NEOPLASM

dr. Imam Sarwono, SpPA

Departement of Anatomic Patology

Faculty of Medicine, Brawijaya University
Malang
 NEOPLASM
I. DEFINITIONS
II. NOMENCLATURE
III. CHARACTERISTICS OF NEOPLASM
IV. TUMOR DEVELOPMENT
V. CLINICAL FEATURES
VI. DIAGNOSTIC PROCEDURES
VII. TUMOR PROGRESSION & HETEROGENEITY
VIII. CARCINOGENESIS
I. DEFINITIONS

Neoplasm is:
an abnormal mass of tissue.
the growth of witch exeeds, uncoordinated with
normal tissue, purposless.
persists in the same maner of growth after
cessation of the stimuli.
grow autonomous ( not complete ) depend on
nutrition of the host.
meningioma
The terms that related with neoplasm:
1. Oncology : is the study of tumors/ neoplasm
2. Cancer : malignat neoplasm / tumor
3. Tumor : benign and malignant neoplasm
4. Neoplasia : New growth .
Neoplasm is the new growth.
5. Transformed cells: neoplastics cells.
6. Dysplasia : a loss of architectural and uniformity
of epithelium.
May or may not progress to cancer.
II. NOMENCLATURE
Two basic component of tumor:
1. parenchyma: proliferating neoplastic cells
(epithelial or mesenchymal).
2. supportive stroma: conective tissue and
blood vessels.

Nomenclature tumor is based on the parenchymal

component.
Benign tumors: are designated by attaching the suffix
“oma” to cell / tissue of origin.
Benign tumor of messenchymal cell generally follow this
rule:
Fibroma: a benign tumor arising from fibroblastic cells.
Chondroma: from catilagenous cell.
Asteoma: from osteoblast.
Nomenclature of benign epithelial tumor is more complex:

Adenoma : benign epithelial tumors that forms glandular

patterns.

Papilloma: benign epithelial neoplasm producing

finger like projection from epithelial.

Cystadenoma: Cystic masses of benign epithelial

neoplasm (ovary).

Papillary Cystadenoma: Cystic masses benign neoplasm

with papillary pattern.

Polyp: Visible projection of mucosal surface.

 Malignant Tumors

SARCOMA
Malignant tumors from mesenchymal tissue/ cells usually
called sarcoma.
Fibrosarcoma from fibroblast.
Liposarcoma from lipoblast.
Leiomyosarcoma from smooth muscle.
Rhabdomyosarcoma from striated muscle.
CARCINOMA
Malignant tumor from epithelial cells, called Carcinoma.
Adeno carcinoma from glandular epithelium.
Squamous cell carcinoma from Squamous
epithelium.
Transtitional cell carcinoma.
Basal cell carcinoma.
Fig. 19.136 A and B, Gross appearances of endometrioid
adenocarcinoma.
The tumor shown in A is polypoid, whereas that depicted in
B is highly infiltrating.
Figure 22-1 Embryology and anatomy of the female genital tract. A, Early in development the mesonephric (red) and müllerian (blue) ducts merge at the urogenital
sinus to form the müllerian tubercle. B, By birth the müllerian ducts have fused to form the fallopian tubes, uterus and endocervix (blue) merging with the
vaginal squamous mucosa. The mesonephric ducts regress but may be found as a remnant in the ovary, adnexa and cervix (Gartner duct). (Adapted from Langman J:
Medical Embryology. Baltimore, Williams and Wilkins, 1981.) C, Normal adult genital tract, with cervix, uterus, fallopian tubes, and ovaries. A small paratubal cyst is
present on the right.

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basal cell carcinoma
MIXED TUMOR

Tumor contain two components, ephithelial &

mesenchymal, that derivat from single germ layer.

1. Mixed tumor of salivary gland tumor contain epithelial

components, myxoid stroma, cartilage or bone.
This tumors arise from epithelial and myoephitelial cell
of salivary.
2. Fibradenoma Mamma.
Neoplasms of Totipotent cells
Totipotent cells in post natal are the Germ cells.
Totipotent cells commonly found in the
gonads, retroperitoneum, mediastinum and
pineal region.

Teratoma is the neoplasm that representatif of

more than one germ layer .
In this tumor, totipotent cells differentiate to
many tissue: skin, brain, bronchus, cartilage,
etc.
Exception to the rules
Neoplasm that “ sound benign “ but really
malignant:

- Lymphoma, from lymphoid cells.

- Plasmacytoma, from plasma cells.
- Melanoma, from melanocyte.
- Astrocytoma, from astrocyte.
- Seminoma, from germ cells in testis.
III. CHARACTERISTICS of
NEOPLASM

There are two extremes character of

tumor :
Benign and Malignant

A. Biologic characters.
B. Morphologic characters.
A. Biologic Characters.
1.Benign tumor:
- Grow slowly.
- Not invade surrounding tissue.
( Compressed surrounding tissue ).
- Not spread to distant side
( not metastasis ).

2. Malignant tumor:
- Rapid growing.
- Invasive/ infiltrate.
- Metastasis.
Rate of Growth
Most benign tumors grow slowly and most
cancer grow rapidly.
The growth rate of tumors correlates with their
level of differentiation.
Undifferentiated tumors usually grow more
rapid than well differentiated.
Blood supply, dependency to hormone, amount
of mitosis influences growth rate of tumors
Host Factors Affecting Tumor Cell
Growth
Blood Supply
• Tumor cell production of angiogenic factors such as
fibroblast growth factor.
Hormones
• Hormonally dependent tumors occur that
proliferate more rapidly with increased hormone.
Immunological
• Host immune response to the tumor versus tumor
cell resistance to the immune response.
B. Morphologic Character

1. Gross features.

a. Benign tumor :
- Smooth surface with fibrous capsule.
- Solid-rubbery consistency.
- Necrosis & hemorrhage uncommon.

b. Malignant tumor :
- Not encapsulated.
- Poorly demarcated.
- Fragile consistency.
- Common with necrosis and hemorrhage.
2. Microscopic features:

a. Differentiation
b. Anaplasia
c. Invasion
d. Metastasis
a. Differentiation.
- Well differentiated : parenchyma
tumors are composed of cell resembling the
mature normal cell.
- Poorly differentiated / Undifferentiated :
tumors have primitive ,
unspecialized cells.

In general, benign tumors are well differentiated.

Malignant tumors can well or poorly
differentiated.
b. Anaplasia (lack of differentiation)
- Pleomorphism ( variation in size and shape )
of cells and nuclei.
- Hyperchromatism ( dark stanning ) of nuclei.
- High nuclear-cytoplasmic ratio.
- Chromatin is often coarsely and clumped.
- Large nucleoli.
- Tumors giant cell.
- Lose of normal structure and polarity of cells.
- Bizarre mitotic figure ( tripolar, quadripolar ).

Anaplasia is a hallmark of malignant transformation.

 INVASION
Benign tumors usually grow by slow
expansion.
Malignant tumors usually infiltrate and
may destroy surrounding tissue (cell
surface and the extracellular matrix play
an important role).
basal cell carcinoma
 Tumor Cell Invasion
Detachment from other tumor cells.
Adhesion to the extracellular matrix.
Proteolytic degradation of the
extracellular matrix.
Motility and migration into the
extracellular matrix.
 Metastasis
A discontinuous spread of the tumor
Methods of metastasis include:
(1)seeding of body cavities, (2)
lymphatic spread, and (3)
hematogenous spread.
 IV. Tumor Development
and Growth
• Transformation
• Growth of transformed cells
• Invasion of tumor cells into the
surrounding tissues
• Metastasis of tumor cells to distant
sites
Properties of Transformed Cells
In Vitro
• Decreased contact inhibition
• Decreased requirement for growth factors
• Anchorage independence
• Failure to differentiate
• Immortality
• Transplantability
• Reduced cohesiveness
TRANSFORMED CELL.
 V. Clinical Features of Tumors

• Local Effects
• Cancer Cachexia
• Paraneoplastic Syndromes
• Endocrinopathies
• Neuromyopathies
• Osteochondral Disorders
• Vascular Phenomena
• Fever
• Nephrotic Syndrome
 Local Effects
• Tumor Impingement on nearby structures
• Pituitary adenoma on normal gland, Pancreatic carcinoma
on bile duct, Esophageal carcinoma on lumen
• Ulceration/bleeding
• Colon, Gastric, and Renal cell carcinomas
• Infection (often due to obstruction)
• Pulmonary infections due to blocked bronchi (lung
carcinoma), Urinary infections due to blocked ureters
(cervical carcinoma)
• Rupture or Infarction
• Ovarian, Hepatocellular, and Adrenal cortical carcinomas;
Melano-carcinoma metastases
Figure 22-1 Embryology and anatomy of the female genital tract. A, Early in development the mesonephric (red) and müllerian (blue) ducts merge at the urogenital
sinus to form the müllerian tubercle. B, By birth the müllerian ducts have fused to form the fallopian tubes, uterus and endocervix (blue) merging with the
vaginal squamous mucosa. The mesonephric ducts regress but may be found as a remnant in the ovary, adnexa and cervix (Gartner duct). (Adapted from Langman J:
Medical Embryology. Baltimore, Williams and Wilkins, 1981.) C, Normal adult genital tract, with cervix, uterus, fallopian tubes, and ovaries. A small paratubal cyst is
present on the right.

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Figure 22-34 A, Leiomyomas of the myometrium. The uterus is opened to reveal the tumors bulging into the endometrial cavity and displaying a firm white appearance on
sectioning. B, Leiomyoma showing well-differentiated, regular, spindle-shaped smooth muscle cells.

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metastatic ovarian carcinoma
 Cancer Cachexia

• Progressive weakness, loss of appetite, anemia and

profound weight loss (>20 lbs.)
• Often correlates with tumor size and extent of
metastases
• Etiology includes a generalized increase in
metabolism and central effects of tumor on
hypothalamus
• Probably related to macrophage production of
TNF-
 Paraneoplastic Syndromes
Endocrinopathies
• Cushing’s Syndrome
• Adrenal carcinoma (cortisol) more common with
benign adrenal processes.
• Small cell undifferentiated lung cancer (ACTH)
released through cleavage of pro-opiomelano-cortin
gene product.
• Inappropriate ADH syndrome (Hyponatremia)
• Small cell undifferentiated lung cancer (vassopressin-
like hormone.
• Hypothalamic tumors (vasopressin)
 Paraneoplastic Syndromes
Endocrinopathies

• Hypercalcemia (Cancer is the most common cause of

hypercalcemia by either humoral or metastatic
mechanisms)
• Squamous cell lung cancer (PTH-like peptide)
• Renal cell carcinoma (prostaglandins)
• Parathyroid carcinoma (PTH)
• Multiple myeloma and T-cell lymphoma (IL-1 and
perhaps TNF-)
• Breast carcinoma, usually by bone metastasis
 Paraneoplastic Syndromes
Endocrinopathies

• Hypoglycemia - caused by tumor over-production of

insulin or insulin like activities
• Fibrosarcoma, Cerebellar hemangioma,
Hepatocarcinoma
• Carcinoid syndrome - Caused by serotonin,
bradykinin or ?histamine produced by the tumor
• Bronchial carcinoids, Pancreatic carcinoma, Carcinoid
tumors of the bowel
 Paraneoplastic Syndromes
Endocrinopathies

• Polycythemia - caused by tumor production of

erythropoietins
• Renal cell carcinoma, Cerebellar hemangioma,
Hepatocarcinoma
• WDHA syndrome (watery diarrhea, hypokalemia, and
achlorhydria) - caused by tumor production of vasoactive
intestinal polypeptide (VIP).
• Islet cell tumors, Intestinal carcinoid tumors
 Paraneoplastic Syndromes
Neuromyopathies

• Myasthenia - A block in neuromuscular transmission

possibly caused by host antibodies against the tumor cells
that cross react with neuronal cells or perhaps caused by
toxins.
• Bronchogenic carcinoma, Breast cancer
• Carcinomatous Myopathy - probably immune-
mediated
 Paraneoplastic Syndromes
Osteochondral Disorders
• Hypertrophic Osteoarthropy - clubbing, periosteal
new bone, and arthritis
• Isolated clubbing occurs in chronic obstructive
pulmonary disease and in cyanotic congenital heart
disease, but the full-blown syndrome is limited to lung
cancer.
 Paraneoplastic Syndromes
Vascular Phenomena

• Altered Coagulability - caused by the release of

tumor products
• Migratory Venous Thromboses (Trousseau’s
sign) Pancreatic, gastric, colon, and bronchogenic
carcinomas; particularly adenocarcinoma of the lung.
• Marantic endocarditis - Small thrombotic
vegetations on mitral or aortic valves that occur with
advanced carcinomas.
 Paraneoplastic Syndromes
Fever

• Associated with bacterial infections

• Common where blockage of drainage occurs
• Decreased immunity may play a role
• Not associated with infection
• Episodic as in Pel-Ebstein fever with Hodkin’s
lymphoma; poor prognostic sign in sarcomas, indicates
dissemination
• Likely caused by response to necrotic tumor cells
and/or immune response to necrotic tumor proteins.
 Paraneoplastic Syndromes
Nephrotic Syndrome

• Excessive loss of protein in the urine

• probably caused by damage to renal glomeruli by
tumor antigen-antibody complexes.
 grading and staging
• Grading is based on the microscopic
features of the cells which compose a
tumor and is specific for the tumor type.
• Staging is based on clinical, radiological,
and surgical criteria, such as, tumor size,
involvement of regional lymph nodes,
and presence of metastases. Staging
usually has prognostic value.
 morbidity and mortality
• metastases
• rupture into major vessels
• compression of vital organs
• organ failure
• infection
metastatic ovarian carcinoma
meningioma
 NEOPLASMA

Dr. Imam Sarwono, Sp.PA.

 VI. Diagnostic procedures
• FN(A)B : Fine Needle (aspiration)
Biopsy
• Cytological smears
• Surgical biopsy : Histopathology.
• Frozen sections
CONTOH KASUS :
Gambar sitologi mamma :
frozen section
staining a frozen section
cytology smear:
adenocarcinoma
Pap smear with dysplasia
 ancillary studies
• immunohistochemistry
• cytogenetics
• flow cytometry
• electron microscopy
 some serological markers
associated with malignant
tumors
hCG choriocarcinoma
AFP hepatocellular ca
calcitonin thyroid medullary ca
prolactin pituitary adenomas
CA 125 ovarian carcinoma
PSA prostate carcinoma
chromogranin A endocrine neoplasias
VII. Tumor Progression and Heterogeneity

• Tumor progression is defined as the

acquisition of permanent changes in
characteristics of selected subpopulations of
the tumor.
normal epithelium
Figure 22-6 Inflammatory vulvar disorders. Lichen sclerosus (upper panel). Lichen simplex chronicus (lower panel). The main features of the lesions are indicated in the
figures.

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Figure 22-19 Spectrum of cervical intraepithelial neoplasia: normal squamous epithelium for comparison; CIN I with koilocytotic atypia; CIN II with progressive atypia in all
layers of the epithelium; CIN III (carcinoma in situ) with diffuse atypia and loss of maturation.

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Figure 22-22 The spectrum of invasive cervical cancer. A, Carcinoma of the cervix, well advanced. B, Early stromal invasion occurring in a cervical intraepithelial
neoplasm.

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 dysplasia
• denotes a loss of architectural organization
and a loss of cell uniformity in epithelium
• pleomorphism and mitoses are more
prominent than in the normal
• usually graded: mild, moderate, severe, and
carcinoma-in-situ
• mild to moderate dysplasia is potentially
reversible
Figure 22-6 Inflammatory vulvar disorders. Lichen sclerosus (upper panel). Lichen simplex chronicus (lower panel). The main features of the lesions are indicated in the
figures.

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Figure 22-19 Spectrum of cervical intraepithelial neoplasia: normal squamous epithelium for comparison; CIN I with koilocytotic atypia; CIN II with progressive atypia in all
layers of the epithelium; CIN III (carcinoma in situ) with diffuse atypia and loss of maturation.

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Figure 22-19 Spectrum of cervical intraepithelial neoplasia: normal squamous epithelium for comparison; CIN I with koilocytotic atypia; CIN II with progressive atypia in all
layers of the epithelium; CIN III (carcinoma in situ) with diffuse atypia and loss of maturation.

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Figure 22-19 Spectrum of cervical intraepithelial neoplasia: normal squamous epithelium for comparison; CIN I with koilocytotic atypia; CIN II with progressive atypia in all
layers of the epithelium; CIN III (carcinoma in situ) with diffuse atypia and loss of maturation.

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Figure 22-8 A, Numerous condylomas of the vulva encircling the introitus. (Courtesy of Dr. Alex Ferenczy, McGill University, Montreal, Quebec.) B, Histopathology of
condyloma acuminatum showing acanthosis, hyperkeratosis, and cytoplasmic vacuolation (koilocytosis, center).

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Figure 22-22 The spectrum of invasive cervical cancer. A, Carcinoma of the cervix, well advanced. B, Early stromal invasion occurring in a cervical intraepithelial
neoplasm.

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 NEOPLASM

dr. Imam Sarwono, SpPA

Departement of Anatomic Patology

Faculty of Medicine, Brawijaya University
Malang
 VIII. Carcinogenesis

• Neoplastic transformation is a progressive process

involving multiple “hits” or genetic changes.
• Alterations in DNA cause changes in one or both
of the following types of genes:
• Proto-oncogenes
• Tumor suppressor genes
 Carcinogenic Agents
• Chemical Carcinogens
• Physical Agents
• Ionizing Radiation
• Oncogenic Viruses
Impact of Environmental Carcinogens

• 80 - 90% of all cancers may be related to

environmental agents including diets, lifestyles,
and viruses.
• Several environmental agents often act together
(co-carcinogenesis).
 Mechanisms in Chemical
Carcinogenesis

• Multi-Step Process Involving:

• Initiation
• Promotion
 Initiation

• Results from interaction of chemical with DNA to activate

a proto-oncogene or inactivate a tumor suppressor gene
by formation of covalent adducts.
• Chemicals that can form adducts are usually electrophiles.
• Many chemical carcinogens require activation by
metabolic pathways (pro-carcinogens or indirect acting
carcinogens)
• Initiation alone does not result in tumors.
• Some initiators can subsequently act as promotors (these
are “complete carcinogens”).
 Promotion

• Promotors are usually irritants or substances that

produce cell activation and proliferation.
• Effects of promotors are reversible.
• Promotors cannot induce neoplasia: i) alone, ii) if
applied before initiator, iii) if applied in too small
an amount for effect, or iv) if too much time
elapses between applications.
 The Initiated Cell

• Initiated cells are susceptible to promotors

which induce proliferation, thus
immortalizing the defect in a clone of
proliferating neoplastic cells.
 Ultraviolet Light

• Strong epidemiologic relationship to

squamous cell, basal cell, and melano-
carcinoma in fair skinned people.
 Asbestos

• Asbestos fiber diameter is important

• Thick fibers lodge in upper respiratory tract
• Thin fibers lodge in terminal alveoli
• Malignant mesothelioma of the pleural and
peritoneal cavities is the characteristic tumor
associated with asbestos.
• Association between cancer of the lung and
asbestos exposure in smokers.
 Foreign Body Carcinogenesis

• Humans are highly resistant to foreign body

carcinogenesis.
• Tumors associated with parasitic infections:
• Squamous carcinoma of the bladder in persons
harboring Schistosoma Haematobium
• Cancer of the bile ducts following infection by the liver
fluke Clonorchis sinensis
 Ionizing Radiation
• Ionizing radiation includes: X-rays, gamma rays,
as well as particulate radiation; alpha, beta,
positrons, protons, neutrons and primary
cosmic radiation. All forms are carcinogenic
with special sensitivity in:
• Bone Marrow: Acute leukemia occurs before other
radiation-induced neoplasia (Seven year mean latent
period in atomic bomb survivors).
• Thyroid: Carcinoma occurs in 9 % of those exposed
during infancy or childhood.
• Lung: Increased frequency of lung cancer in miners
exposed to Radon gas (an alpha particle emitter).
 Tumor Cell Invasion
• Detachment from other tumor cells.
• Adhesion to the extracellular matrix.
• Proteolytic degradation of the
extracellular matrix.
• Motility and migration into the
extracellular matrix.
 Structural Proteins of Extracellular
Matrix

• Basement membrane
• Type IV collagen
• Laminin
• Proteoglycans
• Interstitial Stromal Matrix
• Type I collagen
• Type II collagen
• Fibronectin
• Proteoglycans
 Enzymes that Mediate Tumor Cell
Degradation of Extracellular Matrix

• Matrix metalloproteinases (MMP)

• Type IV collagenases
• Interstitial collagenases
• Stromelysins
• Plaminogen Activator/Plasmin
• Cathepsins B and L
• Glycosidases