Oncology · Lymphoma
The facts most likely to be tested
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The hallmark histologic finding of Hodgkin Lymphoma is the Reed-Sternberg cell, which is a large, multinucleated cell with owl-eye inclusions.
Patients frequently present with a painless, rubbery lymphadenopathy in the cervical or supraclavicular region, often exacerbated by alcohol-induced pain.
Systemic B symptoms, including unexplained fever, night sweats, and weight loss, are critical prognostic indicators and are associated with a worse outcome.
The disease follows a bimodal age distribution, with peaks occurring in young adulthood (ages 15–35) and in older adults (over age 55).
Diagnosis is confirmed via excisional lymph node biopsy, as fine-needle aspiration is insufficient to evaluate the nodular architecture.
The Ann Arbor staging system is used to determine the extent of disease, which dictates the intensity of chemotherapy (ABVD, or A+AVD/N-AVD for advanced stage) and radiation therapy.
Long-term survivors of Hodgkin Lymphoma are at significantly increased risk for secondary malignancies, particularly breast cancer and lung cancer, due to prior radiation exposure.
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A 24-year-old male presents to the clinic with a two-month history of a painless, rubbery mass in his left neck. He reports a 10-pound unintentional weight loss and drenching night sweats over the same period. He notes that the mass becomes tender after he consumes a glass of wine at dinner. Physical examination reveals a 3 cm supraclavicular lymph node and no hepatosplenomegaly.
What is the most likely diagnosis?
Hodgkin Lymphoma
The patient's presentation of B symptoms, painless cervical lymphadenopathy, and the classic finding of alcohol-induced pain strongly points to Hodgkin Lymphoma.
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Etiology / Epidemiology
Bimodal age distribution (20s and >50s). Associated with Epstein-Barr virus infection.
Clinical Manifestations
Painless cervical/supraclavicular lymphadenopathy and Pel-Ebstein fever.
Diagnosis
Excisional lymph node biopsy showing Reed-Sternberg cells.
Treatment
ABVD regimen (Adriamycin, Bleomycin, Vinblastine, Dacarbazine); for advanced stage, bleomycin-free A+AVD (brentuximab vedotin) or N-AVD (nivolumab, FDA-approved 2026) are standard options.
Prognosis
Highly curable; 80-90% 5-year survival rate in early stages.
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Epidemiology & Etiology
Bimodal distribution peaks in young adults (20-30) and older adults (>50). Strong association with Epstein-Barr virus (EBV) in up to 50% of cases. Increased risk in patients with HIV or history of immunosuppression.
Pertinent Anatomy
Typically originates in a single lymph node chain, most commonly the cervical or supraclavicular nodes. Spreads in a predictable, contiguous fashion to adjacent lymph node groups.
Pathophysiology
Malignant transformation of B-lymphocytes leads to the formation of Reed-Sternberg cells. These cells secrete cytokines that recruit inflammatory cells, creating the characteristic inflammatory milieu. The disease is defined by the presence of these cells in a background of reactive lymphocytes.
Clinical Manifestations
Painless, rubbery lymphadenopathy is the hallmark. Patients may present with B symptoms: fever, night sweats, and weight loss >10%. Alcohol-induced pain at the site of lymphadenopathy is a rare but highly specific finding. Pel-Ebstein fever (cyclic fever) is a classic, though uncommon, presentation.
Diagnosis
Excisional lymph node biopsy is the preferred diagnostic procedure. Histology demonstrates Reed-Sternberg cells (large, binucleated or multinucleated cells with an 'owl-eye' appearance) that are CD15+ and CD30+ and characteristically CD20- and CD45-. PET/CT scan is recommended for staging (Lugano 2014) to assess metabolic activity and disease extent, and interim PET after 2 cycles, scored by the Deauville 5-point scale, drives response-adapted escalation or de-escalation of therapy.
Treatment
ABVD remains a standard regimen, particularly for early-stage disease; for advanced-stage (III-IV) disease, brentuximab vedotin + AVD (A+AVD) and nivolumab + AVD (N-AVD) are standard first-line options, with N-AVD FDA-approved in March 2026 (age >=12) after superior PFS vs A+AVD in SWOG S1826. Bleomycin carries a risk of pulmonary fibrosis, requiring baseline and serial pulmonary function tests. Radiation therapy is often used as an adjunct in localized disease. Secondary malignancies are a long-term concern for survivors.
Prognosis
Highly curable with modern chemotherapy and radiation. 80-90% 5-year survival rate. Long-term survivors require monitoring for cardiovascular disease and secondary cancers (breast, lung) due to prior radiation exposure.
Differential Diagnosis
Non-Hodgkin Lymphoma: usually presents with extranodal involvement and non-contiguous spread
Infectious Mononucleosis: acute onset with pharyngitis and positive heterophile antibody
Tuberculosis: associated with night sweats and pulmonary findings on CXR
Sarcoidosis: bilateral hilar adenopathy without Reed-Sternberg cells
Metastatic Carcinoma: usually older patients with a known primary site