TEMA - 05

Neoplasia

FISIOPATOLOGÍA
Prof. Javier Pereda
Prof. Julián Carretero
 Table of contents
1- Conceptos de tumor, neoplasia y cáncer
2- Nomenclatura
3- Características de los tumores malignos
4- Etapas del crecimiento tumoral
4.1- Iniciación
4.2- Proliferación: expansión local
4.3- Proliferación: invasión a distancia
5- Metástasis
6- Respuesta del portador
7- Marcadores tumorales
8- Manifestaciones clínicas
8.1- Manifestaciones locales.
8.2- Manifestaciones generales y a distancia.
9- Etiología y factores de riesgo
El código europeo contra el cáncer
1- Concepts of tumor, neoplasia and cancer
Neoplasia: abnormal growth of a tissue. Altered growth, differentiation and
cell death. Commonly is designated as tumor when mass of cells is
produced: “Autonomous mass of cells without purpose and not
proportional to stimulus”
 Tumor: macroscopic mass due to increased volumen of a tissue
Benign tumor:
No infiltrated, slow growth
most encapsulated
Malignant tumor:
dedifferentiated, local
invasion and metastatic
Cáncer: Group of diseases (>200) involving abnormal growth,
differentiation and cell death with the ability to extend and
invade other parts of the body
1- Concepts of tumor, neoplasia and cancer

Causes
 2- Terms
TNM system
Sufix -oma = tumor T= Tumor
N= Nodes
Benign M=Metastasis
Aden-
Mio-
Angio-

Malignant:
+Sarcoma (mesenchymal origin)
+Carcinoma (epithelial origin)
Adenocarcin-
Lymph- (lymphatic origin)
Gli- ( from glia)
Leukemia
 3- Features of malignant tumors (I)

A) Growth - differentiation - death

High proliferation rate Anaplasia Evade

apoptotic
Non-limited mechanisms
replicative potential

B) Autonomous

Angiogenic Insensitivity to
capacity Secretion of antiproliferative
Growth factors signals
 3- Features of malignant tumors (II)

C) Monoclonality?
D) Disorders of metabolism
E) Morphologic disorderds
 Big nucleus
 Genetic unstability
F) Metastatic capacity
The hallmarks of cancer. Hanahan & Weinberg, Cell 2011
 4- Stages of tumor growth
4.1 – Initiation (I): monoclonality?
a) Accumulation of injury: endogenous or exogenous
Physical (e.g. Rx, UV)
Chemical (e.g. tobacco, benzo[a]pyrenes, diet)
Biological (e.g. papilloma virus)

b) Activation of proto-oncogenes
c) Inactivation of suppressor genes
d) Activation of telomerase
e) Inhibition of apoptosis
Oncogenes

Normal proliferation Suppressor genes Activation of

Differentiation (G0) proliferation
 4- Stages of tumor growth (II)
4.1 – Initiation (II):
Oncogenes: activated proto-oncogenes (usually by mutations) coding
oncoproteins which promote autonomous growth
Regulate differentiation and proliferation
• Positive regulators of cell cycle (e.g., CDK4)
• Transcription factors (e.g., FOS, MYC).
• Growth factor receptors (e.g., EGFR).
• Protein kinases and G proteins (e.g., PI3K, RAS).
• Proteins regulating apoptosis (e.g., BCL2 is antiapoptotic).
• Etc.
They activate; dominant mutación dominante mainly in somatic cells

Normally NON
heritable
 4- Stages of tumor growth (III)
4.1 – Iniciación (III):
Suppressor genes: encode proteins involved in growth and
apoptosis inhibitory mechanisms
E.g.:
• pRB (protein of retinoblastoma)
• p53 “Guardian of the genome” Detects disorders of DNA.
Restores, inhibits or kills the cell if it has mistakes in its genome.

Inhibition; recessive mutation (Both alleles shoud be mutated).

May appear in germinal cells

May be heritable
(susceptibility is inherit in case of receiving
one mutated allele e.g. BRCA1 in breast
cancer)
 4- Stages of tumor growth (IV)
4.2- Proliferation: local expansion (I)
 Increased mitosis leads to genomic instability and
to new mutations
 Dedifferentiation (anaplasia)
 Competition; selection of the worst clones
 Limiting factor : angiogenesis
 4- Stages of tumor growth (V)
4.2- Proliferation: local expansion (II)
 Extracellular matrix adhesion
 Degradation enzymes secretion
 Migration
 Autocrine factors secretion
 Lose of cell-to-cell adhesion
 Angiogenic factors secretion
 4- Stages of tumor growth (VI)
4.3- Proliferation: distant invasion
 Intravasation: go inside lymphatic or blood vessel
Lymphatic s.: no basal membrane
Blood s.: vessels are more permeable in tumors

 Circulation: go through blood or lymph to other place

Lymphatic s.: may stop in the first lymphatic node (sentinel)
or further and/or reach blood and/or produce inflammation
Blood s.: 1 of 1000 survive. Platelets and leukocytes may
aggregate helping or not neoplasia
 Extravasation: endothelial cells or basal membrane
adhesion and come out of the vessel.

 Metastasis: set of active neoplastic cells, coming from a tumor at a

different site with no spatial relation to it.
 5. Metastasis
“set of active neoplastic cells, coming from a tumor at a
different site with no spatial relation to it”
Clinical importance.
 In favor:
─ Anatomy
─ Favorable microenvironment
─ Presence of adhesion molecules or receptors
Against:
─ Angiogenesis is needed
─ Immunologic supervision
 6- Carrier response

Passive support Gives nutrients

Receives products
Defensive response unspecific
Specific

To avoid immune system:

 Low antigenic capacity
 Disguising
 Expression altered
 Blockade of immune response
 7- Diagnosis
 Biopsy
 Image diagnosis: CT: Computerized Tomography - MAGNETIC RESONANCE -
PET: Positron emission tomography

 Tumoral markers:
Transformation and anaplasia
Disorders of metabolism

Secretion of new molecules (or great amount of normal

molecules).
NOT DIAGNOSIS ONLY WITH THEM
USSEFUL FOR FOLLOW-UP
E.G:
• PSA (prostatic specific antigen)
• CA 125 (antigen of ovarian cancer)
• Carcinoembrionary antigen (CEA) (characteristic of colon cancer).
• α-fetoprotein (characteristic of hepatic cancer).
 8- Clinical manifestations
8.1- Local manifestations.
 Presence of weird mass, palpable or demonstrable by imaging

 Pain by compression or irritation of nerve endings

 Functional Insufficiency of affected organ

 Space conflict, if growth is in not distensible cavities

 Stenosis or obstruction of empty organs.

 Ulcerations Disorders by angiogènesis

and necrosis

 Disruption of blood vessels and hemorrhages.

 Hematuria
 Melena
 Hemoptysis
 8- Clinical manifestations (II)
8.2- General and distant manifestations.
 Asthenia, anorexia, paleness, thinning (tumoral cachexia) Lose of
weight
 Hematologic disorders (anemia, leukocytosis, neutrophilia, monocytosis, acute
phase reactants)

 Symptoms of inflammation, fever, opportunist infections.

 Paraneoplastic syndromes: set of manifestations in systems or organs far

from tumor and not produced by metastatic growth.

E.G.: pathologic consequences of ectopic hormone secretion

(ACTH or ADH in lung cancer)
 9- Etiology and risk factors
Carcinogenesis implies acquisition of mutations

 Role of inheritance.
 Exposition to risk factors (radiations, pesticides, hormonal therapies,
contamination, smoking,...).
 Role of immune system (stress, virus, immunosuppression,…)
 Increased incidence of cancer in senescence and aging.
 Importance of an early diagnosis.
 10- El codi europeu contra el càncer

1. No fume; si fuma, abandone este hábito. Si no consigue dejar de fumar, no

fume en presenciade no fumadores.
2. Evite la obesidad.
3. Realice alguna actividad física vigorosa todos los días.
4. Aumente su ingesta diaria de frutas, verduras y hortalizas variadas: coma al
menos cinco raciones al día. Limite el consumo de alimentos que contienen
grasas de origen animal.
5. Si bebe alcohol, ya sea cerveza, vino o bebidas de alta graduación, modere el
consumo a un máximo de dos consumiciones diarias, si es hombre, o a una, si
es mujer.
6. Tome precauciones para evitar la exposición excesiva al sol. Es especialmente
importante proteger a niños y adolescentes. Las personas que tienen tendencia
a sufrir quemaduras deben tomar medidas protectoras durante toda la vida.
7. Aplique de forma estricta la legislación destinada a prevenir cualquier
exposición a sustancias carcinogénicas. Siga las instrucciones de seguridad y
salud sobre el uso de estas sustancias que pueden causar cáncer. Respete las
normas dictadas por las oficinas nacionales de protección radiológica.
 El codi europeu contra el càncer
Acude al médico si
7. Nota cualquier ganglio o úlcera que no cicatriza, una peca
que cambia de color, de tamaño, o si aparece una
hemorragia inexplicable.
8. De forma persistente presenta problemas como: tos,
ronquera, cambios en los hábitos de micción o defecación,
o perdida de peso inexplicable. A los 50 años prueba de
detección de cáncer de colon.
9. Haga revisiones ginecológicas regulares. Detección a los
25 de cáncer de cuello de útero.
10. Comprobar la aparición de nódulos en los pechos.
Detección a los 50 años del cáncer de mama
11. Participe en programes de vacunación contra hepatitis B.