A complete blood count (CBC) test measures the levels of white blood cells (WBCs), red blood cells, platelets, and other components in the blood. The normal reference range for a WBC count is 4,500-11,000 cells per microliter. An elevated WBC count, known as leukocytosis, may indicate the presence of certain diseases or conditions, including lymphoma. Lymphoma refers to cancers that develop in the lymphatic system, which is part of the body’s immune defense. There are two main categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Determining whether an elevated WBC count is caused by lymphoma requires evaluating the results of the CBC alongside other diagnostic information.
What is a normal WBC count?
As mentioned, the normal range for a WBC count in healthy adults is 4,500-11,000 cells per microliter of blood. This range may vary slightly between laboratories. Within the WBC count, there are five main types of white blood cells:
- Neutrophils: The most abundant type of white blood cell, making up 50-70% of all WBCs. They help fight bacterial infections.
- Lymphocytes: The second most common WBC, comprising 20-40% of all WBCs. There are three main types of lymphocytes: T cells, B cells, and natural killer cells. Lymphocytes are a key part of the immune system.
- Monocytes: The largest type of white blood cell, making up 2-10% of all WBCs. They help ingest and destroy pathogens and dead cells.
- Eosinophils: Represent 1-6% of WBCs. They respond to allergic reactions and infections caused by parasites.
- Basophils: The rarest WBC, less than 1% of all WBCs. They release chemicals like histamine during inflammatory immune responses.
In addition to the total WBC count, a CBC will provide a breakdown of the counts for each of these five types of white blood cells. This differential allows doctors to see if any one type of WBC is abnormally high or low, which can indicate certain medical problems.
What causes high WBC counts?
There are many potential reasons for an elevated WBC count, known medically as leukocytosis. Common causes include:
- Infections, especially bacterial infections or sepsis
- Inflammation from conditions like arthritis or inflammatory bowel disease
- Severe physical or emotional stress
- Tissue damage like burns, trauma, or necrosis
- Pregnancy
- Medications including corticosteroids and lithium
- Blood cancers like leukemia and lymphoma
- Bone marrow disorders
- Immune disorders
- Genetic conditions
In many cases, leukocytosis is a normal response of the immune system to help fight infection or inflammation in the body. However, extremely high WBC counts may also result from bone marrow cancers like leukemia, lymphoma, and myeloproliferative disorders. Doctors must investigate the specific causes based on a patient’s symptoms and other test results.
Infectious causes
Bacterial infections are a prime reason for elevated WBC levels. The body mobilizes white blood cells to combat invading pathogens. Viral infections can also raise WBCs, although bacterial infections usually cause a more drastic leukocytosis. Parasitic infections, like malaria, may increase certain types of white blood cells. Sepsis, a life-threatening immune response to severe infection, often leads to very high WBC counts.
Inflammatory causes
Chronic inflammatory diseases commonly cause mild to moderate leukocytosis. These include rheumatoid arthritis, lupus, ulcerative colitis, Crohn’s disease, and vasculitis. Tissue injury from burns, trauma, recent surgery, heart attack, or pancreatitis can spark local and systemic inflammation, also raising WBCs.
Stress and medication causes
Physical stress on the body, like intense exercise, or psychological stress can temporarily increase white blood cell counts. Some medications also increase WBC production. Most notable are corticosteroids like prednisone, which mimic the effects of the stress hormone cortisol. Lithium used for bipolar disorder is another drug known to increase white blood cell counts.
Blood cancer causes
Certain blood cancers directly impact the development of white blood cells in the bone marrow. This leads to abnormal elevations in immature or dysfunctional WBCs. Leukemia refers to cancers arising from early blood-forming cells in the bone marrow. The four main types are:
- Acute myeloid leukemia (AML): Characterized by accumulation of abnormal immature myeloid white blood cells.
- Chronic myeloid leukemia (CML): Also leads to excess myeloid cells, but causes more mature WBCs.
- Acute lymphoblastic leukemia (ALL): Causes proliferation of immature lymphocyte WBCs called lymphoblasts.
- Chronic lymphocytic leukemia (CLL): Results in an excess of abnormal but mature lymphocytes.
In lymphoma, white blood cells are not directly cancerous but higher WBCs can occur as part of the body’s response. Very high lymphocyte counts may be seen in certain types of lymphoma.
How high must the WBC count be to indicate lymphoma?
There is no definitive WBC count that diagnoses lymphoma. Typically, doctors consider a total WBC above 11,000 cells per microliter to be abnormally high and warranting further evaluation. However, lymphoma cannot be ruled out even if the total WBC remains within the reference range. Other factors must be assessed, like:
- Which type of white blood cell is elevated
- How much above the normal limit the value is
- Presence of immature white blood cell forms
- Progressive rise in WBCs over time
- Other concerning symptoms
- Results of imaging tests like CT scans
- Lymph node biopsy findings
While extreme leukocytosis over 50,000-100,000 is highly suspicious for blood cancers, lymphoma-associated counts are typically much lower. Total WBCs in the range of 15,000-30,000 with an abnormal lymphocyte differential could raise suspicion of lymphoma. However, a slight WBC elevation alone cannot distinguish lymphoma from many other causes of reactive leukocytosis. Interpretation of the CBC results relies heavily on the clinical context.
What WBC findings suggest lymphoma?
Some patterns in the CBC results may specifically point to possible lymphoma or lymphocytic leukemia:
- High lymphocytes: Lymphocyte counts greater than 4,000 cells/microliter warrant assessment. Counts from 5,000-20,000 or higher raise concern for lymphoma cancer.
- Atypical lymphocytes: Presence of immature lymphocyte forms like prolymphocytes or blast cells may indicate cancers like ALL or CLL.
- Inverted CD4/CD8 ratio: Inversion of the typical CD4 to CD8 T-cell ratio can be a sign of lymphoma.
- Progressive lymphocytosis: Gradual lymphocyte elevation over weeks to months is worrying for chronic lymphocytic leukemia.
- Leukocytosis with enlarged lymph nodes: Suggests possible lymphoproliferative disorder like lymphoma.
- Other cytopenias: Reduction in other cell lines like low platelets or RBCs raises concern for bone marrow infiltration.
However, none of these are diagnostic on their own. A lymphocyte-predominant leukocytosis above 15,000 cells/microliter would be considered highly suspicious for lymphoma in the right clinical context. But mild lymphocytosis alone is not definitive.
Role of lymphocytes in lymphoma
Lymphocytes are a key part of the immune system and central to lymphoma cancers. There are three main types:
- T lymphocytes (T cells): Activate the immune response against pathogens. T cell lymphomas are the most common lymphoma subtype.
- B lymphocytes (B cells): Generate antibodies. B cell lymphomas include Burkitt lymphoma and CLL.
- Natural killer cells (NK cells): Destroy virus-infected and cancerous cells. NK cell lymphomas are rare.
In many lymphomas, higher numbers of circulating lymphocytes are seen as the malignant cells proliferate. The specific subtype of lymphocyte involved provides clues to the type of lymphoma. Marked lymphocytosis tends to occur more often in leukemic lymphomas that involve the blood in addition to lymph nodes.
How doctors interpret high lymphocyte counts
When facing lymphocytosis in a CBC, doctors must determine if it represents appropriate immune activation or potential malignant disease. Further steps include:
- Repeat testing to confirm an increasing lymphocyte trend.
- Examining the lymphocyte differential for any atypical cells.
- Ordering flow cytometry and immunophenotyping to evaluate lymphocytes.
- Imaging tests like CT scans to check for enlarged lymph nodes.
- Consulting the patient’s symptoms and medical history.
- Considering other potential causes like infections.
- Referring the patient to a hematologist/oncologist for lymph node biopsy.
Only by integrating the CBC results with a full lymphoma workup can doctors arrive at a diagnosis.
Other CBC findings in lymphoma
While high lymphocytes are most indicative of lymphoma, other CBC abnormalities may be seen:
- Normocytic anemia: Generalized low red blood cell counts.
- Thrombocytopenia: Shortage of platelets from marrow displacement.
- Neutropenia: Low neutrophils from bone marrow invasion.
- Blast cells: Immature blood cell forms point to bone marrow involvement.
- Atypical cells: Abnormal shapes or features of cells.
These additional findings can provide clues but are still nonspecific. The whole clinical picture must be synthesized.
CBC patterns with different lymphoma types
Some CBC patterns are more typical for certain lymphoma subtypes:
| Lymphoma Type | Typical CBC Findings |
|---|---|
| Chronic lymphocytic leukemia/small lymphocytic lymphoma | Lymphocytosis of mature lymphocytes, usually >15,000/microliter. |
| Follicular lymphoma | Mild to moderate lymphocytosis, atypical lymphocyte forms. |
| Marginal zone B-cell lymphoma | Variable lymphocytosis, may also see monocytosis. |
| Mantle cell lymphoma | Moderate lymphocytosis with blast cells and cytopenias. |
| Burkitt lymphoma | Massive leukemic spread with >50,000 lymphoid cells/microliter. |
| Hodgkin lymphoma | Typically normal CBC or mild nonspecific changes. |
However, putting these patterns together with biopsy results is key for diagnosis. The CBC cannot definitively classify lymphoma subtypes on its own.
Conclusions
In summary, elevated WBC counts may occasionally accompany lymphoma, but are not independently diagnostic. Mild to moderate lymphocytosis in the range of 15,000-30,000 cells/microliter would raise suspicion in the appropriate clinical context, but lymphoma requires excisional biopsy confirmation. Lymphocyte-predominant leukocytosis with atypical cell morphology points to possible lymphoproliferative disorders. However, the CBC serves only as an initial screen and lymphoma workup requires a multifaceted approach. Careful correlation of CBC with imaging, bone marrow studies, and lymph node histology is crucial for accurate lymphoma diagnosis and subtyping.