cns pathology - iii motor neuron diseasespau.lf1.cuni.cz/file/6420/cns-iii-mndtu.pdf · cns...
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CNS Pathology - III
Motor Neuron Diseases
Jaroslava Dušková
Inst. Pathol. 1st. Med. Fac. Charles University, Prague
Intracranial Tumours
ALS
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Axon
terminals
Node of
Ranvier
Schwann
cellMyelin sheet
Dendrites
Nucleus
Cell
body
NEURON
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Motor Neuron Damage
Axonopathies
toxic
toxoinfectious
metabolic (drugs!)
avitaminoses
traumatic (shearing injury)
malignancy associated
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Motor Neuron Diseases
Neuronopathies
Poliomyelitis anterior acuta
Poliomyelitis anterior chronica
Sclerosis amyotrophica lateralis ALS
Paralysis progressiva bulbaris
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Tractus corticospinalis
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Motor Neuron Diseases
1. paralysis spastica spinalis
2. paralysis progressiva bulbaris C
m. Aran - Duchenne T(poliomyelitis ant. chronica)
m. Werdnig Hoffmann Lmyatonia (amyotonia) congenita Oppenheim
1. + 2. ALS
1.
2.
SMA –Spinal
Muscular
Atrophy
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Classification of Disorders Affecting
Motor Neurons
Primary
– idiopathic (ALS)
– inherited (SMA)
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
genus Lathyrus sweat pea
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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.
Neurolathyrism
is a neurological
disease of
humans and
domestic
animals, caused
by eating certain
legumes of the
genus Lathyrus
sweat pea
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motor neurons
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Spinal Muscular Atrophy -Type I - m. Werdning- Hoffman – autosomal rec. – floppy baby-
survival not beyond 3 years of age
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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
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Amyotrophic Lateral Sclerosis
Clinical features
start: 10 – 60 yrs
palsies spastic/ feeble
neurogenous hand muscle atrophy
„simian hand“
bulbar disturbances
death in several years (aspir. bpn.)
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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
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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)
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Atrophia musculorum interossearum manus neurogenes ALS
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A
L
S
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ALS
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ALS
anterior
roots
atrophy
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ALS – medulla oblongata
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ALS – medulla oblongata
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ALS
MS
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ALS - tractus corticospinalis anterior
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ALS - tractus corticospinalis lateralis
palor
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A
L
S
ALS - tractus corticospinalis lateralis
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PPB ALS
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Paralysis progressiva bulbaris
Clinical features
fonation and deglution disturbancestachycardia, dyspnoe (insuff. n. X)
Morphology
neuronal atrophy nn. IX, X, XI, XII.
chewing muscles, tongue
Prognosis fatal (aspir. bpn.)
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Neurological control of normal speech
Corticobulbar tracts from both of the motor cortices send signals down to the nuclei of the following nerves:
Vagal nerve
Facial nerve
Hypoglossal neve
Phrenic nerve
The motor aspects of speech influenced by the extrapyramidal system via the basal ganglia and the cerebellum.
Phonation: the production of sounds, a result of the vocal cords in the larynx.
Articulation: contractions of the muscles of the various other structures involved in speech, ie the pharynx, palate, tongue and lips. These muscle contractions change the vocal sounds from the larynx, thus resulting in noises recognised as words.
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Case Report ALSman 52 yrs (driver) *1943 †1999
July 1991
physical exercise (mountain bike trip)first symptoms
Disturbance of
pronounciationtransient , later standing expressive aphasia
swallowing
central hemiparesis dx., later sin.
Progression during 4 years death from bronchopneumonia
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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.
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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)
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CNS Neoplasms - Manifestation
epilepsy
focal deficits –palsies
raised intracranial pressure
– headache
– vomiting (esp. in children)
– clouding of consciousness, coma
– papiledema
hydrocephalus
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Ellison & Love.
NEUROPATHOLOGYA reference texts of CNS pathology.
Mosby 2004
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Common
locations of
various
neuroepithelial
neoplasms
Ellison & Love.
NEUROPATHOLOGY
A reference texts of CNS pathology.
Mosby 2004
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The mass effect of a cerebral neoplasm
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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
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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
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Epilepsy – Epileptic Syndromes
Morphology – not always provable
– dysgenetic foci of cortex
– hippocampal sclerosis
– secondary causative pathologies
– secondary posttraumatic lesions caused by
seizures
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WHO – CNS – 2016 – revised 4th edition
117 contributors from
20 countries revised
the 2007 classification.
Three-day Consensus
conference by a
Working group of 35
neuropathologists.
Molecular parameters
incorporated into the
classification
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WHO Classifications
of Tumours of the CNS
1979, 1993, 2000, 2007,
- 134 nosology units
revised 4th 2016
- 154 nosology units
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WHO Grading of Tumours of the
Nervous System (2016)
G I - well circumscribed, slowly progressing,
cured by resection
G II – infiltrative, low proliferation, a higher
likelihood of recurrence
G III – histologically malignant, require more
aggressive adjuvant therapy
G IV – highly malignant, rapidly fatal
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WHO - CNS - 2016
154 nosology units
(WHO 2007 134 nosology units)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 1/6
Gliomas
diffuse astrocytic and oligodendroglial – GII –IV
other astrocytic – e.g. pilocytic, subependymal GI-III
ependymal tumours GI-III
other gliomas - angiocentric, astroblastoma GI-III
tumours of the choroidal plexus – papilloma, atypical
papilloma, papillocarcinoma GI-III
(cont.)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 2/6
Neuronal and mixed glioneuronal (epilepsy
associated)
ganglioglioma GI
ganglioglioma GII
anaplastic ganglioglioma GIII
Tumours of the pineal gland
pineocytoma GI
pinealoblastoma GIV
(cont.)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 3/6
Embryonal tumours (GIV)
Meduloblastomas genetically defined (WNT, SHH)
Meduloblastomas histologically defined
Embryonal tumours
Tumours of the cranial and paraspinal nerves schwannoma, neurofibroma, perineurioma, GI
MPNST GIII
(cont.)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 4/6
Meningeal tumours
meningioma GI, atypical GII, anaplastic GIII
Mesenchymal non-meningotelial tumours
Solitary fibrous tumour GI-III
Hemangioblastoma, hemangioma, hemangioendotelioma,
angiosarcoma, Kaposi sarcoma, Ewing/PNET, lipoma,
liposarcoma, leiomyomas, rhabdomyoma, chondroma,
osteoma, and sarcomas GI-III
(cont.)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 5/6
Melanocytic tumours
meningeal melanocytosis, m. melanocytoma, m. melanoma,
m. melanomatosis
Lymphomas
DLBCL, immunodef. associated, AIDS, EBV..low grade, T
cell, Anaplastic Alk +/Alk -, MALT…
Histiocytární tumory
Langerhans cell histiocytosis, Erdheim-Chester disease,
Rosai Dorfmann disease, histiocytic sarcoma
(cont.)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 6/6
Germ cell tumours
germinoma
embryonal carcinoma
yolc sac tumour
choriocarcinoma
teratoma (mature, immature)
Tumours of the sellar region
craniopharyngeoma
pituicytoma
spindle cell oncocytoma
granular cell tumour of the sellar region
METASTATIC TUMOURS
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 4/6
Meningeal tumours
meningioma GI, atypical GII, anaplastic GIII
Mesenchymal non-meningotelial tumours
Solitary fibrous tumour GI-III
Hemangioblastoma, hemangioma, hemangioendotelioma,
angiosarcoma, Kaposi sarcoma, Ewing/PNET, lipoma,
liposarcoma, leiomyomas, rhabdomyoma, chondroma,
osteoma, and sarcomas GI-III
(cont.)
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Meningeoma
Meningeoma – multiple – brain impression
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Topic frequency of MENINGEOMA ICD-O 9530/0
convexity8561
parasagital
fossa cerebri ant
media
post
24
os sphenoides
medulla
other
multiple
falx
n. olfactorius
sella
n. opticus
tentorium
45
27
35
19
12
33
2
14
8
15
30
• middle aged, elderly
• risk fc. :irradiation
• mutation of NF2 (22q)
• mostly G 1
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Meningeoma GI
ICD-O 9530/0
G I- benign
G II- atypical
G III – anaplastic
(malignant)
G IV - exceptionally
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Meningeoma – Age & Sex Distribution
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Meningeoma
fibrosum
Meningeoma
meningoteliomatosum
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Meningeoma
psammomatosum
Meningeoma
transitorium
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Angioma racemosum cerebri et
meningum
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Hemangioma cavernosum ICD-O 9121/0
Types of CNS vascular malformations
arteriovenous
capillary teleangiectasia
cavernous hemangioma
venous angioma
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Hemangioma – malformatio arteriovenosa
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Chordoma ICD-O 9370/3
• remnants of notochord
• sacral 60%
• sphenooccipital 25%
• cervical 10%
• thoracolumbal 5%
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 1/6
Gliomas
diffuse astrocytic and oligodendroglial – GII –IV
other astrocytic – e.g. pilocytic, subependymal GI-III
ependymal tumours GI-III
other gliomas - angiocentric, astroblastoma GI-III
tumours of the choroidal plexus – papilloma, atypical
papilloma, papillocarcinoma GI-III
(cont.)
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Astrocytic tumours
• difuse – G2
• anaplastic - G3
• glioblastoma – G4
DIFUSELY INFILTRATING ASTROCYTOMAS
PILOCYTIC
ASTROCYTOMA –
BRAF(V600E)
mutation,
Age Distribution
IDH1 -
immunocytochemistry
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Astrocytoma diffusum
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Astrocytoma fibrillare
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Astrocytoma
A. protoplasmicum
A. anaplasticum (GIII)
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Astroblastoma (GIII)
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Astrocytoma pilocyticum (juvenile) –ICD-O 9421/1
WHO G I• Does not share genetic
abnormalities of astrocytoma.
• Better prognosis.
• Associated with
neurofibromatosis type I.
• Children & young adults.
• Often cystic, better
circumscribed
BRAF(V600E)
mutation
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Pilocytic Astrocytoma
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Pilocytic
Astrocytoma
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Pilocytic Astrocytoma - syringomyelia
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Pilocytic Astrocytoma
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Oligodendroglioma ICD-O 9450/3 GII-III
del 1p, 19q
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Oligodendroglioma
Oligoastrocytoma
ICD-O 9382/3
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Glioblastoma (multiforme) ICD-O 9440/3
WHO – G IV
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Glioblastoma multiforme ICD-O 9440/3
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Glioblastoma
multiforme
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Ependymoma
ICD-O 9391/3
associated
frequently with
NF 2
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Ependymoma
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Ependymoma ICD-O 9391/3
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Ependymoma
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Ependymoma
sacrale
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 2/6
Neuronal and mixed glioneuronal (epilepsy
associated)
ganglioglioma GI
ganglioglioma GII
anaplastic ganglioglioma GIII
Tumours of the pineal gland
pineocytoma GI
pinealoblastoma G IV
(cont.)
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Pineocytoma ICD-O 9361/1 G I
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Pineocytoma ICD-O 9361/1 G I
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 6/6
Germ cell tumours
germinoma
embryonal carcinoma
yolc sac tumour
choriocarcinoma
teratoma (mature, immature)
Tumours of the sellar region
craniopharyngeoma
pituicytoma
spindle cell oncocytoma
granular cell tumour of the sellar region
METASTATIC TUMOURS
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WHO Histological Typing
of Tumours of the CNS
TUMOURS OF THE SELLAR REGION
craniopharyngeoma, pituitary tumours
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Craniopharyngeoma
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Craniopharyngeoma
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 3/6
Embryonal tumours (GIV)
Meduloblastomas genetically defined (WNT, SHH)
Meduloblastomas histologically defined
Embryonal tumours
Tumours of the cranial and paraspinal nerves schwannoma, neurofibroma, perineurioma, GI
MPNST GIII
(cont.)
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Medulloblastoma ICD-O 9470/3
G IV
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Medulloblastoma
cerebelli
Isochromosom 17q
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 3/6
Embryonal tumours (GIV)
Meduloblastomas genetically defined (WNT, SHH)
Meduloblastomas histologically defined
Embryonal tumours
Tumours of the cranial and paraspinal nerves schwannoma, neurofibroma, perineurioma, GI
MPNST GIII
(cont.)
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Neurilemmoma ICD-O 9560/0
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Neurofibroma
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 5/6
Melanocytic tumours
meningeal melanocytosis, m. melanocytoma, m. melanoma,
m. melanomatosis
Lymphomas
DLBCL, immunodef. associated, AIDS, EBV..low grade, T
cell, Anaplastic Alk +/Alk -, MALT…
Histiocytic tumours
Langerhans cell histiocytosis, Erdheim-Chester disease,
Rosai Dorfmann disease, histiocytic sarcoma
(cont.)
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Lymphoma malignum
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Lymphoma malignum (prim. cerebri)
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WHO Classification of Tumours of the Central Nervous System 2016 – selection 6/6
Germ cell tumours
germinoma
embryonal carcinoma
yolc sac tumour
choriocarcinoma
teratoma (mature, immature)
Tumours of the sellar region
craniopharyngeoma
pituicytoma
spindle cell oncocytoma
granular cell tumour of the sellar region
METASTATIC TUMOURS
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„Pinealoma anisomorphe“ – seminoma
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Cystis dermoides
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Pseudotumours (diff. dg.!)
Cysts
– Rathke´s cyst
– epidermoid cyst
– dermoid cyst
– colloidal cyst of the 3rd ventrikle…
VASCULAR MALFORMATIONS
– capillary teleangiectasia
– a.– v. malformation
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WHO Histological Typing
of Tumours of the CNS
METASTATIC TUMORS
mostly carcinomas !!!
…… melanoma…..
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Metastases adenocarcinomatis meningum et cerebri
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Carcinosis meningum
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Carcinoma diffusum ventriculi (ad meningos metastaticum)
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M57. History of melanoma.Melan A
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M73. History of bronchogenic carcinoma
MGG
MGG
TTF1
TTF1 -control
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Hippocampus