Neuroendocrine Cancers can sometimes present with one or more vague symptoms which occasionally results in a lengthy diagnostic phase for some. Sure, there can be issues with doctor experience and knowledge that can add to the problem. However, some people do present with multiple and confusing symptoms, some people have comorbidities which can also confuse as they come with similar symptoms and the textbook diagnostics don't make sense - sometimes even when the doctor suspects Neuroendocrine Cancer (i.e. classic symptoms of 'something' but with negative markers). Clearly those are extreme cases and just like other complex diseases, many diagnoses of Neuroendocrine Cancer can be extremely challenging, even for an experienced doctor.
Most types of Neuroendocrine Cancer can be accompanied by a 'syndrome' i.e. the tumours are 'functional' and this is normally (but not always) associated with metastatic disease. At this point it's also worthwhile saying that some Neuroendocrine Cancers can be 'silent' for years before any symptoms show and it's only when they metastasize, that these clinical syndromes come to life. Ironically, the manifestation of the disease with a syndrome can occasionally turn out to be a life saver albeit the cancer is normally incurable at this stage - but still treatable.
The most common Neuroendocrine Cancer is (currently) known as 'Carcinoid' (>50%). It can present as a collection of symptoms known as Carcinoid Syndrome and the most prolific one is flushing with approximately 84% frequency. Others symptoms include (but are not limited to) diarrhoea, heart palpitations, stomach cramps and general abdominal pain/discomfort, shortness of breath, wheezing. You can see the scope for confusion and misdiagnosis.
When you look at these general Carcinoid Syndrome symptoms, flushing seems to be the one that stands out as a 'cardinal sign' whereas many others are vague and easily confused with common/regular illnesses. However, the flushing is reported to be different from most people's perceptions of a 'flush'. The Carcinoid flush is almost always 'dry'. To quote my 'amazing yellow book', ".... a good rule of thumb is if the flushing is wet (accompanied by sweating), it is due to a cause other than Carcinoid". Additionally, there appears to be at least two varieties of flushing in Carcinoid Syndrome related to two different anatomical regions of the primary tumour (again a useful guide from my amazing yellow book):
1. Midgut (generally the small intestines (less the duodenal 1st portion), ascending colon, appendix) - faint pink to red in colour, involved face and upper trunk, normally lasts a few minutes and can occur many times per day.
2. Foregut (generally the stomach, lung, thymic and duodenal 1st portion) - more intense, longer duration, purplish, upper trunk and occasionally limbs.
The flushing sympton has many potential triggers and can be attributed to the secretion of excess hormones associated with Neuroendocrine Tumours. Although many people focus on serotonin as the main culprit, there is significant evidence to suggest that other hormones may be playing a bigger part with this symptom, e.g. histamine (particularly foregut), tachykinins (Substance P), bradykinins, and prostaglandins.
However...... even flushing cannot always be attributed to Carcinoid Syndrome, as mentioned previously, the differential diagnosis of flushing is extremely important and includes (but is not limited to) the following: • Postmenopausal state • Simultaneous ingestion of chlorpropamide and alcohol • Panic attacks • MCT (Medullary Carcinoma of the Thyroid) • Autonomic epilepsy • Autonomic neuropathy • Mastocytosis. If you study the online forums, there are frequent questions about flushing, particularly from those looking for a diagnosis and are suspecting Neuroendocrine Cancer/Carcinoid due to a flushing symptom. 
There is a very useful table in my amazing yellow book which gives the tests required to determine the potential source of a flushing symptom. I strongly suspect this is not an exact science (is anything in medicine?) but it's extremely useful. Personally I would have included Rosacea :-)
My own experience with flushing brings back some memories and it emphasises something I say a lot - the patient has a big part to play in their own diagnosis. I was experiencing a mild and innocuous flushing sensation for some months before I was diagnosed with metastatic Neuroendocrine Cancer. Even though I knew it was weird and something I hadn't experienced before and .....I totally ignored it. I failed to mention it at any of my routine GP appointments or my annual asthma clinic. I failed to mention it to my specialist who was investigating a GP/PCP diagnosis of Iron Deficiency Anemia/weight loss. After a CT scan, the specialist appeared to be scratching his head (at that point he knew I had cancer but he also knew it was unusual). I suddenly mentioned the flushing and 'bingo'. It was the face of a man who had just found a missing piece of a jigsaw and he correctly predicted the output from my subsequent liver biopsy. Flushing is a very important symptom and needs to be reported. I haven't had a flush since Nov 2010 and if this symptom comes back, I'll know I have a problem which needs addressing soonest.
I'll complete this post with an interesting summary from an online forum post in which I was participating (some of you may remember it!). There was a general discussion about the severity of 'syndrome symptoms' including their triggers and I was staggered to read that people were experiencing flushing whilst carrying out routine day-to-day tasks. I'm so happy I don't flush when I eat one square of chocolate (that would be a complete disaster!). The one which caught my attention was the simple act of washing hair! Whilst I initially raised my eyebrows and laughed, it did make me think back to the last flush I experienced (and touch wood it was the last .....). Following my diagnosis, I commenced daily injections of Octreotide (a somatostatin analogue drug designed to reduce the effects of Carcinoid Syndrome (amongst other uses)). These injections reduced the flushing but it didn't eliminate it. However, after my 'debulking' surgery in Nov 2010, my flushing disappeared. However, I do remember a flush coming out of nowhere whilst I was recovering in hospital after that surgery. I was cleaning my teeth and I do vividly remember this minor task taking some effort! I therefore suspect this came under the main triggers for Carcinoid Syndrome (the 5 E's) which you can read in my blog here - Carcinoid Syndrome – Early Signs of a Late Diagnosis.
Thanks for listening
Ronny
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