During Sydney's last set of scans we had several little surprises. Thankfully most were unrelated to neuroblastoma. One of the scans however, MIBG, did show some uptake. Uptake on MIBG scans is always the scariest for kids with neuroblastoma because it has such a high specificity. In other words, it has a pretty good track record of only lighting up what it is supposed to. It is very specific to neuroblastoma. It should also be noted that MIGB is also used to detect other conditions such as pheochromocytoma. The bottom-line, however, is that MIGB is a pretty good tool at finding neuroblastoma and when in lights up on a scan it is a pretty good indication in a child with neuroblastoma that it is indeed neuroblastoma. I have always considered it one of our best weapons of detecting neuroblastoma. I have always considered it an accurate tool. Is it foolproof though?
MIBG dose show false positives. As of this date, a search of pubmed on "MIBG false positive" will bring up 111 articles. It is important to note that the bulk of the literature discussing false positive MIBG scans deals with soft tissue. In fact, until recently, I had never seen a published article which addressed false positives in bone. In soft tissue, there are a myriad of things that will uptake MIBG. Most of these are of sympathetic origin but there are several examples which are not.
One of the most common examples of soft tissue with MIBG uptake is brown fat or brown adipose tissue (BAT). BAT is one of two types of fat found in mammals. It is especially abundant in newborns and its primary function is to generate body heat. It is commonly found in the nape of the neck and is often a source of false positivity in MIBG scans. In fact, there are published reports showing as many as 12% of children with neuroblastoma showing accumulation in the nape of the neck - in none of these cases was the accumulation identified as a tumor by other imaging modalities or follow-up studies. Interestingly, it is also most commonly seen in winter.
There are several other soft tissue examples of false positivity as well. It is well known that MIBG can be taken up by tumors such as pheochromocytomas but it can also be seen in some carcinomas, adenomas, and angiomyolipomas. There are reports of uptake in an excessory spleen, benign liver tumors, and pyelonephritis. Uptake can also be seen when there is an obstruction in the urinary tract or kidneys. It has been seen in arteries and veins with stenosis and capillaries with angiomas. While that probably seems like a rare occurrence, you should note with all of the surgical intervention and chemotherapy seen in children with neuroblastoma it is more common than you may think. We have even seen uptake in the adrenal glands unrelated to neuroblastoma when the children have been treated with chronic adrenocorticotropic hormone. Finally, as you can tell if you have ever seen an MIBG scan, there are many examples of uptake throughout the chest an abdomen as the MIBG radiotracer makes its way through the blood stream and out of the body.
Seeing all of the potential for false positive may make one more wary about the specificity of MIBG. The good news is that most radiologists are trained to be able to tell what is real and what is not. However, it does illustrate the strong potential for false positivity in soft tissue.
Bones are a different story and there are far fewer examples of false positivity for neuroblastoma. Frankly, until recently, I had never even seen one in print. However, in this months Journal of Clinical Oncology (Vol27, 2009) there is a correspondence which seems to indicate some examples of false bony uptake - one on the ribs and another along the vertebra. The authors quote a small cohort but site several examples in the lungs, liver and original tumor bed in which MIBG showed uptake that later became non avid without further therapy indicating that perhaps these historical telltale signs of neuroblastoma relapse may in fact not be real.
So, as a parent of a child with neuroblastoma, what should all of these mean to you? Well, MIBG is still a pretty specific test to find neuroblastoma. However it is not bullet proof. It does fail. It is important to confirm findings with other scans and tests. At times, when you are suspecting a relapse due to a finding in MIBG this post may bring you some hope. More importantly, if you are one of the lucky few to have false positivity it may also prevent unnecessary treatment. Proceed with caution. Look at the entire picture.
That is what purpose is all about.