Download 08-Cancer 1-Self-study-Pathophysio

Cancer
1
KEY POINTS
2
3
INTRODUCTION
 Cancer is a group of more than 100 different diseases that are
characterized by uncontrolled cellular growth, local tissue
invasion, and distant metastases. It is now the leading cause of
mortality in Americans younger than age 85 years.
4
5
6
Cancer Statistics, 2005
NOMENCLATURE
 Neoplasia means “new growth,” and a new growth is called a
neoplasm.Tumor originally applied to the swelling caused by
inflammation, but the non-neoplastic usage of tumor has
almost vanished; thus, the term is now equated with
neoplasm.
7
• “A neoplasm is 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 cessation of the stimuli which evoked the
change.”
• A tumor is said to be benign when its microscopic and gross
characteristics are considered relatively innocent, implying that it will
remain localized, it cannot spread to other sites, and it is generally
amenable to local surgical removal; the patient generally survives.
• Malignant tumors are collectively referred to as cancers.
• Malignant, as applied to a neoplasm, implies that the lesion can invade and
destroy adjacent structures and spread to distant sites (metastasize) to
cause death. Not all cancers pursue so deadly a course.
8
• In general, benign tumors are designated by attaching the suffix -oma to the cell
of origin. Tumors of mesenchymal cells generally follow this rule. For example,
a benign tumor arising in fibrous tisssue is called a fibroma, whereas a benign
cartilaginous tumor is a chondroma. In contrast, the nomenclature of benign
epithelial tumors is more complex. These are variously classified, some based on
their cells of origin, others on microscopic pattern, and still others on their
macroscopic architecture.
• Adenoma is applied to a benign epithelial neoplasm derived from glands,
although they may or may not form glandular structures.
• Benign epithelial neoplasms producing microscopically or macroscopically
visible finger-like or warty projections from epithelial surfaces are referred to as
papillomas. Those that form large cystic masses, as in the ovary, are referred to as
cystadenomas. Some tumors produce papillary patterns that protrude into cystic
spaces and are called papillary cystadenomas. When a neoplasm, benign or
malignant, produces a macroscopically visible projection above a mucosal
surface and projects, for example, into the gastric or colonic lumen, it is termed
a polyp.
9
• All tumors, benign and malignant, have two basic components:
(1) clonal neoplastic cells that constitute their parenchyma and (2)
reactive stroma made up of connective tissue, blood vessels, and
variable numbers of macrophages and lymphocytes. Although the
neoplastic cells largely determine a tumor's behavior and
pathologic consequences, their growth and evolution is critically
dependent on their stroma.
• Malignant tumors arising in mesenchymal tissue are usually called
10
sarcomas (Greek sar = fleshy), because they have little connective
tissue stroma and so are fleshy (e.g., fibrosarcoma,
chondrosarcoma, leiomyosarcoma, and rhabdomyosarcoma).
Malignant neoplasms of epithelial cell origin, derived from any of
the three germ layers, are called carcinomas.
11
12
CARCINOGENESIS
13
14
15
16
GENETIC & MOLECULAR BASIS
17
18
19
20
• As information regarding the role of oncogenes and tumor suppressor
21
genes accumulated, it became evident that a single mutation is
probably insufficient to initiate cancer. Scientists postulate that
combinations of mutations are required for carcinogenesis and that
each mutation is inherited by the next generation of cells.Thus, several
detectable genetic mutations may be present in an established tumor.
Early mutations are found in both premalignant lesions and in
established tumors, whereas later mutations are found only in the
established tumor. This theory of sequential genetic mutations
resulting in cancer has been demonstrated in colon cancer. In colon
cancer, the initial genetic mutation is believed to be loss of the
adenomatous polyposis coli gene, which results in formation of a small
benign polyp. Oncogenic mutation of the ras gene is often the next
step, leading to enlargement of the polyp. Loss of function of DNA
mismatch repair enzymes may occur at many points in the progression
of malignant transformation. Loss of the p53 gene and another gene,
believed to be the "deleted in colorectal cancer" gene, complete the
transformation into a malignant lesion. Loss of p53 is thought to be a
late event in the development and progression of the malignancy.
PATHOLOGY OF CANCER: TUMOR ORIGIN
• Tumors may arise from any of four basic tissue types:
epithelial tissue, connective tissue (i.e., muscle, bone, and
cartilage), lymphoid tissue, and nerve tissue. Although some
malignant cells are atypical of their cells of origin, the
involved cells usually retain enough of their parent's traits to
identify their origin. Benign tumors are named by adding the
suffix -oma to the name of the cell type. Hence, adenomas are
benign growths of glandular origin, or growths that exhibit a
glandular pattern.
22
23
• Some cancers are preceded by cellular changes that are
abnormal, but not yet malignant. Correction of these early
changes could potentially prevent the occurrence of a cancer.
Precancerous lesions may be described as consisting of either
hyperplastic or dysplastic cells. Hyperplasia is an increase in the
number of cells in a particular tissue or organ, which results in
an increased size of the organ. It should not be confused with
hypertrophy, which is an increase in the size of the individual
cells. Hyperplasia occurs in response to a stimulus and reverses
when the stimulus is removed. Dysplasia is defined as an
abnormal change in the size, shape, or organization of cells or
tissues. Hyperplasia and dysplasia may precede the appearance of
a cancer by several months or years.
24