Research around FVPTC

After TT in 2/2009, my pathology showed my thyroid had a 3.5 cm Papillary/Follicular tumor.

Not a single doctor has addressed the 'follicular' aspect of my pathology. But each doctor (2 endos and the surgeon) strongly recommended RAI ablation for me 'some day'.

It was not until here, that I had even heard of follicular variant. So, I started researching and found that there seems to be new and invigorated research studying different aspects of FVPTC.

I found this study interesting and an encouraging sign that the medical community continues to explore thyroid cancer.

This is just one study in the mix of many. It is not meant to alarm, only to inform. I know I will be inquiring to my physician about my particular aspects of follicular characteristics.

http://jcem.endojournals.org/content/91/1/213.1.full

"Context: The clinicopathological characteristics and the molecular features of the follicular variant of papillary thyroid carcinoma (FVPTC) remain controversial.

Objective/Design/Patients: In an attempt to clarify such controversies and to find whether or not FVPTC cases share the molecular features of follicular tumors,...

We think there is enough evidence to rule out the idea that FVPTC, as a whole, should be considered as a subgroup of conventional PTC (Fig. 4A⇓), and we would favor, taking into consideration the metastatic pattern (4, 5, 6, 7, 8, 9) and the molecular features described in the present study, the concept represented schematically in Fig. 4B⇓.

The study of a larger series of FVPTC with long follow-up and detailed data on lymph node and lung metastases is necessary to find out the clinical significance of the occurrence of the three genetic alterations (PAX8-PPARγ rearrangement, RAS mutation, and BRAFK601E) per se, or in association, in FVPTC. It will be interesting to find out whether the tendency for blood-born metastases of some FVPTC may be ascribed to a particular molecular profile of the tumors, namely to the presence of PAX8-PPARγ rearrangement (see above). In the affirmative case, we would suggest that such encapsulated FVPTCs with PAX8-PPARγ rearrangement should be classified, for practical purposes, in the group of FTC rather than as a variant of PTC (Fig. 4C⇑). "

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That's really interesting. Mine was a follicular variant too. They explained to me that it was the rarest of the most common......if that makes sense!! I wasnt overly stressed about it and just did what I was told lol!!

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I like that explanation! :)

Yes, I haven't been stressed about it, but certainly wonder about it.

It's difficult not to 'peek' (research) :D

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Just to point something out, that article originally appeared in 2005, over six years ago. That's not exactly what I'd call up-to-date research. I will point out again, to anyone who is alarmed by such posts, that follicular variant has been shown to behave agresssively, like straight follicular cancer, ONLY in cases where the pathology report shows vascular invasion. If there was no vascular invasion, then it can't have spread into the bloodstream, which is what follicular cancer tends to do. Moreover, FVPTC is less likely than straight papillary to spread to the lymph system.

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In the world of longitudinal studies, 6 - 7 years isn't a lot.

As I said originally, I did not post this to cause alarm, and personally do not find the study alarming.

If you have more studies to add to the conversation, that would be great. I have never read that FVPTC is less likely than PTC to spread to the lymph system. It would be great to see the evidence/research.

If you have research to back up your assertions, that would be appreciated.

I think it is apparent from other discussions here, that you (kat17) and I usually have differing opinions. I'm not here to argue with you.

If you're not going to back up your finding/opinion with some kind of research and articles, your point is lost on me.

The point of my discussion here is to share common knowledge of FVPTC, not accuse on another of being correct or incorrect.

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Did you know that the FVPCT has a lower likleyhood to have the BRAF gene though? The BRAF can make PTC more aggressive , new studies are picking out this gene and targeting it for new drug inhibitors . Good news both sides!

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It is all very interesting and complex! This particular article suggests that the medical community look at three components in FVPTC, BRAFK601E being one of them. Any idea if that is a BRAF gene?

The follicular aspect caught my attention here and as I've started looking at a couple articles, I've started seeing it being mentioned that they see 'mutations' (not necessarily the exact word) come up in FVPTC, which is really concerning because they can't figure out an indicator as to which ones will morph into a more aggressive thyroid cancer.

Which then brings me back to a discussion with my endo (in relation to RAI ablation) where she said something like, we don't do it for the ones we know about, its the ones we don't know about which really scare us.

So for me, I am 'connecting the dots', if you will, to my particular experience. I am not exactly sure I am on the right track, but will most likely talk to my endo about it, when I get the chance.

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Being ABLE (even in limited numbers) to metastasis via the blood stream is an element which just doesn't show up in garden variety PTC. It seems to me that what is likely to shake out is that some FVPTC tumours are going to act like PTC and some like FTC but at this point standard pathology methods can't sort out which is which, let alone which prognosis is great and which is questionable for individuals in either group.

Most of the older studies will be looking at only cancers which were large enough to be palpable or symptomatic due to space occupation, and in most cases tumours that large have been around for quite awhile and may well have had more opportunity to metastasise if they were going to. Tumours like my FVPTC, small ones picked up by accident, are now cluttering up the research (as is the case for small PTC tumours). It will be very difficult for researchers to be sure they are not comparing apples and oranges (classically found tumours versus accidental finds); so I am very pleased that they are looking at genetic markers as a better way to help sort out which tumours are more likely to cause trouble rather than simply following heterogeneous cancer populations and trying to relate outcomes back to patient and original pathology characteristics.

I further believe this will help sort out which Thyroid tumours (of all differentiated types) presenting in older patients are likely to be serious trouble - it seems probable that older individual's tumours had historically been there longer and had more chance to spread than had tumours in younger people, thus the stats look worse for older patients. And they had also been in place long enough to veer toward poor differentiation if they were the type that was going to do that.

We have quite a few women here who have had thyroid signs and symptoms for so many years (or decades) that their docs don't even think there could also be a cancer in the lumpy bumpy thyroids - does this "There, there dear; it's all in your head" attitude further skew the stats because it is taking so long to get these cancers diagnosed? Docs were firmly indoctrinated with the idea that benign thyroid disease somehow also indicated (not through logic) that cancer would not be present. Perhaps younger patients are more inclined to kick medical ass and get diagnosed? Early diagnosis SHOULD reduce the stats for lymphatic spread and vascular spread as well, but we don't really know if that actually is the case or if spread will relate only to the type of mutation rather than the type of cell involved or when the cancer is diagnosed. So we need current studies of recent diagnoses.

Part of what I am getting at is that a study from 2006 seems much more likely to be clinically relevant to today's patient that the older bodies of knowledge. What we have now in thyroid cancer is knowledge going back to the 1920s and 30s - sort of like comparing historical TB to today's TB cases; interesting but not entirely clinically relevant. Longitudinal studies of people diagnosed since, say 2000 - just a vague estimate of when docs in general started really noticing thyroid cancer as a possibility - will take decades for real results. I am hoping that cancer centres will have banked tumour tissue so that genetic testing can be done in conjunction with individual case outcomes to get a more rapid look at what's what. Don't know if that is happening.

My own case is a fine example of how muddled the stats can be. I was 52 at accidental diagnosis - I had large benign adenomas diagnosed by FNA, but the radiologist doing the FNAs was suspicious about the plethora of other nodules, some tiny , some larger. He told me that even just a couple of years earlier he would have been happy to leave it at that, but now he was seeing more cancers tucked away in cases like mine so he sent me to an oncologist (the specialty which follows all cancers here) to sort out what to do. She said the same thing - a few years ago she would have let it rest but now she was interested in having the areas with the large adenomas removed and run through pathology. If I wanted. Or we could wait and see. I had been unable to get my Hashimoto's taken seriously - my TSH was always just under the 5 at the top of the range, so "obviously" I was doing just fine - so I rather thought the surgery might prove useful for that (as well as putting to rest these mild concerns from two different specialties). No one had any real reason to expect cancer, we just wanted to rule it out.

So ... yes. One small nodule of FVPTC and another small possible one (yes from one pathologist, no from the other, LOL). Statistically I was at virtually no risk so we opted to leave the remaining 1/3 of a lobe in place and follow with annual stimulated Tg levels.

Six years later neck pain has triggered an ultrasound and found a 3mm nodule in the bed of the lobe that was entirely removed, plus a suspicious lymph node [these are both nowhere near where the neck discomfort was, of course].

We can't do an RAI scan because of the big lump of leftover thyroid so at this point we are waiting to repeat the u/s at 6 months and see if that node is still looking out of whack, and if that nodule is still there (these things can always be artifacts when that tiny). If they are both there I will be statistically an older patient with a micro incidental original FVPTC tumour, with local recurrence or metastasis (hard to say because the nodule is not right near where the cancer was), PLUS lymph spread. So sorting me into one pile or another would be less than easy! [PLUS the great likelihood that had the original not been found I would STATISTICALLY have gone on to die in my 90s from something else altogether; but once the micro tumour was found we are set on this path whether we need to be or not. There is no way now to sort that out, so we proceed as if this cancer is a threat.]

If things are still there in the spring we may go after it all surgically (which will be difficult in a real mess of old scar tissue in there) and then be able to do an RAI scan to look for any further lymph or vascular metastases.

Each tumour springs from one genetically altered cell which manages to escape the body's immune system surveillance. Some few of these are going to be way worse news than all the others. I am really hoping that researchers will be able to follow the progression of early-found micro tumours to discover genetic markers which will inform treatment depending on REAL prognostic factors rather than on past and current prognosis of large groups of patients as if they are one. And I am expecting that sort of research to enable figuring out which FVPTCs are going to act like FTC or PTC, thus which patients can be safely monitored just by u/s for lymph spread, and which will need RAI scans for follow up in case there will be vascular spread.

[I see I have written a long essay again, laugh-at-self-emoticon.]

- Katy

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so many great points, katy! :)

and the whole crux of the issue (in my opinion) is the old school way lumping all FVPTC into a subset of PTC. I'm glad science is realizing that that is not right. I get the impression there was a lot of lax in studying thyroid cancer because it's so 'treatable', 'curable', and 'survivable'. kind of automated and assembly-lined treatment.

the 'new school' has come in and is saying 'hey wait! there is more to be discovered here!' and maybe it's breathing fresh life into thyca research.

for me, I'd rather have some kind of knowledge that this 'piece of cake' 'good' cancer of the cancers does have tricks up its sleeve. this way I can read my body and monitor my own self and be aware that complications can arise. maybe that will some how get my 'feelers' more receptive :)

I just don't want to have that feeling like the rug has been pulled out from under me, yet at the same time, can not live my life in fear of this sucky cancer. I'm just looking for the healthy balance.

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I too have follicular varient of Papillary ca, which is acting quite aggressively and is functioning (making hormones). I wish I had a dollar for every time I was told this was not possible. Each time my cancer has come back I have been able to tell the Drs. before they can detect it radiographically, and nearly a year before my Tg levels climb high enough to become detectable. ( I get night sweats, hot flashes, heart palpitations and my favorite nearly faint!)

I have found we must be our own advocates! You know you body better than everyone else.

The research is very exciting and validating! Thanks for sharing.

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Very weird that they think thyca won't be functional! The ability to make thyroglobulin is part of that functionality, so why on earth would they doubt hormone production? Geeze. Not enough to budge your TSH, I bet, so not "real". Sorry you are having so much trouble with the cancer, let alone the docs. You likely will make believers of the ones you deal with directly.

Anyhow, welcome!

- Katy :-)

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Jani - It is encouraging to see the continued research on the folicular variant side of our disease. The findings are somewhat concerning to read, though. I questioned the follicular variant from the beginning because I read up on it and formed an opinion that it can be more aggressive than straight forward PTC. My endo never would directly answer the questions.

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I think its tough to answer. And I don't think there are any absolutes, especially right now as they are in the midst of learning and studying more.

I'm with you on the opinion that FVPTC may be more aggressive than straight forward PTC, but not all the time. Not in the majority of cases.

When I talk with my endo, I'm going to ask her, in her medical opinion, might be safe to say that more FVPTC has a higher chance of morphing into a more aggressive cancer than straight up PTC?

And I will probably ask her about this study and if she knows more current info on the PAX8-PPARγ rearrangement, and if it is proving to be clinically significant? If so, was my tissue examined for the PAX8-PPARγ rearrangement?

Or something similar :))

Generally, I bring her a couple questions and then that gets the ball rolling and we have a short 'laundry list' of items that she can either readily address, or look into for me.

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My point exactly, it is tough to answer because the docs are still trying to figure it out through research. I think the medical community has a challenge on their hands when they lump things together to create subsets and then expect these subsets to behave predictably when one could be passive or aggressive, one more than the other. Cancer in itself is unpredictable and though the data may show predictable trends and patterns percentage-wise there are no absolutes. I had to figure out for myself that the follicular variant part of my diagnosis was becoming the dominant aggressor since it appears I may have metastatic disease to the lungs (still don't know yet, it may be vascular in the neck or bones or all???). Maybe treating each part of the disease, i.e. the main cancer and the variants individually would be wise. Maybe follicular was the main cancer but it was mistaken for PTC. I don't know. The research is interesting and it helps me to understand what may be happening since getting answers from the endo's can be difficult. The new one will hopefully be willing to discuss this.

From what I've read here, it seems like the follicular variant gets little mention or explanation and basically gets blurred into the background until it becomes the problem.

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Yep. Totally. No one ever addressed the follicular part of my pathology, ever. I was so confused when I first joined this site. I didn't even know they were separate (papillary & follicular). No one used the word variant either, so I'm still puzzled on that one too.

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I had TT surgery because the FNA pathology was not definitive. Pathology report was FVPTC - capsular extension, vascular invasion, and soft tissue invasion. The surgeon did not remove any lymph nodes. During my pre-RAI scan, they discovered and removed malignant lateral lymph nodes. Fourteen months after my first surgery, I am now stage 4 FVPTC and waiting to find out if I will need a second RAI treatment for elevated Tg. Here's hoping for more research!!

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The final pathology report is the KEY to whether you have to worry about your FVPTC being more agressive than PTC. Capsular invasion, vascular invasion, lymph involvement, unclean margins all up your potential. For those of you who are alarmed by the aforementioned article, I can tell you this. My endo, a thyroid cancer specialist at, arguably, the #1 thyroid cancer hospital in the country, told me that she does not believe I will ever have to worry about my follicular variant cancer again. I had no invasion, clean lymph nodes and clean margins, so that's the key. I can also tell you this: My tumor was not small. It was 2.8 cm. That's sizable and yet it was still entirely encapsulated. Clearly mine was NOT agressive, and all the research I shared with my endo (with which she concurred) indicates that cases like mine have virtually zero chance of recurrence. Each of you must go over you pathology reports with a fine tooth comb with your endos, but there is no need to worry that just because you had the follicular variant you are in a worse position than those with straight PTC.

And Jani, at the risk of pushing my "differing opinion" on you, you need to talk to your endo too. If your pathology report does not say follicular VARIANT, then you could have had a follicular cancer (which is an entirely different beast). Did you have more than one malignant tumor? Perhaps one of them was papillary and another was follicular. I know of at least one other member here who had such a diagnosis, so while not common it does happen. You deserve to know, in plain language, exactly what you're dealing with.

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FVPTC does not equal a more aggressive cancer in the majority.

None of my doctors suspect I will ever have to worry about thyroid cancer, ever again either.

That's great that you have virtually zero chance of recurrence.

I feel like you take this research personally, as if it has some direct indication to your pathology. No one here has said having FVPTC automatically puts a person at a worse prognosis.

I did not have follicular cancer. It is stated "papillary/follicuar" exactly like that. Also, I had one tumor. I did NOT have two tumors, one being pap. and the other fol. I am quite certain I would know something like this and if for some reason I missed that in the discussions and review of my pathology, my husband would NEVER miss information like that.

I do know in plain English, what I am dealing with but now, as time goes by, I have new questions. I do not think that is unreasonable, considering I need to spend the rest of my life being monitored for recurrent cancer.

I, too, have a GREAT endo from a well respected and highly regarded institution. Not only that, I have the added benefit of having a husband with both an MD and a PhD in molecular biology, specifically neuroscience, so I have many great resources at my appreciative disposal.

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As long as you feel comfortable with your situation, that's the important thing. My pathology report explicitly states follicular VARIANT, so the fact that yours doesn't just seems odd. It also seems odd to me that, as you say, "No one ever addressed the follicular part of my pathology, ever." I'm glad your doctors have concluded that you are in a similar situation to me and don't have to worry about this god-awful situation we've all been put in again.

For the record, I don't take any research personally. I am FULLY informed (and continue to stay that way) about my situation, and I know I have the best possible doctors in the country. What I take personally is people posting information that unnecessarily scares others. Any cancer is scary #$!^ to begin with without adding alarming studies to the mix. Of course we should all be as informed as possible, but for every alarming article out there, there are at least two or three that are soothing. Pointing that out is my intention when posting in response to a single study. As you stated yourself, "FVPTC does not equal a more aggressive cancer in the majority." What's more, in several it equals a less agressive cancer.

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Ha, well, if I get right down to it, no one really addressed the papillary part of it either! :D My case has been pretty textbook and unremarkable. The surgeon found exactly what he expected to find and things went the way he thought they would. The pathology is exactly what the doctors expected and there has been no cause for concern. Things look really good for me. My endo says I have a very, very good prognosis. I like those two 'very's. :))

If any person finds the article I posted alarming, I hope they are comfortable enough to write a quick post. I am sure this great support community will help address such alarm and concern.

The article is not alarming. It's pretty straight forward in reasoning. If the article 'scares' anyone, for that I do apologize, as I stated from the get go, that is not the intention.

In reference to your statement, "As you stated yourself, "FVPTC does not equal a more aggressive cancer in the majority." What's more, in several it equals a less agressive cancer."

This is the perfect discussion to share such findings/articles/research. Perhaps, that would help set another person's mind at ease.

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When I was first diagnosed I was better off not reading too much information because it just caused anxiety and overload. Now, I really appreciate looking at the latest research, as long as it come from a reputable source and is current. If I'm having a particulary anxious day I won't seek out that sort of information until I feel like reading it. I can't speak for everyone but I think while it may be scary, I am curious by nature and I appreciate the information. I don't think anyone here puts this stuff out to scare anyone. What we interpret from the research is the responsibility of the reader and how they interpret it. I think we can all agree that cancer in itself is scary, but the research is necessary for us all to fight and hopefully kick this nasty disease. I don't think enough research has gone into the different types of thyca but that seems to be changing.

I think we've established that you both (jani & Kat) have confidence in your medical care & prognosis. That is a wonderful advantage to have! I hope to be joining you soon! While I agree that the final pathology report is key, it's only as good as the docs interpretation and subsequent treatment. I have found out the hard way that having the right team who specializes in thyca so that all of the findings are interpreted correctly & subsequently treated correctly from the start is the most important thing.

It was suggested that the article from Sloan Kettering (with recent information up to 2010, siting same findings by LiVosi and Baloch) that I posted a couple of months back may "scare" people, mostly because the language used in research is hard to understand by non-medical professionals, and one can misinterpret or wrongly internalize the findings. I was mortified because the last thing I'd want to do is scare people. I only want to help and support like everyone else here and thought the information could help. Whether it scared me or not, I'm glad that I read it since, in my case, it correlated with what I thought my treatment should be based on my findings & what my gut was telling me, and it pushed me to get better care, even though my final pathology report seemed straight forward and predictable. The jury is still out as to how the different variants of thyca will act. The article below is promising because they will test tumors at the chromosonal and molecular level in the near future. I know it's very important to stay positive, but I think it can also be dangerous to get too attached to absolutes because it's what we all want to hear, rather than staying informed even if the information is scary and may or may not pertain to our particular case.

This is the part of the article that stuck with me.

"Some authors have suggested that patients with encapsulated, noninvasive FVPTC have an excellent prognosis and, thus, believe that only a lobectomy is needed (5). However, there are no outcome data with long median follow-up from a large number of patients with FVPTC. More important, to our knowledge, there has been no study in which tumor behavior was analyzed
according to histologic "subvariants" of FVPTC (i.e., nonencapsulated [infultrative/diffuse] vs encapsulated that can serve as a basis for a conservative treatment approach for encapsulated, noninvasive FVPTC. In
addition, there is some controversy regarding the classification of FVPTC as a member of the PTC group versus the FTA/FTC group.

Indeed, Baloch and LiVosi showed that some encapsulated FVPTC metastasize to distant sites in the absence of lymph node metastases, mimmiking the
behavior of FTC (9).

Other authors reported that FVPTC has a significantly lower metastatic lymph node rate and more often is encapsulated than classic PTC (10-11).

Recently, several groups have attempted to analyze FVPTC at the molecular and chromosomal levels (10,12,13)

All of those studies concurred that the molecular profile of FVPTC seems to be closer to FTA/FTC group than to classic PTC, supporting further consideration of the classification of FVPTC."

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