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neoplasia
• NEOPLASIA
DEFINISI: NEOPLASIA
PERTUMBUHAN BARU DAN PERTUMBUHAN BARU ADALAH NEOPLASIA
TERMINOLOGI “TUMOR”
NEOPLASIA JUGA MENYEBABKAN PEMBENGKAKAN, TETAPI PADA WAKTU DAHULU, NONNEOPLASTIK “TUMOR” (HAL YANG MENAKUTKAN) SEKARANG NEOPLASIA
ONKOLOGI MEMPELAJARI TUMOR / NEOPLASIA.
KANKER TUMOR GANAS
ONKOLOGI INGGRIS (SIR RUPERT WILLIS) NEOPLASIA
SEMUA NEOPLASIA TERGANTUNG PADA HOST NUTRISI DAN SUPPLY VASKULER,
BEBERAPA AKIBAT PENGARUH HORMONAL.
• NOMENKLATUR
TUMOR (JINAK / GANAS) TERDIRI DARI:
L. SEL NEOPLASIA PROLIFERASI – SEL PARENKHIM
2. STROMA : JARINGAN PENYOKONG DAN PEMBULUH DARAH
SEL PARENKHIM PROLIFERASI PENTING PADA NEOPLASIA AKAN TETAPI PERTUMBUHAN DAN EVOLUSI NEOPLASIA TERGANTUNG DARI SROMA.
PADA BEBERAPA TUMOR, STROMA SEDIKIT NEOPLASIA LUNAK DAN MENGKILAT
KADANG SEL PARENKHIM MEN STIMULI PEMBENTUKAN STROMA KOLAGEN DESMOPLASIA ( SCIRRHOUS – MAMMA )
NOMENKLATUR BERDASARKAN KOMPONEN PARENKHIM
TUMOR JINAK + OMA
GANAS
• NOMENKLATUR TUMOR
TISSUE OF ORIGIN BENIGN MALIGNANT
I. COMPOSED OF ONE PAREN-
CHYMAL CELL TYPE
A. MESENCHYMAL TUMORS
L. CONNECTIVEVTISSUE& DERIVATIVES FIBROMA FIBROSARCOMA
LIPOMA LIPOSARCOMA
CHONDROMA CHONDROSARCOMA
OSTEOMA OSTEOSARCOMA
2. ENDOTHELIAL &RELATED TISSUE
BLOOD VESSELS HEMANGIOMA ANGIOSARCOMA
LYMPH VESSELS LYMPHANGIOMA LYMPHANGIOSARCOMA
SYNOVIUM SYNOVIAL SARCOMA
MESOTHELIUM MESOTHELIOMA
BRAIN COVERINGS MENINGIOMA INVASIVE MENINGIOMA
3. BLOOD CELLS & RELATED CELLS
HEMATOPOIETIC CELLS LEUKEMIAS
LYMPHOID TISSUE MALIGNANT LYMPHOMA
4. MUSCLE
SMOOTH LEIOMYOMA LEIOMYOSARCOMA
STRIATED RHABDOMYOMA RHABDOMYOSARCOMA
B. EPITHELIAL TUMORS l. STRATIFIED SQUAMOUS SQUAMOUS PAPILLOMA SQUAMOUS CELL/EPIDER-
MOID CARCINOMA 2. BASAL CELLS OF SKIN/ADNEXA BASAL CELL CARCINOMA 3. EPITHELIAL LINING
GLANDS/DUCTS ADENOMA ADENOCARCINOMAPAPILLOMA PAPILLARY CARCINOMACYSTADENOMA CYSTADENOCARCINOMA
4. RESPIRATORY PASSAGES BRONCHOGENIC CARCINOMABRONCHIAL “ADENOMA” / CARCINOID
5. NEUROECTODERM NEVUS MALIGNANT MELANOMA 6. RENAL EPITHELIUM RENAL TUBULAR ADENOMA RENAL CELL CARCINOMA 7. LIVER CELLS LIVER CELL ADENOMA HEPATOCELLULAR CARCINOMA 8. URINARY TRACT EPIT TRANSITIONAL CELL PAPILLOMA TRANSITIONAL CELL CA 9. PLACENTAL EPITHELIUM HYDATIDIFORM MOLE CHORIOCARCINOMA l0. TESTICULAR EOITHELIUM/GERM CELL EMBRYONAL CARCINOMA
II. MORE THAN ONE NEOPLASTIC CELL TYPE-MIXED TUMORS
l. SALIVARY GLANDS PLEOMORPHIC ADENOMA MALIGNANT MIXED TUMORS/MIXED TUMOR OF SAL.ORIGIN OF SALIVARY GLAND ORIGIN
2. BREAST FIBROADENOMA MALIGNANT CYSTOSARCOMA PHYLLODES
3. RENAL ANLAGE WILMS’TUMOR
III. MORE THAN ONE NEOPLASTIC CELL TYPE DERIVED FROM MORE THAN ONE GERM LAYER-TERATOMOUS l. TOTIPOTENTIAL CELLS IN GONADS/IN EMBRYONIC RESTS MATURE TERATOMA/DERMOID CYST IMMATURE TERATOMA/TERATOCA
• KARAKTERISTIK NEOPLASMA JINAK DAN GANAS
1. DIFERENSIASI DAN ANAPLASIA
2. RATE OF GROWTH
3. INVASI LOKAL
4. METASTASIS
DIFERENSIASI: TDD WELL LACK OF DIFFANAPLASIA
MODERATE (MORFOLOGI DAN FUNGSI)
POORLY DENGAN TANDA KEGANASAN SEL
UNDIF TERDAPAT PULA TUMOR GIANT CELL
DISPLASIA
CIS
RATE OF GROWTH TUMOR JINAK BERTAHUN2
GANAS CEPAT TERGANTUNG DERAJAT DIFERENSIASI
INVASI LOKAL JINAK EXPANSIF / KAPSUL
GANAS INFILTRATIF. INVASI, DESTRUKSI JARINGAN SEKITAR
• METASTASIS
• SECARA: l. SEEDING OF BODY CAVITY AND SURFACE
RONGGA PERITONEUM, PLEURA, PERIKARDIUM, SUBARACHNOID,
SENDI ( OVARIUM PSEUDOMYXOMA PERITONEI )
2. LIMFATIK
3. HEMATOGEN
• COMPARISONS BETWEEN BENIGN AND MALIGNANT TUMORS
CHARACTERISTICS BENIGN MALIGNANT
DIFFERENTIATED/ANAPLASIA WELL DIFF, STRUCTURE MAY BE SOME LACK DIFF WITH ANAPLASIA
TYPICAL OF TISSUE OF ORIGIN STRCTURE IS PFTEN ATYPICAL
RATE OF GROWTH USUALLY PROGRESSIVE AND ERRATIC AND MAY BE SLOW TO RAPID
SLOW, MAY COME TOA STAND- MITOTIC FIGURES MAY BE NUMEROUS
STILL OR REGRESS. MITOTIC AND ABNORMAL
FIGURES ARE RARE AND NORMAL
LOCAL INVASION USUALLY COHESIVE AND EXPAN- LOCALLY INVASIE, INFILTRATING THE
SILE WELL-DEMARCATED MASSES SURROUNDING NORMAL TISSUES,
THAT DO NOT INVADE OR INFIL- SOMETIMES MAY BE SEEMINGLY COHE-
TRATESURROUNDING NORMAL SIVE ANG EXPANSIVE
TISSUES
METASTASIS ABSENT FREQUENTLY PRESENT, THE LARGER
AND MORE UNDIFF THE PRIMARY,
THE MORE LIKELY ARE METASTASES
• EPIDEMIOLOGI
OK KANKER ADALAH KELAINAN PERTUMBUHAN SEL DAN BEHAVIOR PENYEBAB DIBEDAKAN PADA TINGKAT SELULER DAN SUBSELULER.
PENGETAHUAN TENTANG ASAL KANKER
MISAL: SIR PERCIVAL POTT AGENT KIMIA KANKER INSIDENSI MENINGKAT
KANKER SCROTUM EXPOSE KRONIK (PADA PEKERJA CEROBONG ASAP)
STUDI EPIDEMIOLOGI ETIOLOGI BERHUBUNGAN DENGAN TERUTAMA LINGKUNGAN,
RAS (GENETIK?), KULTUR NEOPLASIA GANAS.
JUGA BEBERAPA PENYAKIT MERUPAKAN FAKTOR RISIKO GANAS
• INSIDENSI KANKER
USA (1994) 538.000 KEMATIAN (23% DARI SELURUH MORTALITAS)DATA INI TIDAK TERMASUK KEMATIAN 700.000 (KURABEL, NON-MELANOMA,
DAN 10.000 CIS, >> SERVIKS, PAYU DARA.
CANCER INCIDENCE AND MORTALITY BY SITE AND SEX
PERKIRAAN CANCER INCIDENCE BY SITE AND SEX (1994)
MALE FEMALE
MELANOMA(SKIN)-3% MELANOMA (SKIN)-3%MOUTH-3% MOUTH-2%LARYNX-1,5% LUNG-13%LUNG-16% BREAST-32%PANCREAS-2% PANCREAS-2%COLON,RECTUM-12% COLON, RECTUM-13%URINARY TRACT-9% OVARY-4%PROTATE-32% UTERUS-8%LEUKEMIA, LYMPHOID TISSUE-7% URINARY TRACT-4%ALL OTHERS-13,5% LEUKEMIS, LYMPHOID TISSUE-6%
ALL OTHERS-13%
• PERKIRAAN CANCER DEATHS BY SITE AND SEX (1994)
MALE FEMALE
BRAIN-2% BRAIN-2%
ESOPHAGUS=3% LUNG-23%
LUNG-33% BREAST-18%
LIVER/BILIARY TRACT-2% LIVER/BILIARY TRACT-2%
PANCREAS-4% PANCREAS-5%
STOMACH-3% COLON, RECTUM-11%
COLON, RECTUM-10% OVARY-5%
URINARY TRACT-5% UTERUS-4%
PROSTATE-13% URINARY TRACT-3%
LEUKEMIA, LYMPHOID TISSUE-8% LEUKEMIA, LYMPHOID TISSUE-8%
ALL OTHERS-17% ALL OTHERS-19%
• FAKTOR GEOGRAFI DAN LINGKUNGAN
TERDAPAT PERBEDAAN INSIDENSI DAN MORTALITAS PADA BERBAGAI NEGARA.
MISAL: MORTALITAS CA GASTER (M/F) 7-8X JEPANG DP USA
CA PARU USA 2X DP JEPANG, BELGIA LEBIH TINGGI DARI USA MELANOMA –6X NEW ZEALAND DR ICELAND
GEOGRAFI <=> LINGKUNGAN
MORTALITAS ORANG2 JEPANG YANG IMIGRASI KE USA DAN ORANG JEPANG YANG
LAHIR DI USA BEDA KARENA PENGARUH LINGKUGAN & KULTUR
(LINGKUNGAN, TEMPAT KERJA, MAKANAN, KEGIATAN ORANG)
UV
ASBESTOS, VINYL CHLORIDE, 2 NAPHTYLAMINE PEKERJAAN
ALKOHOL CA OROFARING, LARING, ESOFAGUS
SIROAIA HCC
SIGARETCA MULUT, FARING, LARING, ESOFAGUS, PANKREAS, BLADDER
ALKOHOL +TOBACCO UPPER AURODIGESTIVE TRACT
CA SERVIKSFIRST INTERCOURSE DAN NUMBER SEX PARTNERS
• USIA
HEREDITERMY MOTHER AND FATHER BOTH DIED OF CANCER. DOES THAT MEANI AM DOOMED TO GET IT?
TIDAK HANYA PENGARUH LINGKUNGAN TAPI FAKTOR PREDISPOSISI HEREDITER.CA PARU CIGARETTE SMOKING +
INHERITED CANCER SYNDROMES (AUTOSOMAL DOMINANT)INHERITED PREDISPOSITION INDICATED BY STRONG FAMILY HISTORY
OF UNCOMMON CANCER AND/OR ASSOCIATED MARKER PHENOTYPE FAMILIAL RETINOBLASTOMA FAMILIAL ADENOMATOUS POLYPS OF THE COLON MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES NEUROFIBROMATOSIS TYPES 1 & 2 VON Hippel-Lindau syndrome
FAMILIAL CANCERSEVIDENST FAMILIAL CLUSTERING OF CANCER BUT ROLE OF INHERITEDPREDISPOSITION MAY NOT BE CLEAR IN AN INDUVIDUAL CASE
BREAST CANCROVARIAN CANCERCOLON CANCER OTHER THAN FAMILIAL ADENOMATOUS POLYPOSIS
AUTOSOMAL RECESSIVE SYNDROMES OF DETICTIVE DNA REPAIR
XERODERMA PIGMENTOSUM
ATAXIA-TELENGECTASIA
BLOOM SYNDROME
FANCONI ANEMIA
• ACQUIRED PRENEOPLASTIC DISORDERS
REPLIKASI SEL TERMASUK TRANSFORMASI KEGANASAN, REGENERASI, HIPERPLASIA DAN PROLIFERASI DISPLASIA ORIGIN NEOPLASIA GANAS.
HIPERPLASIA ENDOMETRIUM ADENOKARSINOMA
DISPLASIA SERVIKS KARSINOMA
PEROKOK SIGARETMETAPLASIA, DISPLASIA MUKOSA BRONKHUS CA BRONKHOGENIK
SIROSIS HEPATIS REGENERASI PARENKHIM AKTIF HCC (80%)
NON-NEOPLASTIS DISOREDERS:
GASTRITIS KRONIK ATROPI-ANEMIA PERNISIOSA
SOLAR KERATOSIS KULIT KONDISI
KOLITIS ULSERATIFA PREKANKER
LEUKOPLAKIA (R. MULUT, VULVA, PENIS)
MOST BENIGN NEOPLASMS DO NOT BECOME CANCEROUS
ADENOMA VILOSA KOLON UKURAN BESAR GANAS (50% KASUS)
TGTG DARI DERAJAT RISIKO?
• BIOLOGI PERTUMBUHAN TUMOR
TUMOR GANAS 4 FASE: l. PERUBAHAN MALIGNAN PADA SEL TARGET
TRANSFORMASI
2. PERTUMBUHAN SEL TRANSFORMASI
3. INVASI LOKAL
4. METASTASIS JAUH
FAKTOR-FAKTOR: l. KINETIK PERTUMBUHAN SEL TUMOR
2. ANGIOGENESIS TUMOR
3. PROGRESI DAN HETEROGENETAS
• KINETIK PERTUMBUHAN SEL
HOW LONG DOES IT TAKE TO PROUCE A CLINICALLY OVERT TUMOR MASS?
ORIGINAL TRANSFORMED CELL(DIAMETER 10UM) 30 POPULATION DOUBLING TO 10(9) SEL (BERAT KIRA2 1 GR) MERUPAKAN MASA YANG PALING KECIL YANG DAPAT DI DETEKSI SECARA KLINIK. 10(12)1 KG, UKURAN MAXIMUM.
PADA SAAT TUMOR DAPAT DI DETEKSI SIKLUS HIDUP SEL KOMPLIT.
NORMAL CELLTRANSFORMATION
SINGLE TUMOR CELLPROGRESSION
30 DOUBLINGSPROLIFERATION OF GENECALLY UNSTABLE CELLS
1 GR –SMALLEST CLINICALLYDETECTABLE MASS
TUMOR CELL VARIANTS HETEROGENETTY
10 DOUBLINGS MICROSCOPIC METASTASES
1 KG MAXIMUM MASSCOMPATIBLE WITH LIFEMETASTASES (cell doubling)
• NORMAL CELL
CARCINOGEN INDUCED CELL CHANGE
TUMOR CELL
TUMOR CELL VARIANTS
CLONAL EXPANSION OF
SURVIVING CELL VARIANT NONANTIGENIC
INVASIVE
METASTATIC
REQUIRING FEWER GROWTH FACTORS
HUMAN SOLID MALIGNANCY (clonal evolution
generation of tumor cell
heterogeneity)
• SIKLUS SEL G0,G1,S,G2 DAN M, TETAPI SEL KANKER HANYA G0 / G1
KEBANYAKAN TIDAK PADA
REPLIKASI POOL
PADA TUMOR YANG TUMBUH CEPAT GROWTH FRACTION KIRA2 20%
-RATE OF TUMOR GROWTH TERGANTUNG DARI GROWTH FRACTION DAN DERAJAT
IMBALAN PRODUKSI DAN CELL LOSS
LEUKEMIA, LIMFOMA, SMALL CELL CA PARU HIGH GROWTH FRACTION PERJLN PENY CEPAT
CA COLON, MAMMAE LOW GROWTH FRACTION DAN CELL PRODUCTION
EXCEEDS CELL LOSS LAMBAT
-GROWTH FRACTION OF TUMOR CELL SUSEPTABILITAS THDP KHEMOTERAPI
PADA TUMOR2 YANG AGRESIF (LIMFOMA) SENSITIF KHEMOTERAPICURED
-MITOSIS
HOW LONG? A CELL CYCLE TIME – 3 HARI DAPAT TAHUN2 DIAGNOSIS
PADA STADIUM LANJUT.
KOLON, PARU SETELAH DIAG. 3 BULAN +
• ANGIOGENESIS
PENTING BLOOD SUPPLY --. PERTUMBUHAN TUMOR
FOLKMAN SEL2 TUMOR PADA KULTUR DAPAT TUMBUH PADA VASKULARISAI –
HANYA PADA NODUL BERUKURAN DIAMETER 1-2 MM.
BILA NODUL INI IMPLANTASI PADA JARINGAN TERJADI BLOOD SUPPLY DARI JARINGAN SEKITARNYA. PERTUMBUHAN TUMOR TERGANTUNG DARI VASKULARISASI.
PADA TUMOR SOLID DAPAT TERJADI NEKROSIS.
ANGIOGENESIS JUGA BERPERAN PADA METASTASIS
PENELITIAN: TERDAPAT KORELASI ANTARAANGIOGENESIS DAN KEMUNGKINAN
METASTASIS (MELANOMA, CA MAMMAE INVASIVE, CA PARU.
TUMOR –ASSOCIATED ANGIOGENIC FACTORS DI HASILKAN OLEH SEL TUMOR /
SEL INFLAMASI (MAKROFAG) PADA TUMOR2 INFILTRASI.
AL; FIBROBLAST GROWTH FACTOR
TGFα, TGFβ,EGF,PDGF,VEGR.
• TUMOR PROGRESSION AND HETEROGENEITY
DENGAN BERJALANNYA WAKTU TUMOR AGRESIF / POTENSIAL MALIGNITAS MENINGKAT. ( CA KOLON LESI PRENEOPLASTIK TUMOR BENIGNA CA INVASIF
KEADAAN INI DISEBUT TUMOR PROGRESSION.
INCREASING MALIGNANCY TUMBUH CEPAT, INVASIF, METASTASIS JAUH.
SEL BERBEDA INVASIF, RATE OF GROWTH, KESANGGUPAN METASTASIS,
KARIOTIPE, RESPONS HORMONAL, SUSEPSIBEL THDP OBAT
ANTIKANKER.
TRANSFORMASI SEL AKIBAT SEL TIDAK STABIL MUTASI
P53 TUMOR SUPPRESSOR GENES DAMAGE DNA AKUMULASI SEL MUTASI
TUMOR GANAS MONOKLONAL BY THE TIME KLINIKHETEROGEN (FASE
SEL DOUBLING) (DPT SEBELUM KLINIK)
SUBKLON MUTANT INI VARIABEL.
OSTEOGENIC SARCOMA METATASIS SUBLLON TELAH
TERJADI SAAT PDRT KE DOKTER
TUMOR2 KELENJAR LIUR; SUBKLON AGRESIF LATE, JRG
• MEKANISME INVASI DAN METATASIS
INVASI DAN METASTASIS MORBIDITAS DAN MORTILITAS
TERLEPASNYA SEL TUMOR DARI MASSA PRIMER KE DALAM SISTIM PEMBULUH DARAH / LIMFATIK PERTUMBUHAN SEKUNDER PADA DISTANT SITE MELALUI BEBERAPA LANGKAH.
PENELITIAN DENGAN TIKUS JUTAAN SEL YANG LEPAS DARI TUMOR PRIMER DAN MASUK KE SIRKULASI SETIAP HARINYA HANYA MENGHASILKAN BEBERAPA METAS
INVASI OF EXTRACELLULAR MATRIXVASCULAR DISSEMINATIONHOMING OR TUMOR CELLS
• INVASION OF ECM
JARINGAN TDD ECM: MEMBRANA BASALIS
JARINGAN PENYOKONG INTERSTITIAL
KOMPONEN: KOLAGEN, GLIKOPROTEIN DAN
PROTEOGLIKAN
STEP: DETACHMENT OF TUMOR CELL FROM EACH OTHER
ATTACHMENT TO MATRIX COMPONENT
DEGRADATION OF ECM
MIGRATION OF TUMOR CELLS
• METASTASIS HEMATOGEN
PRIMARY TUMOR TRANSFORMED CELL
CLONAL EXPANSION, GROWTH,
DIVERSIFICATION
ECM METASTATIC SUBCLONE
ADHESION TO AND INVASION OF BASEMENT
MEMBRANE
PASSAGE OF ECM
INTRAVASATION
VENULE INTERACTION WITH HOST LYMPHOID CELLS
TUMOR CELL EMBOLUS
ADHESION TO BASEMENT MEMBRANE
EXTRAVASATION
METASTATIC TUMOR
METASTATIC DEPOSIT
• AGENT KARSINOGENIK DAN INTERAKSI SELULER
BANYAK AGENT MENYEBABKAN KERUSAKAN GENETIK DAN INDUKSI SEL TRANSFORMASI NEOPLASTIK.
l. KARSINOGEN KIMIA
2.RADIASI
3. VIRUS ONKOGEN
KARSINOGENESIS KIMIA
SIR PERCIVAL POTT KARSINOMA KULIT SKROTUM PADA PEKERJA
PEMBERSIH CEROBONG ASAP AKIBAT EXPOSE KRONIK GELAJA
POLISIKLIK AROMATIK HIDROKARBON
AROMATIC AMINE DAN AZO DYES
NATURALLY OCCURING CARCINOGENS: ASPERGILLUS FLAVUS HCC
AFLATOXIN
NITROSAMINES AND AMIDES
MISCELLANEOUS AGENTS: ASBESTOS, CIGARETTE , VINYL CHLORIDE,
INHALASI CHROMIUM, NICKEL
• CHEMICAL CARCINOGENESIS
CARCINOGEN
DETOXIFICATION
METABOLIC EXCRETION
ACTIVATION
ELECTROPHILIC
DETOZIFICATION
INITIATION
BINDING TO DNA DNA REPAIR NORMAL CELL
ADDUCT FORMATION
CELL DEATH
PERMANENT DNA
LESION: INICIATED CELL
CELL PROLIFERATION:
ALTERED DIFFERENTIATION
PROMOTION
NEOPLASTIC CELL
MAJOR CHEMICAL CARCINOGENS
DIRECT-ACTING CARCINOGENS ALKYLATING AGENTS: BETA-PROPIOLACTONE
DIMETHYL SULFATE DIEPOXYBUTANE ANTICANCER DRUGS (CYCLOPHOSPHAMIDE, CHLORAMBUCIL, NITRO-
SOUREAS) ACYLATING AGENTS: 1-ACETYL-IMIDAZOLE
DIMETHYLCARBAMYL CHLORIDE
PROCARCINOGENS THAT REQUIRE METABOLIC ACTIVATION POPYCYCLIC AND HETEROCYCLIC AROMATIC HYDROCARBONS
BENZ(A) ANTHRACENEBENZO(A,P)PYRENEDIBENZ(A,H)ANTHRACENE3-METHYLCHOLANTHRENE7,12-DIMETHYLBENZ(A)ANTHRACENE
AROMATIC AMINES, AMIDES, AZO DYES2-NAPHTHYLAMINE(BETA-NAPHTHYLAMINE)BENZIDINE2-ACETYLAMINOFLOURENEDIMETHYLAMINOAZOBENZENE (BUTTER YELLOW)
NATURAL PLANTS AND MICROBIAL PRODUCTS
AFLATOXIN B1
GRISEAFULVIN
CYCASIN
SAFROLE
BETEL NUTS
OTHERS
NITROSAMINE AND AMIDES
VINYL CHLORIDE, NICKEL, CHROMIUM
INSECTICIDES, FUNGICIDES
POLYCHLORINATED BIPHENYLS
• RADIASI
SINAR ULTRAVIOLET DARI MATAHARI / IONIZING ELECTROMAGNETICS DAN
PARTIKEL RADIASI DAPAT MENYEBABKAN TRANSFORMASI SEL.
UV CA SEL SKUAMOSA, BASALIOMA, MELANOMA
PEMBENTUKAN PIRIMIDIN DIMERS SEL2 PADA XERODERMA PIGMENTOSUM
(GENETIC HETEROGE DG 7 VARIANT YANG BERBEDA) MUTASI CA KULIT
IONISASI RADIASI , BOM ATOM SETELAH 4 DEKADE KANKER MAMMA
IONISASI RADIASI ATAXIA TELANGIEKTASIA ( PDRT ATAXIA SEREBELUM DAN TELENGIEKTASIA OKULOKUTANEOUS) KEGANASAN LIMFOID
DISERTAI IMUNODEFESIENSI DAN RENTAN TERHADAP INFEKSI SINOPULMONAR.
(GENETIC HETEROGEN. 6 MOLEKUL VARIANT)
ANEMIA FANCONI PREDISPOSISI LEUKEMIA, ANEMIA ANAPLASTIK PROGRESIF
CONGENITAL MALFORMATION (POST EXPOSURE AGENT GENOTOXIC)
SINDR. BLOOM ( IMUNODEFISIENSI BERAT, GROWTH RETARDATION DAN PREDISPOSISI PD BBRP KANKER) HIPERSENSITIF THDP AGENT2 YANG MERUSAK DNA (UV DAN RADIASI) DEFEK DNA REPAIR AUTOSOMAL RECESSIVE
<== DNA DAMAGE
• KARSINOGEN VIRUS
*TRANSFORMASI VIRUS DNA HOST CELL GENOM STABIL.
INTEGRATED VIRUS TIDAK SANGGUP MELAKUKAN SIKLUS REPLIKASI KOMPLIT
GANGGUAN PADA SAAT VIRUS INTEGRASI
*GEN VIRUS TRANSCRIBED EARLY ( SIKLUS HIDUP VIRUS) PENTING UNTUK
TRANSFORMASI ( TAMPAK PADA TRANSFORMED CELL)
VIRUS DNA: HPV
EBV
HBV
VIRUS RNA: HUMAN T-CELL LEUKEMIA VIRUS TYPE 1
• HOST DEFENSE AGAINST TUMORS—TUMOR IMMUNITY
TUMOR ANTIGEN: TUMOR SPECIFIC ANTIGENS (TSaS) TERDAPAT HANYA PADA SEL TUMOR TUMOR ASSOCIATED ANTIGEN (TAAs) TERDAPAT PADA SEL TUMOR
DAN SEL NORMAL.
ANTITMOR EFFECTOR MECHANISMS:CYTOTOXIC T LYMPHOCUTES (PROTEKTIF TU PADA KEGANASAN OLEH VIRUS)
NK CELLS MAKROFAGHUMORAL AKTIFASI KOMPLEMEN
INDUKSI ANTIBODY-DEPENDENT CELLULAR TOXICITY OLEH
IMMUNOSURVEILENCE (DEF IMUN KANKER)
IMMUNOTHERAPY AND GENETHERAPY TUMORSADOPTIVE CELLULAR THERAPY:
IL-2 GENERATES LYMPHOKINE-ACTIVATED KILLER CELLSTUMOR INFILTRATING LYMPHOCYTES (LEBIH POTEN TRANSFECTED DG
GENE FOR TNF-α (POTENT ANTI TUMORCYTOKINE)CYTOKINE THERAPY: IL-2, INTERFERON-α (IFN-α) DAN IFN-γ, TNF-α,
HAEMPOIETIC GROWTH FACTOR, NK CELLSANTIBODY-BASED THERAPY:
? MONOCLONAL ANTIBODIES AGAINT CERTAIN B-CELL LYMPHOMA YANG DIKONYUGASI DG RICIN POTENT TOXIC
HASIL IMMUNOTOXIN LEUKEMIA DAN LIMFOMA
• KLINIK
EFEK TUMOR PADA HOST
1. LOKAI DAN PENGARUH THDP SEKITAR
2. AKTIFITAS FUNGSI (SENTESIS HORMON)
3. PERDARAHAN DAN INFEKSI SEKUNDER (ULSERASI PERMUKAAN)
4. AKUT (RUPTUR & INFARK)
CANCER CACHEXIA
SINDROMA PARANEOPLASTIK
• PARANEOPLASTC SYNDROME
CLINICAL SYNDR MAJOR FORMS OF CAUSAL MECHANISM
UNDERLYING CANCER
ENDOCRINOPATHIES
CUSHING’S SYNDROME SMALL CELL CA OF LUNG ACTH OR AGTH-LIKE
SUBSTANCE
PANCREATIC CA
NEURAL TUMORS
SYNDR OFINAPPROPRIATE SMALL CELL CA OF LUNG ADH OR ATRIAL NATRI-
ADH SECRETION INTRACRANIAL NEOPLASM URETIC HORMONE
HYPERCALCEMIA SQUAMOUS CA OF LUNG PARATHYR.HORMONE
RELATED PEPTIDE TGFα
TNFα, IL-1
BREAST CA
RENAL CA
ADULT T CELL LEUKEMIA/LIMFOMA
OVARIAN CA
HYPOGLICEMIA FIBROSARCOMA INSULIN/INSULIN LIKE
OTHER MESENCHYMAL SARCOMAS
CARCINOID SYNDROME BRONCHIAL ADENOMA (CARCINOID) SEROTONIN, GRADYKININ
PANCREATIC CA HISTAMINE
GASTRIC CA
POLYCYTHEMIA RENAL CA ERYTHROPOIETIN CEREBELLAR HEMANGIOMA HCC
NERVE & MUSCLE SYNDR MYASTHENIA BRONCHOGENIC CA ?IMMUNOLOGIC, TOXIC DISORDERS OF SSP & SST BREAST CA
DERMATOLOGIC DISORDERS ACATHOI\SIS MIGRANS GASTRIC CA ?IMMUNOLOGIC,
LUNG CA ?SECRETION OF EIPDER- UTERINE CA MA GF
DERMATOMYOSITIS BRONCHOGENIC, BREAST CA ?IMMUNOLOGIC, ?TOXIC
OSSEOUS, ARTICULAR & SOFT TISSUE CHANGES HYPERTROPHIC OSTEO- BRONCHOKENIC CA UNKNOWN ARTHROPATHY & CLUBBING OF THE FINGERS
VASCULAR & HEMATOLOGIC CHANGES VENOUS THROMBUS PANCREATIC CA TUMOR PRODUCTS (TRAUSSEAUS’S PHENOMENON) BRONCHOGENIC CA (MUCINS) THT ACTIVATE
OTHERS CANVER CLOTTING NONBACTERIAL THROMBOTIC ADVANCED CANCER HYPERCOAGULABILITY ENDOCARDITIS ANEMIA THYMIC NEOPLASM UNKNOWN
OTHERS NS VARIOUS CANCER TUMOR ANTIGENS, IMMUNE
COMPLEXES
• GRADING DAN STAGING
• LABORATORY DIAGNOSIS OF CANCER
HISTOLOGIC AND CYTOLOGIC
DATA KLINIK DIAGNOSIS OPTIMAL PATOLOGIST
EVALUASI LAB SPICEMEN (ADEKUAT, REPRESENTATIF)
SPICEMENT EKSISI / BIOPSI
NEEDLE ASPIRATION
CYTOLOGIC SMEAR
IMMUNOHISTOCHEMISTRY
MOLECULAR DIAGNOSIS
FLOW CYTOMETRY IDENTIFIKASI CELL SURFACE ANTIGEN; KLAS LEUKEMIA/LIMFOMA SPECIMEN: FRESH VC BIOPSY, EFUSI PLEURA/PERITONEAL,
IRIGASI V.U
TDPT HUB. ANTARA CONTENT DNA ABNORMAL DENGAN PROGNOSIS ANEUPLOIDY
PROG BURUK PADA STADIUM DINI CA MAMMA, V.U, KOLOREKTAL, PROSTAT.
FUMOR MARKER
• TERAPI
OPERASI
RADIASI
KHEMOTERAPI
HORMONAL
PAYUDARA
• PATOLOGI
-MASA PALPABEL
-INFLAMASI
-NIPPLE SECRETION
-ABNORMALITAS MAMMAGRAFI
NO DISEASE 30%
FIBROCYSTIC 40%
MISELLANEOUS 13%
FIBROSADENOMA 7%
CANCER 10%
• KELAINAN KONGENITAL
-SUPERNUMARY NIPPLES
-ACCESSORY AXILLARY BREAST TISSUE
-CONGENITAL INVERSION OF NIPPLES
INFLAMASI -MASTITIS AKUT DAN ABSES
MAMMARY DUCT ECTASIA
FAT NECROSIS
• PENYAKIT FIBROKISTIK
PERUBAHAN MORFOLOGI:
l. PBTK KISTA DAN FIBROSIS (FIBROKISTIK SIMPEL, KISTA2
2. HIPERPLASIA EPITEL DUKTAL, LOBULER
3. ADENOSIS SKLEROSING
HIPERPLSIA EPITEL, BILA TERDAPAT SEL ATIPIK Ca
20-40 th, estrogen >>
PENTING ! l. DD/ Ca
2. MIKROKALSIFIKASI PD MAMMOGRAFI
3. PREDESPOSISI Ca
HUBUNGAN PY.FIBROKISTIK DG Ca?
l. NO INCREASE RISK OF BREAST Ca: FIBROSIS, KISTIK, METAPLASIA
APOKRIN, GI[ERPLASIA RINGAN
2. SLIGHTLY INCREASE RISK 1.5-2X: ADENOSIS SKLEROSING,
HIPERPLASIA SEDANG-FLORID, PAPILLOMATOSIS DUKTAL
3. SIGNIFICANTLY INCREASE RISK 5X: HIPERPLASIA ATIPIKAL
DUKTAL/LOBULER
4. A FAMILY HISTORY OF BREAST CANCER INCREASES THE RISK IN
ALL CARTEGORIES , 10X – HIPERPLASIA ATIPIKAL
• TUMOR
FIBROADENOMA
: JAR FIBROUS DAN GLANDULAR
TUMOR PHYLLODES
PAPILLOMA INTRADUKTAL: SEROUS/ BLOODY NIPPLE DISCHARGE
SMALL SUBAREOLAR TUMOR
RETRAKSI NIPPLE (JARANG)
KARSINOMA
A. NONINVASIVE
1. INTRADUCTAL Ca
INTRADUCTAL Ca + PAGET’S DIS
2.LOBULAR Ca
B. INVASSIVE/ INFILTRATING:
1. INVASSIVE DUCTAL Ca
INVASSIVE DUCTAL Ca + PAGET’S DIS
2. INVASSIVE LOBULAR
3. MEDULLARY Ca
4.COLLOID/ MUSINOUS Ca
5. TUBULAR Ca
6. ADENOID CYSTIC Ca
7. APOCRINE Ca
8. INVASSIVE PAPILLARY Ca
STAGING
I. <2 CM N0M0
II. <5 CM N1 (MOBILE) M0
<5CM N1 M0
III. ANY SIZE, MENGENAI KULIT, M.PEKTORALIS, DINDING DADA N1 (AXILLA,
MAMARIA INTERNA, FIXED M0
IV. ANY FORM OF BREAST CANCER WITH/WITHOUT NODAL (N0/N1),
PECTORAL FIXATION, SKIN ULCERASI OR CHEST WALL FIXATION, M1
PROGNOSIS
1. UKURAN TUMOR PRIMER, < 2CN PROG BAIK
2. KGB, JUMLAHNYA , METASTASIS
KGB NEGATIF 5 YEAR SURVIVAL RATE 80%
1-3 KGB POSITIF 50%
5 KGB POS 21%
3. TIPE HISTOLOGI DAN GRADE
SURVIVAL RATE INTRADUCTAL Ca 74%
PAPILLARY Ca 65%
MEDULLARY Ca 58%
COLLOID Ca 58%
INFILTR LOBULAR Ca 34%
INFILTR DUCTAL 29%
4. ESTROGEN, PROGESTERON RECEPTOR
5. PROLIFERATION RATE OF THE TUMOR DAN ANEUPLOIDY,
INCREASE/SCATTERED DNA
6.ACTIVATED ONCOGEN c-erb B2
7. ANGIOGENESIS
8. ENZIM CATHEPSIN D DAN STROMELYSIN
Gynecomastia
• Enlargement of male breast
• Unilateral or bilateral
• Button-like subareolar enlargement – simulate adolescent female breast
• Occur in imbalance between estrogens & androgens:– Hyperestrinism
– Liver cirrhosis
– Failure of androgenic funtion of the testis in older male
– Drugs
– Klinefelter syndrome