Definition, Etiology, PathogenesisTop
Hodgkin lymphoma (HL) is a form of lymphoma in which a small number of malignant B cells (called Reed-Sternberg cells and Hodgkin cells) reside in an abundant heterogeneous background of nonneoplastic inflammatory cells. The etiology of HL is unknown. Most patients are young adults. Unique clinicopathologic features and treatment requirements differentiate it from other lymphomas (called non-Hodgkin lymphomas [NHLs]).
Clinical Features and Natural HistoryTop
1. General symptoms: Nonspecific symptoms (B symptoms: Table 9.4-3; in ~30% of patients). Sometimes patients have pruritus or pain in the lymph nodes after consumption of alcohol.
2. Lymphadenopathy: Lymph nodes are painless. The most commonly involved nodes are supradiaphragmatic nodes: cervical and mediastinal (60%-80% of patients); as well as axillary nodes (20%-40% of patients). Subdiaphragmatic inguinal and retroperitoneal nodes are affected less frequently.
3. Symptoms related to lymphadenopathy:
1) Mediastinal mass: Dyspnea, cough. Extremely severe lymphadenopathy may cause superior vena cava syndrome.
2) Retroperitoneal lymph nodes: Abdominal discomfort, urine retention, flatulence, constipation, gastrointestinal obstruction in advanced disease.
4. Extranodal lesions: Hepatomegaly, splenomegaly; extralymphatic lesions in bones kidneys, uterus, ovaries, urinary bladder, skin, central nervous system, and testes. Unlike in NHL, involvement of the Waldeyer ring (pharyngeal lymphoid ring), gastrointestinal tract, liver, and bone marrow is uncommon.
5. Natural history: Early HL spreads locally to adjacent regions. In advanced disease, hematogenous spread to remote lymphatic regions and internal organs occurs. In untreated patients 5-year survival rates are ~5%.
6. Staging: The Ann Arbor HL classification with Lugano (2014) modification (see Table 9.4-3).
7. Histologic classification of HL (World Health Organization, 2016):
1) Classical HL includes nodular sclerosis HL (NSHL) (70%-80% of HL cases), mixed-cellularity HL (MCHL), lymphocyte-depleted HL (LDHL), and lymphocyte-rich HL (LRHL). Most patients present with early disease, which is associated with upper cervical lymphadenopathy, usually without constitutional symptoms.
2) Nodular lymphocyte-predominant HL (NLPHL) is observed in ~5% of patients with HL; it affects peripheral lymph nodes (usually in one lymphatic region only). The course is usually very slow, with no clinical progression over many years. Patients with relapse have a good response to treatment.
1. Complete blood count (CBC): Nonspecific abnormalities may include elevated neutrophil and/or eosinophil counts, lymphocytopenia, thrombocytopenia, normocytic anemia (the usual pathogenesis is that of anemia of chronic disease or less frequently autoimmune hemolytic anemia).
2. Bone marrow biopsy: Cells typical for HL are found in ~6% of patients.
3. Histologic and immunohistochemical examination of an involved lymph node (examination of a complete node is recommended) or other involved tissues.
4. Other laboratory tests: Abnormalities may include elevated serum lactate dehydrogenase or alkaline phosphatase, increased erythrocyte sedimentation rate (ESR), elevated gamma-globulin and beta2-microglobulin levels, and low serum albumin levels.
5. Imaging studies: Contrast-enhanced computed tomography (CT) (of the neck, chest, abdomen, and lesser pelvis), chest radiography, and positron emission tomography (PET)-CT.
6. Other studies: Pretreatment electrocardiography (ECG), echocardiography, and pulmonary function tests, HIV and hepatitis testing, pregnancy test in younger women.
Diagnosis is based on histologic and immunohistochemical examination of an involved lymph node or other involved tissue specimens.
Adverse prognostic factors in clinical stages I and II: Large mediastinal mass (>1/3 of the maximum horizontal chest diameter), ESR >50 mm/h (>30 mm/h if B symptoms are present), age ≥50 years, ≥3 nodal areas, extranodal disease.
Adverse prognostic factors in clinical stages III and IV: Serum albumin level <4 g/dL, hemoglobin <10.5 g/dL, male sex, age ≥45 years, clinical stage IV, white blood cell count ≥15×109/L, lymphocytopenia <0.6×109/L or <8%.
Other causes of lymphadenopathy. Classical HL (especially NSHL) should be differentiated from primary mediastinal large B-cell lymphoma.
1. First-line treatment: Chemotherapy (ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine] or BEACOPPesc [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone]), usually in combination with radiotherapy of residual lesions or of the primarily involved field.
2. Progression or relapse: In most cases salvage chemotherapy regimens are used and followed by high-dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT) with or without radiotherapy. In patients not eligible for HSCT or those with late relapses (after 12 months), combination treatment (chemotherapy with radiotherapy) should be considered. In patients not eligible for intensive chemotherapy, consider palliative chemotherapy and/or radiotherapy, and after ≥2 lines of chemotherapy, consider brentuximab vedotin. Options in case of relapse after autologous HSCT include allogeneic HSCT, clinical trials, brentuximab vedotin, checkpoint (PD-1) inhibitors (nivolumab, pembrolizumab), and palliative treatment.
1. Stage IA or IIA disease (excluding cases with >2 involved sites or extensive infradiaphragmatic disease): Surgical resection of the involved lymph nodes followed by radiotherapy.
2. More advanced disease: Chemotherapy (ABVD, CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], CVP [cyclophosphamide, vincristine, prednisone]) ± rituximab ± radiotherapy.
3. Relapse: Radiotherapy (local relapse), combination chemotherapy (symptomatic advanced-stage relapse), watch-and-wait approach (asymptomatic advanced-stage relapse).
Using current treatment strategies, 80% to 90% of patients with HL are cured. In relapsed or refractory patients undergoing autologous HSCT, cure is possible in ~50% of cases.