Introduction
For years, patients, clinicians, and researchers have suspected that the true number of people living with neuroendocrine tumours (NETs) is far higher than official statistics suggest. Registry data only captures those who are diagnosed — but what about those who never receive a diagnosis at all?
Autopsy studies, historical pathology series, and institutional observations provide a rare window into this invisible NET population. When viewed together, they reveal a consistent global pattern: NETs and related neuroendocrine tumours are under‑diagnosed, under‑recognised, and often present for years before anyone realises what they are.
This refreshed article integrates 13 autopsy‑based datasets, two key epidemiologic messages, and updated context — all in a clearer, more structured format.
What is a NET?
A neuroendocrine tumour (NET) is a well‑differentiated neuroendocrine neoplasm arising from neuroendocrine cells found throughout the body. These cells behave like a hybrid between nerve cells and hormone‑producing endocrine cells.
NETs can occur in many organs, including (but not limited to) the small bowel, appendix, rectum, pancreas, stomach, and lungs. They are often slow‑growing, sometimes hormone‑producing, and frequently misdiagnosed.
For tumour‑specific summaries, my Spotlight Series on NEN Types provides structured, patient‑friendly explanations of every major NET and NEC category.
Why Autopsy Evidence Matters
Autopsy studies reveal something registry data cannot: the number of people who lived with a NET but were never diagnosed during life.
These tumours are often:
- small
- indolent
- asymptomatic
- misattributed to other conditions
- or simply never investigated
Autopsy evidence therefore provides a biological prevalence, not just a clinical one.
Two Messages from Global Autopsy Evidence
1. NET incidence is most certainly (and perhaps profoundly) underestimated — despite the age of some of these studies, misdiagnoses may be far more common than awareness messages suggest.
Autopsies repeatedly uncover NETs that were clearly present for years, yet never diagnosed.
We cannot access the medical records of those individuals, so we cannot know what symptoms they experienced. However, given the slow‑growing nature of many NETs, it is reasonable to consider that some may have lived with symptoms that were never fully investigated or correctly attributed.
This mirrors what we still see today: NET symptoms are often labelled as IBS, menopause, anxiety, asthma, gallbladder disease, or “nonspecific abdominal pain”.
Eisenhower’s case is sometimes referenced in discussions about undiagnosed neuroendocrine disease. His autopsy revealed a pheochromocytoma — a catecholamine‑producing tumour — and several of his long‑standing health issues are now recognised as potentially consistent with that diagnosis. While he is not a NET example, his case illustrates how neuroendocrine tumours of various types can remain undetected during life, even in individuals receiving extensive medical care. To read more click here.
2. New autopsy evidence may continue to reveal a global, silent reservoir of NETs that registry data cannot capture.
Across the US, Europe, Asia, and Australia, previous autopsy studies have shown:
- NETs in 0.5–1.2% of all autopsies
- pNETs in 1% of autopsies in Hong Kong
- Small‑bowel NETs in 1 in 150 Mayo Clinic autopsies
- PPGLs in 0.05% of Australian autopsies
This is not a local anomaly — it is a global pattern.
Historical Autopsy Observations
Australia — PPGL in 0.05% of autopsies
Example PPGL autopsy series: click here
Moertel — 1 in 150 autopsies had a small‑bowel “carcinoid”
Historical Mayo Clinic series (Moertel CG et al.). click here
Hong Kong — 1% of autopsies had an islet‑cell tumour (pNET)
Cited by Mayo – click here
Malmö, Sweden — 1.22% of 16,294 autopsies had “carcinoid”
Malmö General Hospital, where researchers found that 1.22% of the 16,294 colorectal autopsies contained “carcinoid” tumors. 90% were incidental. Click here
Additional NET Studies with autopsy content
Modlin et al., 2003 (Cancer) click here
Modlin explicitly references the Japanese autopsy data showing:
- high rates of incidental gastric NETs
- high rates of incidental rectal NETs
- prevalence far exceeding clinical detection
Rindi et al., 2000
A pathology‑based distribution study with autopsy‑informed data.
- Highlighted frequent incidental gastric and duodenal NETs.
- Demonstrated recognition of subclinical NETs even before modern ENETS classification.
Capella et al., 1995
A foundational classification paper that included autopsy‑supported observations.
- Identified incidental NETs across the GI tract.
- Shows that the “invisible NET population” was recognised long before contemporary imaging.
Hakulinen et al., 1986
Finnish registry analysis incorporating autopsy findings.
- Demonstrated a clear gap between registry‑recorded and autopsy‑identified small intestinal NETs.
- Reinforces the under‑diagnosis theme in Nordic populations.
Lamers et al., 1982
Dutch pathology series identifying incidental gastric and duodenal NETs.
- Supports the existence of micro‑NETs that rarely present clinically.
- Adds Western European evidence to the global pattern.
What This Means for Patients and Clinicians
The combined evidence paints a clear picture:
- NETs are more common than registry data suggests (and we know the anatomy based registry system makes it difficult to accurately capture the true NET incidence)
- NETs remain undiagnosed during life
- Symptoms may be present but misattributed
- The “invisible NET population” is real and global
- Awareness, earlier investigation, and better diagnostic pathways are essential
For tumour‑specific education, explore the Spotlight Series on NEN Types
Closing Thoughts
Autopsy evidence doesn’t just tell us about the past — it tells us about the patients we are still missing today. The invisible NET population is not a theory. It’s clearly an issue. I suspect is is less of an issue today due to the expansion and availability of better quality imaging techniques. But no doubt many will remain missed. The more we understand it, the better we can advocate for earlier diagnosis, better symptom recognition, and improved outcomes for everyone living with NETs whether they are formally diagnosed or not.
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I’ve read your articles for a few years and want to thank you for all your amazing contributions to the NET community. Your generosity in sharing your research and talent is very much appreciated. If you ever travel to San Francisco, let me know. Have a blessed holiday season with your family. Evie Ferris
Thank you Evie 😊
Thank you SO much for this article and for ALL you do! Do you know anything about ‘GI Mapping?’ I’ve had 2 physicians approach me with this new diagnostic technology but I have no idea if it’s been used in Nets? My primary tumor was on my pancreas & removed but never scanned so I do not know if it lit up, it was found accidentally. Now I’m having symptoms – seems like carcinoid syndrome, but my scans were clean. I’ve heard it’s possible that tumors can be too small to detect or not light up. My physician doesn’t want to look any further. I’m on Medicaid in the US so I am not allowed to travel out of state. Do you know of any institutions that will see patients anyway? Hardship or financial plans? I’m sure I’m not the only one in this situation.
I don’t know anything about GI mapping, and a quick check online doesn’t give me any clear understanding of its utility with someone already diagnosed with NET. Carcinoid syndrome is rare in a pancreatic NET. I don’t live in the US, but I have thousands in my private Facebook group who do and can help.
Would it be a good idea to get a ct scan as one would get a colonoscopy at a certain age?
I asked my doctor that question. His reply was that it would “ raise to many questions”.
I also believe there wouldn’t be enough scans and resources in existence to meet the demand, you can see how long it’s taking to inoculate the over 50s for COVID
Thanks Ronny, I have read and re-read so many of your posts and am so thankful for your continued education and activism! I am one of the ‘silent’ patients with a diagnosis of Carcinoid Syndrome with Occult Tumor. It has been a frustrating, difficult journey, but I thankfully had a GP that knew enough to be suspicious and at least found the needle-in-the-haystack with persistently elevated plasma 5-HIAA even though no tumors can be found on imaging.
My guess is it’s hiding somewhere in the folds of your small intestine.
Have you had a Ga68 PET scan? Any signs of metastases because carcinoid syndrome is normally only present with liver metastases (there are one or two exceptions such as lung and cervix/ovaries)
My NETs specialist, who is also a research scientist, believes that though the increase in incidence is partially due to earlier diagnosis, NETs is actually on the increase, but it’s not known why.
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Very difficult to prove given the changes in diagnostic technology, physician education and general awareness (social media explosion). I think he’s right though
As usual a very interesting article which makes me think that the most important factor to finding these invisible patients is intensive training for the first-contact points ie our GPs.
Thankyou Ronny.
Thanks Deanna. I’m personally not so sure that GP’s should be the main target of awareness. It is more likely that a patient will be actually diagnosed at secondary care and so gastroenterologists, oncologists, and even pathologists should be a target. Many people are referred to secondary care for “something” based on the presentational symptoms and the action of secondary care is critical. Many people are sent back to primary care from secondary care nothing found. The problem for GPs is that NETs is one of 200 cancers and one of 10,000 conditions and it’s impossible for GPs to be given “intensive training” in every single one of them. Their gut instinct, hopefully honed by 10 years of training, normally works for most. That’s not to say we should not include them in our awareness activities but the ‘NETs primer’ we send them is there alongside the ‘a’ disease primer, the ‘b’ disease primer, the ‘c’ disease primer and so on. Most of these primers will unfortunately and understandably become ‘shelfware’. Just my opinion though.
‘a large invisible NET patient population out there ……. we just need to find them’
thanks for pointing this out. But, begs the question…what can be done about it? i.e. How do we, in fact, “find them?”
Any thought of mounting a case finding campaign? Excellent care is available its just hard then it should be to get to, as you point out.
..perhaps in coordination with world NET day in Nov?
without such a concerted effort, lives among the estimated 200K will be lost due to misdiagnosis, and inappropriate treatment. We can do better
thnx
Jeff D
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Well we are finding them, as you will have read, the increase in incidence is a direct result of earlier diagnosos. Ergo, the figure some years ago was very probably way above 200,000. No-one can deny that my blog is not spreading awareness, so I guess I’m doing my bit. Remember, I’m just a wee Scottish patient. However, I think the community as a whole could be more effective if it dropped the ineffectual and crazy fascination with black and white striped animals. We could certainly do better than that.
p.s. I didn’t initially point it out, Dana Farber NET specialists did! I’m just quoting it.
right. how do we take it from, “we know they are out there,” to having them referred for diagnosis and/or treatment?
As patients, we can spread awareness, I’m already doing this on a large international scale. As I said above, things are improving but these things take time. I suspect the figure was once way above the guestimate of 200,000. To be honest, a lot of other people need to do stuff; and getting them to do it is out of the control of patients. It involves medical staff, those controlling the finances, policy, insurance companies, pubic health authorities, patient advocate organisations and their proficiency in negotiating and marketing. ….it’s a big ask.
Could you please post the full citation for the Dana Farber estimate of ‘hidden; NET patients? I would like to read the report and then possibly reference it.
thanks
Jeff
sure – here https://www.slideshare.net/DanaFarber/finding-the-answer-to-net-cancer?qid=a42b5c1e-ca74-4485-ba94-f953b4f53edb&v=&b=&from_search=1
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Thanks Ronny!
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