Hodgkin's Disease

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Classification 3 Pathology 4 Genetics 5 Clinical-manifestations 6 Laboratory 7 Diagnostic-procedures 8 Radiology 9 Staging 10 Complications 11 Differential-diagnosis 12 Management 13 More General Terms 14 Additional Terms 15 References

More Specific Terms

• Hodgkin's disease, lymphocyte depleted type
• Hodgkin's disease, lymphocyte predominant type
• Hodgkin's disease, mixed cellularity type
• Hodgkin's disease, nodular sclerosing type

Classification

• not a true lymphoma
• malignant cells are not of lymphocytic origin

*     Histology                  prevalence        prognosis 
* lymphocyte predominance           2-10%          excellent 
* nodular sclerosis                40-80%          very good 
* mixed cellularity                20-40%          good 
* lymphocyte depletion              2-15%          poor

Pathology

• lymph node biopsy
• presence of Reed-Sternberg cells ( RSC) is pathognomonic
• number of infiltrating malignant macrophages ( RSC) identified by CD68 immunohistochemistry correlates with treatment failure [6]

Genetics

• implicated genes:

• CD302, LY75, CLIP1, LGALS9

Clinical-manifestations

• palpable lymphadenopathy, generally painless

• most commonly involves neck
• cervical, supraclavicular, mediastinal lymphadenopathy

• B symptoms

• fever, night sweats ( Pel-Epstein fever), weight loss

• malaise
• persistent, non-productive cough
• pruritis
• pain associated with alcohol ingestion (may be due to eosinophil infiltration) [5]

Laboratory

• complete blood count ( CBC)
• liver function tests ( LFTs)
• renal function tests ( BUN & serum creatinine)
• uric acid
• C-reactive protein
• tests which may be useful

• cell surface marker phenotype analysis
• gene rearrangement analysis
• delayed hypersensitivity status
• polymerase chain reaction ( PCR) detects Epstein-Barr virus in 60-80% of patients

Diagnostic-procedures

• surgical excisional lymph node biopsy to examine lymph node architecture (essential)
• bone marrow biopsy, essential for

• B symptoms
• stage 3 or 4 disease [3]

• may be indicated

• liver biopsy
• exploratory or staging laparotomy

Radiology

• essential

• chest radiograph: may show mediastinal mass
• CT of thorax, abdomen & pelvis
• whole body PET scan [3]

• may be indicated

• lymphangiogram
• gallium scan
• bone scan
• bone radiographs
• ultrasonography
• magnetic resonance imaging

Staging

• Clinical staging of Hodgkin's disease (see lymphoma)

Complications

• radiation therapy can result in acute & late complications

• mantle irradiation:

• acute complications:

• dry mouth
• pharyngitis
• fatigue
• weight loss
• Lhermitte's syndrome

• paresthesias in the lower extremities with neck flexion
• generally spontaneously resolves

• pneumonitis (< 5%)
• pulmonary fibrosis (< 1%).

• late complications:

• pericardial effusions
• myocardial injury
• valvular heart disease
• hypothyroidism (30%)
• emergence of second tumors

• breast cancer is the most common solid tumor
• estimated increased risk of tumor occurrence is 2.8 fold
• lung cancer
• skin cancer
• myelodysplastic syndrome -> AML

• para- aortic irradiation:

• rarely associated with side effects

• pelvic irradiation:

• acute complications:

• diarrhea
• bladder irritation

• chronic complications:

• bone marrow suppression
• sterility

• abnormal T-cell function with infection due to:

• intracellular pathogens

• Mycobacterium tuberculosis
• Listeria
• Salmonella
• Cryptococcus
• Mycobacterium avium
  

• disease interaction(s) of cancer with Alzheimer's disease

Differential-diagnosis

• non-Hodgkin's lymphoma
• sarcoidosis
• infections ( CMV, EBV, HIV, toxoplasmosis)
• drug reaction
• see lymphadenopathy

Management

• general

• all patients with Hodgkin's disease should be treated with the intent to cure
• radiation may cure 80% of patients with localized disease
• chemotherapy may cure 50% of patients with disseminated disease
• choice of treatment modality is dependent upon stage of the disease
• combination of chemotherapy + radiation therapy for early disease [3]

• treatment based on stage

• Stage IA & IIA:

• involved field radiation alone
• extended field radiation alone for older patients

• Stage IIIA: radiation or chemotherapy
• Stage IIIB & IV: chemotherapy
• B symptoms: chemotherapy

• radiation therapy:

• 4000 cGy administered 1000 cGy per week
• since Hodgkin's disease spreads largely via lymphatics, 3 types of radiation fields were developed:

• mantle: includes submandibular, cervical, supraclavicular, infraclavicular, axillary, mediastinal, & hilar lymph nodes
• paraaortic: includes transverse processes of abdominal vertebral bodies & spleen
• pelvic: includes common iliac, hypogastric, external iliac, & inguinal nodes

• when there is gross pelvic involvement, femoral nodes are also irradiated
• when pelvic & paraaortic fields are treated as a unit, the field is called an inverted Y field
• palliative radiation for

• airway obstruction
• spinal cord compression

• patients with stage IA or IIA Hodgkin's lymphoma (localized node involvement) treated with mantle or paraaortic radiation have up to 80% long term disease-free survival
• patients with stage IB & IIB have 70% survival
• patients with extensive mediastinal involvement tend to do worse
• patients who relapse with radiation therapy frequently respond to chemotherapy

• chemotherapy

• the first effective combination chemotherapy for Hodgkin's disease was introduced in 1960, MOPP ( mechlorethamine ( nitrogen mustard), vincristine ( Oncovin), procarbazine, prednisone)
• MOPP has been associated with 84% complete remission & 48% 14 year survival
• toxicities of MOPP include

• nausea & vomiting
• bone marrow suppression
• sterility

• MOPP therapy has been associated with a 2% risk of developing secondary leukemia within 10 years of therapy; the leukemia is acute non-lymphocytic leukemia
• none of the newer regimens has proven superior to the original MOPP

• ABVD ( adriamycin, bleomycin, vinblastine, & dacarbazine)

• has been used to treat Hodgkin's disease refractory to MOPP
• toxicities of ABVD are similar to MOPP, but may be associated with fewer secondary malignancies, but increased incidence of myocardial & pulmonary damage
• preferred 1st line agent [3]
• 4 cycles of ABVD; 2 cycles may be sufficient for early stage Hodgkin's disease [7]

• sequential combinations of MOPP & ABVD may show more favorable outcomes
• brentuximab vedotin ( Adcetris) FDA-approved for relapsed or refractory Hodgkin's lymphoma

• chemotherapy alone (without radiation) for stage 3 or 4

• chemotherapy + radiation

• ABVD chemotherapy + involved field radiation for stage 1 & 2
• ABVD chemotherapy + mediastinal radiation for bulky mediastinal disease

• stem cell transplantation

• referal all patients < 70 years of age to a transplantation center
• autologous bone marrow, or
• peripheral blood stem-cell transplantation
• indicated after the 1st relapse from any 1st line treatment for Hodgkin's disease
• if there is evidence of bone marrow disease, allogeneic bone marrow transplantation is appropriate

• sperm cryopreservation prior to therapy if man wishes to preserve fertility
• follow-up

• look for second cancer (see complications)
• mammography begun at age 40 or 8 years following radiation therapy [3]
• all post-radiation patients with chest pain should be evaluated for coronary artery disease regardless of age [3]

More General Terms

• lymphoma (lymphosarcoma)

Additional Terms

• CD15, Lewis X or X-hapten
• CD30; tumor necrosis factor receptor superfamily member 8; CD30L receptor; lymphocyte activation antigen CD30; KI-1 antigen (TNFRSF8, D1S166E)
• doxorubicin (Adriamycin)/bleomycin/vinblastine/dacarbazine (ABVD)
• nitrogen mustard/vincristine (Oncovin)/prednisone/ procarbazine (MOPP)
• Reed-Sternberg cell
• vaccination in patients with Hodgkin's disease

References

1. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1782, 1786
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 423-26
3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 539
5. Ferri's Clinical Advisor, Instant Diagnosis and Treatment, Ferri FF (ed), Mosby, Philadelphia, 2003
6. Steidl C et al Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med 2010 Mar 11; 362:875. Not yet indexed in PubMed [1]
7. Engert A et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med 2010 Aug 12; 363:640. PMID: &dopt=Abstract
8. Hodgkin's Lymphoma: NIH Institute and Center Resources [2]
9. National Guideline Clearinghouse Follow-up of Hodgkin's disease. (American College of Radiology) ngc-guideline: [3]
   - Staging evaluation for patients with Hodgkin's disease. (American College of Radiology) ngc-guideline: [4]
   - ACR Appropriateness Criteria<TM> Hodgkin's lymphoma-favorable prognosis stage I and II. ngc-guideline: [5] ACR Appropriateness Criteria<TM> Hodgkin's lymphoma--stage III and IV ngc-guideline: [6]
   - Pediatric Hodgkin's disease. (American College of Radiology) ngc-guideline: [7]
   - Hodgkin's Disease-unfavorable clinical stage I and II American College of Radiology ngc-guideline: [8]

Hodgkin's disease (Hodgkin's lymphoma)