Saturday, July 25, 2015

Acronyms, and Zebras, and Quarter Billions

Hah.. remember how I've mentioned that my cancer was not only incredibly rare in and of itself, but that I had an incredibly rare form of it (which is one reason why it took years to get a diagnosis)?

Well, today I was looking up some of the long term side effects of the cancer in question, and I actually found a paper about the specific incredibly rare presentation that I had... Which was really cool, because it even has an acronym.

In particular, I had atypical Multi-Endocrine Neoplasia (MEN... tentatively classified as an atypical MEN2 presentation), presenting with primary thyroid carcenoma, and non-metastatic undifferentiated micro-lesions (meaning they were only a few cells each, and couldn't be biopsied or typed accurately) of the pituitary, adrenals, and other endocrine tissue.

These microlesions, and possibly the specific type of primary cancer, also caused associated paraneoplastic syndrome, Basically, they makes your endocrine system go out of control, and make your body act like it has other diseases that it doesn't have.

Most prominent in my case, I developed many of the gross symptoms of Cushings disease; so much so that they attempted to treat me for Cushings at one point. However, the treatment actually made me worse, and the next series of tests showed that I absolutely did NOT have Cushings (but at that point, they still had no idea what I actually had. It was another 2 years before they found the cancer).

Notably, while I had microlesions of the parathyroid (along with all my other endocrine tissues), and reduced parathyroid function (I still do in fact, but I have enough that I can metabolize enough calcium as long as I drink a lot of milk or orange juice, or have a few calcium tablets a day) I had no significant parathyroid masses, and no pheocrtomocytoma (I had microlesions, but not large tumors).

These are atypical for MEN2... and for MEN in general. In addition to the currently formally classified MEN1, and MEN2a, MEN2b, and MEN2-FMTC (which is still controversial and not universally accepted),  they are considering making classifications for MEN3 and MEN4 variants which include such presentations.

MEN2 is in itself incredibly rare... Something like 1 in 500,000 people have the genetic anomalies for it, and most with the anomalies don't ever present with the symptoms necessary for diagnoses. Most doctors... even most oncologists and endocrinologists, will never see a case of MEN2 in their practice. Then further, MEN2-FMTC may be as few as 1 in 20 million.

...But that wasn't the new info.. I already knew about MEN2 from way back. The FMTC part IS new, because that has only provisionally come into use in the last few years, and as it happens I had what appears to be a further sub-variant of FMTC, based on the type of primary thyroid tumor I had.

Because what made my presentation atypical (and difficult to classify properly) and even more rare, was the type of primary thyroid cancer I had developed.

The most common types of thyroid cancer are papillary (about 70-75%), and follicular (about 20-25%), with all other types representing less than 5% combined. Of those, medullary is the most common (about 3%), with anaplastic cancers conventionally considered the rarest (less than 1%).

There are a few more rare presentations however, particularly "mixed" or "complex" presentations, where two or more different types of cancerous cells (mixed), or two or more different types of anomalous cancer cell structures or structural abnormalities (complex) occur, within the same tumor. When these happen together, it's a "Mixed complex" presentation.

My tumor exhibited complex mixed papillary, follicular, and parafollicular (medullary) structure, poorly differentiated, with grossly enlarged and malformed nuclei.

As it turns out, it's possibly the rarest form of thyroid cancer... So rare that they are not sure if it should have its own classification, or not... But they made an acronym for it anyway: MMFC (Mixed Medullary and Follicular structure with C-cell presentation... Which may also include papillary and non-epithelial structures as well. These are WEIRD tumors).

How rare is it? As of 2000, only 40 cases of my primary type of tumor had been confirmed and documented world wide... and of those, only 2 were in males, both of whom had MEN2 (as did about 1/3 of the women).

40... total... ever.... (or at least since 1908 when the first was recorded)

According to the best estimates I can find, approximately 10 billion people have lived on earth between 1900 and today. 40 in 10 billion (well... 41 including me, but we'll round off)...

That's 1 in 250,000,000

 Basically, 1 case in America alive today... me... and another 25 or 30 all around the whole world.

...Though to be fair, it's likely there were more, they just weren't documented; either because they died quickly and their COD was just listed as "natural causes" or "thyroid cancer"; or because the disease was treated before it progressed to the point where MMFC could be diagnosed.

...Or they just didn't notice that it was MMFC, because the presentation is so rare, that histologists and pathologists don't look for it, and assume it's a bad test when they see it (it can look like a bad sample, or one that's been contaminated with cleaning solution or something similar).

My first biopsy in fact, while it showed this unusual presentation, was also annotated by the lab as "inconsistent and unreliable", and they considered it "inconclusive". The pathology wasn't confirmed until the post-excision analysis.

Of all the documented cases, those that progressed far enough, ALL had the same tumor progression. They began as relatively slow growing mild malignancies through stage II. Then after reaching between 10 and 15cm, they exhibited rapid anaplastic transformation, reaching stage IV in a matter of weeks or months. At that point they became extremely aggressive and invasive undifferentiated anaplastic malignancies, with lymphovascular infiltration, and invasion of nearby tissues.

... Which is exactly what mine did.

My cancer had aggressive vascular infiltration by the time they excised the primary mass (the doc said it had built its own blood supply with a couple large blood vessels, and dozens of small malformed blood vessels in and out of the capsule) but thankfully hadn't gone aggressively lymphocytic, because the tumor had remained encapsulated. There were a few small clusters of small speckles of cancerous tissue throughout my body, and LOTS of tiny speckles all over (I lit up like a Christmas tree on the body scan), but there were no large distant masses, or large or dense clusters of cancerous tissue.

When they did my post surgery followup, and got the pathology report, they told me that it was the strangest (with the mixed complex structure) and most aggressive anaplastic thyroid cancer they had seen. They said if I hadn't caught it right then, I would have died in as little as a few weeks to at most 3-6 months, depending on how long it took for the capsule to burst, and for the cancer to completely metastasize through the lymphatic system.

That was when they decided I had to have the most aggressive radiotherapy option... which I'm still suffering side effects from almost 3 years later. Because with that type of cancer, you either nuke it hard, or it kills you more than 90% of the time.

Anaplastic thyroid cancers are generally considered effectively untreatable once they invade other tissue, or if they exhibit lymphocytic metastases.

They have a very very poor survival rate... 4-7% survive five years after SUCCESSFUL treatment, because the cancer aggressively returns, even with surgery, radiation, and chemotherapy...

....Unless the tumors are encapsulated...

Thank God mine stayed encapsulated.

By God I am so lucky, and so blessed, to be alive...

... But anyway...

I now have the right acronym for my MEN subtype: