You are on page 1of 63

11.10.

03 TUMs-PAFKUGM 1

Dasar-dasar
Neoplasma

















T. Utoro
Department of Pathology
Gadjah Mada University School of Medicine


11.10.03 TUMs-PAFKUGM 2
Introduction – 1
Cancer has become increasingly prominent
in modern time

Cancer is not a modern disease

recorded in ancient civilization: mummies from Egypt,
Ramayana history (2500 BC)
• early cultures attributed the cause of cancer
to various gods
11.10.03 TUMs-PAFKUGM 3
Introduction – 2
ancient civilization

middle ages
Hippocrates: ~400BC  1
st
theory
of natural causes of cancer: imbalance between
black humor and the three bodily humors: blood,
phlegm, bile

Cancer house, cancer family, cancer village
11.10.03 TUMs-PAFKUGM 4
Introduction – 3
Sir Percival Pott (1775)
(the 1
st
recorded epidemiological study of cancer)

Young boy as a chimney sweeps  In their twentieth had a
high rate of death due to cancer of the scrotum  then
he suggested frequent washing and changing of clothing
that trapped the soot  reduce exposure to “carcinogen”

Other epidemiological study – identified major
environmental factors: tobacco smoke, various
occupational exposure
11.10.03 TUMs-PAFKUGM 5
Introduction – 4
Invention of microscope

Virchow  every cell is born from another cell  cancer is
a cellular disease
Cell biology  molecular genetics  the advancement of
knowledge about cancer biology  cancer is
a genetic disease

Diagnostic, prognostic factors, therapy  depend on the
study of populations of patients
11.10.03 TUMs-PAFKUGM 6
Introduction – 5
Population study of cancer patients

Recognize the presence of heterogeneity
among patients with certain tumors
Predict the probability of certain outcome (e.g. survival as function of
time), based on the properties of tumors and host

Challenge in therapeutic studies: application of knowledge about:
 produce overall improvements in treatment outcome
with acceptable level of toxicity
11.10.03 TUMs-PAFKUGM 7
NEOPLASIA
• General Comprehension of Cancer
(Definition, Nomenclature, Epidemiology)
• The Pathobiology of cancer
(Molecular basis of cancer, Biology of tumor growth, Immunology of
tumor, Clinical features of tumor)
11.10.03 TUMs-PAFKUGM 8
NEOPLASIA
(BASIC SCIENCES OF ONCOLOGY)


GENERAL DIAGNOSIS
COMPREHENSION


EPIDEMIOLOGY THERAPY


PATHOBIOLOGY MANAGEMENT


11.10.03 TUMs-PAFKUGM 9
• Neoplasia  new growth
• Neoplasm: abnormal tissue mass growing
excessively and indefinitely without
coordination with normal tissue
• Behaviour: progressive, useless,
independent from surrounding tissue,
unrelated to host needs, parasitic,
autonomic.
11.10.03 TUMs-PAFKUGM 10
nomenklatur
Tumor epitelial
• Jinak
• Ganas
Tumor mesenkimal
• Jinak
• ganas
Tumor sel kelamin (germ
cell tumor)
11.10.03 TUMs-PAFKUGM 11
Nomenklatur (tatanama)
Awalan yang menunjukkan asal jaringan
Skuamosa (epitel gepeng berlapis), adeno-(epitel kelenjar),
transisional, fibro- (jaringan ikat fibrosa, leiomio-(otot polos),
rabdomio-(otot lurik), lipo-(lemK), kondro (tulang rawan), osteo-
(tulang), hemangio-(pembuluh darah), limfangio-(pembuluh limfe)
Awalan yang menunjukkan pola pertumbuhan
Folikular, sistik, papilar, vilosa, kribriformis, dll.
Kata tambahan menunjukkan gambaran makroskopik
Scirrhous (keras), medular (lunak, menyerupai sumsum tulang),
koloid)
Teratoma
Berasal dari lebih dari satu germ layer (jinak & ganas)
11.10.03 TUMs-PAFKUGM 12
Benign epithelial tumors
Adenomatous polyp
11.10.03 TUMs-PAFKUGM 13
Benign epithelial tumor
Squamous cell Papilloma
11.10.03 TUMs-PAFKUGM 14
Benign epithelial tumor
Fibroadenoma of the breast
11.10.03 TUMs-PAFKUGM 15
Benign epithelial tumor
Pleomorphic Adenoma of the salivary gland
11.10.03 TUMs-PAFKUGM 16
Benign vs malignant
epithelial tumor
Adenoma Adenocarcinoma
11.10.03 TUMs-PAFKUGM 17
Malignant epithelial tumor
Carcinoma of the breast
11.10.03 TUMs-PAFKUGM 18
Malignant epithelial tumor
Squamous cell carcinoma
11.10.03 TUMs-PAFKUGM 19
Malignant Epithelial Tumors
Carcinoma in situ of the uterine cervix
11.10.03 TUMs-PAFKUGM 20
Malignant
epithelial
tumor
Well differentiated
adenocarcinoma
of the colon
11.10.03 TUMs-PAFKUGM 21
Malignant mesenchymal tumor
Rhabdomyosarcoma
11.10.03 TUMs-PAFKUGM 22
Benign germ cell tumors
Benign cystic teratoma (dermoid cyst)
11.10.03 TUMs-PAFKUGM 23
Malignant germ cell tumor
Cystadenocarcinoma of the ovari
11.10.03 TUMs-PAFKUGM 24
The biology of tumor
Normal cells

Malignant cells

Changes:
• Genotypic
• Phenotypic
11.10.03 TUMs-PAFKUGM 25
Related terms
• Hypertrophy
• Hyperplasia
• Metaplasia
• Displasia
• Anaplasia
• HAMARTOMA
11.10.03 TUMs-PAFKUGM 26
• Hyperplasia: an increase in the number of cells in an
organ/ tissue
• Hyperthropy: an increase in the size of the cells
• Metaplasia : a reversible change in which one adult cell
type is replaced by another adult cell type
• Dysplasia: a loss in the uniformity of the individual cells +
a loss of their architectural orientation
• Anaplasia: lack of differentiation
• Hamartoma: tumor like lesion, consist of two/ more
mature cell type normally found in an organ in which the
lesion arises

11.10.03 TUMs-PAFKUGM 27
Metaplasia
Apocrine metaplasia of the breast
Squamous metaplasia
11.10.03 TUMs-PAFKUGM 28
Diferensiasi
• Suatu proses/keadaan/perkembangan sel
tumor sampai tingkat tertentu di mana ada
kemiripan sel-sel neoplastik dengan sel
asalnya (baik, sedang, buruk  tanpa
diferensiasi / anaplasi)
11.10.03 TUMs-PAFKUGM 29
Anaplasia:
- pleomorfisma selular dan nuklear
- peningkatan rasio inti/sitoplasma
- meningkatnya kromatin inti  clumping /
irregular
- mitosis patologik  bizarre
- hilangnya orientasi (polarisasi sel)
- hilangnya kapasitas fungsional sel
11.10.03 TUMs-PAFKUGM 30
Dysplasia
11.10.03 TUMs-PAFKUGM 31
• Suatu proses/keadaan sampai di mana kemiripan
sel-sel neoplastik dengan sel asalnya (baik,
sedang, buruk  tanpa diferensiasi (anaplasi)
• Anaplasia:
- pleomorfisma selular dan nuklear
- peningkatan rasio inti/sitoplasma
- meningkatnya kromatin inti  clumping /
irregular
- mitosis patologik  bizarre
- hilangnya orientasi (polarisasi sel
- hilangnya kapasitas fungsional sel
11.10.03 TUMs-PAFKUGM 32
Principal characteristics
of benign and malignant tumors
Features Benign Malignant
Growth rate Slow Relatively rapid
Mitotic activity Low High
Histologic resemblance to
normal tissue
Good Variable, often poor
Nuclear morphology Mostly normal Hyperchromatic,multiple
nucleoli, pleomorphic
Invasion No Yes
Metastasis never Frequent
Border Circumscribed/
encapsulated
Poorly defined/ irregular
Necrosis Rare Common
Ulceration Rare Common
Growth Often exophytic Often endophytic
11.10.03 TUMs-PAFKUGM 33
Spread of Malignant Tumors
Metastatic cancer in the liver (pancreatic adenocarcinoma)
11.10.03 TUMs-PAFKUGM 34
Benign vs malignant
• Benign malignant
Circumscribed/ encapsulated
Intact surface
Exophytic growth
Homogenous cut surface
Heterogenous cut surface due to necrosis
Ulcerated surface
Endophytic growth
Vascular permeation
Irregular infiltrative edge
11.10.03 TUMs-PAFKUGM 35
Benign vs malignant
11.10.03 TUMs-PAFKUGM 36
Benign vs Malignant Tumors
11.10.03 TUMs-PAFKUGM 37
Benign vs malignant
mesenchymal tumor
Leiomyoma of the uteri
11.10.03 TUMs-PAFKUGM 38
Cystic lesion of the breast
11.10.03 TUMs-PAFKUGM 39
Metastasis
1. Limfogen
2. Hematogen
- Sistem venas porta  hati
- Sistem venosa sistemik  paru
- Sistem vena paru  jantung kiri  sirkulasi umum
- Ca uteri & abdomen  limfonodi  cisterna chyli 
ductus thoracicus  sistemik
3. Trans-coelomic
4. Intra-epitelial
11.10.03 TUMs-PAFKUGM 40
The Pathobiology of Cancer
Molecular basis of cancer: Oncogenes and regulator genes
Carcinogenic agents and their cellular interaction: chemical,
radiation, viral, bacterial carcinogenesis
Biology of tumor growth: kinetic, angiogenesis, progression
and heterogeneity, invasion and metastasis
Host defense against tumors: tumor antigens and
immunosurveillance
Clinical features of tumors: efect of tumors on host 
grading and staging of tumors
11.10.03 TUMs-PAFKUGM 41
Epidemiologi : Faktor risiko
1. Umur
Makin tua pengaruh karsinogen makin kuat
2. Diet
Perbedaan geografis insiden kanker mencerminkan
perbedaan diet
Minuman alkohol berpengaruh terhadap karsinogenesis
3. Lingkungan
Polusi (rokok, pekerjaan, kendaraan, pabrik)
Ativitas seksual
4. Perubahan genetik
11.10.03 TUMs-PAFKUGM 42
Cancer
epidemiology
11.10.03 TUMs-PAFKUGM 43
Comparison between
native Japanese,
Japanese immigrants
and Calif.white
11.10.03 TUMs-PAFKUGM 44
HEREDITY & CANCER
Question:
Is cancer inherited?
Evidence:
Lung cancer  in most instances clearly related to
cigarette smoking, yet,
mortality to lung cancer has been shown to be four
times greater among non-smoking relatives
(parents & siblings) of lung cancer patients than
non-smoking relatives of controls
11.10.03 TUMs-PAFKUGM 45
Hereditary forms of cancers can
be divided into 3 categories:
1. Inherited Cancer Syndromes
(autosomal dominant)
2. Familial Cancers
3. Autosomal Recessive Syndromes of
Defective DNA Repair
11.10.03 TUMs-PAFKUGM 46
1. Inherited Cancer Syndromes
(autosomal dominant)
• Inheritance of a single mutant gene greatly
increases the risk of developing a tumor
• The predisposition of these tumors shows an
autosomal dominant pattern of inheritance
• Inherited predisposition is indicated by strong
family history of uncommon cancer and/or
associated marker phenotype
11.10.03 TUMs-PAFKUGM 47
1. Inherited Cancer Syndromes
(autosomal dominant)
Contoh tumor
• Familial retinoblastoma
• Familial adenomatous polyposis
of the colon
• Multiple endocrine neoplasia
syndromes (MEN)
• Neurofibromatosis type 1 and 2
• Von Hippel–Lindau Syndromes
11.10.03 TUMs-PAFKUGM 48
Inherited Cancer
Syndromes
RETINOBLASTOMA
• Carriers of mutant Rb
gene have a 10,000 fold
increased risk of
developing
retinoblastoma (familial
type)
• greatly increased of
developing second
cancer (ostreosarcoma)
11.10.03 TUMs-PAFKUGM 49
Inherited Cancer Syndromes
Multiple endocrine neoplasia (MEN)
- The familial occurrence of the combination of:
medullary thyroid Ca, bilateral pheochromocy-
tomas, hyperparathyroidism (due to tumor)
- Mutation of ret proto-oncogene that is transmitted
in the germline
11.10.03 TUMs-PAFKUGM 50
Inherited Cancer Syndromes
Von Recklinghausen neurofibromatosis
type 1 and 2
- multiple benign neurofibromas, cafe au lait
spot, iris hamartoma, increased risk of
developing fibrosarcomas
- mutation of NF-1 and NF-2 (tumor suppressor
genes which functions as a GAP protein that
inactivates ras)
11.10.03 TUMs-PAFKUGM 51
Familial Adenomatous Polyposis Coli
• Another hereditary disorder marked by
an extraordunarily high risk of cancer
• Autosomal dominant mutation from
birth  innumerable polypoid
adenomas  mostly develop colon Ca
by age of 50
Inherited Cancer Syndromes
11.10.03 TUMs-PAFKUGM 52
Adenoma-Carcinoma Sequence
11.10.03 TUMs-PAFKUGM 53
Inherited Cancer Syndromes
Von Hippel-Lindau Syndrome
• Germ line mutation of VHN gene on
chromosome 3p  hereditary renal cell
cancer, phaeochromocytoma,
hemangioblastoma of the CNS, retinal
angioma, renal cyst

11.10.03 TUMs-PAFKUGM 54
2. Familial Cancers
Evident familial clustering of cancer but role of
inherited predisposition may not be clear in an
individual case
– Breast Cancer
– Ovarian cancer
– Colon cancer other than familial
adenomatous polyps

11.10.03 TUMs-PAFKUGM 55
3. Autosomal Recessive Syndromes of
Defective DNA Repair
Xeroderma pigmentosum
Ataxia telangiectasia
Bloom syndrome
Fancony anemia
11.10.03 TUMs-PAFKUGM 56
- autosomal recessive disorder  hypersensitive
to UV
- increased incidence of skin cancers
- defect in genes that function in nucleotide
excision repair, which is required for repair of
UV-induced pyrimidine dimers
Xeroderma pigmentosum
Autosomal Recessive Syndromes of Defective DNA Repair
11.10.03 TUMs-PAFKUGM 57
Autosomal Recessive Syndromes of Defective
DNA Repair
Ataxia Telangiectasia  AT gene (mutation in
single gene)
– Gradual loss of Purkinje cells
– Immunodeficiency
– Acute sensitivity to ionizing radiation
– Profound susceptibility to lymphoid
malignancies
11.10.03 TUMs-PAFKUGM 58
Autosomal Recessive Syndromes of Defective
DNA Repair
Bloom Syndrome
• Hypersensitivity to ionizing
radiation
• Developmental defects
• Predisposition to cancer
11.10.03 TUMs-PAFKUGM 59
Autosomal Recessive Syndromes of Defective
DNA Repair
Fanconi anemia
• Hypersensitivity to DNA cross-
linking agents (nitrogen mustard)
• Anemia
• Predisposition to cancer
11.10.03 TUMs-PAFKUGM 60
Acquired Pre–neoplastic Disorders
• Cell replication is involved in cancerous
transformation
• Fertile soil for the origin of malignant neoplasm:
- regenerative proliferation: hepatoma
- hyperplasia: endometrium
- dysplasia: cervical
- metaplasia: bronchogenic Ca
   the risk to develop neoplasm is
greater than average
11.10.03 TUMs-PAFKUGM 61
• Certain non-neoplastic disorder  pre-neoplastic
- chronic atrophic gastritis
- solar keratosis
- leukoplakia
 The great majority of instances no malignant
neoplasm emerges  the term persists because
it calls attention to the increased risk
Acquired Pre–neoplastic Disorders
11.10.03 TUMs-PAFKUGM 62
The question then …….
Is there any risk with all benign neoplasms?
•  although some risk may be inherent, most benign
neoplasm neoplasms do not become cancerous.
• Some malignant tumors were developed from benign
tumors: leiomyoma  leiomyosarcoma, pleomorphic
adenoma  Ca
Was the tumor an indolent form of cancer from the outset,
or was there a malignant focus in the benign tumor?
• Generalization is impossible because each type of
benign neoplasm is associated with a particular level of
risk ranging from almost zero to frequently present

11.10.03 TUMs-PAFKUGM 63
Try hard, work hard
Be honest, be modest