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Lymphoma is a cancer that attacks the lymphatic system, which is a disease-fighting network of vessels and lymph nodes that spans the body and form part of the immune system. There are multiple types of lymphoma, including Hodgkin lymphoma and the more common non-Hodgkin lymphoma. In all cases, white blood cells (either B cells or T cells), which circulate in the blood and are found in lymph nodes across the body, become abnormal in that they grow uncontrollably. 

How is lymphoma diagnosed?

Many people detect swollen lymph nodes in the form of a lump under the skin around the neck, groin or underarm areas that won't go away. A doctor may first prescribe antibiotics to see if the lymph nodes shrink after a few weeks.

Doctors make a diagnosis of lymphoma based on results from blood and urine tests, a physical exam, a biopsy of lymph nodes and/or bone marrow, and imaging tests. These can include X-ray, computerized tomography (CT) scan, magnetic resonance imaging (MRI) or positron emission tomography (PET). PET is typically used to determine which stage the disease has reached. 

How does a biopsy work?

The most common types of biopsies for suspected lymphoma are called excisional, meaning a surgeon removes the whole lymph node, or incisional, meaning the surgeon removes a small piece from a large tumor. In addition, an imaging study can help guide a needle into the lymph node to remove a small core of tissue. The specimens are sent to a pathologist so that the lymph-node tissue can be analyzed.

A biopsy can detect whether lymphoma is present, along with which type of lymphoma it is.

"The pathologists get the tissues and process them," says Yale Medicine pathologist Samuel G. Katz, MD, PhD. "It's a solid, 3-D structure. We submerge it in a series of chemicals that help embed it into a wax block that is cut with a very sharp instrument to get very thin sections of the tissue onto a slide, then we apply dye to stain with colors that help us recognize the types of cells present."

These types of biopsies almost always reveal enough information to diagnose the type of lymphoma.

What happens after the biopsy?

To better characterize the appearance of the cells, additional tests are usually warranted.

"We can go back to the wax block with the tissue and cut it several more times. Now, instead of staining it with a general dye, we stain it with an antibody that identifies the cells based on what proteins they are making. We may do five to 10 different markers. Then we will decide if we need to submit some of the tissue for molecular testing to help us understand the genetics of the tumor," Dr. Katz says.

"Finally, we report to the oncologist, based on what pathology is seeing, how the sample can best be characterized," he says. "At Yale Medicine, sometimes the primary clinician will stop by to take a look in the microscope with us."

"The pathology report is written primarily for the doctor, who will discuss it with the patient,” Dr. Katz says. “And much of what we do is also analyzing biopsies that have been performed at other institutions, to offer independent second options. And in up to 10 percent of cases, some change in diagnosis is made."

Understanding what cell type a patient’s non-Hodgkin lymphoma derived from can help to determine appropriate treatment options. Most non-Hodgkin lymphomas start in B cells, infection-fighting cells that make antibodies. This category includes follicular lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma and mantle cell lymphoma among others.

Less frequently, non-Hodgkin lymphoma starts in T cells (a white blood cell produced by the thymus gland that assists with immune response), such as with cutaneous T-cell lymphoma and peripheral T-cell lymphoma.

What is adult T-cell leukemia/lymphoma (ATLL)?

While lymphoma is the more common type of blood cancer, a rare sub-type called adult T-cell leukemia/lymphoma can be found in the blood (leukemia) or in lymph nodes (lymphoma). This aggressive form of cancer is linked to a virus called Human T-cell leukemia virus, type 1 (HTLV-1). Approximately two to five percent of people with HTLV-1 will develop adult T-cell leukemia/lymphoma.

What is a bone marrow biopsy and when is it necessary?

A doctor may recommend a bone-marrow biopsy, in which a sample of bone marrow is extracted using a needle inserted into the pelvic (hip) bone. This commonly occurs if the lymph node biopsy is positive for a lymphoma to determine whether lymphoma has spread to your bone marrow.

A bone-marrow biopsy may be requested if there are no enlarged lymph nodes, but the patient has a high white blood count or low platelets or red blood cells, which are made in the bone marrow.

How long does it take to get a diagnosis?

"With lymphoma, we strive to get reports out in 24 to 48 hours," Dr. Katz says, "but it may take up to a week in some cases, where additional markers need to be checked or additional thought and conversations with other experts at Yale is necessary to ensure an accurate diagnosis."

How is lymphoma treatment determined?

Some lymphomas, called indolent, can be slow to develop and grow, and may require no immediate treatment. Whether a patient needs treatment right away or can proceed under surveillance depends on multiple factors, including the stage and severity of the lymphoma.

What makes Yale Medicine’s approach to diagnosing lymphoma unique?

Yale Medicine has a team of pathologists who specialize in blood cancers.

“Not only do I clinically diagnose lymphomas and other blood cancers, but I run a laboratory aimed specifically at finding better ways to treat blood cancers," Dr. Katz says. "Such specialization you tend to only find at high-caliber institutions."

Diagnosis is a bit of an art, he says, and it pays to have expertise and specialization.

"We may not meet our patients in person,” Dr. Katz says, “but our team works extremely hard behind the scenes in concert with the primary physicians. We care very deeply about making sure that each and every patient receives the most accurate and expeditious diagnosis possible to ensure they receive the best treatment for them."