Non-Hodgkin’s lymphoma (NHL) is a cancer that starts in the white blood cells called lymphocytes, which are part of the body’s immune system. NHL can occur at any age and is one of the most common cancers in the US. Detecting NHL early is important for successful treatment. Doctors use various tests to diagnose NHL, including physical exams, imaging tests like CT scans, and lymph node biopsies. In recent years, research has explored using blood tests to detect NHL. Blood tests offer a simpler, less invasive option compared to tissue biopsies. This article reviews using blood tests to detect NHL.
What is non-Hodgkin’s lymphoma?
Non-Hodgkin’s lymphoma is a cancer that begins in lymphocytes, a type of white blood cell. Lymphocytes circulate through the lymphatic system, a network of vessels and nodes that carry fluid and immune cells. NHL causes lymphocytes to multiply uncontrollably and accumulate in lymph nodes or other organs. As NHL grows, it can cause swollen lymph nodes, fever, night sweats, fatigue, and weight loss.
There are over 60 subtypes of NHL, which are classified based on the type of lymphocyte affected:
- B cell lymphomas start in B lymphocytes
- T cell lymphomas start in T lymphocytes
- NK cell lymphomas start in natural killer cells
Some NHL subtypes are more aggressive, while others tend to grow slowly. NHL is the most common blood cancer in adults, with around 77,000 new cases each year in the United States. It can occur at any age but is most common in older adults, with a median age at diagnosis of 66 years old. NHL is highly treatable, especially when detected early. The 5-year survival rate for NHL is 73%.
How is non-Hodgkin’s lymphoma currently diagnosed?
Doctors use a combination of tests to diagnose NHL, including:
- Medical history and physical exam: Doctors ask about symptoms and check for swollen lymph nodes or other signs of NHL.
- Blood tests: A complete blood count can reveal low blood cell levels. Tests like lactate dehydrogenase (LDH) and uric acid can indicate rapid cell turnover.
- Imaging tests: CT, PET, or MRI scans help detect swollen nodes or organs affected by NHL.
- Biopsy: Removing affected lymph node or tissue samples for examination under a microscope is needed for a definitive NHL diagnosis.
Examining a biopsy sample allows doctors to confirm lymphoma and classify the specific subtype. This guides appropriate treatment. The gold standard is an excisional lymph node biopsy, which removes an entire affected node for analysis. Needle biopsies extracting a sample of tissue are sometimes done instead when nodes are difficult to access.
What are the limitations of current NHL diagnostic methods?
While current tests effectively diagnose NHL, they have some drawbacks:
- Invasive biopsies: Surgical biopsies carry risks of pain, bleeding, infection, and scarring. Needle biopsies can miss cancer if the sample is not representative.
- Delayed diagnosis: It takes time to coordinate excisional biopsy surgery and get pathology results.
- Fail to detect relapse: Biopsies only sample certain spots and can miss cancer returning elsewhere in the body.
Blood tests are simpler and safer than tissue biopsies. Developing accurate blood tests could allow earlier NHL detection, diagnosis, and monitoring for recurrence from a basic blood draw.
How could blood tests detect non-Hodgkin’s lymphoma?
Researchers are studying different approaches to detect NHL from blood samples:
Analyzing DNA from lymphoma cells
One method is testing for DNA mutations or structural changes specific to lymphoma cells:
- Cell-free DNA (cfDNA): Fragments of DNA released from dying cancer cells circulate in the blood. Quantifying lymphoma cfDNA could help detect disease or track treatment.
- Circulating tumor DNA (ctDNA): Full lengths of tumor DNA containing cancer mutations can enter the blood when cells die. Detecting lymphoma mutations in ctDNA could indicate cancer presence.
Measuring lymphoma protein biomarkers
NHL alters levels of certain proteins in the blood. Measuring these protein biomarkers could reveal lymphoma:
- Cytokines: Lymphoma disrupts cytokine signaling proteins that regulate immune responses.
- Tumor antigens: Abnormal surface proteins produced by cancerous lymphocytes.
- Immunoglobulins: Lymphoma B cells overproduce abnormal immunoglobulins.
Analyzing blood lymphocyte populations
Flow cytometry uses antibodies tagged with fluorescent dyes to quantify different types of blood cells. It could detect NHL by revealing:
- Increased lymphoma B/T/NK cells
- Decreased normal lymphocytes
- Abnormal shapes, sizes, and protein markers on lymphoma cells
What blood tests detect non-Hodgkin’s lymphoma in research?
Many blood tests show promise for detecting NHL in studies:
| Test | Biomarkers | Performance |
|---|---|---|
| LymphoTrack Dx | Circular DNA with lymphoma mutations | Detected DLBCL with 87% accuracy |
| LymphMark | Tumor DNA methylation patterns | Detected lymphoma with 87% sensitivity, 99% specificity |
| Lymphovision | 11 protein biomarkers | Detected indolent NHL with 90% accuracy |
| Flow cytometry | Lymphocyte cell surface markers | Detected NHL subtypes with 83-97% accuracy |
These tests show potential for accurately diagnosing NHL and its subtypes from blood samples. However, larger studies are still needed to verify performance and standardize methods before they reach clinical use. Ongoing advances in genomics and proteomics continue to uncover new lymphoma biomarkers that could be incorporated into future blood tests.
Could blood tests replace biopsies for NHL diagnosis?
While exciting, blood tests have not yet reached the point where they can definitively diagnose NHL without tissue confirmation:
- Blood tests may not detect very small tumors or provide enough cancer material for classification.
- False positive results could lead to unnecessary biopsies and anxiety.
- Standard biopsy remains essential for initial diagnosis in most cases currently.
However, blood tests have promise for improving NHL detection and management when combined appropriately with biopsy:
- Earlier screening in high-risk groups before lymphoma is clinically suspected.
- Speeding diagnosis by ruling out disease before biopsy.
- Supplementing biopsy with additional prognostic information.
- Precisely monitoring minimal residual disease after therapy.
- Quickly detecting recurrence and guiding the need for repeat biopsy.
Future optimizations could make blood tests a viable biopsy alternative for some NHL cases. But tissue confirmation will remain important, at least initially, for most patients.
Conclusion
Detecting non-Hodgkin’s lymphoma from blood samples holds exciting potential to improve diagnosis and monitoring. Emerging DNA, protein, and cell-based blood tests can identify lymphoma with reasonably high accuracy. While blood tests are not ready to fully replace invasive biopsies yet, they may help screen high-risk individuals, speed diagnoses, and detect recurrence. With future enhancements, blood tests are poised to become invaluable point-of-care tools for managing non-Hodgkin’s lymphoma. Combining minimally invasive blood testing with selective tissue biopsies when needed could offer the best of both worlds for optimized NHL care.