Diagnosis and management of Hodgkin's lymphoma

Diagnosis And Management Of
Hodgkin's Lymphoma
Satria Alam Kadar

Dimas Bayu
VISI
Menjadi pusat pendidikan yang unggul, mandiri dan berwawasan

benua Maritim untuk menghasilkan Dokter Spesialis Penyakit
Dalam yang humanis dan mampu bersaing secara regional,
nasional maupun global pada tahun 2026 dengan didukung oleh
SDM yang professional dan bertanggung jawab.
MISI
1. Menyelenggarakan pendidikan di bidang Ilmu Penyakit Dalam

berbasis evidence based medicine, riset dan berwawasan benua
maritim
2. Memberikan pelayanan kesehatan di bidang Ilmu Penyakit Dalam
yang humanis, paripurna, dan bermutu
3. Meningkatkan kuantitas dan kualitas penelitian dasar dan aplikatif
Ilmu Penyakit Dalam yang bertaraf nasional dan internasional
4. Menerapkan sistem digitalisasi pada proses Pendidikan dan
manajemen Program Studi Ilmu Penyakit Dalam yang transparan,
akuntabel, responsibel, independent, terintegrasi, dan
berkeadilan.
Introduction
Based on
Hodgkin's lymphoma is
histopathology, there are
a malignancy that
2 types, namely non- Ranked 26th of all types
involves the lymphatic
Hodgkin's lymphoma of cancer in the world
system, especially the
and Hodgkin's
B-lymphocyte mutation
lymphoma
Emerging treatment The last few decades

options increase survival have seen significant Has 2 main types CHL
by about 5 years, progress. Currently, the (95%) and NLPHL (5%)
compared to other types LH cure rate is around
of cancer 80%.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., Jemal, A. 2020. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for
36 cancers in 185 countries. CA: A Cancer Journal for Clinicians,
Kusminsky, G., Abriata, G., Forman, D., Sierra, M. S. 2016. Hodgkin lymphoma burden in Central and South America. Cancer Epidemiology
EPIDEMIOLOGY
In Indonesia, there were 1,188 cases in 2020 out of a total of 31,742 cases
in Asia. and cases of death as many as 363 people
ETIOLOGY
The cause of Hodgkin's disease is still unknown. Possibly caused by infection
with the Epstein-Barr virus (EBV)
There is a relationship between immune system malfunctions and the incidence

of Hodgkin's disease. HIV AIDS incidence increased 10 times
People receiving immunosuppressant therapy after organ transplant
Some opinions state that there is a relationship between Hodgkin's lymphoma

and genetics.
Another opinion says exposure to carcinogens, especially in the workplace,

other environmental pollutants such as pesticides, herbicides and various
viruses
Shanbhag, S., and Ambinder, R. F. (2018). Hodgkin lymphoma: A review and update on recent progress. CA: A Cancer Journal for Clinicians, 68 (2), hal.116–132.
Makatini Z, Dr, Mathabatha J, Dr. CMS; Council for Medical schemes. PMB definition guideline for Hodgkin lymphoma Version 1
Age
• There is a bimodal age distribution

in young adults and in older adults.
• Most patients were diagnosed
between the ages of 15 and 30
years, followed by adults over 55
years of age.
Insiden LH berdasarkan usia
Race
White and black

people in the United
States (3.1% cases/
100,000 men) have
the same incidence
Hispanic children
have an increased risk
of LH and are more In South Africa, 293
frequently diagnosed and 356 new cases of
with MCCHL LH were recorded in
women and men,
respectively
Immunosuppression
From EBV-mediated biological

transformation of B cells
Epstein-Barr Virus Presence of a clonal EBV genome in LH

EBV-LH positive reaches up to 40% tumor cells
There is a threefold increased risk of LH

in persons with a history of
The incidence of LH is also increased in mononucleosis.
HIV-infected patients and those associated
with immunodeficiency
Social Economic
Incidence rates are higher in high-income countries
In the United States, Europe, and other high-income countries, LH accounts for about 10% of all
Hodgkin's lymphomas
For young adult disease, the higher a person's socioeconomic status, the greater the risk of developing
Hodgkin's disease.
Pathophysiology of
Hodgkin's Lymphoma
Hodgkin Lymphoma: Practice Essentials, Background, Pathophysiology [Internet]. Emedicine.medscape.com.

CLASSIFICATION
Nodular Sclerosis Classical
Hodgkin Lymphoma
Mixed Cellularity Classical

Hodgkin Lymphoma
CHL (95%)
Lymphocyte-Depleted
Hodgkin's Lymphoma Classical Hodgkin
Lymphoma
NLPHL (5%)
Lymphocyte-Rich Classical
Hodgkin Lymphoma
Ansell SM. Hodgkin Lymphoma: update on diagnosis, risk-stratification, and management. Mayo Clin Proc, 2020
Classic Hodgkin Lymphoma Nodular Sclerosis Classical Hodgkin Lymphoma
Lymphocyte-Rich Classical Hodgkin Lymphoma
Mixed Cellularity Classical Hodgkin Lymphoma
The presence of malignant multinucleated

giant Reed-Sternberg cells is the hallmark
of CHL lymphadenopathy Lymphocyte-Depleted Classical Hodgkin
Lymphoma
Eberle FC, Mani H, Jaffe ES. Histopathology of Hodgkin’s Lymphoma. The Cancer Journal. Volume 15, Number 2, March/April 2009
National Comprehensive Cancer Network. 2020. NCCN Guidelines Version 2.2020 Updates Hodgkin’s Lymphoma. NCCN 2020;18(6):755–781
Nodular Sclerosis Classical Lymphocyte-Rich Classical
Hodgkin Lymphoma Hodgkin Lymphoma
This type has a predilection for lymph nodes Less than 5% of all LH casesIts characteristics
located in the supraclavicular, cervical and are Reed-Sternberg cells with a background of
mediastinum. Characteristic lacunae cells, which lymphocytic cell infiltrates and few eosinophils
are large cells that have a multilobed nucleus and plasma cells that can have a diffuse or
nodular pattern.
Mixed Cellularity Classical Lymphocyte-Depleted Classical
Hodgkin Lymphoma Hodgkin Lymphoma
The most common type in children and patients ≥ 50 Less than 1% of all LH case. The rarest type of
years of age is Reed-Sternberg cells abundant in a LH The infiltrate in this type of LH is more often
heterogeneous inflammatory infiltrate containing diffuse and hypocellular, whereas Reed-
small lymphocytes, eosinophils, plasma cells and Sternberg cells are present in large numbers
macrophages. This type has a predilection for lymph and vary in shape, agressif, in the elderly and
nodes located in the abdomen is often associated with infection with the
HIV/AIDS virus.
Nodular Lymphocyte-Predominant
Hodgkin Lymphoma
• Approximately 5% of all cases of LH

• The histologic characteristic of this type of
LH is the presence of a variety of
lymphohistiocytic Reed-Sternberg cells that
have large, multilobed nuclei that are
smooth and resemble the appearance of
popcorn.
• These cell variants also usually do not
produce CD30 and CD15 like Reed-
Sternberg cells in general but instead
produce CD20
• found in men with B symptoms.
Excisional lymph node biopsy or surgical specimen (WHO
Diagnostic work- up in Diagnosis
classification) Hodgkin and Reed–Sternberg cells define
Hodgkin Lymphoma cHL
NLPHL is characterised by LP cells
Medical history and

physical examination‡ X-
Staging and risk
ray of the chest
Most patients with Hodgkin's stratification†
Contrast-enhanced CT scan of the neck, chest and
lymphoma present with abdomen PET§
supradiaphragmatic Full blood cell count and blood chemistry, ESR
lymphadenopathy, HBV, HCV and HIV screening
retroperitoneal and inguinal
lymphadenopathy occurring less ECG
frequently. Echocardiography
Pretreatment examinations Pulmonary function test
Reproductive counselling (in patients of reproductive
age) Serum pregnancy test (in female patients of
reproductive age)
Consultation of an ear, nose and throat specialist including a
fiberoptic nasolaryngoscopy*
Eichenauer, D. A., Aleman, B. M. P., André, M., Federico, M., Hutchings, M., Illidge, T,Ladetto, M. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up. Annals of Oncology, 2018
History
Weight loss of more than
10%
Symptoms B
Fever over 38 C and night

sweats
Pel-Ebstein Fever
Constitutional symptoms consisting of:
Pruritus
Chest pain, cough, shortness of breath

and back pain or bone pain
Pain that arises in the
lymphatic area
Family history of the same disease
Physical Examination
Asymptomatic lymphadenopathy, which is painless enlargement of lymph nodes,

usually asymmetrical with a dense, rubbery consistency.
The lymph node predilection is usually involved
Splenomegaly and hepatomegaly but rarely massive.
Exam and Tests
Hematological examination
• Complete blood count → anemia, neutrophilia, eosinophilia, lymphopenia
(advanced staging)
• LDH with high protein levels results in a sign of cell damage caused by cancer
or other health problems.
• Erythrocyte sedimentation rate → this test measures how quickly red blood
cells settle to the bottom of a test tube containing a blood sample (not specific)
Exam and Tests
Chest imaging • Mediastinal lymph node involvement
Lymphangiogr •
Lymph node involvement in the iliac and post-aortic regions
aphy
USG • Widely used to see enlarged lymph nodes in the paraaortal
CT • Often used for the diagnosis and evaluation of LH growth
PET-CT • The use of a PET-CT for response assessment after 2 cycles of chemotherapy
is a good prognostic indicator in patients with early disease
Histopathology
• Excisional biopsy of the involved node is preferred to

establish a definitive diagnosis highly recommended
• Fine Needle Aspiration Biopsy (FNAB), can be done with

varied results false positive/false negative
Biopsy
• In areas that are difficult to reach to see the condition of the
lymph nodes in the para-aortic iliac and mesentery 
laparotomy
background of pleomorphic
inflammatory cells was B cellsNon Hodgqin
found on lymph node lymphoma
biopsy examination
● Other tests, such as liver,

kidney and lung function
tests, echocardiography
and electrocardiography
are used to detect signs
and symptoms of other
organ involvement.
Hodgkin's Lymphoma Staging Based on Ann Arbor Criteria
Stadium Tissue involvement
I One lymph node area or one extralymphatic area.
Two or more lymph node areas on the same side of the diaphragmthe same or adjacent
II extralymphatic extension plus one or more lymph node regions on the same side of the
diaphragm.
III Areas of lymph nodes on both sides of the diaphragm that can befollowed by adjacent
extralymphatic expansion.
IV Diffuse involvement of one or more extralymphatic areas or organs.

Symptoms Characteristic
A Without symptoms
There is one of the following symptoms:
• Weight loss > 10% in the last 6 months.
B • Recurrent fever > 38 degrees Celsius
• Sweating at night.

X Bulky tumor which is a single mass > 10 cm in diameter
or a mediastinal mass >1/3 of the maximum transverse transthoracic diameter on Posterior
Anterior (PA) chest radiograph.
Hodgkin Lymphoma Guidelines: Diagnosis, Staging, Risk Stratification [Internet]. Emedicine.medscape.com.
Hodgkin's Lymphoma Staging
Hodgkin Lymphoma Guidelines: Diagnosis, Staging, Risk Stratification [Internet]. Emedicine.medscape.com.
MANAGEMENT
• The management of Hodgkin's lymphoma varies according to the type and stage with
treatment modalities consisting of radiotherapy, chemotherapy and combination therapy.
• About 85% of diseases can be cured
Management of First-line treatment of CHL patients usually consists of a combined

classic modality approach or chemotherapy alone
Hodgkin's • The intensity of treatment depends on the patient's risk profile at
lymphoma diagnosis and on the results of imaging
Eichenauer, D. A., Aleman, B. M. P., André, M., Federico, M., Hutchings, M., Illidge, T,Ladetto, M. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Annals of Oncology, 2018
Diagnosis & treatment of
limited-stage HL
Newly diagnosed patients ≤ 60 years
*Except for stage IA NLPHL

without risk factors (treated with
ISRT alone).
intermediate-stage HL
advanced-stage HL
• Standard treatment: ISRT 30 Gy
Treatment of NLPHL Stage IA without risk
• The ISRT fields for single-modality RT are larger than
factors
those for
combined-modality RT
• Such as rituximab or ofatumumab • NLPHL treated identically to cHL

Other stages
• Addition of an anti-CD20 antibody (e.g. R-
For patients with more disseminated CHOP) may improve treatment
disease at relapse and additional
poor-risk features. efficacy
Based on factors including time to
• New biopsy in patients with suspected NLPHL before salvage
relapse, disease extent at relapse
and prior treatment. therapy (excludes transformation into aggressive non-hodgkin
lymphoma)
Relapsed NLPHL
• Localised NLPHL relapses can be effectively treated with single-
agent anti-CD20 antibodies*
• More aggressive ChT, possibly combined with an anti-CD20
antibody, may be required†
• Salvage therapy should be tailored to the individual‡
• BV is not a treatment option
Therapeutic regimens for Hodgkin's lymphoma
Management in Cases of Relapse
Despite high cure rates with initial therapy, approximately 5%-10% of patients with
LH are refractory to initial treatment, and 10%-30% of patients will relapse after
achieving complete remission on initial treatment.
A number of retrospective analyzes have suggested that patients treated with

ASCT have better long-term outcomes compared to patients treated with
chemotherapy.
Ansell SM. Hodgkin Lymphoma: update on diagnosis, risk-stratification, and management. Mayo Clin Proc, 2020
Targeted Therapy and Immunotherapy in
Hodgkin's Lymphoma
CD30 therapy mechanism PD-1/PD-L1 therapy mechanism

(Brentuximab Vedotin) (Pembrolizumab)
Wang et al. Advances in CD30- and PD-1-targeted therapies for classical Hodgkin lymphoma. Journal of Hematology & Oncology 2018
PROGNOSIS
RECIST Criteria
1. Complete response, if all target lesions
disappear
2. Partial response, if there is a reduction in
size of at least 30% of the total diameter of
the target lesion.
3. Progressive disease, if there is an increase
in size of at least 20% of the total diameter
of the target lesion.
4. Stable disease, if there is no decrease or
increase in size to meet the criteria for
partial response or progressive disease.
Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R et al. New response

evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of
Cancer, 2009
Summary
1. Hodgkin's lymphoma is a malignancy that involves the lymphatic system, especially the
B-lymphocyte mutation
2. Has 2 main types CHL (95%) and NLPHL (5%)
3. The last few decades have seen significant progress. Currently, the LH cure rate is
around 80%.
4. The cause of Hodgkin's disease is still unknown. Possibly caused by infection with the
Epstein-Barr virus (EBV)
5. Excisional biopsy of the involved node is preferred to establish a definitive diagnosis
highly recommended
6. The use of a PET-CT for response assessment after 2 cycles of chemotherapy is a good
prognostic indicator in patients with early disease
7. A number of retrospective analyzes have suggested that patients treated with ASCT have
better long-term outcomes compared to patients treated with chemotherapy.
8. Targeted Therapy and Immunotherapy in Hodgkin's Lymphoma, CD30 , PD-1/PD-L1
THANKS…

Diagnosis and management of Hodgkin's lymphoma

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Diagnosis and management of Hodgkin's lymphoma

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Diagnosis And Management Of

Satria Alam Kadar

Menjadi pusat pendidikan yang unggul, mandiri dan berwawasan

1. Menyelenggarakan pendidikan di bidang Ilmu Penyakit Dalam

Emerging treatment The last few decades

There is a relationship between immune system malfunctions and the incidence

People receiving immunosuppressant therapy after organ transplant

Some opinions state that there is a relationship between Hodgkin's lymphoma

Another opinion says exposure to carcinogens, especially in the workplace,

• There is a bimodal age distribution

Insiden LH berdasarkan usia

White and black

From EBV-mediated biological

Epstein-Barr Virus Presence of a clonal EBV genome in LH

There is a threefold increased risk of LH

Incidence rates are higher in high-income countries

Hodgkin Lymphoma: Practice Essentials, Background, Pathophysiology [Internet]. Emedicine.medscape.com.

Mixed Cellularity Classical

Lymphocyte-Rich Classical Hodgkin Lymphoma

Mixed Cellularity Classical Hodgkin Lymphoma

The presence of malignant multinucleated

• Approximately 5% of all cases of LH

Medical history and

Fever over 38 C and night

Constitutional symptoms consisting of:

Chest pain, cough, shortness of breath

Family history of the same disease

Asymptomatic lymphadenopathy, which is painless enlargement of lymph nodes,

The lymph node predilection is usually involved

Splenomegaly and hepatomegaly but rarely massive.

Chest imaging • Mediastinal lymph node involvement

USG • Widely used to see enlarged lymph nodes in the paraaortal

CT • Often used for the diagnosis and evaluation of LH growth

• Excisional biopsy of the involved node is preferred to

• Fine Needle Aspiration Biopsy (FNAB), can be done with

● Other tests, such as liver,

IV Diffuse involvement of one or more extralymphatic areas or organs.

Management of First-line treatment of CHL patients usually consists of a combined

Newly diagnosed patients ≤ 60 years

*Except for stage IA NLPHL

Newly diagnosed patients ≤ 60 years

Newly diagnosed patients ≤ 60 years

• Such as rituximab or ofatumumab • NLPHL treated identically to cHL

A number of retrospective analyzes have suggested that patients treated with

CD30 therapy mechanism PD-1/PD-L1 therapy mechanism

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R et al. New response

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