Recently, there’s been a debate on forums regarding the validity of the term ‘Carcinoid’. I thought I’d gather my thoughts and put to paper. Although the issue is potentially complex , there is one really simple way of looking at it – Carcinoid is a type of Neuroendocrine Tumour (NET) and you will find that classification in dozens of booklets and websites internationally. However, like anything in the world of ‘Neuroendocrine Tumours’, it would be too easy to leave it there.
You may have noticed that ‘Carcinoid’ is often used as a standalone word and tends not to be suffixed with the word ‘Cancer’ or ‘Tumour’ – unlike Bowel Cancer, Breast Cancer, Prostrate Cancer, Lung Cancer, etc. Nobody goes around saying “Breast” or “Bowel” do they? But they happily say “Carcinoid”. Unfortunately, the term ‘Carcinoid’ has become entrenched in both pathology and clinical literature over the past 100 years. The problem with the word Carcinoid is that it means different things to different people. Some use the term almost exclusively to designate serotonin-producing tumours that result in carcinoid syndrome. Some use it to (incorrectly) refer to all Neuroendocrine Tumours. The most worrying connotation of the use of the word ‘Carcinoid’ is the belief that they all have benign clinical and biological behaviour. That is dangerous thinking and will kill people. Check out my blog post “Benign vs Malignant”.
I’m not a medical professional or scientist and as a consequence I’ve confined my research to a few reputable sites so that I stick to facts. However, the following history of ‘Carcinoid’ is well documented – Siegfried Oberndorfer (1876-1944) became the first to adequately characterise the nature of Carcinoid tumours and refer to them as “benign carcinomas.” During his tenure at the Pathological Institute of the University of Munich, Oberndorfer noted in 1907 that the lesions were distinct clinical entities and named them “karzinoide” (“carcinoma-like“), emphasizing in particular their benign features. However, In 1929 he amended his classification to include the possibility that these small tumours could be malignant and also metastasise. (Author’s note – a name change would have been handy at this point).
According to A Review of Carcinoid Cancer written by Dr. Richard Warner, “…..they were found to arise from enterochromaffin cells (glandular endocrine-hormone producing cells) of the diffuse Neuroendocrine System. These cells are widely distributed in the body but found in greatest amounts in the small intestine and then in decreasing frequency in the appendix, rectum, lung, pancreas and very rarely in the ovaries, testes, liver, bile ducts and other locations. These cells have special peculiar features that make them identifiable under the microscope. They stain in a special way when put in contact with silver containing chemicals. Special stains for the particular hormones that enterochromaffin cells can make will identify the hormone substances in carcinoid tumor cells and thereby confirm the diagnosis of the microscopic exam on biopsied carcinoid tumors.” Dr Warner goes on to describe them as “midway between carcinomas (cancers) and adenomas (benign tumors) adding that if overgrowth is somewhat limited and does not spread to other areas or threaten to squeeze out or replace adjacent structures, it is considered to be a benign tumor, that is, not life threatening. However, if the growth is more aggressive and threatens surrounding tissues or sends “seedlings” (metastases) to grow in distant areas then it has potential to be fatal and is considered malignant; that means it is a cancer.”
The American Cancer Society (ACS) describes them as “…..Like most cells in the body, GI tract neuroendocrine cells sometimes go through certain changes that cause them to grow too much and form tumors. These tumors are known as neuroendocrine tumors (NET) and neuroendocrine cancers. In the past, most abnormal growths of neuroendocrine cells were called carcinoids. But in 2000, the World Health Organization (WHO) reclassified carcinoids as neuroendocrine tumors and neuroendocrine cancers. Neuroendocrine tumors are growths that look benign but that might possibly spread to other parts of the body. Neuroendocrine cancers are abnormal growths of neuroendocrine cells which can spread to other parts of the body”. ACS goes on to say “Neuroendocrine cancers (also known as neuroendocrine carcinomas) are divided into groups based on the way the cells look under a microscope:
- Well differentiated neuroendocrine cancers have cells that do not look very abnormal and are not multiplying rapidly. These tumors tend to be less aggressive, meaning that they tend to grow and spread slowly. Well differentiated neuroendocrine cancers can look identical to benign neuroendocrine tumors when examined under the microscope. Sometimes the only way to know for certain that a mass is a neuroendocrine cancer (and not a benign tumor) is when it spreads to other organs or tissues.
- Poorly differentiated cancers have cells that look very abnormal and are multiplying more rapidly. Poorly differentiated cancers tend to be more aggressive, meaning that they grow and spread quicker”
Other sites (including NANETS and ENETS) refer to the WHO classification and it is here another term is introduced – Neuroendocrine Neoplasms (NENs). NANETs state that “all of the entities under discussion are neoplastic, and neoplasm is therefore a more accurate term than tumor, which means only a mass“. It’s important to understand the difference between grade (aggressiveness) and differentiation (the extent to which the neoplastic cells resemble their non-neoplastic counterparts). Well differentiated tends to align to Grades 1 and 2 and recently in 2017, Grade 3a. Grade 3b is aligned with poorly differentiated. An understanding of Stages and Grades is really fundamental to understanding Neuroendocrine Tumours (READ HERE)
At the crux of the issue is the fact that Carcinoid’s credibility in the cancer world is perhaps underrated due to the legacy medical definition of Carcinoid as ‘Carcimoma like‘, inferring not a ‘proper cancer’. In addition, there is a tendancy by some to use the term Carcinoid and Neuroendocrine Tumours interchangeably which is clearly incorrect. Use of the term “Carcinoid and Neuroendocrine Tumors” as a grouping of cancers in USA, Canada, India and Singapore isn’t helpful either.
I believe that the term Carcinoid is a misnomer when you consider the large amount of malignancies experienced by Neuroendocrine Tumour patients and today’s researching has cemented that view. The historical meaning (i.e. the misunderstanding) of the term ‘Carcinoid’ does not help. The term does not adequately convey the potential for malignant behaviour that accompanies many of these neoplasms (i.e many patients present with metastasis confirming their propensity to spread). Like any suspect growth found anywhere in the anatomy, some are found to be benign (not cancerous) and some are found to be malignant (cancerous). In my humble patient opinion, if cells grow and multiply out of control and have the potential to spread; or have spread – that is cancer. Consequently, ‘Neuroendocrine Cancer’ sounds good to me thus the name of my blog.
I believe we do need to get rid of the term Carcinoid BUT …… new nomenclature to describe what was the original histopathological grouping called ‘carcinoid tumours’ in their various anatomical locations are required as there will still be a need to distinguish those from other types of NETs. For example, when someone wants to know the specific type of NET you have, you can’t just say “NET”. Foregut, midgut and hindgut does not drill down deep enough for understanding. Prefixing your net with an anatomical location sounds feasible, although it does split up pre-defined biological groupings spread across foregut/midgut/hindgut.
However, when someone wants to know which syndrome you have, you can’t just say “small intestine syndrome” or “midgut syndrome”. ‘NET Syndrome’ doesn’t work either as there are several NET syndromes. And of course someone of influence in the medical world needs to come up with suitable and widely accepted terms for ‘Carcinoid Syndrome’, ‘Carcinoid Heart Disease’ and ‘Carcinoid Crisis’. Leaving these terms in place is not a good idea. It doesn’t help that many organisations continue to use the word ‘Carcinoid’ in their organisation titles. It is also not helpful that many patients continue to refer to this disease as “Carcinoid Neuroendocrine Tumour” or variations along these lines.
This needs to be resolved by senior physicians and advocate organisations in the NET Community.
Thanks for reading
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