Symptoms of Lymphoma

Lymphoma is an umbrella term for a group of blood cancers that affect lymphocytes, a type of white blood cell. There are no less than 70 different types and subtypes of lymphoma, broadly classified under two categories:

• Hodgkin lymphoma (HL), of which there are six types, accounts for around 10% of all lymphoma cases in the United States.
• Non-Hodgkin lymphoma (NHL), involving over 60 types and subtypes, represents roughly 90% of all cases.

The distinction between HL and NHL is made with microscopic examination of biopsied tissue. HL features abnormal cells with two nuclei, called Reed-Sternberg cells, that aren't found in NHL. Despite the cellular differences, HL and NHL have many of the same symptoms, particularly in the early stages of the disease.

Frequent Symptoms

Many lymphoma symptoms are non-specific and can be confused with other, less serious diseases. The warning signs of lymphoma are often subtle and it may take years before you realize that anything is wrong. Even so, if you think you may have lymphoma or have a family history of the disease, you can watch for tell-tale clues, including:

• Lymphadenopathy (swollen lymph nodes)
• Fever
• Night sweats
• Anorexia (loss of appetite)
• Pruritus (itching)
• Dyspnea (shortness of breath)
• Unintended weight loss
• Persistent fatigue

Of all of the symptoms of lymphoma, lymphadenopathy is the central defining feature. The swollen nodes are usually firm, rubbery, and movable in the surrounding tissues. Unlike the tender lymph nodes associated with viral infections like HIV, lymphadenopathy caused by lymphoma is rarely painful.

Progression and Types

The pathogenesis (the manner in which the disease develops) differs significantly between lymphoma subtypes. The location of swollen lymph nodes can provide clues as to the type:

• With HL, which moves in a sequential fashion through the lymphatic system, lymphadenopathy will almost invariably start in the upper body—typically the neck (cervical lymph nodes), chest (mediastinal lymph nodes), or armpits (axillary lymph nodes)—before progressing to the lower body.
• With NHL, the disease develops haphazardly and can affect lymph nodes in any part of the body, including the abdomen (peritoneal lymph nodes) and groin (inguinal lymph nodes).

The very fact that you have swollen lymph nodes that do not resolve should prompt you to see a doctor.

Symptoms by Organ

The symptoms of lymphoma are defined by the type and subtype of lymphoma involved as well as its stage, grade (severity), and location in the body. This is especially true if the disease is extranodal, meaning that it occurs outside of the lymph nodes.

Two main categories of extranodal lymphoma are:

• Primary extranodal lymphoma: Originates outside of the lymphatic system. The vast majority of primary extranodal cases occur with NHL; it's uncommon with HL.
• Secondary extranodal lymphoma: Originates in the lymphatic system and then spreads to other organs. This can occur with both HL and NHL.

The definition of extranodal can vary slightly based on whether HL or NHL is involved. With HL, the spleen, tonsils, and thymus are considered nodal sites since the disease spreads within the confines of the lymphatic system. By contrast, these same organs are considered extranodal with NHL given that the disease develops spontaneously in any part of the body.

While nodal lymphoma is characterized by lymphadenopathy and other classic symptoms, the symptoms of extranodal lymphoma are dictated by the organs affected.

Gastrointestinal Tract

The stomach and small intestine are the first and second most common sites for extranodal lymphoma. Symptoms of gastrointestinal (GI) lymphoma may include:

• Abdominal tenderness, pain, and cramps
• Indigestion, nausea, and vomiting
• Constipation
• Diarrhea
• Malaise (a general feeling of unwellness)
• Feeling full after a few bites of food
• Rectal bleeding
• Black, tarry stools
• Unintended weight loss

Skin

Cutaneous (skin) lymphoma occurs with both HL and NHL. Around 25% of nodal lymphomas will manifest with skin symptoms, while 65% of all NHL cases will be attributed to a subtype known as cutaneous T-cell lymphoma. One of the most common subtypes is mycosis fungoides.

Symptoms of cutaneous lymphoma may include:

• Round skin patches that may be raised, scaly, or itchy
• Lightened patches of skin
• Skin tumors that can spontaneously break open
• Thickening of the palms or soles
• An itchy, rash-like redness covering much of the body
• Alopecia (hair loss)

Bone and Bone Marrow

The primary involvement of the bone in NHL is classified as Stage 1 lymphoma, while the secondary involvement with widespread (disseminated) disease is considered Stage 4. The vast majority of bone lymphomas are associated with NHL and caused by a type known as B-cell lymphoma. HL almost never affects the bone.

When lymphoma affects the bone marrow, it can drastically impair the production of red and white blood cells, causing anemia (low red blood cells) and thrombocytopenia (low platelets). It also suppresses a specific white blood cell produced in the bone marrow called a leukocyte, leading to leukopenia. (Leukocytes are also involved in leukemia, a related blood cancer.)

Symptoms of bone lymphoma include:

• Bone pain
• Limb swelling
• Loss of range of motion in a limb
• Fatigue
• Easy bruising and bleeding

Central Nervous System

Lymphomas of the central nervous system (CNS) represent between 7 and 15% of all brain cancers. They are usually classified as B-cell lymphoma and occur most commonly in immunocompromised people, such as those with advanced HIV infection.

Symptoms of primary or secondary CNS lymphoma include:

• Headaches
• Muscle weakness in a specific body part
• Loss of sensation in a specific body part
• Problems with balance, memory, cognition, and/or language
• Changes in vision or partial vision loss
• Nausea and vomiting
• Seizures

Lungs

Pulmonary (lung) lymphoma is a rare disease and it is more common with HL than NHL. Secondary involvement of lung in lymphomas is more common than primary lymphoma in both NHL and HL. Mediastinal lymph nodes may be involved in both HL and NHL.

Symptoms of pulmonary lymphoma are often non-specific in the early stages of the disease and may include:

• Coughing
• Chest pain
• Fever
• Shortness of breath
• Crepitus (audible lung crackles)
• Hemoptysis (coughing up blood)
• Unintended weight loss

Liver

Primary liver lymphoma is extremely rare and almost exclusively associated with NHL. With that said, there will be secondary liver involvement in 15% of people with NHL and 10% of those with NL. In most cases, the malignancy will have spread from the retroperitoneal lymph nodes situated to the back of the abdominal cavity to the liver.

Symptoms of liver lymphoma are often mild and non-specific and may include:

• Pain or swelling in the upper right abdomen
• Extreme fatigue and lethargy
• Unintended weight loss
• Night sweats
• Nausea and vomiting
• Rarely, jaundice (yellowing of the skin and/or eyes)
• Loss of appetite
• Dark urine

Kidneys and Adrenal Glands

Primary lymphoma of the kidneys and adrenal glands is rare. Primary or secondary kidney lymphoma often mimics renal cell carcinoma, a type of cancer that starts in the small tubes of the kidney. Kidney lymphoma causes symptoms such as:

• Flank pain
• A lump or swelling in the side or lower back
• Hematuria (blood in urine)
• Loss of appetite
• Fever
• Persistent fatigue
• Unintended weight loss

Genitals

Testicular lymphoma accounts for around 5% of all abnormal growth in the testicles. It typically manifests with painless swelling, usually in one testicle only. What makes testicular lymphoma especially concerning is that it tends to involve aggressive B-cell lymphomas that move quickly into the central nervous system.

Females can develop lymphoma in tissues surrounding the genitals, known as the adnexa. Genital involvement in females is rare, although cases involving the cervix and uterus have been reported.

Complications

Because lymphoma weakens the immune system, it can lead to serious long-term complications. This is especially true with low-grade lymphomas, many of which cannot be cured.

While modern therapies have afforded near-normal life expectancies in people with lymphoma, ongoing exposure to chemotherapy drugs may trigger the early development of aging-related diseases, such as cancer, heart disease, hormonal disorders, and infertility.

Cancer

Secondary cancers, including leukemia and solid tumors, are among the leading causes of death in people with lymphoma. Leukemia can develop years and even decades after exposure to alkylating chemotherapy drugs, while between 70% and 80% of all secondary solid tumors occur in people with previous exposure to combined radiation and chemotherapy.

Breast cancer in females with HL often occurs between 10 and 15 years after chest irradiation, particularly in those under 35. Similarly, lung cancer rates are higher in people with HL who are smokers and have previously undergone radiation and/or chemotherapy.

Heart Disease

Heart disease is believed to be the leading, non-cancer cause of death in people with lymphoma. Among the chief concerns is coronary artery disease (CAD), which occurs up to five times greater than in the general population. Most CAD cases develop between 10 and 25 years after exposure to chest radiation therapy for lymphoma.

Similarly, radiation to the neck is associated with an up to five-fold increase in stroke risk. Typical cardiac risk factors including pre-existing heart disease, smoking, diabetes, and high blood pressure may add to the risk, but their influence is likely small.

Hormonal Disorders and Infertility

As a disease that often affects organs of the endocrine system, lymphoma may cause hormonal imbalances or insufficiencies that can persist for years following the successful treatment of the disease.

The most common complication is hypothyroidism (low thyroid function), affecting as many as 60% of people with HL. The risk is hypothyroidism is directly related to the amount of radiation used to treat the disease, particularly in advanced, late-stage lymphoma.

Infertility is a common concern in people with lymphoma. While testicular lymphoma can impact male fertility, the alkylating chemotherapy drugs used to treat lymphoma are the most common causes of infertility in males and females.

People treated with the BEACOPP regimen of chemotherapy drugs (bleomycin, etoposide, doxorubicin, cyclophosphamide, procarbazine, and prednisone) were most severely affected.

Other chemotherapy regimens (such as AVBD) are less impactful. By and large, males and females with chemotherapy-induced infertility will experience restored fertility after the completion of therapy, although some may end up experiencing permanent sterility.

When to See a Doctor

In many cases, lymphoma has no early signs, and overt symptoms develop only when the disease is advanced. The most telling clue—persistently lymphadenopathy with no known cause—should warrant prompt medical attention.

However, in cases where the disease is confined to the chest or abdomen, you may have no visible signs of lymphadenopathy at all. Moreover, the so-called "B" symptoms (fever, night sweats, weight loss) are often mistaken for other conditions.

Risk Factors

If you believe you're at-risk for lymphoma, it pays to be proactive and get any symptoms checked out early. Your risk is elevated if:

• You have a first-degree relative (parent, brother, or sister) with lymphoma, which is known to increase your risk of NHL by 1.7 fold and HL by 3.1 fold.
• You've had long-term exposure to industrial chemicals.
• You have a compromised immune system.

Your lymphoma risk also increases with age.

Frequently Asked Questions

What causes lymphoma?

Researchers haven't yet uncovered the exact cause(s) of lymphoma, but they believe genetics, environmental and lifestyle factors, and certain infections all play a role. The cause of lymphoma symptoms is better understood.

The lymphatic system is a network of vessels and organs that help isolate and kill germs in the body. Central to this system are lymphocytes and lymph nodes. Lymphocytes are part of the body's first line of defense against infection.

Lymphocytes are transported throughout the lymphatic system in a fluid known as lymph. Scattered along the route are dense clusters of lymph nodes that filter bacteria, viruses, and other microorganisms from lymph. Under normal circumstances, lymphocytes move freely in and out of the lymph nodes while carrying on their immune functions.

However, when lymphoma develops, lymphocytes start to accumulate in the lymph nodes. This accumulation, along with the destruction of other white blood cells, such as macrophages and monocytes, can lead to a cascade of symptoms characteristic to both HL and NHL.

How is lymphoma diagnosed?

If your doctor suspects lymphoma based on your symptoms, history, and a physical exam, they'll likely order an array of blood tests and imaging. Blood tests will look at:

• Levels of red and white blood cells: Complete blood count (CBC)
• Markers of blood cancers: Beta-2 microglobulin (ß2M), lactate dehydrogenase (LDH)
• Markers of inflammation: Erythrocyte sedimentation rate (ESR or sed rate)

They may also check your liver function and screen for certain viruses including HIV and hepatitis B and C.

When symptoms occur alongside a drop in red blood cell or white blood cell count, lymphoma is a possibility. That's especially true if you're immunocompromised or over the age of 60.

Imaging

If you don't have signs of lymphoma in the neck, armpit, or groin, your doctor may order an X-ray, computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI) to look at the lymph nodes in your chest or abdomen.

Biopsy

Blood tests and imaging can't diagnose lymphoma, but they can provide evidence that it's worthwhile to perform a lymph node biopsy, which is the gold standard for a diagnosis. All or part of a lymph node may be removed and examined for cancerous lymphocytes that accumulate in the nodes.

After going through this process, if you don't have a clear diagnosis or if you are having a hard time deciding how to proceed with treatment, seek a second opinion.

What does a lymphoma rash look like?

A rash produced by lymphoma can have different appearances, and you may have more than one type. It may be itchy and scaly, cover large areas of your body, and the color can range from red to purple. You may have:

• Papules, which look like small pimples
• Patches, which are flat
• Plaques, which are thick and either raised or depressed into your skin

You may also be able to see lumps under the skin caused by nodules or tumors.

A Word From Verywell

While risk factors can often point you in the direction of lymphoma diagnosis, you can have none of the risk factors and still get the disease. To this end, the most important thing you can do is to never ignore symptoms that persist, however mild they may be.

For example, even if non-specific gastrointestinal symptoms temporarily improve with antacids and other medications, let your doctor know if they don't go away completely. Don't live with them in silence just because they're a little better.