NEOPLASIA

• Latin word: “new growth”

• abnormal mass of tissue which grows in an uncoordinated manner
even after cessation of the stimuli which evoked the change
NOMENCLATURE

Neoplasm

Benign Malignant

Carcinoma Sarcoma
 NEOPLASTIC PROLIFERATION

• Benign
• Localized, non-invasive.

• Malignant
• Spreading, Invasive.
BENIGN TUMORS
• Benign tumors are named using -oma as a suffix with the organ name
as the root
• Resembles the normal looking tissue
• Encapsulated and well-define
• Ex: benign tumor of fibrous tissue is called a fibroma

Confusingly, some types of malignant also use the - oma suffix

• Melanoma
• Seminoma
THYROID ADENOMA
MALIGNANT TUMORS
◼ classified by the type of cell that the tumor resembles and is
therefore presumed to be the origin of the tumor.
◼ Carcinoma:

◼ derived from epithelial cells, ex: the breast, prostate, lung,

pancreas, and colon
◼ Sarcoma:
◼ arising from connective tissue, ex: fibrous, muscles, fat, bone,
cartilage
CARCINOMA
▪ Malignant tumor arise from epithelial tissue
• Adenocarcinoma – malignant tumor of glandular cells
• Squamous cell carcinoma – malignant tumor of squamous cells
CARCINOMA
◼ Malignant neoplasm of epithelial cell origin derived from any
of the three germ layers called carcinomas
◼ Arising from epidermis of ectodermal origin (squamous cell carcinoma)
◼ Carcinoma arising from cells of renal tubules are of mesodermal origin (renal cell
carcinoma)
◼ Ca derived from cells lining the gastrointestinal tract are of
endodermal origin (adenocarcinoma)
 ORIGIN OF TUMORS BENIGN MALIGNANT
SKIN SQUAMOUS CELL PAPILLOMA SQUAMOUS CELL CARCINOMA
GLANDS (EX: COLON) ADENOMA ADENOCARCINOMA
THYROID ADENOMA FOLLICULAR CARCINOMA
PAPILLOMA PAPILLARY CARCINOMA

CYST (EX: OVARY) CYSTADENOMA CYSTADENOCARCINOMA

RENAL EPITHELIUM RENAL TUBULAR ADENOMA RENAL CELL CARCINOMA
LIVER HEPATIC ADENOMA HEPATOCELLULAR CARCINOMA
URINARY TRACT TRANSITIONAL CELL PAPILLOMA TRANSITIONAL CELL CARCINOMA
BENIGN AND MALIGNANT: OVARY
SARCOMA
◼ Malignant tumor arising from connective tissue
• (bone, cartilage, fat, nerve) develop from cells originating in
mesenchymal cells outside the bone marrow
• Examples:
• Angiosarcoma – malignant tumor of blood vessels
• Rhabdomyosarcoma – malignant tumor of skeletal muscle cells
TISSUE OF BENIGN MALIGNANT
ORIGIN

Connective Tissue and masenchymal origin

Fibroma Fibrosarcoma

Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteosarcoma
BENIGN AND MALIGNANT
liposarcoma
lipoma
◼

LYMPHOMA AND LEUKEMIA

• Cancer that arise from hematopoietic cells
• Leukemia- tend to proliferate in the intravascularly
• Lymphoma- tend to proliferate in the lymph nodes and lymph tissues
GERM CELL TUMOR
• Cancers derived from pluripotent cells, most often presenting in the
testicle or the ovary
• Seminoma- tumor in the testis
• Dysgerminoma- tumor in the ovary
 SPECIALISED TUMORS
◼ Collision tumor: Two different cancers in ◼ Mixed tumor: more than one cell type but
the same organ which do not mix with arising from only one germ layer (ex:
each other carcinosarcoma)
SPECIALIZED TUMORS
◼ Teratoma: tumor made up of a mixture of tissue types arising from
totipotent cells derived from the germ layers – ectoderm,
mesoderm, endoderm
◼ Most common sites are ovaries and testis
MATURE TERATOMA
 SPECIALIZED TUMORS
▪ Blastoma: malignant tumors that arise from embryonal or partially differentiated
cells which would form blastoma of the organs and tissue during embryogenesis

▪ Tumors occur more frequently in infants and children under 5 y/o

◼ Neuroblastoma
◼ Hepatoblastoma
◼ Retinoblastoma
◼ Medulloblastoma
BLASTOMA
Medulloblastoma Retinoblastoma
 BENIGN VS MALIGNANT
CHARACTERISTICS BENIGN MALIGNANT
SURFACE SMOOTH IRREGULAR
RATE OF GROWTH SLOW AND EXPENSILE ERRATIC
CAPSULE WELL-ENCAPSULATED INVASIVE
SIZE USUALLY SMALL OR LARGE SMALL TO LARGE
SOMETIMES
COURSE RARELY FATAL USUALLY FATAL
DIFFERENTIATION RESEMBLES NORMAL TISSUE LACK OF DIFFERENTIATION
CELL FEATURES RESEMBLES NORMAL CELL MARKED VARIATION
MITOSIS NORMAL INCREASED
NECROSIS UNUSUAL COMMON
METASTASIS ABSENT PRESENT
GROSS EXAMINATION: BREAST
BENIGN MALIGNANT
FEATURES OF LACK OF DIFFERENTIATION
1. PLEOMORPHISM- refers to the variation on size and shape of cell
and nuclei
2. HYPERCHROMATISM- nuclei contain abundant chromatin and are
dark stained
3. INCREASED NUCLEAR-TO-CYTOPLASMIC RATIO- normal: 1:4 to 1:6
4. MITOSIS- reflect the proliferative activity
5. LOSS OF POLARITY- growth in disorganized fashion
6. BIZZARE AND GIANT CELLS
7. NECROSIS
PAP SMEAR
WHAT IS DYSPLASIA?
• Term that literally means disordered growth
• Characterized by loss in the uniformity of the individual cells as well
as loss in their architectural orientation
DYSPLASTIC SQUAMOUS EPITHELIUM
mitoses are not confined to the
basal layers but instead may
appear at all levels, including
cell surface
GRADING OF DYSPLASIA
• Mild, Moderate, Severe: reversible
• Severe: usually progresses to carcinoma in-situ
WHAT IS CARCINOMA IN-SITU?
• dysplastic changes are marked and involve the entire thickness of
the epithelium but remains confined by the basement membrane
• Considered pre-invasive neoplasm
• Once the tumor cells breach the basement membrane , the tumor is
said to be invasive (MALIGNANT).
WHAT IS METASTASIS?
• Denotes the development of secondary implants from the
primary tumor
• Describes the spread of malignant tumor to distant areas of the
body
MODE OF METASTASIS
◼ Lymphatic
◼ Hematogenous
◼ Retrograde
◼ Transcoelomic
LYMPHATIC SPREAD
• Transport through lymphatics is the most common pathway for the
initial dissemination of carcinomas but also seen in sarcomas may
also use this route.
HEMATOGENOUS SPREAD
◼ Hematogenous spread is typical of sarcomas but is also seen with carcinomas
◼ Arteries, with their thicker walls, are less readily penetrated than are veins
◼ Metastatic tumors usually lodge onto the capillary beds
◼ The liver and lungs are most frequently involved in hematogenous
dissemination because all portal area drainage flows to the liver and all
caval blood flows to the lungs.
RETROGRADE METASTASIS
• Due to obstruction of the lymphatics by the tumor cells the lymph
flow is disturbed and tumor cells spread against the flow of lymph
causing retrograde metastasis
◼ Ca. of prostate to the supraclavicular lymph nodes
◼ Metastatic deposits from bronchogenic ca to axillary lymph nodes
TRANSCOLEOMIC SPREAD
◼ Carcinoma of stomach seeding both the ovaries
◼ Carcinoma of the ovary spreading to entire peritoneal cavity without
infiltrating the underlying structures.
◼ Pseudomyxoma peritonei is the gelatinous coating of the
peritoneum from mucin secreting cancer of ovary or appendix
◼ Cancer of bronchus and breast seeding to the pleura and pericardium.
Carcinoma of stomach seeds to both ovaries
TUMOR EXTENSION
contiguous growth of the
primary tumor within the organ
or direct extension into
neighboring organs
SPREAD ALONG EPITHELIAL LINED SURFACE
• Through fallopian tubes-endometrium
• Through fallopian tubes-ovaries
• Through bronchus-alveoli
• Through ureter-kidney
TNM STAGING
• Staging depends on the malignancy (source: AJCC 8th edition)
• refers to the extent of malignancy
• understand the prognosis
• plan for the best treatment
• identify clinical trials that may be a treatment options
• Tumor- tumor depth of invasion/ tumor size
• Node (lymph nodes) involvement
• Metastasis- distant implants
CONCEPTS OF INFLAMMATION & REPAIR
INFLAMMATION
• Response of vascularized tissues to infection, damage tissues that
brings cells and molecules to the site inorder to eliminate offending
agents

1. Recognize offending agent

2. Recruitment of leukocytes and plasma proteins
3. Removal of agent
4. Regulate control of response
5. Resolution and repair
HISTOLOGICAL HIGHLIGHTS
• CELSUS- 4 cardinal signs: rubor , tumor, calor, and dolor
• RUDOLF VIRCHOW- functio laesa
• JOHN HUNTER- inflammation is not a disease but a reaction
• ELIE METCHNIKOFF- phagocytosis
• THOMAS LEWIS- histamine mediate the vascular changes of
inflammation
FIVE CARDINAL SIGNS
OF INFLAMMATION
• RUBOR- redness (blood flow to the injury)
• CALOR- heat (increase blood flow and cells)
• TUMOR- swelling (capillary permeability causing
fluid extravasation)
• DOLOR- pain (increase pressure detected by
sensory nerves)
• FUNCTIO LAESA- loss of function (destruction of
functional units)
EXUDATE VS TRANSUDATE
 INFLAMMATION ACCORDING TO
CHARACTERISTICS OF EXUDATES
• SEROUS INFLAMMATION: exudation of cell poor
fluid into spaces created by cell injury or into body
cavities lined by the peritoneum, pleura, or
pericardium.
• FIBRINOUS INFLAMMATION: develops when the
vascular leaks are large or there is a local
procoagulant stimulus, fibrin appears as an
eosinophilic meshwork of threads
• SUPPURATIVE INFLAMMATION: production of pus,
an exudate consisting of neutrophils, the liquefied
debris of necrotic cells, and edema fluid
• CATARRHAL INFLAMMATION: due to hypersecretion
of mucosa
ACUTE VS CHRONIC INFLAMMATION
FEATURES OF ACUTE AND CHRONIC
INFLAMMATION
• ACUTE
• Blood vessel dilatation
• Increase permeability
• Emigration of leukocytes- neutrophils

• CHRONIC INFLAMMATION
• Mononuclear cell – macrophages and lymphocytes
• Tissue destruction
• Attempts of healing- fibrosis
PRINCIPAL MEDIATORS OF INFLAMMATION
CYTOKINES VS CHEMOKINES
• Cytokines are proteins produced by many cell types (principally
activated lymphocytes, macrophages, and dendritic cells, endothelial,
epithelial, and connective tissue cells) that mediate and regulate
immune and inflammatory reactions

• Chemokines are a family of small proteins that act primarily as

chemoattractant for specific types of leukocytes
CYTOKINES IN INFLAMMATION
ROLE OF COMPLEMENT IN INFLAMMATION
CHRONIC INFLAMMATION
• MACROPHAGE ACTIVATION
• Classic- kills ingested organism
• Alternative- tissue repair

• LYMPHOCYTES
• TH1- produce INF-y (activates macrophages- classic)
• TH2- produce IL-4, IL-5, IL-13: activates eosinophils (hypersensitivity)
• TH17- produce IL-17 recruit neutrophils and monocytes
CHRONIC INFLAMMATION: GRANULOMA
• FOREIGN BODY GRANULOMA: absent T-cell mediated response

• IMMUNE GRANULOMA: persistent T-cell mediated response

• Tuberculosis
• Leprosy
• Syphilis
• Cat-scratch disease
• Sarcoidosis
• Crohn disease
TISSUE REPAIR
• Repair or healing- refers to the
restoration of tissue
architecture and function after
an injury
• 2 processes: regeneration and
scar formation (CT deposition)
• TGF-β: most important cytokine
for the synthesis and deposition
of connective tissue proteins
TISSUE REPAIR
• Wound strength: 70% to
80% of normal skin by 3
months
• Excessive scarring:
• Hypertrophic scar: accumulation of
excessive amounts of collagen,
does not grow beyond the
boundaries of original wound
• Keloid: scar tissue grows beyond
the boundaries of the original
wound and does not regress