MANAGEMENT OF LYMPHADENOPATHY :

FOCUSED ON LYMPHOMA

Irza Wahid,
Subdivision of Hematology & Medical Oncology
Departement of Internal Medicine
Faculty of Medicine, Andalas University
Padang

INTRODUCTION

LYMPHADENOPATHY
Lymph nodes that are abnormal in size,
consistency or number
Generalized / Localized

Lymphatic System
Network that filters antigens from the interstitial fluid
Primary site of immune response from tissue antigens
Lymphatic drainage in all organs of the body except
brain, eyes, marrow and cartilage
600 lymph nodes in body
Slow flow, low pressure system returns interstitial fluid
to the blood system

Lymph nodes
Capsular shell
Fibroblasts and reticulin
fibers
Macrophages
Dendritic cells
T cells
B cells

Peripheral lymphadenopathy

Most cases benign, self limited illness

Primary or secondary manifestation of many illnesses
The CHALLENGE is to decide if it is representative of a
serious illness

Parameters to help distinguish between

benign and serious illness
Age
Character
Duration
Location

Malignancy much more

common in patients greater 50
yrs of age

Lymph node character

Size

Greater than one centimeter generally considered --abnormal

Exception inguinal area, lymph nodes commonly palpated (>1.5 cm)
Supraclavicula, iliaca , poplitea in any size are abnormal, epitrochlear > 5 mm is
abnormal.
Size does not indicate a specific disease process

Pain

Indication of rapid increase in size: stretch of capsular shell

NOT useful in determining benign vs malignant state
Inflammation, suppuration, hemorrhage

Consistensy

Stone hard: typical of cancer usually metastatic

Firm rubbery: can suggest lymphoma
Soft: infection or inflammation

Duration
Lymphadenopathy :
- onset < 2 weeks
- duration > 1 year
- no progression

usually benign

Location

Post cervical: scalp, neck skin of arms thorax cervical and axillary nodes (lymphoma, head/neck ca)

Location

DIFFERENTIAL DIAGNOSIS
M ALIGNANT
I NFECTION
A UTOIMMUNE
M ISCELLANEOUS/UNUSUAL
I ATROGENIC

DIAGNOSIS

BIOPSY

LYMPHADENOPHATY
NEOPLASM
PRIMARY
HODGKIN

NON NEOPLASM
METASTATIC

NON HODGKIN

B-CELL

T-CELL

LIMFOMA MALIGNUM NON HODGKIN

DEFINISI
Sekelompok keganasan primer limfosit
yang dapat berasal dari limfosit B,
limfosit T dan kadang
( amat
jarang ) berasal dari sel NK ( natural
killer ) yang berada dalam sistim limfe,
sangat heterogen baik tipe histologis,
gejala, perjalanan klinis, respon terapi
maupun prognosis

ETIOLOGI DAN FAKTOR RISIKO

Etiologi pasti tidak diketahui beberapa faktor
risiko :
Immundefisiensi
Agen infeksius seperti EBV, HIV
Paparan lingkungan dan pekerjaan seperti peternak
pekerja hutan / pertanian yang disebabkan paparan
herbisida dan pelarut organic serta paparan ultraviolet
Diet tinggi lemak hewani dan merokok

CA Cancer J Clin 2011;61:212-236. VC 2011 American Cancer Society.

Jacqueline Kennedy Onassis

Former First Lady

King Hussein of Jordan

Mr. T
(Lawrence Tureaud)

Television star, The A-Team.

Sylvester Stallone's adversary in "Rocky III.

Lymphoma Classification

( WHO, 2001 )

B-cell neoplasms

Precursor B-cell neoplasms (2 types)

Mature B-cell neoplasms (19) Diffuse large B cell lymphoma
B-cell proliferations of uncertain malignant potential (2)

T-cell & NK-cell neoplasms

Precursor T-cell neoplasms (3)

Mature T-cell and NK-cell neoplasms (14)
T-cell proliferation of uncertain malignant potential (1)

Hodgkin lymphoma

Classical Hodgkin lymphomas (4)

Nodular lymphocyte predominant Hodgkin lymphoma (1)

Lymphoma Classification
A.

( WHO, 2001 )

B-Cell Neoplasms

I.
Precursor B-cell neoplasm : Precursor B- acute lymphoblastic leukemia /
lymphoblastic lymphoma (B-ALL, LBL)
II. Mature (peripheral) B-neoplasms
a.
B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma
b.
B-cell prolymphocytic leukemia
c.
Lymphoplasmacytic lymphoma
d.
Mantle cell lymphoma
e.
Folliculer lymphoma
f.
Splenic marginal zone B-cell lymphoma (+ villous lymphocytes)
g.
Hairy cell leukemia
h.
Plasma cell myeloma/plasmacytoma
i.
Extranodal marginal zone B-cell lymphoma of MALT type
j
Nodal marginal zone B-cell lymphoma (+ monocytoid B cells)
k.
Diffuse large B-cell lymphoma
l.
Burkitts lymphoma/Burkitt cell leukemia

LYMPHOMA GRADATION ( NCCN 2010 )

Indolent (slow growing) B-celllymphomas
Follicular lymphoma
Chronic lymphocytic leukemia / small
lymphocytic lymphoma
MALT
Splenic marginal zone lymphoma
Nodal marginal zone
Aggressive (fast growing) B-cell lymphomas
Diffuse large B-cell lymphoma
Mantle cell lymphoma
Highly aggressive B-cell lymphomas
Burkitt lymphoma
Lymphoblastic lymphoma
AIDS-related B-cell

Non-Hodgkins Lymphomas

DLBCL
35%

PENDEKATAN DIAGNOSTIK
1. Anamnesis
Umum
Pembesaran KGB atau organ
BB menurun 10 % dalam waktu 3 bulan
Demam tinggi 38 C 1 minggu tanpa sebab
Keringat malam
Keluhan anemia
Keluhan organ ( seperti lambung, nasofaring )
Penggunaan obat ( Diphantoine )

Khusus
Penyakit autoimun ( SLE, syogren, reuma )
Kelainan darah
Infeksi ( Toxoplasmosis, mononucleosis, tuberculosis, lues, cakar kucing

2. Pemeriksaan fisik
Pembesaran KGB
Kelainan / pembesaran organ
Performance status : WHO, Karnofsky

Laboratorium
* Rutin Darah perifer lengkap ( DPL ), Gambaran darah
tepi ( GDT )
Urine lengkap
* Kimia Klinik
* Imunophenotyping parafin panel CD 20, CD 3
Radiologi
* Foto torak CT Scan torak
* USG Abdomen CT Scan abdomen
* Limfografi
Biopsi KGB
BMP & biopsi SST

Minimal immunohistochemistry CD20 is mandatory

MANAGEMENT
CHOP Regimen
Cyclophosphamide 750mg/m2, iv, day 1
Doxorubicine 50mg/m2, iv, day 1
Vincristine 1.4mg/m2, max. dose 2mg, iv, day1
Prednisone 100 mg/day, oral, days 1-5
6-8 cycles, 3-weekly schedule
OR 80%-90%, CR 50%-60%
Curative < 40%

CHOP was a good standard

It was associated with
a good efficacy

100
80

It was easy to use

60
Overall survival (%)

It gave reproducible
results

CHOP
MACOP-B
ProMACE-CytaBOM
m-BACOD

40
20
0

10

15

GELA-LNH 98.5: CHOP vs MabThera +

CHOP in previously untreated DLBCL
GELA phase III trial
Cyclophosphamide 750mg/m
Doxorubicin (Doxotil) 50mg/m
Vincristine 1.4mg/m
Prednisone 100mg /day x 5 days

3 weeks

8 cycles

MabThera + CHOP 375mg/m

Coiffier B, et al. N Engl J Med 2002;346:23543

LIMFOMA MALIGNUM HODGKIN

Khas sel Reed Steinberg
Klasifikasi
1. Tipe lymphocyte predominant prognosis baik
2. Tipe mixed cellularity prognosis lebih buruk
3. Tipe lymphocyte depleted prognosis buruk
4. Tipe nodular sclerosis prognosis: diantaranya

PENATALAKSANAAN
1. Radioterapi
2. Radioterapi + Kemoterapi
3. Kemoterapi
ABVD
CHOP
CVP
EPOCH ( CHOP + Etoposide)