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Hodgkin Lymphoma

(Hodgkin’s Disease)


Peter Martin

, MD, Weill Cornell Medicine;

John P. Leonard

, MD, Weill Cornell Medicine

Last full review/revision Jun 2020| Content last modified Jun 2020
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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.

(See also Overview of Lymphoma.)

In the US, about 8,000 new cases of Hodgkin lymphoma are diagnosed annually. 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.

The cause is unknown, but genetic susceptibility (eg, family history) and environmental associations (eg, occupation, such as woodworking); history of treatment with phenytoin, radiation therapy, or chemotherapy; infection with Epstein-Barr virus [EBV], Mycobacterium tuberculosis, herpesvirus type 6, HIV) play a role. Risk is slightly increased in people with

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 or axillary 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. Constitutional symptoms include fever, night sweats, and loss of appetite resulting in unintentional weight loss (> 10% of body weight in previous 6 months), which 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 produce 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, including

  • Jaundice secondary to intrahepatic or extrahepatic bile duct obstruction

  • Leg edema (lymphedema) secondary to lymphatic obstruction in the pelvis or groin

  • Severe dyspnea and wheezing secondary to tracheobronchial compression due to mediastinal disease

  • Lung cavitation or mass secondary to infiltration of lung parenchyma, which may simulate lobar consolidation or bronchopneumonia

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

  • Sometimes bone marrow biopsy

Hodgkin lymphoma is usually suspected in patients with painless lymphadenopathy or mediastinal adenopathy detected on physical examination or routine chest x-ray (1). Similar lymphadenopathy can result from viral infections such as infectious mononucleosis (EBV) or cytomegalovirus (CMV) infection, toxoplasmosis, non-Hodgkin lymphoma, or leukemia. Similar chest x-ray findings can result from lung cancer, sarcoidosis, or tuberculosis. Evaluation of a mediastinal mass 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 thorocoscopy (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); 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, 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.

Hypersplenism may occur in patients with marked splenomegaly.

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). 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.


Histopathologic Subtypes of Hodgkin Lymphoma (WHO Classification)

Histologic Type

Morphologic Appearance

Tumor Cell Immunophenotype



Nodular sclerosis

Dense fibrous tissue surrounding nodules of Hodgkin tissue

CD15+, CD30+, CD20–


Mixed cellularity

A moderate number of Reed-Sternberg cells with a mixed background infiltrate

CD15+, CD30+, CD20–



Few Reed-Sternberg cells

Many B cells

CD15+, CD30+, CD20–



Numerous Reed-Sternberg cells

Extensive fibrosis

CD15+, CD30+, CD20–


Nodular lymphocyte-predominant

Few neoplastic cells (lymphocytic or histiocytic cells or both)

Many small B cells

Nodular pattern

CD15–, CD30–, CD20+, EMA+


EMA = epithelial membrane antigen.


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

  • Symptoms

  • Physical examination findings

  • Results of imaging tests, including CT of the chest, abdomen, and pelvis, and functional imaging with FDG-PET

  • Sometimes bone marrow biopsy

Laparotomy is not required for staging.


Lugano Staging of Hodgkin Lymphoma and Non-Hodgkin Lymphoma



Limited stage


In 1 lymph region only or single extranodal site


In 2 lymph regions on the same side of the diaphragm, and may include limited contiguous extranodal involvement

Advanced stage


In the lymph nodes, spleen, or both and on both sides of the diaphragm


Extranodal involvement (eg, bone marrow, lungs, liver)

* Subclassification E indicates single extranodal site involvement in stage I or limited contiguous extranodal involvement in stage II. Involvement of non-contiguous extranodal sites is considered stage IV. Hodgkin lymphoma stages can be further classified by A to indicate the absence or B to indicate the presence of systemic symptoms (weight loss, fever, or night sweats). Bulky disease is defined as a single nodal mass of 10 cm in maximum dimension based on CT imaging. Bulky disease in limited-stage Hodgkin lymphoma is occasionally defined as ≥ 7 cm as opposed to the traditional 10-cm cutoff.

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 of 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, the presence of bulky disease, ≥ 4 nodal sites involved, age > 50, and 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, and signs of tumor-induced inflammation (low albumin, anemia, leukocytosis, and lymphopenia). However, which risk factors are recommended 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. 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 prednisone1). 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).

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 should be considered.

Brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab are used for treatment of patients with Hodgkin lymphoma who have received at least 2 prior forms of therapy.

Complications of treatment

Chemotherapy, particularly with drugs such as the alkylating agents (mechlorethamine, cyclophosphamide, procarbazine), doxorubicin, and etoposide, increase the risk of leukemia between years 3 and 10 post-therapy. Radiation therapy carries increased risk of malignant solid tumors (eg, breast, gastrointestinal, lung, thyroid, soft tissue). Doxorubicin as well as mediastinal radiation increases the risk of cardiomyopathy, coronary atherosclerosis and valvular heart disease. Bleomycin can induce lung injury, which can be severe and rarely fatal.

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 should have imaging with PET/CT or CT alone. Routine, scheduled imaging in asymptomatic patients is no longer considered mandatory. For a schedule of posttreatment surveillance, see table Hodgkin Lymphoma Posttreatment Surveillance.


Hodgkin Lymphoma Posttreatment Surveillance



History and physical examination, complete blood count with differential, creatinine, liver tests

First 1–2 years, every 3‒6 months

Years 2‒3, every 6 months

> 3 years, every 12 months


Anytime during follow-up if symptoms or findings arise

Thyroid-stimulating hormone levels

Every 6 months after radiation to neck

Breast cancer screening

Annually beginning at 8–10 years after treatment or at age 40 if radiation therapy above the diaphragm was given

Include breast MRI if radiation therapy administered at age ≤ 30 years

Treatment references

Key Points about Hodgkin Lymphoma

  • 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 exam.

  • Biopsy shows pathognomonic, binucleated Reed-Sternberg cells.

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

  • Brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab are newer therapies that are rapidly changing the landscape of therapy for Hodgkin lymphoma.

More Information about Hodgkin Lymphoma

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.

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