This document summarizes Hodgkin lymphoma, including:
1. Epidemiology, risk factors, and association with Epstein-Barr virus infection. Hodgkin lymphoma incidence peaks between ages 25-30 and 75-80 and is more common in males. Risk is increased with a history of infectious mononucleosis.
2. Presentation, staging, pathology, and prognostic factors. Hodgkin lymphoma typically presents with painless lymphadenopathy and B symptoms. Staging uses the Ann Arbor system and prognostic factors include age, stage, ESR, and albumin levels.
3. Management involves chemotherapy, radiation therapy, or combined modality treatment depending on stage and risk factors. Standard first-line
2. EPIDEMIOLOGY
AND RISK
FACTORS
• Incidence less than 3 per 100,000.
• Accounts for 0.56% of all cancers
diagnosed.
• Male predominance (1.2:1).
• Rare in children <10 years of age.
• Median age at diagnosis 26 years.
3. • Incidence has a bimodal peak as a function of age.
• Early peak from ages 25 to 30 years.
• Second peak from age 75 to 80 years.
• Peak in older adults “contaminated” by cases that were
actually anaplastic large-cell or diffuse large-cell lymphoma.
4. • Weiss et al. : Relation between HD and EBV infection.
• EBV genome in the DNA of Reed-Sternberg (RS) cells.
• Mueller et al. :
a) Elevated levels of IgG and IgA against the EBV capsid antigen.
b) Antibody against EBV nuclear antigen.
c) Antigen D in the serum
3 to 156 months before the diagnosis of Hodgkins lymphoma.
5. • Risk for development of Hodgkin lymphoma 2.55 times higher among
individuals who have a history of infectious mononucleosis.
• Several series demonstrated an association between EBV infection and
mixed-cellularity Hodgkin lymphoma, especially in children in
developing countries.
• Ultimate relationship between EBV infection and development of
Hodgkin lymphoma remains undefined.
6. NATURAL HISTORY AND CLINICAL PRESENTATION
• Present with painless lymphadenopathy 90% of patients contiguous
sites of involvement.
• Systemic symptoms such as :
a) Unexplained fevers : classic waxing-and-waning Systemic ‘B’
Pel-Ebstein pattern.
b) Drenching night sweats. Symptoms
c) Significant weight loss.
d) Generalized pruritus.
e) Fatigue.
f) Alcohol-induced pain in tissues involved by Hodgkin lymphoma.
g) Diagnosed after detection of a mediastinal mass on a routine chest
radiograph.
7. • Organ involvement by Hodgkin lymphoma secondary to
extension from adjacent lymph nodes.
Eg: Spread from enlarged mediastinal or pulmonary hilar
nodes:
a) Directly into the pulmonary parenchyma or
b) Hematogenous such as nodular disease in the liver or
multiple bony sites.
• Involvement of the bones cause blastic changes in the
vertebrae (creating the classic “ivory vertebra” on plain
radiographs), pelvis, sternum, or ribs.
8.
9. • Nearly all patients with hepatic or bone marrow involvement
by Hodgkin lymphoma extensive involvement of the
spleen.
• Rarely involves the gut-associated lymphoid tissues such as
Waldeyer ring and Peyer patches.
• Rarely involves the upper aerodigestive tract, central nervous
system, and skin.
10. • Children good prognosis compared with adults.
• Older adults (>60 years) worse prognosis secondary to
intercurrent illness or the ability to tolerate standard
therapies, especially bleomycin, anthracyclines and extended-
field irradiation.
12. D. Hematologic evaluation :
1. Complete blood count , differential and platelet :
• Anemia, leukopenia, lymphopenia, or thrombocytosis.
• Paraneoplastic effect but it may be indicative of bone marrow
involvement.
• Anemia, lymphopenia, and hypoalbuminemia adverse
prognostic factors, especially for patients with advanced disease
(stage III–IV).
13. 2. Serum alkaline phosphatase nonspecific marker of tumor
activity or hepatic, bone marrow, or bone disease.
3. Erythrocyte sedimentation rate (ESR) correlate with
response to treatment and subsequent disease activity and is a
prognostic factor for patients with limited disease (stage I–II).
4. Other useful markers lactate dehydrogenase and β2-
microglobulin levels.
14. E. Radiographic evaluation :
1. PA and lateral chest radiographs :
• Mediastinal adenopathy quantitated by a measurement of
the maximum width of the mediastinal mass divided by the
maximum intrathoracic diameter (near the level of the
diaphragm) on a standing PA chest radiograph.
• If ratio exceeds 1:3 disease is defined as bulky and this
affects assignment to many clinical trials.
• Other definitions of bulky mediastinal adenopathy:
a) A mass >10 cm.
b) Ratio of mediastinal mass to the chest diameter at T5-6
exceeding 0.35 (EORTC clinical trials).
15.
16. 2. Contrast-enhanced (diagnostic) computed tomographic
(CT) scans of the chest, abdomen, and pelvis reveal
adenopathy or organ involvement.
• Splenomegaly or hepatomegaly alone cannot be interpreted
to represent involvement by Hodgkin lymphoma enlarged
spleens often are not involved at the time of splenectomy.
• Presence of focal nodules indicative of involvement.
17. 3. Positron emission tomography (PET) : using 2-fluoro-2-deoxy-D-
glucose (FDG), especially with fused CT images (PET-CT scan) an
important component of initial staging in Hodgkin lymphoma.
• FDG-PET more sensitive than CT for detecting disease reveal
unsuspected bone or bone marrow disease.
• Essential study for response assessment useful for the evaluation of
residual masses detected by CT scanning.
• Useful prognostic indicator when repeated after just a portion of
chemotherapy has been administered.
18. 4. Magnetic resonance imaging : alternative to chest or abdominal-
pelvic CT scanning for initial staging.
• For staging evaluation of women during pregnancy.
5. Bone marrow biopsy : posterior iliac crest bone marrow
selected patients.
• Bone marrow biopsy rarely positive.
• Not required Stages I–IIA disease.
• Should be done if : CBC is abnormal.
Stages III and IV disease.
B symptoms.
• Overall incidence of bone marrow involvement in Hodgkin
lymphoma ~5%.
19. STAGING
• Ann Arbor staging system used since 1971.
• Includes designation of a clinical stage, based on:
Results of the initial biopsy and clinical staging studies and
a pathologic stage.
Any subsequent biopsies, including bone marrow biopsy and
those obtained at staging laparotomy.
20. THE ANN ARBOR STAGING
CLASSIFICATION FOR HODGKIN’S DISEASE
21.
22. PATHOLOGIC CLASSIFICATION
• Neoplastic cell of classic Hodgkin lymphoma Reed–Sternberg cell.
Binucleate.
A prominent centrally located nucleolus in each nucleus.
A well-demarcated nuclear membrane.
Eosinophilic cytoplasm with a perinuclear halo.
• Account for <1% of the cells in a lymph node involved by Hodgkin
lymphoma.
• Majority are lymphoid cells, eosinophils, plasma cells, and other
normal cells.
24. • 5 histologic subtypes of Hodgkin lymphoma as defined by
the WHO modification of the Lukes and Butler system.
1. Nodular lymphocyte-predominant Hodgkin lymphoma.
• Four subtypes of classic Hodgkin lymphoma:
2. Nodular sclerosis.
3. Mixed cellularity.
4. Lymphocyte-rich.
5. Lymphocyte-depleted.
25. 1. NODULAR LYMPHOCYTE PREDOMINANT
HODGKIN LYMPHOMA (NLPHD)
• Accounts for <5% of HL.
• Characterized by the presence of an RS cell variant known as L & H
cell or popcorn cell.
• Express Bcell markers CD20+, CD79a+, CD45+ and J chain+.
• CD15 -ve and CD30 -ve.
• Usually presents in middle-aged males.
• Present with early-stage disease.
• Localized peripheral lymph node involvement (cervical, axillary, and
inguinal regions).
• Systemic symptoms uncommon (<10%).
26. • Natural history most favorable.
• Occasional patients demonstrate a pattern of late relapse but good
survival similar to that observed in the follicular (B-cell)
lymphoma.
• 14% of patients with nLPHD may transform to an aggressive B-cell
lymphoma.
• A reactive process termed progressive transformation of germinal
centers may be observed in conjunction with nLPHD.
27. CLASSIC HODGKINS LYMPHOMA
•4 histologic subtypes.
•Classical HL the RS cells are
Positive CD30 and CD15.
Negative CD45 and the J chain.
28. 2. NODULAR SCLEROSIS CLASSICAL
HODGKIN LYMPHOMA (NSHD)
•Most common histologic subtype accounting for
65–70% of cases.
•Characterized by :
a) Nodular growth pattern.
b) Presence of collagen bands.
c) RS cell variant known as the lacunar cell.
29. • Only subtype without a male predominance male : female ratio
approximately 1:1.
• Clinical presentation mediastinal involvement, and
1/3rd of patients have B symptoms.
• Natural history Less favorable than that of nLPHD.
30. 3. MIXED-CELLULARITY CLASSIC
HODGKIN LYMPHOMA (MCHD)
• Represents 10–15% of cases
• Present with advanced disease.
• Tendency to involve spleen, bone marrow and a lesser
tendency for mediastinal involvement.
• Slightly older than those with NSHD or nLPHD.
• Natural history Less favorable than that of NSHD.
31. 4. LYMPHOCYTE-RICH CLASSIC
HODGKIN LYMPHOMA (LRHD)
• Represents ~5% of HL.
• Nodular growth pattern.
• Clinical characteristics of patients affected by LRHD are
similar to those of nLPHD
Early stage.
Absence of B symptoms.
Excellent prognosis.
32. 5. LYMPHOCYTE-DEPLETED CLASSIC
HODGKIN LYMPHOMA (LDHD)
• Uncommon subtype.
• Difficult to differentiate from anaplastic large-cell
lymphoma.
• Older patients.
• Associated with advanced disease and B symptoms.
• Worst prognosis.
34. INTERNATIONAL PROGNOSTIC SCORE FOR
ADVANCED HODGKIN LYMPHOMA
FACTOR UNFAVOURABLE COVARIATE
Serum albumin <4 g/dl
Hemoglobin <10.5 g/dl
Sex Male
Age > = 45yrs
Stage IV (Ann Arbor)
Leukocyte count >= 15,000/mm3
Lymphocyte count <600/mm3 or <89% of white
count
36. CHEMOTHERAPY
• Initial successful drug combination : MOPP reported by DeVita et al. from the
National Cancer Institute in 1970.
a) Nitrogen mustard.
b) Vincristine.
c) Procarbazine and
d) Prednisone
• Acute toxicities significant.
• Late effects of concern sterility (especially in men) and risk for secondary
myelodysplastic syndrome or leukemia.
• MOPP-like programs chlorambucil, vinblastine, procarbazine, and
prednisone (ChlVPP) comparable results with similar drugs and less
toxicity
37. • ABVD Doxorubicin
Bleomycin
Vinblastine
Dacarbazine
• Replaced MOPP.
• Gold standard of chemotherapy for Hodgkin lymphoma.
39. COMBINED-MODALITY THERAPY
• Important considerations :
a) Sequence of therapy.
b) Selection of irradiation fields.
c) Decision to irradiate all involved sites :
- only initially “bulky” site or
- only sites that have not responded
completely to chemotherapy.
d) Prescription of dose.
e) Potential overlapping toxicities.
40. • Treatment is almost always initiated with chemotherapy.
• Advantages of treating all sites of disease at the outset
(especially important in stage III or IV) reducing bulky
disease to facilitate subsequent irradiation (especially in the
mediastinum).
• Irradiation dose used in combined-modality studies in adults
ranges from 20 to 36 Gy.
41. • Radiation therapy is used in the combined-modality setting
Doses vary depending on the :
a) Prognostic category of patients.
b) Bulk of disease and
c) Type and duration of chemotherapy.
• The range of doses considered acceptable according to the
NCCN guidelines :
a) 20 to 30 Gy for nonbulky and 1.5 to 1.8 Gy
b) 30 to 36 Gy for bulky sites of disease per fraction
42. • In the context of combined-modality therapy programs
Clinical trials have demonstrated an equivalence of
“involved-field” treatment (IFRT) with “extended-field” or
“subtotal-lymphoid” irradiation.
• Involved-field irradiation adopted as the standard for
combined-modality therapy.
• More recent trials application of even more restricted
fields “involved-node radiotherapy” (INRT) of “involved-
region” or “involved-site” irradiation.
43. RADIATION THERAPY
• Classic field configurations for the treatment of Hodgkin
lymphoma by radiotherapy alone Mantle and inverted-Y.
49. TREATMENT OF ADVANCED-STAGED DISEASE
• ABVD 6 to 8 cycles Standard treatment.
• Alternative approach of Stanford V being acceptable.
• BEACOPP better disease control in patients with adverse
prognosis increased treatment toxicity.
51. TREATMENT OF REFRACTORY AND RELAPSED HL
• Refractory HL progression of disease during initial therapy or
within 3 months of completion of treatment.
• Relapsed HL disease progression after a CR to primary treatment
(early relapse is further defined as within 12 months of CR)