Sel Kanker &

Pengantar Onkologi
dr. Indrayanti, Sp.PA
 Pendahuluan – 1

HISTORY
Kanker menjadi semakin penting
di zaman modern

Kanker bukan penyakit modern

tercatat dalam peradaban kuno: mumi dari Mesir,

Sejarah Ramayana (2500 SM)
budaya awal menyatakan bahwa penyebab kanker dikaitkan
dengan para dewa

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 Introduction – 1

HISTORY
ancient civilization

middle ages
Hippocrates: ~400BC  1st theory
penyebab alami kanker: ketidakseimbangan antara
humor (keseimbangan cairan dalam tubuh manusia)
‘hitam’ dan tiga humor tubuh: darah, dahak, empedu

Cancer house, cancer family, cancer village

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 Introduction – 1

HISTORY
Sir Percival Pott (1775)
(studi epidemiologi kanker yang tercatat pertama)

Penyapu cerobong asap  mempunyai resiko tingkat kematian

20 x lebih tinggi karena kanker skrotum 
Kemudian dia menyarankan untuk sering mencuci dan mengganti
pakaian, sehingga bisa menghilangkan jelaga  mengurangi
paparan "karsinogen“

Studi epidemiologi lain yaitu mengidentifikasi faktor lingkungan

utama, misal : asap tembakau & berbagai paparan pekerjaan

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 Introduction – 1

HISTORY
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

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 Bagaimanakah proses terjadinya lesi pre kanker/pre
neoplastik menjadi tumor ganas dari sel normal?

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 Introduction – 1

HISTORY
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

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 General Comprehension of Cancer
This lectures of the first week will discuss about
• Introduction  Perspective, definition, nomenclature, and
characteristic of benign and malignant tumors
• Clinical relevancies of cancer, when cancer is seeding in
the body
• General Principles and Scopes of Cancer Epidemiology
that is discussing descriptive epidemiology of cancer,
data sources and trends, geographic and age distribution,
and iceberg phenomenon
• Risk factor of cancer: tobacco, alcohol, diet, hormonal
and reproductive factors, occupational and other environ-
ment exposures
• and screening of cancer
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 Basic Principles of Pathobiology of Cancer
Molecular basis of cancer: Oncogenes and regulator
genes
Heredity and acquired pre-neoplastic disorders
Carcinogenic agents and their cellular interaction:
chemical, radiation, viral, bacterial, paracite
carcinogenesis
Biology of tumor growth: kinetic, angiogenesis,
progression and heterogeneity, invasion and
metastasis
Efect of tumors on host, host defense against tumors:
tumor antigens, and immunosurveillance
Clinical features of tumors:  grading and staging of
tumors
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 Basic Principles of Cancer Diagnosis

Laboratory Diagnosis:
histopathology, cytology, serologic
Clinical Diagnosis:
physical diagnosis, radiography, endoscopy

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 Basic Principles of Cancer Therapy

Oncologic surgery: basic principles of cancer operation

Chemotherapy: chemotherapeutic agents with their
limitations
Radiotherapy: molecular and cellular response
Hormonal therapy: pharmacologic application and
resistance of hormonal therapy
Biological therapy: gene therapy

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 Basic Principles of Cancer Management

• Early cancer detection and prevention of cancer

• Community cancer promotion
• The role of palliative therapy in the management of cancer
• Nutrition – supportive measure to increase the quality of
live
• Pain management of cancer patient
• Drugs for cancer pain
• Futility, end of lie ad discoure of patient acceptance
• Truth telling

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 The biology of tumor
Normal cells

Malignant cells

Changes:
• Genotypic
• Phenotypic

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 Neoplasia
• 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.

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 Related terms

• Hypertrophy
• Hyperplasia
• Metaplasia
• Displasia
• Anaplasia
• HAMARTOMA
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11/17/21 16
11/17/21 17
 Diagram pertumbuhan
neoplasma jinak dan ganas
Keterangan :
1.Sel-sel yang tumbuh sebagai tumor jinak
di jaringan epitel
2.Sel-sel tumor yang menerobos lamina
basalis
3.Sel tumor menyerang pembuluh kapiler
(perjalanan melalui aliran darah kurang
dari 1 di dalam 1000 sel akan bertahan
dan bermetastasis).
4.Sel tumor melekat atau menempel di
dinding pembuluh darah di hepar
5.Sel mulai keluar dari pembuluh darah
6.Sel berkembang biak dan bermetastasis
di dalam hepar.

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 Chemical Carcinogenesis
Experimental model: Normal Cells

INITIATION

PROMOTION

Cancer Cells
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 Initiation-promotion scheme

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 INITIATION

• Initiator alone is not sufficient for tumor

formation (Group 1)
• Initiation results from exposure of cells to an
appropriate dose of initiator (carcinogenic agents)
• Initiation  irreversible mutation (DNA damage)
 memory  months later +promoter  tumor
(Group 2&3)

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 PROMOTER

• Non-tumorigenic by itself
• Induce tumors in initiated cells (Group 5)
• When promoter is applied before initiator, no
tumor developed (Group 4)
• When the time between multiple application is
extended  the effect of promoter is reversible
 tumors failed to develop (Group 6)

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 Major Chemical Carcinogen
Direct-acting Carcinogens
• Alkylating Agents
• Acylating agents
Procarcinogen that Require Metabolic activation
• Polycyclic & Heterocyclic Aromatic Hydrocarbons
• Aromatic Amines, Amides, Azo Dyes
• Natural Plant and Microbial Products
• Others

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 Initiation of Carcinogenesis
1. Direct acting compound  do not require chemical
transformation for their carcinogenicity
2. Indirect acting compound / procarcinogen, require
metabolic conversion in vivo to produce ultimat
carcinogen
Property in common:
= They are highly reactive electrophiles that can react with
nucleophilic sites in the cell  electrophilic reaction
sub-lethal damage to DNA
= Molecular “fingerprint”

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 Carcinogen  tumor types (fingerprinting)

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 Events in Chemical
Carcinogenesis

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 Promotion of Carcinogenesis

• Promoters: phorbol esters, hormone, phenols, drugs

• Not mutagenic  how do they contribute to tumorigenesis
 study of TPA
• TPA: - phorbol esters
- powerful activator for protein kinase C, an
enzyme that phophrylates several substrates
involved in signal transduction pathways

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 Initiation
&
Promotion

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 Initiation & promotion

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 Radiation Carcinogenesis
• Transform all kind of cells in vitro and induce neoplasms in
vivo, in human & experimental animal
• UV light  skin cancer
• Ionizing radiation of medical, occupational, and bomb of
origins  produce a variety of malignant neoplasms
• The effect of UV light is somewhat differ from those of
ionizing radiation

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 UV
• UV effects on cells inhibition of cell division, inactivation
of enzymes, induction of mutation, and killing the cells
• UV type:
- UVA (320 – 400 nm): non-mutagenic
- UVB (280 – 320 nm): mutagen, not filtered by ozone
- UVC (200 – 280 nm): mutagen, filtered by ozone
• Type of cancer results are skin cancers: SCC, BCC,
melanoma
• UVB also causes mutation in oncogenes (ras) and tumor
suppressor genes (p53)

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 The carcinogenicity of UVB is attributed to its
formation of pyrimidine dimers in DNA

This DNA damage is repaired by NER (nucleotide excision

repair)
1. Recognition of the DNA lesion
2. Incision of the damage strand on both sites of the
lesion
3. Removal of the damage nucleotide
4. Synthesis of a nucleotide patch
5. Synthesis of its ligation

11/17/21 32
 NER (nucleotide excision repair)

• This process needs at least the product of 20 genes

• Postulation: excessive sun exposure  capacity of NER
pathway in overwhelmed  some DNA damage remains
unrepaired  large transcription errors  cancer
• Xeroderma pigmentosum (photosensitivity, 200-fold risk of
ckin cancer) has several mutated genes involved in NER

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 Ionizing Radiation

• Electromagnetic radiation
- X-rays and gamma rays
• Particulate radiation
- α particles, β particles, proton,
neutron

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 Hirarki Kerentanan
Hierarchy of Vulnerability

1. Leukemia
2. Thyroid
3. Breast, lung, salivary gland (intermediate)
4. Skin, bone, gastrointestinal tract
(relatively resistant)

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11/17/21 36
 Sel tumor
ASAL
•Epithelial : papilloma sel squamosa, squamous
cell carcinoma
•Mesenchimal : fibroma, fibrosarcoma
•Germ cells : teratoma matur, teratoma immatur

JENIS
•Jinak : papilloma sel squamosa,
•Ganas : squamous cell carcinoma
•Pre-kanker : leukoplakia
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 Benign epithelial tumors

Adenomatous polyp
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 Benign germ cell tumors

Benign cystic teratoma (dermoid cyst)

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 Benign vs Malignant Tumors

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 Spread of Malignant Tumors

Metastatic cancer in the liver (pancreatic adenocarcinoma)

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 TUMORS &
TUMOR-LIKE CONDITIONS
I.C. TUMORS & TUMOR-LIKE CONDITIONS
1. Benign tumors of the oral mucosa
a. Papilloma: the most common benign epithelial oral mucosal
tumor  tongue, lips, gingivae, buccal
b. Fibroma: it is often a non-neoplastic hyperplastic lesion due
to chronic irritation
c. Nevus
d. Granuloma piogenicum:
e. Hemangioma: tongue, lips, buccal mucosa
f. Lymphangioma:
g. Epulis: any abnormal swelling of the gingiva, as a reparative
growth rather than a true neoplasm
h. Ameloblastoma:
i. Osteoma
j. Fibrous dysplasia
k. Lipoma
 I.C. TUMORS & TUMOR-LIKE CONDITIONS

2. Leukoplakia:
a. clinical term describing irregular white mucosal
patches
b. pre-cancer
 I.C. TUMORS & TUMOR-LIKE CONDITIONS
3. Odontogenic tumors
a. Odontoma: hamartoma derived from odontoblastic epithelium
b. Ameloblastoma:
- epithelial tumor arising from precursor cells of the enamel organ
- usually before age 35, and most fequently in mandible
- irregular local extension
4. Oral cancer
- mostly squamous cell carcinoma
- often associated with abuse of tobacco and alcohol
- may be associated with irritants: pipe smoking, chewing tobacco
or betel nuts
II. Diseases of the SALIVARY GLAND
A. Sialadenitis
B. Mucocele
C. Ranula
D. Tumors
Pleomorphic adenoma (Mixed tumor)
Warthin tumor / adenolymphoma / Papillary cystadenoma
lymphomatosum
Oncocytoma
Adenoid cystic carcinoma
Mucoepidermoid tumor
a. PAPILLOMA (1)
Squamous cell papilloma
(HE) x 25
PAPILLOMA
PAPILLOMA
Fibroma
I.C. TUMORS & TUMOR-LIKE CONDITIONS

1. Benign tumors of the oral mucosa

a. Papilloma: the most common benign epithelial oral
mucosal tumor  tongue, lips, gingivae, buccal
b. Fibroma: it is often a non-neoplastic hyperplastic
lesion due to chronic irritation
c. Hemangioma: tongue, lips, buccal mucosa
d. Epulis: any abnormal swelling of the gingiva, as a
reparative growth rather than a true neoplasm
2. Leukoplakia:
a. clinical term describing irregular white mucosal
patches
b. pre-cancer
 Fibroma

Abdominal wall Shoulder

 Fibroma.
Smooth, pink, exophytic nodule on the buccal mucosa.
Fibroma
Fibroma
 Fibroma

Less vessels, more hyalin matrix

NEVUS (2)
DERMAL NEVUS
Dermal Nevus
JUNGTIONAL
NEVUS
 Nevus Junctional type

Small lesion, somewhat flat,

symmetric, and uniform

Rounded nest of nevus cells originating at the tips of

rete ridges along the dermo-epidermal junction
Junctional nevus
(HE) x 25
COMPOUND
NEVUS
 Nevus
compound type

More raised than junctional nevus, Combination of features of junctional nevi

dome shaped. The symmetri and uniform (intraepidermal nevus cells nest) with nest
pigment suggest a benign process of nevus cells in the underlying dermis
DYSPLASTIC
NEVUS
 Nevus
dysplastic nevus

More pigmented and raised central zone (A: compound nevus component) and an
assymetric “shoulder” (B:junctional nevus component  cytologic atypia: irregularly
shaped, dark staining nuclei). The dermis underlying atypical cells 
linear or lamellar fibrosis  desmoplasia.
NEVUS
 3.
GRANULOMAPYOGENICUM
 Pyogenic granulomas are usually solitary lesions. The fingers and
hands are common locations for these to develop. A history of minor
trauma at the site shortly before development of the lesion is frequent.
Pyogenic granulomas usually bleed with little or no trauma.
This patient shows a positive bandage sign. Because the
lesions bleed so easily, patients frequently present with a
bandage covering the site.
 Pyogenic granulomas usually have a distinct margin that
consists of a rim of keratin (dry skin). Notice the moist area
of skin produced by the bandage, which was removed
shortly before the photograph was taken.
Pyogenic granulomas may occur at various sites. More
than 60% of all lesions develop on the head and neck.
Pyogenic granulomas may be pedunculated and quite
large. An area of necrosis is also common.
Pyogenic Granuloma on the
inner lip.
Pyogenic granulomas
Unlike pyogenic granulomas, cherry angiomas such as these are slow
to develop, do not bleed easily, are frequently multiple, are more
commonly found on the trunk, and seldom have a history of prior
trauma.
Hemangioma Pyogenic granuloma
 Several malignant tumors may mimic pyogenic granulomas. This lesion is a squamous
cell carcinoma. Amelanotic melanomas (little or no overt pigment) are also included in the
differential diagnosis. These tumors are usually slower growing than pyogenic
granulomas and are uncommon in children. Tissue removed as part of the treatment
process should be sent for histopathologic examination to confirm the diagnosis.
Pyogenic granulomas
Pyogenic granulomas
Pyogenic granulomas
Pyogenic granulomas
I.C. TUMORS & TUMOR-LIKE CONDITIONS

1. Benign tumors of the oral mucosa

a. Papilloma: the most common benign epithelial oral
mucosal tumor  tongue, lips, gingivae, buccal
b. Fibroma: it is often a non-neoplastic hyperplastic
lesion due to chronic irritation
c. Hemangioma: tongue, lips, buccal mucosa
d. Epulis: any abnormal swelling of the gingiva, as a
reparative growth rather than a true neoplasm
2. Leukoplakia:
a. clinical term describing irregular white mucosal
patches
b. pre-cancer
c. Hemangioma (6)
Lymphangioma
Hemangioma Pyogenic granuloma
 Capillary Hemangioma

Congenital capillary hemangioma at birth (A), and at 2 years

after spontaneous regression
Capillary hemangioma
Capillary hemangioma
Capillary hemangioma
Cavernous hemangioma
Cavernous hemangioma
 Lymphangioma,
retropancreatic and intraabdominal
Lymphangioma
hygroma
hygroma
I.C. TUMORS & TUMOR-LIKE CONDITIONS

1. Benign tumors of the oral mucosa

a. Papilloma: the most common benign epithelial oral
mucosal tumor  tongue, lips, gingivae, buccal
b. Fibroma: it is often a non-neoplastic hyperplastic
lesion due to chronic irritation
c. Hemangioma: tongue, lips, buccal mucosa
d. Epulis: any abnormal swelling of the gingiva, as a
reparative growth rather than a true neoplasm
2. Leukoplakia:
a. clinical term describing irregular white mucosal
patches
b. pre-cancer
d. EPULIS (4)
 Reparative lesion:
EPULIS

Excessive reparative process

-Granulomatous epulis
-Fibromatous/fibroid epulis
-Giant cell epulis
-Haemangioform epulis
-Pregnancy epulis
Fibromatous/fibroid epulis
7. OSTEOMA
OSTEOMA
OSTEOMA
OSTEOMA
OSTEOMA
OSTEOMA
FIBROUS DYSPLASIA
 Fibrous displasia terdiri dari trabekula tulang menipis berbentuk
anyaman lengkung (huruf C). Bagian tepi yang tidak didapatkan
osteoblastik. Proliferasi jaringan fibrosa nampak mencolok, sebagai
latar belakang.
 FIBROUS DYSPLASIA

• Microscopical
– Consists of bone of connective tissue components
– C letter-like trabecules without osteoblastic rimming
Lipoma (8)
"Knapsack” tumor: lipoma
 Lipoma

Well defined, lobulated

 Lipoma

Normal mature fat cells

 Lipoma

Myxoid changes: myxolipoma

 Lipoma

Angiolipoma, capillary-sized vessels some with thrombi

surrounded by spindle cells
I.C. TUMORS & TUMOR-LIKE CONDITIONS

1. Benign tumors of the oral mucosa

a. Papilloma: the most common benign epithelial oral
mucosal tumor  tongue, lips, gingivae, buccal
b. Fibroma: it is often a non-neoplastic hyperplastic
lesion due to chronic irritation
c. Hemangioma: tongue, lips, buccal mucosa
d. Epulis: any abnormal swelling of the gingiva, as a
reparative growth rather than a true neoplasm
2. Leukoplakia:
a. clinical term describing irregular white mucosal
patches
b. pre-cancer
LEUKOPLAKIA
- white patches of keratosis
- premalignant lesion
- hyperkeratosis, hyperplasia of the squamous epithelium
- dysplastic changes

SQUAMOUS CELL CARCINOMA

Ameloblastoma (9)
 I.C. TUMORS & TUMOR-LIKE CONDITIONS
3. Odontogenic tumors
a. Odontoma: hamartoma derived from odontoblastic epithelium
b. Ameloblastoma:
- epithelial tumor arising from precursor cells of the enamel organ
- usually before age 35, and most fequently in mandible
- irregular local extension
4. Oral cancer
- mostly squamous cell carcinoma
- often associated with abuse of tobacco and alcohol
- may be associated with irritants: pipe smoking, chewing tobacco
or betel nuts
 KASUS I
Laki-laki, 30 tahun, dengan benjolan seperti pada gambar :
Dilakukan operasi dengan hasil mikroskopis sbb.:
Dilakukan operasi dengan hasil mikroskopis sbb.:
Dilakukan operasi dengan hasil mikroskopis sbb.:
Dilakukan operasi dengan hasil mikroskopis sbb.:
 A3.
• Apa diagnosis kasus diatas ?

• Sebutkan salah satu tanda/ciri khas

gambaran mikroskopis kasus I !
A4.

Bangunan yang ditunjuk panah merah ini menunjukkan

adanya degenerasi …………
B4.

Bangunan yang ditunjuk panah merah ini secara klinis

menimbulkan gejala klinis yang disebut …………..
 Pharynx & Tonsil
Pharyngitis
-Viral pharyngitis: common feature of the CC, influenza, measles, etc
-Streptococcal pharyngitis: less common but more important than viral
pharyngitis because the complication  rheumatic fever, acute
proliferative glomerulonephritis, Henoch Schonlein purpura
-Ulcerative pharyngitis & tonsillitis  diphtheria
Tonsilitis:
-Follicular tonsilitis, streptococcus/ Borrelia / virus
-Parenkhimal tonsilitis: quincy, Peritonsiler abses
-Angina agranulositic netropenic
-Tonsilitis morbili: Warthin Finkeldey giant cells

Malignant tumors: NPC, squamous cell ca, lymphoma

Kelenjar liur
Pleomorphic adenoma /
Mixed tumor (5)
II. Diseases of the SALIVARY GLAND
A. Sialadenitis
B. Mucocele
C. Ranula
D. Tumors
Pleomorphic adenoma (Mixed tumor)
Warthin tumor / adenolymphoma / Papillary cystadenoma
lymphomatosum
Oncocytoma
Adenoid cystic carcinoma
Mucoepidermoid tumor
Anatomy of parotid gland
Anatomy of parotid gland
Pleomorphic adenoma (parotid)
Pleomorphic adenoma (gross)
Pleomorphic adenoma
Pleomorphic adenoma
 Warthin tumor

Benign tumor mostly occur in parotid gland

 Warthin tumor

Cystic spaces lined by double-layered eosinophilic epithelium,

and all embedded in lymphoid stroma
 Oncocytoma

Mostly in parotid gland

 Oncocytoma

Large granular appearing, eosinophilic-staining epithelial cells

 Tumor ganas di oral dan kelenjar liur

1. Karsinoma Epidermoid
2. Basal Cell Carcinoma
3. Melanoma
4. Undifferentiated carcinoma
5. Carcinoma ex pleomorphic adenoma
6. Adenoid cystic carcinoma
7. Mucoepidermoid tumor
SQUAMOUS CELL
CARCINOMA
KARSINOMA EPIDERMOID DENGAN
PERTANDUKAN
 SQUAMOUS CELL CARCINOMA
• Common, derived from keratinocytes in
epidermal layer
• Usually men, associated with
– sun exposure (UV light may induce p53 mutations
and diminish surveillance function of Langerhans cells
in epidermis),
– PUVA treatment for psoriasis, arsenic, tars/oils,
chronic ulcers,
– draining osteomyelitis,
– old burn scars,
– necrobiosis lipoidica,
– hidradenitis suppurativa,
– ionizing radiation
• Risk factors:
– immunosuppression (post-transplant or HIV),
– xeroderma pigmentosa (disorder with diminished capacity for
DNA repair after UV light exposure, due to gene at 9q22.3;
associated with squamous cell, basal cell carcinoma and
melanoma),
– lack of pigmentation in skin,
– actinic keratosis (precursor lesion),
– epidermodysplasia verruciformis;
– very rare in blacks
• 5% are node positive at diagnosis; metastatic rate is 5-
10% in transplant patients, who do poorly with metastatic
disease
• Slow growing, locally invasive but rarely metastasizes
outside nodes (but see above); most common site is
lung
• Metastases more likely in tumors that originate in scars
or ulcers
 SQUAMOUS CELL CARCINOMA

• Prognosis: excellent; metastases uncommon if tumor <

1.5 cm deep; 5% metastasize if 2 cm or more and
definite dermal invasion
• Good prognostic factors:
– low stage,
– no/superficial dermal invasion, small vertical tumor thickness (<
4 mm),
– well differentiated,
– short duration,
– location other than scalp, ears, lips, nose, eyelids or soft tissue
(which readily invade subcutaneous tissue)
• Treatment: surgical excision with adequate margins;
also currettage, electrodesiccation, cryotherapy,
radiation therapy
• Gross: often white plaque (leukoplakia); may have
induration, ulceration, hemorrhage
• Micro: nampak sel-sel tumor atypia di semua
stratum/lapisan epidermis; 80% diferensiasi baik/sedang
dengan didapatkan mutiara keratin dan jembatan antar
sel, tidak ada / langka adanya butiran keratohyaline, sel
tumor infiltrasi ke dermis. Pada keadaan tertentu:
– mungkin didapatkan sel melanosit non-neoplastik yang
mentransfer melanin ke sel tumor; terutama jenis clear cells,
signet ring cells
– Varian spindle, adenoid, verrucous, dan acantholytic
(pseudoglandular, celah tumor yang dihasilkan oleh acantholysis
sel tumor) dan pseudoangiosarcomatous (clefts separate
neoplastic lobules)
 Low grade (well differentiated): cell differentiation, uniform cell
size, intact intercellular bridges, no/rare mitotic figures, no/mild
pleomorphism
 High grade (poorly differentiated): little cell differentiation,
pleomorphism with spindle cells, necrosis, marked mitotic activity,
deep invasion
 SQUAMOUS CELL CARCINOMA
• Positive stains:
– high molecular weight keratin,
– EMA,
– involucrin,
– p53 (50%),
– variable CEA
• Negative stains:
– Ber-EP4, usually CK7 and CK20 (head and neck
tumors, Mod Path 2004;17:407)
• DD: keratoacanthoma (for well differentiated
tumors)
Squamous Cell Ca
Squamous Cell Ca
Squamous cell carcinoma
(HE) x 75
Squamous cell carcinoma
(HE) x 150
Selected cases of squamous cell carcinoma: (a) a representative case
of moderately differentiated squamous cell carcinoma (H&E, X 40); (b)
intranuclear staining for human telomerase reverse transcriptase
activity (X 200); (c) intracytoplasmic COX-2 stain (X 200); (d) strong
intranuclear p53 expression (X 400).
Selected cases of keratoacanthoma: (a) a representative case of early
keratoacanthoma with overhanging lips and central horn-filled crater
(H&E, 40); (b) negative for telomerase activity ( 400); (c) basal
staining for p53 ( 100); (d) negative COX-2 stain ( 200).
 Histopathologic criteria to
differentiate early keratoacanthoma
from a well to moderately
differentiated squamous cell
carcinoma (Ackerman et al and Cribier et al)

TABLE …..
 Keratoacanthoma Squamous cell
carcinoma
Exoendophytic lesion with a Predominantly endophytic with no
central horn-filled crater horn-filled crater
Overhanging 'lips' of epithelium No epithelial 'lips'
Rarely ulcerated Commonly ulcerated
Abundant pale staining cytoplasm Less common
of keratinocytes
Intraepithelial abscesses within the lesion Rare
Acantholytic cells within the Acantholytic cells form without
intraepithelial abscesses often associated neutrophils
Gland-like formations rare Pseudoglandular formations often
Lack of anaplasia Common
Sharp outline between tumor nests Indistinct
and stroma
Absence of stroma desmoplasia Present
 Immunohistochemical
expression of telomerase
activity, COX-2, and p53 in
keratoacanthoma (KA) and
squamous cell carcinoma
(SCC).
TABLE …..
 KA a SCC a 'P' value
(n=24) (n=17)
Telomerase Negativeb 01(4.2) 0 (0)  
  Weakc 20(83.3) 06(35.3) 0.001
  Strongd 03(12.5) 11(64.7)  
COX-2 Negative 16(66.7) 04(23.5)
  Weak 07(29.2) 04(23.5)  0.001
  Strong 01(4.2) 09(52.9)  
p53 Negative 10(41.7) 02(11.8)
Weak 13(54.2) 04(23.5)  0.000
Strong 01 (4.2) 11(64.7)

a  Number of samples (percentage in brackets).

b  Negative — no staining.
c  Weak — Combined score of <= 3.
d  Strong — Combined score of >3.
Undifferentiated
carcinoma
 Nasopharynx

Inflammation
• Acute
• Chronic
Neoplasm
• Juvenile angiofibroma
• Undifferentiated carcinoma
a McIvor mouth gag is applied and a left nasopharyngeal
mass is visible behind the soft palate and left posterior
pillar. The final diagnosis was lymphoepithelioma
Nasopharingeal Ca, non-keratinizing, undiff.
Nasopharingeal Ca, non-keratinizing, undiff.
 EBV
(IH; LMP-1) x 600
Anaplastic (undifferentiated)
Carcinoma

Metastasic tumor
LARYNX: benign vs malignant
Laryngeal papillomatosis
 Laryngeal Carcinoma

Gross: fungating/papillar Microscopical: well.diff.

SCC
BASAL CELL CARCINOMA
 BASAL CELL CARCINOMA
• Most frequent form of skin cancer
• Usually sun exposed skin (not mucosal surfaces), in
proportion to number of pilosebaceous units present
• Rosai claims these tumors attempt to differentiate toward
pilosebaceous units, but often this is not readily apparent
• Often multiple tumors
• Usually older adults
• Slow and indolent, untreated cases may invade subcutis,
skeletal muscle and bone; facial tumors may invade
skull, nares, orbit or temporal bone; only 100 metastatic
cases described, often associated with basal cell nevus
syndrome or basosquamous histology, on sunlight-
protected skin
• Metastases are rare; 60% to regional lymph nodes, also
lung, liver, bone
• Risk factors:
– fair skin, blue eyes,
– immunosuppression (higher incidence, more
aggressive tumors),
– xeroderma pigmentosum
• Also associated with
– nevus sebaceus of Jadassohn,
– chronic venous stasis of lower leg,
– arsenic, X rays,
– skin injury, chickenpox scars,
– tattoos, hair transplant scars,
– immunosuppression
• Less common in children or young adults,
sunlight-protected skin; rarely coexists with
benign nevus
Basal cell carcinoma
Basal cell carcinoma
(HE) x 75
MALIGNANT MELANOMA
 Melanoma
• Incidence increasing worldwide - 48,000 cases
and 9,200 deaths in US in 2000
• Usually due to sun (UV light) exposure
• Warning signs: change in color of pigmented
lesion, enlargement of existing mole, itching or
pain in preexisting mole, development of new
pigmented lesion in adult life, irregular borders in
pigmented lesion, variegation of color in
pigmented lesion
• Head and neck, lower extremities (particularly in
women); rarely subungual (“melanotic whitlow”),
palm, sole. Also oral and anogenital mucosa,
esophagus, meninges, eye
• Populations at higher risk: whites with fair skin, red
hair, tendency to burn or freckle from sun exposure,
large number of melanocytic nevi, xeroderma
pigmentosum, familial dysplastic nevi, melanosis, vitiligo,
possibly neurofibromatosis type I
• Up to 10% may be familial due to CMM1 gene at 1p36
• Blacks have low risk, their common melanoma sites are
palms, soles, nail beds or mucous membranes
• Usually after puberty, occasionally children - all have
same morphology
• 5% are multiple, although prognosis is related to type
and stage of largest lesion, not number of lesions; must
distinguish multiple lesions from “hot nevi” / nevus
activation
• Achilles tendon tumors are often spindled
• Tend to grow laterally and deep; common metastases to
regional lymph nodes, also liver, lungs, GI tract, bone,
CNS, heart (50% at autopsy), skin (satellite tumors
within 2 cm of primary tumor), other sites
• Overall 5 year survival is 60%
• Poor prognostic factors:
– increased Breslow (vertical) thickness in primary
tumor,
– high stage (TNM),
– males (do worse than females),
– high mitotic rate,
– ulceration,
– microscopic satellites (tumor nests 50 microns or
larger and separated from main tumor mass),
– deeper level of invasion for T1 tumors,
– higher % tumor area/volume in sentinel node,
– increased density of dendritic leukocytes in nodal
paracortex (associated with risk of tumor in non-
sentinel nodes, recurrence and death, Mod Path 2004;17:747)
• Overall behavior is variable, with occasional late
deaths or long survival even with widespread
satellite nodules
 Melanoma
• S100:
– nuclear and cytoplasmic, 90%+ sensitive but not specific (although
usually negative in tumors considered in the differential)
• HMB45:
– less sensitive but more specific than S100; negative in desmoplastic
melanoma
• MelanA/Mart1:
– sensitive, but also stains steroid-producing cells in ovary, testis, adrenal
cortex
• Tyrosinase:
– sensitive, but also stains peripheral nerve sheath and neuroendocrine
tumors
• Microphthalmia transcription factor:
– sensitive, but also stains dermatofibroma and smooth muscle tumors;
negative in spindle cell / desmoplastic melanoma
• NKI-C3 and NSE: nonspecific
• Negative stains: p53
Nevus Pigmentosus  Melanoma
steps of tumor progression in dysplastic nevi

A. Melanocytic hyperplsia, B. Junctional nevus, C. Dysplastic nevus (compound

nevus with abnormal architectural and cytologic freatures, D. early melanoma
(radial growth phase melanoma  large dark cells in epidermis), E.advanced
melanoma (vertical growth phase)
 Malignant Melanoma

Lesions are irregular in contour and pigmentation. Macular areas correlated

with the radial growth phase, while raised areas usually correspond to
nodular aggregation of malignant cells in the vertical cell growth
Malignant Melanoma
 Malignant Melanoma
radial growth phase of melanoma

Irregular nested and single cell growth of melanoma cells within the
epidermis and an underlying inflammatory response within the dermis
Malignant Melanoma
vertical phase growth

Nodular aggregates of infiltrating cells

 Malignant Melanoma

High-power view of malignant melanoma cells

Nodular malignant melanoma
(HE) x 10
Superficial spreading melanoma
Superficial spreading melanoma
(HE) X 100
MALIGNANT MELANOMA
QUIZ
 KASUS I
Laki-laki, 68 tahun, dengan lesi kehitaman sbb.:
Dilakukan operasi dengan hasil mikroskopis sbb.:
Mikroskopis pembesaran kuat sbb.:
 A1.
• Apa diagnosis kasus diatas ?
 B1.
• Sebutkan salah satu tanda/ciri khas
gambaran mikroskopis kasus I !
 A2

Bangunan yang ditunjuk panah merah ini menunjukkan ..

………
 B2.
• Faktor prognosis lesi primer pada kasus I
paling dipengaruhi oleh :
A. kedalaman invasi
B. ukuran sel tumor
C. jumlah sel raksasa berinti banyak
D. Banyaknya sel inflamasi di sekitar tumor
E. banyaknya produksi melanin
Carcinoma ex
pleomorphic
adenoma
Keterangan gambar : carcinoma ex
pleomorphic adenoma
Karsinoma mioepitel atau carcinoma ex
pleomorphic adenoma (kanan) timbul pada
Adenoma Pleomorfik (kiri) kelenjar liur
parotis. Didapatkan pula pola pertumbuhan
multinodular dengan infiltrasi tumor di
dermis
Adenoid cystic carcinoma
Adenoid cystic carcinoma

Minor salivary gland

Adenoid cystic carcinoma
 Adenoid cystic carcinoma

Most characteristic appearance consists of cribriform pattern

with masses of small, dark-staining cells arrayed arround
cystic spaces
Adenoid cystic carcinoma
Mucoepidermoid
tumor
Mucoepidermoid tumor
(Palatal gland)

Mostly in parotid gland

 Mucoepidermoid tumor
(Low grade)

Comprised of mucus-producing and epidermoid omponents

and cells intermediate between the two
Mucoepidermoid tumor
(moderate grade)
Mucoepidermoid tumor
(High grade)
 Respon Imun Terhadap Tumor
• Imunologi adalah ilmu yang mencakup kajian mengenai
semua aspek sistem imun (kekebalan) pada semua
organisme.
• Imunologi kanker adalah studi tentang interaksi antara
sistem kekebalan tubuh dengan sel-sel kanker.
• bidang penelitian yang bertujuan untuk menemukan
immunoterapi inovatif guna mengobati kanker /
menghambat perkembangan sel kanker.
• Kanker adalah suatu kondisi di mana sel telah
kehilangan pengendalian dan mekanisme normalnya,
sehingga mengalami pertumbuhan yang tidak normal,
cepat dan tidak terkendali.

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Ada 4 jenis sel-sel imun yang dapat
membunuh target tumor in vitro maupun in
vivo.
1. Sel pembunuh alami (Natural Killer (NK) Cell)
2. Cytolytic thymus dependent Lymphocytes
(CTLs)
3. Lymphokine-activated killer cells (LAK cells),
4. Macrophages

11/17/21 218
 Hallmark Kanker dan terapi target

11/17/21 219
 NEOPLASIA
basic science of oncology

GENERAL COMPREHENSION DIAGNOSIS

OF CANCER

THERAPY

PATHOBIOLOGY OF CANCER MANAGEMENT

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