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

Tumour

swelling of any kind

NEOPLASIA

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…!

Unique codes

for neoplastic

diseases

overcome the

variable

frequently

historic

terminology…

Adenoma

polyposum

tubulovillosum

recti

M 8263/0

Craniopharyngioma

M 9350/1

Ependymoma

M 9391/3

Carcinoma renis

M 8317/3

Ca recti –

exophytic

growth

M 8140/3

ca ventriculi – endophytic growth

M 8140/3

Lymphoma malignum (prim. cerebri)

infiltrative growth

Carcinoma – infiltrative growth

AE 1-3

Metastasis

Def.:

development of secondary

tumour foci in the distant

places

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!!!

Peritonitis carcinomatosa – ca ventriculi

alc.blue pH 2,5 M 8140/6

Metastases multiplices hepatis – ca pancreatis

M 8500/6

ca pulmonis

meta gl. suprarenalis

lymphangiopathia

carcinomatosa

Metastasis lnn.

tracheobronchialium

M 8310/3

M 8310/6

M 8310/6

M 8310/6

Embolia carcinomatosa

Embolia carcinomatosa

Nephroblastoma

– Wilms´ tumour

M 8960/3

Nephroblastoma – Wilms´ tumour

M 8960/6

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

Leiomyoma

intramurale corporis

uteri

Glioblastoma

multiforme

Lipoma intestini tenuis

Clear cell kidney

carcinoma

10 mm

Hemangioma

Naevi naevocellulares (N. verrucosus)

Melanoma

Splenomegalia

(CML)

norm

ca ventriculi – endophytic growth

Glioblastoma multiforme

Glioblastoma

multiforme

NEOPLASIA – histological

architecture

solid

glandular

papillary

cystopapillary

dissociated

Neurilemmoma M 9560/0

Papillocarcinoma

vesicae urinariae

M 8130/21

M 8130/23

Papilloma M 8120/0

Ca endometrii endometroides 25 yrs

Adenocarcinoma endometrioides endometrii

norm, day 8

Metastases adenocarcinomatis meningum et cerebri

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!

EMA

TGB

vimentin

Undifferentated (anaplastic) carcinoma

General Oncology - 2

Biology of the neoplastic growth

Precanceroses (& pseudotumours)

Classification of the neoplasms

Methods of tumour diagnostics

Neoplasm prognostification

Pseudotumors

Definition:

- pathological lesions of

different etiology masquerading

real neoplasms

Pseudotumors

cysts

pseudocysts

deposits of pathol. material

(gout, ganglion, amyloid)

inflammatory pseudotumors(tuberculoma)

hyperplasia (esp. nodular)

embryonal development disturbance (choristia, hamarcia)

Eutopic

pregnancy

Ectopic

pregnancy

Graviditas tubaria

Mamilla accessoria

Mastopathia virilis - gynaecomastia

Tumor Schlofferi

Macrocystosis renum

Gout

Arthritis uratica

Urocystolithiasis

Hyperplasia

adenomyomatosa

prostatae

Hypertrophia

trabecularis

tunicae

muscularis

vesiace

urinariae

Toxoplasmosis cerebri cyst

Trichinosis

Cystis

parasitaria

hepatis

(Echinococcus)

CYST is not always

a pseudotumour !

Cystis dermoides M 9084/0

Hydrosalpinx

„chocolate“ cyst

on the ovary

surface

ovary

endometriosis

Leukoplakia

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)

Junctio

squamocolumnaris

repair

Metaplasia squamocellularis

L SIL

CIN I

PSEUDOTUMORS and

PRECANCEROSES (preblastomatoses)

pseudotumorsprecanceroses

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