon, endometrium, breast, appendix, and stomach. To find the original source, it’s important to look closely at the clinical history and gross appearance of the tumor. Certain features under the microscope – like "dirty necrosis," which points to colorectal cancer, or signet ring cells, which suggest a stomach or appendix origin – can also help guide the diagnosis.
How has molecular testing or next-generation sequencing (NGS) contributed to your diagnostic workflow in suspected metastatic cases?
While this paper focuses primarily on histologic and immunohistochemical techniques, molecular testing and NGS can be very helpful when a diagnosis is unclear. These tests can find genetic mutations that may suggest where the cancer started. However, since many mutations appear in different types of cancer, molecular results are most helpful when they can be compared to a known primary tumor to narrow down the options.
How much do you rely on imaging or patient history when making your diagnosis?
I rely heavily on clinical history and imaging when diagnosing metastatic ovarian tumors. A detailed history, even from years ago, can offer important clues, and asking follow-up questions often reveals useful information. Imaging is also key – findings like tumors in both ovaries or smaller masses can strongly suggest metastasis and should inform histologic evaluation.
When you diagnose a metastatic tumor in the ovary, how do you communicate that with the clinical team – especially if the primary cancer hasn’t been found yet?
If I suspect a metastatic ovarian tumor, particularly from a non-gynecologic origin, I immediately communicate with the clinical team. This allows for an exchange of critical information that might have been overlooked and helps expedite further diagnostic workup, such as colonoscopy or endoscopy, which can aid in identifying the primary tumor source.
What advice would you give to pathologists – especially those early in their careers – on recognizing metastatic ovarian tumors?
Early-career pathologists should always include metastasis in their differential diagnosis, even if it seems unlikely at first. It's easy to overlook, and without considering it, multiple rounds of immunohistochemistry might be needed before realizing a metastatic origin. Don't hesitate to ask for help and discuss cases with colleagues. Knowing when to seek guidance is crucial in avoiding diagnostic delays.
What are the next steps in this area of research?
The next step is to optimize the algorithm outlined in the paper and determine the best initial immunohistochemical panel based on the patient’s history and imaging findings. I also believe molecular and NGS testing will play a bigger role in the future as these methods become faster and more affordable.
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