Follicular Lymphoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and David Li MD
April 14, 2026

Follicular lymphoma is a group of closely related blood cancers that start in B cells — specialized white blood cells that normally help the body fight infection. These cancers are called “follicular” because the abnormal cells grow in round clusters called follicles, resembling the normal structures found inside healthy lymph nodes. Follicular lymphoma is the second most common lymphoma in adults and includes several subtypes that differ in their microscopic appearance, underlying genetics, and behavior. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What are the symptoms of follicular lymphoma?

Many people with follicular lymphoma feel well at the time of diagnosis. The most common finding is one or more painless, slowly enlarging lumps caused by swollen lymph nodes — small bean-shaped glands that are part of the immune system and are found throughout the body. Swollen nodes are most often noticed in the neck, armpits, or groin, though any group of lymph nodes can be involved.

In some people the lymphoma also involves the spleen, bone marrow, liver, gastrointestinal tract, or other sites, and this can cause a feeling of fullness or discomfort in the abdomen, fatigue, or reduced blood counts. Some people experience general symptoms sometimes called B symptoms — unintentional weight loss of more than 10% of body weight, fever, and drenching night sweats. Because most follicular lymphoma subtypes grow slowly, symptoms may be present for many months before the diagnosis is made. The exception is follicular large B cell lymphoma, which can grow more quickly and cause symptoms sooner.

What causes follicular lymphoma?

The exact cause of follicular lymphoma is not known. Most cases arise from an acquired genetic change — a chromosomal rearrangement called t(14;18) — that occurs by chance in a single B cell during its normal development inside a lymph node structure called the germinal center. This rearrangement places the BCL2 gene next to a powerful growth-promoting switch in the cell’s DNA, causing continuous overproduction of the BCL2 protein. BCL2 normally prevents cells from dying when they should; when it is overproduced, abnormal B cells accumulate rather than dying off naturally. Over many years, additional genetic changes accumulate in these cells, eventually driving overt lymphoma. This t(14;18) rearrangement is present in approximately 85–90% of classic follicular lymphoma cases and can actually be detected at very low levels in the blood of most healthy adults — the vast majority of whom never develop lymphoma, indicating that additional events are required.

Several factors have been associated with an increased risk of developing follicular lymphoma, including exposure to certain pesticides, cigarette smoking (particularly in women), hepatitis C infection, Sjögren’s syndrome (an autoimmune condition), obesity, and having a first-degree relative previously diagnosed with follicular lymphoma or another blood cancer. Environmental factors — including herbicide exposure and living near industrial areas — have also been linked to higher rates in some populations. In most people, however, no clear cause is identified.

How is the diagnosis made?

The diagnosis of follicular lymphoma can only be made by examining tissue under the microscope. A biopsy is performed to remove a piece of a swollen lymph node or affected tissue, which is then examined by a pathologist. An excisional biopsy — removal of an entire lymph node — is strongly preferred, because it preserves the full architectural pattern of the tissue, which is essential for accurate diagnosis and subtype classification. A core needle biopsy may be used when an excisional biopsy is not feasible, though it provides less tissue and can make subtype determination difficult or impossible. Fine needle aspiration alone is not sufficient to diagnose follicular lymphoma. Under the microscope, the pathologist identifies the growth pattern, the types of cells present, and any features that suggest a specific subtype. Additional tests including immunohistochemistry, flow cytometry, and genetic tests such as FISH are routinely performed to confirm the diagnosis and determine the subtype. Once the diagnosis is confirmed, imaging — typically a PET/CT scan — is used to determine how widely the lymphoma has spread.

What are the subtypes of follicular lymphoma?

The current World Health Organization (WHO) classification (2022) divides follicular lymphoma into four main subtypes, plus three additional distinct entities that share some features but behave differently. Each subtype is described below. Your pathology report will state which subtype you have — this is important because it affects prognosis and treatment.

Classic follicular lymphoma (cFL)

Classic follicular lymphoma is by far the most common subtype, accounting for approximately 90% of all follicular lymphomas. It is defined by the presence of a mixture of two types of abnormal B cells — centrocytes and centroblasts — in at least a partly follicular growth pattern. Centrocytes are small, irregularly shaped cells with folded or cleaved nuclei; centroblasts are larger, rounder cells. Both types normally develop inside lymph node germinal centers during the immune response to infection, which is why classic follicular lymphoma cells look and behave the way they do.

The growth pattern — how the cells are arranged in the tissue — is an important feature of classic follicular lymphoma. When more than 75% of the tumor is arranged in round follicular clusters, the pattern is described as predominantly follicular. When substantial areas of flat, sheet-like growth — called a diffuse pattern — are present alongside follicular areas, the report may describe the tumor as “follicular and diffuse.” A significant diffuse component is associated with a somewhat less favorable prognosis. Classic follicular lymphoma is an indolent (slow-growing) disease. Many people live for 15–20 years or more after diagnosis, though the disease is rarely cured with standard treatment and tends to follow a pattern of response and relapse over many years.

In the past, classic follicular lymphoma was graded as grade 1, 2, or 3A based on the number of large centroblast cells counted under the microscope. However, long-term studies have shown that grades 1, 2, and 3A behave similarly and respond to similar treatments, so the current classification no longer requires grading. If your report uses grade 1, 2, or 3A, this describes the same disease as classic follicular lymphoma. Grading may still appear in some reports as optional information.

For a detailed discussion of classic follicular lymphoma — including immunohistochemistry, biomarker testing, staging, prognosis, and treatment — see the dedicated article: Classic Follicular Lymphoma: Understanding Your Pathology Report.

Follicular lymphoma with unusual cytological features (uFL)

This is a rare and newly recognized subtype in which the lymphoma cells have an unusual appearance under the microscope that differs from the typical centrocyte-centroblast mixture of classic follicular lymphoma. In some cases, the cells have immature or blastoid (blast-like) chromatin — the material inside the cell nucleus appears more open and loosely arranged than usual, resembling less mature cells. In others, the cells are unusually large centrocytes with irregular or highly folded nuclei. These variations in cell appearance are important because they change both the diagnosis and potentially the prognosis.

Compared with classic follicular lymphoma, follicular lymphoma with unusual cytological features tends to have a higher Ki-67 proliferation index (indicating faster cell division) and more frequent expression of a protein called IRF4 (also known as MUM1), which is normally absent or rare in classic follicular lymphoma. The BCL2 rearrangement is less commonly found in this subtype. Because the cells can look different from typical follicular lymphoma, additional testing — including FISH for IRF4 gene rearrangement — may be needed to distinguish this subtype from other lymphomas, particularly large B cell lymphoma with IRF4 rearrangement. The prognosis of follicular lymphoma with unusual cytological features is not yet fully established, as this is a recently defined category with limited published data. Your care team will explain what this means for your individual situation.

Follicular lymphoma with a predominantly diffuse growth pattern (dFL)

This subtype is defined by a predominantly diffuse growth pattern — meaning the lymphoma cells spread in flat sheets through the tissue rather than forming the round follicular clusters seen in classic follicular lymphoma. A small number of residual follicles, sometimes very small (called microfollicles), may still be present. The lymphoma cells are composed almost entirely of centrocytes (the smaller, irregular-nucleus cell type), with very few or no centroblasts.

Follicular lymphoma with a predominantly diffuse growth pattern has several distinctive features that set it apart from other subtypes. It most commonly arises in the inguinal region (groin lymph nodes) and can form large masses there. It frequently presents at a limited stage (stage I or II), meaning the disease has not spread widely at the time of diagnosis. The BCL2 rearrangement that is characteristic of classic follicular lymphoma is usually absent. Instead, mutations in a gene called STAT6 are frequently found, often together with CD23 expression. Because of its limited-stage presentation and distinct biology, follicular lymphoma with a predominantly diffuse growth pattern tends to have a more favorable prognosis than advanced-stage classic follicular lymphoma. This subtype should not be diagnosed on a core needle biopsy alone, as an adequate sample of the full tissue architecture is required.

Follicular large B cell lymphoma (FLBCL)

Follicular large B cell lymphoma — formerly called grade 3B follicular lymphoma — is a distinct and more aggressive subtype. It is defined by a follicular growth pattern in which the follicles are composed entirely of sheets of large centroblasts, with no centrocytes present. This complete absence of the smaller centrocyte population is the key microscopic feature that distinguishes follicular large B cell lymphoma from classic follicular lymphoma.

Follicular large B cell lymphoma is biologically more closely related to diffuse large B cell lymphoma (DLBCL) than to classic follicular lymphoma. The BCL2 rearrangement is uncommon in this subtype, whereas BCL6 rearrangements and other genetic changes more typical of aggressive lymphoma are more frequent. Follicular large B cell lymphoma frequently coexists with areas of DLBCL in the same lymph node, and careful sampling is needed to exclude concurrent DLBCL before a pure diagnosis of follicular large B cell lymphoma is made. For this reason, a definitive diagnosis should not be made on a core needle biopsy. Because of its aggressive behavior, follicular large B cell lymphoma is treated with intensive chemoimmunotherapy — the same approach used for diffuse large B cell lymphoma — rather than the gentler regimens or watch-and-wait strategy used for classic follicular lymphoma.

Other distinct entities related to follicular lymphoma

Three additional conditions share features with follicular lymphoma but are considered separate diseases by the WHO 2022 classification. They may appear in pathology reports in specific clinical settings and are important to understand.

In situ follicular B cell neoplasm

In situ follicular B cell neoplasm is a very early, pre-lymphoma condition in which cells carrying the t(14;18) BCL2 rearrangement are found confined to the germinal centers of otherwise normal-looking lymph nodes. The lymph node architecture is preserved, and there is no mass-forming lymphoma. This finding is often discovered incidentally — for example, in a lymph node removed during surgery for another reason — and by itself does not mean the person has lymphoma.

The risk that in situ follicular B cell neoplasm will progress to overt follicular lymphoma is low. Most people with this finding are monitored with periodic examinations and imaging rather than treated. However, it is important that a thorough evaluation be performed to rule out concurrent follicular lymphoma elsewhere in the body, because in situ follicular B cell neoplasm can occasionally coexist with established follicular lymphoma at another site.

Pediatric-type follicular lymphoma

Pediatric-type follicular lymphoma is a rare subtype that occurs predominantly in children and young adults, most often in males, and typically involves lymph nodes in the head and neck region. Despite its name, it can occasionally occur in adults. It is defined by a purely follicular growth pattern with an abundance of large centroblasts (a high-grade appearance) but, unlike follicular large B cell lymphoma, has an excellent prognosis.

The genetic profile of pediatric-type follicular lymphoma is distinct: the BCL2 rearrangement is absent, and BCL2 protein expression is typically weak or absent. Mutations in a gene called IRF4 (or its rearrangement) should be tested for and excluded, as large B cell lymphoma with IRF4 rearrangement can look similar and requires different treatment. Pediatric-type follicular lymphoma is typically treated with surgical removal of the involved lymph node alone or with limited chemotherapy, and long-term outcomes are excellent. It should not be treated with the intensive regimens used for classic follicular lymphoma or follicular large B cell lymphoma.

Duodenal-type follicular lymphoma

Duodenal-type follicular lymphoma is a very indolent subtype that arises almost exclusively in the duodenum (the first part of the small intestine) and is typically found incidentally during upper endoscopy. It may also involve other parts of the small intestine. It is defined by follicular lymphoma cells — usually resembling classic follicular lymphoma with BCL2 expression and the t(14;18) rearrangement — confined to the mucosa of the bowel wall, without spreading to deeper layers or distant lymph nodes.

Despite its follicular lymphoma biology, duodenal-type follicular lymphoma has an exceptionally favorable outcome. Many cases are managed with watchful waiting alone, and spontaneous regression has been reported. Radiation therapy to the involved area or rituximab may be considered in some patients. The risk of transformation to aggressive lymphoma is very low.

What does follicular lymphoma look like under the microscope?

Regardless of subtype, follicular lymphoma is recognized under the microscope by the combination of its cell types and growth pattern. The characteristic cell types — centrocytes and centroblasts — are described in detail in the classic follicular lymphoma section above. The growth pattern describes how the cells are arranged in the tissue:

Follicular pattern — Lymphoma cells form round or oval clusters called follicles, resembling the germinal centers of normal lymph nodes but lacking their normal features, such as a light and dark zone and prominent macrophages. Follicles in lymphoma tend to be crowded, back-to-back, and poorly defined at their edges, whereas reactive (non-cancerous) follicles are well spaced with sharper borders.
Diffuse pattern — Lymphoma cells grow in flat, sheet-like areas without forming follicles. The proportion of diffuse growth matters — a high diffuse component in classic follicular lymphoma is associated with a worse prognosis, and an entirely diffuse pattern raises the possibility of follicular lymphoma with a predominantly diffuse growth pattern or transformation to diffuse large B cell lymphoma.

Immunohistochemistry and flow cytometry

Immunohistochemistry (IHC) and flow cytometry detect specific proteins on or within lymphoma cells, helping the pathologist confirm the diagnosis and determine the subtype. The typical protein profile shared by most follicular lymphoma subtypes is listed below, along with what each result means.

CD20 — Positive. Confirms the cells are B cells. CD20 is also the target of rituximab and obinutuzumab, the anti-cancer antibodies used in treatment.
CD10 — Positive in most cases. A marker of germinal center B cells. May be absent in follicular lymphoma with a predominantly diffuse growth pattern.
BCL2 — Positive in most classic follicular lymphoma cases. Overproduction of BCL2 protein is caused by the t(14;18) rearrangement and is a key feature distinguishing follicular lymphoma from reactive (non-cancerous) follicular hyperplasia, in which germinal center cells are BCL2 negative. BCL2 may be negative or weak in follicular lymphoma with a predominantly diffuse growth pattern, pediatric-type follicular lymphoma, and a minority of classic follicular lymphoma cases.
BCL6 — Positive. A marker of germinal center activity expressed by the lymphoma cells in most subtypes.
CD23 — Variable. Usually negative in classic follicular lymphoma but frequently positive in follicular lymphoma with a predominantly diffuse growth pattern.
CD3 — Negative. Confirms the lymphoma cells are not T cells.
CD5 — Negative. Helps distinguish follicular lymphoma from small lymphocytic lymphoma and mantle cell lymphoma, which are CD5 positive.
Cyclin D1 — Negative. Helps exclude mantle cell lymphoma, which can occasionally grow in a follicular pattern.
IRF4 (MUM1) — Usually negative in classic follicular lymphoma. Positive or strongly expressed in follicular lymphoma with unusual cytological features and in large B cell lymphoma with IRF4 rearrangement. When strongly and uniformly positive, FISH testing for IRF4 gene rearrangement should be performed.

Ki-67 and the proliferation rate

The Ki-67 labelling index measures the proportion of lymphoma cells that are actively dividing. A higher percentage means more cells are dividing at any given moment, indicating a more rapidly growing tumor. In classic follicular lymphoma, the Ki-67 index is typically low, reflecting the indolent nature of the disease. Follicular lymphoma with unusual cytological features and follicular large B cell lymphoma tend to have higher Ki-67 values. A high Ki-67 index in what otherwise appears to be classic follicular lymphoma may signal an increased risk of aggressive behavior or impending transformation and is one of the features your pathologist will record and your care team will consider.

Biomarker and molecular testing

Molecular and genetic testing provides important additional information beyond what is visible under the microscope. The tests most commonly performed in follicular lymphoma are described below.

BCL2 rearrangement — t(14;18)

The t(14;18) rearrangement is present in approximately 85–90% of cases of classic follicular lymphoma. It is detected by FISH or PCR. Its presence supports the diagnosis of classic follicular lymphoma and helps distinguish it from other small B cell lymphomas. It is typically absent in follicular lymphoma with a predominantly diffuse growth pattern, in follicular large B cell lymphoma, in pediatric-type follicular lymphoma, and in duodenal-type follicular lymphoma.

BCL6 rearrangement

BCL6 rearrangements are found in 15–20% of classic follicular lymphoma cases and in approximately 40% of follicular large B cell lymphoma cases. BCL6 rearrangement is more commonly detected at the time of transformation to diffuse large B cell lymphoma and is one of the markers assessed when transformation is suspected.

EZH2 mutation

EZH2 mutations are among the most common mutations in classic follicular lymphoma, found in approximately 20–25% of cases. EZH2 is a gene that controls how DNA is packaged inside cells and affects which genes are switched on or off. When mutated in follicular lymphoma, it contributes to abnormal cell survival. EZH2 mutations are associated with a somewhat favorable prognosis when patients are treated with chemoimmunotherapy, and they predict response to a drug called tazemetostat — an EZH2 inhibitor approved for relapsed or refractory follicular lymphoma. Testing for EZH2 mutation is therefore clinically relevant, particularly at relapse.

TP53, CDKN2A, and MYC — markers of transformation risk

Mutations or deletions in TP53 and CDKN2A, as well as MYC rearrangements, are found more often in follicular lymphoma that has transformed to diffuse large B cell lymphoma than in follicular lymphoma that has not yet transformed. Their detection in a follicular lymphoma biopsy raises concern for transformation or imminent transformation and may prompt a more aggressive treatment approach. If your report mentions any of these findings, ask your care team what they mean for your situation.

STAT6 mutation

STAT6 mutations are found in more than 50% of cases of follicular lymphoma with a predominantly diffuse growth pattern and are much less common in classic follicular lymphoma. Their presence in a case with diffuse architecture and CD23 expression supports the diagnosis of this subtype.

Next-generation sequencing

Comprehensive molecular profiling by next-generation sequencing is not required in the routine workup of follicular lymphoma but is increasingly performed in clinical practice and clinical trials to better characterize the disease, identify mutations that may affect prognosis (such as TP53), and detect actionable alterations (such as EZH2) that may guide treatment choices. Commonly mutated genes in follicular lymphoma include KMT2D, CREBBP, EZH2, TNFRSF14, BCL2, and several others involved in regulating gene activity and cell survival.

For more information about biomarkers and molecular testing in blood cancers, visit the Biomarkers and Genetic Testing section.

Staging

Follicular lymphoma is staged using the Lugano classification, which describes how widely the lymphoma has spread throughout the body. Staging is determined primarily by PET/CT imaging and, in some cases, bone marrow biopsy. Bone marrow is involved in 40–70% of classic follicular lymphoma cases at diagnosis, which means most patients present with advanced-stage (stage III–IV) disease — a finding that, unlike in many solid tumors, does not necessarily indicate a poor prognosis given the indolent nature of the disease.

Stage I — A single lymph node region or a single site outside the lymph nodes is involved.
Stage II — Two or more lymph node regions on the same side of the diaphragm (the muscle separating the chest from the abdomen) are involved.
Stage III — Lymph node regions on both sides of the diaphragm are involved.
Stage IV — The lymphoma has spread to one or more organs outside the lymphatic system, such as the bone marrow, liver, or lung.

The letters A and B are added to indicate the absence (A) or presence (B) of B symptoms — fever, drenching night sweats, and unintentional weight loss of more than 10% of body weight over six months.

Transformation to a more aggressive lymphoma

One of the most important concepts in follicular lymphoma is transformation — the process by which the slow-growing lymphoma acquires additional genetic changes and converts into a faster-growing, more aggressive type of cancer. In most cases, transformation produces a diffuse large B cell lymphoma. Transformation occurs in approximately 1–3% of people per year, with a median time to transformation of 2.5-4 years after diagnosis.

Transformation should be suspected when there is a sudden, rapid increase in the size of one or more lymph nodes, new B symptoms, a sharp rise in LDH (a blood marker of cell turnover), or new involvement of unusual sites such as the liver, bone, muscle, or central nervous system. A new biopsy of the most clinically suspicious site is essential to confirm transformation, as transformed disease may be present only in part of the tumor. PET/CT scanning is used to identify areas of high metabolic activity that are most likely to harbor transformed disease.

Genetic changes associated with a higher risk of transformation include TP53 and CDKN2A inactivation, MYC rearrangements, and certain copy-number changes. These may be identified on molecular profiling at the time of the original biopsy or at relapse. All follicular lymphoma tissue is examined for evidence of transformation at the time of diagnosis and at any subsequent biopsy; if transformation is identified, it will be described in your pathology report.

What is the prognosis?

Prognosis varies significantly by subtype. Classic follicular lymphoma is an indolent disease with a median overall survival exceeding 17 years with modern treatment. Progression occurs continuously over time — most people experience a pattern of response and relapse — but each relapse is generally manageable with different therapies, and newer treatments continue to improve outcomes. Approximately only 10–15% of patients present with limited-stage (stage I–II) disease; the majority present at advanced stage but still have a long life expectancy.

The most widely used prognostic tool for classic follicular lymphoma is the Follicular Lymphoma International Prognostic Index (FLIPI), which assigns a score based on five factors: age over 60, stage III–IV disease, hemoglobin below 12 g/dL, more than four nodal sites involved, and elevated LDH. Patients are divided into low-risk (0–1 factors), intermediate-risk (2 factors), and high-risk (3–5 factors) groups. One of the strongest adverse prognostic markers is progression of disease within 24 months of starting first-line treatment (called POD24) — people whose disease progresses within this window have a substantially worse overall survival. EZH2 mutations are associated with a favorable response to chemoimmunotherapy in most patients. TP53 mutation, 9p21 deletion (affecting CDKN2A), and 17p deletion are associated with a less favorable outcome.

Follicular lymphoma with a predominantly diffuse growth pattern has a more favorable prognosis than advanced-stage classic follicular lymphoma because it more commonly presents at a limited stage. Pediatric-type follicular lymphoma has an excellent prognosis with very high rates of long-term cure. Duodenal-type follicular lymphoma has an exceptionally favorable course, with many patients managed without treatment. Follicular large B cell lymphoma has a prognosis and treatment approach more closely resembling aggressive lymphoma.

What happens after the diagnosis?

Management depends on the subtype, stage, FLIPI score, symptoms, and individual health factors. For classic follicular lymphoma at an advanced stage without symptoms or with slow-growing disease, active surveillance (watch and wait) is a standard initial approach — because treatment is not curative and starting therapy early does not improve overall survival, treatment is typically deferred until the disease causes symptoms, grows rapidly, or involves critical organs. When treatment is needed, the standard first-line approach is chemoimmunotherapy — most commonly bendamustine or CHOP-based chemotherapy combined with rituximab or obinutuzumab — followed by maintenance rituximab in many patients. For limited-stage disease, involved-site radiation therapy is used with curative intent in some patients.

For relapsed or refractory classic follicular lymphoma, options include alternative chemoimmunotherapy combinations, tazemetostat (particularly for EZH2-mutated disease), PI3K inhibitors, the lenalidomide-rituximab combination, CAR T cell therapy, or autologous stem cell transplantation in eligible patients. For follicular large B cell lymphoma, intensive chemoimmunotherapy, similar to that used for diffuse large B cell lymphoma, is used from the outset. For pediatric-type follicular lymphoma, surgical excision alone or limited treatment is typically used. Duodenal-type follicular lymphoma is often managed with watchful waiting.

Questions to ask your doctor

Which subtype of follicular lymphoma do I have — classic follicular lymphoma, follicular lymphoma with unusual features, the diffuse growth pattern subtype, follicular large B cell lymphoma, or one of the distinct entities?
What stage is my lymphoma, and what does that mean for my prognosis and treatment options?
What is my FLIPI score, and what does it tell you about my prognosis?
Does my report show any diffuse areas of growth, and if so, how much of the tumor is diffuse?
What is the Ki-67 index, and does it suggest the lymphoma is growing faster than typical?
Was molecular testing performed, and were any mutations found — such as EZH2, TP53, or BCL2 rearrangement?
Is watch and wait an option for me, and what signs or symptoms should prompt me to contact you?
If treatment is recommended, what regimen are you proposing, and why?
What are the warning signs that my lymphoma might be transforming to a more aggressive type?
How will you monitor my response to treatment or disease stability over time?
What happens if the lymphoma comes back, and what are the options at that point?
Are there clinical trials I should consider?