Table of ContentsView AllTable of ContentsSelf-ChecksPhysical ExamLabs and TestsClassificationStagingDifferential DiagnosisFrequently Asked QuestionsNext in Lymphoma GuideHow Lymphoma Is Treated

Table of ContentsView All

View All

Table of Contents

Self-Checks

Physical Exam

Labs and Tests

Classification

Staging

Differential Diagnosis

Frequently Asked Questions

Next in Lymphoma Guide

Diagnosinglymphomacan often be challenging. It not only involves surgery to check for cancer in thelymph nodesbut also requiresadditional teststo determine whichtype and stage of canceryou have.

The road to a definitive diagnosis may involve a variety of specialists, including a surgicaloncologist, ahematologist-oncologist(a specialist in blood cancers), and ahematopathologist(a specialist in the diagnosis of blood diseases).

warning signs of lymphoma

How to Find the Best Oncologist

Lymphomais a form of cancer that starts in the type of white blood cell called alymphocyte. The disease affects the lymphatic system, a closed system is comprised of lymphatic vessels,lymph nodes, lymph fluid as well as thespleen,tonsils,adenoids,thymus gland, andbone marrow. When you have lymphoma, lymphocytes will change (mutate) and grow out of control.

A medical history may reveal certain risk factors that increase your likelihood of lymphoma, includingadvanced HIV infection,previouschemotherapyorradiation therapy, or a family history of the disease. The physical exam will focus on the lymph nodes as well as parts of the lymphatic system that can be physically felt (palpated).

Unlike other types ofchronic lymphadenopathy, the swollen lymph nodes in lymphoma will usually be painless. On palpation, the nodes will also appear firm, rubbery, and movable in the surrounding tissues.

An enlarged spleen or liver may also be suggestive of lymphoma. Certain types of lymphoma, known ascutaneous lymphoma, will manifest with dry, discolored patches of skin or reddish nodules or tumors.

Your healthcare provider will perform tests to either support the diagnosis or exclude other causes. These include such standard blood tests as:

Imaging

If lymphoma is suspected but there are no signs of lymphadenopathy in the armpit, groin, or neck, your healthcare provider may order a CT scan of the chest to look for swollen lymph nodes in the chest or anabdominal ultrasoundormagnetic resonance imaging (MRI)to look for swollen lymph nodes in the abdomen.

Neither blood nor imaging tests can diagnose lymphoma. They can, however, provide ample evidence to move you to the next stage in the diagnosis: the excisional biopsy.

Understanding Lymphoma Tumor Markers

Excisional Biopsy

The lymph node biopsy is the gold standard for the diagnosis of lymphoma. It not only provides definitive proof of the malignancy but also begins the process of classifying and staging the disease should cancer cells be found.

The biopsy will target the lymph nodes which act as filters in the lymphatic system. If cancerous lymphocytes are present, they will accumulate in the lymph nodes and cause cellular changes that can be detected under the microscope.

There are two types of biopsies commonly used to diagnose lymphoma, both of which can be performed on an outpatient basis:

The surgery is performed underlocal anesthesiain a hospital operating room or outpatient surgical center. It usually takes around 30 to 45 minutes to perform.

Imaging studies—such as X-ray, ultrasound, MRI, andcomputed tomography (CT)—may be used to guide the surgeon into the correct position. Real-timepositron emission tomography (PET)scans, viewed in a digital monitor, are especially useful when performing chest node biopsies.

An excisional biopsy is generally preferred because the architecture of the lymph node is as important to the classification of the disease as the presence of cancer cells. It also avoids the need for a second biopsy should lymphoma be found.

Needle biopsies, such asfine-needle aspiration (FNA), are less commonly used because they can often fail to obtain enough tissue to render an accurate diagnosis. Core biopsy, a less invasive procedure, is being used more frequently, though accuracy may not be as high as surgical biopsy.

The classification of lymphoma is rarely a straightforward process since there are so many types and subtypes of lymphoma, each with different outcomes and treatment protocols. The process involves a series of tests that differentiate the various types of lymphoma based on their physical and genetic characteristics as well as their location.

Among the tests commonly used to classify lymphoma:

Together, these characteristics can accurately classify lymphoma so that the appropriate treatment is delivered.

Hodgkin vs. Non-Hodgkin Lymphoma

The first step in classification involves the differentiation of the two main categories of lymphoma, namely:

The lack of Reed-Sternberg cells generally excludes HL as the cause.

B-Cell vs. T-Cell Lymphoma

If NHL is diagnosed, hematopathologists will want to establish the type of lymphocyte involved in the disease. This may either involveB-cellsderived from bone marrow (whose role it is to target disease-causing microorganisms) andT-cellsderived from the thymus gland (which directly kills the microorganism).

The differences are important for several reasons:

Both B-cell and T-cell lymphomas can occur with non-Hodgkin lymphoma. Hodgkin lymphoma involves B-cells only.

Areas of Involvement

The organs and tissues affected can further aid in the classification of lymphoma. For example, lymphoma in the lining of the stomach is more likely to bemucosa-associated lymphoid tissue (MALT) lymphoma, while skin lesions are far more likely to occur with NHL than HL (at least in the early stages).

Based on the area of involvement, the mutation type, and other differentiating factors, lymphoma will be classified as one of 33 types or subtypes under the Revised European American Lymphoma Classification (REAL) system or one of over 70 types and subtypes under the expanded World Health Organization (WHO) Classification of Lymphoid Neoplasms.

After the initial diagnosis and classification, lymphoma staging will be performed to determine the appropriate course of the treatment as well as the likely outcome (referred to as theprognosis).

The staging is based on a number of factors, including the number of lymph nodes affected, their location above or below thediaphragm, and whether organs outside of the lymphatic system are involved.

The staging criteria for Hodgkin and non-Hodgkin lymphoma are the same, wherein “low-grade” lymphomas are known to grow slowly (but are generally incurable) while “high-grade” lymphomas spread quickly (but respond better to treatment).

According to the Lugano classification system for lymphoma revised in 2015, the stages of lymphoma are broken down as follows:

Stage 3 and stage 4 lymphomas are still highly treatable and often curable depending on their type and location.

Lymphoma Survival Rates

Because the signs and symptoms of lymphoma are subtle in the early stages, they are easily mistaken for other diseases. Even with advanced-stageextranodal lymphoma(lymphoma occurring outside of the lymphatic system), the symptoms can vary dramatically based on which organ is affected. Oftentimes, the disease will only be diagnosed when multiple extranodal sites are involved.

When diagnosing lymphoma, your healthcare provider will want to rule out any other possible cause, particularly if the results of your biopsy are inconclusive. These may include:

A Word From Verywell

Lymphoma can be a difficult disease to diagnose, particularly in the early stages. Symptoms are frequently missed or misdiagnosed with few tell-tale clues to rely on.

In the end, if you have persistently swollen lymph nodes or any other systemic symptom that fails to resolve despite treatment, see a healthcare provider as soon a possible. Even if lymphoma is not the cause, persistent symptoms of any sort warrant thorough investigation.

This is especially true if you have risk factors for lymphoma, including acompromised immune system, previous exposure to radiation or chemotherapy, long-term exposure to industrial chemicals, and a first-degree relative (parent, brother, or sister) with lymphoma.

Non-Hodgkin lymphoma is one of the most common forms of cancer in the U.S., whereas Hodgkin lymphoma is less common. The American Cancer Society estimates that there will be over 81,000 new cases of non-Hodgkin lymphomaand only 8,800 new cases of Hodgkin lymphoma in 2021.

No, you should not feel pain. Depending on the type and location of the biopsy, you will be numbed or put under general anesthesia.

How Lymphoma Is Treated

11 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Mohseni S, Shojaiefard A, Khorgami Z, et al.Peripheral Lymphadenopathy: Approach and Diagnostic Tools.Iran J Med Sci.2014 Mar;39(2 Suppl):158-70.Bagherania N, Smoller BR.An overview of cutaneous T cell lymphomas.F1000Res. 2016;5:F1000 Faculty Rev-1882. doi:10.12688/f1000research.8829.1Fei B, Schuster DM.PET Molecular Imaging–Directed Biopsy: A Review.AJR Am J Roentgenol. 2017 Aug;209(2):255-69. doi:10.2214/AJR.17.18047Baron BW, Baron JM.The diagnostic value of biopsy of small peripheral lymph nodes in patients with suspected lymphoma.Am J Hematol.2012 Feb;87(2):228-30. doi:10.1002/ajh.22240Pileri SA, Leoncini L, Falini B.Revised European-American Lymphoma Classification.Curr Opin Oncol.1995 Sep;7(5):401-7.Quintanilla‐Martinez L.The 2016 updated WHO classification of lymphoid neoplasias.Hematol Oncol.2017 Jun;35(Suppl 1):37-45. doi:10.1002/hon.2399Cheson BD.Staging and response assessment in lymphomas: the new Lugano classification.Chin Clin Oncol. 2015 Mar;4(1):5. doi:10.3978/j.issn.2304-3865.2014.11.03American Cancer Society.Lymph nodes and cancer.American Cancer Society.Key statistics for non-Hodgkin lymphoma.American Cancer Society.Key statistics for Hodgkin lymphoma.MedlinePlus.Lymph node biopsy.Additional ReadingAl-Naeeb AB, Ajithkumar T, Behan S, Hodson DJ.Non-Hodgkin lymphoma.BMJ.2018;362:k3204. doi:10.1136/bmj.k3204Ansell SM.Hodgkin lymphoma: 2018 update on diagnosis, risk‐stratification, and management.Am J Hematol.2018;93(5):704-15 doi: https:10.1002/ajh.25071

11 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Mohseni S, Shojaiefard A, Khorgami Z, et al.Peripheral Lymphadenopathy: Approach and Diagnostic Tools.Iran J Med Sci.2014 Mar;39(2 Suppl):158-70.Bagherania N, Smoller BR.An overview of cutaneous T cell lymphomas.F1000Res. 2016;5:F1000 Faculty Rev-1882. doi:10.12688/f1000research.8829.1Fei B, Schuster DM.PET Molecular Imaging–Directed Biopsy: A Review.AJR Am J Roentgenol. 2017 Aug;209(2):255-69. doi:10.2214/AJR.17.18047Baron BW, Baron JM.The diagnostic value of biopsy of small peripheral lymph nodes in patients with suspected lymphoma.Am J Hematol.2012 Feb;87(2):228-30. doi:10.1002/ajh.22240Pileri SA, Leoncini L, Falini B.Revised European-American Lymphoma Classification.Curr Opin Oncol.1995 Sep;7(5):401-7.Quintanilla‐Martinez L.The 2016 updated WHO classification of lymphoid neoplasias.Hematol Oncol.2017 Jun;35(Suppl 1):37-45. doi:10.1002/hon.2399Cheson BD.Staging and response assessment in lymphomas: the new Lugano classification.Chin Clin Oncol. 2015 Mar;4(1):5. doi:10.3978/j.issn.2304-3865.2014.11.03American Cancer Society.Lymph nodes and cancer.American Cancer Society.Key statistics for non-Hodgkin lymphoma.American Cancer Society.Key statistics for Hodgkin lymphoma.MedlinePlus.Lymph node biopsy.Additional ReadingAl-Naeeb AB, Ajithkumar T, Behan S, Hodson DJ.Non-Hodgkin lymphoma.BMJ.2018;362:k3204. doi:10.1136/bmj.k3204Ansell SM.Hodgkin lymphoma: 2018 update on diagnosis, risk‐stratification, and management.Am J Hematol.2018;93(5):704-15 doi: https:10.1002/ajh.25071

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Mohseni S, Shojaiefard A, Khorgami Z, et al.Peripheral Lymphadenopathy: Approach and Diagnostic Tools.Iran J Med Sci.2014 Mar;39(2 Suppl):158-70.Bagherania N, Smoller BR.An overview of cutaneous T cell lymphomas.F1000Res. 2016;5:F1000 Faculty Rev-1882. doi:10.12688/f1000research.8829.1Fei B, Schuster DM.PET Molecular Imaging–Directed Biopsy: A Review.AJR Am J Roentgenol. 2017 Aug;209(2):255-69. doi:10.2214/AJR.17.18047Baron BW, Baron JM.The diagnostic value of biopsy of small peripheral lymph nodes in patients with suspected lymphoma.Am J Hematol.2012 Feb;87(2):228-30. doi:10.1002/ajh.22240Pileri SA, Leoncini L, Falini B.Revised European-American Lymphoma Classification.Curr Opin Oncol.1995 Sep;7(5):401-7.Quintanilla‐Martinez L.The 2016 updated WHO classification of lymphoid neoplasias.Hematol Oncol.2017 Jun;35(Suppl 1):37-45. doi:10.1002/hon.2399Cheson BD.Staging and response assessment in lymphomas: the new Lugano classification.Chin Clin Oncol. 2015 Mar;4(1):5. doi:10.3978/j.issn.2304-3865.2014.11.03American Cancer Society.Lymph nodes and cancer.American Cancer Society.Key statistics for non-Hodgkin lymphoma.American Cancer Society.Key statistics for Hodgkin lymphoma.MedlinePlus.Lymph node biopsy.

Mohseni S, Shojaiefard A, Khorgami Z, et al.Peripheral Lymphadenopathy: Approach and Diagnostic Tools.Iran J Med Sci.2014 Mar;39(2 Suppl):158-70.

Bagherania N, Smoller BR.An overview of cutaneous T cell lymphomas.F1000Res. 2016;5:F1000 Faculty Rev-1882. doi:10.12688/f1000research.8829.1

Fei B, Schuster DM.PET Molecular Imaging–Directed Biopsy: A Review.AJR Am J Roentgenol. 2017 Aug;209(2):255-69. doi:10.2214/AJR.17.18047

Baron BW, Baron JM.The diagnostic value of biopsy of small peripheral lymph nodes in patients with suspected lymphoma.Am J Hematol.2012 Feb;87(2):228-30. doi:10.1002/ajh.22240

Pileri SA, Leoncini L, Falini B.Revised European-American Lymphoma Classification.Curr Opin Oncol.1995 Sep;7(5):401-7.

Quintanilla‐Martinez L.The 2016 updated WHO classification of lymphoid neoplasias.Hematol Oncol.2017 Jun;35(Suppl 1):37-45. doi:10.1002/hon.2399

Cheson BD.Staging and response assessment in lymphomas: the new Lugano classification.Chin Clin Oncol. 2015 Mar;4(1):5. doi:10.3978/j.issn.2304-3865.2014.11.03

American Cancer Society.Lymph nodes and cancer.

American Cancer Society.Key statistics for non-Hodgkin lymphoma.

American Cancer Society.Key statistics for Hodgkin lymphoma.

MedlinePlus.Lymph node biopsy.

Al-Naeeb AB, Ajithkumar T, Behan S, Hodson DJ.Non-Hodgkin lymphoma.BMJ.2018;362:k3204. doi:10.1136/bmj.k3204Ansell SM.Hodgkin lymphoma: 2018 update on diagnosis, risk‐stratification, and management.Am J Hematol.2018;93(5):704-15 doi: https:10.1002/ajh.25071

Al-Naeeb AB, Ajithkumar T, Behan S, Hodson DJ.Non-Hodgkin lymphoma.BMJ.2018;362:k3204. doi:10.1136/bmj.k3204

Ansell SM.Hodgkin lymphoma: 2018 update on diagnosis, risk‐stratification, and management.Am J Hematol.2018;93(5):704-15 doi: https:10.1002/ajh.25071

Meet Our Medical Expert Board

Share Feedback

Was this page helpful?Thanks for your feedback!What is your feedback?OtherHelpfulReport an ErrorSubmit

Was this page helpful?

Thanks for your feedback!

What is your feedback?OtherHelpfulReport an ErrorSubmit

What is your feedback?