Lymphoma is a type of blood cancer that develops in the lymphatic system. It occurs when white blood cells called lymphocytes grow abnormally and accumulate in lymph nodes or other tissues. There are two main types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Lymphoma can cause many symptoms, but some of the key early warning signs are painless swelling of lymph nodes, fever, night sweats, unexplained weight loss, and fatigue. While a biopsy of an enlarged lymph node is required to definitively diagnose lymphoma, certain lab tests can provide clues that lymphoma may be present.
Complete Blood Count
One of the most common abnormal labs with lymphoma is an irregular complete blood count (CBC). A CBC measures levels of different cells in the blood, including red blood cells, white blood cells, and platelets. In lymphoma, it is common to see:
- Low red blood cell count (anemia) – This can cause fatigue.
- Low white blood cell count (leukopenia) – This can increase risk of infections.
- Low platelet count (thrombocytopenia) – This can lead to easy bruising and bleeding.
- Abnormal white blood cell differential – There may be too many immature white blood cells called lymphocytes or “lymphoblasts.”
These CBC abnormalities develop because the abnormal lymphocytes crowd out healthy blood cell production in the bone marrow. The degree of abnormalities can provide information about how advanced the lymphoma is.
Lactate Dehydrogenase
Another common lab finding with lymphoma is elevated lactate dehydrogenase (LDH). LDH is an enzyme found in many body tissues, including lymphocytes. When lymphocytes are damaged or dying, LDH is released into the bloodstream. High LDH correlates with high tumor burden and more advanced stage lymphoma.
Erythrocyte Sedimentation Rate
The erythrocyte sedimentation rate (ESR) test measures inflammation in the body. In lymphoma, the ESR is often elevated because the cancer triggers inflammation. However, a high ESR is non-specific and can also occur with many other inflammatory conditions besides lymphoma.
Beta-2 Microglobulin
Beta-2 microglobulin is a protein found on the surface of lymphocytes. When lymphocytes multiply too rapidly in lymphoma, more beta-2 microglobulin is released into the blood. High levels indicate greater lymphoma tumor burden and more advanced disease. Beta-2 microglobulin is more specific for diagnosing and monitoring lymphoma than the ESR.
Immunoglobulins
Immunoglobulins (antibodies) are proteins made by plasma cells, a type of white blood cell. In some lymphomas, plasma cells grow uncontrollably and produce abnormal amounts of immunoglobulins. Checking IgG, IgA, and IgM levels can reveal a clonal spike in one type of immunoglobulin, which raises suspicion for lymphoma.
Uric Acid
A high uric acid level can sometimes occur with lymphoma. This is thought to be caused by increased cell turnover and death releasing nucleic acids that are broken down into uric acid.
Kidney and Liver Function
Lymphoma can impair kidney and liver function, either by direct infiltration of lymphoma cells into these organs or just from the cancer’s overall effects on the body. Labs to check kidney function like BUN and creatinine and liver function tests like ALT, AST, albumin, and bilirubin may be abnormal.
Calcium
High blood calcium (hypercalcemia) affects approximately 20% of people with advanced Hodgkin lymphoma. It is less common in non-Hodgkin lymphoma. Excess calcium can cause symptoms like frequent urination, excessive thirst, nausea, and constipation. The mechanism involves abnormal signaling by lymphoma cells that leads to excessive bone resorption and calcium release.
Summary of Key Abnormal Labs
In summary, the most characteristic lab abnormalities that can indicate the possibility of lymphoma include:
- Irregular complete blood count
- High lactate dehydrogenase
- High erythrocyte sedimentation rate
- High beta-2 microglobulin
- Abnormal immunoglobulins (IgG, IgA, IgM)
- High uric acid
- Kidney/liver dysfunction
- High calcium
While these lab tests can provide clues, a lymph node biopsy is still needed to confirm a diagnosis of lymphoma. Imaging like CT scans and PET scans are also important to determine the stage and extent of disease.
Ongoing lab monitoring during and after lymphoma treatment is critical to assess response to therapy and check for relapse. Some of the key labs that are followed include CBC, LDH, ESR, and beta-2 microglobulin.
Typical Reference Ranges for Lymphoma-Related Labs
| Test | Normal Range |
|---|---|
| White blood cells | 4,500-11,000 per microliter |
| Hemoglobin | 12-16 grams/dL (women); 13-18 grams/dL (men) |
| Platelets | 150,000-450,000 per microliter |
| Lymphocytes | 1,000-4800 per microliter |
| Lactate dehydrogenase | 140-271 units/L |
| Erythrocyte sedimentation rate | 0-29 mm/hr |
| Beta-2 microglobulin | 0.7-3.4 mg/L |
| Immunoglobulin G (IgG) | 694-1618 mg/dL |
| Immunoglobulin A (IgA) | 61-356 mg/dL |
| Immunoglobulin M (IgM) | 46-304 mg/dL |
| Uric acid | 2.5-7.5 mg/dL |
| Blood urea nitrogen (BUN) | 7-25 mg/dL |
| Creatinine | 0.6-1.3 mg/dL |
| Alanine aminotransferase (ALT) | 7-52 units/L |
| Aspartate aminotransferase (AST) | 13-39 units/L |
| Albumin | 3.4-5 g/dL |
| Total bilirubin | 0.2-1.2 mg/dL |
| Total calcium | 8.4-10.2 mg/dL |
Key Differences from Normal
In lymphoma, key lab abnormalities that differ from normal reference ranges include:
- Low hemoglobin, white blood cells, platelets
- High or low lymphocytes
- Elevated LDH
- Elevated ESR
- Elevated beta-2 microglobulin
- Abnormal spikes in IgG, IgA, or IgM
- High uric acid
- High BUN/creatinine, low albumin
- Elevated AST/ALT, bilirubin
- High calcium
Staging and Prognosis
In addition to establishing a lymphoma diagnosis, lab tests are critical for lymphoma staging and determining prognosis. Staging assesses how widespread the lymphoma is throughout the body. Some key factors that define staging and influence expected outcomes include:
- Number and locations of lymph node areas involved – Widespread lymphadenopathy indicates more advanced stage.
- Presence in extranodal sites – Involvement of organs like liver, lungs, bone marrow connotes later stage.
- Elevated LDH – High LDH predicts poorer prognosis.
- CBC results – Severe cytopenias signify advanced bone marrow infiltration and disease.
- Beta-2 microglobulin level – Higher levels predict worse outcomes.
By analyzing results of clinical and laboratory evaluations, oncologists determine the lymphoma stage, which ranges from stage I (early) to stage IV (advanced). In general, higher stage lymphoma is more difficult to treat and has poorer prognosis.
Staging Systems
There are two main lymphoma staging systems:
- Ann Arbor staging system – Originally developed for Hodgkin lymphoma but now applied to many non-Hodgkin lymphomas too. Uses Roman numerals I to IV based on sites involved.
- Lugano classification – More modern system used for many aggressive non-Hodgkin lymphomas. Adds letters A vs B to denote presence/absence of specific symptoms.
Monitoring Treatment Response
After a lymphoma diagnosis is established, serial lab tests are vital to monitor response to treatment and watch for relapse. Some key tests that are followed include:
- CBC – Improving blood counts indicate effective treatment.
- LDH – Decreasing levels signify tumor cell death.
- ESR – Declining results reflect disease response.
- Beta-2 microglobulin – Drop towards normal shows treatment efficacy.
- Immunoglobulins – Reduction of abnormal spikes is positive sign.
In addition to lab tests, repeat imaging with CT or PET scans is also important during and after lymphoma therapy to assess if lymph nodes and organ involvement are improving.
Definitions of Treatment Response
Standard criteria are used to categorize lymphoma treatment response based on lab results, imaging, and clinical findings:
- Complete response – Disappearance of all evidence of lymphoma with treatment.
- Partial response – At least 50% reduction in lymphoma with treatment.
- Stable disease – Lymphoma is still present but not worsening substantially with treatment.
- Progressive disease – Lymphoma is worsening despite treatment.
- Relapse – Lymphoma returns after a period of complete response.
Conclusion
There are many possible abnormal lab findings with lymphoma, but some of the most common include irregular CBC, elevated LDH, high ESR, abnormal immunoglobulins, and electrolyte disturbances like high calcium. These lab abnormalities not only help diagnose lymphoma but also provide valuable information about disease extent, prognosis, and response to treatment that can guide clinical decision making. Ongoing monitoring of key lab tests is essential throughout the course of lymphoma management.