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General Pathology
Basic Principles of Cellular and Organ
Pathology
Oncology - II
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
General Oncology - I
Disorders of the cell proliferation and growth (hypertrophy, hyperplasia,
metaplasia)
Neoplasms – disorders of cell proliferation and differentiation
Molecular biology of neoplasia - oncogenesis
Host - neoplasm interactions
General Oncology - II
Biology of the neoplastic growth
Precanceroses (& pseudotumours)
Classification of the neoplasms
Methods of tumour diagnostics
Neoplasm prognostification
Neoplasia (Tumour) DNA disease:
Stepwise accumulation
of genetic abnormalities
Escape of
immunological clearing
systems
Dejeans N. et al: Addicted to secrete – novel concepts and targets in cancer
therapy. Trends in molecular medicine, 20, 5, May 2014, pp.242–250
General Oncology - II
Biology of the neoplastic growth
Precanceroses (& pseudotumours)
Classification of the neoplasms
Methods of tumour diagnostics
Neoplasm prognostification
NEOPLASIA – classification
BEHAVIORAL
benign
borderline
malignant
histological vs. clinical behaviour
NEOPLASIA – growth
benign expansive
borderline - locally
destructive
malignant infiltrative
METASTASES
Clinical manifestation of neoplasmsBenign
no
mass (palpable or visible on
imaging)
compression
obstruction
pressure
bleeding
hormonal production
Malignant
no
mass
pressure
bleeding hormonal production
destruction
inflammatory
response
distant metastases
Borderline
combined…!
Invasion & Metastasis - steps
Invasion into the extracellular matrix - ECM
– dyscohesion of cells – loss of E-cadherine
– ECM degradation – proteolytic enzymes (Matrix
Metaloproteinases – MMPs, cathepsin D, urokinase plasminogen activator)
– migrationepithelio-mesenchymal conversion
ameboid migration or
groups
Angioinvasion – esp. into newly formed vessels
Extravasation – local factors promoting or inhibiting the subsequent growth tropism – adhesion molecules, chemokines
late metastases - dormancy
Metastases - pathways
seeding (body cavities)
lymphatic spread
hematogenous spread
cellular embolism!!!
ca pulmonis
meta gl. suprarenalis
lymphangiopathia
carcinomatosa
Metastasis lnn.
tracheobronchialium
Rapidity of Tumour Growth
Energy metabolism reprogrammed –Warburg effect – aerobic glycolysis shift – increase in glucose
uptake visible on PET
Evasion of the immune system – aberrant
self proteins expressed – recognized by CD8+ cells
– selective outgrowth of antigen-negative variants
– loss of reduced expression of histocompatibility molecules
– immunosuppression
– antigen masking – external glycocalyx molecules
– downregulation of T– cell co-stimulating molecules
NEOPLASIA – macroscopy
whittish/grayish mass yellow nodule lipoma, clear cell kidney carcinoma,
adrenocortical adenoma
red nodule hemangioma
brown nodule nevocellular nevus, melanoma, pigm. basalioma
organ enlargement leukemia
organ consolidation (& superficial ulceration)
tongue carcinoma
organ softening – necrosis glioblastoma
branched outgrowth papilloma, villous adenoma
cystic (cystopapillary) cystadenoma, ca
NEOPLASIA – cytology
Benign similar to nonneoplastic
Malignant cellular pleomorphism
NUCLEAR FEATURES:
hyperchromasia
(polyploidy, aneuploidy)
rough chromatine structure
irregular nuclear outline
large and/or multiple nucleoli
!or undifferentiated monotonous cellularity!
General Oncology - 2
Biology of the neoplastic growth
Precanceroses (& pseudotumours)
Classification of the neoplasms
Methods of tumour diagnostics
Neoplasm prognostification
Pseudotumors
cysts
pseudocysts
deposits of pathol. material
(gout, ganglion, amyloid)
inflammatory pseudotumors(tuberculoma)
hyperplasia (esp. nodular)
embryonal development disturbance (choristia, hamarcia)
Urocystolithiasis
Hyperplasia
adenomyomatosa
prostatae
Hypertrophia
trabecularis
tunicae
muscularis
vesiace
urinariae
Precanceroses (preblastomatoses)
Def.:
Pathology lesions known to
increase statistically the frequency
of malignancies
Precanceroses exhibit some but not all features of malignancy on genetic,
microscopy, and macroscopy level
Precanceroses (preblastomatoses)
most pseudotumorous
processes with dysplasia
features
dysplastic lesions looking not
like tumours (SIL, intest. metaplasia
with dysplasia)
Nonneoplastic
Growth Disturbances – II
repair
hypertrophy / atrophy
hyperplasia
metaplasia dysplasia anaplasia – undifferentiation
Dysplasia
Definition:
- disturbance of cell growth, maturation, architecture
(frequently, but not always preneoplastic condition)
Diagnosis early less complicated therapy
pseudotumors– clinical
– morphological
precanceroses
– screening
– morphological
General Oncology - II
Biology of the neoplastic growth
Precanceroses (& pseudotumours)
Histogenetic classification of the
neoplasms
Methods of tumour diagnostics
Neoplasm prognostification
NEOPLASIA – classification
HISTOGENETIC
mesenchymal epithelial neuroectodermal mixed germ cell, teratoma, choriocarcinoma
mesothelioma
General Oncology - I
Disorders of the cell proliferation and growth (hypertrophy, hyperplasia,
metaplasia)
Neoplasms – disorders of cell proliferation and differentiation
Molecular biology of neoplasia - oncogenesis
Host - neoplasm interactions
General Oncology - II
Biology of the neoplastic growth
Precanceroses (& pseudotumours)
Classification of the neoplasms
General Oncology - III Methods of tumour diagnostics
Neoplasm prognostification and
Prediction of the response to the therapy