CNS Pathology - III Motor Neuron Diseases Intracranial Tumours

CNS Pathology - III Motor Neuron Diseases Intracranial Tumours

CNS Pathology - III
Motor Neuron
Diseases
ALS
Intracranial Tumours
Jaroslava Dušková
Inst. Pathol. 1st. Med. Fac. Charles University, Prague
NEURON
Axon
terminals
Dendrites
Cell
body
Node of
Ranvier
Schwann
cell
Myelin sheet
Motor Neuron Damage
Axonopathies






toxic
toxoinfectious
metabolic (drugs!)
avitaminoses
traumatic (shearing injury)
malignancy associated
Motor Neuron Diseases
Neuronopathies

Poliomyelitis anterior acuta

Poliomyelitis anterior chronica

Sclerosis amyotrophica lateralis ALS

Paralysis progressiva bulbaris
Tractus
corticospinalis
Motor Neuron Diseases
2.
1. paralysis spastica spinalis
2. paralysis progressiva bulbaris C
m. Aran - Duchenne
(poliomyelitis ant. chronica)
T
m. Werdnig Hoffmann
L
myatonia (amyotonia) congenita
Oppenheim
SMA –
1. + 2. ALS
Spinal
Muscular
Atrophy
1.
Classification of Disorders Affecting
Motor Neurons
Primary

– idiopathic (ALS)
– inherited (SMA)
genus Lathyrus sweat pea
Secondary

–
–
–
–
–
–
infective :acute poliomyelitis, HIV, syphilis, prions
metabolic: hyper/hypo thyr, hyperparathyr…
immune. paraproteinemia
Environmental/toxic: Pb, Sb, Cd…neurolathyrism
vascular
paraneoplastic: nHML, MLH
Multisystem neurodeg. diseases affecting motor neurons

–
–
–
–
Western Pacific ALS /Parkinson/dementia complex
spinocerebellar degeneration
Huntington´s disease
prionoses
Neurolathyrism
is a neurological
disease of
humans and
domestic
animals, caused
by eating certain
legumes of the
genus Lathyrus
sweat pea
β-ODAP
= 3-N-oxalyl-L-2,3diaminopropionic acid
The level of this compound in the dry
seeds varies depending on genetic
factors and environmental conditions.
motor neurons
Spinal Muscular Atrophy -Type I - m. Werdning- Hoffman – autosomal rec. – floppy babysurvival not beyond 3 years of age
Amyotrophic Lateral Sclerosis
Def.
motor neuron disease affecting
both 1st and 2nd neuron of pyramidal
tract
5-10% familiar, autosomal dominant SOD I
(SuperOxidDismutase) gene on chromosome 21
Amyotrophic Lateral Sclerosis
Clinical features
10 – 60 yrs
 palsies spastic/ feeble
 neurogenous hand muscle atrophy
„simian hand“
 bulbar disturbances
 death in several years (aspir. bpn.)
 start:
Amyotrophic Lateral Sclerosis
Etiopathogenesis
(Greenfield´s Neuropathology 9th ed., 2015)
„IDIOPATHIC“

genetic factors (9, 18, 21…ALS 1…ALS5 types)

mostly sporadic forms

5-10% autosom. dom. familial form – starts 10 years
earlier

autosomal recessive described as well

environmental factors – toxic, infectious

autoimmune
Amyotrophic Lateral Sclerosis
Morphology
macro:
micro:

atrophy of gyrus praecentralis

atrophy of ventral roots

atrophy of muscles („simian“ hand)

loss of neurons (GPC, ant. horns)

funicular demyelinisation

atrophy (denervation type)
Atrophia musculorum interossearum manus neurogenes
ALS
A
L
S
ALS
ALS
anterior
roots
atrophy
ALS – medulla oblongata
ALS – medulla oblongata
MS
ALS
ALS - tractus corticospinalis anterior
palor
ALS - tractus corticospinalis lateralis
A
L
S
ALS - tractus corticospinalis lateralis
PPB
ALS
Paralysis progressiva bulbaris
Clinical features
fonation and deglution disturbances
tachycardia, dyspnoe (insuff. n. X)
Morphology
neuronal atrophy nn. IX, X, XI, XII.
chewing muscles, tongue
Prognosis
fatal (aspir. bpn.)
Case Report
man 52 yrs (driver)
ALS
*1943
†1999
July 1991
physical exercise
(mountain bike trip)
first symptoms
Disturbance of
 pronounciation
transient , later standing expressive aphasia


swallowing
central hemiparesis dx., later sin.
Progression during 4 years death from
bronchopneumonia
Guerreiro R et al.:
SnapShot: Genetics of ALS and
FTD.
Cell. 2015 Feb 12;160(4):798

Frontotemporal dementia (FTD) and amyotrophic lateral
sclerosis (ALS) are considered to be part of a spectrum.
Clinically, FTD patients present with dementia frequently
characterized by behavioral and speech problems. ALS patients
exhibit alterations of voluntary movements caused by
degeneration of motor neurons. Both syndromes can be present
within the same family or even in the same person. The genetic
findings for both diseases also support the existence of a
continuum, with mutations in the same genes being found in
patients with FTD, ALS, or FTD/ALS.
CNS neoplasms
 primary CNS neo:
– approx. 2% of all cancers
– approx. 20% of cancers in children under 15

secondary
– 25-50% (lung, breast, kidney, melanoma)

fewer than 5% associated with hereditary syndromes
(NF1,NF2, tuberous sclerosis, von Hippel-Lindau,
…MEN I)
CNS Neoplasms - Manifestation



epilepsy
focal deficits –palsies
raised intracranial pressure
– headache
– vomiting (esp. in children)
– clouding of consciousness, coma
– papiledema

hydrocephalus
Epilepsy – Epileptic Syndromes
an „umbrella diagnosis“ for a broad
family of neurologic disorders
characterized by seizures of different
quality
 after stroke the commonest neurological
disorder
 up to 2% of population worldwide

Epilepsy – Epileptic Syndromes

Primary
– genetic disorders of ion channels, brain neuronal
architecture – many different genes involved

Secondary
–
–
–
–
brain malformations, metabolic diseases
glioses (postinfectious, posttraumatic, postnecrotic…)
neurodegenerations ( m. Alzheimer, m. Huntington…)
NEOPLASMS
Epilepsy – Epileptic Syndromes
Morphology – not always provable
– dysgenetic foci of cortex
– hippocampal sclerosis
– secondary causative pathologies
– secondary posttraumatic lesions caused by
seizures
WHO – CNS - 2007
WHO (2007) Classification
of Tumours of the CNS
(4th ed. - 1979, 1993, 2000, 2007)
- 134 nosology units
WHO (2007) Classification of of Tumours of the CNS
A new introductory chapter titled
„WHO Grading of Tumours of
the Nervous System“
WHO Grading of Tumours of the
Nervous System (2007)
G
I - well circumscribed, slowly progressing,
cured by resection
II – infiltrative, low proliferation, a higher
likelihood of recurrence
G
III – histologically malignant, require more
aggressive adjuvant therapy
G
G
IV – highly malignant, rapidly fatal
WHO (2007) Classification of
Tumours of the CNS

NEUROEPITHELIAL TISSUE T.

TUMOURS OF PERIPHERAL NERVES

TUMOURS OF THE MENINGES

LYMPHOMAS & HAEMOPOIETIC NEO

GERM CELL TUMOURS

TUMOURS OF THE SELAR REGION

METASTATIC TUMOURS
WHO Histological Typing of Tumours of the CNS
TUMORS OF THE MENINGES
 Tumours
of meningotelial cells
– meningioma
 Mesenchymal non meningotelial
– lipoma, angiolipoma, hibernoma, solitary fibrous tumor,
fibrosarcoma, MFH, leiomyoma, rhabdomyoma,
rhabdomyosarcoma,
chondroma,chondrosarcoma,osteoma, osteosarcoma,
hemangioma epith. hemangioendothelioma,
hemangiopericytoma,angiosarcoma,Kaposi sarcoma
 Primary
melanocytic lesions
– diff. melanocytosis, melanocytoma, malignant melanoma
convexity
parasagital
85
61
24
fossa cerebri ant
media
post
45
27
• middle aged, elderly
35
19
• risk fc. :irradiation
12
• mutation of NF2 (22q)
• mostly G 1
33
2
14
8
15
30
Topic frequency of
MENINGEOMA
falx
n. olfactorius
sella
os sphenoides
n. opticus
tentorium
medulla
other
multiple
ICD-O 9530/0
Meningeoma
parasellare
Meningeomata multiplicia cum impressione corticis cerebri
Meningeoma GI
ICD-O 9530/0
G I- benign
G II- atypical
G III – anaplastic
(malignant)
G IV - exceptionally
Meningeoma – Age & Sex Distribution
Meningeoma
fibrosum
Meningeoma
meningoteliomatosum
Meningeoma
psammomatosum
Meningeoma
transitorium
Angioma racemosum cerebri et
meningum
Hemangioma cavernosum
ICD-O 9121/0
Types of CNS vascular malformations




arteriovenous
capillary teleangiectasia
cavernous hemangioma
venous angioma
Hemangioma – malformatio arteriovenosa
Chordoma ICD-O 9370/3
• remnants of notochord
• sacral 60%
• sphenooccipital 25%
• cervical 10%
• thoracolumbal 5%
WHO Histological Typing
of Tumours of the CNS
NEUROEPITHELIAL
–
–
–
–
–
–
–
–
–
astrocytic
oligodendendroglial
mixed
ependymal
choroid plexus
neuronal and mixed neuronal-glial
neuroblastic
pineal cell
poorly differentiated, embryonal
Astrocytic tumours
DIFUSELY INFILTRATING ASTROCYTOMAS
• difuse – G2
• anaplastic - G3
Age Distribution
PILOCYTIC
ASTROCYTOMA –
BRAF(V600E)
mutation,
• glioblastoma – G4
IDH1 immunocytochemistry
Astrocytoma diffusum
Astrocytoma fibrillare
Astrocytoma
A. protoplasmicum
A. anaplasticum (GIII)
Astroblastoma (GIII)
Astrocytoma pilocyticum (juvenile) –
ICD-O 9421/1
WHO G I
•
•
•
BRAF(V600E)
mutation
•
•
Does not share genetic
abnormalities of astrocytoma.
Better prognosis.
Associated with
neurofibromatosis type I.
Children & young adults.
Often cystic, better
circumscribed
Pilocytic Astrocytoma
Pilocytic
Astrocytoma
Pilocytic Astrocytoma - syringomyelia
Pilocytic Astrocytoma
del 1p, 19q
Oligodendroglioma ICD-O 9450/3
GII-III
Oligodendroglioma
Oligoastrocytoma
ICD-O 9382/3
Glioblastoma (multiforme) ICD-O 9440/3
WHO – G IV
Glioblastoma multiforme ICD-O 9440/3
Glioblastoma
multiforme
WHO Histological Typing
of Tumours of the CNS
NEUROEPITHELIAL
–
–
–
–
–
–
–
–
–
astrocytic
oligodendendroglial
mixed
ependymal
choroid plexus
neuronal and mixed neuronal-glial
neuroblastic
pineal cell
poorly differentiated, embryonal
Ependymoma
ICD-O 9391/3
associated
frequently with
NF 2
Ependymoma
Ependymoma
ICD-O 9391/3
Ependymoma
Ependymoma
sacrale
WHO Histological Typing
of Tumours of the CNS
NEUROEPITHELIAL
– astrocytic
– oligodendendroglial
– ependymal, choroid plexus
– pineal cell: pineocytoma, pineoblastoma,
intermediate; germinal cell tumours
– neuronal
– poorly differentiated, embryonal
Pineocytoma
ICD-O 9361/1
G II
Pineocytoma
ICD-O 9361/1
G II
„Pinealoma anisomorphe“ – seminoma
WHO Histological Typing
of Tumours of the CNS
GERMINAL TUMOURS
– germinom
– embryonal carcinoma
– choriocarcinoma
– teratoma
– mixed
WHO Histological Typing
of Tumours of the CNS
TUMOURS OF THE SELLAR REGION
craniopharyngeoma, pituitary tumours
Craniopharyngeoma
Craniopharyngeoma
WHO Histological Typing
of Tumours of the CNS
NEUROEPITHELIAL
–
–
–
–
–
–
–
–
–
astrocytic
oligodendendroglial
mixed
ependymal
choroid plexus
neuronal and mixed neuronal-glial
neuroblastic
pineal cell
poorly differentiated, embryonal

medulloepithelioma, ependymoblastoma, medulloblastoma,
medullomyoblastoma melanotic meduloblastoma, supratentorial PNET,
neuroblastoma, ganglioneuroblastoma, atyp. rhabdoid tumour
Medulloblastoma ICD-O 9470/3
G IV
Medulloblastoma
cerebelli
Isochromosom 17q
WHO Histological Typing
of Tumours of the CNS
TUMOURS OF CRANIAL & PERIPHERAL NERVES
–
neurilemmoma
–
neurofibroma
–
perineurioma
–
malignant peripheral nerve sheet tumour /MPNST/
Neurilemmoma
ICD-O 9560/0
Neurofibroma
WHO Histological Typing
of Tumours of the CNS
LYMPHOMAS AND HAEMOPOIETIC NEO
 ML (mostly B-cell) - DLBCL
 plasmocytoma
 granulocytic sarcoma
Lymphoma malignum
Lymphoma malignum (prim. cerebri)
Pseudotumours (diff. dg.!)
Cysts
– Rathke´s cyst
– epidermoid cyst
– dermoid cyst
– colloidal cyst of the 3rd ventrikle…
VASCULAR MALFORMATIONS
– capillary teleangiectasia
– a.– v. malformation
Cystis dermoides
WHO Histological Typing
of Tumours of the CNS
METASTATIC TUMORS
mostly carcinomas !!!
…… melanoma…..
Metastases adenocarcinomatis meningum et cerebri
Carcinosis meningum
Carcinoma diffusum ventriculi (ad meningos metastaticum)
M57. History of melanoma.
Melan A
M73. History of bronchogenic carcinoma
MGG
MGG
TTF1
TTF1 -control
Hippocampus