Hodgkin Lymphoma: Symptoms, Survival Rates, Diagnosis, and Treatment

What is Hodgkin Lymphoma?

Hodgkin lymphoma (HL), also called Hodgkin’s disease, is a cancer that develops in the cells of the immune system, specifically in the lymphatic system. It is one of the most treatable forms of cancer, with cure rates that have improved dramatically over the past five decades.

To understand Hodgkin lymphoma, it helps to know the basic structure of the lymphatic system, which is part of the immune system and consists of:

• Lymphatic vessels: A branching network of thin vessels that extends to virtually every tissue in the body, draining fluid from the interstitial spaces back into the bloodstream.
• Lymph: The clear fluid that flows through the lymphatic vessels, carrying white blood cells, primarily B and T lymphocytes, throughout the body.
• Lymph nodes: Small, bean-shaped collections of immune tissue connected along the lymphatic vessels. They are clustered in the neck, armpits (axillae), chest, abdomen, and groin. Lymph nodes filter lymph fluid and harbor white blood cells that trap and destroy bacteria, viruses, and other potentially harmful substances.
• Other lymphoid organs: Including the tonsils, the thymus gland, and the spleen. Lymphoid tissue is also found in the stomach, skin, and small intestine.

Because lymphoid tissue is distributed throughout the entire body, Hodgkin lymphoma can potentially develop anywhere. It most commonly originates in a lymph node above the diaphragm (the thin muscle separating the chest from the abdomen), but it can arise in any lymph node group or, in some cases, in other parts of the lymphatic system.

The most common presenting symptom is painless swelling of a lymph node in the neck, armpit, or groin. In some patients, additional symptoms may appear:

• Night sweats
• Unexplained weight loss
• Persistent fever
• Persistent cough, breathlessness (dyspnea), or chest pain
• Generalized itching (pruritus)

Overall, Hodgkin lymphoma carries an excellent prognosis. More than 86% of patients survive at least five years from diagnosis, and in younger patients, the 10-year survival rate exceeds 90%. It is widely regarded as one of the most curable cancers in modern oncology.

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Causes

Hodgkin lymphoma occurs when a genetic abnormality develops in a lymphocyte, typically a B lymphocyte and only rarely a T lymphocyte. This abnormal cell, known as the Reed-Sternberg cell, serves as the pathological hallmark of Hodgkin lymphoma.

The Reed-Sternberg cell is a large, abnormal cell with a distinctive microscopic appearance. Under normal circumstances, aging or damaged cells undergo programmed cell death (apoptosis). Reed-Sternberg cells, however, escape this regulatory mechanism and continuously divide and replicate, producing ever-increasing numbers of abnormal cells that:

• Do not die as healthy cells periodically do.
• Cannot protect the body against infections or disease.
• Accumulate to form a mass of diseased tissue, known as a tumor.

The exact genetic events that trigger this malignant transformation remain incompletely understood, but several risk factors have been identified.

Risk Factors

In most cases, it is not possible to identify a clear reason why Hodgkin lymphoma develops in a specific individual. However, research has identified certain risk factors that increase the probability of developing this cancer:

• Viral infections: Infection with the Epstein-Barr Virus (EBV), the virus responsible for infectious mononucleosis, is one of the most well-established risk factors. EBV DNA is found in Reed-Sternberg cells in approximately 30–40% of Hodgkin lymphoma cases. Infection with HIV also significantly increases the risk. Importantly, Hodgkin lymphoma is not contagious; it cannot be transmitted from one person to another.

• Immunodeficiency: A weakened immune system, whether caused by an inherited disorder, HIV infection, or immunosuppressive medications used after organ transplantation, increases susceptibility to Hodgkin lymphoma.

• Age: The disease shows a characteristic bimodal age distribution, with peak incidences in two distinct age groups: adolescents and young adults aged 15–35, and adults over 55 years of age. This bimodal distribution is one of the distinctive epidemiological features of Hodgkin lymphoma.

• Family history: First-degree relatives, particularly siblings, of a person with Hodgkin lymphoma have a modestly increased risk of developing the disease. This may reflect shared genetic susceptibility factors, though the precise genes involved have not been fully characterized.

Having one or more risk factors does not mean a person will develop Hodgkin lymphoma. The majority of individuals with risk factors never develop the disease.

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Symptoms

Hodgkin lymphoma can produce a variety of symptoms. In many cases, the earliest and most distinctive sign is painless lymph node enlargement. This is why the disease may be discovered incidentally or initially dismissed.

Key symptoms include:

• Painless swelling of lymph nodes in the neck, armpits, or groin is the most common presenting feature.
• Alcohol sensitivity: Pain in the lymph nodes after drinking alcohol is a rare but distinctive symptom. It is considered highly suggestive of Hodgkin lymphoma.
• Unexplained weight loss, particularly losing more than 10% of body weight within 6 months.
• Persistent fever, which does not resolve on its own.
• Drenching night sweats, severe enough to soak bedclothes and sheets.
• Generalized itching (pruritus): diffuse and occurring without a rash.
• Cough, breathlessness (dyspnea), or chest pain may occur when mediastinal lymph nodes are involved.
• Persistent fatigue and weakness that does not improve with rest.

“B symptoms” (the triad of fever, drenching night sweats, and significant weight loss) are of particular clinical importance. Their presence or absence is used to classify the disease (A = absent, B = present) and has significant prognostic and therapeutic implications.

Patients with bone marrow involvement may additionally experience:

• Increased susceptibility to infections
• Abnormal or excessive bleeding, including nosebleeds, heavy menstrual periods, or unexplained bruising (such as hematomas)

Important: The vast majority of these symptoms are far more commonly caused by ordinary infections or benign inflammatory conditions than by cancer. However, if any of these symptoms persist for more than two weeks, you should consult your doctor for evaluation.

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Survival Rates

Hodgkin lymphoma is one of the most curable cancers known to medicine, and outcomes have improved dramatically with modern treatment approaches.

In pediatric patients, the 10-year survival rate after diagnosis exceeds 90%, a testament to the remarkable therapeutic progress of recent decades.

In adult patients, 5-year survival rates vary with age at diagnosis:

The overall 5-year relative survival rate across all age groups is approximately 87–89% in Western countries. The decline in survival in older patients reflects both the greater challenge of administering intensive chemotherapy in this population and the increased prevalence of comorbidities.

Importantly, survival also depends on disease stage at diagnosis, the presence of B symptoms, the patient’s general health status, and the specific histological subtype of Hodgkin lymphoma.

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Diagnosis

The diagnostic workup for Hodgkin lymphoma is today highly standardized. It aims not only to confirm the presence of the disease but also to precisely define its extent (staging), which is essential for personalizing treatment and predicting prognosis.

Physical Examination and Medical History

The first step is a thorough clinical assessment. The physician systematically palpates all accessible lymph node stations (neck, armpits, groin, and abdominal nodes) and examines the abdomen to detect possible enlargement of the spleen (splenomegaly) or liver (hepatomegaly).

During the medical history interview, particular attention is paid to:

• The “B symptoms”: fever, night sweats, and weight loss exceeding 10% of body weight in the preceding 6 months, all of which affect staging and treatment decisions.
• The duration and progression of lymph node enlargement.
• Any prior infections, particularly EBV (mononucleosis).
• Family history of lymphoma or hematological cancers.

Lymph Node Biopsy

A biopsy is the definitive diagnostic test for Hodgkin lymphoma. Without histological confirmation, no diagnosis can be made.

The current gold standard is the excisional biopsy, the surgical removal of an entire suspect lymph node. This approach is strongly preferred over fine-needle aspiration (FNA) or core-needle biopsy, because it provides the pathologist with the complete tissue architecture of the lymph node. This is essential for identifying the characteristic Reed-Sternberg cells within their appropriate inflammatory cellular background, which is the diagnostic hallmark of Hodgkin lymphoma.

The histopathological examination also determines the histological subtype of Hodgkin lymphoma:

• Classical Hodgkin lymphoma (cHL), which accounts for approximately 95% of cases, is subdivided into four subtypes: nodular sclerosis (the most common), mixed cellularity, lymphocyte-rich, and lymphocyte-depleted.
• Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL): a rare variant (about 5% of cases) with distinct biology and somewhat different clinical behavior.

Imaging and Staging

Once the diagnosis is histologically confirmed, staging (determining the extent of disease spread) is the next critical step. Staging follows the Lugano Classification (derived from the original Ann Arbor system), defining stages I through IV based on the number and location of involved lymph node regions and the presence of extranodal disease.

Key investigations for staging:

• FDG-PET/CT (Fluorodeoxyglucose Positron Emission Tomography combined with CT): This is now the cornerstone examination for Hodgkin lymphoma staging. PET maps the metabolic activity of tumor cells throughout the entire body, detecting active disease in lymph nodes and organs with far greater accuracy than CT alone. FDG-PET/CT is also used for interim response assessment, typically after two cycles of chemotherapy. This allows for early identification of patients who may need treatment intensification or de-escalation. Such an approach is known as “response-adapted therapy”.

• Blood tests: Include a complete blood count (CBC), comprehensive metabolic panel (renal and hepatic function), and measurement of prognostic biomarkers including:

  • ESR (Erythrocyte Sedimentation Rate): elevated in active disease and carries adverse prognostic significance.
  • LDH (Lactate Dehydrogenase) is a non-specific marker of tumor burden.
  • Albumin: low levels indicate poorer nutritional status and are incorporated into prognostic scoring systems.

• Bone marrow biopsy: Previously a routine component of staging, bone marrow biopsy (sampling a fragment of pelvic bone marrow) is no longer routinely performed when PET/CT is available, as PET is highly sensitive for detecting bone marrow involvement. It is reserved for cases where PET shows suspicious marrow uptake or when clinical decisions depend critically on marrow status.

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Treatment

The primary goal of therapy in Hodgkin lymphoma is definitive cure, rather than just disease control, while also minimizing the risk of long-term treatment toxicity. Thanks to modern therapeutic strategies, the majority of patients can today achieve durable complete remission.

Treatment is planned by a multidisciplinary team and is tailored to the patient’s stage, risk group, age, general health, and specific treatment goals.

First-Line Treatment Strategies

Standard first-line treatment integrates multiple therapeutic approaches:

Chemotherapy

Chemotherapy is the cornerstone of treatment for Hodgkin lymphoma. The most widely used regimen globally is ABVD (Adriamycin [doxorubicin], Bleomycin, Vinblastine, Dacarbazine), which is administered in repeated cycles with intervals allowing the body to recover. ABVD has an excellent efficacy/toxicity balance for most patients with early and advanced-stage classical HL.

For patients with advanced or high-risk disease, more intensive regimens may be used, such as:

• BEACOPP (escalated): More intensive than ABVD, associated with higher rates of complete remission in advanced disease but also greater toxicity (particularly fertility effects and risk of secondary malignancies)
• A+AVD: Brentuximab vedotin combined with AVD (ABVD without bleomycin). This regimen is increasingly used as a first-line option for advanced-stage cHL, as it offers superior progression-free survival data.

Chemotherapy is typically administered as outpatient infusions, with cycles every 2–4 weeks depending on the regimen.

Radiation therapy

Radiotherapy is often used after chemotherapy to consolidate the response, specifically targeting areas where the disease was initially most bulky or where metabolic activity persists on interim PET assessment.

Modern radiotherapy for Hodgkin lymphoma uses Involved-Site Radiation Therapy (ISRT) techniques, which precisely target only the originally involved lymph node regions, minimizing radiation exposure to surrounding healthy tissues (heart, lungs, breasts) and thereby reducing the risk of serious late effects such as:

• Secondary breast cancer (particularly relevant in young women)
• Cardiac disease
• Pulmonary fibrosis
• Secondary solid tumors

The decision on whether to include radiotherapy is increasingly guided by interim PET response. Patients who achieve a complete metabolic response after chemotherapy may safely omit radiotherapy, which reduces long-term toxicity.

Innovative Therapies and Biological Drugs

The introduction of novel drug classes has revolutionized treatment of Hodgkin lymphoma, particularly for patients with relapsed or refractory disease.

Antibody-Drug Conjugates:

• Brentuximab vedotin (BV): A “smart missile”, an antibody that specifically targets the CD30 protein found on the surface of Reed-Sternberg cells. It delivers a potent cytotoxic payload, monomethyl auristatin E, directly into the tumor cell. BV has shown remarkable activity in relapsed/refractory HL and is now incorporated into first-line regimens for advanced-stage disease.

Immune Checkpoint Inhibitors (Immunotherapy):

• Nivolumab and Pembrolizumab (PD-1 inhibitors): These drugs “release the brakes” on the patient’s own immune system, enabling it to recognize and destroy lymphoma cells. Hodgkin lymphoma responds remarkably well to PD-1 blockade. This sensitivity stems from the characteristic amplification of the PD-L1 gene in Reed-Sternberg cells. As a result, response rates are among the highest observed with checkpoint inhibitors in any cancer type. These agents have shown remarkable efficacy even in heavily pre-treated patients and are now being studied in earlier lines of therapy.

Stem Cell Transplantation

For patients with relapsed or refractory Hodgkin lymphoma (disease that returns after initial treatment or does not respond), the standard of care involves:

1. Salvage chemotherapy is used to reduce tumor burden and demonstrate chemosensitivity.
2. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT): The patient’s own stem cells are harvested before high-dose chemotherapy is administered to eradicate residual cancer cells. The previously stored stem cells are then reinfused to restore the bone marrow and immune system.

The combination of brentuximab vedotin and/or checkpoint inhibitors as consolidation or maintenance therapy after ASCT has further improved outcomes in this setting.

Allogeneic stem cell transplantation (using donor stem cells) is reserved for highly selected patients with multiply relapsed or refractory disease, where the graft-versus-lymphoma immune effect may provide additional anti-tumor activity.

Lifestyle and Supportive Care

Maintaining a healthy lifestyle is an integral component of the care pathway, both during and after treatment.

• Physical activity: Moderate, regular physical exercise, tailored to the patient’s current clinical condition, has been shown to effectively reduce treatment-related fatigue (one of the most debilitating side effects of chemotherapy and radiotherapy). It also improves psychological well-being, mood, and quality of life. Activities such as walking, yoga, or swimming are generally well-tolerated and beneficial.

• Nutritional support: Adequate nutrition is fundamental during treatment to prevent muscle wasting, support immune function, and maintain energy levels. A registered dietitian with oncology expertise can provide personalized guidance.

• Psychological support: A cancer diagnosis and the challenges of treatment have profound psychological impacts. Psychological counseling, peer support groups, and mindfulness-based interventions are valuable complementary resources.

• Fertility preservation: Given that Hodgkin lymphoma predominantly affects young people, fertility counseling and preservation options (sperm banking for men, oocyte/embryo cryopreservation for women) should be discussed before starting chemotherapy or radiotherapy, as some treatments can impair fertility.

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Diet, Physical Activity, and Follow-Up

Taking care of your overall health through a balanced diet and staying as active as possible are important priorities during treatment. These habits remain just as crucial after treatment ends.

Nutrition: Maintaining a healthy body weight requires consuming an appropriate number of calories. It is equally important to consume adequate protein to preserve muscle strength and support immune recovery. Good nutrition will help you feel better and maintain energy levels throughout treatment.

During therapy, many patients experience:

• Loss of appetite
• Nausea or vomiting (from chemotherapy)
• Changes in taste perception
• Mouth sores (mucositis)

If you struggle to eat adequately, your oncologist, dietitian, or nursing team can suggest strategies for managing these symptoms, including oral nutritional supplements, antiemetic medications, and dietary modifications (small, frequent, nutrient-dense meals).

Physical activity: Many people report feeling significantly better when they remain as active as possible. Walking, yoga, swimming, and other moderate activities help:

• Preserve muscle strength and stamina
• Reduce nausea, fatigue, and pain
• Improve mood and psychological resilience
• Enhance tolerance to therapy and stress

Always consult your medical team before starting any new exercise program, and immediately report any exercise-induced pain, breathlessness, or other concerning symptoms.

Follow-Up Care

After completing treatment for Hodgkin lymphoma, regular follow-up appointments are essential. Even when symptoms have completely resolved, residual cancer cells may remain in the body. Long-term surveillance serves two critical purposes:

1. Early detection of relapse enables prompt retreatment.
2. Monitoring for late treatment effects is important because some side effects of chemotherapy and radiotherapy may not appear for years or even decades.

Questions to ask your doctor after treatment:

• How often should I come for check-ups?
• What monitoring tests do you recommend?
• What symptoms or changes should prompt me to contact you between appointments?

Long-term risks in Hodgkin lymphoma survivors: Patients treated for Hodgkin lymphoma have an elevated long-term risk of developing certain secondary conditions, primarily as late effects of chemotherapy and/or radiation therapy. These include:

• Cardiovascular disease (including coronary artery disease and valvular disease, particularly after mediastinal irradiation)
• Secondary cancers:
  • Leukemia
  • Melanoma
  • Non-Hodgkin lymphoma
  • Breast cancer (especially in women who received chest radiotherapy before age 30)
  • Lung cancer
  • Stomach cancer
  • Thyroid cancer
  • Bone tumors
• Hypothyroidism (after neck irradiation)
• Pulmonary complications (bleomycin-induced lung toxicity)
• Infertility

Routine follow-up examinations typically include:

• Regular clinical visits
• Blood tests (complete blood count, metabolic panel)
• Chest X-rays
• CT scans and other imaging as clinically indicated
• Cardiac assessments (such as echocardiogram or ECG), particularly in patients who received anthracyclines or mediastinal radiation

Vaccinations: After treatment, patients may receive the influenza vaccine and other recommended vaccines to restore immune protection. The appropriate vaccination schedule should be discussed with your medical team, as timing relative to immunosuppressive therapy is important.

If any health concerns arise between scheduled appointments, contact your medical team promptly rather than waiting for the next routine visit.

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Frequently Asked Questions

What is a lymphoma?

“Lymphoma” is a medical term for a cancer of the blood that specifically affects lymphocytes, a subtype of white blood cell and a specialized cell of the immune system. Lymphomas arise when lymphocytes undergo malignant transformation and multiply uncontrollably.

What is Hodgkin lymphoma specifically?

There are more than 60 types of lymphoma. The defining feature that distinguishes Hodgkin lymphoma from all others is the microscopic identification of a specific type of malignant cell, the Reed-Sternberg cell, within the affected lymph node tissue. All other lymphomas are classified as non-Hodgkin lymphomas.

How long can you live with Hodgkin lymphoma?

Hodgkin lymphoma is associated with excellent survival rates. On average, more than 86% of patients survive at least five years from diagnosis. In younger patients (under 45), 10-year survival rates exceed 90%. Survival rates decrease with advancing age, reflecting the greater challenges of intensive treatment in older patients and the presence of comorbidities.

What are the characteristic symptoms?

The most distinctive symptoms include:

• Painless swelling of a lymph node, most often in the neck, armpit, or groin
• Persistent, unexplained fatigue
• Unexplained weight loss (more than 10% of body weight over 6 months)
• Night sweats, particularly drenching
• Generalized itching (pruritus)
• Fever not caused by infection

What does lymphoma-related itching feel like?

The itching associated with Hodgkin lymphoma is characteristically diffuse (affecting the whole body) and occurs without any visible skin rash. It tends to be particularly bothersome in warm environments. That said, itching with these characteristics can also be caused by many other, far more common conditions. It is not in itself a definitive sign of lymphoma.

Can lymph nodes remain swollen permanently?

Lymph node swelling can persist for a long time, particularly when caused by ongoing infectious or inflammatory processes. Lymph nodes that remain enlarged for more than two weeks without an obvious cause should always be medically assessed.

What does it mean to have “reactive” lymph nodes that won’t go down?

Reactive lymph nodes are lymph nodes that have enlarged in response to an immune stimulus, typically an infection or inflammation. While they usually shrink as the triggering condition resolves, they can remain palpable for months or even years, especially if an underlying condition continues to stimulate the immune system. Persistent reactive lymphadenopathy should be evaluated by a physician to exclude serious underlying causes.

Is an enlarged lymph node always a sign of cancer?

Absolutely not. The vast majority of enlarged lymph nodes are caused by common infections, like upper respiratory tract infections, ear infections, or dental infections, or by other benign inflammatory conditions, not by cancer. However, lymph nodes that are persistently enlarged (more than 2 weeks), growing, very firm, fixed (not mobile), or accompanied by systemic symptoms (fever, night sweats, weight loss, fatigue) warrant medical evaluation without delay.

Can Hodgkin lymphoma be missed on a complete blood count (CBC)?

Yes, it can. The CBC may be entirely normal, particularly in early-stage disease, because Hodgkin lymphoma does not always alter the blood cell counts. This is especially true before bone marrow involvement occurs. This is one reason why a biopsy of an enlarged lymph node is required to make the diagnosis: blood tests alone are not sufficient.

When should I see a doctor about swollen lymph nodes?

You should consult a doctor if swollen lymph nodes:

• Persist for more than two weeks without a clear infectious cause
• Continue to grow in size
• Are very firm, rubbery, or fixed in position (unable to be moved under the skin)
• Are accompanied by B symptoms: fever, drenching night sweats, or unexplained weight loss
• Are associated with persistent fatigue, itching, or breathlessness

Early diagnosis is a key determinant of treatment outcome.

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Sources and Bibliography

• National Cancer Institute – Hodgkin Lymphoma
• SEER Cancer Statistics – Hodgkin Lymphoma
• AIEOP – Linfoma di Hodgkin (Pediatric Hodgkin Lymphoma)
• Connors JM, et al. “Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma”. New England Journal of Medicine. 2018;378:331–344. doi:10.1056/NEJMoa1708984
• Ansell SM. “Hodgkin Lymphoma: A 2020 Update on Diagnosis, Risk-Stratification, and Management”. American Journal of Hematology. 2020;95(8):978–989. doi:10.1002/ajh.25856
• Engert A, et al. “Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial”. The Lancet. 2012;379(9828):1791–1799.
• American Cancer Society – Hodgkin Lymphoma
• MedlinePlus – Hodgkin Lymphoma