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Limfoma Maligna

Heri Sutrisno
SMF / Bagian Penyakit Dalam RSUD Prof Dr WZ Johannes
Hematopoietic Malignancies

Lymphoma is a general term for


hematopoietic solid malignancies of the
lymphoid series.

Leukemia is a general term for liquid


malignancies of either the lymphoid or the
myeloid series.
What is Lymphoma?

Neoplasms of lymphoid
origin, characterized by the
abnormal proliferation B or
T cells in lymphoid tissue
typically causing
lymphadenopathy
Clonal expansions of cells at
certain developmental
stages
What is Lymphoma

Lymphomas are cancers that begin by the


malignant transformation of a lymphocyte in
the lymphatic system
Many lymphomas are known to be due to
specific genetic mutations
Follicular lymphoma due to overexpression of
BCL-2 (gene that blocks programmed cell
death)
What is the Lymphatic System?
Made up of organs, such as the tonsils,
spleen, liver, bone marrow and a network
of lymphatic vessels that connect glands,
called lymph nodes
Lymph nodes located throughout the body
Lymph nodes filter foreign particles out of
the lymphatic fluid
Contain B and T lymphocytes
Lymphatic System

Lymph nodes act as a filter to


remove bacteria, viruses, and
foreign particles
Most people will have had swollen
glands at some time as a response
to infection
Blood Cell and Lymphocyte
Development
STEM CELLS

Multipotential Multipotential
myeloid cells lymphocytic cells

Differentiate & mature Differentiate & mature


into 6 into 3
Types of blood cells Types of lymphocytes

red cells basophils T lymphocytes


neutrophils monocytes B lymphocytes
eosinophils platelets Natural Killer Cells
Lymphocytes
Most lymphocytes are in lymph nodes,
spleen, bone marrow and lymphatic vessels
20% of white blood cells in blood are
lymphocytes
T cells, B cells, natural killer cells
B cells produce antibodies that help fight
infectious agents
T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells

Immature lymphocytes that travel to the


thymus differentiate into T-Cells
T is for thymus
Immature lymphocytes that travel to the
spleen or lymph nodes differentiate into B
cells
"B" stands for the bursa of Fabricius, which is
an organ unique to birds, where B cells mature.
ALL CLL Lymphomas MM
germinal center
nave

B-lymphocytes

Plasma
Lymphoid cells
progenitor T-lymphocytes

AML Myeloproliferative disorders


Hematopoietic Myeloid Neutrophils
stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
Classification

Biologically Clinically useful


rational classification
classification
Diseases that have distinct Diseases that have distinct
morphology clinical features
immunophenotype natural history
genetic features prognosis
clinical features treatment
Classification

Usually classified by how the cells look under


a microscope and how quickly they grow and
spread
Aggressive lymphomas (high-grade lymphomas)

Indolent Lymphomas (low-grade lymphomas)


Lymphoma classification
(2001 WHO)
B-cell neoplasms
precursor
mature Non-
Hodgkin
T-cell & NK-cell neoplasms Lymphomas
precursor
mature
Hodgkin lymphoma
Three common lymphomas

Follicular lymphoma
Diffuse large B-cell lymphoma
Hodgkin lymphoma
Relative frequencies of
different lymphomas

Non-Hodgkin Lymphomas

Diffuse large B-cell

Hodgkin NHL Follicular


lymphoma

Other NHL

~85% of NHL are B-lineage


Mechanisms of lymphomagenesis

Genetic alterations
Infection
Antigen stimulation
Immunosuppression
Epidemiology of lymphomas

males > females


incidence
NHL increasing
Hodgkin lymphoma stable
in NHL: 3rd most frequently diagnosed cancer in males
and 4th in females
in HL: 5th most frequently diagnosed cancer in males
and 10th in females
Incidence/100,000/annum

0
20
40
60
80
100

0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
Age (years)

50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Age distribution of new NHL
Risk factors for NHL

immunosuppression or immunodeficiency
connective tissue disease
family history of lymphoma
infectious agents
ionizing radiation
Clinical manifestations

Variable
severity: asymptomatic to extremely ill
time course: evolution over weeks, months, or years

Systemic manifestations
fever, night sweats, weight loss, anorexia, pruritis

Local manifestations
lymphadenopathy, splenomegaly most common
any tissue potentially can be infiltrated
Other complications of
lymphoma
bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures (eg spinal cord, ureters)
pleural/pericardial effusions, ascites
>10 cm

Bulky disease
Lymphoma Staging

Stage is the term used to describe the


extent of tumor that has spread through
the body ( I and II are localized where as
III and IV are advanced.
Each stage is then divided into categories
A, B, and E
A: No systemic symptoms
B: Systemic Symptoms such as fever, night
sweats and weight loss
E: Spreading of disease from lymph node to
another organ
Staging of lymphoma

Stage I Stage II Stage III Stage IV

A: absence of B symptoms
B: fever, night sweats, weight loss
Staging
Stage I : Involvement of single LN region (I) or
extra lymphatic site (IAE )
Stage II : Two or more LN regions involved (II)
or an extra lymphatic site and lymph node
regions on the same side of diaphragm
Stage III : Involvement of lymph node regions
on both sides of diaphragm, with (IIIE) or without
(III) localized extra lymphatic involvement or
involvement of the spleen (IIS) or both (IISE)
Stage IV : Involvement outside LN areas (Liver,
bone marrow)

A : Absence of B symptoms
B : B symptoms present
Diagnosis

Diagnosis requires an adequate biopsy

Diagnosis should be biopsyproven before


treatment is initiated

Need enough tissue to assess cells and


architecture

open bx vs core needle bx vs FNA


PROSEDUR DIAGNOSTIK

Ditegakkan berdasarkan anamnesis, pemeriksaan fisik, dan


pemeriksaan penunjang.
1. Anamnesis Umum
Pembesaran kelenjar getah bening (KGB) atau organ
Malaise umum
Berat badan menurun 10% dalam waktu 3 bulan
Demam tinggi 38C selama 1 minggu tanpa sebab
Keringat malam
Keluhan anemia (lemas, pusing, jantung berdebar)
Penggunaan obat-obatan tertentu
PROSEDUR DIAGNOSTIK

Anamnesis Khusus
Penyakit autoimun (SLE, Sjorgen, Rheuma)
Kelainan Darah
Penyakit Infeksi (Toxoplasma, Mononukleosis, Tuberkulosis, Lepara )
PROSEDUR DIAGNOSTIK

2. Pemeriksaan Fisik
Pembesaran KGB
Kelainan/pembesaran organ
Performance status: ECOG atau WHO/karnofsky
3. Pemeriksaan Diagnostik
Biopsi
Biopsi KGB dilakukan cukup pada 1 kelenjar yang paling representatif,
superfisial, dan perifer. Jika terdapat kelenjar superfisial/perifer yang paling
representatif, maka tidak perlu biopsi intraabdominal atau intratorakal. Spesimen
kelenjar diperiksa:
Rutin: Histopatologi: sesuai kriteria REAL-WHO
Khusus: Imunohistokimia
PROSEDUR DIAGNOSTIK

3. Pemeriksaan Diagnostik
Biopsi
Diagnosis harus ditegakkan berdasarkan histopatologi dan tidak cukup hanya
dengan sitologi. Pada kondisi tertentu dimana KGB sulit dibiopsi, maka
kombinasi core biopsy FNAB bersama-sama dengan teknik lain (IHK, Flowcytometri
dan lain-lain) mungkin mencukupi untuk diagnosis
Tidak diperlukan penentuan stadium dengan laparotomy

Laboratorium
Rutin: DPL, gbrn darah tepi, UL
Kimia klinik: GOT, GPT, Bilirubin , LDH, Protein total, Albumin-globulin, Alkali
fosfatase, asam urat, ureum, kreatinin, Gula Darah Sewaktu, Elektrolit: Na, K, Cl, Ca,
P, HIV, TBC, Hepatitis C (anti HCV, HBsAg)
Khusus: Gamma GT, Serum Protein Elektroforesis (SPE), Imunoelektroforesa (IEP),
Tes Coomb, B2 mikroglobulin
PROSEDUR DIAGNOSTIK

Aspirasi Sumsum Tulang (BMP) dan biopsi sumsum tulang dari 2 sisi spina
illiaca dengan hasil spesimen 1-2 cm
Radiologi: Untuk pemeriksaan rutin/standard dilakukan pemeriksaan CT Scan
thorak/abdomen. Bila hal ini tidak memungkinkan, evaluasi sekurang-
kurangnya dapat dilakukan dengan : Toraks foto PA dan Lateral dan USG
seluruh abdomen.
Konsultasi THT Bila Cincin Waldeyer terkena dilakukan laringoskopi
Cairan tubuh lain (Cairan pleura, cairan asites, cairan liquor
serebrospinal)
Imunofenotyping: Minimal dilakukan pemeriksaan imunohitstokimia (IHK)
untuk CD 20 dan akan lebih ideal bila ditambahkan dengan pemeriksaan
CD45, CD3 dan CD56 dengan format pelaporan sesuai dengan kriteria
WHO (kuantitatif).
Konsultasi jantung: Menggunakan echogardiogram untuk melihat fungsi
jantung
Bone Marrow Aspiration/Biopsy
Differential Diagnosis

Ca Nasopharynx
TB Kelenjar
Metastasis tumor
Infectioan: Viral,
Treatment

RT
Chemo
BMT / SCT
Antibody treatment: Rituximab target CD-20
Supportive
Treatment - Guidelines
Indications for RT:
Stage I disease
Stage II disease with 3 or lesser areas involved
For Bulky disease
For pressure problems

Indications for CT
All with B symptoms
Stage II disease with >3 areas involved
Stage III and IV disease
Treatment
Stage IA , Stage IIA with 3 or < 3 areas
involved: Radiotherapy

Stage IB, Stage II A with > 3 areas , Stage


IIB:
Chemotherapy every 3-4 weeks, 6-8
cycles; either alone, or in combination with
radiotherapy

Stage III & IV :


Chemotherapy + Radiotherapy ( for
bulky disease or palliation of symptoms)
Chemotherapy pro LNH

Chemotherapy: mainstay CHOP


-every 3 weeks, at least 6
cycles
Cyclophosphamide,
Doxorubicin Hydrochloride,
Oncovin (Vincristine),

Prednisolonone
Chemotherapy pro LH

MOPP :
Nitrogen
Mustard,
Vincristine (Oncovin),
Procarbazine,
Prednisolone

ABVD:
Adriamycin,
Bleomycin,
Vinblastine,
Dacarbazine
Prognosis
Terima kasih . . .