Lymphoma may or may not cause obvious symptoms that may lead to a lymphoma diagnosis. You may visit your doctor because of swollen lymph nodes or bumps near your lymph nodes, unexplained weight loss, or you may have “cold and flu-like” symptoms that do not go away, such as a fever for no reason or fatigue.

Your doctor will perform a physical exam and, if lymphoma is suspected, may suggest additional tests. A pathologist and/or a hematopathologist (a pathologist who is experienced in diagnosing blood cancers) will analyze any blood, bone marrow or tissue samples.

If you are diagnosed with lymphoma, these and other tests may be ordered to subtype, determine the extent of the disease, or monitor and manage the disease.

Biopsy and Blood Tests

Doctors run blood tests and remove and examine lymph nodes or other tissues to check for lymphoma cells. Additional tests may be used to distinguish different cell types, and biopsy samples can be examined to determine specific molecular characteristics of the lymphoma. Some of those tests include the following:

  • Beta-2 microglobulin
  • Complete blood count (CBC)
  • Comprehensive metabolic panel
  • Cytogenetics
  • Erythrocyte sedimentation rate (ESR)
  • Flow cytometry
  • Fluorescent in situ hybridization (FISH)
  • Immunophenotyping
  • Polymerase chain reaction (PCR)
  • Serum lactate dehydrogenase (LDH)
  • Uric acid

Bone Marrow Biopsy, Aspiration and Lumbar Puncture

A bone marrow biopsy involves removal of a sample of marrow from within the bone, usually the pelvic bone. For bone marrow aspiration, liquid bone marrow is removed. Often, both a biopsy and aspiration are done to collect multiple samples. A lumbar puncture is used to determine if lymphoma cells are present in the cerebrospinal fluid.

Imaging Tests

Imaging tests are used to help determine the extent and spread of disease:

  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Positron emission tomography (PET)
  • Ultrasound
  • X-ray


Staging is how physicians determine the extent of cancer. Hematologic cancers are often classified or staged according to factors, such as the type and subtype, the microscopic appearance of the lymphoma cells, lab results, chromosome abnormalities or the results of molecular testing, in addition to the specific sites of involvement. Different classification systems are then used to describe these factors as they relate to your diagnosis.

Hodgkin lymphoma and non-Hodgkin lymphoma are staged using the Lugano Classification system. With this system, lymphoma is assigned a stage of I, II, III, or IV, with or without additional factors (see Table 1). These stages can be divided into two groups: limited stage and advanced stage. A higher stage number indicates more advanced disease.

In addition to this staging system, some oncologists also use the International Prognostic Index (IPI) to predict the risk of disease recurrence and overall survival for patients with non-Hodgkin lymphoma. The IPI accounts for the age and general health of the patient, the stage of the disease, whether organs outside the lymphatic system are involved, and the presence or absence of elevated levels of lactate dehydrogenase (LDH) in the blood.

The IPI assigns one point for each of the following risk factors:

  • Age older than 60 years
  • Late-stage disease (Stage III or IV)
  • Performance status: poor general health
  • Two or more extranodal areas
  • High LDH level

The overall IPI score is the total number of points assigned to a patient. The lower the score, the better the prognosis (predicted outcome from treatment).

Some doctors may use additional prognostic indices to evaluate the outcome for a specific type of lymphoma. Your doctor will help explain if your type of non-Hodgkin lymphoma has an additional index used for classification.

Table 1. Lugano Classification For Hodgkin and Non-Hodgkin Lymphoma

Stage Description
Limited Stage
Stage I Involvement of a single lymphatic site (i.e., nodal region, Waldeyer’s ring, thymus or spleen).
Stage IE Single extralymphatic* site in the absence of nodal involvement (rare in Hodgkin lymphoma).
Stage II Involvement of two or more lymph node regions on the same side of the diaphragm.
Stage IIE Contiguous (touching or near) extralymphatic* extension from a nodal site with or without involvement of other lymph node regions on the same side of the diaphragm.
Stage II bulky** Stage II with disease bulk. (Bulk is defined as a mass greater than one third of the thoracic diameter on CT of the chest or a mass more than 10 cm.)
Advanced Stage
Stage III Involvement of lymph node regions on both sides of the diaphragm; nodes above the diaphragm with spleen involvement.
Stage IV Diffuse or disseminated involvement of one or more extralymphatic* organs, with or without associated lymph node involvement; or noncontiguous (not touching or near) extralymphatic organ involvement in conjunction with nodal Stage II disease or any extralymphatic organ involvement in nodal Stage III disease. Stage IV includes any involvement of the CSF (cerebrospinal fluid), bone marrow, liver or multiple lung lesions (other than by direct extension in Stage IIE disease).
*Extralymphatic sites are areas outside of the lymphatic system and include the adrenal glands, blood, bone, bone marrow, central nervous system (CNS; leptomeningeal and parenchymal brain disease), gastrointestinal (GI) tract, gonads, kidneys, liver, lungs, skin, ocular adnexae (conjunctiva, lacrimal glands, and orbital soft tissue), uterus and others.
**Stage II bulky may be considered either early or advanced stage based on lymphoma histology and prognostic factors.
Each stage may be accompanied by a letter(s) to indicate whether additional factors are present:
A: Fever, night sweats and weight loss are not present.
B: Fever, night sweats and weight loss are present.
Note: Hodgkin lymphoma uses A or B designation with stage group.
A/B is no longer used in non-Hodgkin lymphoma.
Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.


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