II. Risk Factors

  1. Epstein-Barr Virus Related Infectious Mononucleosis history (1 case per 1000 persons)
  2. Family History of Hodgkin Lymphoma
    1. Same-sex sibling confers 10 fold risk
    2. Higher risk in monozygotic twins
  3. Immunocompromised conditions
    1. Human Immunodeficiency Virus infection (10 fold increased risk)

III. Epidemiology

  1. Second most common solid Hematologic Malignancy
    1. Most common is Non-Hodgkin's Lymphoma
    2. Accounts for one seventh of all Lymphomas
  2. Incidence: 8200 new cases per year in United States (2008)
  3. Age of onset
    1. Bimodal peaks: Age 15 to 34 years old and over age 60 years
    2. Rare under age 5

IV. Symptoms

  1. Painless lymph node enlargement
    1. Lymph node pain provoked by Alcohol is reported, but uncommon
  2. Dermatologic symptoms
    1. Pruritus
    2. Erythema Nodosum
    3. New-onset Eczema
    4. Mycosis Fungoides
  3. Miscellaneous symptoms
    1. Fatigue
    2. Abdominal Pain
  4. B Symptoms
    1. Periodic low grade fever and Night Sweats
    2. Cachexia

V. Signs

  1. Lymphadenopathy
    1. Firm to Rubbery, discrete, nontender nodes
    2. Nonsuppurative
  2. Hepatomegaly
  3. Splenomegaly

VI. Staging (Ann Arbor classification)

  1. Stage I
    1. I: Single Lymph Node region (I) or
    2. IE: One extranodal site
  2. Stage II
    1. II: Two or more lymph nodes on same side of diaphragm or
    2. IIE: Local extralymphatic extension and one or more lymph nodes on same side diaphragm
  3. Stage III
    1. III: Lymph nodes involve both sides diaphragm or
    2. IIIE: Lymph nodes on both sides of diaphragm and localized Spleen or extralymphatic involved
  4. Stage IV
    1. Diffuse or disseminated disease
    2. Liver or Bone Marrow involvement
  5. Modifier
    1. A: Asymptomatic
    2. B: Fever (>100 F), Night sweat, or weight loss (>10% in 6 months)

VII. Labs: Secondary (for staging)

VIII. Imaging (for staging)

  1. Chest XRay
    1. Anterior mediastinal or hilar Lymphadenopathy
    2. Osteosclerotic or osteoporotic lesions
  2. Ultrasound Liver and Spleen
  3. CT scan of Abdomen
  4. Bipedal lower extremity lymphangiography

IX. Diagnosis: Lymph node excisional or needle biopsy

  1. See Reed-Sternberg Cells
  2. Avoid biopsy of inguinal or axillary nodes due to super-imposed inflammation

X. Classification: Pathology (Histologic Types)

  1. Nodular Sclerosis (60-80% of classical Hodgkin Disease cases)
    1. More common in young adults and teens
    2. Overall good prognosis since it tends to present as localized disease (early stage)
  2. Mixed cellularity (15-30% of classical Hodgkin Disease cases)
    1. More frequent in third world countries and associated with HIV Infection
    2. Bimodal distribution: More common in children and in the elderly
    3. Worse prognosis due to its presentation at later stages
  3. Lymphocytic predominance (2-7% of classical Hodgkin Disease cases)
    1. Abundance of Reed-Sternberg Cells
    2. Overall good prognosis since it tends to present as localized disease (early stage)
  4. Lymphocyte depletion (1-6% of classical Hodgkin Disease cases)
    1. Paucity of cellular elements
    2. More common in the elderly
    3. Worse prognosis as presents at later stage
    4. Associated with retroperitoneal nodes and extranodal involvement, as well as symptoms
  5. Nodular Lymphocyte-predominant (3-8% of all Hodgkin Disease cases)
    1. Non-Classical Hodgkin's that lacks Reed-Sternberg Cells
    2. Characterized by atypical lymphocytic and histiocytic cells
    3. Overall good prognosis with localized disease with indolent course

XI. Management: Chemotherapy Regimens

  1. Protocol
    1. Given in 2 to 8 cycles as determined by staging listed below
  2. ABVD Regimen (standard regimen)
    1. Adriamycin (Doxorubicin)
    2. Bleomycin
    3. Vinblastine
    4. Dacarbazine
  3. Stanford V (experimental)
    1. Adriamycin (Doxorubicin)
    2. Bleomycin
    3. Vinblastine
    4. Mechlorethamine
    5. Vincristine
    6. Etoposide
    7. Prednisone
  4. BEACOPP regimen (experimental)
    1. Adriamycin (Doxorubicin)
    2. Bleomycin
    3. Vincristine
    4. Procarbazine
    5. Gemcitabine
    6. Prednisone
  5. MOPP regimen (no longer used, listed for historical purposes)
    1. Mechlorethamine
    2. Vincristine
    3. Procarbazine
    4. Prednisone
  6. Monoclonal Antibodies (experimental)
    1. Anti-CD30 antibodies (SGN-30, MDX-060)
    2. Anti-CD20 antibodies (Rituximab)

XII. Management: Approach

  1. Stage IA and Nodular Lymphocyte Predominant (non-classical)
    1. Involved Region Radiation Therapy (35 Gy)
  2. Classical Hodgkin (and non-classical above Stage IA)
    1. Involved Region Radiation Therapy (30-35 Gy)
      1. In stage III-IV, radiation directed at sites of bulky disease up to 10 cm diameter
    2. Combination Chemotherapy of ABVD Regimen (see above)
      1. Stage I-II Favorable: 2-3 cycles at 28 day intervals
      2. Stage I-II Unfavorable: 4-6 cycles at 28 day intervals
      3. Stage III-IV: 6-8 cycles as 28 day intervals

XIII. Management: Monitoring following treatment

  1. Clinic visits
    1. Year 1-2: Every 3 months
    2. Year 3: Every 4 months
    3. Year 4-5: Every 6 months
    4. After year 5: Annually
  2. Labs: Follow local protocols (controversial due to low yield)
    1. Consider at each visit
      1. Complete Blood Count
      2. Erythrocyte Sedimentation Rate
      3. Chemistry panel (e.g. chem8)
    2. Consider annually in first 5 years (if neck Radiation Therapy)
      1. Thyroid Stimulating Hormone (TSH)
  3. Imaging: Follow local protocols (controversial due to low yield)
    1. Chest XRay or Chest CT every 6-12 months for 2 years
    2. Abdomen and Pelvis CT every 6-12 months for 2 years
  4. Cardiovascular screening
    1. Lipid panel annually
    2. Consider Stress Imaging and Echocardiogram every 10 years

XIV. Prevention: Secondary

  1. Routine Health Maintenance and monitoring as described above
  2. Tobacco Cessation
  3. Vaccination
    1. Influenza Vaccine annually
    2. See Asplenism for additional Vaccinations if indicated

XV. Prognosis: General

  1. Prior to Chemotherapy had been uniformly fatal
  2. Large majority are now cured with Chemotherapy
  3. Overall survival rates after treatment
    1. Post-treatment by 1 year: 94% survival rate
    2. Post-treatment by 5 years: 85% survival rate
    3. Post-treatment by 10 years: 82% survival rate
    4. Post-treatment by 15 years: 74% survival rate
    5. Post-treatment by 20 years: 63% survival rate
  4. Five years survival rates based on staging (see above)
    1. Stage I: 90-95%
    2. Stage 2: 90-95%
    3. Stage 3: 85-90%
    4. Stage 4: 80%

XVI. Prognosis: Localized Hodgkin Lymphoma

  1. Adverse Factors
    1. Mediastinal mass ratio >0.33 (N) or >0.35 (E/G)
    2. Nodal mass >10 cm (N)
    3. Age >50 years (E)
    4. Nodal regions >2 (G) or >3 (E)
    5. Increased Erythrocyte Sedimentation Rate (E/G)
    6. B Symptoms of fever, Night Sweats and weight loss present (N)
  2. Legend
    1. North America study group including United States and Canada (N)
    2. European Organization for Research and Treatment of Cancer (E)
    3. German Hodgkin Study Group (G)

XVII. Prognosis: Advanced Hodgkin Lymphoma

  1. Based on International Prognostic Factors for Advanced Hodgkin Lymphoma (I)
  2. Risk Factors
    1. Stage IV Disease
    2. Male gender
    3. Age 45 years or older
    4. Hemoglobin <10.5 g/dl
    5. White Blood Cell Count >15,000/ul
    6. Lymphocyte Count <600/ul
    7. Albumin <4g/dl
  3. Interpretation: 5 year survival based on number of risk factors present
    1. No risk factors: 84%
    2. 1 risk factors: 77%
    3. 2 risk factors: 67%
    4. 3 risk factors: 60%
    5. 4 risk factors: 51%
    6. 5-7 risk factors: 42%

XVIII. Complications

  1. Secondary malignancy (related to Chemotherapy and radiation)
    1. Breast Cancer in women
      1. Follows latency of at least 10-15 years
      2. Higher risk with high dose radiation and age of treatment under 35
      3. Risk approaches 20% by age 45 years old
      4. Start annual Breast MRI and Mammogram 8-10 years after chest or axillary radiation (or by age 40 years)
    2. Lung Cancer
      1. Higher risk with Alkylating Agent exposure (old MOPP Chemotherapy protocols)
      2. Tobacco use compounds risk
    3. Leukemia (1-3% risk)
      1. Types: Acute Myeloid Leukemia, Large cell lympoma, Myelodysplastic Syndromes
      2. Higher risk with Alkylating Agent exposure (old MOPP Chemotherapy protocols)
        1. Lower risk with ABVD regimen used currently
    4. Thyroid Cancer
      1. Associated with prior neck irradiation
  2. Other adverse effects
    1. Cardiovascular disease
      1. Coronary Artery Disease (most common cardiovascular adverse effect)
        1. Associated with mediastinal radiation and Adriamycin exposure
      2. Cardiomyopathy
        1. Associated with Adriamycin exposure
        2. Increased risk in younger women and with higher Adriamycin doses
    2. Pulmonary disease
      1. Pulmonary fibrosis associated with Bleomycin use
    3. Hypothyroidism
      1. Typically occurs in first 5 years after treatment (can occur up to 20 years later)
    4. Premature Ovarian Failure
    5. Male Infertility
      1. Due to decreased spermatogenesis following Chemotherapy
      2. Lower risk with ABVD regimen
    6. Osteoporosis

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Ontology: Hodgkin Disease (C0019829)

Definition (MEDLINEPLUS)

Hodgkin disease is a type of lymphoma. Lymphoma is cancer of lymph tissue found in the lymph nodes, spleen, liver, and bone marrow. The first sign of Hodgkin disease is often an enlarged lymph node. The disease can spread to nearby lymph nodes. Later it may spread to the lungs, liver or bone marrow. The cause is unknown.

Hodgkin disease is rare. Symptoms include

  • Painless swelling of the lymph nodes in the neck, armpits, or groin
  • Fever and chills
  • Night sweats
  • Weight loss
  • Loss of appetite
  • Itchy skin

Doctors can diagnose Hodgkin disease with a biopsy. This involves removing and examining a piece of tissue under a microscope. Treatment varies depending on how far the disease has spread and often includes radiation therapy or chemotherapy.

The earlier the disease is diagnosed, the more effective the treatment. In most cases, Hodgkin disease can be cured.

NIH: National Cancer Institute

Definition (NCI_NCI-GLOSS) A cancer of the immune system that is marked by the presence of a type of cell called the Reed-Sternberg cell. The two major types of Hodgkin lymphoma are classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Symptoms include the painless enlargement of lymph nodes, spleen, or other immune tissue. Other symptoms include fever, weight loss, fatigue, or night sweats.
Definition (NCI) An obsolete term referring to Hodgkin lymphoma.
Definition (NCI) A lymphoma, previously known as Hodgkin's disease, characterized by the presence of Reed-Sternberg cells. There are two distinct subtypes: nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma. Hodgkin lymphoma has a bimodal age distribution, and involves primarily lymph nodes. Current therapy for Hodgkin lymphoma has resulted in an excellent outcome and cure for the majority of patients.
Definition (CSP) malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue, and the presence of large, usually multinucleate, cells (Reed-Sternberg cells) of unknown origin.
Definition (MSH) A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.
Concepts Neoplastic Process (T191)
MSH D006689
ICD9 201.1, 201.0, 201.2, 201.9, 201
ICD10 M9661/3 , M9662/3, C81, M9650/3, C81.9, M9660/3
SnomedCT 118599009, 118602004, 118606001, 52337003, 14537002, 189992008, 188595005, 188543002, 188522003, 188552006, 309831004, 189987006, 188542007, 189991001, 154582001, 269509006, 188521005, 188605006, 188596006, 188532005, 188533000, 74189002, 46923007, 70600005, 118605002
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Spanish morfología: linfoma de Hodgkin, no clasificado como subtipo en CIE - O, Enfermedad de Hodgkin NEOM, Sarcoma de Hodgkin, Linfogranulomatosis, Enfermedad de Hodgkin de tipo no especificado, Hodgkin, Paragranuloma de Hodgkin, Linfoma de Hodgkin, Granuloma de Hodgkin, Granuloma Maligno, granuloma de Hodgkin, SAI (trastorno), granuloma de Hodgkin de localización no especificada, [M]enfermedad de Hodgkin, SAI, paragranuloma de Hodgkin, SAI, paragranuloma de Hodgkin - RETIRADO -, Hodgkin's disease NOS, [M]paragranuloma de Hodgkin, enfermedad de Hodgkin de localización no especificada, SAI (trastorno), enfermedad de Hodgkin de localización no especificada, SAI, enfermedad de Hodgkin, SAI, sarcoma de Hodgkin de localización no especificada (trastorno), [M]paragranuloma de Hodgkin (anomalía morfológica), sarcoma de Hodgkin de localización no especificada, [M]linfoma de Hodgkin, SAI, sarcoma de Hodgkin, SAI, [M]linfogranuloma maligno (anomalía morfológica), paragranuloma de Hodgkin, SAI (trastorno), enfermedad de Hodgkin, SAI (trastorno), paragranuloma de Hodgkin, nodular - RETIRADO -, paragranuloma de Hodgkin (trastorno), granuloma de Hodgkin de localización no especificada (trastorno), paragranuloma de Hodgkin de localización no especificada, paragranuloma de Hodgkin de localización no especificada (trastorno), paragranuloma de Hodgkin - RETIRADO - (concepto no activo), granuloma de Hodgkin, SAI, [M]linfogranuloma maligno, linfoma de Hodgkin de localización no especificada, SAI, [M]enfermedad de Hodgkin, SAI (anomalía morfológica), sarcoma de Hodgkin, SAI (trastorno), Linfogranulomatosis Maligna, (M)enfermedad de Hodgkin, enfermedad de Hodgkin (trastorno), enfermedad de Hodgkin, granuloma de Hodgkin (anomalía morfológica), granuloma de Hodgkin (trastorno), granuloma de Hodgkin, linfoma hodgkiniano maligno, linfoma maligno de Hodgkin, morfología: linfoma de Hodgkin, no clasificado como subtipo en CIE - O (anomalía morfológica), paragranuloma de Hodgkin, sarcoma de Hodgkin (anomalía morfológica), sarcoma de Hodgkin (trastorno), sarcoma de Hodgkin, Linfomas de la enfermedad de Hodgkin, Enfermedad de Hodgkin, Linfogranuloma Maligno
Italian Linfoni della Malattia di Hodgkin, Linfogranulomatosi, Malattia di Hodgkin NAS, Paragranuloma di Hodgkin, Di Hodgkin, Sarcoma di Hodgkin, Malattia di Hodgkin, tipo non specificato, Linfoma di Hodgkin, Malattia di Hodgkin, Linfogranuloma maligno, MH, Granuloma di Hodgkin, Morbo di Hodgkin
Dutch ziekte van Hodgkin NAO, ziekte van Hodgkin, niet-gespecificeerd type, Hodgkins, Hodgkins paragranuloom, lymfogranulomatose, Hodgkins granuloom, Hodgkins sarcoom, Hodgkins lymfoom, Ziekte van Hodgkin/non-Hodgkin lymfoom, Hodgkin; granuloom, Hodgkin; lymfoom, Hodgkin; paragranuloom, Hodgkin; sarcoom, granuloom; Hodgkin, granuloom; maligne, lymfoom; Hodgkin, maligne; granuloom, paragranuloom; Hodgkin, sarcoom; Hodgkin, ziekte; Hodgkin, Ziekte van Hodgkin, niet gespecificeerd, Hodgkin-lymfomen, ziekte van Hodgkin, Ziekte van Hodgkin, Hodgkin-ziekte, Lymfogranuloom, maligne, Ziekte, Hodgkin-
French Sarcome de Hodgkin, Maladie de Hodgkin, type non précisé, Hodgkins, Maladie de Hodgkin SAI, Paragranulome de Hodgkin, Lymphogranulomatose, Lymphome hodgkinien, Granulome de Hodgkin, Lymphogranulome malin, Granulome malin, Lymphome de Hodgkin, Lymphomes Hodgkiniens, Maladie de Hodgkin, Lymphogranulomatose maligne
German Hodgkin-Granulom, Hodgkin-Lymphom, Morbus Hodgkin NNB, Hodgkin-Paragranulom, Hodgkin-Sarkom, Hodgkin's, Morbus Hodgkin, unspezifischer Typ, Lymphogranulomatose, Hodgkin-Krankheit [Lymphogranulomatose], Hodgkin-Krankheit, nicht naeher bezeichnet, Morbus Hodgkin Lymphome, Hodgkin-Krankheit, Lymphogranulomatose, Hodgkin-, Lymphogranulomatose, maligne, Morbus Hodgkin
Portuguese Linfogranulomatose, Paragranuloma de Hodgkin, Sarcoma de Hodgkin, Doença de Hodgkin NE, Doença de Hodgkin de tipo NE, Linfoma de Hodgkin, Granuloma de Hodgkin, Granuloma Maligno, Doença de Hodgkins, Linfomas de doença de Hodgkin, Doença de Hodgkin, Linfogranuloma Maligno
Japanese ホジキンリンパ腫, ホジキン肉腫, リンパ肉芽腫症, ホジキン病、型詳細不明, ホジキン病NOS, ホジキン側肉芽腫, ホジキンニクゲシュ, ホジキンソクニクゲシュ, ホジキンビョウNOS, ホジキンビョウ, ホジキンリンパシュ, ホジキンニクシュ, リンパニクゲシュショウ, ホジキンビョウカタショウサイフメイ, 悪性リンパ肉芽腫, ホジキン病, ホジキン肉芽腫, リンパ肉芽腫症-悪性, リンパ肉芽腫-悪性, 肉芽腫-ホジキン, 悪性肉芽腫, 悪性リンパ肉芽腫症, ステルンベルグ病, 肉芽腫-悪性, Hodgkin肉芽腫, Hodgkin病
Swedish Hodgkins sjukdom
Czech Hodgkinova nemoc, lymfogranulom maligní, Hodgkinské lymfomy, Hodgkinova choroba NOS, Hodginský sarkom, Lymfogranulomatóza, Hodgkinský granulom, Hodgkinský paragranulom, Hodgkinova choroba, blíže neurčeného typu, Hodgkinský lymfom, Hodgkinův lymfom, Hodgkinova choroba
Finnish Hodgkinin tauti
Russian GRANULEMA KHODZHKINA, LIMFOGRANULEMATOZ, GRANULEMA ZLOKACHESTVENNAIA, KHODZHKINA BOLEZN', ГРАНУЛЕМА ЗЛОКАЧЕСТВЕННАЯ, ГРАНУЛЕМА ХОДЖКИНА, ЛИМФОГРАНУЛЕМАТОЗ, ХОДЖКИНА БОЛЕЗНЬ
Korean 호지킨병, 상세불명의 호지킨병
Croatian HODGKINOVA BOLEST
Polish Choroba Hodgkina, Chłoniak Hodgkina, Ziarnica złośliwa, Chłoniak ziarniczy, Limfogranulomatoza
Hungarian Hodgkin, Hodgkin-kór, Hodgkin betegség, nem meghatározott típus, Hodgkin-paragranuloma, Lymphomás Hodgkin-kór, Hodgkin-kór k.m.n., Hodgkin-granuloma, Hodgkin-lymphoma, Hodgkin-sarcoma, Lymphogranulomatosis
Norwegian Hodgkins sykdom, Hodgkins lymfom