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Hodgkin Lymphoma

(Hodgkin’s Disease)


Peter Martin

, MD, Weill Cornell Medicine;

John P. Leonard

, MD, Weill Cornell Medicine

Reviewed/Revised May 2022 | Modified Sep 2022
Topic Resources

Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms typically include painless lymphadenopathy, sometimes with fever, night sweats, unintentional weight loss, pruritus, splenomegaly, and hepatomegaly. Diagnosis is based on lymph node biopsy. Treatment is curative in most cases and consists of chemotherapy with or without other treatment modalities, including antibody-drug conjugates, immunotherapy, and radiation therapy.

In the US, about 8,000 new cases of Hodgkin lymphoma are diagnosed annually, and about 900 people die of the disease. The male:female ratio is 1.4:1. Hodgkin lymphoma is rare before age 10 and is most common between ages 15 and 40; a 2nd peak occurs in people > 60.

Pathophysiology of Hodgkin Lymphoma

Hodgkin lymphoma results from the clonal transformation of cells of B-cell origin, giving rise to pathognomic binucleated Reed-Sternberg cells.

Most patients also develop a slowly progressive defect in cell-mediated immunity (T-cell function) that, in advanced disease, contributes to common bacterial and unusual fungal, viral, and protozoal infections. Humoral immunity (antibody production) is depressed in advanced disease. Death can result from infection or progressive disease.

Symptoms and Signs of Hodgkin Lymphoma

Most patients with Hodgkin lymphoma present with painless cervical adenopathy. Although the mechanism is unclear, pain rarely may occur in diseased areas immediately after drinking alcoholic beverages, sometimes providing an early indication of the diagnosis.

Other manifestations develop as the disease spreads through the reticuloendothelial system, generally to contiguous sites. Intense pruritus refractory to usual therapies may occur early. Systemic symptoms include fever, night sweats, and loss of appetite resulting in unintentional weight loss (> 10% of body weight in previous 6 months), which are referred to as "B symptoms." B symptoms are significant to prognosis and staging because they may signify involvement of internal lymph nodes (mediastinal or retroperitoneal), viscera (liver), or bone marrow. Splenomegaly is often present; hepatomegaly is unusual. Pel-Ebstein fever (a few days of high fever regularly alternating with a few days to several weeks of normal or below-normal temperature) occasionally occurs. Cachexia is common as disease advances.

Bone involvement is often asymptomatic but may cause vertebral osteoblastic lesions (ivory vertebrae) and, rarely, pain with osteolytic lesions and compression fractures. Intracranial, gastric, and cutaneous lesions are rare and when present can suggest uncontrolled HIV-associated Hodgkin lymphoma.

Local compression by tumor masses often causes symptoms and signs, including

Epidural invasion that compresses the spinal cord may result in paraplegia. Horner syndrome and laryngeal paralysis may result when enlarged lymph nodes compress the cervical sympathetic and recurrent laryngeal nerves. Neuralgic pain follows nerve root compression.

Diagnosis of Hodgkin Lymphoma

  • Lymph node biopsy

  • FDG-PET/CT of chest, abdomen, and pelvis for staging

  • MRI if neurologic symptoms are present

Hodgkin lymphoma is usually suspected in patients with painless lymphadenopathy or mediastinal adenopathy detected on physical examination or routine chest x-ray (1 Diagnosis reference Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more Diagnosis reference ). Similar lymphadenopathy can result from viral infections such as infectious mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more Infectious Mononucleosis (EBV) or cytomegalovirus (CMV) infection Cytomegalovirus (CMV) Infection Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. A syndrome of infectious mononucleosis that lacks severe pharyngitis is common. Severe... read more , toxoplasmosis Toxoplasmosis Toxoplasmosis is infection with Toxoplasma gondii. Symptoms range from none to benign lymphadenopathy, a mononucleosis-like illness, to life-threatening central nervous system (CNS) disease... read more Toxoplasmosis , non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more Non-Hodgkin Lymphomas , or leukemia Overview of Leukemia Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms... read more . Similar chest x-ray findings can result from lung cancer Lung Carcinoma Lung carcinoma is the leading cause of cancer-related death in men and women worldwide. About 85% of cases are related to cigarette smoking. Symptoms can include cough, chest discomfort or pain... read more Lung Carcinoma , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis , or tuberculosis Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more Tuberculosis (TB) . Evaluation of a mediastinal mass Diagnosis Mediastinal masses are caused by a variety of cysts and tumors; likely causes differ by patient age and location of the mass (anterior, middle, or posterior mediastinum). They may be asymptomatic... read more is discussed elsewhere.

Chest x-ray or physical examination abnormalities should be confirmed with CT or positron emission tomography (PET) scan of the chest in order to choose the most efficient biopsy procedure. If only mediastinal nodes are enlarged, mediastinoscopy, video-assisted thoracoscopy (VATS), or a Chamberlain procedure (a limited left anterior thoracostomy allowing biopsy of mediastinal lymph nodes inaccessible by cervical mediastinoscopy) may be indicated. CT-guided core needle biopsy may also be considered; fine-needle aspiration is often inadequate for the diagnosis of Hodgkin lymphoma.

Biopsy reveals Reed-Sternberg cells (large, binucleated cells) in a characteristically heterogeneous cellular infiltrate, consisting of histiocytes, lymphocytes, monocytes, plasma cells, and eosinophils. Classic Hodgkin lymphoma has 4 histopathologic subtypes (see table Histopathologic Subtypes of Hodgkin Lymphoma Histopathologic Subtypes of Hodgkin Lymphoma (WHO Classification) Histopathologic Subtypes of Hodgkin Lymphoma (WHO Classification) ); there is also a nodular lymphocyte-predominant type that represents only about 5% of all Hodgkin lymphoma cases. Certain antigens on Reed-Sternberg cells may help differentiate Hodgkin lymphoma from non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more Non-Hodgkin Lymphomas , and classic Hodgkin lymphoma from the nodular lymphocyte-predominant type.

Complete blood count (CBC) with differential, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and kidney function and liver tests are generally done. Test results may be abnormal but are nondiagnostic.

CBC may show slight polymorphonuclear leukocytosis. Lymphocytopenia may occur early and is an adverse prognostic factor. Eosinophilia is present in about 20% of patients, and thrombocytosis may be present. Anemia, often microcytic, usually develops with advanced disease. In advanced anemia, defective iron reutilization is characterized by low serum iron, low iron-binding capacity, an elevated serum ferritin, and increased bone marrow iron. Pancytopenia is occasionally caused by bone marrow invasion, more commonly in the lymphocyte-depleted subtype.

Elevated serum alkaline phosphatase levels may be present, but elevations do not always indicate bone marrow or liver involvement. Increases in leukocyte alkaline phosphatase, serum haptoglobin, and other acute-phase reactants usually reflect the presence of inflammatory cytokines from active Hodgkin lymphoma. These tests are sometimes done to evaluate non-specific symptoms and can suggest Hodgkin lymphoma; they are not done on all lymphoma patients. Erythrocyte sedimentation rate (ESR), an indirect marker of inflammation, is more commonly ordered and predicts a less favorable outcome.

A combined fluorodeoxyglucose (FDG)-PET/CT scan of the chest, abdomen, and pelvis is the imaging study of choice for staging Hodgkin lymphoma (see below Staging Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more Staging ). Bone lesions are detected more commonly with the use of FDG-PET imaging. If combined FDG-PET/CT is not available, a contrast-enhanced CT scan of the chest, abdomen, and pelvis is done.

Other tests are done depending on findings (eg, MRI for symptoms of cord compression). A bone marrow biopsy is usually only done if a PET/CT scan is not obtained and if the findings might alter management. Other recommended tests include cardiac ejection fraction if the use of anthracyclines is anticipated and pulmonary function tests if bleomycin is being considered.



After diagnosis, stage is determined to guide therapy. The commonly used Lugano staging system (see table Lugano Staging of Hodgkin and Non-Hodgkin Lymphomas Lugano Staging of Hodgkin Lymphoma and Non-Hodgkin Lymphoma Lugano Staging of Hodgkin Lymphoma and Non-Hodgkin Lymphoma ) incorporates

Laparotomy is not required for staging.


Diagnosis reference

  • 1. Cheson BD, Fisher RI, Barrington SF, et al: Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol 32(27):3059-3068, 2014.

Prognosis for Hodgkin Lymphoma

About 85 to 90% of patients with limited-stage classic Hodgkin lymphoma are cured compared with 75 to 80% of patients with advanced-stage disease. Limited-stage disease is frequently subdivided into favorable and unfavorable prognostic groups. Unfavorable disease is based on risk factors, for example

  • Presence of bulky disease

  • 4 nodal sites involved

  • Age > 50 years

  • Erythrocyte sedimentation rate (ESR) > 50 mm/hour with no B symptoms or > 30 mm/hour with B symptoms (weight loss, fever, or night sweats)

Risk factors in advanced-stage Hodgkin lymphoma include

  • Male sex

  • Age > 45 years

  • Signs of tumor-induced inflammation (low albumin, anemia, leukocytosis, and lymphopenia)

However, selection of which risk factors to use in estimating prognosis is still subject to revision. Patients who do not achieve complete remission with treatment or who relapse within 12 months have a poor prognosis.

Treatment of Hodgkin Lymphoma

  • Chemotherapy

  • Antibody-drug conjugate (eg, brentuximab vedotin)

  • Immunotherapy (eg, immune checkpoint inhibitors)

  • Radiation therapy

  • Sometimes autologous stem cell transplantation

The choice of treatment modality is complex and depends on the precise stage of disease. Before treatment and when applicable, men should be offered sperm banking, and women should discuss options to preserve fertility with their oncologists and a fertility specialist.

Initial treatment

Limited-stage disease is generally treated with an abbreviated chemotherapy regimen of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiation therapy Radiation Therapy for Cancer Radiation therapy can cure many cancers (see also Overview of Cancer Therapy), particularly those that are localized or that can be completely encompassed within a radiation field. Radiation... read more . In patients with bulky mediastinal disease, chemotherapy may be of longer duration or of a different type, and radiation therapy is often included.

Advanced-stage disease may be treated based on the findings of one of two large randomized trials. In the RATHL (Response-Adapted Therapy in Advanced Hodgkin Lymphoma) trial, patients were treated with ABVD, and those who had a negative PET scan after 2 cycles received 4 additional cycles with AVD (no bleomycin), while those who had a positive PET scan were escalated to BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [ 1 Treatment references Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more Treatment references ]). In the ECHELON-1 trial, patients treated with AVD plus the anti-CD30 antibody-drug conjugate brentuximab vedotin had superior outcomes to patients treated with ABVD, with higher-risk younger patients appearing to benefit more (2, 3 Treatment references Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more Treatment references ). Bleomycin is generally avoided in patients >60 years due to increased risk of pulmonary toxicity, and optimal management of older or frail patients is not standardized.

Subsequent treatment

Multiple second-line chemotherapy regimens are considered acceptable for patients who are not cured with first-line therapy. For patients who achieve a good response to second-line therapy, high-dose chemotherapy and autologous stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more should be considered, while non-responders may be candidates for subsequent lines of therapy or allogeneic stem cell transplantation.

Brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab can be used for treatment of patients with Hodgkin lymphoma who have received at least 2 prior forms of therapy but are increasingly being used in second-line regimens.

Complications of treatment

Posttreatment surveillance

All patients who are not PET-negative at the end of induction therapy should have a biopsy or be followed closely with serial imaging; if residual disease is present, additional treatment is necessary. Once in remission, patients should be followed for signs and symptoms of relapse for 5 years. Those with manifestations of relapse, defined as reappearance of disease at sites of prior disease or at new sites, should have imaging with PET/CT or CT alone. Routine, scheduled imaging in asymptomatic patients is not mandatory. For a schedule of posttreatment surveillance, see table Hodgkin Lymphoma Posttreatment Surveillance Hodgkin Lymphoma Posttreatment Surveillance Hodgkin Lymphoma Posttreatment Surveillance .


Treatment references

  • 1. Johnson P, Federico M, Kirkwood A, et al: Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med 374(25):2419– 2429, 2016.

  • 2. Connors JM, Jurczak W, Straus DJ, et al: Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med 378(4):331–344, 2018. Epub 2017 Dec 10.

  • 3. Straus DJ, Długosz-Danecka M, Connors JM, et al: Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol 8(6):e410–e421, 2021. doi: 10.1016/S2352-3026(21)00102-2

Key Points

  • Hodgkin lymphoma is of B cell origin.

  • Patients usually present with painless lymphadenopathy or with incidental cervical or mediastinal adenopathy discovered on chest x-ray or physical examination.

  • Biopsy shows pathognomonic, binucleated Reed-Sternberg cells.

  • Most patients are cured using combination chemotherapy and sometimes additional systemic therapies or radiation therapy.

  • Subsequent therapeutic options include high-dose chemotherapy, autologous stem cell transplantation, or brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab.

More Information

The following is an English language resource that provides information for clinicians and support and information for patients. THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Drug Name Select Trade
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
Adriamycin, Adriamycin PFS, Adriamycin RDF, Rubex
Etopophos, Toposar, VePesid
Cyclophosphamide, Cytoxan, Neosar
Oncovin, Vincasar PFS
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
Mustargen, VALCHLOR
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