Non-Hodgkin’s Lymphoma Unspecified Histology Aggressive

Aggressive non-Hodgkin lymphomas grow and spread quickly, requiring immediate treatment — but many patients can be cured with intensive combination therapy.

Table of contents

• What is Aggressive Non-Hodgkin Lymphoma?
• Where the Disease Occurs
• Signs and Symptoms
• Who Is Affected and Why
• How the Disease Is Diagnosed
• Treatment Options
• Outlook and Survival

What is Aggressive Non-Hodgkin Lymphoma?

Aggressive non-Hodgkin lymphoma is a type of blood cancer that develops when certain white blood cells, called lymphocytes (cells that help fight infections), grow out of control in the body’s lymphatic system (the network of organs and vessels that help protect the body from disease). These cancers spread faster than other forms of lymphoma^[1].

Non-Hodgkin lymphoma is a broad group of cancers that can develop from either B cells or T cells, which are two different types of lymphocytes. About 85% of all non-Hodgkin lymphomas come from B cells^[4]. Healthcare providers classify these lymphomas as either aggressive or indolent (slow-growing). Aggressive lymphomas grow and spread more quickly and often require more intensive treatment than indolent types^[1].

While aggressive non-Hodgkin lymphoma has a more serious outlook in the short term compared to slow-growing forms, a significant number of patients can be cured with intensive combination chemotherapy treatments^[4]. More than 70% of patients with aggressive forms can be cured^[4].

• Lymph nodes
• Spleen
• Thymus
• Bone marrow
• Tonsils

Where the Disease Occurs

Non-Hodgkin lymphoma usually starts in the lymphoid tissues, which are found throughout the body. The lymphatic system includes the lymph nodes (small bean-shaped glands), spleen, thymus, bone marrow, tonsils, and lymph vessels that carry fluid throughout the body. Lymph tissue is also found in many other parts of the body, including the small intestine^[4].

The abnormal lymphoma cells usually form in the lymph nodes and create tumors. However, they can also develop in other lymph system organs, like the thymus or spleen, or in lymph tissue found in other places^[1]. Without treatment, non-Hodgkin lymphoma can spread beyond these starting points.

Non-Hodgkin lymphoma is much less predictable than another type of lymphoma called Hodgkin lymphoma. It has a far greater tendency to spread to sites outside the lymph nodes, called extranodal sites^[4]. Between 10 and 35 percent of patients have lymphoma outside the lymph nodes at the time of diagnosis^[2].

Signs and Symptoms

The most common symptom of non-Hodgkin lymphoma is painless swelling in the neck, armpits, or groin. This swelling is caused by enlarged lymph nodes in those areas^[1]. Other signs and symptoms depend on where the lymphoma cells are located in the body.

Aggressive lymphomas often cause specific symptoms known as B symptoms, which include fever, night sweats, and unexplained weight loss. Healthcare providers use these symptoms to help classify the type of lymphoma^[1]. Aggressive forms can result in death within a few weeks if left untreated^[2].

Additional symptoms may include:

• Persistent tiredness
• Chest pain
• Coughing or trouble breathing
• Belly pain or swelling
• Feeling full even when you haven’t eaten much
• Unexplained fever, especially one that stays above 103 degrees Fahrenheit (39.5 degrees Celsius) for two or more hours after home treatment or lasts longer than two days
• Drenching night sweats that soak your sheets
• Unexplained weight loss, such as losing 10% of your total body weight over six months^[1]

It’s important to remember that many conditions share these symptoms. Having one or more doesn’t necessarily mean you have lymphoma. However, it’s a good idea to contact a healthcare provider anytime you notice changes in your body that last for several weeks^[1].

Who Is Affected and Why

Non-Hodgkin lymphoma is relatively common. It is the 8th most common cancer diagnosis in the United States, with 80,620 new cases expected in 2024. Worldwide, it is the 11th most common cancer^[1]. In 2025, an estimated 80,350 new cases and 19,390 deaths are expected in the United States^[4].

Non-Hodgkin lymphoma can occur at any age, but the chances of developing the condition increase as you get older. Just over a third of cases are diagnosed in people over 75 years old. Slightly more men than women are affected^[7].

With non-Hodgkin lymphoma, genes inside B cells or T cells change, or mutate, at some point during a person’s lifetime. The exact cause of these changes is unknown. However, your risk of developing the condition increases if:

• You have a medical condition that weakens your immune system
• You take medicines that suppress your immune system
• You have previously been exposed to a common virus called the Epstein-Barr virus, which causes glandular fever (also known as mononucleosis)^[7]

You also have a slightly increased risk if a close relative, such as a parent or sibling, has had the condition^[7]. These tumors may result from chromosomal translocation (when pieces of chromosomes switch places), various toxins, infections, and chronic inflammation^[2].

How the Disease Is Diagnosed

Diagnosing non-Hodgkin lymphoma often begins with a physical exam. A healthcare professional checks for swollen lymph nodes in your neck, underarms, and groin, and also checks for a swollen spleen or liver^[12].

Several tests are used to detect non-Hodgkin lymphoma. The tests used may depend on the cancer’s location and your symptoms:

Blood and urine tests may help rule out an infection or other disease^[12].

Imaging tests look for lymphoma cells in other parts of the body. These may include CT (computed tomography) scans, MRI (magnetic resonance imaging), and PET (positron emission tomography) scans^[12].

Lymph node biopsy is the only way to confirm a diagnosis of non-Hodgkin lymphoma. This is a procedure to remove all or part of a lymph node for testing in a laboratory. The sample is examined to show whether you have non-Hodgkin lymphoma and, if so, which type^[12].

Bone marrow tests involve collecting cells from the bone marrow. In a bone marrow aspiration, a needle is used to draw a sample of the fluid portion. In a bone marrow biopsy, a needle is used to remove a small piece of bone tissue and the enclosed marrow. These procedures are usually done at the same time^[12].

Treatment Options

The treatment of aggressive non-Hodgkin lymphoma varies greatly, depending on the tumor stage, grade, type of lymphoma, and various patient factors such as symptoms, age, and overall health^[2].

Aggressive lymphomas require immediate treatment because they spread and grow more quickly. The main treatments used include:

Chemotherapy uses powerful medicines to kill cancer cells. Intensive combination chemotherapy treatments can cure many patients with aggressive non-Hodgkin lymphoma^[4].

Radiotherapy uses high-energy radiation to destroy cancer cells^[7].

Monoclonal antibody therapy is a targeted treatment that uses laboratory-made proteins that can recognize and attach to specific proteins on cancer cells^[7].

For some patients, aggressive consolidation with bone marrow or stem cell support may be used to help achieve sustained complete remissions (no signs or symptoms of cancer)^[4].

People with non-Hodgkin lymphoma are living longer than ever, thanks to new treatments. In some cases, treatments cure the condition. Other times, the goal of treatment is to put the disease into remission for as long as possible^[1].

Outlook and Survival

Aggressive non-Hodgkin lymphoma has a worse outlook in the short term compared to slow-growing forms. However, a significant number of these patients can be cured with intensive combination chemotherapy treatments^[4].

In general, with modern treatment of patients with non-Hodgkin lymphoma, the 5-year overall survival rate is over 60%. More than 70% of patients with aggressive non-Hodgkin lymphoma can be cured^[4]. Most relapses occur in the first 2 years after therapy^[4].

The outlook depends on several factors, including the specific type of lymphoma, the stage of disease, and the treatment used. Advances in diagnosis and treatment of non-Hodgkin lymphoma have helped improve the prognosis for people with this condition^[3].

Late effects of treatment have been observed. Impaired fertility may occur after exposure to certain chemotherapy drugs called alkylating agents. For as many as three decades after diagnosis, patients are at a significantly elevated risk of developing another type of cancer^[4].