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Tumour differentiation - does it change?

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Posted 3/3/2017 4:51 PM (GMT 0)
Hi all, I have a question about tumour differentiation. A Gleason 8 is poorly differentiated, right? But what about when it's tiny and just starting to grow? Is it less poorly differentiated at that stage and could be described as well-differentiated?

Eg if there's a met from a cancer that's gleason 8, and that met has just started to grow...is it poorly differentiated at that stage and is it still a gleason 8?!

Sorry if I'm not wording this very well, my brain is a little overwhelmed at the moment but it's something I've always been confused about and haven't found a straight answer on (maybe there isn't one?!)
Posted 3/3/2017 5:12 PM (GMT 0)
It's generally understood that it is, and remains, what it is "born" as...


Read this Harvard Medical School publication titled Prostate cancer lives as it is born: slow-growing and benign or fast-growing and dangerous
Posted 3/3/2017 5:23 PM (GMT 0)
After it's metastasized, it is no longer Gleason 8. Gleason grades describe the cellular architecture within the prostate gland, and does not apply to metastases. Metastatic cells undergo genetic and phenotypic transitions. Metastatic cells mutate more rapidly than cancer cells within the prostate, if that is what you're asking.
Posted 3/3/2017 5:37 PM (GMT 0)
Its controversial...I think it is born a particular way but over time can...not always...be come more from less...it makes sense to me...the attribute of more from less{the possibility thereof}...seems to be a common thread...yea or nay...in life...whereas in "death" the opposite is true...unless of course you...

side note...replication is different than growth by a sliver of nuance...You will just have to figure that one out on your own...apologize for that...I am unable to not see the dots once connected...
Posted 3/3/2017 5:43 PM (GMT 0)

JackH said...
It's generally understood that it is, and remains, what it is "born" as...


Read this Harvard Medical School publication titled Prostate cancer lives as it is born: slow-growing and benign or fast-growing and dangerous



I should add this comment for completeness: Just because you have 4+4 now doesn't mean that you might not grow some new 5+5 later, or some new 3+3. Each is born separately.
Posted 3/3/2017 5:45 PM (GMT 0)
thanks all. didn't realise gleason isn't applied to mets! my dad's lesion is listed as poorly differentiated in the pathology report - we're trying to figure out how "normal" that is and whether we should be majorly concered. as he's a gleason 8, we figured it wouldn't be too unusual for the met to also be poorly differentiated and have a negative psa (his cancer has never produced much psa) but maybe we've got it wrong? if he's on casodex is it possible that's why his pathology report said the bone specimen was negative for PSA? the uro is very concered while the radiation onc isn't. i'm not sure who to believe!

would this met have been less poorly differenitated in its early stage of growth and did this +1 year of delay in treatment make it more poorly differentiated and stronger? the uro ignored psa rises for a year and then the met came up because of severe back pain. just wondering what else may be lurking but not showing up on scans :\
Posted 3/3/2017 5:48 PM (GMT 0)
to give more background, the uro is convinced this is small cell/anaplastic which may also influence his concern around the fact that it's negative for psa.

if it was anaplastic, wouldn't the pathology say "extremely undifferentiated" or even just "undifferentiated" instead of just "poorly differentiated"? am i overthinking this?
Posted 3/3/2017 6:03 PM (GMT 0)
Gleason 8 is, by definition, poorly diferentiated, I believe. It's not whether differentiation has changed that determines whether the delay it's what those cells did, where they went.

Yes, I think you are overthinking. But that's easy for me to say to another. I do it all the time.
Posted 3/3/2017 6:06 PM (GMT 0)
thanks, pratoman. so far they have only been able to find one met at t6 on his spine - hopefully that's all there is. 80% of that met was removed during surgery. do you know any way of figuring out how aggressive and fast-growing it is? it has grown 19mm at that one spot in just over a year (though maybe longer, dad first began feeling mild pain there in jan 2016)

or maybe that's a question for another thread!
Posted 3/3/2017 6:24 PM (GMT 0)
snowcake-

I thought you said the path report said it was ordinary metastatic PC. Differentiation of mets is a complex issue. Neuroendocrine mets, for example, are more differentiated. Cancer stem cells are less differentiated. Some of the less differentiated mets show less PSA. What really is important is what they will respond to.

Yes, you are overthinking this. That is an understandable symptom of your anxiety. There is no way of knowing what the met might have looked like if found earlier or if you'd waited longer. You can only deal with what you know when you know it. Focusing on what might have been and what might be distract you from the real issues that ought to be the focus of your attention. The questions you ought to be asking are all about what is the best course of action now.
Posted 3/3/2017 7:06 PM (GMT 0)
thank you again, as ever, tall allen. what we previously thought the report said wasn't what it actually said - it was just the radiation onc paraphrasing. so we got the actual copy of the report today and it said it's a "poorly differentiated carcinoma whose tumour cells are ck8/18. they are PSA and PAP negative."

our next course of action is to get another assessment done ASAP and then once those results come in we can go to the medical and radiation oncs at our major cancer centre (which is supposed to be great)

it's just the waiting and beuarorcracy...the uro has to put in a request for another assessment and only then can we proceed. so hopefully it'll be quick.

in the meantime my dad is on lupron/casodex and hopefully that is helping!
Posted 3/3/2017 7:36 PM (GMT 0)
Well, they didn't identify neuroendocrine markers, which is encouraging. The ck8/18 markers usually mean they express enough androgen receptor to make them susceptible to hormone therapy. The negative PSA and PAP means that it will be difficult to use PSA to monitor progression. I wonder whether they looked for PSMA - if it's positive for that, they may be able to use Prostascint or one of the new PET scans to monitor progression.

These less well differentiated types are always more radioresistant, so if they are following up with SBRT, that would be a better choice than IMRT.
Posted 3/3/2017 8:35 PM (GMT 0)
thank you so much, tall allen! this is what i needed to hear in this moment to tide me over for a little while. it's encouraging that these markers may be good for hormone therapy. i think in my dad's case PSA has never been ideal to monitor progression, his last check a few weeks ago it was 0.45 (went down by itself from 1) despite the fact that he had a met. it's been rising but low for a year while this met has been progressing. so from that point of view i guess the negative psa make sense?

i wonder if they even looked for neuroendocrine markers. hopefully they did and nothing suspicious showed up! at this point we just don't know what they looked at but think it was just a standard pathology. i guess the reassessment will include a wider variety. this report did say they're gonna do additional expanded panel of immunostains (no idea what that includes) but no indication of when.

just hoping this is the "standard variety" of pc so we have a bigger range of tools to fight it off
Posted 3/3/2017 8:37 PM (GMT 0)
oh and yes, the plan is to follow up with SBRT - we have an appointment on monday to assess whether he's a good candidate for it. thanks for mentioning that, as it makes us feel more confident in our decision to pursue it!
Posted 3/3/2017 8:57 PM (GMT 0)
They almost always look for neuroendocrine markers, and most kinds are pretty obvious under the microscope. It sounds like the pathologists are looking at it very closely. From everything you've said, it sounds like he is getting excellent care.
Posted 3/3/2017 9:47 PM (GMT 0)
thank you for the reassurance, tall allen! once we get the sample reassessed we can be more sure (and the urologist can be more sure too) but i think the fact that an androgen receptor is there is a good sign so far. and if neuroendorcine markers are usually assessed that makes me feel better too since it means they've probably already looked for those signs. fingers crossed!
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