Hodgkin Lymphoma: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Hodgkin lymphoma (HL) is a B-cell malignancy defined by the presence of pathognomonic Reed-Sternberg cells — large binucleated or multinucleated cells arising from germinal center B-cells that have lost their B-cell identity and aberrantly activate NF-κB and JAK-STAT signaling. Approximately 8,500 new US cases are diagnosed annually. HL has a characteristic bimodal age distribution: a first peak in young adults aged 20–34 years, and a second peak in adults over 55. Classical HL (CHL) comprises 95% of cases and is subdivided into four histological subtypes: nodular sclerosis (most common, 65–70%), mixed cellularity (20–25%), lymphocyte-rich (5%), and lymphocyte-depleted (rare). Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents 5% of cases and behaves more like an indolent B-cell lymphoma. HL is one of the most curable of all cancers, with an overall 5-year survival of approximately 87%, and early-stage disease achieving cure rates greater than 95%.

Epstein-Barr virus (EBV) is the most clearly established etiological factor, particularly for the mixed cellularity and lymphocyte-depleted subtypes and for HL in immunocompromised individuals and older patients. EBV-positive HL accounts for approximately 40% of all classical HL cases in developed countries. Prior infectious mononucleosis (glandular fever) from EBV doubles the lifetime risk of HL, with most attributable cases occurring within 5 years of acute mononucleosis. HIV infection increases HL risk approximately 10-fold, and HIV-associated HL tends to be EBV-positive and of mixed cellularity subtype. HLA associations and familial clustering (sibling pairs with concordant diagnosis) suggest a genetic predisposition component. Immunosuppression from organ transplantation or autoimmune disease treatment also elevates risk. No chemical or occupational carcinogen has been definitively confirmed as a causative agent.

The most common presentation is painless, firm, rubbery cervical (neck) or supraclavicular lymphadenopathy, present in over 70% of patients at diagnosis; axillary and inguinal lymphadenopathy are less common. B-symptoms — unexplained fever exceeding 38°C, drenching night sweats requiring clothing or linen change, and unexplained weight loss exceeding 10% of body weight over the preceding 6 months — occur in approximately 40% of patients and indicate more extensive disease. Large mediastinal lymphadenopathy causes cough, dyspnea, or superior vena cava syndrome. Pruritus (generalized itching) may precede diagnosis by months and is considered a systemic symptom. A rare but characteristic symptom is alcohol-induced pain in involved lymph nodes within minutes of drinking alcohol. Fatigue and reduced exercise tolerance are common. Splenomegaly occurs in approximately 30% of cases.

Excisional lymph node biopsy is strongly preferred over core needle biopsy to provide adequate tissue for immunohistochemistry and lymph node architecture assessment. Reed-Sternberg cells are CD30-positive, CD15-positive, and CD45-negative (unlike almost all other lymphomas). EBV status is assessed by EBER in situ hybridization or LMP-1 immunohistochemistry. NLPHL shows CD20+ lymphocyte-predominant 'popcorn cells' expressing CD45, CD79a, and OCT2 but lacking CD30 and CD15. PET-CT with 18F-FDG is the gold standard for staging — HL is uniformly FDG-avid, enabling detection of nodal and extranodal involvement. Lugano modification of Ann Arbor staging (Stage I–IV, A/B suffix for B-symptoms) guides treatment. Interim PET-CT after 2 cycles of ABVD (using Deauville 5-point scale) guides response-adapted therapy. International Prognostic Score (IPS, 0–7) stratifies advanced-stage disease risk. Bone marrow biopsy is replaced by PET-CT in most patients.

Early-stage favorable HL (Stage I–II, no bulk, no B-symptoms): 2 cycles ABVD plus 20 Gy involved-site radiation therapy (ISRT), or escalated to 4 cycles ABVD plus ISRT if interim PET is positive. Early-stage unfavorable (Stage I–II with adverse features): 4 cycles ABVD plus 30 Gy ISRT; HD response-adapted escalation to eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Advanced-stage (III–IV): BV-AVD (brentuximab vedotin 1.2 mg/kg plus doxorubicin, vinblastine, dacarbazine, cycles 1–6) is preferred over ABVD based on ECHELON-1 trial (improved 5-year PFS 82.1% vs 75.3%) while avoiding bleomycin pulmonary toxicity. PET-adapted de-escalation is standard: PET-negative after 2 cycles may omit ISRT for early-stage disease. Relapsed/refractory HL: brentuximab vedotin (ORR 75%), nivolumab or pembrolizumab (ORR 65–70%); high-dose chemotherapy (BEAM) plus autologous SCT for chemosensitive relapse; allogeneic SCT for multiply relapsed disease.

Five-year overall survival is approximately 87% across all stages. Early-stage disease (I–II) achieves cure rates exceeding 95% with modern PET-adapted therapy. Advanced-stage disease (III–IV) has a 5-year OS of 75–80% with ABVD or BV-AVD. PET-negative after 2 cycles (Deauville score 1–2) identifies patients with an excellent prognosis who may de-escalate radiation. Long-term survivors face treatment-related late effects including secondary malignancies (breast cancer from mantle radiation, lung cancer from smoking plus radiation), cardiovascular disease (accelerated coronary artery disease from mediastinal radiation), hypothyroidism, and pulmonary fibrosis from bleomycin. The prognosis for Hodgkin Lymphoma: Causes, Symptoms, Diagnosis and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.

No established primary prevention exists for Hodgkin lymphoma. Effective HIV antiretroviral therapy (ART) reduces the incidence of HIV-associated HL by maintaining CD4 counts. EBV vaccination is under active development (mRNA-based LMP2 vaccines in trials) and may eventually reduce EBV-related HL incidence. Long-term HL survivors require structured surveillance for secondary cancers and cardiovascular complications from treatment. Women who received breast-field radiation before age 30 require annual mammogram plus breast MRI beginning at age 25 or 8 years after radiation (whichever is later). Cardiovascular risk factor optimization (blood pressure, cholesterol, smoking cessation) reduces risk of radiation-accelerated coronary artery disease. All HL survivors should receive counseling about late effects during transition to long-term follow-up care.

Seek prompt evaluation for painless, persistent lymph node swelling in the neck, armpits, or groin that lasts more than 4 weeks and does not shrink after a course of antibiotics. Lumps that are firm, rubbery, non-tender, and progressively enlarging are particularly concerning and require biopsy evaluation. B-symptoms — unexplained fever, soaking night sweats, and weight loss of more than 10% of body weight over 6 months — combined with lymphadenopathy require urgent hematology-oncology referral. New-onset unexplained cough or breathlessness combined with a visible neck mass may indicate mediastinal lymphadenopathy from HL. Intense generalized itching (pruritus) without skin rash in a young adult should prompt blood tests and lymph node examination. Any person known to have HIV who develops new lymphadenopathy or B-symptoms should be evaluated for HIV-associated HL, as prognosis is best with early diagnosis and treatment.