General Pathology for Lecture 11 Dr. Mukhallad A.

Ramadhan
College of Dentistry

Neoplasia

Neoplasia: an abnormal mass of tissue the growth of which exceeds and is

uncoordinated with that of the normal tissues and persists in the same excessive
manner after the cessation of the stimuli which evoked the change.

Fundamental to the origin of all neoplasms are heritable (genetic) changes that
allow excessive and unregulated proliferation that is independent of physiologic
growth-regulatory stimuli.

The study of the tumors is known as oncology, According to the tumor potential
and clinical presentation, tumors are divided in to:-
1- Benign
2- Malignant: also known as cancers.

Component of tumors:

Benign and Malignant, have two basic components:

A. The parenchyma: made up of neoplastic cells which is largely determines the

biologic behavior of the tumor, and from which the tumor derives its name.

B. The stroma: which is supporting, host-derived, non-neoplastic, made up of

connective tissue, blood vessels, and host-derived inflammatory cells
therefore it is crucial to tumor growth.

13 Page 1 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

Comparison between Benign and Malignant tumors

Benign tumor Malignant tumor

(1) Usually surrounded by fibrous (1) Have no capsule

capsule.

(2) Slow growing (2) Grow fast

(3) Grow locally, project over the (3) Grow by invasion

affected surface.

(4) No metastasis (4) Metastasize to distant areas from

the site of origin

(5)Well differentiated parenchymal (5) Range from well to moderate to

cells undifferentiated(anaplastic)

(6) Amenable to local surgical (6) Return after surgical removal and
removal need for chemo or radiotherapy

NOMENCLATURE

13 Page 2 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

1. Benign Tumors: Benign tumors are designated by attaching the suffix -oma to
the cell type from which the tumor arises.

2. Malignant tumors: Malignant neoplasms arising in mesenchymal tissue or its

derivatives are called sarcomas.

13 Page 3 of
 Numenclature of Benign Tumors
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry Mesenchymal tumors

Name of the tissue Name of the tumor

fibrous tissue fibroma

benign cartilaginous tumor chondroma.

Benign Epithelial Tumors

Name of the tissue Name of the Tumor

Tumors or glandular Origin Adenoma

Tumors of the superficial Papilloma

epithelium forming finger like
projections

Tumors Appear as a mass over Polyp

mucosal epithelium

Tumors of the glandular Cystadenoma

epithelium which form cystic
dilations

Numenclature of Malignan Tumors

Mesenchymal Tumors (name by adding suffix Sarcoma

Name of the tissue Name of the Tumor

Fibrous tissue Fibrosarcoma

Cartilaginous tissue Chondrosarcoma

Epithelial malignant tumors (name by adding suffix carcinoma)

Name of the tissue Name of the tumor

Glandular Tissue Adenocarcinoma

Squamous epithelial tissue Squamous cell carcinoma

13 Page 4 of

Glandular tumors with cyst Cystadenocarcinoma

General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS:

POLYP Papilloma

13 Page 5 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

There are four fundamental features by which benign and malignant tumors can be
distinguished. These are :-
1) Differentiation and anaplasia
2) Rate of growth
3) Local invasion
4) Metastasis.

Differentiation and Anaplasia

 Refer only to the parenchymal cells that constitute the transformed elements of
neoplasms.

 The differentiation of parenchymal cells refers to the extent to which they

resemble their normal forebears morphologically and functionally. Ex. In
benign tumor lipoma is made up of mature fat cells.
 Malignant neoplasms are characterized by a wide range of parenchymal cell
differentiation, from surprisingly well differentiated to completely
undifferentiated. Ex. Well-differentiated squamous cell carcinomas elaborate
keratin.
 Malignant neoplasms that are composed of undifferentiated cells are said to be
anaplastic.

 Anaplastic cells display marked pleomorphism (i.e., marked variation in size

and shape), nuclei are extremely hyperchromatic and large the nuclear-to-
cytoplasmic ratio may approach 1: 1 instead of the normal 1: 4 or 1: 6, the
chromatin is coarse and clumped, and nucleoli may be of astounding size. More
important, mitoses are often numerous and distinctly atypical; anarchic multiple
spindles may be seen and sometimes appear as tripolar or quadripolar forms.

13 Page 6 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

Squamous cell carcinoma

Anaplasia Mitotic figure

Metastasis
 This term connotes the development of secondary implants discontinuous with
the primary tumor, in remote tissues.

13 Page 7 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

 Malignant neoplasms disseminate by one of three pathways:-

1. Seeding within body cavities.
2. Lymphatic spread.
3. Hematogenous spread.

CARCINOGENESIS
THE MOLECULAR BASIS OF CANCER

13 Page 8 of
Environmental factors: chemicals,
radiation or viruses.
 Nonlethal genetic
damage (mutation)
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
lies
College of Dentistry
at the heart of
carcinogenesis;
this result from

Inheritance with the germ line.

Tumor target genes :-

 The following classes of normal regulatory genes are the principal targets of
genetic damage :-
1. Growth-promoting Proto-oncogenes and the mutant form known Oncogene.
2. Growth-inhibiting tumor suppressor genes these are tow types:

A. Promoters: directly inhibit cell growth such as RB and P53

B. Caretakers: are responsible for processes that ensure the integrity of the
genome such as DNA repair genes.

3. Genes that regulate programmed cell death

Carcinogenesis
 Is a multistep process at both the phenotypic and the genetic levels, resulting
from the accumulation of multiple mutations.
 It is best to consider cancer-related genes in the context of seven fundamental
changes in cell physiology that together dictate the malignant phenotype.
1. Self-sufficiency in growth signals
2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Limitless replicative potential (i.e., overcoming cellular senescence)
5. Development of sustained angiogenesis
6. Ability to invade and metastasize
7. Genomic instability resulting from defects in DNA repair.

13 Page 9 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

1- Self-sufficiency in growth signals

A - Growth Factors: tumor cell synthesizes growth factors for themselves.

B- Growth Factor Receptors: Some cancers result from the overexpression or

mutation of growth factor receptors.
 EX. HER2/NEU, is amplified in breast cancers

C- Signal-Transducing Proteins: Some cancers result from mutations in genes

that encode various components of the signaling pathways that couple growth
factor receptors to their nuclear targets.
 EX, mutation of RAS colonic adenocarcinoma and ABL, in leukemia.

D- Nuclear Transcription Factors: The ultimate consequence of signaling

through oncogenes like RAS or ABL is inappropriate and continuous stimulation of
nuclear transcription factors that drive growth-promoting genes.

2. Evasion of Apoptosis
 Apoptosis induced by signaling through the death receptor CD95 (Fas).
 CD 95 produced by TP53.
 tumors result from mutation in Tp53 mutation reduce the synthesis of Fas
then the cell will be less susceptible to apoptosis.
EX. hepatocellular carcinoma.

3. Limitless Replicative Potential

 Tumor cells activate the enzyme telomerase, which can maintain normal
telomere length.

4. Development of Sustained Angiogenesis

 Neovascularization has a dual effect on tumor growth:
 Perfusion supplies nutrients and oxygen.
 Newly formed endothelial cells stimulate the growth of adjacent tumor cells
by secreting growth factors.

5. Ability to Invade and Metastasize

 Invasion of extracellular matrix and migrate away from the site of origin.

ETIOLOGY OF CANCER: CARCINOGENIC AGENTS

13 Page 10 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

1. Chemical Carcinogens
 Chemical carcinogens are divided into the following types:

A. Direct reacting: require no chemical transformation (e.g., alkylating agents).

B. Indirect reacting: become active only after metabolic conversion this is
known as procarcinogens, and their active end products are called ultimate
carcinogens.

C. Promoters: these agents have little, or no , transforming activity by themselves

but it can augment the carcinogenicity of some other chemicals.

2. Radiation Carcinogenesis
 UV light cause DNA damage by forming pyrimidine dimers.

3. Microbial Agents: this includes

A. Viruses:
i. RNA oncogenic viruses. Ex. T cell leukemia virus.
ii. DNA oncogenic viruses. Ex.

1- Human papilloma Virus (HPV)

2- Epstein-Barr virus (EBV).
3- Human herpesvirus 8 (HHV-8).
4- Hepatitis B&C Virus (HBV, HCV).

iii. Oncogenic Bacteria. Ex. Helicobacter pylori.

HOST DEFENSE AGAINST TUMORS: TUMOR IMMUNITY

 The term immune surveillance is referring to recognition and destruction of
non-self-tumor cells on their appearance.

Antitumor Effector Mechanisms

13 Page 11 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

1. Cytotoxic T lymphocytes:
2. Natural killer cells:
3. Macrophages:
4. Humoral mechanisms. These may participate in tumor cell destruction by two
mechanisms:
(1) Activation of complement
(2) Induction of antibody-dependent cellular cytotoxicity by NK cells.

How Dose Tumour Escape Immunosurveillance

1. Selective outgrowth of antigen-negative variants.
2. Loss or reduced expression of histocompatibility antigens.
3. Immunosuppression. Many oncogenic agents (e.g., chemicals and ionizing
radiation) suppress host immune responses. Tumors or tumor products also may
be immunosuppressive.

CLINICAL FEATURES OF NEOPLASIA

1. CANCER CACHEXIA: Many cancer patients suffer from progressive loss of
body fat and lean body mass, profound weakness, anorexia, and anemia. This
wasting syndrome is referred to as cachexia.

2. PARANEOPLASTIC SYNDROMES
 This includes:
1. Cushing syndrome.
2. Hypercalcemia.
3. Nonbacterial thrombotic endocarditis.

 Cushing syndrome is usually related to ectopic production by the cancer of

ACTH or ACTH-like polypeptides.
 Hypercalcemia: result from synthesis of a parathyroid hormone-related
protein (PTHrP) by tumor cells.

Grading and Staging of Cancer

1. The grading of a cancer attempts to establish estimation to the cytologic
differentiation of tumor cells and the number of mitoses within the tumor.

13 Page 12 of
General Pathology for Lecture 11 Dr. Mukhallad A. Ramadhan
College of Dentistry

 Cancer may be classified as grade I, II, III, or IV, in order of increasing

anaplasia.

2. Staging of cancers is based on

A. The size of the primary lesion.
B. Its extent of spread to regional lymph nodes.
C. The presence or absence of metastases.
 This assessment is usually based on clinical and radiographic examination.

The End

13 Page 13 of