PATHOLOGY

TOPIC :NEOPLESIA: 1
PRESENTED
BY

DR MAIBOUGE SALISSOU (PhD)

2024
TOPIC OUTLINE

Introduction
Classification of tumors.
Carcinogenic agents
Epidemiology
 INTRODUCTION

 Cancer is not one disease but many disorders that share a profound growth dysregulation.

 Controlling cancer lies in learning more about its pathogenesis, is a genetic disorder caused by

DNA mutations.

 This alter function of key genes that regulate fundamental cellular processes, such as growth,

survival, and senescence.

 Genetic alteration in cancer cells are heritable, being passed to daughter cells upon cell division
 INTRODUCTION

 Cancer is caused by failure of genetic mechanisms that control

growth ,proliferation of cells.

 Cumulative damage to multiple genes via physical and chemical agents,

replication errors, genetic background contribute to oncogenesis.

 In cancer, a single transformed cell grows to become a primary tumor,

accumulates more mutations and becomes more aggressive, then metastasizes to

another tissue .
 HOW DOES CANCER BEGIN?

 Cancer begins with malignant transformation of a normal cell involving an irreversible

alteration of its DNA.
 Cancer-inducing genetic alterations involve normal genes involved in cell replication and
death.
 Four types of genes are typically affected:
 Genes encoding growth factors, growth factor receptors, and signaling proteins involved in
various steps of cell division
 Genes regulating apoptosis
 Genes belonging to the family of tumor suppressor genes
 Genes encoding DNA repair enzymes
 COMMON PROPERTIES OF CANCER CELLS

 Cancer cells typically exhibit the alterations listed in Fig. 1.

 The most aggressive cancer cells display all of these
features.
 Alterations are caused by mutations that affect growth
factor receptors and signal transduction genes, cell cycle
regulatory genes, DNA repair genes, or genes controlling
apoptosis.
 Depending on whether the affected gene normally
stimulates or inhibits proliferation, the mutated gene is
called an oncogene or a tumor-suppressor
 Tumor and Tumor Cell Morphology
 In early stages diagnosis of cancer involves a histological examination of the affected tissue (Fig.2).
 Microscopically, cancer cells show abnormal location and morphology, loss of structural features characteristic
of a differentiated cell, and an abnormally large nucleus and prominent nucleoli.
 The cytoskeleton typically also is abnormal. Karyotyping may show gross chromosomal abnormalities.
 metastatic lung tumor of the liver Fig..2
 CANCER STEM CELLS

 Cancers are thought to typically originate in dividing cells, such as precursor (progenitor)

stem cells that give rise to differentiated tissues in the adult.

 These cells already possess one of the key properties needed for malignancy--the ability to

continue to divide indefinitely.

 Tumors contain dangerous cancer stem cells that divide to produce a copy of themselves, and

another cell of more limited replicative potential.

 Many cancer therapies that shrink tumors kill the more differentiated cells, leaving the cancer

stem cells alive and capable of seeding additional tumors

 NOMENCLATURE

 Neoplasia “new growth.” Neoplastic cells continue to replicate, oblivious to the regulatory

influences that control normal cells

 Neoplasms has autonomy and increase in size regardless of their local environment.

 Neoplasms depend on the host for their nutrition and blood supply

 Division of neoplasms into benign and malignant categories is based on a judgment of a

tumor’s potential clinical behavior.

 Benign :microscopic, gross characteristics are considered relatively innocent :remain

localized

 Malignant: invade and destroy adjacent structures and metastasize to cause death : cancers
 BASIC COMPONENTS OF TUMORS

 All tumors, benign and malignant, have two basic components:

 (1) parenchyma, made up of transformed or neoplastic cells

 (2) Supporting, host-derived, non-neoplastic stroma, made up of connective tissue, blood

vessels, and host-derived inflammatory cells.

 Parenchyma of neoplasm determines its biologic behavior, from it tumor derives its name.

 Stroma is crucial to growth of neoplasm, it carries blood supply , provides support for the

growth of parenchymal cells.

 HISTOGENESIS OF TUMOR

 Tumours are classified according to the cell type that they resemble, i.e. their differentiation.

 This property is determined by the tumour’s appearance on light microscopy, i.e. its phenotype.

 ‘Histogenesis’: tissue of origin is used because most tumours resemble to some extent the tissue from which

they arise

 Some malignant tumours do not show any definite form of differentiation and are described as undifferentiated

or anaplastic.
 HISTOGENESIS OF TUMOR

 (B) The cells of benign tumours closely resemble those of the normal tissue in which they arise (D)
 The nuclei are usually enlarged and the nucleoli active, indicating that the cell is active.
 The nuclei are often darkly staining –hyperchromatic – and variable in size and shape – pleomorphic – as the DNA content of the nucleus is frequently
increased.
 Mitoses are often numerous and they are frequently abnormal in form, indicating that the process of cell division may be abnormal.
 A tripolar mitosis
 BENIGN TUMORS

 Benign tumors are designated by attaching suffix -oma to cell type from which the tumor

arises. Eg: fibrous tissue is a fibroma; cartilage : chondroma.

 Adenoma applied not only to benign epithelial neoplasms that produce glandlike structures,

but also to epithelial neoplasms derived from glands but lack a glandular growth pattern.

 Epithelial neoplasm arising from renal tubule cell and growing in glandlike pattern: adenoma

 Papillomas :benign epithelial neoplasms, growing on any surface, that produce microscopic

or macroscopic fingerlike fronds

 Cystadenomas are hollow cystic masses that typically arise in the ovary
 MALIGNANT TUMORS

 Nomenclature of malignant tumors follows that of benign tumors, with additions , exceptions.

 Malignant neoplasms arising in “solid” mesenchymal tissues or its derivatives are called

sarcomas, those arising from mesenchymal cells of the blood are leukemias or lymphomas.

 Sarcomas are designated based on their cell-type composition, which presumably reflects their

cell of origin. Eg if comprised of fat-like cells is a liposarcoma

 Malignant neoplasms of epithelial cells are called carcinomas regardless of the tissue of origin.

 Carcinomas are subdivided further. Carcinomas that grow in a glandular pattern are called

adenocarcinomas Those that produce squamous cells are called squamous cell carcinomas
 MALIGNANT TUMOR

 In unusual instances tumor cells undergo divergent differentiation, creating “mixed tumors”.

 These tumors have obvious epithelial components dispersed throughout a fibromyxoid stroma,

sometimes harboring islands of cartilage or bone: pleomorphic adenoma.

 Fibroadenoma of female breast is another common mixed tumor: mixture of proliferating

ductal (adenoma) embedded in loose fibrous tissue (fibroma).

 Teratoma is mixed tumor contains recognizable mature or immature cells derived from more

than one germ cell layer, or all 3. Teratomas originate from totipotential germ cells
.
CHARACTERISTIC OF BENIGN AND MALIGNANT TUMOR
Nomanclature Epithelial tumor
 BENIGN EPITHELIAL TUMOURS/ PAPILLOMAS

 Arise from both covering epithelium, e.g. of squamous type, forming papillomas, and from
glandular epithelium, e.g. of colon or thyroid, forming adenomas.
 Papillomas : proliferating epithelium is thrown upwards into folds, and does not invade the
underlying connective tissue.
 Between these folds of epithelium are cores of fibrous tissue and blood vessels, which bring
nutrition to the epithelium.
 Epithelium is well differentiated and closely resembles the normal epithelium from which it
arises eg squamous papillomas of skin
 Papillomas may arise within duct structures, e.g. intraduct papillomas of the breast often
cause a blood-stained nipple discharge.
 ADENOMAS

 Adenomas are benign tumours of glandular epithelium such a tumour form

glandular structures mimicking the arrangement of the normal tissue
 Cells are well differentiated and often continue to secrete the normal
product of the gland; thus the cells thyroid adenoma thyroxine.
 If glands become distended by secretion they may form cysts resulting in
a multiloculated lesion described as a cystadenoma,(in ovary or pancreas).
 In the ovary, there is proliferation of epithelium within the cyst, often in the
form of papillary structures and the term ‘papillary cystadenoma’ is used.
 Adenomas of viscera eg colon tend to grow into lumen, often adopt a
papillary architecture.
 Colonic adenomas show a degree of cytological atypia , high
 ADENOMA OF COLON

Fig. Adenoma of colon: several gland-like Fig. Tubular adenoma of the colon: this is a
structures are present, mimicking structure of small pedunculated polyp on a slender stalk.
normal colonic mucosa.
Malignant Epithelial Tumours
(Carcinomas)
 SQUAMOUS CARCINOMAS

 Carcinomas are the most common type of malignant tumour in humans.

 They are several subtypes, depending on form of differentiation they show.
 Squamous cell carcinoma showing squamous differentiation in the form
of keratin production
 Squamous carcinomas can arise from pre-existing squamous epithelium,
e.g. of skin or larynx,
 Squamous carcinomas resemble normal squamous epithelium to a varying
extent.
 Well-differentiated tumours show maturation from proliferating basal cells,
to heavily keratinized cells.
 SQUAMOUS CELL CARCINOMA

Fig. Squamous cell carcinoma. This is an example of a well differentiated

tumour with irregular islands of squamous epithelium, one of which shows
central keratinization.
 ADENOCARCINOMA

 These tumours showing glandular differentiation. They arise from glandular

epithelium, e.g. within the colon, and from metaplastic glandular tissue.
 Adenocarcinomas may be well differentiated forming well-defined
glandular structures:acini
 In some tumours, typically of the stomach, individual cells contain
intracytoplasmic globules of mucin; these push the nucleus to one side and
the tumour cells are known as signet-ring cells .
 In other mucin-producing tumours there is extensive extracellular
accumulation of mucin; this forms large lakes in which scattered epithelial
cells are seen.
 These are known as mucoid carcinomas and are seen in the stomach, colon,
 ADENOCARCINOMA

Fig. Adenocarcinoma: the tumour cells form an acinar Fig. Signet-ring cell carcinoma of stomach: the tumour cells have
structure. eccentric nuclei, pushed to the side by a central globule of mucus.
The nuclei contain prominent nucleoli
 TRANSITIONAL CELL CARCINOMA AND SMALL CELL CARCINOMA

 Transitional cell carcinoma arises from the transitional epithelium of the

urogenital tract.
Small cell carcinoma is a tumour that shows neuroendocrine differentiation
in the form of neurosecretory granules which may be found on electron
microscopy or immunostaining for vesicle membrane proteins such as
synaptophysin.
 Typically, it arises in the bronchus, where it is the most aggressive form of
lung cancer, but occasionally in other sites such as the cervix and
oesophagus.
Other forms of carcinoma include hepatocellular carcinoma, the malignant
CONNECTIVE TISSUE TUMOR
 CONNECTIVE TISSUE TUMOURS

 Benign Connective Tissue Tumours the name consists of a prefix

indicating the type of differentiation, e.g. lipo- (fat), chondro- (cartilage),
haemangio- (blood vessel), with the suffix -oma denoting a benign tumour.
 Are slowly growing encapsulated tumours composed of the appropriate
differentiated tissue.
 The most common form is a leiomyoma, a benign tumour showing smooth
muscle differentiation(in uterine muscle)
 Lipomas usually occurring in the subcutaneous tissues of adults, typically
on the back and shoulders.
 They consist of an encapsulated mass of mature fat.
 MALIGNANT CONNECTIVE TISSUE TUMOURS

 Known as sarcomas occur within the deep soft tissue of the limbs and trunk,
although some arise within viscera.
 The nomenclature indicates the form of differentiation shown: e.g. a
leiomyosarcoma is a malignant tumour showing smooth muscle
differentiation
 Rhabdomyosarcomas show skeletal muscle differentiation
 The diagnosis is made on the basis that proteins found in skeletal muscle
(e.g. desmin, myoglobin) or involved in skeletal muscle differentiation (e.g.
MyoD1) can be demonstrated by immunochemistry.
 Sarcomas tend to occur in soft tissue, e.g. liposarcoma, leiomyosarcoma.
 LEIOMYOSARCOMA

Fig. Leiomyosarcoma: this tumour consists of elongated cells with cigar-shaped, but
pleomorphic and hyperchromatic, nuclei and eosinophilic cytoplasm. There are several
mitoses in this field
Tumours of Haematopoietic and Lymphoid
Tissues
 LEUKAEMIAS

 Are malignant tumours of haematopoietic cells, derived from stem cells

within bone marrow.
 From the marrow, the malignant cells, similar to their normal white cell
counterparts, tend to migrate into the peripheral blood so that there is
usually an elevated white cell count
 Leukaemia is a diffuse form of tumour, and usual concepts of tumour
spread do not apply.
 Leukaemias fall into two broad categories: tumours of lymphoid and
myeloid cells; within each group the cells may be primitive or fairly mature
 The four main types :
 acute lymphoblastic leukaemia,
 LYMPHOMAS

 Are malignant solid tumours of lymphocytic origin, most of which arise in

the lymph nodes, spleen, thymus, or bone marrow.
 A smaller proportion, around 30%, arise in other organs such as the
gastrointestinal tract, thyroid, and brain
 Usually within lymphoid tissue it resulting from chronic inflammatory
conditions, such as helicobacter gastritis and Hashimoto’s thyroiditis.
 They are divided into 2 groups: Hodgkin lymphoma and non-Hodgkin
lymphoma, on the basis of the distinctive large cells known as Reed–
Sternberg cells present in Hodgkin lymphoma.
 Non-Hodgkin lymphoma falls into two main groups: those derived from B
 HODGKIN LYMPHOMA

Fig. Hodgkin lymphoma: a typical Reed–Sternberg cell is present in the middle of the
field. It is binucleate with an ‘owl’s eye’ appearance due to the large eosinophilic
nucleoli.
GERM CELLS TUMOR
 GERM CELL TUMOURS

 Tumours may arise from the germ cells, usually found within the testis or
ovary; may arise from nests of germ cells, which have been left behind
during embryonic migration of germ cells .
 Found in pineal, base of skull, mediastinum, and retroperitoneum to the
sacrococcygeal region.
 Normal germ cells are totipotent the tumours may contain differentiated
tissue from any of the three layers of the embryo are called teratomas.
 These are most common in the ovary and benign
 Some germ cell tumours consist of undifferentiated cells that resemble
primitive germ cells.
BENIGN CYSTIC TERATOMA OF OVARY

Benign cystic teratoma of ovary: this cyst is lined by squamous

epithelium and is filled with sebaceous material and hair.
 SECTION C
CARCINOGENESIS
 WHAT ARE CARCINOGENS?

 The clues to our understanding of the causes of cancer come

from several sources, but it is clear that environment, genetic
predisposition, and interindividual variability in coping with
toxic injuries are all important
 Carcinogens are cancer-inducing factors that can be classified
as:
 Physical forces—UV light, x-rays, and gamma radiation
 Chemicals
 Viruses
CHEMICAL CARCINOGENESIS: INITIATION, PROMOTION, AND PROGRESSION OF TUMORS.

 Initiation: This is the first step that will induce the irreversible
but not lethal change in the genetic material of the affected cell.
 Promotion: This is the second step required for the formation
of tumor.
 It promotes the replication of the initiated cells.
 Promoters cannot induce cancer on their own.
 Some carcinogens may act as initiators and promoters.
 Progression: This is the third phase of tumor formation in
which the growth of tumor becomes autonomous.
 WHAT IS THE DIFFERENCE BETWEEN DIRECT-ACTING AND INDIRECT CARCINOGENS?

 Direct-acting carcinogens (e.g., nitrogen mustard and some metals such

as nickel): capable of binding to the DNA and directly causing genetic
damage.
 Indirect carcinogens: must be metabolized into an active form (proximal
carcinogen) that can bind to the DNA. Typical examples are:
 Polycyclic hydrocarbons from cigarette smoke are metabolized by
cytochrome P450 into DNA-binding epoxides in the bronchial epithelium.
 Aromatic amines ingested in food are metabolized in the liver, and the
proximal carcinogens are excreted in urine.
 These carcinogens act on the transitional epithelium of the urinary
bladder
 ENVIRONMENTAL CARCINOGENS AND NEOPLASMS THEY MAY CAUSE.

 Polycyclic aromatic hydrocarbons: found in tobacco smoke and tar; may

cause lung cancer and skin cancer
 Aromatic azo dyes: urinary bladder cancer in workers in aniline dye
industry
 Benzene: leukemia in chemical-industry workers
 Aflatoxin B-1: toxin produced by Aspergillus flavus that grows on moldy
grains and peanuts; suspected as cause of liver cancer in underdeveloped
countries
 Nickel: cancer of nasal cavity and lungs in mine workers
 Arsenic: skin cancer in vineyard workers
 WHAT ARE ONCOGENES?

 Oncogenes are cancer-inducing genes derived from normal cellular genes called
protooncogenes.
 Human oncogenes, named cellular oncogenes (c-oncogenes), are homologous to
viral oncogenes (v-oncogenes), known for some time to cause cancer in animals.
 All these genes are involved in cell proliferation and differentiation and are classified
on the basis of their function into four groups.
 WHAT ARE TUMOR SUPPRESSOR GENES?

 Tumor suppressor genes are regulatory genes that act

as autosomal dominant genes, preventing the abnormal
division of cells.
 Loss of heterozygosity due to deletion or mutation of a
tumor suppressor gene allows the cell to proliferate and
is important for the initiation of malignant tumors.
EPIDEMIOLOGY
MOST COMMON FORMS OF CANCER IN MEN AND WOMEN

The most common tumors in men and women are skin

neoplasms. The three most common malignant tumors of
internal organs are as follows:
Men Women
Prostate (31%) Breast (31%)
Lung (14%) Lung (13%)
Large intestine (10%) Large intestine
(11%)
INCIDENCE AND MORTALITY OF CANCER WORLDWIDE
MOST COMMON CAUSES OF CANCER-RELATED DEATH

Men Women
Lung cancer (31%) Lung cancer
(25%)
Prostate cancer (11%) Breast cancer
(15%)
Large intestine cancer (10%) Large intestine
cancer (11%)
GEOGRAPHIC VARIATION OF COMMON CANCER
IMPORTANT DISEASES THAT ARE ASSOCIATED WITH AN INCREASED INCIDENCE OF
CANCER.

DISEASE TYPE OF
CANCER
Solar keratosis of the skin Squamous
carcinoma
Cirrhosis Hepatocellular
carcinoma
Ulcerative colitis Colic
adenocarcinoma
Reflux esophagitis/Barrett esophagus Esophageal
adenocarcinoma
IMPORTANT INFECTIOUS DISEASES ASSOCIATED WITH AN INCREASED INCIDENCE OF SOME
CANCERS.
END