Aspek Klinis Neoplasia

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ASPEK KLINIS

NEOPLASIA

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ASPEK KLINIS NEOPLASIA
Tumor ganas & jinak dapat menimbulkan
masalah karena :
1. Lokasi & penekanan terhadap struktur
sekitar
2. Aktivitas fungsional seperti sintesis
hormon ataupun sindrom
paraneoplastik
3. Perdarahan & infeksi
4. Gejala akibat ruptur atau infark
5. Cahexia/wasting
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ASPEK KLINIS NEOPLASIA
Sindrom Paraneoplastik
 Kelompokan gejala pd penderita kanker yg
dapat diakibatkan penyebaran lokal/jauh
atau oleh pengeluaran hormon yg berasal
dari tumor asal.
• Terjadi pd ±10% penderita malignant
disease
• Penting untuk dikenali :
• Manifestasi awal ‘occult’ neoplasma
• Menimbulkan penyakit klinis yg jelas,
bahkan mematikan
• Mirip penyakit metastasis sehingga
mengacaukan terapi. 3
TABLE 7-11 -- Paraneoplastic Syndromes
Major Forms of
Clinical Syndromes Underlying Cancer Causal Mechanism
ENDOCRINOPATHIES
Cushing syndrome Small-cell carcinoma of ACTH or ACTH-like
lung substance
Pancreatic carcinoma
Neural tumors
Syndrome of Small-cell carcinoma of Antidiuretic hormone or
inappropriate antidiuretic lung; intracranial atrial natriuretic hormones
hormone secretion neoplasms
Hypercalcemia Squamous cell carcinoma Parathyroid hormone–
of lung related protein (PTHRP),
TGF-α, TNF, IL-1
Breast carcinoma
Renal carcinoma
Adult T-cell
leukemia/lymphoma
Hypoglycemia Ovarian carcinoma
Fibrosarcoma Insulin or insulin-like
substance
Other mesenchymal
sarcomas
Carcinoid syndrome Hepatocellular carcinoma
Bronchial adenoma Serotonin, bradykinin
(carcinoid)
Pancreatic carcinoma
Polycythemia Gastric carcinoma
Renal carcinoma Erythropoietin
Cerebellar hemangioma
Hepatocellular carcinoma
NERVE AND MUSCLE SYNDROMES
Myasthenia Bronchogenic carcinoma Immunological
Disorders of the central Breast carcinoma 4
and peripheral nervous
system
TABLE 7-11 -- Paraneoplastic Syndromes
Major Forms of
Clinical Syndromes Underlying Cancer Causal Mechanism
DERMATOLOGIC DISORDERS
Acanthosis nigricans Gastric carcinoma Immunological; secretion of
epidermal growth factor
Lung carcinoma
Uterine carcinoma
Dermatomyositis Bronchogenic, Immunological
breast carcinoma
OSSEOUS, ARTICULAR, AND SOFT-TISSUE CHANGES
Hypertrophic Bronchogenic Unknown
osteoarthropathy and carcinoma
clubbing of the fingers
VASCULAR AND HEMATOLOGIC CHANGES
Venous thrombosis Pancreatic Tumor products (mucins
(Trousseau phenomenon) carcinoma that activate clotting)
Bronchogenic
carcinoma
Other cancers
Nonbacterial thrombotic Advanced cancers Hypercoagulability
endocarditis
Red cell aplasia Thymic neoplasms Unknown
OTHERS
Nephrotic syndrome Various cancers Tumor antigens, immune
complexes
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GRADING & STAGING OF
TUMORS
• Metode untuk mengukur kemungkinan
agresifitas tumor secara klinis &
kuantitatif  prognosis.
• Grading tumor  klasifikasi
berdasarkan tingkat diferensiasi
sitologi sel tumor, jumlah mitosis dan
gambaran pola pertumbuhan.
• Grade I,II,III
• Tumor diferensiasi
baik/sedang/buruk

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GRADING & STAGING OF
TUMORS
• Staging (stadium) tumor klasifikasi
berdasarkan tingkat penyebaran kanker
pd pasien, sebagai parameter keparahan
penyakit :
• Sistem TNM : Ukuran tumor primer (T);
Tingkat penyebaran ke kelejar getah
benig (N); Adanya metastase (M)
• Sistem AJC : Stadium 0-IV
• Stadium tumor mempunyai nilai klinis
yang lebih bermanfaat dibandingkan
grading tumor.

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DIAGNOSIS LABORATORIUM
KANKER
METODE MORFOLOGI
•Histopatologi
• Eksisi/biopsi
• Data klinis sangat penting untuk
diagnosis optimal patologik
• Spesimen yagng dikirim adekuat,
representative & fiksasi baik
•Frozen sections (Potong beku)
•Aspirasi jarum halus (FNAB)
•Sediaan hapus sitologi (Pap smear; cairan
pleura; sikatan bronkus)
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Biopsi Aspirasi jarum Halus (FNAB)
Pap Smear
Figure 7-47 A normal cervicovaginal smear shows large,
flattened squamous cells and groups of metaplastic
cells; interspersed are some neutrophils. There are no
malignant cells. (Courtesy of Dr. P.K. Gupta, University
of Pennsylvania, Philadelphia, PA.)

Figure 7-48 An abnormal cervicovaginal smear


shows numerous malignant cells that have
pleomorphic, hyperchromatic nuclei; interspersed
are some normal polymorphonuclear leukocytes.
(Courtesy of Dr. P.K. Gupta, University of
Pennsylvania, Philadelphia, PA.)

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DIAGNOSIS LABORATORIUM
KANKER
METODE MORFOLOGI
•Imunohistokimia
• Menggunakan Ab spesifik untuk
mengidentifikasi produk sel maupun
marker permukaan tumor
Kegunaan :
• Klasifikasi “undifferentiated malignant
tumors”
• Penentuan asal tumor metastasis
• Deteksi molekul yg memiliki nilai penting
prognostik/terapeutik
•Flowcytometry  klasifikasi leukemia &
limfoma
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Figure 7-49 Anti-cytokeratin immunoperoxidase stain of a tumor of epithelial origin (carcinoma). (Courtesy of Dr. Melissa 15
Upton, University of Washington, Seattle, WA.)
DIAGNOSIS LABORATORIUM
KANKER
TUMOR MARKER (PENANDA TUMOR)
• Uji biokimia enzim yang berkaitaan
dengan tumor, hormon, & tumor marker
lain dlm darah  tidak dapat digunakan
untuk diagnosis defenitif kanker.
• Tumor marker dapat berperan dalam
mendeteksi kanker, menentukan
efektifitas terapi, ataupun terjadinya
rekurensi.

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TABLE 7-12 -- Selected Tumor Markers
HORMONES
Human chorionic gonadotropin Trophoblastic tumors,
nonseminomatous testicular tumors
Calcitonin Medullary carcinoma of thyroid
Catecholamine and metabolites Pheochromocytoma and related tumors
Ectopic hormones See “Paraneoplastic Syndromes” (
Table 7-11 )
ONCOFETAL ANTIGENS
α-Fetoprotein Liver cell cancer, nonseminomatous
germ cell tumors of testis
Carcinoembryonic antigen Carcinomas of the colon, pancreas,
lung, stomach, and heart
ISOENZYMES
Prostatic acid phosphatase Prostate cancer
Neuron-specific enolase Small-cell cancer of lung,
neuroblastoma
SPECIFIC PROTEINS
Immunoglobulins Multiple myeloma and other
gammopathies
Prostate-specific antigen and prostate- Prostate cancer
specific membrane antigen
MUCINS AND OTHER GLYCOPROTEINS
CA-125 Ovarian cancer
CA-19-9 Colon cancer, pancreatic cancer
CA-15-3 Breast cancer
NEW MOLECULAR MARKERS
p53, APC, RAS mutants in stool and Colon cancer
serum
p53 and RAS mutants in stool and Pancreatic cancer
serum
p53 and RAS mutants in sputum and Lung cancer
serum
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p53 mutants in urine Bladder cancer
DIAGNOSIS LABORATORIUM
KANKER
DIAGNOSIS MOLEKULER
•PCR
•FISH
•DNA microarray
Kegunaan :
•Diagnosis keganasan
•Prognosis dan sifat tumor
•Deteksi penyakit residual minimal setelah terapi
•Diagnosis predisposisi kanker herediter
•Menentukan terapi

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DIAGNOSIS LABORATORIUM
KANKER
PROFIL MOLEKULAR TUMOR
• Metode yg dapat mengukur ekspresi
seluruh gen dalam genom secara
bersamaan  KEPENTINGAN TERAPI
& PENENTUAN PROGNOSTIK
• Metode yg umum digunakan sekarang
ini : ‘DNA microarray technology’

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TERIMA KASIH

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