MYELOPROLIFERATIVE

DISORDERS
LYMPHOMA

Edited by:
Djoko Heri Hermanto
Hematology-Medical Oncology Division, Department of Internal Medicine

Faculty of Medicine
University of Brawijaya
 Lymphoma

• The incidence of Hodgkin's disease appears fairly

stable, with ~7800 new cases diagnosed in 2004 in
Incidence the United States.
• Hodgkin's disease is more common in whites than in
blacks and more common in males than in femal

Clinical • Superficial lymphadenopathy with cervical

nodes
Features • Fever and drenching night sweats

• Eestablished by review of an adequate

Diagnosis biopsy specimen and depends on finding
multinucleated Reed-Sternberg (RS) cell

Faculty of Medicine
University of Brawijaya
 The right cervical and axillar lymphadenopathy

Faculty of Medicine
University of Brawijaya
 Hodgkin Lymphoma

Histologic classification
1. Lymphocyte-predominat HD: limited disease (stage I
or II) in the neck
2. Nodular sclerosis HD: the most common subtype,
associated with mediastinal mass & hilar
lymphadenopathy in addition to disease in the neck
3. Mixed cellularity HD
4. Lymphocyte-depleted HD
The mixed cellularity HD & lymphocyte-depleted HD are
more common in constitusional symptom and advace
disease.
Faculty of Medicine
University of Brawijaya
Clinical Features
Superficial lymphadenopathy with cervical nodes
Usually begins in the neck and spreads to adjacent lymph
nodes with occasional spread to nonlymphoid
structure e.g. the mediastinum into the lung
The lymph nodes are usualy nontender & firm or rubbery
Fever (>38o C), drenching night sweats and/or weight loss
of > 10% of usual weight  a poor prognosis
Pruritus & alcohol-induced pain in areas of disease
involment

Faculty of Medicine
University of Brawijaya
Laboratory Findings
In the peripheral blood:
- anemia
- neutrophilia
- eosinophilia
- monocytosis
- lymphocytopenia
- trombocytosis or thrombocytopenia
Liver function test may be abnormal & the LDH may be
elevated
 Diagnosis
Biopsy specimen : multinucleated Reed-Sternberg (RS)
cells
RS cells or their variants are usually large cells with ≥ 2
nuclei, each with a prominent nucleolus that
sometime give it an “owl’s eyes” appearance
FNA is inadequate for initial diagnosis
Determination of an accurate anatomic stage is an
important part of the evaluation. The staging system
is the Ann Arbor staging system originally developed
for Hodgkin disease

Faculty of Medicine
University of Brawijaya
 Reed-sternberg cell (Owl’s eyes)
Faculty of Medicine
University of Brawijaya
 Table 1. The Ann Arbor Staging System for Hodgkin’s Disease
Stage Definition
I Involvement of a single lymph node region or lymphoid structure (e.g.,
spleen, thymus, Waldeyer's ring)
II Involvement of two or more lymph node regions on the same side of the
diaphragm (the mediastinum is a single site; hilar lymph nodes should be
considered “lateralized” and, when involved on both sides, constitute
stage II disease)
III Involvement of lymph node regions or lymphoid structures on both sides
of the diaphragm
III1 Subdiaphragmatic involvement limited to spleen, splenic hilar nodes,
celiac nodes, or portal nodes
III2 Subdiaphragmatic involvement includes paraaortic, iliac, or mesenteric
nodes plus structures in III1

IV Involvement of extranodal site(s) beyond that designated as “E”. More

than one extranodal deposit at any location. Any involvement of liver or
bone marrow
A No symptoms
B Unexplained weight loss of >10% of the body weight during the 6 months
before staging investigation
Unexplained, persistent, or recurrent fever with temperatures >38°C
during the previous month
Recurrent drenching night sweats during the previous month
E Localized, solitary involvement of extralymphatic tissue, excluding liver
and bone marrow

Faculty of Medicine
University of Brawijaya
 Management
Localized Hodgkin's disease are cured >90%
Extended field radiotherapy in patients with good
prognostic factors: a high cure rate
Chemotherapy: initial therapy in all stages of Hodgkin's
disease
Combination chemotherapy and radiotherapy
Relapse after primary therapy of Hodgkin's disease can
frequently still be cured.
Autologous BM transplantation can cure half of patients
who fail effective chemotherapy regimens

Faculty of Medicine
University of Brawijaya
Non Hodgkin Lymphoma (NHL)
Most NHLs are neoplasm of B-lymphocyte origin
with characteristic cell membrance surface
Incidence markers.
NHL are more frequent in the elderly and more
frequent in men.

• Superficial lymphadenopathy, with cervical

Clinical nodes being most common
Features • Fever, weight loss and night sweats

Lactate dehydrogenase (LDH)

Laboratory β2-microglobulin
Features Uric acid
Creatinine

Faculty of Medicine
University of Brawijaya
 Etiology
• The etiology of non-Hodgkin’s lymphoma
are environmental factors that have been
implicated in the occurrence of non-
Hodgkin's lymphoma, including infectious
agents, chemical exposures, and medical
treatments.
 Classification of NHL
• Before Rappaport classification (before 1956):
Gall & Mallory (1942), Jackson & Parker (1947),
Custer & Bernhard (1948).
• Rappaport: 1956  1966 1972.
• Lukes & Collins: 1974  1977.
• IWF (International Working Formulation): 1982
• REAL: 1993, 1997
• WHO: 2003  revised 2008
 IWF Rappaport Lukes & Collins

•Low Grade
- Small Lymphocytic DLWD SL, Plasmacytoid L
- Follicular, small cleaved cell NLPD SC – FCC
- Follicular, mixed small & large cell NML SC – FCC; Lg C - FCC
•Intermediate Grade
- Follicular, large cell LgC; LgNC – FCC
NH
- Diffuse small cleaved cell SC – FCC – D
DLPD
- Diffuse mixed small and large cell SC – D; Lg C – D
DM
- Diffuse large cell Lg NC – FCC – D
DH
•High Grade Lg C- FCC – D; Lg NC –
FCC – D
- Immunoblastic large cell
DH Lbl sarcoma (of T Cell or
- Lymphoblastic B Cell)
Lbl (convulated or Convulated T Cell
non convulated)
- Small non cleaved cell
DU (Burkitt or non SNC - FCC
Burkitt)
 Notes:
• DLWD : Diffuse lymphocytic well differentiated
• NLPD : Nodular lymphocytic poorly differentiated
• DLPD : Diffuse lymphocytic poorly differentiated
• DM : Diffuse mixed lymphoma
• DH : Diffuse histiocytic lymphoma
• DU : Diffuse Undifferentiated lymphoma
• NML : Nodular mixed lymphocytic – hystiocytic
• NH : Nodular histiocytic
• NC : Non cleaved
• FCC : Follicular centre cell
• Lbl : Lymphoblastic
• L: lymphocyte, C : Cleaved, S : Small, Lg : Large, D : Diffuse
 WHO/ REAL Classification of the NHL According to Clinical
Aggressiveness
The Indolent Lymphomas
B-cell neoplasms
Small lymphocytic lymphoma/B-cell chronic lymphocytic leukemia
Lymphoplasmacytic lymphoma ( Waldenstrom’s macroglobulinemia)
Plasma cell myeloma / plasmacytoma
Hairy cell leukemia
Follicular lymphoma (grade I and II)
Marginal zone B-cell lymphoma
Mantle cell lymphoma
T-cell neoplasms
T-cell large granular lymphocyte leukemia
Mycosis fungoides
T-cell prolymphocytic leukemia
Natural killer cell neoplasms
Natural killer cell large granular lymphocyte leukemia
The aggressive lymphomas
Follicular lymphoma (grade III)
Diffuse large B-cell lymphoma
Peripheral T-cell lymphoma
Anaplastic large cell lymphoma, T/null cell
The highly aggressive lymphomas
Burkitt’s lymphoma
Precusor B lymphoblastic leukemia/lymphoma
Adult T-cell lymphoma / leukemia
Precusor T lymphoblastic leukemia / lymphoma
REAL: Revised European-American Classification of Lymphoid Neoplasms
 NCCN, Version I.2013

NHL: Classification
 NCCN, Version I.2013

NHL: Classification
 Diagnosis
• Ax: mass, no pain, systemic symptom at present
• Physical Exam (PE): a complete PE with particular attention to
lymphadenopathy at node bearing areas, enlargement of liver & spleen,
Performance status, BSA
• Laboratory: CBC, LFT, RFT, LDH, Uric Acid, BMP, HBsAg, Anti HBc,
pregnancy test
• Imaging: especially for staging, include: Chest X-ray, Abdominal USG, CT
Scan, Echocardiography, MRI, PET Scan (if needed).
• Histopathology: very important to be done before treatment, include IHC
panel or Cell surface marker analysis by flowcytometry for DLBCL (CD20,
CD3, CD5, CD10, CD19, CD45)
• The diagnosis of NHL should mention: origin, histopathology, and Stage…!!!
– E.g.: NHL Colli S, DLBCL, Stage IIB
 Principles management of NHL
• Based on histopathology and stage of NHL
• Concern to prognostic factors, years of age, and
co-morbidity factors
• Treatment modality:
– Radiotherapy (for localized disease: stage I, II)
– Chemotherapy (for advanced disease: stage III, IV)
– NO SURGERY, except NHL with ulcerative disease
 Treatment of NHL according to IWF
criteria
• Low grade
Localized : Observation or radiation (if symptom +)
Advanced : Chemotherapy (chlorambucil or CVP)
• Intermediate grade
Localized : Chemotherapy + Radiation
Advanced : Combined chemotherapy
• High grade
Localized : Intensive chemotherapy & radiation
Advanced : Intensive chemotherapy & radiation
 Principles
Treatment of NHL according to
Clinical Aggressiveness
 The indolent lymphoma
• Stage I/II (early stage):
Thigh Observation or radiation
• Stage III/IV (advanced stage):
Single or combined chemotherapy &
locoregional radiation
• Transformation, histologically:
Combined chemotherapy or high dose
chemotherapy followed by BMT
 The aggressive lymphoma

• Stage I/II (early stage), non Bulky disease:

Chemotherapy and adjuvan radiation
• Stage I/II (early stage), Bulky disease:
Chemotherapy, and locoregional radiation
• Stage III/IV (advanced stage):
Chemotherapy, local radiation for bulky disease
• Age >60 years:
Individual chemotherapy, concern to co-morbidity factors
 The Highly Aggressive lymphoma
• Lymphoblastic :
Chemotherapy with similar regiment for
leukemia lymphoblastic acute (hyper-
CVAD/Ara-C-MTX)
• Burkitt’s dan Burkitt’s like lymphoma :
Chemotherapy with Stanford’s protocol
 Prognosis
• Prognosis limfoma maligna sangat tergantung dari 2 faktor:
- Tipe dari limfoma (histopatologi)
- Stadium klinis
• Noduler mempunyai prognosis lebih baik daripada difus, tetapi
tipe noduler sering relaps.
• Usia : > 60 th prognosis kurang baik
• Ukuran tumor : > 10 cm, terutama di mediastinum  kurang
baik
• Terserang ekstra nodal multipel, t.u: hati dan Sutul  kurang
baik
• Penyakit progresif selama tx, atau relaps < 1 thn setelah
kemoterapi  kurang baik.
 International Prognostic Index
• Factors:
- Age >60 y.o
- Performance status ≥ 2 (ECOG)
- Extranodal sites ≥ 2
- LDH increased (N: 240-480 mg/dL)
- Stage III/IV
International Prognostic Index
Factors Risk Response DFS at 5 years
Rate
0-1 low risk 87% 73%
2 low – intermediate 67% 51%
risk
3 high – 55% 43%
intermediate risk
4-5 high risk 44% 26%
 MODUL TASK

1. Describe histologic classification of Hodgkin’s disease!

2. Describe in brief The Ann Arbor Staging System for
Hodgkin’s Disease !
3. Describe clinical features and laboratory findings to
diagnose Hodgkin’s disease !
4. Describe in brief the treatment of Hodgkin’s disease !
5. Describe etiology of non-Hodgkin’s lymphoma !

Faculty of Medicine
University of Brawijaya
 MODUL TASK…..cont’d

6. Describe clinical features and laboratory findings to

diagnose non-Hodgkin’s lymphoma !
7. Describe in brief The International Prognostic Index for
non-Hodgkin’s lymphoma !

Faculty of Medicine
University of Brawijaya
 THANK YOU

Faculty of Medicine
University of Brawijaya