Pathophysiology -

Neoplasia

Meng-Chih Lin, MD
Department of Respiratory
Care,
Chang Gung Institute of
Technology, Chiayi
18/010/2007 1
 Introduction
• Neoplasia is a potentially grave
growth abnormality whose more
serious form is known as cancer.

• Neoplasia is the 2nd ranking cause of

death in North America.

• 1st ranking cause of death in Taiwan

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Tissue Growth Disorders
• Tumor = neoplastic mass or
neoplasm

• Hyperplasia

• Metaplasia: the conversion of one

cell type to another.

• Dysplasia: architecture is
disordered and cells are 3
Metaplasia and Dysplasia
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Dysplasia Neoplasia

Dysplasia and Neoplasia: varying pleomorphism 5

Growth of a Neoplasm
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Tissue growth pattern

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 Tumor growth
• The tumor’s ability to avoid growth
inhibition factors means that it has
escaped the control that limit growth
to the degree necessary for normal
function.

• Tumor’s growth is autonomous ( 自

發性 ).
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 Tumor Terminology
• Oncology: the study of tumors

• Benign: growth is relatively slow and

localized

• Malignant: fast and will invade

aggressively to adjacent normal
tissues.
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• Carcinoma: mailgnant tumors
arising in tissues derived from these
primitive layers –skin, alimentary and
the respiratory passages.
– Adenocarcinoma vs Adenoma

• Sarcoma ( 肉瘤 ): malignancies
developing in tissues that derive
from mesoderm (third embryonic
layer).
– Leiomyosarcoma vs leiomyoma 10
 Cell Growth Regulation

a) Extracellular matrix components

bound by surface receptors and
plasma-borne and cellular growth
factors provide appropriate growth
control.

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 12
Damaged receptors reduced normal interaction
Table 6.1 Tumor Terminology and Classification
Tissue of Origin Benign Malignant
Ectoderm/Endoderm
Epithelium Epithelioma (papilloma if projecting from Carcinoma
surface)
Gland Adenoma (if cysts present; cystadenoma) Adenocarcinoma
Melanocytes Malignant melanoma
Neuroglia Glioma Glioma
Embryonic nervous tissue* Neuroblastoma
Embryonic retinal cells* Retinoblastoma
Mesoderm
Adipose tissue Lipoma Liposarcoma
Cartilage Chondroma Chondrosarcoma
Bone Osteoma Osteosarcoma
Fibrous tissue Fibroma Fibrosarcoma
Lymphoid tissue Lymphosarcoma
Smooth muscle Leiomyoma Leiomyosarcoma
Embryonic skeletal muscle* Myoblastoma
Multiple tissues (usually gonadal)* Teratoma
Leukocyte-Producing Tissues Myeloid leukemia
Red bone marrow Lymphocytic leukemia
Lymphoid tissue
*Less well-differentiated cells not normally present in adults 13
 Tumor Structure
• Malignant cells typically lose some of
the specialized functional capabilities
characteristic of their tissue of origin.

• The pattern of change that reflects

an earlier cell form is called
anaplasia.

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Tumor Pleomorphism: gastric carcinoma 15
 Fibrosous Stroma
• Another major component of a tumor
is the fibrous stoma (connective
tissue framework) that supports the
tumor cells.

• At the other extreme is a scirrhous

(ski’rus) tumor: the stromal
response is exaggerated and a
densely collagenous tumor results.
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Scirrhous tumor. A) the dominat feature is fibrous tissue
B) Which tightly linds the neoplastic cells. 17
 Vascular Stroma
• Blood vessels.
• Angiogenesis ( 血管新生 ): the
process of new vessel formation.
Regulated by a group of tissue
growth and inhibition factors.

• VEGF (vascular endothelial growth

factor)
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Angiogensis

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 Tumor Products
• Hormones and Mucus

• Tumor diagnosis may be aided by a

tumor’s overproduction of enzymes.
Biomarkers

• Squamous cell carcinoma  keratin

• Adenocarcinoma  CEA
(Carcinogenic Embryonic Antigen) 20
Table 6.2 Characteristics of Benign and Malignant
Tumors
Characteristic Benign Malignant

Cell structure Near normal Abnormal shapes, larger cell

and nucleus
Tissue structure Orderly Disordered, irregular

Growth rate Above normal Rapid

Invasive growth Uncommon Typical

Metastasis Never Typical

Capsule Typical Rare, incomplete if present

Anaplasia Minimal Typical

Prognosis Good Poor

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Typical Tumor Structure.
b) Benign tumor
c) Malignant tumor: abnormal cytology and irregular,
invasive growth
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Characteristics of Benign and Malignant tumors

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 Tumor Growth Rate
• Generation time – the time
between successive cell divisions.
Included mitosis and rest

• Doubling time – the time required

to double the number of tumor cells
or the size of the tumor

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Tumor growth
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Tumor growth

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Tumor Invasion

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Tumor invasion; tumor in isolation produces randomly directed
cords of cells. 28
An adjacent sheet of normal cells draws the tumor to it
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 ECM: extracelluar matrix
BM: basement membrane

The mechanisms of tumor invasion

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 Tumor Metastasis
• Metastasis via embolism
– Blood vessel metastasis
– Lymphatic vessel metastasis
• Metastasis via body cavities
– Adenocarcinoma of the pancreas to the
inferior extremes of the pelvic cavity.
• Metastasis via natural passage
– GI tracts, urethers, and bile ducts
• Iatrogenic metastasis
– Chest tube and biopsy tract
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Metastasis by Embolism

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 Breast cancer and lympha-
tic metastasis

Metastasis via Embolism

Colon cancer and portal system

metastasis
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The process of tumor metastasis:
requirements for successful metastasis
of a tumor cell embolus.

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 Table 6.3 Typical Sites of Metastasis for Selected
Primary Tumors
Primary Tumor Typical Sites of Metastasis

Carcinoma and breast Bone (especially vertebral column), brain, liver,

adenocarcinoma adrenals, regional lymph nodes

√ Bronchogenic carcinoma Brain, spinal cord, bone, regional lymph nodes,

liver
Osteosarcoma Lung, brain

Renal carcinoma Lung, liver, bone, brain

Prostatic carcinoma Bone (especially vertebral column)

Colon carcinoma Liver, brain, ovary, lung, regional lymph nodes

Neuroblastoma Bone, regional lymph nodes

Malignant melanoma Lung, liver, spleen, regional lymph nodes

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 Tumor Effects
• Tissue destruction
• Organ compression
• Obstruction
• Infection
• Anemia
• Pain

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Tumors and the blood 39
 Tumor Effects- II
• Hormonal effects

• Paraneoplastic syndromes
– Leg vein thrombosis in pancreatic or
lung tumor
√
• Cachexia
– Tumor necrosis factor-alfa (TNF- α)
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 41
normal
 Tumor joining adjacent organs

An invading lung tumor has penetrated to the heart, joining the two organs and
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restricting their normal freedom of movement
Flow Obstruction
veins are more vulnerable than arteries
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Tumor effects
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 Oncogensis
• Tumor formation = oncogensis

• The rare primary tumor thought to

derive from skeletal muscle or
neurons probably originate in
embryonic cells that haven’t fully
differentiated.

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 Genes and Cancer
• Cells division is regulated by
exogenous growth factors (GFs)
that may stimulate or inhibit mitosis.
• Protooncogenes: the genes that
regulate these processes. Defective
oncogenes

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 Mechanisms of
Oncogenesis
• Initiation: the process in which
oncogenes give rise to an
accumulation of excessive tissue.

• Promoters: act on initiated cells

that are particularly sensitive to their
action.

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Oncogensis and growth factors: oncogenes can cause excessive
tissue formation by failure to produce inhibitory GFs or overproduction
GFs that stimulate mitosis

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Apoptosis in oncogensis: inadequate stimulation of apotosis or excessive
Inhibition of apoptosis means more survival of cells susceptible to
transformation

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Chemical oncogenesis

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 Heredity 遺傳性
• Little is known of the role of heredity
in oncognesis because of the great
difficulties associated with human
genetic studies.

• Only a small number of tumors can

be ascribed to directly transmitted
genetic defects. –retinoblastoma
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Etiological factors in oncogenesis
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Initiation and promotion in
oncognesis

E* - the role of adaptive

enzyme responses in coping
with initiator’s effect

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 Environmental Factors
• Physical agents
– Increased exposure to radiation
increased rates of carcinogenesis
• Ultraviolet radiation of the sun
• Ionzing radiation from industrial or medical
sources.
• Viruses
– The only biological agents implicated in
the carcinogenesis
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Table 6.4 Viruses Associated with Human Tumors

Virus Associated Tumor

Hepatitis B (HBV) and Hepatocellular

hepatitis C virus (HCV)

Human papilloma virus Skin and cervical carcinomas

(HPV)
Epstein-Barr virus

Human T-cell leukemia Burkitt’s lymphoma* and nasopharyngeal carcinoma

virus
Cytomegalovirus Some leukemias

* AIDS-related tumors Kaposi’s sarcoma*

The role of these viruses in tumor etiology, if any, and their links to tumor
pathogenesis are not well understood.
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Environmental Factors-II
• Environmental chemicals:
chemical carcinogens alter DNA,
typically by binding to it.
• Polycyclic hydrocarbons:
benzopyrene – a common constituent
of cigarette smoke
• Aromatic amines
– Methylaminobenzene, metabolized in
the liver to produce a carcinogenic
agent hepatic tumors 56
Environmental Factors-III
• Nitrosamines

• Aflatoxin-
– Aspergillus

• Inorganic carcinogens

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 Tumor
Immunology
Factors that limit the ability of the immune
system to suppress tumor growth

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Antitumor Therapy
• Surgery
• Radiotherapy
• Chemotherapy
• Immunotherapy
• Combination therapy

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Table 6.5 Selected Tumors Grouped According to Their Relative
Radiosensitivity
Radiosensitive
Neuroblastoma
Chronic leukemia
Lymphomas
Wilm’s tumor (renal tumor of childhood)
Moderately Radiosensitive
Squamous cell carcinoma

Genital carcinomas
Esophageal carcinoma
Bronchogenic carcinoma
Nonradiosensitive
Fibrosarcoma
Osteogenic carcinoma
Various adenocarcinomas
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Table 6.6 Tumor Susceptibility to Chemotherapeutic
Agents
Highly Susceptible
Retinoblastoma
Hodgkin’s disease
Wilm’s tumor (renal tumor of childhood)
Testicular tumors
Acute lymphoblastic leukemia
Choriocarcinoma

Moderately Susceptible
Small cell carcinoma of lung
Lymphocytic lymphoma
Leukemia: acute and chronic myeloid
Carcinoma of breast and ovary

Resistant
Malignant melanoma
Carcinomas generally
Lung cancer ???
Soft tissue sarcomas
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 Chemotherapeutic agents

Chemotherapy outcomes

Sensitive mormal Insensitive

Tumor tissue
tissue normal tissue

Necrosis Necrosis Minimal necrosis

Significant side Tumor Limited side

effects suppression effects
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Immune therapy 63
TNM staging system-
b) T1N0M0 T:tumor
b) T2N1M0 N: lymph node
c) T3N2M1 M: metastasis
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Table 6.7 The Relationship between Tumor Grade and Prognosis
in Selected Tumors
Tumor Site Grade % Survival 5 Yrs after
Diagnosis
Thyroid gland I 85

II 55

III 11

Salivary gland I 85

II 80

III 38

IV 18

Testis I 85

II 55

IV 7
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Lung Cancer

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PET-CT scan for lung cancer
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Oncol
ogy !

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