Indolent lymphoma and the difficulty of diagnosis

So, in Sept 2008, I was diagnosed with Stage 1 Follicular NHL by a major East Coast cancer center (they provided my second opinion) after being dx'd Stage 4 here at home. I had 20 rounds of radiation after which another node (still on the right side of the diaphragm) was found so 20 more rounds were administered. In July 09, I was said to be in remission. In May 2010, I was found to have a new node north of the diaphragm so was declared Stage 3. In the April 2010, I developed multi-focal neuropathy. Since then, I have been fully examined by the neurologist team at my local medical center, in consultation with my oncology care team.

We spent some a lot of time talking about the root cause and, as I understand it, the lymphoma has caused a reduced expression of the GM1 antibody in my blood, which leads to the deterioration of the nerve sheath.

What is interesting (after more research) is that this under expression is most often associated with Marginal Zone Lymphoma. This type is very rare (1.6% of lymphomas are Nodal MZL) which would seem to correlate with the 1-2% occurrence rate of non treatment related neuropathy. My original pathology, which was rejected by second opinion, said "both follicular center cell lymphoma (small cleaved and large cell, follicular becoming diffuse) and marginal zone lymphoma present." As I have now found multiple references to cases in which both FL and MZL were present in patients I am becoming more convinced that we (yes, the collective we) blew the original diagnosis. NMZL is also associated with slightly elevated aggressiveness and poorer outcomes based on what I read.

My oncologist and I have discussed at length the original diagnosis and the fact that MZL was in the first report along with FL. There was also an initial report of lymphoma in the marrow, also discounted by second opinion. So, we are having the tissues from the node biopsy and the marrow biopsy sent to the top histopathologist in my area for re-analysis. I had a PET/CT and a CT scan over the past two weeks and they show stable tumor mass and no new hot spots so I am comfortable that the cancer is indolent and behaving the way it should. We also discussed a new biopsy and are agreed that we will decide after the other analysis and test. We think a bone marrow sample is the best to get the most meaningful information so will go there first if needed.

This just reiterates what Ross has stated in other posts that specific lymphoma diagnosis is really difficult and, in my case, it may be the major cancer center that got it wrong (it may not be but I think the evidence is leaning against them). My concern is that I may have lost two years of Stage 4 status when I may have taken action other than watch and wait which is what I opted for based on the failure of the radiation to stop the disease and the facts as I knew them.

My point in this very long post is that you must question everything, do research to the best of your ability and take charge of your case. My oncologist is very much on board with what we are doing now, has the same questions in his mind and thinks I may actually be presenting with both MZL and FNHL. I should have the analysis from the pathologist next week. Maybe then I can, with my care team, figure out what the appropriate next step should be...

Good health,

Kermica

Kermica-
What a nightmare. What a total nightmare. Your post is illustrative of the world of lymphoma in general-- unlike most other cancers, lymphoma is changing all the time. In fact, believe it or not, according to the governing body that establishes staging for all cancers in the US, the American Joint Committee on Cancer (AJCC), you don't even have lymphoma --- you have a lymphoid neoplasm, the term lymphoma having been reserved now for clinical presentation (solid tumors), while the term leukemia is reserved to describe free-moving cancer cells. If the disease shows both, it's described as lymphoma/leukemia.

From 1982 to 1994, the classification system used by everyone in the US for lymphoma recognized just 10 subtypes/categories. that was replaced by a new system that recognized about 25, and THAT one has now been replaced by another one, which is the current standard, which recognizes, by my count, about 51. Although this is not entirely an accurate thing to say, I'll say it anyway for effect-- this is like discovering 40 totally new and very poorly-understood cancers in the span of 15 years.

While I would still count on an NCCN cancer center to have the last say on one's pathology results/lymphoma dx, this just goes to show that, as Kermica so deftly points out, that you really do have to question everything, from everyone, even though the questions to ask aren't necessarily intuitive. Bottom line, this isn't the Milgram experiment; don't fall for the authority of a lab coat.

Ross

Ross,

You seem to know a lot about this. I’m praying that maybe you or someone else can help me. My 38 year old duaghter was just diagnosed with Peripheral T-cell lymphoma. This is a particularly rare lymphoma cancer. Peripheral T-cell lymphoma accounts for about 1 in 100 of all cases of NHL. It is a type of T-cell lymphoma, and the abnormal T-cells are found in the peripheral circulating blood. Peripheral T-cell lymphomas can also be subdivided into different types. Some sub-types of peripheral T-cell lymphomas, like my daughters, are quite rare in the western world. They are more common in the Far East in countries such as Japan and China, where a viral infection called HTLV-1 is very common. HTLV-1 infection can make people more likely to develop some types of peripheral T-cell lymphoma.

No doubt Tara picked up the HTLV-1 cells as a child when we were assigned for three years in Japan when I was in the Army.

Everything that I have read so far on this particular kind of lymphoma does not show a good treatment prognosis. I am desperately looking for hope. I’m distressed, distraught, and shaken to more core about this. Does anyone out their have any good news about this form of cancer. Any at all?

Yes, Ross, it is a nightmare, just one you have to stay awake to go through it. I thought I would have some definition by now but not yet. I called the oncologist on Wednesday and the nurse got a message to my doc but I haven't heard back as of now. Waiting is, as for all of us, one of the featured elements of the nightmare, of course.

I am a positive person so don't have a lot of trouble staying on the up side of all of this (if there is one, I'm there). For example, I am still working and relatively mobile, though the neuro stuff and fatigue challenge me a bit. Next step is to lob another call in next week. I don't know if I should be encouraged or discouraged by the lack of response and the length of time (two weeks) since we agreed on this approach. I guess I think if it was straight up FNHL I would know that by now but prefer to wait for facts rather than assume I'm in deep doo-doo.

Thanks for the support you extend to all of us, you are a special person, indeed.

best regards,

kermica

So, I finally heard back from my doctor regarding the re-exam of the original biopsy materials. It is confirmed to be Follicular NHL and not some kind of mixed environment. So far, so good.

No explanation for the GM1 antibody isse yet and, since we both have continuing questions about staging, I am going to have another bone marrow extract done on 10/8. Beginnings of clarity perhaps, we will see what the next steps show…good health to all.

Kermica

Kermica-
Ok, so that is 'good' news at least in terms of nailing down a dx.

Regarding the gm1 antibody --- I'm on far too shaky ground here to intelligently comment-- I have a very poor grasp of the relationship between gm1 expression, neuropathy, and autoimmune disorders like guillain-barre. I'm very curious to learn the connection, if they provide you with one. Not to say I don't adore molecular science, sadly one of my guilty pleasures is the atlas of genetics and cytogenetics in oncology, I can lose myself there for hours. I always close the site convinced I was never meant for molecular genetics, but wishing I had been.

At any rate, please keep up the posts. Yours is a case study in some of the many potholes in lymphoma, and I think it could almost serve as a cautionary tale if readers really realized the difficulty you've had thus far.

Ross

You are right, Ross, there is not an awful lot out there but here is a complete report reporting on one case, if interested:

http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2003.04651.x/full

A good paper from eMed describing the condition and treatment (with a reference to the rare but measurable connection between it and B cell lymphoma- my understanding is that it presents in around 1% of all cases) is here: http://emedicine.medscape.com/article/1174021-overview

I will be happy to continue posting and welcome any questions or comments folks may have. I am maintaining my watch , wait and verify position for now, pending results of the bone marrow. We will then finalize a diagnosis and a plan. Given that this is indolent, I don't know what that plan will be yet, I may choose to deal with the neuropathy first since that is a bit more bothersome on a daily basis than the cancer, at least physically.

Anyway, I will keep posting as events unfold and will respond should anyone want to contact. Based on the cold I have had for the past week (very nasty) I would guess that the immune system is a bit depressed here right now.

good health to all,

kermica

kermica-
thank you for the link to the paper. Just reading the abstract one time, and I was clinging on to the safety bar, hoping it wouldn't shake me off but it's the kind of intellectual thrill I love. I rarely consult my Kuby immunology textbook that I got for a steal but with that paper I have no choice ....

thanks, and good luck shaking that cold. let it be a reminder to you that you are immunocompromised. Planning on a flu shot this season by the way?

Ross

Yes, it is a reminder that I am immunocompromised, Ross, a good thing for all of us to remember. I do plan on getting my flu shot soon but thought I would at least shake this cold first. Interesting fluff on the Internet about flu shots increasing your odds of getting lymphoma (they claim 98% increase for FL, by the way) but I figure that, even if true, I already have it so what does it matter? I also doubt it is true after looking at the source cited.

Other more interesting fact oriented stuff about Rituxin and flu shots, basically, Rituxin attenuates the response of B cells which causes the vaccination to be less effective. Good to know for those in or planning R based treatment if they are also planning to get a flu shot. Doesn’t impact me since I am doing W+W (at least until I get the new bone marrow results back next month).

Cheers,

kermica

Spot on, kermica--- while all cancer patients should make a point of discussing getting the inactivated flu vaccine with their doctors, patients on Rituxan are especially urged to have the conversation because it's much more complicated.

Being immunocompromised during flu season is bad enough. But being that way while going in and out of clinics, hospitals, for appointments and treatments, where so many other people with health issues are coming and going .... yikes.

One thing that has come out of all of this back and forth I have been through is a positive. That is that the NCCN cancer center did get the diagnosis correct two years ago and my local pathologist got it wrong. If I didn't have the GM1 issue, I probably never would have gone down the path I've followed to date. I would have trusted the second opinion rendered by the major cancer center as having more validity.

That is what I did until the odd secondary issues presented themselves. It is good to know that you can have confidence when escalating for a second opinion (which imho, everyone should consider if diagnosed with lymphoma) if you go to a rated cancer center for that second. They really do have the experience and the resources to provide the most accurate analysis, far more often than not. I am not sorry I have forced the degree of diagnostic thought that has gone into my case. I still have more questions and they may not have good answers but I am glad that I forced the rigor that is being applied by my doc.

We will see where it leads...

good health,

kermica

take good care of yourself. rest lots and get that bone marrow biopsy done. i just got diagnosed but my tests haven't come back yet about exact treatment they will do. if you know of additional sites with good treatment info let me know. i need a flu shot as well but as was being talked about whenever i go to oncologist office or hospital everyone is coughing and sniffling so i have a cold as well. I'm just admiring your being able to get a doctor to do the tests you need. i was just diagnosed with b-cell follicular lymphoma and would like to write you back and forth. feel free to write me. i will lend support as much as i can. i'm new here. take care of yourself

mbh456

Hi, MBH 456 and welcome to the place none of us wants to be. When you know your stage and grade, let us know, they are very important factors in determining treatment options for Follicular NHL (FL).

Because the cancer we have is indolent (slow growing) many people can function well for a long time before treatment is advisable. Of course some folks want treatment because they cannot abide knowing they have cancer and are doing "nothing" (not so, watch and wait is a valid strategy like chemo or radiation, its just counter-intuitive on its face), On the other hand, if found early, localized radiation of the affected lymph gland offers the possibility of a cure. I had this done twice but the cancer has spread anyway. I am now Stage 3 as far as I know (that is why the new bone marrow, to make sure I am not Stage 4).

While the official literature states that FL is incurable, the fact is that most of us with the disease still have the possibility of many years of productive life. The average person lives between 8 and 12 years after diagnosis. Since that's the average, that means a whole bunch of folks live longer than that so the motivation is to do all you can to be one of those folks.

I think it is important to take notes, ask questions, challenge authority and do your own research about everything. I knew nothing about lymphoma or FL when I started this journey and do not have a scientific or medical background. I don't pretend to understand the details of the histochemistry but can certainly fathom the text around the formulae.

My personal favorite site for information is nhlcyberfamily at:
http://www.nhlcyberfamily.org/types/follicular.htm

This page is specific to FL and there is access to a lot of the research currently out there if you scroll to the bottom of the page. Good luck in your journey, feel free to visit anytime. If you like, you can start your own record of your experiences with a group post here. Good luck and good health,

kermica

hi kermica, thanks for the warm welcome. unfortunately I’m past the wait and see time and the radiation stage. we are waiting for my pet scan results and bone marrow biopsy results to learn what chemo the doctor will do. i see her next Thursday. my husband understands more medical talk than me. I’ve been overwhelmed with this and all the tests the doctor has ordered. thanks for the website you mentioned. i will visit it tonight. I’m sure thankful for the support I’m discovering here. i wasn’t sure how to post a introduction to everyone but will next weekend when i learn my stage and grade. thanks for being helpful to me. how is your cold tonight? i hope you sleep well. my cold was caught very fast and is a bad one then I’ve ever had. well, you take care of yourself and let me know how your bone biopsy goes. i survived mine ok. wasn’t very pleasant but i think my biopsy of my largest lymph node hurt worst. i think my sore back and upper thighs hurt worst. i know you’ve had one before and already know what to expect but i think nothing really prepares you for these tests we go through and then the long not knowing till we see our oncologists again afterward. I’ll write again Thursday night. i check everyday though. my email is [email protected] please feel free to write me.

take care.
mbh456

So, just back from the latest bone marrow extraction. The lidocaine is wearing off so the discomfort level is going up but it is really not bad. For those facing one who have not had the experience, no matter what you have heard, it is a pretty fast and relatively (repeat relatively) painless procedure. The only discomfort I had is when my doc was getting the actual marrow sample and that was just a burning sensation that passed as soon as he was finished. The bone sample extraction would remind one of having a tooth pulled in some ways - lots of pressure with some twisting and then done.

I talked with them about my experience and the nurse told me that a lot of it has to do with how nervous the patient is and how much anticipatory fear they have about the procedure. There are cases in which the doctor will hit a "dry space" when getting the marrow and will have to repeat that part (which is the painful part) but that is a rare occurrence, according to her.

Now that it is over, I am back to a waiting game - one more week. Then, I should have clarity and definition regarding the lymphoma, finally. The neuropathy is another story. I told my doc it was getting worse and he said whenever you are ready we can do the ivig infusion. I said I would let him know but not yet as I am still fully functional, despite the numbness and pins and needles.

Anyway, just wanted to pass on my experience with the BMP, for those who are going to have one. It is not as bad as you may have heard. In my book, it is easier than holding my arms over my head for 20-30 minutes in a PET machine, that's for sure.

Cheers and good health,

Thanks so much for the update Kermica. It's amazing how far across the spectrum are people's experiences with a bone marrow biopsy.

I'm curious if your doctor has at all talked to you about either Zevalin or Bexxar? These are tailor-made for FL but more than a few recent studies show that docs are not hip to recommending them because you have to be referred to the proper nuclear medicine dept, which is typically not in their office ...

Ross

Ross, no, I haven't had those discussions yet. Since tumor progression is stable at this point (I hope), my plan is to get the BMB results next week and, if there is no significant change to stay in watch and wait mode. If the marrow is involved, then I will be actively considering treatment alternatives as I see Stage 4 as a firm trigger point for pushing the cancer back. I will definitely get myself schooled on these treatment options before I have those conversations with my doc, who I suspect will be recommending CVP-R as that seems to be the routine choice for FL from what I have read.

Thanks for the tip and be well,

kermica

dear kermica,
have you heard of r-chop therapy? mine starts on the 11th. i'm glad your biopsy went well. mine was minor pain as well. nothing to fear. sounds scarier than it actually is i think. my cold is gone. i also got a tour of treatment building and especially infusion room. i think i came away with a large stack of papers and pamphlets to read this weekend. i'll have four chemo treatments then retuxin every six months for two years. my doctor thinks i'll go into remission fast. i've never heard of the drug you and ross were talking about. is it better than r-chop for fl. well, you take care. i wish you the best.
mbh456

mbh, yes I have heard of R-CHOP, it is the gold standard for treating aggressive NHL. It is also used for FL but there are a number of different lines of thought regarding whether R-CHOP should be a first or second line regimen - many oncologists start with CVP-R and reserve R-CHOP for use if a relapse occurs. It seems your FL is more advanced than mine and your doctor is opting to treat it aggressivly. That is not a bad thing and, if you are Grade 3, it is the treatment of choice as I understand things.

here is an excerpt from the FL treatment page at NHLCyberfamily which may help explain things:

Next would be combination chemotherapy such as:

CVP+Rituxan (R-CVP)
CHOP + Rituxan (R-CHOP)

Bendamustine + Rituxan (B-R)
Radioimmunotherapy such as Bexxar or Zevalin
Fludarabine + Rituxan (RF)
Fludarabine combination such as FND or FC; both with Rituxan

Historically CVP+Rituxan and R-CHOP have been the most widely used treatments when therapy is required. CVP is highly effective and reserves the option of using the anthracycline (the Doxorubicin) in CHOP for later if required.

However recent data is beginning to suggest that Bendamustine+Rituxan may be superior to R-CHOP. Although Bendamustine has been around for many decades in Europe, it has only recently (around 20007) started to be used in North America.

Here is the link to the page, which has great links to the actual research and ASH studies: http://www.nhlcyberfamily.org/types/follicular.htm

The extract above is about half way down the page. Also, as Ross pointed out, Bendamustine is gaining favor with oncologists for a number of reasons, which are also discussed on that page.

Sorry for going deeep and technical, but I wanted to answer your question. I am off to Connecticut to watch my daughter race on the Housatonic River (she is on a crew team) so enjoy your day and I will check in later.

Good luck with your treatments and good health,

kermica

kermica, hi, thanks for the information on different therapies. yes, my doctor is treating my cancer aggressively right now. i went for my first chemo yesterday but they couldn't find my port. well, i had to go to hospital where under fluoroscope they found it and marked it so they could find it today. so i go today for a another round at trying to access my port for chemo. this was frustrating to say the least but I'm trying to remain calm and relaxed because it doesn't help me to get upset at nurses. how was your daughters race on the Hudson? was it nice out there? my brother and sister in law live in Rochester new york and I'm always wanting to visit. take care.
mbh456