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