GROSS TUMORS OF THE NERVOUS SYSTEM (VI

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GROSS TUMORS OF THE NERVOUS SYSTEM (VI VII)
Diffuse tumors Multiple tumors

• Cheng-Mei Shaw, MD
• Ellsworth C. Alvord, Jr. MD
• Neuropathology Laboratory
• University of Washington Medical
• School, Seattle, WA

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• Classification by Anatomical Location
• Supratentorial
• 1. Cerebrum and its coverings
• a. extra-axial (meningeal)
• b. intra-axial (cerebral)
• 2. Sellar, parasellar hypothalamic
• Tentorial (pineal region)
• III. Subtentorial
• IV. Spinal cord spine
• Nerves, cranial peripheral
• VI. Diffuse tumors
• VII. Multiple tumors

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• Although multicentric primary tumors are known
  to occur, neoplastic transformation usually takes
  place in a solitary focus, perhaps in a single
  cell.
• There are two major patterns of neoplastic
  growth
• Tumor mass expands as tumor cells proliferate
  with very little or no migration of cells to
  adjacent host tissue. This type of tumor is seen
  in encapsulated tumors, such as metastatic
  carcinoma, meningioma and schwannoma. It is
  circumscribed, compresses the adjacent normal
  tissue, usually remains localized. When it
  disseminates, it does so through vascular or
  lymphatic system to remote sites.
• Tumor cells proliferate and migrate though the
  host tissue, as is seen in most gliomas and
  sarcomas. The interface between the tumor tissue
  and normal tissue is usually not clear and a
  total extirpation is difficult if not impossible.
  

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A patient may be cured when a tumor of the first
type can be excised completely before metastatic
seeding takes place. The tumor may recur if a
small number of tumor cells is left behind. These
patients usually die because of extensive
metastases or when a vital organ is invaded or
compressed by the tumor. In contrast, surgical
excision of the second type of tumor is almost
always incomplete. The volume of tumor can be
reduced by excision, radiation and chemotherapy
temporarily, but the patient usually succumbs to
extensive infiltration of tumor cells involving a
large territory of the target organ. Gliomas,
which usually start at a small focus, grow into
the adjacent tissue in more or less radiating
fashion. When the patients die, the end result at
autopsy is diffuse glioma involving a large
amount of the CNS.
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Difuse glioma, gliomatosis, gliomatosis cerebri,
diffuse astrocytoma, etc are only a few of the
terms used to describe an expanded infiltrating
glioma, the condition one frequently sees at
autopsy, the end result of the natural course of
an infiltrating glioma. There are other
examples of a glioma involving an extremely large
area of the CNS, apparently from the outset,
difficult to accept the idea that it began from a
single focus. One alternative is to consider
widespread simultaneous neoplastic
transformation of many cells or a fusion of
multicentric neoplasms. From a mathematical model
involving only two factors, net rates of
proliferation and diffusion, such gliomas may
simply be the result of diffusion beginning so
early that a local mass cannot develop. Indeed,
the model requires an incubation period without
diffusion to produce a mass of 1 cu mm first.
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Gliomatosis cerebri is a diffuse glioma
involving a large territory of the CNS without
forming a localizable mass and without disruption
of gross anatomical architecture. The definition
is arbitrary and subjective, without stating how
much is too much. The is no definite criterion,
and in some cases there may be a localized mass
in addition to the diffuse neoplasm.
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We will tentatively define gliomatosis cerebri
as a glioma which involves more than two lobes of
the cerebrum and/or more than two sub-structures
of the CNS. Gliomas involving two lobes of either
one or two hemispheres, cerebral gliomas
extending into deep nuclei or gliomas in the base
of the brain extending into the brainstem are too
common at autopsy and will be excluded. When
three lobes or three sub-structures or more are
involved, then a diagnosis of gliomatosis cerebri
may be considered.
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Solving the quantitative problem tentatively, we
still face a qualitative problem. The cases,
which could be categorized as gliomatosis cerebri
based on above-mentioned quantitative criteria,
seem to be qualitatively quite heterogeneous.
We have seen several anatomically different
growth patterns of gliomas which have been
equally diagnosed under the term, gliomatosis
cerebri. 1. Central type more or less
unique, predominantly involving thalami extending
outward to other deep cerebral nuclei, upper
brainstem and medial temporal lobe(s) 2.
Longitudinal type mainly arising in the
brainstem, extending both directions into the
diencephalon rostally and brainstem distally and
even spinal cord caudally 3. Basal type rare
form involving the optic nerves, chiasm, tracts,
hypothalamus and brainstem 4. Diffuse white
matter type involves large areas of cerebral
white matter, brainstem and cerebellum 5.
Diffuse gray matter type predominantly involving
cerebral cortex, often breaks into and spread
along subarachnoid spaces, commonly with
oligodendroglioma
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In the files of Neuropathology Laboratory,
University of Washington from 1960 to 2000 there
are more than 50 autopsied cases which were
diagnosed as gliomatosis cerebri, depends on
just how many of these terms are accepted. The
introduction of CT-MRI makes the diagnosis of
gliomatosis cerebri easier since the extent of
the tumor can be visualized and assessed long
before the patient comes to autopsy. Some
examples, which may belong to this group, are
already presented in Gross tumor (2) and (5A)
under separate titles. Additional and preferred
examples of gliomatosis, using the criteria
established earlier, will be presented in the
following.
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Diffuse tumors

• Parenchymatous
• 1. Gliomatosis, diffuse glioma,
• 2. Lymphomatosis
• 3. Melanomatosis
• 4. Carcinomatous
• Leptomeningeal ventricular
• Leptomeningeal gliomatosis
• Leptomeningeal PNET
• Leptomeningeal carcinomatosis and lymphomatosis

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NP6151 16 year-old female

• Rt temporal lobe grade II astrocytoma for 4 - 5
  yrs
• Temporal lobectomy, 8/75 XRT, improved
• Relapse 1.5 - 2 yrs before death, chemotherapy
• Seizures, choking, could not talk, could not move
  head 2/78, died 3/78
• Autopsy gliomatosis cerebri involving 2/3 of the
  cerebrum, including deep cerebral nuclei, whole
  brainstem and cerebellum, central type

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NP5809 13 year-old female

• 3 weeks history of altered behavior
• Precipitous deterioration with acute respiratory
  arrest
• Autopsy delayed. autolysed brain showed
  gliomatosis cerebri, central type

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NP7531 53 year-old male

• History of dementia for unknown duration
• CT 8 mos before death showed a mass in the left
  basal ganglia
• Autopsy gliomatosis cerebri involving bilateral
  thalamus, striatum, amygdaloid nucleus,
  hippocampus, midbrain, pons and medulla,

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CONTROL
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NP5438 36 year-old male

• Presented following 6 mos of psychomotor seizures
  with sensory aura
• Abnormal EEG, EMI ? Rt fronto-temporal lesion
• EMI angiogram 3 mos later showed a mass in the
  basal ganglia, died one year later
• Autopsy Gliomatosis cerebri, central type,
  involving thalamus, temporal lobe, frontal lobe
  and midbrain tegmentum

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NP14910 30 years-old male

• Onset of seizures in 1986
• CT in 3/87 Rt cerebral mass, thought to be
  traumatic lesion papilledema 12/87 CT lesion
  enlarged Bx low grade glioma (NP13438)
• XRT, worse 7/88, Lt hemiparesis Rt leg
  weakness, more resection 2/89 low grade glioma
  (NP14607), died 9 days after surgery
• Autopsy gliomatosis cerebri, predominantly
  oligodendroglioma, involving 3/4 of Rt cerebral
  hemisphere, left frontal, basal ganglia,
  midbrain, pons and medulla

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NP19379 8 years old male

• Long Hx of Lt facial droop, unknown etiology
• Severe headache Rt hemiparesis, 1991
• CT low density, MRI T2 enhanced lesion in left
  thalamus resected 7/91, Dx GM (NP17385) XRT
  chemotherapy
• Diplopia lethargy 9/92, CT tumor extended to
  midbrain, VP shunt
• Unresponsive 9/92, died 1/93, 19 mos after Dx
• Autopsy GM in thalamus, hypothalamus, midbrain,
  pons, Lt internal capsule, caudate , anterior
  corpus callosum, colliculi, anterior vermis

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NP3873 49 years old male

• Presented with papilledema bitemporal
  hemianopsia 4 mos prior to death
• Craniotomy, optic glioma found grossly, no Bx
• XRT, p.o. pneumonia
• Quadriparesis 2 mos PTD, myelogram laminectomy
  large cervical spinal cord, no Bx progressive
  pulmonary complications, died
• Autopsy gliomatosis cerebri, involving optic
  nerves, chiasm, tracts, cerebral peduncle,
  medulla cervical spinal cord

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Optic chiasm
Optic chiasm
Optic chiasm
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NP12779 8.5 years old female

• Neurofibromatosis
• Rt optic glioma Dx by BX 7 yrs earlier, XRT
• Lt thalamic brainstem lesions found 4 yrs later
• Lt intraventricular meningioma removed 2 yrs
  before death, Dx of brainstem glioma 1 year
  before death
• Hospitalized for seizures aspiration, developed
  Lt MCA occlusion, Rt hemiparesis
• Autopsy gliomatosis cerebri, pilocytic
  astrocytoma involving optic nerves, chiasm,
  tracts, thalamus, Lt internal capsule, globus
  pallidus, brainstem, cerebellar white matter,
  hippocampi, upper cervical cord, subarachnoid
  gliomatosis ischemic infarct in left
  fronto-parieto-temporal lobes

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NP 6779 50 years old female

• Rt carotid body tumor removed 4.5 yrs PTD
• Status epilepticus 6 mos after surgery
• Lt hemiparesis, progresive, shortly after MVA
• Total occlusion of Rt ICA found at arteriogram
• PNG unsuccessful, coma 1 hour later
• Rt frontal oligo resected 2.5 yrs ago (NP5697)
• PO XRT, progressively deteriorated died
• Autopsy I) Gliomatosis cerebral, central
  cerebrum, oligo astro. 2) Multiple sclerosis
  (demyelinating and necrotizing patchy white
  matter lesions)

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LFB-PAS-H
LFB-PAS-H
LFB-Homes
LFB-Homes
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NP8057 45 years old female

• Headache for 7-8 mos, developed papilledema
• Dx pseudotumor, no localizing signs
• Repeated LP, then VP shunt
• Lethargy ataxia 1 mo PTD, Rt fronto-parietal
  mass found by arteriogram, Basal ganglia lesion
  by EMI
• Craniotomy, grade II astro, died 3 days later
• Autopsy Gliomatosis cerebri, right cerebrum,
  basal ganglia, brainstem

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Right
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Right
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NP9142 12 years old male

• Osteosarcoma, Rt maxilla resected 5 years ago
• PO chemotherapy for 2 years, then developed
  visual difficulty
• CT left thalamic tumor. Bx non-diagnostic
• XRT. CT Lt fronto-parietal mass, Bx
  non-diagnostic
• CT 4 mos PTD large Rt cerebellar mass, tumors
  continued to enlarge
• Autopsy Gliomatosis cerebri, thalamus,
  brainstem, cerebellum, left temporal lobe and
  subarachnoid gliomatosis

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NP9417 46 years old female

• Bx of Rt fronto-parietal low grade glioma
  (NP8442) after 1 mo of sensory seizures of Lt
  face
• CTs 7 mos 14 mos po showed no change
• Generalized seizure followed by coma 15 mos po
  CT showed large mass VP shunt but died
• Autopsy diffuse astrocytoma (gliomatosis
  cerebri) with focal glioblastoma

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NP13430 30 years old male

• 2/86 2 mos history of tremor incoordinationCT
  showed plaques in posterior fossa, Dx MS
• 9/86 headaches, dizziness, nausea,
  incoordination for several weeks, no effects with
  steroids
• 11/86 headaches, ataxia, diplopia, gaze
  paralysis, CT aqueductal obliteration,
  displacement of 4th ventricle to Left
• 12/86 Bx of vermis, grade II astrocytoma
  (NP12369) VP shunt
• XRT, died at home in 12/87, 2 yrs after onset
• Autopsy Gliomatosis cerebri predominantly of the
  whole brainstem extending into the cerebellum,
  diencephalon, ventral fronto-temporal lobes,
  striate nuclei, olfactory carrefour, corpus
  callosum and walls of lateral and 4th ventricles
  histology varied from area to area, astrocytoma
  grade I - III oligodendroglioma

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HE
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Leptomeningeal gliomatosis
As gliomas grow to extend to the surface of the
CNS parenchyma, and/or when contiguity between
the tumor and the subarachnoid spaces is created
by surgical intervention, the tumor cells
frequently spread out into the subarachnoid
spaces and disseminate along the CSF circulation.
Focal leptomeningeal extension of glioma cells is
a common autopsy finding in patients previously
treated by surgical intervention . However,
extensive subarachnoid dissemination of glioma
cells causing obstructive hydrocephalus as the
major clinical presentation is relatively
uncommon.
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When the primary site of a tumor is near the CNS
surface, subarachnoid dissemination may occur
early. The primary site may be so small and
inconspicuous as to be missed by diagnostic
studies or even at autopsy. Without a primary
site, leptomeningeal gliomatosis originates in
subarachnoid glial heterotopia. Extensive
leptomeningeal gliomatosis appears to be
increasing, especially in terminal glioblastoma,
perhaps because of more thorough autopsy studies
due to rising interests in treatments of
glioblastoma, or to life-prolongation of patients
because of newer treatments or multiple surgical
interventions.
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Leptomeningeal gliomatosis consisting of low
grade glioma is otherwise rare, tending to occur
in young patients with oligodendroglioma. When
oligodendroglioma cells extend into the
subarachnoid spaces, their nuclei tend to become
spindle-shaped but GFAP usually remains negative.
These tumors have been frequently diagnosed as
astrocytoma in the past but still frequently bear
that diagnosis even today.
It appears that tumor cells devoid of
extensive cellular processes, such as
oligodendroglioma, PNET and lymphoma, can spread
through the subarachnoid spaces readily.

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NP 8246 22 years old female

• Lt temporal glioblastoma resected 3 yrs before
  death (NP6999)
• XRT with Neutron Photon and VP shunt
• Rebiopsy (NP8132)
• Autopsy Residual glioblastoma, left superior
  temporal lobe, disseminated glioblastomatosis in
  subarachnoid and perivascular spaces and walls of
  ventricles

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Reticulin
LFB-PAS-H
Reticulin
HE
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HE
Reticulin
HE
GFAP
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GFAP
GFAP
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NP 3969 19 years old female

• Age 12 SA hemorrhage, etiology unproved
• Age 13 headache, decreased L vision, arteriogram
  showed a mass in L optic nerve, extra-axial mass
  under L optic nerve tract extending into middle
  fossa interpeduncular fossa, Dx astrocytoma
  III
• Post-operative XRT
• Age 17 seizures, fatigue, lightheadness, ataxia,
  amenorrhea
• Age 19 died outside
• Autopsy1) leptomeningeal oligodendrogliomatosis,
  2)multiple cystic infarcts, left thalamus
  globus pallidus, 3) diffuse cerebellar
  degeneration, 4)hippocampal sclerosis

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NP 5696 22 years old female

• No detailed history, except that she had carried
  a Dx of right temporal high grade astrocytoma
  which had been resected 1 yr 10 mos prior to
  death
• Autopsy 1) glioblastoma, right cerebral peduncle
  and basis pontis, 2) leptomeningeal
  glioblastomatosis, 3) cystic infarct, right
  lateral geniculate nucleus

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NP 5605 81 years old male

• Rapid onset of dementia (less than a month)
• Left sphenoid wing tumor resected glioblastoma
  but unusual histology showing multiple tumor
  nodules separated by fibrous tissue septa, tumor
  cells frequently polygonal (NP5605-1)
• P.O. XRT, improved but steroid-dependent
• Died of rupture of diverticulum of colon 2 mos
  after surgery
• Autopsy Monstrocellular glioblastoma, surface of
  cerebral parenchyma extending into subarachnoid
  spaces where tumor forms multiple nodules
  separated by fibrous tissue septa

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NP18272 19 months old female

• A twin born at 26 wks gestation, presented with
  ataxia, nausea, vomiting following a fall 3 mos
  prior to death
• Choroid plexus carcinoma in Rt lateral ventricle
  found resected (NP17941)
• P.O chemotherapy complicated by emesis, fever
  neutropenia
• Hydrocephalus treated with shunt 10 days before
  death, CT showed probable carcinomatous
  meningitis, CSF positive for tumor cells
• Autopsy 1) residual recurrent choroid plexus
  carcinoma, Rt parieto-occipital surgical defect,
  2) extensive leptomeningeal tumor dissemination,
  3) obstructive hydrocephalus

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NP16306 65 years old male

• Presented with progressive confusion, multiple
  peripheral neuropathies and L facial paralysis
• Imaging showed hydrocephalus, CSF positive for
  malignant cells
• Died 4 months after onset, no primary tumor found
• Autopsy Carcinomatous meningitis, Hydrocephalus

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Lymphoma frequently infiltrates a large
territory of the CNS parenchyma without forming
nodular masses and without disrupting gross
anatomy of the CNS, even rather inconspicuous at
autopsy. CT/MRI are most helpful for making a
diagnosis of cerebral lymphomatosis. Lymphoma
also has a tendency to spread along the
ventricular walls and subarachnoid spaces as well
as infiltrating the septum pellucidum and fornix.
In this respect, lymphoma behaves like PNET,
especially like medulloblastoma and treated
malignant gliomas.
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NP12782 61 years old female

• History of CNS lymphoma for about 3 yrs, treated
  with systemic intraventricular Methotrexate via
  Omayas reservoir
• Thoracic laminectomy resection of epidural
  lymphoma 2.5 yrs before death
• MRI diffuse cerebral white matter enhancement,
  ? lymphoma, PML, MTX leucoencephalopathy, BX
  non-diagnostic 6 mos PTD
• Autopsy 1) Diffuse lymphomatosis, cerebral white
  matter, cortex, basal ganglia, cerebellum
  brainstem,
• (perivascular) 2) MTX leucoencephalopathy

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NP13259 10 years old female

• Presented with fever, rash, lymphadenopathy
  splenomegaly
• Multiple BX and bone marrow exam revealed
  atypical immunoproliferative malignancy vs B-cell
  lymphoma
• Died of respiratory failure secondary to
  pulmonary lymphoma
• Autopsy Leptomeningeal lymphomatosis, diffuse
  perivascular lymphoma infiltration in cerebral
  white matter, cortex, thalamus, midbrain
  cerebellum

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NP7392 73 years old male

• 10 days of left leg dragging frequent falls
• Bells palsy 1 year earlier, mental deterioration
  and ptosis for 1 year
• Dx TIA, anti-platelet therapy
• CT increased density, Rt thalamus, third
  ventricle shifted to L improved with steroids
• Steroids tapered down, mental deterioration,
  progressive SOB, died of sepsis
• Autopsy 1) disseminated lymphomatosis,
  multifocal, cerebral cortex, white matter, basal
  ganglia and subarachnoid spaces, 2) old cystic
  infarct, left caudate nucleus internal capsule

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NP15362 70 years old male

• 1 month history of memory speech difficulty, Rt
  upper extremity weakness
• CT low density lesion, corpus callosum
• MRI lesions in periventricular regions pons
• Dx lymphoma, improved with steroids, then
  deteriorated, died 4 mos after onset
• Autopsy lymphoma, corpus callosum, ventricular
  walls, pons

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NP19885 34 years old male

• Headaches, nausea vomiting, HIV(), no clinical
  AIDS
• CT (), Toxo(-), PPD(), LP(-), EBV()
• Rx with anti-tbc for 1 month
• Improved with steroids, then deteriorated
• Autopsy lymphomatosis, thick corpus callosum,
  fornices, pituitary stalk, subarachnoid spaces

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NP 9932 59 years old male

• 8/83, meningitis-like syndromes, then ataxia
  dysarthria
• 11/83, abnormal CT brain abscess, Rx with
  antibiotics
• 1/84, brainstem signs with bilateral internuclear
  ophthalmoplegia, Rt 7th nerve palsy, ataxia
• Brain Bx non-diagnostic
• 3/84, CT periventricular lesions, lymphoma XRT
  2000 rad, died 9 mos after onset
• Pt was a chicken farmer, a son had leukemia at
  age 17
• Autopsy periventricular lymphomatosis

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HE
LFB-PAS-H
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Multiple Tumors

• 1. Same tumors
• primary tumor gliomas, lymphoma, meningioma,
  schwannoma, neurofibroma
• Metastatic carcinoma, sarcoma, lymphoma
• 2. Different tumors
• Different sites neurofibromatosis, multiple
  primary tumors, primary metastatic tumors
• Same sites different primary tumors, metastatic
  to primary tumors

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NP14268 64 years old male

• 1 week Rt arm weakness speech difficulty
• CT L thalamic lesion, infarct vs abscess
  rapidly spread to brainstem no improvement with
  steroid, 5/88
• - Bx ? Abscess, no improvement with antibiotics
• Rebiopsy 2 weeks later GM
• Died 3 mos later outside
• Autopsy Bicentric glioblastoma involving left
  basal ganglia and pons

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Neurofibromas involving nerves in the Rt side of
the neck, 30x5x10 cm, carotid artery, jugular
vein some intact nerves in the center
Rt brachial plexus plexiform neurofibroma
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NP15476 59 years old female

• Presented with 2 months of mental decline
• Multiple enhancing lesions, left frontal, right
  temporal, basal ganglia and pineal gland
• Biopsy lymphoma, treated with Methotrexate x 3,
  no XRT,
• Died 4 months after diagnosis
• Autopsy Multifocal b-cell lymphoma

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Multiple Tumors

• 1. Same tumors
• primary tumor gliomas, lymphoma, meningioma,
  schwannoma, neurofibroma
• Metastatic carcinoma, sarcoma, lymphoma
• 2. Different tumors
• Different sites neurofibromatosis, multiple
  primary tumors, primary metastatic tumors
• Same sites different primary tumors, metastatic
  to primary tumors

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Multiple Tumors

• 1. Same tumors
• primary tumor gliomas, lymphoma, meningioma,
  schwannoma, neurofibroma
• Metastatic carcinoma, sarcoma, lymphoma
• 2. Different tumors
• Different sites neurofibromatosis, multiple
  primary tumors, primary metastatic tumors
• Same sites different primary tumors, metastatic
  to primary tumors

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Meningioma
Renal cell ca