Hodgkin lymphoma is diagnosed through a combination of physical examination, lymph node biopsy, lab work, and imaging scans. The single most important step is a surgical biopsy of an enlarged lymph node, which allows a pathologist to look for the distinctive abnormal cells that define this cancer. The full diagnostic process, from first suspicion to a confirmed diagnosis with staging, typically takes several weeks.
Signs That Trigger a Diagnostic Workup
Most people first notice a painless, swollen lymph node, usually in the neck, armpit, or groin. The swelling may have been there for weeks or even months without causing pain, which is part of what distinguishes it from the tender, swollen nodes you get with a routine infection. A doctor will feel for enlarged nodes during a physical exam and ask about a specific cluster of symptoms known as “B symptoms”: unexplained weight loss of more than 10% of body weight, persistent fevers, and drenching night sweats that soak through clothing or sheets.
Not everyone with Hodgkin lymphoma has B symptoms, but their presence matters. These symptoms factor into how the disease is staged and what treatment looks like. Other signs that raise suspicion include unexplained fatigue, itching, or pain in a lymph node after drinking alcohol, which is uncommon but fairly specific to Hodgkin lymphoma.
Why a Biopsy Is Essential
No blood test or scan can confirm Hodgkin lymphoma on its own. The definitive diagnosis requires removing part or all of an enlarged lymph node so a pathologist can examine the tissue under a microscope. The preferred method is an excisional biopsy, where a surgeon removes an entire lymph node through a small incision, usually under local or general anesthesia. This is a same-day procedure in most cases.
Excisional biopsy is the gold standard because it preserves the full architecture of the lymph node, giving pathologists the context they need to classify the disease accurately. A large French survey published in Blood found that surgical excision provided a definitive diagnosis in 98.1% of cases, compared to 92.3% for core needle biopsy. Needle biopsies also carried a higher rate of disagreement between pathologists and increased the risk of a nondefinitive or incorrect conclusion. When a suspicious lymph node is accessible, guidelines consistently recommend surgical excision over needle biopsy.
That said, core needle biopsy is sometimes used when a lymph node is deep inside the chest or abdomen and difficult to reach surgically. In those situations, imaging-guided needle biopsy is a reasonable starting point, though a follow-up surgical biopsy may still be needed if results are unclear.
What Pathologists Look For
The hallmark of classical Hodgkin lymphoma is a type of abnormal cell called the Reed-Sternberg cell. These are large, distinctive cells with a characteristic appearance that a trained pathologist can recognize on a stained tissue slide. But visual identification alone isn’t enough. The pathologist uses a technique called immunohistochemistry, which applies special stains to detect specific proteins on the surface of the cells.
In classical Hodgkin lymphoma, Reed-Sternberg cells typically test positive for two surface markers called CD15 and CD30. This immunophenotype is a key part of confirming the diagnosis and distinguishing Hodgkin lymphoma from other cancers that can look similar under the microscope, including certain types of non-Hodgkin lymphoma and anaplastic large cell lymphoma.
There is also a rare subtype called nodular lymphocyte-predominant Hodgkin lymphoma, which accounts for a small fraction of cases. Its abnormal cells express B-cell markers instead of CD15 and CD30, and the disease behaves differently. Only about 2 to 7% of patients with this subtype have a mass in the chest, compared to roughly 60% of patients with classical Hodgkin lymphoma. The distinction matters because the two subtypes are treated differently.
Biopsy results typically take one to two weeks. The tissue has to be preserved, sliced into extremely thin sections, and stained with chemicals before it can be examined. If the case is complex, it may be sent to a specialist pathologist for a second opinion, which can add several more days.
Blood Tests in the Workup
While blood tests can’t diagnose Hodgkin lymphoma, they’re a standard part of the evaluation. A complete blood count checks for abnormalities in red cells, white cells, and platelets. Results are often nonspecific but can hint at how much the disease has spread or how the body is responding to it.
Two other markers are routinely measured. The erythrocyte sedimentation rate (ESR) reflects general inflammation in the body. An elevated ESR has been linked to worse prognosis in Hodgkin lymphoma, though it’s not specific enough to be used as a screening tool on its own. Lactate dehydrogenase (LDH) is an enzyme that rises when cells are damaged or turning over rapidly, and higher levels can correlate with a greater volume of disease. Blood chemistry panels and liver function tests round out the baseline workup, helping doctors assess organ function before treatment begins.
How PET-CT Scans Map the Disease
Once biopsy confirms Hodgkin lymphoma, imaging is used to determine how far it has spread. The most important scan is a PET-CT, which combines two types of imaging into one. The CT portion creates detailed cross-sectional images of the body, while the PET portion detects areas of unusually high metabolic activity, which is a signature of cancer cells.
Hodgkin lymphoma is highly metabolically active, which makes it light up reliably on PET scans. PET-CT is more accurate than a standard CT scan alone, particularly for detecting disease in unexpected locations outside the lymph nodes, such as the spleen, liver, lungs, or bones. This matters because finding disease in these areas changes the stage and influences treatment decisions.
PET-CT has also largely replaced bone marrow biopsy for most patients. Bone marrow involvement used to require a separate procedure where a needle was inserted into the hip bone to extract a small sample. Research has shown that PET-CT has 100% sensitivity for detecting bone marrow involvement in Hodgkin lymphoma, with a specificity of about 85%. For patients whose PET-CT shows no signs of marrow disease, the bone marrow biopsy is now considered unnecessary.
Staging After Diagnosis
Staging tells you how far the lymphoma has spread and directly shapes the treatment plan. Hodgkin lymphoma uses a four-stage system based on the Lugano classification:
- Stage I: Cancer is in a single lymph node region.
- Stage II: Cancer is in two or more lymph node regions, but all on the same side of the diaphragm (the muscle that separates the chest from the abdomen).
- Stage III: Cancer is in lymph node regions on both sides of the diaphragm.
- Stage IV: Cancer has spread beyond the lymph nodes into organs like the liver, lungs, or bone marrow.
Each stage also gets a letter. “A” means no B symptoms are present. “B” means the patient has fevers, night sweats, or significant weight loss. So a diagnosis of “Stage IIB,” for example, tells the treatment team both where the disease is and that systemic symptoms are present.
Conditions That Can Mimic Hodgkin Lymphoma
Several other conditions can cause swollen lymph nodes or even look similar on a biopsy slide, which is part of why expert pathology review is so important. Reactive lymph node swelling from infections, particularly Epstein-Barr virus (the virus that causes mono), can produce enlarged nodes and some overlapping features on biopsy. Non-Hodgkin lymphomas, especially anaplastic large cell lymphoma, can also share surface markers or microscopic patterns with Hodgkin lymphoma. In borderline cases, the tissue may be sent to a lymphoma specialist for review. Studies show that expert pathologists resolve ambiguous cases about 90% of the time, with greater success when working from a full surgical excision rather than a needle biopsy sample.