Nodular Lymphocyte Predominant Hodgkin Lymphoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 16, 2026

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare, slow-growing blood cancer that starts in B cells — the white blood cells that help the body fight infections. It belongs to the Hodgkin lymphoma family but differs fundamentally from the more common type, classic Hodgkin lymphoma, in its cell biology, behavior, and treatment. Compared with classic Hodgkin lymphoma, NLPHL grows more slowly, tends to present at an earlier stage, and has a distinct protein expression profile, making rituximab — rather than the traditional Hodgkin lymphoma chemotherapy backbone — an important part of treatment.

A note on naming: the World Health Organization (WHO) uses the term “nodular lymphocyte-predominant Hodgkin lymphoma,” while the International Consensus Classification uses “nodular lymphocyte-predominant B cell lymphoma” for the same condition. Both names refer to the same disease, and you may see either in your pathology report or correspondence. 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 nodular lymphocyte-predominant Hodgkin lymphoma?

Most people with NLPHL feel well at the time of diagnosis. The most common presentation is one or more painless, slowly enlarging lumps caused by swollen lymph nodes, most often in the neck, armpit, or groin. Unlike classic Hodgkin lymphoma, NLPHL very rarely involves the lymph nodes in the chest (the mediastinum), and chest symptoms such as cough or shortness of breath are uncommon.

General symptoms — fever, drenching night sweats, and unintentional weight loss of more than 10% of body weight over six months, collectively called B symptoms — are uncommon in NLPHL compared to classic Hodgkin lymphoma, and their presence should prompt a careful re-evaluation to confirm the diagnosis and rule out transformation to a more aggressive lymphoma. Fatigue may be present. Because lymph node swelling can have many causes, including infections, a biopsy is required to confirm the diagnosis.

What causes nodular lymphocyte-predominant Hodgkin lymphoma?

The exact cause is not known. NLPHL arises from acquired genetic changes — changes that occur during a person’s lifetime in a single B cell rather than being inherited — that cause the cell to grow uncontrollably. The cell of origin is a B cell that has undergone germinal center reactions, the normal process by which B cells mature and learn to recognize infections inside the lymph node. When this process goes wrong, the abnormal B cell gives rise to the characteristic LP cells that define the disease.

Unlike the mixed cellularity and lymphocyte-depleted subtypes of classic Hodgkin lymphoma, NLPHL is not associated with Epstein-Barr virus (EBV) infection in most cases, and it is not strongly linked to immune deficiency. No specific environmental, dietary, or lifestyle risk factor has been identified. A small number of cases occur in people with a personal or family history of lymphoma, but most cases arise without any identifiable predisposing condition.

How is the diagnosis made?

The diagnosis of NLPHL requires tissue examination and cannot be made on clinical findings or imaging alone. An excisional biopsy — removal of an entire lymph node — is strongly preferred, because the full architectural pattern of the node is essential for identifying the nodular growth pattern and LP cells, and for distinguishing NLPHL from classic Hodgkin lymphoma and from other B cell lymphomas that can look similar. A core needle biopsy may be used when an excisional biopsy is not accessible, though it provides less tissue and can make the diagnosis more difficult. Fine needle aspiration alone is not sufficient.

The pathologist first examines the tissue under the microscope to identify the characteristic nodular growth pattern and LP cells, then performs immunohistochemistry (IHC) — a laboratory test that detects specific proteins in the cells — to confirm the diagnosis. IHC is essential because NLPHL shares some microscopic features with classic Hodgkin lymphoma and with certain B cell lymphomas, and the protein expression profile is the definitive way to distinguish them. A positive CD20 result, combined with negative CD30 and CD15, is the most important IHC pattern for confirming NLPHL and distinguishing it from classic Hodgkin lymphoma. Once the diagnosis is established, PET/CT imaging and blood tests are used to determine the extent and stage of disease.

What does nodular lymphocyte-predominant Hodgkin lymphoma look like under the microscope?

Under the microscope, NLPHL has a distinctive appearance that differs from classic Hodgkin lymphoma in several important ways.

The most characteristic feature is the nodular growth pattern — the lymphoma cells form round or oval clusters called nodules within the lymph node, rather than spreading diffusely. These nodules are filled predominantly with small, normal-appearing B cells and scattered large, abnormal cells. A layer of intact normal lymph node tissue may still be visible at the outer edge of the affected node. In some cases, a more diffuse growth pattern is present alongside the nodular areas, and a purely diffuse pattern can occasionally be seen — this is noted in the pathology report because it may be associated with a somewhat less favorable prognosis.

The defining abnormal cells are called LP cells — short for lymphocyte-predominant cells. LP cells are large, with nuclei (the DNA-containing compartments of the cell) that are folded, multi-lobed, or have a crinkled shape often compared to the appearance of a popcorn kernel, which is why they are informally called “popcorn cells.” Unlike the Reed-Sternberg cells of classic Hodgkin lymphoma, LP cells do not have the characteristic prominent owl-eye nucleoli. LP cells are typically scattered sparsely within the nodules and usually make up only a small fraction of the overall tumor, surrounded by many non-cancerous lymphocytes.

The background cells within and surrounding the nodules are predominantly normal small B cells with a pattern resembling the cells found in lymph node mantle zones — the region just outside germinal centers. Surrounding the LP cells are many T cells (another type of immune cell) that form close associations called rosettes — rings of T cells wrapping around individual LP cells. These T cell rosettes are a helpful microscopic clue that distinguishes NLPHL from other lymphomas. Eosinophils and neutrophils — types of white blood cells commonly seen in the background of classic Hodgkin lymphoma — are typically absent from NLPHL.

Immunohistochemistry results

Immunohistochemistry (IHC) is the most important part of confirming the diagnosis. The protein profile of LP cells in NLPHL is strikingly different from the Reed-Sternberg cells of classic Hodgkin lymphoma, and understanding this difference explains why the two diseases are treated differently despite both being called Hodgkin lymphoma.

CD20 — Positive. CD20 is a protein expressed on the surface of normal B cells and is strongly expressed by LP cells in NLPHL. This is the single most important clinical difference from classic Hodgkin lymphoma, where CD20 is absent or only weakly expressed in Reed-Sternberg cells. CD20 is the target of rituximab, an antibody treatment that binds to CD20-positive cells and helps eliminate them. The strong CD20 positivity of LP cells is why rituximab is an important part of treatment for NLPHL.
CD79a — Positive. Another B cell surface marker confirming B cell origin.
OCT2 and BOB1 — Positive. These are transcription factors — proteins that control gene activity — that are strongly expressed in normal B cells and in LP cells, but are characteristically absent or very weakly expressed in the Reed-Sternberg cells of classic Hodgkin lymphoma. Their strong co-expression in LP cells is one of the most reliable IHC features supporting a diagnosis of NLPHL over classic Hodgkin lymphoma, particularly in cases where the morphology is ambiguous.
BCL6 and LMO2 — Positive. Markers of germinal center B cells, reflecting the stage of B cell development from which NLPHL arises.
CD30 — Negative in LP cells (or only rarely and weakly positive). CD30 is the protein that is almost universally expressed by Reed-Sternberg cells in classic Hodgkin lymphoma and is the target of brentuximab vedotin, a targeted drug used in classic Hodgkin lymphoma. Its absence from LP cells means brentuximab vedotin is not effective in NLPHL and is not used.
CD15 — Negative. CD15 is another classic Hodgkin lymphoma marker expressed by Reed-Sternberg cells but absent from LP cells. Its absence, together with negative CD30, is a key finding that distinguishes NLPHL from classic Hodgkin lymphoma.
CD10 — Negative in LP cells. Helps exclude follicular lymphoma, which also has a nodular growth pattern and can look similar to NLPHL in some cases.
IgD — Positive in some cases. Expression of IgD (an immunoglobulin protein) on LP cells is seen in a subset of NLPHL cases, most often in young men with peripheral lymph node involvement. This IgD-positive variant has specific microscopic and clinical features that your pathologist may note in the report.

The surrounding T cells in NLPHL also show a characteristic immunophenotype, expressing markers such as PD1, CD57, BCL6, CXCL13, and ICOS — a combination that identifies them as T follicular helper cells. These T cells form the tight rosettes around LP cells visible under the microscope. Their presence is an additional diagnostic clue when LP cells are scarce.

Staging

NLPHL is staged using the Lugano classification, which describes how widely the lymphoma has spread in the body. Staging is based on PET/CT imaging and helps guide treatment decisions.

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 lymph nodes, such as the liver or bone marrow.

The letters A and B are added to indicate whether B symptoms (fever, drenching night sweats, and significant weight loss) are absent (A) or present (B). As noted above, B symptoms are uncommon in NLPHL. Unlike classic Hodgkin lymphoma, which frequently presents at advanced stages, the majority of NLPHL patients — approximately 70–80% — are diagnosed with limited-stage (stage I or II) disease, which contributes to the generally excellent prognosis.

Transformation to a more aggressive lymphoma

One of the most important long-term considerations in NLPHL is the risk of transformation — a process in which the slow-growing lymphoma acquires additional genetic changes and converts into a more aggressive cancer. Transformation in NLPHL most commonly produces a diffuse large B cell lymphoma. This occurs in approximately 5–15% of patients over many years and is more common in patients with repeated relapses or those who have received multiple prior treatments.

Transformation should be suspected when there is a sudden rapid increase in the size of a lymph node or mass, new B symptoms, a sharp rise in LDH (a blood marker of cell turnover), or involvement of new sites. A new biopsy of the most rapidly growing or metabolically active site — identified by PET/CT — is needed to confirm transformation. Transformed NLPHL is treated as an aggressive lymphoma with intensive chemoimmunotherapy, and outcomes depend on how extensively the disease has spread at the time of transformation. Regular follow-up is important because transformation can occur many years after initial diagnosis and treatment.

What is the prognosis?

NLPHL has an excellent overall prognosis. Long-term survival rates exceed 90% in most published series, and many patients achieve durable remission after a single course of treatment. The disease is considered highly treatable at all stages.

However, NLPHL has a distinctive pattern that sets it apart from classic Hodgkin lymphoma: late relapses are more common. Even after achieving complete remission, some patients experience disease recurrence many years — sometimes more than a decade — after initial treatment. For this reason, long-term follow-up is important even in patients who appear to be doing well. Importantly, most patients who relapse can still be successfully retreated, and late relapse does not necessarily translate to a poor outcome.

Factors associated with a less favorable prognosis include advanced stage at diagnosis, a predominantly diffuse (rather than nodular) growth pattern on biopsy, older age, and transformation to an aggressive lymphoma. The IgD-positive variant in young men tends to have a particularly favorable prognosis. Early-stage disease treated with radiation therapy alone carries an excellent prognosis, with disease-free survival rates of approximately 80–90% at ten years in many series.

What happens after the diagnosis?

Because NLPHL is slow-growing and most patients present with limited-stage disease, treatment is approached differently from classic Hodgkin lymphoma. The management strategy is highly stage-dependent, and a multidisciplinary team — including a hematologist or lymphoma oncologist and a radiation oncologist — will guide decisions.

For limited-stage disease (stage I–II) without unfavorable features, involved-site radiation therapy alone — radiation directed at the affected lymph node region — is a standard approach that achieves excellent long-term disease control in most patients. Rituximab alone (four to six doses) is an alternative for patients unsuitable for radiation, or can be combined with radiation. The combination of rituximab and radiation achieves very high remission rates in early-stage disease.

For more advanced or symptomatic disease, rituximab-based chemoimmunotherapy is the standard approach. Rituximab is typically combined with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) — given as R-CHOP — which is the most commonly used regimen. Unlike in classic Hodgkin lymphoma, the ABVD chemotherapy regimen is not routinely used in NLPHL, because the strong CD20 expression of LP cells makes rituximab-based combinations more appropriate. Rituximab maintenance therapy after initial treatment may be recommended in some patients to prolong remission.

For selected patients with very limited stage I disease and no unfavorable features, active surveillance — careful monitoring without immediate treatment — may occasionally be discussed, though this is less common than in some other indolent lymphomas.

In the event of relapse, retreatment with rituximab-based regimens is often effective. Transformation to diffuse large B cell lymphoma requires a change to intensive chemoimmunotherapy appropriate for aggressive lymphoma.

Questions to ask your doctor

Is my diagnosis nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or nodular lymphocyte-predominant B cell lymphoma (NLPBCL) — and are these the same thing in my case?
Was CD20 confirmed as positive and CD30 confirmed as negative in my biopsy?
What stage is my lymphoma, and what does that mean for my treatment options?
Is my growth pattern predominantly nodular, or are there significant diffuse areas?
What treatment are you recommending — radiation, rituximab, R-CHOP, or a combination?
Is watch and wait an option for me, or does my disease require treatment now?
How will you monitor me for transformation to a more aggressive lymphoma over time?
What signs or symptoms should prompt me to contact you between appointments?
What is the risk of the lymphoma coming back, and if it does, what are the treatment options?
How long will I need follow-up, given that late relapses can occur many years after treatment?
Are there clinical trials I should consider?