My NET is different than yours

When you manage a large support group, you see a lot of posts. Many of them highlight a lack of knowledge about the heterogeneity of Neuroendocrine Neoplasms. The issue is not always with those answering the question but often it is the person asking the question. Sometimes intervention is needed to focus responses. So, what are the key issues? Read on…..

If you read any authoritative source on this cancer, it will normally begin with “Neuroendocrine Neoplasms (NENs) are heterogeneous tumours ………….”

“Heterogeneous” means consisting of dissimilar parts or elements, essentially meaning “mixed” or “diverse,” but I used the term “heterogeneity” to refer to the quality or state of being heterogeneous, meaning the presence of diverse components within a group or system; both terms indicate a lack of uniformity or consistency.

You will note I used the term Neuroendocrine Neoplasms here – that is in line with formal naming conventional per agreed International Agency for Research on Cancer (IARC) terms. It is an umbrella term for all types regardless of primary location, grade, differentiation, stage. Neuroendocrine Neoplasms (NENs) comprises all well differentiated Neuroendocrine Tumours (NETs) and very aggressive poorly differentiated Neuroendocrine Carcinomas (NECs), which has been described as a dichotomy (a division or contrast between two things that are or are represented as being opposed or entirely different). You will see the term “Neuroendocrine Neoplasm” and the acronym “NEN” appear more frequently in specialist papers and presentations. See my staging and grading blog – click here.

Exploring NEN heterogeneity

If you drill further down into NECs and NETs, you find many examples of heterogeneity. Some examples below.

(1) The most common primary locations of NECs and NETs can be very different. NETs are common in the small intestine (particularly the ileum), rectum, pancreas and lung, less commonly in the stomach, appendix, colon; and much less common in several other places including the retroperitoneum and head/neck. NECs are more common in the lung than NET*, less commonly in the Gastroenteropancreatic coverage and genitourinary tract; and much less commonly in several other areas.

* small cell lung cancer is classified as a Neuroendocrine Carcinoma but is commonly included in Lung Cancer statistics and the vast majority of patients are treated by Lung Multidisciplinary Teams (MDTs). But within NEN epidemilogy, it becomes the most common type and appears to never be incuded in NEN statistics, along with some other types of NEC.

(2) The propensity of a primary NET to metastasise is common in some primary types but much less common in others. Stage IV is common in small intestine, pancreas, thymus, lung, type 3 Gastric NETs and although primary tumour size can increase the risk of metastases, less commonly in most other places including the stomach, rectum, duodenum and appendix.

(3) NETs can vary from low stage low grade very indolent to high grade high stage very aggressive. But many low grade NETs may still metastasise over a long period, i.e. there isn’t a direct correlation between grade and stage. When discussing Grade 3, it’s vital to distinguish between well differentiated NETs and poorly differentiated NECs. It’s also important to differentiate stage, as this can have an affect on treatment and surveillance choices.

(4) Even at the lower grades, it’s often difficult to compare someone at the top end of Grade 2 (ki67 20%) with someone at the bottom end of Grade 1 (ki67 of 1%).

So what does all that mean?

To use the most extreme example – in a patient group, you simply cannot compare a stage I low grade well differentiated NET with a stage IV poorly differentiated NEC. Even when you reduce that wide spectrum to a narrower sample, you must be careful to avoid correlations.

Syndromes and Symptoms

If you then drill further down into NETs, you’ll find complications of ‘functional’ primary types producing hormonal syndromes. Often there are multiple possible hormonal syndromes that can be associated with a single organ, particularly the pancreas (but it would be highly unusual to have more than one hormonal syndrome simultaneously).

The Carcinoid problem

It is bad enough that we have to put up the the word ‘carcinoid‘ (a misnomer that drives our awareness backwards) but when everybody is pointing questioners to ‘carcinoid syndrome‘ with undo regard to this person’s primary location, stage, surgery and comorbidities, this can be quite misleading. Other syndromes exist and are more likely, particularly in the pancreas.

Symptoms

A cancer diagnosis can understandably lead to anxiety and a tendency to attribute many physical symptoms to the illness, even if they are unrelated. This is often driven by fear, a desire to understand and control the situation, and the psychological impact of a life-altering diagnosis. This is one of the reasons I started blogging on a serious basis! I do note many people trying their best to convince you that your symptom is almost certainly related to the cancer, or one of the syndromes. Well it might be but not ‘certainly‘. I have to quote Dr Eric Liu here “even NET patients get regular illnesses”.

p.s. Incidental diagnoses of comorbidity (other health conditions) are common in cancer patients. Many cancer patients are found to have comorbidities during the diagnosis or treatment of their cancer, often discovered during imaging or other tests.

Heterogeneity also applies to peripheral issues

I also see a number of questions where people ask what to eat. This is similar to above, many people won’t even need to change diet and others may need specialist advice. No single diet suits everyone and questions should be answered along these lines.

Summary

I outlined a similar text in the blog I cited above “The Heterogeneity of Neuroendocrine Neoplasms” where I also discussed the issues that can be experienced in online patient forums. It is clear that many people don’t quite get how diverse this cancer types is as they submit there questions and receive misleading responses. To some extent, these issues can also surface with doctors who are unaware of the dichotomy described above.

Tumour heterogeneity. The NEC vs NET differences are well known to most. However, it is also true to apply this heterogeneity to individual NEN types, e.g. knowledge that there can be Intra- tumour (within the same tumour) and inter-tumour (different tumour behaviour) heterogeneity in Gastroenteropancreatic NENs (GEP NENs), so even comparing someone with the same primary type diagnosis could be misleading, e.g. receptor availability, molecular profile, prognostics, treatment. There are many things different between GEPNENs and Thoracic NENs (e.g. lung/thymus) You will often see confusion in patient groups. Personalised treatment is not here yet, it’s a work in progress.

Of course, the issues are not just confined to patient groups. Worryingly, some people and organisations still think all NETs are called carcinoid, they all come with carcinoid syndrome and that a (say) Neuroendocrine Carcinoma or Tumour of pancreatic origin is actually Pancreatic Cancer. Some even think they’re all benign. But that’s another 4 blog posts at least!

So, my message to you:

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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Ronny

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