Modul 1 Blok 25 Kel Tutorial 19

8/13/2019 Modul 1 Blok 25 Kel Tutorial 19

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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



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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.



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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.



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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)



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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

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Modul 1 Blok 25 Kel Tutorial 19