Hodgkin S Lymphoma
Introduction
- 1832 —> British physician Thomas Hodgkin
- Development of kilovoltage equipment in the 1920s
- Gilbert, a Swiss radiotherapist
Etiology and Epidemiology
- Relatively uncommon
- 8000/yr
- 1% of all cancer diagnoses
- Age-incidence curve
- Developed countries
- Initial peak —> around age 25 yrs
- Mostly nodular sclerosis
- Reflection of delayed exposure to infectious agents
- Higher socioeconomic status
- Early birth order
- Small sibship size
- Growing up in single-family
- Having few playmates
- Parents with a high level of education
- Second peak —> 60-70 yrs
- Male>Female (in this peak)
- Initial peak —> around age 25 yrs
- Developing countries
- Rare among young adults
- Mostly mixed cellularity
- Initial peak —> childhood
- Boys>girls
- Late peak —> older patients
- Developed countries
- Epstein-Barr virus (EBV)
- Infectious mononucleosis —> threefold increased risk
- Elevated levels of the IgG and IgA against the EBV capsid Ag
- + months to years prior to clinical Hodgkin's lymphoma development
- ~ 1/3-1/2 of cases of classical HL (in Western populations)
- Monoclonal EBV genome can be detected in the Reed-Sternberg cells
- EBV + —> associated with the Mixed Cellularity
- (MC): More common among young children and older adults
- EBV + is less frequent in NS ( and remeber NS is more in young adult
- Familial
- First-degree relatives —> x5 risk
- Siblings —> x7 risk
- Monozygotic twins —> x100!
- Certains HLAs
Molecular Biology
- Reed-Sternberg cells
- Large
- Binucleated cells( but malignant cells in HL can be uni or multinucleated as well)
- 1% of the cells present in the sample
- Most of the tissue —>
- Non-neoplastic inflammatory cells & fibrosis
- Monoclonal immunoglobulin gene rearrangements:
- No Ig gene expression
- Resistant to apoptosis
- Mature B lymphocytes
- Mutated VH genes
- Specific markers for germinal center B cells and their descendants
- Activation of nuclear factor kappa B (NFκB)
- Constitutive NFκB is required for proliferation and survival of Hodgkin's lymphoma tumor cells
- What activates (NFκB)?
- REL gene may be responsible!
- Mutations in NFκB inhibitors
- Somatic mutations in the novel tumor suppressor gene TNFAIP3
- TNFAIP3 encodes A20!
- EBV inactivates A20!
- Some common pathogenesis?!!!!
- CD95 is upregulated
- Another NFκB-dependent regulator of apoptosis
Cellular Classification of HL
WHO/Revised European-American Lymphoma (REAL) classification:
- Classical
- Nodular sclerosis
- Mixed-cellularity
- Lymphocyte depletion
- Lymphocyte-rich
- Immunophenotype:
- CD15+, CD20-, CD30+, CD45-
- CD20+ <40%
- CD3 -
- CD15+, CD20-, CD30+, CD45-
- Nodular Lymphocyte–Predominant HL
- Distinct from classic HL
- CD15-, CD20+, CD30-, CD45+
- CD3 -
- Usually earlier-stage disease, longer survival, and fewer treatment failures than those with classic HL
- However, there is a tendency for histologic transformation to diffuse large B-cell lymphoma in around 10% of patients by 10 years
- Present in asymptomatic young males with cervical or inguinal lymph nodes
- Usually without mediastinal involvement
- Limited-field radiation therapy is the most common treatment approach for patients with early-stage disease
Few things on staging
- If there is any involvement of following organs then that's stage IV:
- Liver
- Lung
- Bone Marrow
- CSF
- One single LN —> stage I
- Two LN —> stage II
- Focal involvement of one extralymphatic ONLY( no LN ) —> stage I
- Focal involvement of one extralymphatic + LN(if same side of diaohragm) —> stage II
- Focal involvement of one extralymphatic + LN(if both side of diaohragm) —> stage III
Natural History and general work-up:
History:
- Ask about B symptoms
- Fever
- Drenching sweat
- Weight loss
- Other general symptoms:
- Performance status
- ALWAYS check as important for tolerance to therapy
- Fatigue
- Alcohol intolerance
- pruritis
- Lump/bump
- Performance status
- Ph/E
- Check for total LN
- Pre-popliteal
- trochlear
- Cachetia?
- Fever?
- Skin rash —> scratch for pruritis
- Splenomegaly
- Hepatomegaly
- Remember any liver involvement is stage IV and poor prognostic
- Check for total LN
- Investigation:
- Excisional biopsy
- FNA to be avoided
- Blood work:
- CBC-diff
- Remember high WBC and low lymph is poor prognostic factor in advance stage
- ESR
- If >30 in B and >50 in A is a poor prognostic factor for early stage
- LDH
- >4.0 is poor prognostic factor for advance stage
- Albumin
- as LFT
- Biochem and kidney and liver function test
- Is patienta chemo candidate?
- Check HIV if high risk
- Check beta-HCG for pregnancy if young patient
- CBC-diff
- Imaging:
- CT C/A/P
- PET scan
- Other:
- EF test
- For Adriamycin contatining regimen
- PFT
- RT in chest
- or ABVD or BEACCOPP regimen
- Pneumococcal, H-flu, Meningococceal vaccination
- If spleen RT
- EF test
- Excisional biopsy
- 5% involvement of bone marrow.
- biopsy is indicated if:
- Constitutional B symptoms
- Stage III and IV
- as per NCCN
- Anemia
- Leukopenia
- Thrombocytopenia
- as per pdq
- Staging laparotomy is no longer recommended
- Considered only if substantial reduction in treatment
- It should not be done in patients who require chemotherapy. Risks of potential morbidity should be considered
- biopsy is indicated if:
Keys on Management of HL
page revision: 29, last edited: 04 Dec 2012 07:13