The Hans algorithm is a tool pathologists use to sort diffuse large B-cell lymphoma (DLBCL) into subtypes based on which proteins the cancer cells make. DLBCL is the most common type of non-Hodgkin lymphoma, and it can be divided into two main groups, called cell-of-origin subtypes, based on the normal B cell the lymphoma most resembles: germinal center B-cell-like (GCB) and activated B-cell-like (ABC, also called non-GCB). These subtypes can behave differently and respond differently to treatment. The Hans algorithm is one way of telling them apart. This article explains what the Hans algorithm measures, what the results mean, and how the subtype can affect treatment.
How is the Hans algorithm performed?
The Hans algorithm is based on immunohistochemistry (IHC), a test that uses antibodies to detect specific proteins inside the lymphoma cells. When an antibody attaches to its target protein, it produces a color change that the pathologist can see under the microscope. The algorithm looks at three proteins:
- CD10 — A protein typically made by cells of the germinal center, a region within normal lymph nodes.
- BCL6 — A protein also associated with germinal center cells.
- MUM1 — A protein more often made by activated B cells.
The pathologist records whether each protein is present or absent, then follows the algorithm to place the lymphoma into the GCB or ABC (non-GCB) subtype. The algorithm is essentially a simple decision tree: it starts with CD10, then uses BCL6 and MUM1 to reach a result.
What do the results mean?
The Hans algorithm sorts diffuse large B-cell lymphoma into one of two subtypes:
- Germinal center B-cell-like (GCB) — The pattern of proteins suggests the lymphoma resembles cells of the germinal center. In general, CD10-positive cases fall into this group.
- Activated B-cell-like (ABC), also called non-GCB — The pattern suggests the lymphoma resembles activated B cells, typically with MUM1 present and CD10 absent.
The Hans algorithm is a widely used and practical tool, but it is not perfect. It is an estimate based on three proteins, and more detailed gene-based tests can sometimes place a lymphoma in a different subtype. For this reason, the subtype is considered together with the rest of the pathology report and the clinical picture, rather than on its own.
Why does the subtype matter?
Historically, when diffuse large B-cell lymphoma was treated with standard chemotherapy (a regimen called R-CHOP), patients with the GCB subtype tended to have better outcomes than those with the ABC (non-GCB) subtype. Because of this, the subtype has long been used as a biomarker that provides information about prognosis (the likely course of the disease).
More recently, the subtype has also become useful for choosing treatment. A newer regimen adds a targeted drug called polatuzumab vedotin to chemotherapy (a combination known as Pola-R-CHP). Studies have found that the added benefit of this drug is concentrated in the ABC (non-GCB) subtype, while patients with the GCB subtype appear to do just as well with standard R-CHOP. In other words, the Hans algorithm can now help predict which patients are most likely to benefit from adding this drug. This reverses the older idea that the ABC subtype simply had fewer options; today it is often the subtype for which the newer targeted regimen is chosen.
How does the Hans algorithm affect treatment?
Because the subtype can influence which chemotherapy regimen is recommended, the Hans algorithm result is one piece of information the treatment team uses when planning care. In current practice, many teams consider Pola-R-CHP for patients with the ABC (non-GCB) subtype and standard R-CHOP for patients with the GCB subtype, though the final choice depends on many factors, including lymphoma stage, other tumor features, overall health, and patient preferences. Clinical trials of newer therapies may also be an option for some patients. The medical oncology or hematology team makes treatment decisions based on the complete clinical picture.
Questions to ask your doctor
- Did you use the Hans algorithm to determine my lymphoma subtype?
- Is my diffuse large B-cell lymphoma the GCB or the ABC (non-GCB) subtype?
- What do CD10, BCL6, and MUM1 show in my case?
- Does my subtype affect which chemotherapy regimen you recommend?
- Would I benefit from adding a targeted drug such as polatuzumab vedotin?
- How does my subtype affect my prognosis?
- Are there clinical trials that might be right for me?
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