DONE BY

Seba Saqer
Roaa Saqer
Rozana Mousa
Ahmed Al-Hourani

SUPMETTED FOR
Dr. Hani Al-Anqar

Pathology
Neoplasia

April 2020
Neoplasia:
Neoplasia literally means new growth, which is an abnormal mass of tissue, that 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.
It is referred to as a tumor, and the study of tumors is called oncology.

Basic Structure:
All tumors have two basic components:
• Parenchyma: made up of transformed or neoplastic cells, largely determines its
biologic behavior and tumor derives its name.
• Stroma: supporting, host-derived, non-neoplastic, made up of connective tissue, blood
vessels, and host-derived inflammatory cells.

Classifications of Tumors:

Biological Classifications
According to their behavior:

Benign neoplasm, have good prognosis.

Malignant neoplasms, have poor prognosis.

Intermediate tumors.

Histological Classifications
According to tissue of origin.

Epithelial tumors.

Mesenchymal tumors.
Benign Neoplasms:
In general, the name of a benign neoplasm often ends with –oma.

• Examples: Adenoma (benign neoplasm of glandular epithelium), fibroadenoma (benign

neoplasm of the breast), and leiomyoma (benign neoplasm of smooth muscle).

• Its microscopic and gross characteristics are considered to be relatively innocent, remain
localized, non-metastatic and can be surgically removed; the patient generally survives.

• Generally slow growing, depending upon the location, may remain Asymptomatic:
subcutaneous lipoma or Symptomatic: meningioma in the nervous system.

• Local invasion: Form encapsulated or circumscribed masses, expand and push aside the
surrounding normal tissues, without actually invading, infiltrating or metastasizing.

• Gross appearance: spherical or ovoid in shape, encapsulated or well-circumscribed, freely

movable, more often firm and uniform, unless secondary changes like hemorrhage or
infarction supervene.

Malignant Neoplasms:
In general, the name of a malignant neoplasm often ends with –carcinoma or –sarcoma.

• Examples: Adenocarcinoma (malignant neoplasm of glandular tissue), rhabdomyosarcoma

(malignant neoplasm of skeletal muscle).

• Grow rapidly, may ulcerate on the surface, invade locally into deeper tissues, may spread to
distant sites (metastasis).

• Local invasion: Initially enlarge by expansion and some well differentiated tumors may be
partially encapsulated as well. But later they can be distinguished by invasion, infiltration and
destruction of the surrounding tissue.

• Gross appearance: Irregular in shape, poorly circumscribed and extend into the adjacent
tissues. Secondary changes like hemorrhaged, infarction and ulceration are seen more often.

• Anaplasia: Hyperchromatism nuclear chromatin of malignant cell is increased and coarsely

clumped, due to increase in the amount of nucleoprotein resulting in dark-staining nuclei.
Nucleolar changes: prominent nucleolus or nucleoli in the nucleus reflecting.
 BENIGN
An abnormal growth that does not invade
surrounding tissue or spread to other
parts of the body.
MALIGNANT
An abnormal growth that can invade and
destroy nearby tissue and that may
spread (metastasize) to other parts of the
body

Have a slow growth rate Have a fast growth rate

Most cells in benign tumors are normal Cells have abnormal DNA and
chromosomes, which make the nucleus
larger and darker

Cells are not cancerous Cells are cancerous

Do not invade the issues around them Invade the tissues around them

Do not spread to the other parts of the Spread to the other parts of the body
body either through the bloodstream or
lymphatic tissue

Easy to remove Difficult to remove

Have less chance to recur More likely to recur

Secrete hormones including benign Secrete substances, which cause fatigue

pheochromocytomas and weight loss

Can be treated with surgery Treated with chemotherapy, radiation

therapy or immunotherapy treatments

Spread of Malignant Tumors:

Metastasis, the spread of malignant cells from a primary tumor to distant sites, poses
the biggest problem to cancer treatment and is the main cause of death of cancer
patients. It occurs in a series of discrete steps, which have been modeled into a
“metastatic cascade”.
 Mechanism of spread
1) Invasion of Extracellular Matrix (ECM):
cancers are able to manipulate and utilize the ECM components, including stromal cells (fibroblasts,
inflammatory cells) to their advantage
This type includes:
- Loss of cellular cohesion.
-Attachment of tumor cells (through receptors) to matrix components.
- Degradation of the ECM by proteolytic enzymes secreted by the tumor cells or by stimulated host
cells (fibroblasts & macrophages).
Migration(mobility) of tumor cells (by pseudopodia).

2) Vascular Dissemination and Homing of Tumor Cells:

Tumor cells frequently escape their sites of origin and enter the circulation as single cells or emboli.
also, Tumor cell penetrate lymphatic, but rarely arterioles (thick-walled).
Steps of this type :
1. Tumor cells invade through vessel wall via proteolytic enzymes
2. Tumor cells will aggregate into small clumps that contain tumor cells and platelets; this may help
increase survival and implantability
3. The tumor embolus will flow downstream and eventually adhere to epithelial cell membranes at a
distance site
4. Tumor cells burrow through the basement membrane of vessel into new tissue; metastasis is
complete and tumor cells will proliferate, develop a vascular supply and evade host defenses.
* Intravasation of tumor cells involves:
• Adhesion molecules
• Proteolysis (of basement membrane of blood vessels)
* Vulnerable to destruction and apoptosis due to loss of adhesion (anoikis)
Anoikis is the phenomenon in which tumor cells can undergo death when come into circulation.

Formation of tumor emboli within vessels

Tumor cells tend to aggregate with each other by:
1. Homotypic adhesion among tumor cells
2. Heterotypic adhesion between tumor cells and blood cells, particularly platelets.

* Extravasation of tumor emboli involves:

1. Adhesion to vascular endothelium
2. Adhesion molecules i.e. ( Integrins , Laminin , CD44 receptors)

Course of tumor emboli depends on anatomical factors:

1)Emboli derived from primary tumors of organs drained by systemic vein as: (vena cava).
2)Emboli derived from tumors of lungs (whether primary or metastatic).
3) Emboli derived from primary tumors of organs drained by the portal vein as:(tumors of
gastrointestinal tract).
4)Emboli reaching the vertebral system of veins from tumors as (tumor of pelvic).
 Pathology of organ metastases:
The most common sites of metastases are the liver, lungs, bones &brain, but rare in
muscles, spleen, pancreas &intestine.
Gross picture: Metastases appear as scattered round nodules of variable sizes.
Microscopic picture: Metastases resemble the primary tumor from which they are
derived.
Routes of spread:
Malignant tumors spread locally to surrounding tissues and distantly to remote sites
(metastases).
Local Spread:also called as local Invasion
* Malignant tumor spreads to its surrounding tissue by forming claw like projections
(spread in all directions along lines of least resistance)
* This tumor cells release proteolytic enzymes and damage the local basement
membrane/ capsule of the organ.

Local spread is explained by the following:

1. The malignant cells have amoeboid movement because they have
less adhesive power than the normal cells. This is due to deficiency of
calcium in the cell membrane of the malignant cells.
2. The malignant cells secrete hyaluronidase enzyme which dissolves
the ground substance which contains hyaluronic acid, thus
facilitating the spread of malignant cells in tissues.

Examples of locally malignant tumors:

1. Basal cell carcinoma.

2. Adamantinoma.

3. Carcinoid tumor of appendix.

4. Some gliomata.

5. Giant cells tumor of bone (osteoclastoma, grade I, II).

6. Some structures as cartilage, periosteum & elastic tissue delay direct spread.

7. Direct spread to a surface (skin or mucosa) leads to ulceration (malignant ulcer) and from one hollow
organ to anther adjacent one causes a malignant fistula.
Distant spread:
Development of secondary malignant implants, discontinuous with the primary tumor. The most
common of which is lymphatic & vascular spread.
A) Hematogenous Route:Sarcoma are usually surrounded by and rich in blood capillaries. This
causes easier dissemination by hematogenous route.
Some carcinoma like those of lung, liver, kidney and prostate also spread by hematogenous route.
* The direction of spread and the final site of metastasis depends on 2 factor :
1. Direction of blood flow. 2. Micro environment of the tissue
This is explained by two theories

Mechanistic theory: Determined by the pattern of blood flow.

Seed and soil theory: The provision of a fertile environment in which compatible tumor cells could
grow.
Spleen is stuffed with lymphocytes, so cancer cells which reach spleen does not survive, get killed.
Some blood vessels may be devoid of valves. Through this blood vessels metastasis can occur in a
direct opposite to the direction of normal blood flow.
B)Lymphatic Spread:(Lymphatic Embolism,Lymphatic permeation)
- Carcinoma usually spread by lymphatics. The cancer cells are surrounded by a rich network
of lymphatic. Also follows mechanistic theory and seed and soil theory.
- The first lymph node that is affected by metastasis in a cancer is called as Sentinel Lymph Node.
Sentinel Lymph Node biopsy is sometimes performed intra operatively to diagnose the presence
(absence of lymphatic metastasis )
- Sometimes a metastatic deposit can occlude a lymphatic channel. The metastatic cells can flow in
reverse direction or this is called as retrograde lymphatic metastasis.
- Tumor emboli reaching regional lymph nodes proliferate and subsequently replace lymphoid tissue
Tumor infiltrates the capsule and perinodal tissue. Emboli pass through efferent lymphatic to other
nodes or sometimes to nodes on the other side of body.
- Lymphatic permeation:
The tumor invades a lymphatic vessel and forms a solid cord in its lumen, the lumen is blocked by a
mass of malignant cells and the flow of lymph may be reversed, and the malignant cells are carried to
unusual sites, sometimes known as retrograde lymphatic spread.
C) Transcoelomic Spread: Sometimes cancer cells can move along the peritoneal surface and
spread through the body cavity. Which may be associated with hemorrhagic effusion.
Malignant tumors in organs covered by serous membranes infiltrate the serosa and afterwards drop in
therelated cavity to become implanted on serosa of other organs as intestine, ovary, and omentum
depending on the site of the primary tumor
This type includes:
▪ Trans-peritoneal spread
▪ Trans-pleural and trans-pericardial spread
▪ Trans CSF spread may occur in malignant tumors of brain.
 Krukenberg tumor:
-Gastric carcinoma with secondary deposits in the ovary and pouch of Douglas.
-Colonic carcinoma with secondary deposits in the ovary and pouch of Douglas.
D) other method of spread:
▪ Transluminal implantation
▪ Surgical implantation:During surgery cancer cells may be implanted from one sided to another
by a surgical scalpel contaminated with malignant cells may cause secondary tumor deposits.
▪ Implantation from carcinoma of lower lip may lead to a secondary tumor in the upper lip.

Characteristics of carcinoma and sarcoma:

There are a number of differences between sarcomas and carcinomas, though individual
cancers within each category can vary tremendously. Carcinomas account for the
majority of cancers with only 1% of cancers in adults being sarcomas. In children,
however, sarcomas account for over 15% of cancers, making research critical.
Carcinomas arise out of epithelial cells that line the surface and organs of the body,
whereas sarcomas arise from connective tissues such as bone, cartilage, fibrous tissue,
blood vessels, and nerves.
There are many differences between sarcomas and carcinomas, so it is helpful to begin by
talking about the similarities. Some of these include:
►Both are cancer (malignant): There are a number of differences between malignant tumors
and benign tumors, with a major difference being that malignant tumors can spread to distant
regions of the body.
►Both can be relatively treatable or life-threatening: Low-grade sarcomas and some
carcinomas such as basal cell carcinoma of the skin can be very treatable. Likewise, some
sarcomas as well as some carcinomas (for example, pancreatic cancer) are very challenging to
treat with saddening five-year survival rates.
►Both can occur at any age: While sarcomas are more commonly found in young people, both
sarcomas and carcinomas may be diagnosed at any age.
►With both, the cause is often unknown: While certain genetic syndromes as well as
exposures may be associated with both sarcomas and carcinomas, the exact cause of either
type of cancer is often unknown.
►Both can be difficult to diagnose: Both sarcomas and carcinomas may be misdiagnosed at
first.
►Both require people to be their own advocates: With both sarcomas and uncommon types
of carcinomas, finding physicians who specialize in these rare or uncommon cancers may
improve outcomes.
There are also many differences between sarcomas and carcinomas. Carcinomas are
much more common, accounting for 85% to 90% of cancers. Sarcomas, in contrast,
represent slightly less than 1% of cancer types. (The other types of cancer include
leukemias, lymphomas, and myelomas, although some cancers may have characteristics
of more than one type, for example, carcinosarcomas.)
Carcinomas tend to be more common in people over the age of 50, but can occur in
young adults and children. Sarcomas may occur at any age, but are often diagnosed in
children and young adults. Roughly 15% of cancers diagnosed in people less than 20
years of age are sarcomas.

Characteristics of intermediate tumor:

Willis ( 1960) proposed a workable definition for distinguishing true tumors from
inflammatory and reparative proliferations, hyperplasias, and malformations with
excess of tissue. A tumor "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." Every pathologist can
think of exceptions but these do not invalidate the general applicability of the definition.
Histological classification of tumor:
The commonly used and most useful classification of tumors is histogenetic, that is, the
tumors are named according to the tissues from which they arise and of which they
consist. In most tumors the neoplastic tissue consists of cells of a single type and, with
experience, one can readily classify them. The types of histological differentiation found
in tumors appear to be inherent in the parent tissues. Foulds ( 1940) concluded that
most adult normal cells have a greater capacity for divergent differentiation than was
formerly supposed and that it is unlikely that tumor cells acquire new capacities. The
few kinds of tumors in which there is uncertainty regarding the precise tissue of origin
require further histopathological research. Meanwhile in these cases we must settle for
noncommittal identifying names.The tissue of malignant→ add (sarcoma or carcinoma)
to the type of tissue forexample, the glandular epithelium called adenocarcinoma but
the fibrous connective tissue called fibrosarcoma.
Willis ( 1960) illustrated the application of histogenetic classification to both human and
animal tumors. Cloudman ( 1941) presented a histological classification of mouse
tumors. Dunham and Stewart ( 1953) gave a classification of transplantable and
transmissible animal tumors.
Benign and malignant:
In addition to histogenetic classification, it is of practical value in human oncology to attempt to predict
the behavior of a tumor from its morphology. The tumors of any given cell type may show a wide range
of difference in structure, mode of growth, rate of growth, and danger to the host. Some, called
benign, are well differentiated, grow only by expansion with the formation of a capsule, grow slowly,
and are dangerous only in terms of position, accidental complication, or excessive hormone
production. Others, often less well differentiated, grow rapidly, invade adjacent tissues, spread by
metastasis, and unless extirpated at an early stage will kill the host; these are malignant tumors.
Between these extremes there may be tumors of intermediate behavior. Thus, the terms benign and
malignant are relative and arbitrary.
Criteria for diagnosing malignancy include imperfect differentiation and variation in the size, shape,
and staining quality of the cell and the nucleus, invasion of adjacent tissues, and metastasis. In general
the degree of malignancy is roughly proportional to the degree to which tumors fail to attain
histological differentiation; the most anaplastic tumors are the most malignant. Metastasis depends on
the invasion of blood vessels, lymphatics, or serous and other cavities, with the detachment of tumor
cells or cell clusters and the establishment of distant secondary deposits. Lymphatic metastasis is less
common in mice than in man. When tumors occur in inbred animals, there is available an additional
criterion of malignancy: successful transplantation with progressive growth.

Embryonic tumors:
Male germ cell tumors result from the transformation of premeiotic or early meiotic
germ cells and exhibit embryonal like differentiation of the three germinal layers. They
are the most common malignant neoplasms of males aged 15-35 years and a major
cause of cancer-induced deaths in this age group. In females, germ cell tumors account
for 30% of all ovarian tumors, but only 1–3% of ovarian cancers in North America. In
younger women, germ cell lesions are more common, accounting for 60% of ovarian
tumors arising under the age of 21. Worldwide, the highest incidence for germ cell
tumors is in Scandinavia.
Germ cell tumors may develop extragonadally. Mediastinal germ cell tumors are rare
growths that predominantly affect young males. They may represent isolated
metastases from inapparent gonadal primary sites, potentially as a consequence of the
abnormal migration of germ cells during embryogenesis.
Hamartoma:
A hamartoma is a noncancerous tumor made of an abnormal mixture of normal tissues
and cells from the area in which it grows.
Hamartomas can grow on any part of the body, including the neck, face, and head. In
some cases, hamartomas grow internally in places such as the heart, brain, and lungs.
Epidemiology of cancer:
The epidemiology of cancer is the study of the factors affecting cancer, as a way to infer possible
trends and causes. The study of cancer epidemiology uses epidemiological methods to find the cause
of cancer and to identify and develop improved treatments.
This area of study must contend with problems of lead time bias and length time bias. Lead time bias is
the concept that early diagnosis may artificially inflate the survival statistics of a cancer, without really
improving the natural history of the disease. Length bias is the concept that slower growing, more
indolent tumors are more likely to be diagnosed by screening tests, but improvements in diagnosing
more cases of indolent cancer may not translate into better patient outcomes after the
implementation of screening programs. A related concern is overdiagnosis, the tendency of screening
tests to diagnose diseases that may not actually impact the patient's longevity. This problem especially
applies to prostate cancer and PSA screening.
Some cancer researchers have argued that negative cancer clinical trials lack sufficient statistical power
to discover a benefit to treatment. This may be due to fewer patients enrolled in the study than
originally planned .

Factors that affect CA incidence:

1-Geographic location. 2- Environmental variable.
3- Age. 4- Heredity. 5-Acquired preneoplasticdisorders.
Geographic location
Geographic differences are environmental rather than genetic.
Gastric CA→ high in Japan.
Skin CA → high in New Zealand.
Breast CA, Prostatic CA and Colorectal CA → high in USA.

Environmental factor:
• Tobacco: The most significant environmental risk factor for cancer is
tobacco, whether they're using products like cigarettes, pipes, cigars,
chewing tobacco, snuff or vaping, or being exposed to secondhand smoke.
• Alcohol.
• Obesity.
• Ultraviolet radiation.
• Asbestos.
• Viruses.
• Ionizing radiation.
Age:

We investigated to determine whether colposcopic, histologic, and virologic

parameters of cervical intraepithelial neoplasia are influenced by a patient’s age.
Study Design: A cohort of 967 women with a mean age of 37.1 years underwent
screening for detection of cervical intraepithelial neoplasia by colposcopy, cytologic
examination, and testing for high-risk human papillomaviruses with the Hybrid Capture
System (Digene, Silver Springs, Md) and a general primer and type-specific primer
polymerase chain reaction system. Cervicography was used for documentation and
reproducible evaluation of the colposcopic appearance of the cervix. In 86% of
patients with trivial colposcopic changes of doubtful significance (100/116) and 89% of
patients with colposcopic changes consistent with cervical intraepithelial neoplasia
(89/99), punch biopsy specimens were taken for histologic evaluation. Results: In
patients with trivial colposcopic changes of doubtful significance, histologically
confirmed cervical intraepithelial neoplasia was almost as frequent (32%, 37/116) as in
patients with colposcopic changes consistent with cervical intraepithelial neoplasia
(43%, 43/99, difference not significant). The ratio between colposcopic evidence of
cervical intraepithelial neoplasia and trivial colposcopic changes was 1.9 in patients
<35 years old with cervical intraepithelial neoplasia, versus 0.5 in patients ≥35 years old
with cervical intra-epithelial neoplasia (P = .005). Patients with trivial colposcopic
changes of doubtful significance were older (median age 36 years) than were
patients with colposcopic changes consistent with cervical intraepithelial neoplasia
(median age 29 years, P = .008). In patients with cervical intraepithelial neoplasia who
had no or trivial colposcopic changes, the thickness of neoplastic epithelium was
smaller (P = .008) and the number of cellular layers was lower (P = .01) than in patients
with cervical intraepithelial neoplasia who had colposcopic changes consistent with
cervical intraepithelial neoplasia. In patients <35 years old the rate of positive results for
a high-risk human papillomavirus (P < .005) and the viral load (difference not
significant) were higher than in women ≥35 years old. The rate of positive results for
high-risk human papillomaviruses differed independently of age among patients with
normal colposcopic findings, patients with trivial colposcope changes of doubtful
significance, and patients with colposcopic changes consistent with cervical
intraepithelial neoplasia (P < .005). Conclusions: In women ≥35 years old cervical
lesions associated with intraepithelial neoplasia are thinner and thus less
colposcopically conspicuous than those in women <35 years old. Patients ≥35 years
old with acetowhite cervical lesions consistent with trivial changes of doubtful
significance should therefore undergo punch biopsy for histologic evaluation.
Heredity:

5-10% The frequency of colorectal neoplasia was assessed through colonoscopy in 114
patients with a family history of colorectal cancer. In over 90 percent of patients, a
first-degree relative was affected. Twenty-one percent of patients who were studied
endoscopically were positive for neoplastic disease, including two invasive cancers.
Twenty-eight percent of patients had adenomas beyond the splenic flexure. Multiple
primary relatives further increased risk with 36 percent positive for neoplasia. Neoplasia
was common in young patients, with 25 percent under the age of 40 years positive for
adenomas. These findings are identical to recent pedigree studies and further support
a genetic basis for common colorectal cancers. First-degree relatives of patients with
colorectal cancer should be considered at high-risk for colorectal neoplasia.
Screening and surveillance with colonoscopy are recommended.
 References

• Geiger TR, Metastasis mechanisms, Reviewed at Aug 14 2009, Available in

https://www.ncbi.nlm.nih.gov/pubmed/19683560?fbclid=IwAR05Vlndabm_
n8d-lA8b5yf1ZxR_aWrSuBQZmy5tU5LfP56x9q3AT05GNuw

• Lynne Eldrige, Sarcoma vs. Carcinoma, Reviewed at Jan 13 2020, Available

in
https://www.verywellhealth.com/sarcoma-vs-carcinoma-4694486

• American Journal of Obstetrics and Gynecology, Endometrial cancer,

Reviewed at Apr5 2020, Available in
https://www.sciencedirect.com/science/article/abs/pii/S0002937820303835

• Deep Deep, Benign Tumors, Reviewed at May 7 2009, Available in

https://www.slideshare.net/deepak15/benign-tumors