Tumors of the nervous

system. Pigmented lesions

Synopsis

Tumors of the central nervous system.

Tumors of the peripheral nervous
system.
Tumors of melanocyte origin.

Tumors of the central nervous system

General features of the CNS tumors

85 % - intracranial tumors, 15% - intraspinal tumors

primary tumors and metastatic

20% of all tumors of childhood.

differ from those in adults both in histologic subtype and location

tumors are likely to arise in the posterior fossa, while in adults they are mostly supratentorial.

Tumors of the nervous system have unique characteristics

Histologic distinction between benign and malignant lesions may be more subtle in
the CNS than in other organs
The pattern of growth of low-grade lesions (low mitotic rate, cellular uniformity, and
slow growth) may include infiltration of large regions of the brain

The anatomic site of the neoplasm can have lethal consequences irrespective of
histologic classification

With serious clinical deficits and poor prognosis.

a benign meningioma, by compressing the medulla, can cause cardiorespiratory arrest

The ability to resect a lesion may be limited

The pattern of spread of primary CNS neoplasms differs from that of other tumors

rarely metastasize outside the CNS,

the subarachnoid space - a seeding along the brain and spinal cord can occur

CNS TUMORS

GLIOMAS

Astrocytes (I, II,

III,

IV)

Oligodendroglioma
Ependymoma

NEURONAL
POORLY DIFFERENTIATED
MENINGIOMAS
LYMPHOMAS
METASTATIC

(medulloblastoma)

CNS TUMORS

Symptoms?

Headache
Vomiting
Mental Changes
Motor Problems
Seizures
Increased Intracranial Pressure

any localizing CNS abnormality

CNS TUMORS

History
Physical
Neurologic exam
LP (including cytology)
CT
MRI
Brain angiography
Biopsy

Gliomas

Tumors of the brain parenchyma that

histologically resemble different types
of glial cells

astrocytomas,
Oligodendrogliomas
ependymomas

Astrocytomas

There are several different categories

of astrocytic tumors
Fibrillary
pilocytic astrocytomas

characteristic histologic features,

distribution within the brain
age groups

Fibrillary astrocytomas

80% of adult primary

brain tumors
Age 40 -60 y
Localization

cerebral hemispheres

seizures, headaches, and

focal neurologic deficits

Macroscopy

a poorly defined, gray,

infiltrative tumor
cut surface - firm, or soft and
gelatinous
cystic degeneration and
hemorrhage

Fibrillary astrocytomas

Microscopy

I IV grades

cellularity
nuclear pleomorphism
Necrosis
mitoses

Low grade
High grade anaplastic
Glioblastoma
vascular or endothelial
cell proliferation and
pseudo-palisading nuclei

Glioblastoma Multiforme

Glioblastoma Multiforme

GFAP (+)

Pilocytic Astrocytoma

Relatively benign tumors

Age - children and young adults
Localization

Macroscopy

Cerebellum, in the floor and walls of the

third ventricle
the optic nerves, and occasionally the
cerebral hemispheres
well circumscribed
often cystic, with a mural nodule in the
wall of the cyst

Microscopy

areas with bipolar cells with long, thin

"hairlike" processes

GFAP positive

Rosenthal fibers (eosinophilic granular

bodies)
Microcysts
Necrosis and mitoses are rare.

Oligodendrogliomas

Frequency -5-15%
Age 40-50 y
Localization

Macroscopy

cerebral hemispheres
infiltrative tumors - gelatinous, gray
cysts, focal hemorrhage, and calcifications

Microscopy

sheets of regular cells with spherical nuclei

containing finely granular chromatin (similar
to normal oligodendrocytes) surrounded by a
clear halo of cytoplasm
And a delicate network of anastomosing
capillaries.
Calcifications
Mitoses -rare

Except in anaplastic oligodendroglioma

Oligodendrogliomas

Ependymoma

Frequency -5-10%
Age 10-20 y
Localization

IV th ventricle

Macroscopy

hydrocephalus

solid or papillary masses

Microscopy

cells with regular, round to oval

nuclei with abundant granular
chromatin

perivascular pseudo-rosettes

Variants

Anaplastic

increased cell density, high

mitotic rates, necrosis

Ependymoma

Neuronal Tumors

Central neurocytoma

Gangliogliomas

a low-grade neuronal neoplasm

within the lateral or third ventricles)
round, uniform nuclei and often islands of
neuropil.
tumors with a mixture of glial elements and
mature-appearing neurons.
slow growing

Dysembryoplastic
neuroepithelial tumor

low-grade tumor of childhood

A relatively good prognosis
located in the superficial temporal lobe
small round cells with features of neurons in
columns and around central cores of
processes, with myxoid background.

Poorly Differentiated Neoplasms

Medulloblastoma

Neuroectodermal cells
Age - children
Localization

cerebellum (vermis)

well circumscribed, gray, and

friable,

Histology

with sheets of anaplastic

("small blue") cells

with little cytoplasm and

hyperchromatic nuclei
mitoses - abundant.

Rossetes of Homer-Wright

Medulloblastoma

Meningiomas

Benign tumors of adults

from the meningothelial cell of the

arachnoid

Localization

any of the external surfaces of the

brain
ventricular system

from the arachnoid cells of the

choroid plexus

Macroscopy

well-defined dural-based masses

compress underlying brain

Meningiomas

Microscopy -variants

Syncytial - whorled clusters of cells

Fibroblastic - with elongated cells and
abundant collagen deposition
Transitional - shares features of the
syncytial and fibroblastic types
Psammomatous - with numerous
psammoma bodies
Secretory - with PAS-positive
intracytoplasmic droplets
Microcystic - with a loose, spongy
appearance
atypical meningiomas a higher mitotic

rate

Anaplastic (malignant) meningiomas

resemble a high-grade sarcoma

Meningeoma

Metastatic brain tumors

Most common brain tumor in

adults.
Common primary sites:
melanoma, lung, breast, GI
tract, kidney.
Most are in cerebrum

in gray-white junctions due to

rich capillarity

Single or multiple.
Discrete, globoid, sharply
demarcated tumors

amenable to surgical resection.

Tumors of the peripheral

nervous system

Tumors of the peripheral

nervous system

Arise from cells of the peripheral nerve

Schwann cells,
perineurial cells
Fibroblasts

Schwannoma
Neurofibroma

Malignant Peripheral Nerve Sheath Tumor

Schwannoma

From Schwann cells

Symptoms

local compression of the involved nerve,

or to compression of adjacent structures (such as
brain stem or spinal cord).

Localization

in the cerebellopontine angle, where they are

attached to the vestibular branch of the eighth nerve

Macroscopy

tinnitus and hearing loss (vestibular schwannoma)

sensory nerves, large nerve trunks

well-circumscribed encapsulated masses that are

attached to the nerve

Morphology 2 growth patterns

Antoni A pattern of growth

elongated cells with cytoplasmic processes - fascicles

little stromal matrix

Antoni B pattern of growth

the "nuclear-free zones" of processes that lie between the

regions of nuclear palisading - Verocay bodies.

less densely cellular areas

microcysts and myxoid changes

Immuhistochemistry - S-100 protein

Schwannoma
Antoni A - Antoni B

Neurofibroma

Well differentiated, benign

Epi & endoneurial

fibroblasts.
Form whorls of fibroblasts

Two types:

Classic form

Cutaneous / nerves solitary

collagen matrix, spindle cells,

Plexiform

Neurofibromatosis type 1
Multiple, infiltrative
Myxoid stroma.

Malignant Peripheral Nerve

Sheath Tumor

Sarcoma

Origin

De novo
plexiform neurofibroma

Macroscopy

Highly malignant
multiple recurrence
metastases

poorly defined tumor masses

infiltration along the axis of nerve
invasion of adjacent soft tissues

Histology

A wide range of histologic findings

the tumor cells resemble Schwann cells - elongated nuclei and

prominent bipolar processes, fascicle formation
Mitoses, necrosis, nuclear anaplasia
Some but not all tumors - S-100 protein (+).

FAMILIAL TUMOR SYNDROMES

NF1

NF2

Schwannomas
Meningiomas

Tuberous Sclerosis

Neurofibromas
Gliomas

CNS and somatic hamartomas

Von-Hippel-Lindau Syndrome

CNS hemangioblastomas, chiefly cerebellar

Renal carcinoma
pheochromocytomas

Neurofibromatosis
Type I (common,

17q

AD,

Plexiform & solitary

neurofibromas
Optic nerve gliomas, Lisch
nodules, Caf au lait spots.

Type II (rare,

1:3000)

1:40,000)-22q

Bilateral acoustic
schwannoma/osis
Multiple meningioma/osis,
ependymoma of spinal cord

Tuberous Sclerosis

Dominant inheritance

Clinical triad

Seizures
mental retardation
adenoma sebaceum

Retinal hamartoma (phakoma)

Tubers in cerebral cortex

Subependymal giant cell

astrocytoma

Hamartomas in other organs: heart,

kidney

Tumors and Tumor-Like

Lesions of Melanocytes
Benign melanocytic nevus
Malignant - melanoma

Melanocytic nevus

Benign congenital or acquired

neoplasm of melanocytes
Numerous types, with varied clinical
appearance
Macroscopy

relatively small,
symmetric,
and uniformly pigmented

Morphology

Junctional

more pigmented,

more closely associated with

melanoma)

Intradermal
Compound (both)

Melanocytic nevus
Dermal nevus

Junctional nevus

Dysplastic nevus

Sporadic
Familial form

Macroscopy

AD inheritance
Precursors of melanoma
> 5mm in diameter
with irregular borders
and variable pigmentation

Morphology - compound nevi

with architectural abnormal growth

Enlarged nevus cell nests and fusion with

adjacent nests within the epidermis and
superficial dermis

Cytologic atypia

lentiginous hyperplasia

irregular, often angulated, nuclear contours

hyperchromasia

sparse lymphocytic infiltrate

loss of melanin pigment with phagocytosis
by dermal macrophages
linear fibrosis

Dysplastic nevus

MALIGNANT MELANOMA

Malignant proliferations of melanocytes.

Incidence rising,

The only primary skin cancer that can quickly

metastasizes
Sporadic
Hereditary -5-10%

Related to sun like all other skin cancers

Germ-line mutations in the CDKN2A gene (9p21)

Difficult to differentiate from nevus clinically

and often microscopically

MALIGNANT MELANOMA

Difficult to differentiate from

nevus clinically and often
microscopically
Clinical features

Skin

a change in the color or size of a

pigmented lesion

less common sites - oral and

anogenital mucosal surfaces, the
esophagus, the meninges, eye.

Morphology

Vertical growth phase

Horizontal growth phase

Related with prognosis

Breslow, Clarks staging

MALIGNANT MELANOMA

Morphology

Malignant cells with large

nuclei with irregular
contours

chromatin characteristically
clumped at the periphery of
the nuclear membrane
prominent eosinophilic
nucleoli -"cherry red"

nests or individual cells at

all levels of the epidermis
dermal balloon-like
nodules

MALIGNANT MELANOMA