HODGKIN’S DISEASE

AND
NON-HODGKIN’S
LYMPHOMA
WHO/REAL Classification of Lymphoid Neoplasms
B-Cell Neoplasms
Mature (peripheral) T neoplasms
Precursor B-cell neoplasm
T-cell chronic lymphocytic leukemia / small
Precursor B-lymphoblastic leukemia/lymphoma
lymphocytic lymphoma
(precursor B-acute lymphoblastic leukemia) T-cell prolymphocytic leukemia
Mature (peripheral) B-neoplasms T-cell granular lymphocytic leukemiaII
B-cell chronic lymphocytic leukemia / small lymphocytic Aggressive NK leukemia
lymphoma
Adult T-cell lymphoma/leukemia (HTLV-1+)
B-cell prolymphocytic leukemia
Extranodal NK/T-cell lymphoma, nasal type#
Lymphoplasmacytic lymphoma‡
Splenic marginal zone B-cell lymphoma Enteropathy-like T-cell lymphoma**

(+ villous lymphocytes)* Hepatosplenic γδ T-cell lymphoma*

Hairy cell leukemia Subcutaneous panniculitis-like T-cell lymphoma*

Plasma cell myeloma/plasmacytoma Mycosis fungoides/Sézary syndrome

Extranodal marginal zone B-cell lymphoma of MALT type Anaplastic large cell lymphoma, T/null cell,
Nodal marginal zone B-cell lymphoma primary cutaneous type
(+ monocytoid B cells)* Peripheral T-cell lymphoma, not otherwise characterized
Follicular lymphoma Angioimmunoblastic T-cell lymphoma
Mantle cell lymphoma
Anaplastic large cell lymphoma, T/null cell,
Diffuse large B-cell lymphoma
primary systemic type
Mediastinal large B-cell lymphoma
Hodgkin’s Lymphoma (Hodgkin’s Disease)
Primary effusion lymphoma†
Nodular lymphocyte predominance Hodgkin’s lymphoma
Burkitt’s lymphoma/Burkitt cell leukemia§
Classic Hodgkin’s lymphoma
T and NK-Cell Neoplasms
Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)
Precursor T-cell neoplasm
Precursor T-lymphoblastic leukemia/lymphoma Lymphocyte-rich classic Hodgkin’s lymphoma

(precursor T-acute lymphoblastic leukemia Mixed cellularity Hodgkin’s lymphoma

Lymphocyte depletion Hodgkin’s lymphoma
‡ Formerly known as lymphoplasmacytoid lymphoma or immunocytoma
II Entities formally grouped under the heading large granular lymphocyte † Not described in REAL classification
leukemia of T- and NK-cell types
§ Includes the so-called Burkitt-like lymphomas
* Provisional entities in the REAL classification
** Formerly known as intestinal T-cell lymphoma
# Formerly know as angiocentric lymphoma
Hematopoietic System
B cell malignancies

Lymph node, Lymph node,

lymph, blood, lymph, blood,
Bone marrow Bone marrow
bone marrow bone marrow

Progressive B lymphocyte maturation

Lymphoid stem cell Maturing B cell Mature B cell Plasma cell

many stages

Pre-B acute lympho- B cell lymphoma Chronic lympho- Multiple myeloma

cytic leukemia
blastic leukemia
 Hodgkin’s Disease/Lymphoma
In the Beginning
First described in 1832 by Dr. Thomas Hodgkin

Neoplasm of B lymphocytes – large pleomorphic prominent

nucleolus in a halo - Hodgkin cells

Reed-Sternberg cell – binucleate Hodgkin cell with owl eye

appearance

Classification:
Classical Hodgkin’s
Nodular sclerosis – low grade
Mixed cellularity
Lymphocyte rich classical 1798-1866
Lymphocyte depleted. – high grade

Nodular lymphocyte-rich Hodgkin’s

 Hodgkin’s Disease/Lymphoma
In the Beginning
 Bimodal age distribution
 first peak between 2nd - 3rd decade of life
 second peak between 5th - 6th decade of life

 Male: Female 2:1 in kids, adults almost equal M:F

 Mixed cellularity (MC) Hodgkin’s Disease is more

common at younger ages

 More common in immune deficiency patients

 Hodgkin’s Disease/Lymphoma
In the Beginning
Fatal disease with 90% of untreated patients dying
within 2 to 3 years

With chemotherapy, >80% of patients suffering from

HD are cured.

Pathogenesis of HD is still largely unknown.

HD nearly always arises and disseminates in lymph

nodes
Hodgkin’s Disease/Lymphoma
Clinical Presentation
 Nontender lymph nodes enlargement (localized)
 neck and supraclavicular area
 mediastinal adenopathy
 other (abdominal, extranodal disease)
 systemic symptoms (B symptoms)
 fever
 night sweats
 unexplained weight loss (10% per 6 months)
 other symptoms
 fatigue, weakness, pruritus
 cough , chest pain, shortness of breath, vena cava
syndrome
 abdominal pain, bowel disturbances, ascites
 bone pain
Hodgkin’s Disease/Lymphoma
Clinical Presentation
SIGNS & SYMPTOMS % OF PATIENTS
Lymphadenopathy 90
Mediastinal mass 60
“B” symptoms 30
Fever, weight loss, night sweats
Hepatosplenomegaly 25

 Most commonly involved lymph nodes are the

cervical and supraclavicular in 75%
 Bone marrow is involved in 5% of patients
Reed-Sternberg Cells
CD 30 Immunostain
Hodgkin’s Disease/Lymphoma
Clinical Presentation
Stage Definition

I Involvement of a single lymph node region (I) or of a single extralymphatic organ or site
(IE)

II Involvement of two or more lymph node regions on the same side of the diaphragm (II)
or localized involvement of an extralymphatic organ or site and one or more lymph node
regions on the same side of the diaphragm (IIE)

III Involvement of lymph node regions on both sides of the diaphragm (III) which may be
accompanied by involvement of the spleen (IIIS) or by localized involvement of an
extralymphatic organ or site (IIIE) or both (IIISE)

IV Diffuse or disseminated involvement of one or more extra lymphatic organs or tissues

with or without associated lymph node involvement

B symptoms: fever > 38ºC for three consecutive days, drenching night sweats or unexplained loss 10% or more
of weight the preceding 6 months
Hodgkin’s Disease/Lymphoma
Treatment
 Unfavorable prognostic factors:
- Stage IIIB, IV
- B symptoms
- Bulky disease
- High ESR >50
Hodgkin’s Disease/Lymphoma
Treatment
 Adolescent patients who have achieved
maximum growth can be treated as adult
patients

 Chemotherapy alone protocols for

localized disease has been used in
developing countries with some success

Lobo-Sanahuja F: Medical and Pediatric Oncology 22(6);1994

Hodgkin’s Disease/Lymphoma
Treatment
With appropriate treatment about 85% of
patients with Hodgkin’s disease are curable

 I A,B Radiation Therapy

 II A Combination Chemo +
Radiotherapy
 IIB; IIIA,B; IVA,B Combination Chemo
(+/- radiotherapy)
Hodgkin’s Disease/Lymphoma
Treatment
 Radiation therapy (35-40 Gy) 80-90% RC
 Mantle field
 Paraaortic field
 Pelvic field

 Combination chemotherapy
 ABVD 80% RC
 BEACOPP 90% RC
Limfoma non Hodgkin merupakan
sekelompok keganasan yang berasal dari
sistem kelenjar getah bening, yang
biasanya menyebar ke seluruh tubuh.
Diagnosis limfoma non Hodgkin
ditegakkan berdasarkan konfirmasi
patologis melalui pemeriksaan biopsi
jaringan
 Patogenesis terjadinya limfoma non Hodgkin adalah
translokasi kromosom dan perubahan molekuler,
seperti t(14;18)(q32;q21), t(11;14)(q13;q32), dan
lainnya.
 Beberapa virus mempengaruhi patogenesis
terjadinya limfoma non Hodgkin, oleh karena
kemampuan mereka untuk menginduksi stimulasi
antigen dan disregulasi sitokin, yang akhirnya
menyebabkan stimulasi, proliferasi, dan
limfomagenesis sel B dan sel T yang tak terkontrol.
Virus-virus ini antara lain yaitu virus Epstein Barr,
hepatitis C, human T cell leukemia virus type 1 (HTLV-
1).
 NHL: Inseden 5x lbh sering dari pada HL
 Laki-laki >> wanita
 Rata-rata usia 42 th-an
 Aggressive lymphoma merupakan limfoid
yang paling sering ditemukan.
 Non-Hodgkin’s Lymphoma
Rappaport Classification
Nodular (follicular) Diffuse

Indolent Aggressive

Small cell Large cell

Non-Hodgkin’s Lymphoma
Rappaport Classification

 Small cell, follicular

 Small cell, diffuse
 Large cell, follicular
 Large cell, diffuse
 Non-Hodgkin’s Lymphoma
Immunophenotyping
 Immunohistochemistry
 Immunofluorescence
 Flow cytometry

 Identification of CD’s (cluster determinants)

 CD5 = T cell type
 CD20 = B cell type
Non-Hodgkin’s
Lymphoma
Cluster
Determinants
Non-Hodgkin’s Lymphoma
Working Classification
 Low Grade
 Small Lymphocytic
 Follicular small-cleaved cell
 Follicular mixed small-cleaved and large cell
 Intermediate Grade
 Follicular large cell
 Diffuse small cleaved cell
 Diffuse mixed small and large cell
 Diffuse large cell
 High Grade
 Large cell immunoblastic
 Lymphoblastic
 Small non-cleaved cell (Burkitt's and non-Burkitt's type)
 Hodgkin Non Hodgkin Lymphoma
Lymphoma
Classical HL Indolent Aggressive Highly
(NS, MC, LR, Aggressive
LD)
B cell B cell B cell
Nodular Follicular DLBCL Pre-B
lymphocyte SLL/CLL FLg3 and tFL lymphoblastic
Predominant Marginal zone Mantle cell Burkitt
(NLPHL) LP (WM) Primary effusion

T/NK cell T/NK cell T/NK cell

Mycosis fungoides ALCL Pre-T
Sezary syndrome Angioimmunoblastic lymphoblastic
Primary cut ALCL Subq panniculitis-like
Blastic NK
Extnanodal NK/T
nasal
Enteropathy-type
Hepatosplenic
Multiple
PTCL nos
Myeloma
Non-Hodgkin’s Lymphoma
REAL Classification
 Revised European-American Lymphoma
 Mid 1990’s – International Lymphoma
Study Group (informal group of
hematopathologists)

 Using immunophenotype, cytogenetics,

molecular diagnostics
 Reclassified lymphomas by diagnostic
criteria and not by risk categories
 Frequency of NHL Subtypes in Adults

Mantle cell (6%)

Peripheral T-cell (6%)

Indolent (35%)
Other subtypes with a
frequency 2% (9%)

Composite
lymphomas (13%)

Diffuse large
Armitage et al. J Clin Oncol. 1998;16:2780–2795
B-cell (31%)
WHO/REAL Classification of Lymphoid Neoplasms
B-Cell Neoplasms
Mature (peripheral) T neoplasms
Precursor B-cell neoplasm
T-cell chronic lymphocytic leukemia / small
Precursor B-lymphoblastic leukemia/lymphoma
lymphocytic lymphoma
(precursor B-acute lymphoblastic leukemia) T-cell prolymphocytic leukemia
Mature (peripheral) B-neoplasms T-cell granular lymphocytic leukemiaII
B-cell chronic lymphocytic leukemia / small lymphocytic Aggressive NK leukemia
lymphoma
Adult T-cell lymphoma/leukemia (HTLV-1+)
B-cell prolymphocytic leukemia
Extranodal NK/T-cell lymphoma, nasal type#
Lymphoplasmacytic lymphoma‡
Splenic marginal zone B-cell lymphoma Enteropathy-like T-cell lymphoma**

(+ villous lymphocytes)* Hepatosplenic γδ T-cell lymphoma*

Hairy cell leukemia Subcutaneous panniculitis-like T-cell lymphoma*

Plasma cell myeloma/plasmacytoma Mycosis fungoides/Sézary syndrome

Extranodal marginal zone B-cell lymphoma of MALT type Anaplastic large cell lymphoma, T/null cell,
Nodal marginal zone B-cell lymphoma primary cutaneous type
(+ monocytoid B cells)* Peripheral T-cell lymphoma, not otherwise characterized
Follicular lymphoma Angioimmunoblastic T-cell lymphoma
Mantle cell lymphoma
Anaplastic large cell lymphoma, T/null cell,
Diffuse large B-cell lymphoma
primary systemic type
Mediastinal large B-cell lymphoma
Hodgkin’s Lymphoma (Hodgkin’s Disease)
Primary effusion lymphoma†
Nodular lymphocyte predominance Hodgkin’s lymphoma
Burkitt’s lymphoma/Burkitt cell leukemia§
Classic Hodgkin’s lymphoma
T and NK-Cell Neoplasms
Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)
Precursor T-cell neoplasm
Precursor T-lymphoblastic leukemia/lymphoma Lymphocyte-rich classic Hodgkin’s lymphoma

(precursor T-acute lymphoblastic leukemia Mixed cellularity Hodgkin’s lymphoma

Lymphocyte depletion Hodgkin’s lymphoma
‡ Formerly known as lymphoplasmacytoid lymphoma or immunocytoma
II Entities formally grouped under the heading large granular lymphocyte † Not described in REAL classification
leukemia of T- and NK-cell types
§ Includes the so-called Burkitt-like lymphomas
* Provisional entities in the REAL classification
** Formerly known as intestinal T-cell lymphoma
# Formerly know as angiocentric lymphoma
Burkitt’s Lymhoma
Starry, Starry Night
 Non-Hodgkin’s Lymphoma
Lymphoblastic NHL

 Very aggressive
 Treatment is with acute lymphocytic
leukemia regimen
 Often requires high-dose therapy and
allogeneic transplantation for
relapsed/refractory disease
Gamma Delta-T-cell NHL

 Very, very aggressive

 Very poor outcome with standard-dose
therapy
 High-dose therapy and allogeneic
transplantation is standard-of-care in first
remission
 CD57 protein positivity
Gejala

 Pembesaran KGB tidak nyeri

 Demam, keringat malam, penurunan BB,
lemah badan

 Lab :
 Hematologi: Anemia, eosinofilia, LED naik
 Flow cytometry: detelsi limfosit abnormal
 LFT, RFT,hiperurecemia, LDH, FOTO
THORAX, USG ABD
Monoclonal Abs - Rituxan