Follicular Lymphoma Grade and Stage (2023)

A while back, one of my readers asked if I would make a postabout “grading” in follicular lymphoma.She has been a great help to me in attracting readers to this blog so Ipromised her I would write something up.Unfortunately I think I’ve had a mental cramp on this one for a while –but I am trapped on a seemingly endless flight (Dang Texas is big) so I thoughtI would give it a try. The flightdoesn’t have internet so this one may be a little brief on the outsidereferences.

Most of you know about “staging.” In lymphoma, staging is a clinicalmeasurement of how much disease you actually have. Stage I disease is typically one affectedlymph node or a few that are tightly clustered in one place. Stage II disease is when there are multipleaffected lymph nodes in different areas, yet on the same side of the diaphragm(ie all in abdomen/pelvis or all in neck, chest, armpits). In stage III disease you can have lymph nodeson both sides of the diaphragm. Stage IVdisease is when it either involves the marrow or more than one site outside ofthe lymph nodes (ie skin, liver, lungs, bone lesions).

I should make a comment here that frequently comes up in myclinic. Patients often ask me, “whatstage am I?” There is nothing worse thanthe look you get when you tell someone they have stage IV disease. We are primed from our knowledge of a lot ofcancers that stage IV means you are going to die. It can sometimes be a challenge to “pick upthe pieces” after you tell someone their disease is that far advanced.

(Video) Challenges in grade 3B follicular lymphoma management

Stage IV lymphoma is very different than stage IV lungcancer. I tell my patients that lymphomais a cancer of the immune system and that the immune system is pretty mucheverywhere to begin with (ok – we can make exceptions for both the brain andtesticles which are considered immune “privileged” - draw your own conclusions).

In diseases like lung cancer, if that cancer has spreadoutside of the lung or adjacent lymph nodes – that becomes an incurable diseaseand the prognosis is often comparatively short.Same thing holds true with a bunch of other “solid” tumors for thatmatter (bladder, kidney, pancreas, colon, stomach, and so forth). It is certainly true that less lymphoma isbetter than more lymphoma – but not to the same degree as those other cancers. Stage IV lymphoma is very common but oftenstill quite manageable (and even curable in DLBCL). In fact stage III/IV follicular isconsiderably more common than limited stages of disease – so most of thestatistics you hear about survival are typically for patients with advanced stage disease (which are often way outdated since by their very definition are retrospective and do not necessarily account for improvements in therapy).

OK – moving on – this was supposed to be about gradingright? Grade has absolutely NOTHING todo with stage. I tell patients, “gradeis what it looks like under the microscope – stage is what it looks like on theCT scan.” Unfortunately, there is a fundamental problem with using appearance under a microscope as an objectivemeasurement – it is difficult to reproduce this well. Even though there are well establishedcriteria about grading lymphoma – trying to make solid black / whitedistinctions can be hard when the biology does not conform to the rules. You can look at different regions of the samenode and come to a different answer, or you can even look at the same regionand have two different pathologists give you a different answer if they countthings a little differently – and that is easy to do!

(Video) Diagnosis and Staging for Follicular Lymphoma

Grading typically applies to cases of follicularlymphoma. We assign one of four grades –you would probably guess I, II, IIIa and IIIb right? The way we distinguish between these are thenumber and arrangement of “large cells” within a node. Large cells are typically called “centroblasts”while small cells are called “centrocytes.”Large cells are thought to be more rapidly proliferating. Since faster proliferation is bad, the morelarge cells you have the worse we think it would be.

Ultimately, there is VERY LITTLE difference between thegrade I’s and the grade II’s either biologically or clinically. Even grade IIIa disease is pretty muchsomething we can lump together. We treatthem exactly the same way, they do just as well. It is pretty much just a pathologydistinction without much clinical impact.

Distinguishing between grade IIIa and IIIb though can have clinical implications. In grade IIIathere are enough centroblasts seen in the lymph node (15per “high poweredfield”) to be categorized differently than grade II yet clinically we stilltreat all these exactly the same. GradeIIIb on the other hand has “sheets” of centroblasts within the node and reallystarts to behave more like diffuse large B cell lymphoma (DLBCL). In the past that often meant the differencebetween getting R-CVP or R-CHOP (the latter being more intensive and causing hair loss – see my post about it). For a lot of docs though, R-CHOP was historically(and still is in some cases) the choice though even in grade I-IIIa follicular lymphoma so the distinction didn’tmatter quite so much.

(Video) Focus on follicular lymphoma: the patient’s journey

Now it is more significant because in grade I-IIIautilization of bendamustine-rituxan is extremely common yet R-CHOP wouldprobably still be considered standard for IIIb.Since BR is both superior and better tolerated than R-CHOP in I-IIIa, Isometimes anguish a little when I see a IIIb come into clinic. I will oftencall the pathologist to get a better feel as to how “clear” the distinction isto them in the sample. Alternatively, I may look for other clues about the aggressiveness of the disease. Does a PET scan show one area to be a lot worse than others to suggest a transformation? Does the clinical pace or labs suggest higher grade disease? etc.?

There are a few problems with this though. 1) This is an area where pathologistreproducibility is not so great. This isnot to say they are not good pathologists but that there is a lot of judgmentinvolved as well as sampling differences.2) It is not clear thatappearance is a good surrogate for biology.We are learning about the remarkable complexity of these cancers and Iam not convinced that appearance gives us adequate insight into the molecularmechanisms that are going on. 3) Ashumans we like to compartmentalize things even if they are really continuousvariables. In other words, if we use thenumber 50 as a cutoff – are patients with 49 or 51 really all that differentfrom one another?

(Video) What Are the Stages of Follicular Lymphoma?

If good researchers come to different conclusions whenasking some of the same questions – it is often because the data input isfaulty (ie. in a study of 100 patients- 15 are categorized incorrectly and resultsin a smaller difference than would have occurred if everyone was put in propergroup). Other times we may be fallingvictim to the belief that appearance is a surrogate for biology AND that thebiology is actually different.

(Video) Non-Hodgkin Follicular Lymphoma - Carol's Story of Hope

One other key point I should make before wrapping up. Grade IIIb is not the same thing ashistologic transformation which is evolution from low grade disease to highgrade disease. We are getting to understandthat biology better and histologic transformation is likely worse than gradeIIIb on account of a different mutation profile.

For now, grades I-IIIa can be treated with rituxan, R-CVP,R-CHOP, BR, or any of the new research drugs.See my posts on “my approach to follicular lymphoma part 1 and part2.” Grade IIIb I will use R-CHOP eventhough I have all the questions I ask above.

I hope that helps – thanks Anjou!

(Video) What is follicular lymphoma?


What is the difference between stage and grade follicular lymphoma? ›

FL gets its name from the follicles, or clumps of B cells, that form inside your lymph nodes. The cancer's grade provides information about how your B cells appear when examined under a microscope. The stage explains where in your body the lymphoma is located and how far it has spread.

Is follicular lymphoma grade 1 or 2? ›

Grade 1 has the fewest large lymphocytes and grade 3B has the most. Grades 1 and 2 are often grouped together. Your doctor might call this 'grade 1 to 2' follicular lymphoma. Grades 1 to 2 and 3A follicular lymphoma are all slow-growing and are treated in the same way.

What are the different grades of follicular lymphoma? ›

The grade is based on the number of large, follicular lymphoma cells (centroblasts) that they can see. Grade 1, 2 and 3A are generally thought to be low grade or slow growing. Grade 3B follicular lymphoma is faster growing and is likely to be treated as a high grade lymphoma.

What is stage 4 grade 1 follicular lymphoma? ›

In stage 4, the disease has spread to organs such as the liver, bone marrow, or lungs. Systemic symptoms are fever, night sweats, and weight loss. When the disease spreads from the lymph node to an organ, or when the disease involves a single organ other than the lymphatic system, it is considered to be stage 4.

Is Grade 3 follicular lymphoma curable? ›

Follicular non-Hodgkin lymphoma grades 3A and 3B have a similar outcome and appear incurable with anthracycline-based therapy.

Is Grade 2 follicular lymphoma curable? ›

Follicular lymphoma is usually not considered to be curable, instead categorized as more of a chronic disease. Patients can live for many years with this form of lymphoma.

What does follicular lymphoma grade 2 mean? ›

Listen to pronunciation. (... fuh-LIH-kyoo-ler lim-FOH-muh) An indolent (slow-growing) type of non-Hodgkin lymphoma marked by enlarged lymph nodes and a mix of large cells and small cells that have cleaved (u-shaped) nuclei.

Can follicular lymphoma become aggressive? ›

Follicular lymphoma (FL) is an indolent subtype of non‐Hodgkin lymphoma (NHL). Transformation of FL (TL) to an aggressive lymphoma is a well‐recognized phenomenon. FLs most commonly transform to diffuse large cell lymphoma (DLBCL).

What is follicular lymphoma grade3? ›

fuh-LIH-kyoo-ler lim-FOH-muh) A type of non-Hodgkin lymphoma marked by large cells and enlarged lymph nodes. Grade 3 follicular lymphoma is less common, and more aggressive than grades 1 or 2 follicular lymphoma.

Is stage 4 follicular lymphoma curable? ›

Yes. The more advanced your cancer is, the more challenging your odds may become. However, stage 4 lymphoma is treatable and many people live for many years after getting this diagnosis.

How long can you live with Stage 1 follicular lymphoma? ›

How long can you live with follicular lymphoma? Follicular lymphoma is a slow-growing condition that's considered a chronic illness. Studies about half of all people diagnosed with follicular lymphoma are alive nearly 20 years after diagnosis. About 90% of people are alive five years after diagnosis.

Does follicular lymphoma always come back? ›

Even if you initially go into complete remission (where there's no sign of the lymphoma left) after treatment, the lymphoma will often come back. This is called relapsing. If you've relapsed, your next treatment will depend on: how long you've been in remission.

What is stage 3 or 4 follicular lymphoma? ›

Stages III and IV are both advanced follicular lymphoma. In stage III, cancer has spread to lymph nodes on both sides of your diaphragm. In stage IV, your lymphoma has spread beyond your lymph nodes to organs like your liver, bone marrow, or lungs.

How is stage 1 or 2 follicular lymphoma treated? ›

Radiation therapy is the traditional technique for treating stage I-II follicular lymphoma. However, results from small clinical trials suggest that more patients experience long-term survival if chemotherapy is administered. (Large clinical trials are necessary to confirm these observations.)

Do you need chemo for Stage 1 lymphoma? ›

Limited (early) stage Hodgkin lymphoma

Limited stage usually means stage 1 or 2A lymphoma. You will probably have a short course of chemotherapy if you have limited disease. Your doctor might then recommend radiotherapy to the affected lymph nodes. You might also have radiotherapy to your spleen or other lymph nodes.

How long can you live with stage 3 follicular lymphoma? ›

For people with stage II, III, or IV disease (table 1), the average survival is greater than 20 years. Despite its slow-growing nature, it is unclear whether most cases of follicular lymphoma can be cured with currently available therapies.

How do you treat Grade 3A follicular lymphoma? ›

Very low-dose radiotherapy (VLDRT) is effective for treating grade 3A follicular lymphoma and provides patients with a shorter treatment course and fewer side effects.

Can you beat follicular lymphoma? ›

The most common type of low grade NHL is follicular lymphoma. For limited disease, you are most likely to have radiotherapy to the affected lymph nodes. This can help control the lymphoma for a long time, and may cure it.

How often does follicular lymphoma come back? ›

Approximately 20% of patients with follicular lymphoma will relapse within 2 years of diagnosis.

Why did I get follicular lymphoma? ›

Doctors don't know what causes follicular and other non-Hodgkin's lymphomas. Unlike some cancers, they are not passed down in families. In some cases, radiation or cancer-causing chemicals, or certain infections, may be a cause. But other times there is no known cause.

Can you beat Stage 2 lymphoma? ›

There are very few cancers for which doctors will use the word “cure” right off the bat, but Hodgkin lymphoma (HL), the most common cancer diagnosis among children and young adults, comes pretty darn close: More than 90 percent of patients with stages 1 and 2 go on to survive five years or more, and even patients with ...

What is the survival rate of Grade 2 lymphoma? ›

For stage II the 5-year survival rate is 77%, and for stage III it is more than 71%. For stage IV NHL, the 5-year survival rate is almost 64%. These survival rates vary depending on the cancer's stage and subtype.

Does Stage 2 lymphoma require chemo? ›

Treatment for stage 2 Hodgkin lymphoma is usually 2 to 4 cycles of chemotherapy. You might also have radiotherapy.

How many grades of lymphoma are there? ›

Doctors will determine whether the lymphoma is low grade (indolent or slow growth rate), intermediate grade (moderate growth rate) or high grade (aggressive or rapid growth rate).

Can you live a full life with follicular lymphoma? ›

Follicular lymphoma, like other types of low-grade non-Hodgkin lymphoma, is rarely 'cured', but it can be treated so that you can live normally and enjoy a good quality of life. For most people, the disease is slow to develop, and some people who have no symptoms may not need any treatment at all in their lifetime.

What is the latest treatment for follicular lymphoma? ›

Rye Brook, N.Y., June 2, 2022 – The U.S. Food and Drug Administration (FDA) has approved CAR T-immunotherapy tisagenlecleucel (Kymriah®) for patients with follicular lymphoma (FL) whose cancer has returned or worsened despite at least two earlier treatments.

Can stress cause follicular lymphoma? ›

There is no evidence that suggests stress causes lymphoma or other types of cancer. Researchers cannot provide evidence that psychological stress worsens lymphoma in humans, either.

What is stage 3 non Hodgkin's follicular lymphoma? ›

Stage 3. This means that you have lymphoma on both sides of the diaphragm. One example is that the lymphoma is in lymph nodes on both sides of the diaphragm. Another example (see below) is that the lymphoma is in lymph nodes above the diaphragm, as well as lymphoma in the spleen.

What does grade mean in lymphoma? ›

The grade is a description of how the cancer cells look and behave compared to normal cells. How different the cancer cells are is described as differentiation. The different types and subtypes of NHL are usually described as either indolent (low grade, slow growing) or aggressive (high grade, fast growing).

What is stage 4 grade 3 follicular lymphoma? ›

Stages III and IV are both advanced follicular lymphoma. In stage III, cancer has spread to lymph nodes on both sides of your diaphragm. In stage IV, your lymphoma has spread beyond your lymph nodes to organs like your liver, bone marrow, or lungs.

What is a grade 1 follicular lymphoma? ›

Listen to pronunciation. (... fuh-LIH-kyoo-ler lim-FOH-muh) An indolent (slow-growing) type of non-Hodgkin lymphoma marked by enlarged lymph nodes and small cells that have cleaved (u-shaped) nuclei.

What is grade in lymphoma? ›

Grade 1 follicular lymphoma showed less than 5 centroblasts per high power field, grade 2 lymphoma showed 5–15 centroblasts per high power field and grade 3 disease showed more than 15 centroblasts per high power field.

Is low-grade lymphoma worse than high-grade? ›

Low-grade NHL: this usually develops slowly and is said to be a more 'chronic' disease. This means that people may not need treatment for many years. – High-grade NHL: this usually develops quickly and needs treatment straight away.

Is follicular lymphoma serious? ›

Yes, follicular lymphoma can be a serious and challenging illness. Here's why: Transformation: Follicular lymphoma can change or transform into diffuse large B-cell lymphoma (DLBCL).

How is low-grade follicular lymphoma treated? ›

For follicular lymphoma, you are most likely to have a combination of chemotherapy and a type of targeted immunotherapy called a monoclonal antibody (MAB). For example, R-CVP includes the following: the chemotherapy drugs cyclophosphamide and vincristine. the steroid prednisolone.

What is grade 2 follicular lymphoma? ›

An indolent (slow-growing) type of non-Hodgkin lymphoma marked by enlarged lymph nodes and a mix of large cells and small cells that have cleaved (u-shaped) nuclei.

Can Stage 1 follicular lymphoma be cured? ›

Overview. Patients with stage I or II follicular non-Hodgkin lymphomas have limited disease; limited disease is potentially curable.

What is the best treatment for stage 1 follicular lymphoma? ›

Stage I disease — Some people with stage I follicular lymphoma may be treated with radiation therapy alone. This approach can lead to long term remission in approximately half of people in this situation.


1. What is follicular lymphoma?
2. Challenges within follicular lymphoma treatment
(VJHemOnc – Video Journal of Hematological Oncology)
3. Follicular Lymphoma | Indolent B-Cell Non-Hodgkin’s Lymphoma
(Medicosis Perfectionalis)
4. When Is It Time to Treat Follicular Lymphoma?
(Patient Empowerment Network)
5. Diagnosis and Prognosis of Follicular Lymphoma
6. Lymphoma: Diagnosis, stages, treatment and life afterwards
(Fortis Memorial Research Institute)
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