Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)

NLPHL is a cancer of B cells, the white blood cells that make antibodies. The cancer cells are large cells called lymphocyte-predominant (LP) cells. They are sometimes called popcorn cells because of their folded nucleus. They sit among many normal immune cells in a lymph node.

It is grouped with Hodgkin lymphoma, but it behaves differently from classic Hodgkin lymphoma. Its cells carry the B-cell marker CD20 and lack CD15 and usually CD30, the reverse of classic Hodgkin cells. Because of this, a 2022 international classification renamed it nodular lymphocyte-predominant B-cell lymphoma. The World Health Organization keeps the Hodgkin name for now but accepts the new one.

NLPHL is rare. European transplant experts note that it makes up only about 5% of Hodgkin lymphoma. Around 220 people are diagnosed with it in the UK each year.

The cause of most NLPHL is not known. Like other lymphomas, it starts when a B cell picks up changes that let it grow out of control. Research has found repeated changes in genes such as SOCS1, DUSP2, JUNB and SGK1 in the lymphoma cells themselves.

NLPHL is much more common in males, and scientists do not know why. Unlike some classic Hodgkin lymphoma, it is only rarely linked to Epstein-Barr virus. Having a parent, brother or sister with Hodgkin lymphoma raises the risk of Hodgkin lymphoma in general.

One form of NLPHL has cells that carry a protein called IgD, and it is more common in young people. In this form, research points to a role for a common bacterium, Moraxella catarrhalis. This is an area of active study, and most people with NLPHL have no known cause.

The most common sign is a painless swollen lymph node, often in the neck, armpit or groin. Most people have no other symptoms when it is found. Unlike classic Hodgkin lymphoma, it usually does not involve the middle of the chest (mediastinum). Fever, night sweats and weight loss (B symptoms) are also uncommon.

Most people are diagnosed at an early stage. About 1 in 4 have advanced disease when they are diagnosed. NLPHL grows slowly, but it can come back, sometimes years after treatment.

Sometimes NLPHL changes (transforms) into a faster-growing lymphoma, such as diffuse large B-cell lymphoma or T-cell/histiocyte-rich large B-cell lymphoma. NCI reports this in about 10% of people by 10 years. That is why a new biopsy is usually done if NLPHL comes back.

NLPHL is diagnosed with a biopsy, usually removing a swollen lymph node or part of one. An expert lymphoma pathologist looks for the large LP (popcorn) cells. Marker tests (immunophenotyping) show that these cells carry CD20 and other B-cell markers and lack CD15. This tells NLPHL apart from classic Hodgkin lymphoma.

It can be hard to tell NLPHL from a harmless lymph node change called progressive transformation of germinal centers, or from T-cell/histiocyte-rich large B-cell lymphoma. The pathologist also notes the growth pattern. Some less typical patterns have been linked to more aggressive behavior.

Staging tests show where the lymphoma is. They usually include a CT or PET-CT scan and blood tests; children may have an MRI scan instead. Some people have a bone marrow biopsy. An international score counts age 45 or older, stage III or IV, low hemoglobin and spleen involvement as risk factors.

Treatment depends on the stage, symptoms, age and other personal factors. Because the outlook is usually very good, care teams try to limit long-term side effects. For some people with little disease and no symptoms, active monitoring (“watch and wait”) is an option.

For early-stage NLPHL in adults, radiation to the affected area is often used, sometimes with a short course of chemotherapy. If surgery removes all of the lymphoma, some people need no more treatment and have regular checkups instead. In a Children’s Oncology Group trial, children with early-stage disease were watched after surgery removed a single node, or had a short course of chemotherapy.

Advanced NLPHL is often treated with rituximab, an antibody that targets CD20, together with chemotherapy such as R-CHOP or R-CVP. Rituximab alone is another option, including for people who are not well enough for chemotherapy.

A stem cell transplant is rarely used. European transplant recommendations limit it to high-risk patients whose disease has come back. When it is used, for example if NLPHL returns soon or several times, it is usually an autologous transplant. That means high-dose chemotherapy followed by the person’s own stored stem cells.

Many people with NLPHL live for many years with few symptoms. Being watched without treatment can feel strange after a cancer diagnosis, but for some people it is a standard choice, with regular checkups. Lymphoma Action notes that for advanced NLPHL that is not causing problems, treatment works just as well for people who wait until they need it.

After treatment, follow-up visits are about every 3 months at first, then less often. Long-term follow-up matters. In a large German study, more deaths came from second cancers and other conditions possibly linked to treatment than from NLPHL itself.

Treatment can affect fertility, so care teams may offer a referral to a fertility specialist before it starts. In children, care teams try to avoid more chemotherapy and radiation than needed. Radiation alone, at the doses needed to control the lymphoma, can harm growing bones and muscles.

Most people with NLPHL will never need a stem cell donor. Treatment is usually monitoring, surgery, radiation or rituximab-based medicine.

When a transplant is used, it is usually autologous. It gives back the person’s own stored stem cells, so no registry donor is involved. Published transplant studies in NLPHL mostly describe this kind of transplant.

Joining a registry is not the usual next step for someone with NLPHL. But registries serve patients with many blood cancers and blood disorders, and each volunteer widens the choices for a patient without a matched relative.

The outlook for NLPHL is very good for most people. NCI notes that people with NLPHL tend to have earlier-stage disease and longer survival than people with classic Hodgkin lymphoma. Children and teens tend to do even better than adults.

NLPHL can come back, sometimes years later, but it usually responds well to more treatment. Transformation to a faster-growing lymphoma is uncommon. When it happens, it needs stronger treatment, which often works well.

Long-term effects of treatment matter. In the German Hodgkin Study Group’s long-term study, 10 of 43 deaths were caused by NLPHL. Most of the others were due to second cancers or other conditions possibly linked to treatment.