"I’m assuming enlarged compared to resting (given the length) etc.
Correct. It's not small enough to be resting size. But it is normal length for being reactive, and most especially is normal shape (length compared to width).
"if they got one of the enlarged ones, even if it’s not the largest it should show if cancer was present right?"
No, not with certainty. I have seen cases where the largest is lymphoma, yet several nearby ones are large-ish but merely reactive/benign.
"Given they popped up around the same time?"
If within several days of each other, that tends a lot more toward both of them being reactive.
Before a resection, I'd want a trial of a carefully chosen Abx, just to see what happens. Then a trial of a steroid such as prednisone or dexamethasone. Same reason, it's a worthwhile fishing expedition.
"I have weak positive ANA"
Yes, I remember that from long ago. You had the Mayo type of automated test and classification system.
"but docs say they aren’t worried about autoimmune diesease in me"
Right, but the drug allergy still tells us that you have an inclination.
"The potential histoplasmosis was as a child so I don’t know why that would inflame nodes until now."
It's a possibility. Granulomas trap the pathogen inside, and if/when the granulomas get somehow weakened they can release the pathogens, like a jailbreak. (That's why powerful anti-inflammatory biologic drugs won't be given to people with latent TB.)
"Isn’t that etiology for a virus kind of strange? Could that tie into it?"
Yes, especially with the way you summarized it so well just now. As you know, an Abx doesn't treat a virus, but a virus can pave the way for a followup bacterial infection. Some Abx have anti-inflammatory effects, too. Some are anti-fungal as well as anti-bacterial.
"they were giving them antibiotics immediately vs me who suffered for nearly 3 weeks before they gave them."
I can sense that is important, but can't put my finger on why. You being delayed let some change happen inside, but what? Speculating: (1) the virus got into areas where your immune system couldn't get to it, aka evading immune surveillance, but it can later emerge like Lyme (2) your immune system changed, and became over reactive, or (3) that somehow let the histoplasmosis fungus escape.
That likely somehow ties in with what you say about the lymphadenopathy occurring after the Abx.
"given it’s in the same area would still rule out cancer by looking at it. Is that true??"
Well, it's complicated. If it is directly downstream of the most suspicious node, then you might suspect that cancer cells would escape the 1st node then get trapped in the downstream one. Probably so, but not for a certainty. So you'd have to decide if the resection is worth it to you, since it might be the only available option for a resection - but it's not the best option.
This authoritative site mentions lymphadenopathy as a possible reaction to doxycycline.
https://www.drugs.com/cons/doxycycline.html
However, that shouldn't typically last for years.
Whatever you have is atypical, else they'd have found it by now. The focus on a possible cancer was getting in the way, though.
You can try to find any case reports (not clinical trials) of post doxycycline chronic lymphadenopathy.
Better yet, post histoplasmosis chronic lymphadenopathy.
"no evidence of granulomous disease from the biopsy"
Okay, that leaves possible fibrosis, which could be detected by resection and possibly maybe by core needle (not fine needle).
"the FNA doesn’t rule out the lower grade stuff right?"
Low grade cancer? No distinction there between high versus low. But if you mean "not advanced", then you are correct as there is less likelihood of finding malignant cells if fewer are present. But you almost certainly do not have malignant cells, because an alternative Dx (inflammation, with possible infection) is far more likely.
"Also I thought prednisone was a big no no given it can shrink even cancerous things?"
Any cytotoxic effect is very small, almost theoretical, else they'd routinely give it alone in lieu of heavy duty chemo. But pred can reduce cancer associated inflammation/edema, yes. However, if you get a big big reduction in size and other markers, that says there is/was an inflammatory cause of the enlarged nodes.
"While I did improve it got slightly worse again afterwards and THATS when the nodes came. After the antibiotics."
That's quite interesting to me, and takes some mulling. But docs don't typically mull, they just pattern match.
"Making me think another round may not hurt."
I'd agree with you there.
"I am allergic to many antibiotics in the penicillin family"
Then if you are ever asked if you have any immune system oddities, that's one.
https://pubmed.ncbi.nlm.nih.gov/31636024/
"Granulomatous inflammation diagnosed by fine-needle aspiration biopsy "
2019
The interferon gamma test is ~$150
https://www.walkinlab.com/products/view/quantiferon-tb-gold-plus-blood-test
I'd also mentioned last time that you might have a new doc now that will concentrate on finding the real cause. But unfortunately, this pathology investigation just went only as far as ruling out cancer, then stopping. However, you'll likely only have real peace of mind when the real cause for the nodes is found.
So we have, "my wife tested positive for influenza A I took care of her and was in close proximity and never caught it, haven’t had a flu shot in years making me thing my immune system is still on the defensive)"
You are correct, in thinking that probably means you have a very strong anti-viral immune system, and so then I'd posit that your nodes are probably enlarged from a virus. The virus you have is keeping your anti-viral immunity heightened. That's a guess, but it's what we have to go on at this time.
Since nothing is simple, some bacteria like TB or histoplasmosis also can increase blood levels of virus-fighting chemicals like interferon. I'm pretty sure that I'd said to you long ago, and maybe more than once, that I'd want an interferon gamma blood test. If that's high, then a doc has to go about finding out the infectious cause.
TB or histoplasmosis and possibly some others can cause granulomas. I'd want to know if the pathologist looked for granulomas. We've talked about granulomas many times. They should get pulled out in a needle aspiration biopsy, but they might require special staining to see.
"we first try antibiotics"
You've had multiple ABs, right? As mentioned in the past, I'd try an anti-inflammatory like prednisone instead to see what happens.
"I get he’s following a procedure here with the whole 3 months thing but does this sound okay to you?"
Yes, and this end result is what I'd referred to when I'd said last time that we know how the FNA will turn out: not cancer.
"he’s very relieved by the results"
Relieved? Well, I don't know why he'd been alarmed/worried in the first place. Everything about your case says "not cancer", since way back. So to me, the latest result now is kind of a yawner, being completely expected :)
"he wants to see me in three months"
Well, it'll maybe/probably be in your mind eventually that there is some necessity to check in three months. Instead, I would have phrased it, "there's no reason to think anything bad will show up in three months, but we'll check just as a matter of an over abundance of caution".
"is still a very good sign of reactive node?"
Yes. Pain isn't merely like a simple on/off switch. There are also the inflammatory biochemicals that can make pain receptors sensitized.
I suppose it's a threshold thing. AFAIK, normally pain from FNA would be minor, as from a blood draw. But sometimes lidocaine or similar is given beforehand. Some inflamed nodes are tender, some aren't. (Some pimples are tender, some aren't.)
If you repeatedly rubbed that node, it would probably become tender.
My guess is that this doesn't matter, re: palpation versus needle stick.
"Either way is this a good sign?"
Yep, all around good.
"...the ENT plans on investigating more."
And that, my friend, is doubly good. It sounds like you have finally gotten the kind of doc you want. I salute you on your persistence.
Just be 100% sure of what I've been saying to you since way back: if you get the resection, make sure the pathologist does not merely look for (and not find) cancer. Make sure they are instructed by the ENT/surgeon to also look for everything inflammatory... such as prevalence and type of inflammatory cells, any fibrosis and granulomas, blood vessels, etc.
I'll be looking forward to the results from your needle biopsy. But we pretty much know what it's going to say: no cancer.
"So finally another ENT agreed to biopsy my 3cm node."
Your persistence does pay off :)
"...usually people only feel a tug not necessarily pain and that to her that points to reactive things going on. Is there any merit to this?"
Yep, absolutely. Inflammatory biochemicals such as Substance-P and bradykinin cause pain. A cancerous node wouldn't typically be painful - unless there is a necrotic center that's bleeding and causing internal pressure, but that situation would have shown on an ultrasound.
"... it’s potentially possible to get an incisional biopsy without being put under."
Maybe she means twilight anesthesia? Or is it just a locally injected painkiller? Risks from an incisional biopsy are (1) infection, and (2) a problem from the anesthesia, and (3) nicking a nerve or blood vessel. A doc deciding whether to do the resection means considering the risk versus the benefit. Being very near the surface reduces #3. Then if you also eliminate the #2 anesthesia risk, the balance can then tip in your favor and you are therefore more likely to get the resection done.