A fairly common disposition of Neuroendocrine Neoplasms is a primary with associated local/regional secondary’s (e.g. lymph nodes), and often with liver metastases. Technically speaking, the liver is distant. However, many metastatic patients appear to have additional and odd appearances in even more distant places, including (but not limited to) the extremities and the head & neck. Certain things are known about the behaviour of Neuroendocrine Neoplasms (NENs) (a term for Neuroendocrine Tumours and Neuroendocrine Carcinoma) and specialists will be analysing many factors when working out the type of NEN and how it might behave. This is useful in cases of unknown primaries as it can give them clues to the possible location(s). Read more about these issues in my article “Needle in a Haystack“.
How does cancer spread?
In addition to the primary growing into other areas, cancer can form metastases through the blood steam and the lymphatic system. This is a system of thin tubes (vessels) and lymph nodes that run throughout the body in the same way blood vessels do. The lymph system is an important part of our immune system as it plays a role in fighting bacteria and other infections; and destroying old or abnormal cells, such as cancer cells. The lymphatic system also contains organs, some of which feature regularly in NETs. If cancer cells go into the small lymph vessels close to the primary tumour they can be carried into nearby lymph glands where they stick around. In the lymph glands they may be destroyed (that is actually one of the jobs of the lymph glands) but some may survive and grow to form tumours in one or more lymph nodes.
Why is the liver frequent site for metastases?
According to the University of California Surgery Department, the risk of cancer spreading to the liver depends on the site of the original cancer. For example, cancers of the GI tract often spread to the liver because their blood drains directly through the liver, this might explain the many metastatic cases of NETs (amongst other factors). Liver metastases are sometimes present when the original (primary) cancer is diagnosed, or it may occur months or years after the primary tumor is removed. After the lymph nodes, the liver is the most common site of metastatic spread. Most liver metastases originate from the colon, rectum, pancreas, stomach, esophagus, breast, lung, and some less common sites. Several factors influence the incidence and pattern of liver metastases. These include the patient’s age and sex, the primary site, the histologic type, and the duration of the tumor (important point for NETs). The majority of liver metastases present as multiple tumors. Only 10% of all cases present with a solitary metastatic lesion. Moreover, in more than three-quarters (3/4) of patients with liver metastases, there is involvement of both lobes of the liver.
My own experience
As a metastatic Small Intestine NET case, I had the usual bulky chains of lymph node metastases in or around the mesentery that frequently appear with an abdominal primary. Most of these were removed along with my primary resection. However, I had known since shortly after diagnosis in 2010 that I had ‘hotspots’ in my left ‘axillary’ lymph nodes (armpit) and my left ‘supraclavicular fossa’ (SCF) lymph nodes (clavicle). These were found on Octreoscan but at the time, they were not pathologically enlarged – just showing uptake. Of course I also had multiple liver metastases and subsequent surgery (read more about that here).
In early 2012, 15 months after removal of primary and 10 months after liver resection, one of the axillary lymph nodes became palpable (signs of growth) and this coincided with a small spike in Chromogranin A. A total of 9 lymph nodes were removed very shortly after this surveillance, 5 of which tested positive for NETs (Ki-67 <5%). As part of the same operation, 5 SCF left clavicle nodes were removed but tested negative. On a subsequent Octreoscan, the armpit was clear but the clavicle area still lit up. However, there is no pathological enlargement or pain – so this is just monitored. The SCF nodes also light up on Ga68 PET (and also sub-pectoral nodes).
I also have a 3mm lung ‘nodule’, discovered in 2011 and has been tracked since then. Apparently, lung nodules are a pretty common incidental finding with 1 per 500 X-rays and 1 per 100 CT scans finding them. This is monitored and does not light up on any nuclear scan (Octreotide or Ga68 PET).
My Ga68 PET scan in 2018, added right rib number 11 to my “metastases CV” – read more here.
False Alarms (let’s hope so!)
- I have a 19mm thyroid ‘lesion’ which was pointed out to me in 2013. This has been biopsied with inconclusive results. Although the thyroid is an endocrine gland, it looks like a non-NET problem to date. Thyroid nodules are in fact very common and statistically, 50-70% of all 50-70 year olds will have at least one ‘nodule’ present (i.e. if you are in your 50s, there is a 50% chance you will have one nodule and so on). The vast majority will never bother a person while they live. That said, my thyroid blood tests are abnormal and on 20th March 2018, following an Endocrine appointment, I was put on a trial dose of 50mcg of Levothyroxine to counter the thyroid panel results indicating hypothyroidism. Levothyroxine is a thyroid hormone replacement.
- Early in 2017, during my Endocrine MDT, a surveillance ultrasound spotted a slightly enlarged lymph node on the right side (measuring 9mm x 9mm) described as a ‘level 4’ node (a location indicator meaning the ‘lower jugular group’). The report was passed to the NET MDT for their consideration with the surgical rep on the Endocrine MDT recommending a conservative approach – the NET MDT agreed. I suspect that’s right, it’s still below the worry threshold, nothing is palpable (no lumps) and I don’t have any specific symptoms. There could have been a number of reasons for the enlargement and it might even be back to normal size on my next scan (spoiler alert – it was). All my issues have been left-sided to date, so that was an interesting diversion.
- I had an MRI in 2014 to investigate pain and a swelling at the site of my right ‘sternoclavicular’ joint – subsequently declared a non-issue. However, it got a mention in my 2018 Ga68 PET as “inflammation”.
- Ga68 Pitfalls? So is the uptake showing on Ga68 PET just physiologic for the above-mentioned left SCF nodes, left sub-pectoral nodes, and the thyroid (albeit it is a lesion)? Are these areas just ‘reacting’ to the tracer? It would seem to when you look at CT scans and ultrasounds which indicate a lack of pathological enlargement. Clearly that doesn’t include the thyroid but they seem to produce uptake.
Life as a metastatic Neuroendocrine Cancer patient is interesting and efficient surveillance is absolutely critical.
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