Follicular Lymphoma With a Predominantly Diffuse Growth Pattern: Understanding Your Pathology Report

Section Editor: David Li MD
August 28, 2026

Follicular lymphoma with a predominantly diffuse growth pattern is a rare subtype of follicular lymphoma. Follicular lymphomas are slow-growing blood cancers that start in B cells, the white blood cells that help the body fight infection. In the more familiar form of follicular lymphoma, the cancer cells grow in round clusters called follicles. In this subtype, they grow instead in flat, sheet-like areas that spread through the lymph node. Most people are diagnosed at an early, localized stage, and the outlook is favorable. Because it looks different from classic follicular lymphoma and carries a different genetic profile, it needs extra testing to diagnose accurately. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What causes follicular lymphoma with a predominantly diffuse growth pattern?

The exact cause of follicular lymphoma with a predominantly diffuse growth pattern is not known. Like all follicular lymphomas, it starts from B cells that have passed through the germinal center. The germinal center is a structure inside a lymph node where B cells mature and learn to recognize specific infections. B cells rewrite parts of their own DNA during this process. An error during that rewriting can produce a clonal population of abnormal B cells, meaning a group of cells all descended from one original abnormal cell.

The most important genetic change in this subtype is a mutation in a gene called STAT6. STAT6 is part of a signaling pathway, a chain of molecular messages inside the cell. That pathway normally tells B cells how to respond to immune system signals. A STAT6 mutation leaves the pathway switched on when it should be off. The cells then receive a continuous growth signal. STAT6 mutations are found in more than half of cases of this subtype. They are much less common in classic follicular lymphoma, which makes them a useful distinguishing feature.

One further difference sets this subtype apart. Most cases of classic follicular lymphoma are driven by a swap of genetic material between chromosomes 14 and 18, written as t(14;18). That swap causes the cell to overproduce a survival protein called BCL2. The t(14;18) rearrangement is absent in follicular lymphoma with a predominantly diffuse growth pattern. The underlying mechanism is therefore different, even though the cell of origin is similar. Why this subtype favors the groin lymph nodes is not understood. Researchers have not identified any environmental, infectious, or lifestyle risk factors.

What are the symptoms of follicular lymphoma with a predominantly diffuse growth pattern?

Most people with follicular lymphoma with a predominantly diffuse growth pattern notice a painless lump in the groin, where the thigh meets the lower abdomen. The lump grows slowly. It is caused by enlarged lymph nodes in the inguinal region, which is the most common site for this subtype. The mass may be large at diagnosis, and several nodes can be matted together. It usually stays confined to that area.

Some people also notice swelling in nearby lymph nodes in the pelvis or abdomen. Others feel mild discomfort or pressure in the groin from the enlarged nodes. General symptoms are uncommon in this subtype. These are fever, drenching night sweats, and unintentional weight loss, sometimes called B symptoms. When they are present, your care team will look carefully for signs that the disease has progressed or changed into a faster-growing lymphoma. Many people feel well at diagnosis, and the mass is found during a routine examination or an imaging study done for another reason.

How is the diagnosis made?

Doctors diagnose follicular lymphoma with a predominantly diffuse growth pattern by examining lymph node tissue under a microscope. This subtype lacks the round follicular clusters that make most follicular lymphomas recognizable at low magnification. An adequate tissue sample is therefore essential. A core needle biopsy alone is usually not enough because the full tissue architecture must be assessed. An excisional biopsy, meaning removal of an entire lymph node, is strongly preferred. It allows the pathologist to evaluate the overall growth pattern, the cell types present, and any residual normal lymph node structures.

After examining the tissue, the pathologist performs immunohistochemistry, a laboratory test that detects specific proteins in the cells. Flow cytometry is often performed as well to characterize the cells in more detail. Genetic testing for the BCL2 rearrangement and for STAT6 mutation is also typically done. These tests support the diagnosis and confirm that this is not classic follicular lymphoma or another lymphoma type. Once the diagnosis is established, imaging with a PET/CT scan shows whether the disease is localized or has spread.

What does this lymphoma look like under the microscope?

Under the microscope, follicular lymphoma with a predominantly diffuse growth pattern looks different from most follicular lymphomas. That difference is central to the diagnosis. The lymphoma cells grow in a predominantly diffuse pattern, spreading in flat, sheet-like areas through the lymph node. They do not form the round, tightly organized clusters called follicles that give follicular lymphoma its name. Very small residual follicles called microfollicles can sometimes still be found. These are scattered and inconspicuous rather than dominant.

The lymphoma cells are almost entirely centrocytes. Centrocytes are the smaller cell type that normally lives in germinal centers. Their nuclei are irregular, folded, or cleaved, meaning notched along one edge. Classic follicular lymphoma contains a mixture of centrocytes and larger cells called centroblasts. This subtype has very few or no centroblasts. The cells therefore look relatively uniform and small. Pathologists assign classic follicular lymphoma a grade from 1 to 3 based on how many centroblasts are present. Because this subtype is almost purely centrocytic, pathologists generally do not assign a formal grade, and your report may not include one.

The absence of follicular dendritic cells is another key feature. These are supporting cells normally found inside follicles, where they help B cells develop. Pathologists use immunohistochemistry stains for CD21 or CD23 to highlight them. Their absence throughout the diffuse areas confirms that the tissue lacks true follicular organization. Small residual follicles, where present, may show faint remnants of these supporting cells.

Patches of scar-like fibrous tissue, called sclerosis, may be seen within or around the lymphoma. Sclerosis is a recognized feature of this subtype and does not indicate a worse outcome.

Immunohistochemistry results

Immunohistochemistry (IHC) is a laboratory test performed on the biopsy tissue. It uses antibodies that attach to specific proteins and produce a visible color change under the microscope. In follicular lymphoma with a predominantly diffuse growth pattern, IHC confirms that the cells are B cells and separates this subtype from other lymphomas that look similar. Each result is reported as positive, meaning the protein is present, or negative, meaning it is absent. The profile below differs from classic follicular lymphoma in several important ways.

CD20 — Positive. Confirms the lymphoma cells are B cells. CD20 is also the target of rituximab, an antibody drug used in treatment.
CD10 — Usually positive. Expression may be variable or absent in some cases. CD10 marks germinal center B cells and is also positive in classic follicular lymphoma.
BCL6 — Positive. Another marker of germinal center origin.
BCL2 — Negative or weakly positive. This is one of the most important differences from classic follicular lymphoma. In classic follicular lymphoma, BCL2 is strong and uniform because of the t(14;18) rearrangement. Here it is absent or faint, reflecting the absence of that rearrangement. Residual small follicles may also stain weakly or not at all.
CD23 — Frequently positive. CD23 is usually negative in classic follicular lymphoma. It is expressed in most cases of this subtype, particularly those with STAT6 mutations. CD23 positivity in a diffuse-pattern follicular lymphoma is an important clue to this diagnosis.
CD21 and CD35 — Absent or markedly reduced. These stains highlight follicular dendritic cells, which are missing from the diffuse areas. Their absence confirms the lack of true follicular architecture.
CD3 — Negative. Confirms the lymphoma cells are not T cells.
CD5 — Negative. Helps exclude small lymphocytic lymphoma and mantle cell lymphoma.
Cyclin D1 — Negative. Helps exclude mantle cell lymphoma.

Molecular and genetic testing

Molecular testing plays a large role in diagnosing follicular lymphoma with a predominantly diffuse growth pattern. No single feature establishes the diagnosis on its own. Instead, the diagnosis rests on the combination of what the cells look like, which proteins they express, and which genetic changes are present. The tests below are the ones most often named on a report for this subtype.

BCL2 rearrangement, t(14;18)

The t(14;18) rearrangement drives most cases of classic follicular lymphoma. Testing for it is an essential part of the workup. It is absent in follicular lymphoma with a predominantly diffuse growth pattern, and that absence helps define this subtype. Testing is performed by FISH or PCR. A negative result, combined with the other supporting features, helps separate this subtype from classic follicular lymphoma and from other B cell lymphomas.

STAT6 mutation

STAT6 encodes a protein involved in immune cell signaling. Normally, STAT6 is activated only briefly, in response to immune signals called IL-4 and IL-13. Mutations in STAT6 leave the protein permanently switched on, so the lymphoma cells receive a continuous growth signal. STAT6 mutations are found in more than 50% of cases of this subtype. Together with CD23 expression, they are strongly associated with tumors arising in the inguinal region. STAT6 mutations are uncommon in classic follicular lymphoma and in other low-grade B cell lymphomas. Testing is performed by next-generation sequencing or targeted mutation testing.

TNFRSF14 deletion and mutation

Deletion of a region of chromosome 1p36 is frequently found in this subtype. That region contains a gene called TNFRSF14. Losing it changes how the lymphoma interacts with the surrounding immune cells, creating conditions that favor lymphoma cell survival. TNFRSF14 mutations also occur in classic follicular lymphoma, but 1p36 deletions appear to be particularly common in this subtype. These findings usually come from comprehensive molecular profiling rather than routine testing.

Immunoglobulin gene clonality testing

Like all follicular lymphomas, this subtype shows a monoclonal rearrangement of the immunoglobulin heavy chain (IGH) and light chain genes. All the lymphoma cells carry the same unique rearrangement, confirming they descend from a single original abnormal cell. This testing helps confirm that the process is clonal, meaning a true cancer, rather than a reactive immune response.

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

Why can this diagnosis be challenging?

Follicular lymphoma with a predominantly diffuse growth pattern overlaps under the microscope with several other lymphomas. This is why the pathologist orders a long list of additional stains and genetic tests before settling on a final diagnosis. Knowing what each test was looking for can make a complex report easier to follow.

The most important condition to exclude is nodal marginal zone lymphoma. This is a different slow-growing B cell lymphoma that can also grow in a diffuse pattern and involve the inguinal lymph nodes. The distinction matters because the two diseases behave differently and have different genetic profiles. Features favoring follicular lymphoma with a predominantly diffuse growth pattern include CD10 positivity, BCL6 positivity, a mostly centrocytic cell population, STAT6 mutation, and 1p36 deletion. Features favoring nodal marginal zone lymphoma include expression of proteins called MNDA and IRTA1, which are usually absent in follicular lymphoma.

Classic follicular lymphoma with extensive diffuse areas must also be excluded. In classic follicular lymphoma, BCL2 is strongly positive and the t(14;18) rearrangement is present. Both are absent in this subtype. Classic follicular lymphoma also contains a mixture of centrocytes and centroblasts, whereas this subtype is almost entirely centrocytic.

Diffuse large B cell lymphoma is the third condition to exclude, particularly when the cells are large or the Ki-67 proliferation index is high. The small centrocytic cell population and low proliferation rate help distinguish this subtype. Because these distinctions depend on the full tissue architecture, a core needle biopsy is often not sufficient. If your report was based on a core biopsy and notes uncertainty, your care team may discuss an excisional biopsy before making treatment decisions.

Staging

Follicular lymphoma with a predominantly diffuse growth pattern is staged using the Lugano classification. Staging describes how widely the lymphoma has spread through the body and is based primarily on PET/CT imaging. A bone marrow biopsy is sometimes performed to look for involvement outside the lymph nodes. A defining feature of this subtype is that it usually presents at a limited stage (stage I or II). The disease is generally confined to the inguinal nodes and sometimes adjacent pelvic nodes. Limited-stage presentation is far more common here than in classic follicular lymphoma, where most patients present at stage III or IV.

Stage I — A single lymph node region is involved. For most patients with this subtype, that means inguinal lymph nodes on one side.
Stage II — Two or more lymph node regions on the same side of the diaphragm are involved. This may include inguinal and pelvic nodes.
Stage III — Lymph node regions on both sides of the diaphragm are involved.
Stage IV — The lymphoma has spread to an organ outside the lymphatic system, such as the bone marrow or liver. This is uncommon at diagnosis in this subtype.

What is the prognosis?

Follicular lymphoma with a predominantly diffuse growth pattern has a favorable prognosis. Most patients present with limited-stage disease, which is the main reason outcomes are good. Published series report high rates of durable remission after involved-site radiation therapy or rituximab for limited-stage disease. Many patients achieve long-term disease control.

Even patients with more widespread disease tend to follow a slow-growing course. The risk of transformation to a faster-growing lymphoma such as diffuse large B cell lymphoma appears low. Long-term data remain limited, because this subtype was only formally recognized as a distinct entity in the WHO 2022 classification. Studies to date report favorable progression-free and overall survival. Large cohorts with long follow-up are still being assembled.

This subtype has a different biology from classic follicular lymphoma, lacking the BCL2 rearrangement and frequently carrying a STAT6 mutation. Whether prognostic tools built for classic follicular lymphoma, such as the FLIPI score, apply equally here is not yet established. Your care team can give you an individual estimate based on your stage, your specific findings, and your overall health.

What happens after the diagnosis?

Once your doctor confirms follicular lymphoma with a predominantly diffuse growth pattern, the next steps depend mainly on the stage recorded in your report. Most patients have limited-stage disease, meaning stage I or II. For these patients, the treatment team will usually consider involved-site radiation therapy, which directs radiation at the affected lymph node region. This approach achieves durable disease control in a high proportion of patients. Rituximab, an anti-CD20 antibody, alone or with limited chemotherapy, is an alternative where radiation is not suitable. For a single small mass, the team may discuss careful observation instead.

For the smaller group with advanced-stage disease, management follows the principles used in advanced-stage classic follicular lymphoma. Active surveillance, sometimes called watch and wait, may be appropriate when there are no symptoms and no rapid progression. When treatment is needed, chemoimmunotherapy with rituximab is typically used, often followed by rituximab maintenance. This subtype lacks a BCL2 rearrangement. Drugs that specifically target BCL2, such as venetoclax, therefore have an uncertain role here and would generally be used only in a clinical trial.

All patients need ongoing monitoring with periodic blood tests and imaging. This checks for progression, new sites of disease, and the uncommon event of transformation to a faster-growing lymphoma. Your care team will set the schedule based on your stage and your response to treatment.

Questions to ask your doctor

Is my diagnosis definitely follicular lymphoma with a predominantly diffuse growth pattern, or are there features that still need clarification?
Was an excisional biopsy performed, and if not, will one be needed to confirm the diagnosis?
Was testing for the BCL2 rearrangement performed, and was the result negative as expected for this subtype?
Was a STAT6 mutation found, and what does that mean for my diagnosis?
Was CD23 positive on my biopsy?
Was nodal marginal zone lymphoma considered and excluded?
What stage is my lymphoma, and is it limited to the groin?
What treatment options do my stage and pathology findings make appropriate?
If radiation is being considered, which area would be treated?
Is watch and wait an option for me, and what signs should prompt me to contact you?
How does this subtype differ from classic follicular lymphoma in outlook and treatment?
How will you monitor me for recurrence or transformation over time?
Are there clinical trials open to me for this subtype?