Brain tumours

2015-06-08
Brain tumours/Nowotwory
ośrodkowego układu nerwowego
2015
Etiologia
• Nie jest znana
• Sugerowano związek występowania guzów
mózgu z pestycydami, herbicydami
(rolnicy, weterynarze), z polem
elektromagnetycznym (elektrycy, piloci
samolotów), polichlorkiem winylu
(pracownicy zakładów chemicznych)- brak
przekonujących dowodów
By MB
Etiologia
cd
Aetiology
• Doznane w dzeiciństwie urazy mózgu ?
• Pierwotne chłoniaki – u chorych
zarażonych wirusem HIV i u biorców
przeszczepów narządów poddawanych
immunosupresji
Mobile phone use and risk of brain
neoplasms and other cancers: prospective
study.
Benson VS, et all Int J Epidemiol:
2013 Jun;42(3):792-802
• The relation between mobile phone use and incidence of
intracranial central nervous system (CNS) tumours and
other cancers was examined in 791,710 middle-aged
women in a UK prospective cohort
• In this large prospective study, mobile phone use was
not associated with increased incidence of glioma,
meningioma or non-CNS cancers.
Effects of electromagnetic radiation of mobile
phones on the central nervous system: on
neuronal activity, metabolism, neurotrasmitter
balance and sleep; most of the reported effects
are small
At present, there is little evidence that microwave
exposure at power and frequencies related to
mobile communication could interfere with the
functional and structural integrity of the brain
Bioelectromagnetics.2003 Jan;24
CNS tumors - genetics
Genetic predisposition appears relatively
uncommon, but
• Germline mutations of tumor-suppressor
genes occur in some rare genetic
syndromes:
-NF (neurofibromatoses)
-Turcot syndrome (mutation of APC)
-Li-Fraumeni syndrome (mutation of TP53)
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2015-06-08
p 53 protein
TP53 tumor suppressor gene
• The TP53 gene located on chromosome 17 p13.1
• One of the most commonly mutated genes in
encodes a 53 kDa protein playing a role in
several cellular processes:
– cell cycle
– response of cells to DNA damage
– cell death
– cell differentiation
– neovascularization
Li-Fraumeni syndrome
human cancers
• Assists in DNA repair by inducing DNA repair
•
genes; a cell with damaged DNA that cannot be
repaired is directed by TP53 to undergo
apoptosis („a guardian of the genome”)
Individuals who inherit a mutant TP53 allele
develop Li-Fraumeni syndrome (a 25-fold
greater chance of developing a malignant tumor
before age 50)
Guzy mózgu – główne objawy
• Inactivaton of TP53 suppressor gene;
autosomal dominant cancer syndrome
• Tumors that develop in patients with this
syndrome:
Sarcomas
Breast cancer
Leukemia
Brain tumors
Carcinomas of the adrenal cortex
• Wzrost ciśnienia wewnątrzczaszkowego bóle głowy
• Napady padaczkowe
• Neurologiczne objawy ogniskowe
(ubytkowe)
1.Objawy kliniczne związane ze
wzrostem ciśnienia śródczaszkowego
2. Objawy kliniczne
• Bóle głowy
• Senność i zaburzenia świadomości
• Pogorszenie widzenia
• Nudności i wymioty
• Zaburzenia równowagi
• Sztywność karku
• Objawy neurologiczne związane z
lokalizacją guza
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Objawy ogniskowe guza płata
czołowego
• Brak inicjatywy i niechęć do działania,
apatia
• Impulsywność, drażliwość, labilność
emocjonalna
• Upośledzenie zdolności pisania
• Niedowłady ze spastycznością i
wygórowaniem odruchów ścięgnistych
Inne lokalizacje
Guz płata skroniowego
• Afazja jeżeli guz w półkuli dominującej
• Zaburzenia percepcji muzyki (amuzja)
• Zachwianie umiejętności wzrokowej oceny
stosunków przestrzennych
Clinical symptoms
• Headache - the most common presenting
• Płat ciemieniowy: różnego rodzaju
zaburzenia (po stronie przeciwnej)
• Płat potyliczny: niemal wszyscy chorzy
wykazują zaburzenia pola widzenia
symptom, is related to mass effect and
occurs in ~ 35% of patients
• Nausea
• Blurred vision
• Seizures – occur in 1/3 of patients
• Personality changes
• Local or generalized neurologic symptoms
• Astrocytes form a glial “scar” composed of
• The brain has specialized interstitial cells called
•
•
glia.
They play reparative, supportive and metabolic
role.
There are three kinds of glial cells:
– Astroglia (astrocytes) and
– Oligodendrocytes – of ectodermal origin
– Microglia – mesodermal
– Ependymal cells line the cerebral ventricles
cellular processes, but do not produce
collagen !
• Oligodendrocytes are the CNS equivalent
of Schwann cells and produce myelin
• Microglia – phagocytosis
• Tumors may derive from each kind of glial
cells
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2015-06-08
The WHO classification of tumors of the
central nervous system; Working Group
Heidelberg 2006
I. tumors of neuroepithelial tissue
A. Astrocytic tumors
1. pilocytic astrocytoma
2. diffuse astrocytoma
3. anaplastic astrocytoma
4. glioblastomas
B. Oligodendroglial tumors
C. Ependymal tumors
1.Ependymomas
2.Anaplastic ependymoma
3.Myxopapillary e.
4.Subependymomas
The WHO classification of tumors of the
central nervous system; Working Group
Heidelberg 2006
II. Tumors of cranial and spinal nerves
Schwannomas
Neurofibromas
Malignant peripheral nerve sheath tumors MPNST
III. Tumors of the meninges
Tumors of meningothelial cells
Meningiomas (15 variants)
Mesenchymal tumors
Primary melanocytic lesions
IV. Malignant lymphomas
V. Metastatic tumors
– 1.2. Oligodendroglial tumours
• 1.2.1 Oligodendroglioma (ICD-O 9450/3, WHO grade II)
• 1.2.2 Anaplastic oligodendroglioma (ICD-O 9451/3, WHO grade III)
– 1.3. Oligoastrocytic tumours
• 1.3.1 Oligoastrocytoma (ICD-O 9382/3, WHO grade II)
• 1.3.2 Anaplastic oligoastrocytoma (ICD-O 9382/3, WHO grade III)
– 1.4. Ependymal tumours
•
•
•
•
1.4.1
1.4.2
1.4.3
1.4.4
Subependymoma (ICD-O 9383/1, WHO grade I)
Myxopapillary ependymoma (ICD-O 9394/1, WHO grade I)
Ependymoma (ICD-O 9391/3, WHO grade II)
(ICD-O 9392/3, WHO grade III)
The WHO classification of tumors of the
central nervous system; Working Group
Heidelberg 2006
I. tumors of the neuroepithelial tissue
(continued)
D. Mixed gliomas
E. Tumors of uncertain origin
F. Pineal tumors
G. Embryonal tumors
1. Primitive neuroectodermal tumors (PNETs)
2. Medulloblastomas
3. Other
Tumours of neuroepithelial tissue
2007
– Astrocytic tumours Astrocytomas
• 1.1.1 Pilocytic astrocytoma, WHO grade I)
• 1.1.2 Subependymal giant cell astrocytoma WHO grade I)
• 1.1.3 Pleomorphic xanthoastrocytoma ( WHO grade II)
• 1.1.5 Anaplastic astrocytoma (ICD-O 9401/3, WHO grade III)
• 1.1.6.Glioblastoma (ICD-O 9440/3, WHO grade IV)
– 1.1.6a Giant cell glioblastoma WHO grade IV)
– 1.1.6b Gliosarcoma WHO grade IV)
• 1.1.7 Gliomatosis cerebri (ICD-O 9381/3, WHO grade III)
– 1.5. Choroid plexus tumours
• 1.5.1 Choroid plexus papilloma (ICD-O 9390/0,
WHO grade I)
• 1.5.2 ( ICD-O 9390/1, WHO grade II)
• 1.5.3 Choroid plexus carcinoma (ICD-O 9390/3,
WHO grade III)
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2015-06-08
WHO grading of tumors of CNS
– Embryonal tumours
• 1.9.1 Medulloblastoma WHO grade IV)
• 1.9.2. CNS Primitive neuroectodermal tumour
WHO grade IV)
– 1.9.2a CNS Neuroblastoma WHO grade IV)
• 1.9.3 Atypical teratoid/rhabdoid tumour (ICD-O
9508/3, WHO grade IV)
• Histological grading is a means of
predicting the biological behaviour of a
neoplasm
• In the clinical setting, tumor grade is a
key factor influencing the choice of
therapies (specific chemotherapy
protocols)
WHO grading of tumors of the CNS
WHO grading of tumors of the CNS
• Grade I lesions include tumors with low
• Grade III is reserved for lesions with
proliferative potetntial and possibility of
cure following surgical resection alone
• Grade II lesions are infiltrative in nature
and often recur; some progress to higher
grades of malignancy
HISTOLOGICAL GRADING
histological evidence of malignancy;
patients with grade III tumor receive
adjuvant radiation and /or chemotherapy
• Grade IV: cytologically malignant, necrosis
prone neoplasms associated with rapid
disease evolution and a fatal outcome
St. Anne/Mayo grading system
• Presence or absence of four histologic
• Infiltrative capacity of brain tumors – an
essential feature of malignancy (speed of
growth rather than their ability to metastasize)
•
• Unfortunately, most gliomas are characterized
by diffuse infiltration of white matter tracts,
making surgical extirpation impossible
variables:
– Endothelial proliferation – apparent
multilayering of endothelium
– Necrosis - with or without palisading of tumor
cells around a necrotic area
– Mitoses – number of mitotic figures have no
special significance
– Atypia - variation in nuclear shape or size
with hyperchromasia
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EPIDEMIOLOGY
St Mayo system
• Four grades: I, II, III, IV
– I – (ie.) pilocytic astrocytoma
– II – (ie.) oligodendrogliomas
– III – (ie.) anaplastic tumors
– IV –(ie.) glioblastoma, PNET
EPIDEMIOLOGY
• Increase with age
• Male predominance (except for
meningiomas and neurilemmomas)
• No geographic variations
• In adults two-thirds of tumors are located
supratentorially
Epidemiology
• In children the most common tumors are
the astrocytomas of the cerebellum and
brain stem (pilocytic), PNET,
medulloblastomas, ependymomas
• Adults more commonly have metastases,
glioblastomas, meningiomas, cerebral
astrocytomas, neurilemmomas of the eight
nerve
• Primary malignant central nervous system
tumors represent about 2% of all
malignant neoplasms but account for a
disproportionate rate of mortality !
• Malignant brain tumors are the leading
cause of death from tumors in children
and the third leading cause of death from
cancer in young adults
Epidemiology
Międzynarodowa Agencja Badań
nad Rakiem ; 2002
• An estimated 40 000 new cases of benign and
• Polska na tle innych krajów europejskich
malignant brain tumors are diagnosed annually
in the United States ; of these patients ~ 13 000
will die
Mayo Clin Proc 2007;82 (10)
• Brain tumors incidence has increased over the
last 20 years in all age groups, in the USA
(reasons include increase in lymphoma due to
HIV)
•
•
zajmowała 4 miejsce pod względem częstości
występowania pierwotnych nowotworów mózgu.
Nowotwory złośliwe mózgu są w Polsce
przyczyną około 2% zachorowań na nowotwory
złośliwe i około 3% zgonów nowotworowych.
Ok. 3000 nowych zachorowań/rok
NeuroOncol 2001 Jul;3(3) USA
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Krajowy Rejestr Nowotworów
Centrum Onkologii w Warszawie
• Rocznie z powodu pierwotnych nowotworów
OUN umiera w Polsce około 2300 chorych.
• Nowotwory mózgu są 10 przyczyną zgonów na
nowotwory złośliwe u mężczyzn i 9 u kobiet
Zachorowalność na nowotwory
mózgu w Polsce w latach 20082010 w zależności od wieku
Krajowy Rejestr Nowotworów
• Liczba zachorowań na nowotwory
mózgu wynosiła w 2010 roku
ponad 2700, z czego około 1380 u
mężczyzn i ponad 1350 u kobiet.
• W ciągu ostatnich trzech dekad liczba
zachorowań wzrosła około 2-krotnie
GROWTH PATTERN
• Tumors tend either to compress or to
infiltrate the brain
• Expanding tumors – partially encapsulated
or circumscribed (ependymomas,
meningiomas, metastatic carcinomas)
• Infiltrating tumors – perineuronal
satellitosis, perivascular spread, subpial
extension (neuroepithelial tu, sarcomas)
• Cells may also disperse within the
cerebrospinal fluid
IMMUNOLOGIC REACTION
METASTATIC TUMORS
• 30% of gliomas show perivascular
• Cerebral metastases – in 30% of patients
lymphocytic infiltration.
• Survival time is significantly longer in
patients with such a cellular response ?
• Patients with defects of immunity are at
increased risk of primary brain lymphomas
with cancer
• In 50% of patients with cerebral
metastases, metastatic disease is found
only in CNS
• ½ - solitary change (surgically treated)
• Sites of origin: lung, melanoma, kidney,
colon, soft tissue sarcomas, breast
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Glejaki
• Glejaki - łac. glioma, l.mn. gliomata ,
• z gr. γλία (glía) -
1. „klej”,
2. „coś lepkiego / śliskiego /
tłustego”
Astrocytomas (gwiaździaki)
• The term : „astrocytoma” was used in the
late 19th century by Virchow, but
• Firmly was introduced into
histopathological classification in 1926 by
Bailey and Cushing
Astrocytomas
• Peak incidence : fourth and fifth decades
• Involve cerebral hemispheres
• Neoplastic cells resemble normal fibrillary
(fibrous), protoplasmic (reactive) or
embryonic stellate astrocytes
• Mitotic activity – absent
ASTROCYTIC TUMORS
• Together with multiforme glioblastoma
they account for 80 to 90% of all the glial
tumors of adults.
Harvey Williams Cushing
1869 –1939
• American
neurosurgeon. A
pioneer of brain
surgery, he was the
first person to
describe Cushing’s
syndrome. He is often
called the "father of
modern
neurosurgery."
WHO grading of tumors
• Histological grading is a means of
predicting the biological behaviour of a
neoplasm. In the clinical setting, tumor
grade is a key factor influencing the
choice of therapies (adjuvant radiation
and specific chemotherapy protocols)
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2015-06-08
WHO grading of astrocytic tumors
WHO grading of astrocytic tumors
• Grade I – tumors with low proliferative
• Grade III – lesions with histological
Pilocytic astrocytoma WHO grade I
(gwiaździak włosowatokomórkowy)
Gwiaździak
włosowatokomórkowy
• A slowly growing, cystic tumor occuring in
• Komórki z wydłużonymi wypustkami,
potential and the possibility of cure
following surgical resection alone
• Grade II – tumors generally infiltrative in
nature, often recur; some tend to progress
to higher grades of malignancy (diffuse
astrocytomas to glioblastoma)
children and young adults
• Most can be surgically removed
• Rare examples even spontaneously
regress
• Long survival is the rule
evidence of malignancy; patients receive
adjuvant radiation and/or chemotherapy
• Grade IV – cytologically malignant,
mitotically active, necrosis-prone
neoplasm, often associated with rapid preand postoperative disease evolution and a
fatal outcome
przypominające włosy; ponadto jaskrawo
różowe (eozynofilne) obszary – włókna
Rosenthala
• Ze względu na odmienne cechy kliniczne i
łagodny przebieg został wyłączony z grupy
włókienkowych nowotworów
astrocytarnych
Fibrillary astrocytoma WHO grade II
(gwiaździak włókienkowy)
Pilocytic astrocytoma
Biphasic (cystic
and solid) p.
astrocytoma
• Nuclear density at
•
least twice normal
brain. Almost always
at least a few
atypical nuclei;
No necrosis or
vascular
proliferation.
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Diffuse astrocytoma
Diffuse astrocytoma
• An astroctyic neoplasm characterized by a high
• May be located in any region of CNS but
•
degree of celllular differentiation and diffuse
infiltration of neighbouring brain structures.
Typically occurs in young adults and has
tendency for malignant progression.
Incidence: epidemiological data suggest that in
Scandinavian countries and North America the
incidnece of a. has increased during the past 3
decades !
most commonly they develop
supratentorially
• 60% occur between 20-45 years of age
• Predominance for males
Glioblastoma multiforme GBM
(glejak wielopostaciowy)
GBM - history
• 1863 – Rudolf Virchow was the first one to
• The most malignant astrocytic tumor
• This tumor is among the most malignant
recognize the glial origin of this tumor
• 1888 – Bramwell is pointing out the surgical
human neoplasm with a mean total length
of disease of less than one year
• Treatment - resistant to therapeutic
interventions (surgery, very aggressive
radio- and chemotherapy)
•
GBM
Glioblastoma multiforme
• Glioblastoma is multiforme - the
heterogenity is exhibited by this tumor in
its every aspect: clinical presentation,
pathology, genetic signature, resistance to
therapy”
•
dilemma „the tumor tissue is never limited by a
capsule…it is impossible to say without
microscopical examination where the tumor
tissue ceases”
1914 – Mallory coined the term „glioblastoma
multiforme”
Iacob G ”Current data and strategy in GBM” JMedLife 2009
• Accounts for 60-75 % of all astrocytic tumors
• Adults (a peak incidence at between 45 -75
years of age)
• Preferentially located in subcortical white
•
•
matter of the hemispheres (temporal lobe)
Clinical symptoms: epileptic seizure, headache
Rapid growth and spread into the contralateral
hemisphere
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Glioblastoma – macroscopy
Glioblastoma multiforme
macroscopic features
• Poorly delineted, the cut surface shows a
variable colour with peripheral greyish and
central yellow areas of necrosis
• Red and brown foci of recent and remote
hemorrhages
• Cystic degeneration
Large tumor in the left frontal lobe
extending trough the corpus callosum
to the contralateral white matter
Invasion of the fornices and
the left ventricle
WHO Classification of tumors 2000
Glioblastoma multiforme GBM
Glioblastoma multiforme GBM
• Glioblastomas may develop from diffuse or
• In about 50% of cases they are
anaplastic astrocytomas („secondary
GBM”)
• More frequently (up to 95% of all GBM),
they manifest after a short clinical historyusually<3months- (rapid development of
increased intracranial pressure), without
evidence of a less malignant precursor
lesion („primary glioblastoma”).
characterized by the over-expression of
epidermal growth factor receptor
EGFR/HER1 or its mutational variants –
molecular therapy: anti-EGF receptor
inhibitors !
•
Eur J Pharm 625 (2009) 23-30
Epidermal Growth Factor EGF
Glioblastoma multiforme
• EGF receptor signalling can promote
• Development and progression are
tumorigenesis by
Increasing cell proliferation
Tissue invasion
Neoangiogenesis
Tumor cell chemoresistance
Inhibiting apoptosis of cancer cells
• Several inhibitors are now available in the clinic
accompanied by the formation of blood
vessels (glioblastomas are among the
best-vascularized tumors)
• In addition to necrosis, the presence of
microvascular proliferations is a hallmark
of glioblastomas
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Glioblastoma multiforme treatment
Tumor angiogenesis:
• Angiogenesis and vascular proliferation are
• Creation of new blood vessels by the induction
particulary important in the growth of
malignant gliomas. It is now evident, that
after the initial formation of malignancy,
the continued growth of a glioma is
critically dependent on its angiogenetic
potential. Clinical studies have shown that
angiogenesis inhibition is a valid approach
as a theraputic strategy against gliomas
of endotelial cells in preexisting vasculatur
• Preexisting vessels are co-opted by the tumor
• Formation of new vessels from circulating
endothelial precursor cells
Tumor angiogenesis combines all these
mechanisms
•
CurrOpin Oncol 2015,27:79-86
Cancer Treat Res 2004; 117, USA
Tumor neovascularization
There are fundamental differences between tumor
vessels and host tissue vessels
• Tumor vessels are irregular and leaky
• The endothelial cells are disorganized, irregular
and overlapped
• The basement membrane is abnormal, with
changes in matrix proteins
• There is no distinction between arterioles and
veinules
• Blood flow in tumor vessels is chaotic
• The tumor tissue is relatively hypoxic with poorly
oxygenated blood
Angiogenic factor antagonists
• The combination of various angiogenesis
inhibitors should be used for the
treatment of human cancers, bacause
these inhibitors interfere with
angiogenesis on different levels; this
therapy should be combined with chemo-,
radio- or immune therapy
New methods of the brain tumour
treatment
Treatment
• Genetic modification of normal brain cells
• The treatment of glioblastomas remains
around a neoplasm to block tumor growth
• Transduction of normal cells with an
adeno-associated virus (AAV) vector
encoding interferon – beta
• This was sufficient to completely prevent
tumor growth in models of glioblastoma
multiforme
difficult in that no contemporary
treatments are curative
• Upon initial diagnosis of GBM standard
treatment consists of maximal surgical
resection, radiotherapy, and concomitant
and adjuvant chemotherapy
Mol Ther 2008 Oct;16 (10); Maguire CA,
Harvard Medical School, Boston, USA
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GBM - epidemiology
Glioblastoma multiforme
• The incidence is fairly constant worldwide,
•
•
•
leading to the logical inference, that
environmental, geographical and nutritional
factors probably don’t play a role in this
particular tumor
The incidence is lower in blacks, than in whites,
latinos and Asians
Most GBM patients are born in winter, 40% in
February (a perinatal viral infection?)
Iacob G, GB, 2009
Glioblastoma multiforme (GBM)
• High cellularity, with
vascular proliferation
• Cytological
appearance highly
variable
„Pseudopalisading” – a histological
hallmark of the glioblastoma
• Band-like or
serpiginous foci of
necrosis
surrounded by
radially oriented
fusiform glioma
cells
• Histopathology
– Poorly differentiated, pleomorphic (fusiform,
round, multinucleated giant) cells
– Abundant necrosis (serpentine, with
pseudopalisading tumor cells) 80% of the total
tumor mass –poor prognosis
– Microvascular proliferations (multilayered
endothelial cells), often with thrombosis
– Metaplasia (foci displaying features of squamous
epithelial cells !)
GBM
• Large ischaemic
necrosis – an
essential diagnostic
feature
„Glomeruloid tufts”microvascular proliferation
• Multilayered,
mitotically active
endothelial cells
and smooth muscle
cells
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Glioblastoma multiforme
GFAP – Glial Fibrillary Acidic Protein
• Immunohistochemistry
• GFAP– labels astrocytes and some CNS
– GFAP reactivity – highly variable, but
always at least focally positive
– Vimentin expression- common
ependymal cells
• In the peripheral nervous system –
Schwann’s cells
• Negative staining is found in the skin,
connective, adipose and lymphatic tissue,
GI tract, bladder.
Treatment
GBM - chemotherapy
• GBM is highly infiltrating tumor, so surgery is
• The chloroethylating agents (carmustine)
•
always incomplete , but
advantages: relief of ICP, lowering seizure
incidence, a definitive pathology diagnosis
• GBM is radioresistant (lower oxygenation of
tumor compared with surrounding cortex)
readily penetrate the blood-brain barrier
• Methylating agents (temozolomide)-are
used in the majority of GBM clinical
protocols
• brachyterapy: stereotactic techniques to
accurately place radioactivr isotopes within the
tumor (125I)
EDL-360: A Potential Novel
Antiglioma Agent Cancer Sci Ther. ; 6(9):
370–377. 2014
• EDL-360, a tetrahydroisoquinoline (THIQ) analog, as
being highly cytotoxic to human glioma cell cultures.
EDL-360 significantly induced apoptosis in human glioma
cell lines
Skąpodrzewiaki
(oligodendrogliomata)
• Stanowią od 5 -15% glejaków
• Najczęściej w 4-5 dekadzie życia
• Zmiany lokalizują się w płatach
skroniowych lub czołowych
• Powolny wzrost – kilkuletni wywiad
dolegliwości neurologicznych/napadów
padaczkowych
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Skąpodrzewiaki
(oligodendrogliomata
• Leczenie (chirurgiczne, chemio-
radioterapia) dają przeżycie
od 10-20 lat w zmianach stopnia II wg
WHO lub
5-10 dla stopnia III
Oligodendroglioma(skąpodrzewiak)
• Well-differentiated (grade II), diffusely
infiltrating tumor
• Adults (50-60)
• Cortex and white matter of the cerebral
hemispheres
• Incidence: 5 -18% of all gliomas (Norwegian
Cancer Registry 4,2%)
• Clinical features: a long pre-operative history
of neurological symptoms (5 years)
Oligodendroglioma
Oligodendroglioma
• Histopathology
– Moderately cellular
– Rounded homogenous nuclei and swollen
cytoplasm: “honeycomb appearance”
• Microcalcifications, mucoid and cystic degeneration
• Immunohistochemistry
Well-circumscribed haemorrhagic
tumor of the frontal lobe
Recurrent tumor with bilateral,
diffuse infiltration
WHO Classification of tumors 2000
Oligodendroglioma
– No specific marker
– S-100 protein positive↑
– Vimentin may be expressed
– GFAP
Oligodendroglioma
• Guz zbudowany z monomorficznych
komórek o okrągłych jądrach
komórkowych, otoczonych przejaśnieniem
cytoplazmy (obraz „plastra miodu”)
• Bardzo liczne mikro- i makrozwapnienia
występują w 90% zmian
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Oligodendroglioma
Diagnostyka –bad.histopatologiczne
• Prognosis
• Badanie histopatologczne guza usuniętego
– Usually local recurrences
– Prognostic significance of the Ki-67
(proliferation index); more than 5% -worse
prognosis
– Median post-operative survival times range
from 3 to 5 years
Biopsja przezczaszkowa
chirurgicznie lub materiału pobranego na
drodze biopsji otwartej determinuje
rokowanie i leczenie
Diagnostyka – badania obrazowe
• MR – rezonans magnetyczny z
zastosowaniem kontrastu (wykazuje guz,
jego granice, i jego wysycenie po podaniu
kontrastu, pozawala na ocenę przestrzeni
płynowych oraz obrzęku)
• KT – tomografia komputerowa z
kontrastem (w przypadku niedostępności
MR), do oceny zmian w kościach, złamań i
zwapnień
Leczenie
• Cele leczenia chirurgicznego:
 całkowite usunięcie guza
Uzyskanie efektu cytoredukcyjnego i
• Rezonans
magnetyczny –
zmiana łagodna
(oponiak), o
wyraźnych granicach
• nowotwór złośliwy
(glejak), naciekający
okoliczne tkanki
palczastymi
wypustkami
zmniejszenie ciasnoty
wewnątrzczaszkowej
 Urządzenia wspomagające:
usg, mikroskopy
operacyjne, neuronawigacja (określa położeni narzędzi w
polu oper., identyfikację struktur uwidocznionych w
badaniach przedoperacyjnych)
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Leczenie chirurgiczne
Radioterapia
• W obrębie OUN tylko wyjątkowo możliwe
• Stereotaktyczna radioterapia
jest usunięcie nowotworu zgodnie z
obowiązującą w chirurgii onkologicznej
zasadą resekcji całkowitej guza w jednym
bloku z marginesem zdrowej tkanki zakres resekcji ograniczany jest ryzykiem
powikłań (przede wszystkim deficytem
neurologicznym) oraz sąsiedztwem
ważnych życiowo struktur
Chemioterapia
• Ograniczone znaczenie, w związku z niską
chemiowrażliwością pierwotną, wczesną
chemioopornością wtórną, barierą krewmózg oraz niekorzystnymi interakcjami
leków cytotoksycznych z innymi lekami
(głównie przeciwdrgawkowymi)
Meningiomas
frakcjonowana SFR – napromienianie
ściśle określonej i niewielkiej objętości
tkanki (średnicy 3-4 cm)
• Brachyterapia – wprowadzenie do guza
lub loży pooperacyjnej preparatów
promieniotwórczych w celu uzyskania
równomiernego rozkładu dawki
Meningiomas
Slowly growing, benign tumors attached to
the dura mater and composed of neoplastic
meningothelial (arachnoidal) cells
They typically manifest in adults (sixth
decade) and show a predominance for
women
Most are benign tumors, graded into WHO
grade I
Constitute between 13 and 26% of primary
intracranial tumors
Multiple meningiomas „clinically
malignant tumors”
• Well-demarcated, firm lesions attached to
the meninges
• Cause symptoms by the compression of
adjacent brain (seizures, headaches)
The impressions caused in the crebral hemisphere
WHO Classification of tumors 2000
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Meningiomas - aetiology
• Induced by both: low-and high-dose
radiation
• Role of sex hormones ? 2/3 of tumors
express progesterone receptors –
hormonal therapy ? (progesteronereceptor-negative meningiomas tend to be
larger than receptor positive tumors)
Histological features of meningioma
A. Meningothelial
with
intranuclear
inclusions
B. Fibrous
C. Transitional with
concentric onionlike structures
D. Psammomatous
meningioma
Histologic variants of meningiomas
• Meningothelial; cells with typical intranuclear
•
•
•
inclusions form lobules surrounded by
collagenous septae
Fibrous (fibroblastic); spindle cells resembling
fibroblasts showing fascilcles or whorl formation,
(onion-like), some psammoma bodies
Transitional (mixed); features transitional
between two previous types
Psammomatous; abundant spherical calcium
deposits
Meningiomas with greater likehood of
aggressive behaviour
• Atypical,
• Clear cell
• Chordoid
GRADE II
• Rhabdoid
• Papillary
• Anaplastic (malignant)
GRADE III
WHO Classification of tumors 2000
Meningiomas - treatment
• In most cases meningiomas can be
surgicaly removed
• The major clinical factor in recurrence is
the extent of resection (influenced by the
site of occurrence and attachment to other
intracranial structures)
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Thank you for your attention
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