NEOPLASIA

Dr.Ayesha Sana
 Neoplasia
• literally means "new growth.“
• Definition: 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
the cessation of the stimuli which evoked the
change."
 Neoplasia
• In common medical usage, neoplasm is often referred to
as Tumor
• Oncology - study of tumors (oncos –tumor logos - study
of").
• Division of Neoplasms into 2 categories based on
judgment of a neoplasm's potential clinical behavior.
– Benign
– Malignant
 Benign neoplasm
• A tumor is said to be benign when
– its microscopic and gross characteristics are
considered to be relatively innocent
– implying that it will remain localized, cannot
spread to other sites
– is amenable to local surgical removal;
– the patient generally survives.
 Malignant neoplasm
• Malignant tumors collectively referred to as
cancers (crab).
• Malignant neoplasm, implies that
– the lesion can invade and destroy adjacent
structures
– spread to distant sites (metastasize) to cause
death.
• Two Basic Components of tumors
• (1) Parenchyma: made up of transformed or
neoplastic cells
• (2) Stroma: supporting, host-derived, non-
neoplastic, made up of connective tissue, blood
vessels, and host-derived inflammatory cells.
 Nomenclature of Benign tumors
• is more complex. Classified on the basis of their :
– cells of origin
– microscopic pattern
– macroscopic pattern
• Generally, designated by attaching the suffix -oma to
the cell type from which the tumor arises.
• tumor arising in fibrous tissue – fibroma
• cartilaginous tissue - chondroma.
Term adenoma is applied to benign epithelial
neoplasm producing gland patterns and to neoplasm
derived from glands but not necessarily exhibiting
gland patterns
Papillomas are benign epithelial neoplasms,
growing on any surface, that produce
microscopic or macroscopic finger-like fronds.
Papillomas
 A polyp is a mass that projects above a mucosal
surface to form a macroscopically visible structure.
E.g. gut. Benign, malignant, inflammatory
Polyp
Laryngeal polyp
 Nomenclature of Malignant neoplasms
• Essentially follows benign with additions and exceptions
• Arising in solid Mesenchymal tissue or its derivatives
Sarcomas.
– fibrous tissue origin - fibrosarcoma,
– composed of chondrocytes - chondrosarcoma.
• Arising from mesenchymal cells of blood – leukemia,
lymphoma
• Epithelial cell origin - Carcinomas (endo, ecto,or mesoderm)
• Growing in glandular pattern – adenocarcinoma
• Producing squamous cells – squamous cell carcinoma
 Nomenclature…
• Degree of differentiation – poor or undifferentiated
• Divergent differentiation – mixed tumors. Both epithelial
and fibrous tissue elements.
• Pleomorphic adenoma of salivary glands
• Fibroadenoma breast
• Teratoma – mature or immature cells or tissues from one
or more germ cell layers. Totipotential germ cells in ovary
and testis
• Malignant – lymphoma, melanoma, seminoma
• Hemartoma: mass of disorganized tissue indigenous to a
particular site
• Choristoma: congenital anomaly consisting of
heterotropic rest cells
 Nomenclature of tumors
Tissue of Origin Benign Malignant
Composed of One
Parenchymal Cell
Type
Connective tissue Fibroma Fibrosarcoma
and derivatives
Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteogenic
sarcoma
 Nomenclature of tumors
Benign Malignant

Endothelial and
related tissues
Blood vessels Hemangioma Angiosarcoma

Lymph vessels Lymphangioma Lymphangiosarcoma

Synovium Synovial sarcoma

Mesothelium Mesothelioma

Brain coverings Meningioma Invasive meningioma

 Nomenclature of tumors
Benign Malignant

Blood cells and

related cells

Hematopoietic Leukemias
cells
Lymphoid tissue Lymphomas
Smooth Leiomyoma Leiomyosarcoma
Striated Rhabdomyoma Rhabdomyosarco
ma
 Benign Malignant
Tumors of epithelial origin
Stratified squamous Squamous cell papilloma Squamous cell or
epidermoid carcinoma
Basal cells of skin or adnexa Basal cell carcinoma
Epithelial lining of glands or ducts Adenoma Adenocarcinoma

Papilloma Papillary carcinomas

Cystadenoma Cystadenocarcinoma
Respiratory passages Bronchial adenoma Bronchogenic carcinoma

Renal epithelium Renal tubular adenoma Renal cell carcinoma

Liver cells Liver cell adenoma Hepatocellular carcinoma

Urinary tract epithelium (transitional) Urothelial papilloma Urothelial carcinoma

Placental epithelium Hydatidiform mole Choriocarcinoma

Testicular epithelium (germ cells) Seminoma
Embryonal carcinoma
Tumors of melanocytes Nevus Malignant melanoma
More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from One Germ Cell
Layer

Salivary glands Pleomorphic adenoma Malignant mixed tumor of

(mixed tumor of salivary salivary gland
gland)

Renal anlage Wilms tumor

More Than One Neoplastic Cell Type Derived from More Than One Germ Cell Layer-
Teratogenous

Totipotential cells in gonads Mature teratoma, dermoid Immature teratoma,

or in embryonic rests cyst teratocarcinoma
 Characteristics of benign and
malignant tum
• Differentiation and anaplasia
• Rate of growth
• Local invasion
• Metastasis.
 Differentiation and anaplasia
• The differentiation of parenchymal cells refers to
the extent to which they resemble their normal
forebears morphologically and functionally.
• Benign tumors well differentiated , rare mitoses
• Malignant have range of differentiation
• Term Anaplasia literally means "to form backward."
It implies dedifferentiation or loss/ lack of
structural and functional differentiation of normal
cells.
• Anaplasia is considered hallmark of malignancy.
 Differentiation and anaplasia
• Anaplastic cells display marked
• Pleomorphism: variation in size and shape
• Nuclear hyperchromatism: extremely (darkly stained) and
large.
• Nuclear-to-cytoplasmic ratio may approach 1 : 1 instead of
normal 1 : 4 or 1 : 6.
• Anaplastic nuclei variable. bizarre in size and shape.
• Mitoses Numerous and atypical (anarchic multiple spindles,
tripolar or quadripolar)
• Loss of polarity: cells usually fail to develop pattern of
orientation to one another
Squamous cell carcinoma. Squamous cell appearance and
keratin nest
Rhabdomyosarcoma. cellular & nuclear pleomorphism,
hyperchromatic nuclei, giant cells
Anaplasia tripolar spindle

→
 Rate of growth
• Benign tumors
• Most grow slowly. Exceptions leiomyoma grow faster due to
estrogens, in pregnancy, regress in menopause. Blood supply,
pressure restraints – necrosis / growth.
• Malignant tumor
• Most cancers grow much faster
• rate of growth correlates with their level of differentiation.
• Exceptions are always there. Slow growth. Aggressive sub
clone of cells. Disappear due to necrosis
• Take variable time to be detected clinically
 Local invasion
• Benign neoplasm remains localized at site of
origin. It does not have capacity to infiltrate,
invade, or metastasize to distant sites.
encapsulation is the rule, but the lack of a capsule
does not imply that a tumor is malignant. Fibrous
capsule / zone of compressed normal tissue,
plane of cleavage
• Malignant neoplasms grow by progressive
infiltration, invasion, destruction, penetration of
the surrounding tissue and metastasize to distant
sites
Fibroadenoma breast with capsule
Ca breast stromal invasion by nest and cords of tumor cells.
No capsule
Comparison of benign and malignant tumors
 Metastasis
• Development of secondary implants (metastases)
discontinuous with the primary tumor and located
in remote tissues
• Properties of invasiveness and metastasis identify a
neoplasm as malignant. Variable metastatic ability.
Some diagnosed by metastases
• Disseminate by one of three pathways:
– Direct spread and seeding within body cavities
– lymphatic spread
– hematogenous spread
 Metastasis - Seeding within body cavities
• Spread by seeding occurs when neoplasms invade
a natural body cavity.
• Colon cancer – peritoneal cavity
• Lung cancer – pleural cavity
• Ovarian cancer – peritoneal cavity
• CNS cancer – CSF in ventricles to meninges
 Metastasis lymphatic spread
• There are numerous interconnections between the
lymphatic and vascular systems, so all forms of cancer
may disseminate through either or both systems.
• is more typical of carcinomas
• pattern of lymph node involvement depends on site
of primary neoplasm and natural pathways of
lymphatic drainage of the site.
• "Sentinal lymph node" - first lymph node in a regional
lymphatic basin that receives lymph flow from a
primary tumor.
 Metastasis lymphatic spread
• Although enlargement of nodes near a primary
neoplasm should arouse strong suspicions of
metastatic spread, it does not always imply
cancerous involvement. The necrotic products of
neoplasm and tumor antigens often evoke reactive
changes in the nodes, such as enlargement and
hyperplasia of follicles (lymphadenitis) and
proliferation of macrophages in subcapsular
sinuses (sinus histiocytosis).
 Metastasis Hematogenous spread
• is favored more by sarcomas.
• arteries are penetrated less readily than veins.
• liver and lungs - most frequently involved
secondary sites
• Ability to invade and metastasize
• the metastatic cascade can be subdivided into
two phases:
1. Invasion of ECM and vascular dissemination
2. Homing of tumor cells.
 Invasion of Extracellular Matrix (ECM)
• Tissues are organized into a series of compartments
separated from each other by two types of ECM: basement
membranes and interstitial connective tissue.
• components of both types is composed of collagens,
glycoproteins and proteoglycans, but organized differently
• An active process requiring four steps.
1. Detachment of tumor cells from each other
2. Invasion and Degradation of ECM
3. Attachment of tumor cells to ECM proteins
4. Migration of tumor cells
 First step - Detachment of tumor cells
from each other
• Loosening of tumor cells.
• E-cadherins act as intercellular glues, and their
cytoplasmic portions bind to β-catenin. Adjacent E-
cadherin molecules keep the cells together
• E-cadherin function is lost in almost all epithelial
cancers by
– mutational inactivation of E-cadherin genes
– activation of β-catenin genes.
Mutual Attachment of cells
Second step - Invasion & Degradation of ECM
• local degradation of basement membrane and interstitial
connective tissue.
• Secretion of proteolytic enzymes - by
– Tumor cells themselves
– stromal cells induced by tumor cells e.g fibroblasts and
inflammatory cells
• Cathepsin D, Urokinase and Matrix Metalloproteinases
(MMPs) e.g. MMP-9 cleaves type IV collagen of epithelial
and vascular basement membrane
• Malignant tumors over express this enzyme. levels of
metalloproteinase inhibitors are reduced.
 Third step -Attachment of tumor cells to
ECM proteins
• Receptors (integrins) on epithelial cells for laminin and
collagen of basement membrane maintain cells in
resting state. Loss of adhesion – induction of
apoptosis.
• Cleavage of the basement membrane proteins collagen
IV and laminin by MMP-2 or MMP-9 generates novel
sites that bind to receptors on tumor cells and
stimulate migration.
• Carcinoma cells have many more receptors distributed
all around the cell membrane.
 Fourth step - Locomotion

• Propelling tumor cells through the degraded

basement membranes and zones of matrix
proteolysis.
• Migration a complex, multistep process , that
involves many families of receptors and
signaling proteins that eventually impinge on
the Actin cytoskeleton.
 Fourth step - Locomotion
• Chemotactic factors potentiate and direct
movement. Tumor cell-derived cytokines
(autocrine motility factors), cleavage products of
matrix components and some growth factors (
Insulin-like growth factors I and II)
• Stromal cells also produce paracrine effectors of
cell motility, such as Hepatocyte growth
Factor/Scatter factor (HGF/SCF), which bind to
receptors on tumor cells.
 Vascular Dissemination and Homing of
Tumor Cells
• In the bloodstream, some tumor cells form emboli by
aggregating and adhering to circulating leukocytes,
particularly platelets; aggregated tumor cells are thus
afforded some protection from the antitumor host
effector cells.
• Extravasations of free tumor cells or tumor emboli
involves adhesion to the vascular endothelium,
followed by egress through the basement membrane
into the organ parenchyma by mechanisms similar to
those involved in invasion.
 Vascular Dissemination and Homing of
Tumor Cells
• site of extravasation and organ distribution of
metastases generally can be predicted by location of
primary tumor and its vascular or lymphatic drainage.
Many tumors metastasize to the organ that
represents the first capillary bed they encounter after
entering the circulation.
• In many cases the natural pathways of drainage do
not readily explain the distribution of metastases. As
some tumors (e.g., lung cancers) tend to involve the
adrenals with some regularity but almost never
spread to skeletal muscle.
 Vascular Dissemination and Homing of
Tumor Cells
• Such organ tropism may be related to the
expression of adhesion molecules by tumor
cells whose ligands are expressed preferentially
on the endothelium of target organs.
• Another mechanism of site-specific homing
involves chemokines and their receptors on
tumor cells e.g. CXCR4, CCR7
• Colonization at target site not undestood.
Receptive stroma may have role
Vascular Dissemination and Homing of
Tumor Cells
• Millions of tumor cells shed present in blood
but metastases less or none
• Concept of dormancy
• Secretion of cytokines and growth factors acting
on stroma may help in habitation of tumor cells
• Understanding can help in therapeutic
interventions
 Epidemiology
• Geographical incidence and Environmental
variables
• Age childhood, old age
• Hereditary predisposition
• Autosomal dominant cancer syndromes
• Autosomal Recessive cancer syndromes
• Familial cancers of uncertain inheritance
 Acquired preneoplastic lesions
• Precancers which increase the likelihood of cancers. Most do not
progress to ca
• Chronic tissue injury or inflammation stimulating continuing
regeneration, exposing cells to byproducts which lead to
mutation
• Recognition leading to removal or reversal is important for
prevention
• Squamous metaplasia and dysplasia – bronchial mucosa - lung
ca
• Endometrial hyperplasia and dysplasia –ca
• Leukoplakia oral cavity, vulva,
• Villous adenoma colon- colorectal ca
• Benign tumors are generally not precancerous. But each type is
associated with a particular level of risk