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Kelompok 19
Angrety S. B. 1010030
Stefanie K. 1010095
Claudia I. 1010003
Felix Hansen 1010101
Juni 1010070
Ray B. 1010140
Charisa Lazarus 1010093
Jason A. S. 1010074
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LIMFOPOIESIS & HISTOLOGINODULUS LIMFATIKUS
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Pluripoten stemsel
Limfoid stem sel
Prosel BProsel TProsel NK
Sel limfosit TSel limfosit B
Sel NKSel plasma
Sel TcSel Tk
makrofag
fagositosis
antibodi
Lsg hancurkanantigen
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Cortex
Cortex luar : nodulus limfatikus (sel B, sel
retikular, sel dendritik, serat retikular)
Cortex dalam(zona paracortex): jaringanlimfoid padat (sel T)
Medulla Terdapat Medullary cordyaitu jaringan limfoid
yang tersusun di sekitar pembuluh darah.
Hillus : arteri, vena, saraf, p.limfeP.L. aferensinussubkapsularissinus
trabekularissinus medularisP.L. eferen
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Komponen
Sistem Imun
Imunogenitas
Tumor
Mekanisme
efektor sistem
imun
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Immunologi tumor
Pertumbuhan sel kanker ditentukan oleh
kemampuan sel kanker berproliferasi dan
kemampuannya menghindari respon imun
(immune surveillance)
Sel kanker akan mengekspresikan antigen
permukaan yg khas dan seringkali memicu
respon imun.
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Respon imun terhadap tumor
Sel NK dapat mengenali sel terinfeksi dan selyg mengalami stress dan meresponnya denganlangsung membunuh sel tersebut, mensekresi
sitokin unflamasi dan juga merupakan sumberINF-a yg utama, yg dapat mengaktivasimakrofag untuk membunuh mikroba ygdifagositosisnya
Aktivasinya tergantung keseimbanganreseptor aktivasi dan inhibisi
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Sel NK mempunyai 2 reseptor: KARs dan KIRsdimana aktivasi KARs dihambat o/ KIRs
Pada sel kanker, ekspresi MHC1 seringkali
menurun bahkan tidak diekspresikan, maka tidakada yg menghambat aktivasi KARs dan terjadilahlisis sel target
Salah satu kompleks reseptor aktivasi pada sel NK
adalah reseptor NKG2D (sbg reseptor aktivasiprimer, dpt mengatasi inhibisi o/ ikatan KIRs dgMHC1)
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ONKOGENESIS
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P b h f d t l d l
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Perubahan fundamental pd sel yg
menyebabkan timbulnya fenotip
malignan Memenuhi kebutuhan growth factor
Penurunan sensitivitas terhadap growth
inhibitory signal
Menghindar dari apoptosis
Kapasitas untuk membelah terus
Membentuk vaskularisasi baru Kemampuan metastasis
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Memenuhi kebutuhan growth factor
Oncogeneada lah gen yang berasal dari mutasiproto-oncogeneyang menyebabkan terjadinyacell growth.
Growth factor
Growth factor receptor
Perubahan genetik pd reseptor menyebabkanterjadinya proliferasi sel tanpa adanya perangsangan
dari growth factor Cth: ekpresi berlebihan dari gen ERBBterdapat
pada 80% kasus squamous cell CA pd Paru
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Signaling Transduction Proteins
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Penurunan sensitivitas terhadap
growth inhibitory signal
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Menghindar dari apoptosis
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Kapasitas untuk membelah terus
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Membentuk vaskularisasi baru
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Definition
Non-Hodgkins Lymphoma (NHL)
NHL is a cancer that starts in cells called
lymphocytes, which are part of the bodys
immune system. Lymphocytes are in the
lymph nodes and other lymphoid tissues(spleen & bone marrow).
Cells in the lymphatic system either grow
without control or do not die as cells normallydo.
www.cancer.org ;www.emedicinehealth.com
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Epidemiology & Incidence
-US: 66,000 cases of NHL / year, about 19,500 die.
-The median age at presentation for most subtypes ofNHL is older than 50 years.
- In general, the incidence of NHL is slightly higher in
men than in women, with a male-to-female ratio ofapproximately 1,4:1
-It is estimated to be the sixth most common cancer inthe United States
-NHL is more common in : immunodef, autoimmundisease, immunosupresant, >> White males.
-Higesht ratesUS, Europe, Australia. LowestAsia
www.cancer.org ;www.emedicinehealth.com
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Etiology
- Unknown, the abnormal cell may be triggered
by an infection or expossure to something in the
environment.
- NHLs may result from chromosomaltranslocations, environmental factors,
immunodeficiency states, and chronic
inflammation.
www.cancer.org ;www.emedicinehealth.com
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Ann Arbor Staging System
Stage I
The lymphoma is in only 1 lymph node area or lymphoidorgan.
Stage II
The lymphoma is in 2 or more groups of lymph nodes onthe same side of (above or below) the diaphragm.
Stage III
The lymphoma is found in lymph node areas on both
sides of (above and below) the diaphragm. Stage IV
The lymphoma has spread outside of the lymph systeminto an organ that is not right next to an involved node.
www.cancer.org ;www.emedicinehealth.com
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Risk Factors
Older age
Gender (men>women)
Rase,ethnicity,geography
Exposure to certain chemicals
Radiation Exposure
Immune system deficiency
Autoimmune diseases
Infection (viruses, bacteria)
www.cancer.org ;www.emedicinehealth.com
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KLASIFIKASI & PROGNOSIS
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Rappaport Classification (berdasarkan
sitologi dan pola pertumbuhan)
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Working Formulation
Low Grade Intermediate Grade High Grade
Small lymphocytic Follicular large cell Large cell immunoblastic
Follicular small-cleaved cell Diffuse small cleaved cell Lymphoblastic
Follicular mixed small-
cleaved and large cell
Diffuse mixed small and
large cell
Small non-cleaved cell
(Burkitt and non-Burkitt
type)
Diffuse large cell
Th R i d E A i L h
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The Revised European American Lymphoma
Classification (REAL)/WHO
I. Precursor B-cell neoplasm:
Precursor B-lymphoblastic leukemia/lymphoma
II. Mature (peripheral) B-cell neoplasms
A. B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma
B. B-cell prolymphocytic leukemia
C. Lymphoplasmacytic lymphoma
D. Splenic marginal zone B-cell lymphoma (+/- villous lymphocytes)
E. Hairy cell leuekmia
F. Plasma cell myeloma/plasmacytoma
G. Extranodal marginal zone B-cell lymphoma of mucosa-associatedlymphoid tissue type
H. Nodal marginal zone lymphoma (+/- monocytoid B-cells)
I. Follicle center lymphoma, follicular,
J. Mantle cell lymphoma
K. Diffuse large cell B-cell lymphoma
L. Burkitt's lymphoma/Burkitt's cell leukemia
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T-Cell and Natural Killer Cell Neoplasms
I. Precursor T cell neoplasm:
Precursor T-lymphoblastic lymphoma/leukemia
II. Mature (peripheral) T cell and NK-cell neoplasms
A. T cell prolymphocytic leukemia
B. T-cell granular lymphocytic leukemia
C. Aggressive NK-Cell leukemia
D. Adult T cell lymphoma/leukemia (HTLV1+)
E. Extranodal NK/T-cell lymphoma, nasal type
F. Enteropathy-type T-cell lymphoma
G. Hepatosplenic gamma-delta T-cell lymphoma
H. Subcutaneous panniculitis-like T-cell lymphoma
I. Mycosis fungoides/Szary's syndromeJ. Anaplastic large cell lymphoma, T/null cell, primary cutaneous
type
K. Peripheral T cell lymphoma, not otherwise characterized
L. Angioimmunoblastic T cell lymphoma
M. Anaplastic large cell lymphoma, T/null cell, primary systemic type
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Hodgkin lymphoma
Nodular lymphocyte predominance Hodgkin's
lymphoma
Classical Hodgkin's lymphoma
Nodular sclerosis Hodgkin's lymphoma
Lymphocyte-rich classical Hodgkin's lymphoma
Mixed cellularity Hodgkin's lymphoma
Lymphocyte depletion Hodgkin's lymphoma
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Stadium Berdasarkan Ann Arbor
Stadium Keterangan
I Pembesaran KGB hanya 1 regio
IE : jika hanya terkena 1 organ extralimfatik tidak difuse / batas tegas
II Pembesaran 2 regio KGB / lebih, tetapi masih 1 sisi diafragma.
II2 : pembesaran 2 regio KGB dlm 1 sisi diafragma
II3 : pembesaran 3 regio KGB dlm 1 sisi diafragmaIIE : pembesaran 1 regio / lbh KGB dlm 1 sisi diafragma & 1 organ
extralimfatik tidak difuse / batas tegas
III Pembesaran KGB di 2 sisi diafragma
IV Jika mengenai 1 organ extralimfatik / lebih tetapi secara difus dengan
atau tanpa melibatkan limfatik
Semua stadium dibagi berdasarkan ada atau tidaknya gejala sistemik : demam,
keringat malam, hilangya berat badan lebih dari 10% berat normal (jika terdapat
gejala sistemik tersebut beri huruf B,jika tidak ada beri huruf A)
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Patogenesis
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White Blood Cells Neoplasm
Non-random chromosomal abnormalities
Most common : translocation
Genes that mutated or altered : development,
growth, or survivalof the malignant cell
Oncoproteins genomic aberrations block normalmaturation
BCL-6
Proto-oncogenes are activated in lymphoid cells byerrors that occur during antigen receptor gene
rearrangement and diversification
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Non Hodgkin Lymphoma(Diffuse Large B-Cell Lymphoma)
Disregulation of BCL6
overexpressionholds cells in
undifferentiated, proliferative state ; repress
p53
c-MYC : proliferative
Chromosome 14 and 18
overexpression BCL2 disregulation BCL
6
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Patofisiologi + GK
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Mass (DLCBL) :
rapidly enlarging mass at nodal or extranodal Cancer Cachexia (weakness, anorexia, anemia,
weight loss)
BMR cytokine: tumor and host (TNF, IL-1, interferon-)
soluble factors produced by tumors
proteolysis, lipid mobilizing, catabolismhomeostatic change
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Erosive, Infiltrativehematochezia,
constipation, abdominal pain Febris : cytokine
Sweating : febris compensation
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Komplikasi
GIT Perdarahan
Infeksi
Peritonitis
Leher
Thyroid, parathyroid
Jalan nafas
Terapi
Gagal ginjal
Kerusakan hepar
Keganasan
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Diagnosis Dasar Bpk L, 54thn (FR60Y)
KU:
benjolan RLQ 2bln yll, makin membesar(sus. neoplasia,lymphadenopathy, lymphadenitis)
Sjk 1 bln: benjolan di leher, febris hilang timbul (febris
recurrens), srg berkeringat mlm hr (night sweat) (sus.Lymphadenitis TB, lymphoma)
1 mgg terakhir: nyeri terus menerus (continua) seluruh (difus)bag.perut, benjolan leher x nyeri
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X bertani krn malaise, anorexia, nausea, kadvomitus (GK sistemik) Sejak 6bln: BB menurun ~10kg (sus.
Lymphadenitis TB, lymphoma)
BAB agak sulit & lbh jarang (konstipasi),kad.hematochezia R.Kebiasaan: merokoksjk muda & pekerjaan srg
pakai pestisida(FR u/ NHL) Respirasi: 24x/min (batas atas) Suhu: 380C (febris)
P ik Fi ik
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Pemeriksaan Fisik
KU: CM , tampak kesakitan
Kepala : conjunctiva anemis +/+ (krn hematochezia,mgkn kronis)
Leher: teraba masa a/r coli dextra, 2X1,5cm, oval,
soliter, batas tegas, permukaan licin, nyeri tekan(-),
terfiksasi, tidak ikut bergerak ketika menelan, tdk
tampak tanda2 radang. (sus. Neoplasia)
Abdomen:
Perkusi:dull(+) RUQ & LUQ (krn ada masa) Palpasi: nyeri tekan slrh Q, defance muscular(+),
benjolan di RUQ x jls teraba
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Pem Lab: Hb():Anemia
Ht(): Anemia
WBC(): Leukositosis
LED(): inflamasi
Diff countLimfositosis
SADT: mgkn infeksi berat
SGOT & SGPT (): fx
hepar
BUN & Creatinine (): fxhepar
LDH: dbn
As.urat (): Hyperuricemia
B2M ():
MM/leukemia/lymphoma CEA (): mgkn krn perokok
berat
CA 19-9: N
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CT scan abd:
Tampak dinding ileum yg menebal dislrh bag yg memberikan gbrn hipodensyg berbatasan dgn cairan kontras dgnketebalan s/ 5,2cm hingga 7,45cm yg
menimbulkan penyempitan lumenileum serta tampak mukosa iregular.Tampak adanya masa nodular di kananyg memberikan enhancement postpemberian kontras dgn ukuran 6,5 x 5x 4,4 cm
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Biopsi kgb coli dextra: Diffuse Non Hodgkins Lymphoma
Lymphocytic Type (Low Grade Lymphoma)
DK: Diffuse Non Hodgkins LymphomaLymphocytic Type (Low Grade Lymphoma)+ Anemia ringan + Hyperuricemia
P P j
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Pem. Penunjang
Pem. hematologi rutin
Hb, Ht Leukosit, trombosit
hitung jenis
LED
SADT Pem. fungsi hepar: SGOT, SGPT
Pem.fungsi ginjal: BUN, Creatinine
Pem.elektrolit: Na, K, Mg, Ca
Asam urat
Tumor marker: CEA, CA 19-9, B2M
LDH
Beta-2 microglobulin
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CT Scan (thorax, abdomen, pelvis)
PET Scan
MRI
Chest Xray
Biopsy
Immunophenotyping
Lymphangiogram
Gallium scan
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TREATMENT
Depends on :
The type of non-Hodgkin's lymphoma
Its stage
How quickly the cancer is growing
The patient's age
Whether the patient has other health problems
If there are symptoms present (fever and night
sweats)
Slow growing non Hodgkin's
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Slow-growing non-Hodgkin's
lymphoma without symptom
Might not require treatment for years
Close follow-up is necessary
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Aggressive type of lymphoma
A combination of chemotherapy and
biological therapy is usually indicated
Sometimes radiation therapy will be added
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1. Chemotherapy
A drug treatment either as an injection or oral
form that kills cancer cells
Can involve one medication or multiple
medications and be given alone or inconjunction with other therapies
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2. Radiation therapy
High doses of radiation are used to kill cancer
cells and shrink tumors
This modality can be used alone or in
conjunction with other therapies
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3. Stem cell transplant
Allows to receive large doses of chemotherapy
or radiation therapy to kill the lymphoma
cells, that might not be killed with standard
levels of therapy This therapy is used if lymphoma returns after
treatment !
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4. Biological drugs
Medications that enhance immune system's
ability to fight cancers
In NHL, monoclonal antibodies are used for
treatment
Rituximab (Rituxan) is such a drug used in the
treatment of B cell lymphoma
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Additional aspects of cancer
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Additional aspects of cancer
treatments
Supportive care
Moderate physical activity
Eating the appropriate amounts of foods
Vitamin (especially vitamin D)
Acupuncture
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PROGNOSIS
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Quo ad vitam : dubia ad malam
Quo ad functionam : dubia ad malam
Quo ad sanationam : dubia ad malam