Diffuse Large B-Cell Lymphoma: Diagnosis

Signs and Symptoms of DLBCL 

The initial signs and symptoms of DLBCL may include a rapid swelling in the neck, underarms, or groin caused by enlarging lymph nodes. The swollen nodes are usually painless, although in some cases the swelling may be painful. Patients may also experience symptoms including night sweats, fever, unexplained weight loss, fatigue, loss of appetite, shortness of breath (trouble breathing), or pain. 

If someone experiences any of the symptoms listed above for more than two weeks, or if the symptoms are severe enough to impact daily activities, he or she should see a doctor. It is important to understand that most people exhibiting any or some of these symptoms may not have lymphoma. The symptoms of lymphoma are non-specific and may be seen in patients with an infection. Patients should be prepared to describe their symptoms in detail during the appointment with their physician and come prepared to answer specific questions about their medical history. If the physician cannot rule out a lymphoma diagnosis upon completing the physical examination, other tests may need to be performed. 


How is DLBCL diagnosed? 

A tissue biopsy is needed for a definite diagnosis of DLBCL. This requires a surgical incision to remove part or all of an affected lymph node or other abnormal area so it can be viewed under a microscope. A biopsy can be performed under local or general anesthesia. An excisional or incisional biopsy is generally considered the best way to establish an initial diagnosis of lymphoma because it allows the removal of bigger samples compared to other biopsy procedures. The surgeon cuts through the skin to remove an entire lymph node (excisional biopsy) or a large portion of a lymph node or other tissue (incisional biopsy). 

A core needle biopsy (sometimes called a needle core biopsy) is used when the lymph nodes are deep in the chest or abdomen or in other locations that are difficult to reach surgically, or when there are medical reasons for avoiding an excisional or incisional biopsy. This involves inserting a special needle into the lymph node suspected to be cancerous and withdrawing a small tissue sample using a syringe attached to the needle. A needle biopsy can be done under local anesthesia, and stitches are usually not required. 

A fine needle aspiration (FNA) biopsy is a procedure using a needle that is very thin and smaller than those used in a core needle biopsy. Because of the small needle size, the sample will only contain scattered cells without preserving how the cells are actually arranged in the lymph node. Therefore, this test cannot provide enough information for a definitive diagnosis. An FNA biopsy is most often used to check for return of the disease (relapse), not for an initial diagnosis. 

The following tests may be used to confirm a DLBCL diagnosis: 

  • Standard tests 

    • Bone marrow biopsy with or without aspiration – removal of a small piece of bone to examine the cells inside the bone marrow, sometimes preceded by removal of fluid and cells from within the bone marrow itself using a needle 
    • Lymph node biopsy – see the three types of biopsies described above 
    • Complete blood count (CBC) with differential – a blood test that measures the number and size of red blood cells, number and types of white blood cells, number of platelets, hemoglobin (iron concentration), and hematocrit (red blood cell concentration) 
    • Blood smears – examination of a blood sample under a microscope to detect abnormalities in the size, shape, or color of the blood cells 
    • Immunophenotyping by flow cytometry or immunohistochemistry – examination of cancerous white blood cells to identify specific proteins expressed on the surface of the cells 
    • Cytogenetics or molecular genetic test – examination of a specific gene or a short piece of DNA to identify mutations or variations in the genes 
    • Lumbar puncture (spinal tap) – removal and examination of cerebrospinal fluid (fluid surrounding the brain and spinal cord) through a needle inserted in the lower back 
    • Pleural or peritoneal fluid sampling – removal and examination of fluid in the chest (pleura) or abdomen (peritoneum) through a needle inserted into that area 


  • Imaging studies 

    • Computed tomography (CT) scan – an imaging technique that uses a computer to combine many X-ray images taken from different angles to create cross-sectional images of a specific part of the body 
    • Magnetic resonance imaging (MRI) – an imaging test that uses a large magnetic field and radio waves to create an image of an area of the body; can create a more detailed picture than a CT scan 
    • Positron emission tomography (PET) scan – an imaging technique that uses a radioactive substance introduced into the body to trace the chemical activities in a certain area of the body; can be used for initial diagnosis or to detect possible recurrence (return of lymphoma after treatment) or metastasis (spread of lymphoma to other areas) 
    • Chest X-ray – a regular radiograph (X-ray) of the chest, usually taken while standing, that shows the heart, lungs, and bones of the spine and chest 


Monitoring Disease Recurrence 

Recurrence of DLBCL, known as relapse, occurs in up to 40 percent of DLBCL patients. Relapses most commonly occur due to minimal residual disease (MRD), which means that the disease still exists in the body, but at such low levels that it cannot be detected by standard imaging studies. However, highly sensitive genetic tests can be used to detect MRD by identifying DNA fragments of a few DLBCL cells circulating in the blood. There are several types of tests used to detect MRD, most of which are based on a process called polymerase chain reaction (PCR). These PCR-based tests are important because earlier detection of relapsed disease enables doctors and patients to make treatment decisions before further growth of the cancerous cells. 


Prognostic Indices 

International Prognostic Index (IPI) 

A prognostic index helps patients and doctors understand the prognosis for lymphoma patients. The International Prognostic Index (IPI) was first developed for aggressive (fast-growing) lymphomas. The IPI is based on five predictive factors, known by the acronym APLES: age, performance status, lactate dehydrogenase blood level, extranodal (outside the lymph nodes) progression, and stage of disease.


International Prognostic Index

Factor Good Prognostic Factor Poor Prognostic Factor
Age 60 years or younger Older than 60 years
Stage I or II III or IV
Location of the lymhpoma Only in lymph nodes or in only one are outside of the lymph nodes In two or more organs outside of lymph nodes
Performance status Able to function normally Needs help with daily activities
Serum lactate dehydrogenase Normal Above normal


An enhanced IPI (NCCN-IPI) for patients with DLBCL treated in the rituximab era

The introduction of the drug rituximab (Rituxan) has had a dramatically positive effect on DLBCL treatment, and it has changed the approach to managing the disease. A revised IPI created specifically for DLBCL patients treated since the availability of rituximab has been developed by the National Comprehensive Cancer Network (NCCN). The NCCN-IPI measures the same five factors (APLES) as the original IPI. However, the enhanced NCCN-IPI uses an 8-point scoring system, with between 1 and 3 points being awarded for each risk factor that a patient has. Thus while the original IPI identified only two risk categories, the enhanced IPI further refined risk definition into four categories – low risk (0–1), low-intermediate risk (2–3), high-intermediate risk (4–5), and high risk (6–8).

Factor Score
Age, y  
> 40 to 60 1
> 60 to 75 2
>75 3
LDH, normalized  
> 1 to < 3 1
> 3 2
Ann Arbor Stage III-IV 1
Extranodal disease 1
Performance status > 2 1


It is important to note that having a poor score on the IPI or a high-risk score on the NCCN-IPI does not mean that there is nothing that can be done to treat the lymphoma. Prognostic indices are used to compare a person’s level of risk to that of others with the same disease, and this information can be used to help make treatment decisions. However, a prognostic index cannot predict the outcomes of an individual patient with DLBCL.


Next Section:  Staging