CNS Tumors CPC-44: 22y Sam G, Seizure. Mr. SG, 22y, previously healthy male. On bus, became agitated, combative, had a seizure and became unresponsive. From Boston, USA, on holidays, 3 days. No H/O neck stiffness, no skin lesions/rash Pupils minimally reactive and 6mm bilaterally; fundoscopy normal.
pathology lecture on CNS tumours to 4th year pre-clinical medical students.
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CNS Tumors
CPC-44: 22y Sam G, Seizure. Mr. SG, 22y, previously healthy male. On bus, became agitated, combative, had a
seizure and became unresponsive. From Boston, USA, on holidays, 3 days. No H/O neck stiffness, no skin lesions/rash Pupils minimally reactive and 6mm bilaterally;
fundoscopy normal.
CNS Tumors
CPC-4.3.7 – Jenna 27y teacher. Jenna is a 27 year old teacher in Ingham who
collapsed in her classroom today. She was seen by her pupils to ‘shake all over’.
Brought to ED by paramedics, accompanied by teaching colleague. Collapsed approx 30 mins ago.
Tutors: ..look at a broad range of differential diagnoses for a witnessed, generalized tonic- clonic seizure. Focus… on epilepsy, infection (meningitis), and brain tumour.
Scenario: Meningitis ABC breathing spontaneously rr 18/min 4l O2 via
mask, sats 90%; pulse 110 bpm reg small volume; BP 90/60 mmHg T39.6C
GCS - E2V3M4 Detailed check - petechiae non blanching rash
trunk, buttocks, Neck stiffness Small contusion L temperoparietal area Capillary refill time > 3 secs, peripheral cyanosis+ Brudzinski sign positive Ix skin scraping from lesion : gram negative
Scenario: Epilepsy: ABC breathing spontaneously rr 14/min; 4l O2 via
mask , sats (O2 Sat study) 96% ; pulse 100 bpm regular good volume T 36.1 C BP 148/94.
GCS E2V3M4 Detailed check no neck stiffness, no skin lesions/rash Tongue has been bitten; pupils equal and reactive to
light; fundoscopy normal Decreased tone R upper limb, ?normal tone other limbs Reflexes increased on R upper + lower limb; decreased
on L upper +lower; Plantar reflexes upgoing Evidence of urinary incontinence All other systems : nil abnormal Ix - BSL : 5.1; toxicology screen : negative
Negative signs, family / past history
CNS Tumors
Core Learning Issues: Pathology Major CLI:
Raised ICP – Pathology & Clinical features. Pathology of common CNS tumors in different age
In every person who comes near you look for what is good and strong;
honor that; try to learn it, and your faults will drop off like dead leaves
when their time comes.
--John Ruskin
Look for good in others “No one is without faults and everyone has good qualities…!”
Pathology of CNS Tumors
Dr. Venkatesh M. Shashidhar, MDAssociate Professor & Head of Pathology
CNS Tumors
CNS Tumors: General Features
10% of all tumors. (10 to 17 per 100,000) Commonest solid cancers in children.(2nd to Leuk) Age: double peak 1st & 6th decade Adults - 70% supratentorial Children - 70% infratentorial Metastatic tumors are
the most common (50-70%) Primary - glial origin. Very rare extraneural
mutations of the metabolic enzyme Isocitrate DeHydrogenase (IDH1 and IDH2) are common in lower-grade astrocytomas. As a result, immunostaining for the mutated form of IDH1 has become an important diagnostic tool for low grade gliomas.
CNS Tumors
Astrocytoma-Lowgrade fibrillary
CNS Tumors
Astrocytoma
CNS Tumors
Glioma Brain Stem – note diffuse tumor
CNS Tumors
Glioma Cerebrum cystic degeneration
CNS Tumors
Glioma:
CNS Tumors
Astrocytoma: * Lat. Vent. *petechial hem.
CNS Tumors
Astrocytoma (Glioma) – brain stem
CNS Tumors
Glioma Brain Normal
CNS Tumors
Astrocytomas
Adults:Commonest 80%, Cerebral.Low Gr: Solid, Fibrillary. High Gr: glioblastoma multiforme
Glioblastoma Multiforme (GBM): High grade Astrocytoma - Grade IV Commonest & malignant brain tumor in adults –
mean survival <1y – cerebral supratentorial. Loss of heterozygosity on Chromosome 10 (80%) Most GBMs have lost one entire copy of C – 10 2 types: Primary (worst) or Secondary from low grade
Genetic abnormalities in Glioma:Low grade Anaplastic GBM
* GBM can occur alone without prior glioma
In glioblastoma, loss-of-function mutations in the p53 and Rb tumor suppressor pathways and gain-of-function mutations in the oncogenic PI3K pathways have central roles in tumorigenesis.
CNS Tumors
Glioma: high grade
CNS Tumors
GBM: MRIEnhancement with peritumoral edema.
CNS Tumors
Glioblastoma – high grade Astrocytoma
CNS Tumors
Glioblastoma – high grade Astrocytoma
Note: Looks like abscess, but it is necrosis..!
CNS Tumors
Glioblastoma Multiforme (high grade Astrocytoma)
CNS Tumors
Glioblastoma Cerebrum
CNS Tumors
High Gr.: Glioblastoma multiforme(high grade- Hypercellularity, necrosis, hemorrhage & palisading)
Hem
Necro
Hyper cel. Palis.
CNS Tumors
Glioblastoma Multiforme
Palisading
B.V
Necrosis
CNS Tumors
Glioblastoma Multiforme
A Astrocytoma Low gradeB Glioblastoma Multiforme(GBM)C Necrosis with pseudopalisading in GBM.
CNS Tumors
Astrocytomas
Adults:Commonest 80%, Cerebral.Low Gr: Solid, Fibrillary. High Gr: glioblastoma multiforme
Mutations in IDH1 and IDH2 (common in low-grade diffuse astrocytomas) are not found in pilocytic tumors. These genetic distinctions support the division of these astrocytomas into two diagnostic categories.
CNS Tumors
Pilocytic Astrocytoma - children
CNS Tumors
Pilocytic Astrocytoma: solid, brightly contrast-enhancing mural component and associated cyst.
CNS Tumors
Pilocytic Astrocytoma: Microscopy
Palisading pilocytic astrocytes – note plenty of Rosenthal fibres between cells.
Contusion of the inferior temporal lobe (blue arrow) has resulted in diffuse edema. (compressed and flattened gyri on the right).
This has resulted in subfalcine herniation of the cingulate gyrus (red arrow), with a secondary hemorrhagic infarction above that (black arrow). A midline shift from right to left is also present, as is uncal herniation (yellow arrow).
CNS Tumors
acute brain swelling + Uncal Herniation
Swelling of the left cerebral hemisphere has produced a shift with herniation of the uncus of the hippocampus through the tentorium, leading to the groove seen at the white arrow.
CNS Tumors
Herniation: Central Pontine / Duret Hem.
CNS Tumors
Cerebellar Tonsil - Herniation Note the cone shape of the
herniated tonsils around the medulla in this cerebellum specimen.
Results in compression and Duret hemorrhages in the pons.
basis of clinical features. CNS tumours: common features. Adult and childhood CNS tumors. Meningioma, astrocytoma & Glioblastoma. Children astrocytoma & medulloblastoma. Epilepsy – clinical.
CNS Tumors
Learning Medicine...! Learning medicine should be a JOY, not an ordeal. Everyone learns according to their own best style. The Hippocratic oath issues of patient privacy,
compassion, and FREE sharing of knowledge have to be honored.
Exam and grade anxieties are the CANCERS of medical education.
If your school admitted students which they feel need to be whipped, the SCHOOL has failed, not YOU!
If you claim you NEED to be pushed, I do not want you as my doctor.
John R. Minarcik, MD (http://www.medicalschoolpathology.com)
50y Female smoker - Headache.This 50 year-old female smoker known for hypertension and diabetes mellitus type 2 was in her usual state of health until 2 years ago, when she began to have morning headaches that would usually go away by themselves. Year later began to have hearing problem on her left side. Recently, she noticed intermittent loss of sensation of the left side of her face. She is taking a thiazide diuretic, captopril, glyburide, and metformin. She has no known allergies.
Physical exam: Slight drooping in the left mouth and lower eyelid. Incomplete closure of the left eyelid with corneal touch. Reduced pain and light touch on the left side. Fundoscopic exam revealed bilateral papilledema.
CNS Tumors
35y Male, depression2-year history of loss of initiative, depression. He had slowly lost his drive to win all the big deals he always done so well at work. 3 months ago he began to experience headache, which did not respond to acetaminophen or aspirin. His wife noticed that his lethargic state had increased in the past few months. 3 days ago his right arm began to convulse uncontrollably for 1 minute. 1 day ago the patient began again violently shaking his right arm, and the right side of face began to twitch at the dinner table. No fever.
Physical exam: Bilateral papilledema, increased deep tendon reflexes of the right bicep, tricep, +ve babinski sign on the right foot, reduced leg strength on the right.
CNS Tumors
35y Male, depression
Axial T1 weighted MRI
Axial T2 weighted MRI
CNS Tumors
35y Male, depression
Coronal T1 weighted MRI
Coronal T2 weighted MRI
CNS Tumors
3y Male, constant cry….Constant crying and not interacting with other children at daycare since 1m. Mother noticed that he was pointing to his head often. Family physician who stated that he was developing normally, and that the “ terrible two’s” are difficult period for parents. Recently started vomiting on a daily basis and started wobbling even though he learned to walk 6 months ago.
Physical: Bilateral papilledema and gait ataxia was noted on the physical exam.
CNS Tumors
Axial T1 weighted MRI Axial T2 weighted MRI
3y Male, constant cry….
CNS Tumors
Coronal T1 weighted MRI
3y Male, constant cry….
CNS Tumors
1. Glioblastoma m.
2. Astrocytoma
3. Meningioma
4. Ependymoma
5. Medulloblastoma
What is the most likely diagnosis?
CNS Tumors
65y Fem morning headache.Morning headache 2y, Progressive right upper limb weakness. She woke up this morning obtunded, and did not initially respond to her husband’s cries. She screamed to her husband that she could not see anything to her right, and that she that her left arm and leg were very weak. At this point her husband rushed her to the nearest hospital.Physical Exam: left lid ptosis, left-pupillary dilation, and failure of her left eye to constrict to light directly or consenually. Patient had bilateral lower limb weakness, with increased deep tendon reflexes on the left side, and a +ve babinski on the left side. Bilateral Papilledema. Homonymous hemianopia of the right side. Visual acuity was corrected to 20/20 with glasses.
CNS Tumors
65y Fem morning headache.
CNS Tumors
Brain Metastasis: Lung, Breast, Skin,
Kidney, GIT. Prostate – never..! Well demarcated,
usually multiple with surrounding rim of inflammation.
Carcinomatosis: Meningeal CSF spread of malignant cells.
CNS Tumors
Metastatic Melanoma: multiple
CNS Tumors
Brain Metastases: Surrounding edema.
CNS Tumors
1. Glioblastoma m.
2. Astrocytoma
3. Meningioma
4. Ependymoma
5. Medulloblastoma
What is the most likely diagnosis?
CNS Tumors
SAQ / KFP Are there clinical signs of
nerve compression? What is the most likely cause
of the homonymous hemianopia?
Why does the patient have progressive right upper limb weakness, and paroxysmal left upper and lower limb weakness?
Should a lumbar puncture be performed?
Why was the patient obtunded?
Why was an-x-ray taken?
Yes, ptosis, pupils 3rd Optic pathway -
occipital. Motor cortex
compression – tum. Risky. Brainstem
compression. Meningioma
hyperostosis.
Other CNS tumors
CNS Tumors
Nerve Sheath Tumors:
Neurofibroma: Epi & endoneurial fibroblasts. Form whorls of fibroblasts with nerves Well differentiated, benign, capsulated.
Schwannoma: Schwann cells, elongated form whorls Nuclear palisading
CNS Tumors
Schwannoma / Neurofibroma
CNS Tumors
Schwannoma 8th Nerve:
CNS Tumors
Bilateral 8th nerve schwannomas.
CNS Tumors
Schwannoma:
Neurofibromatosis:
Café-au-lait spot
Neurofibromatosis:
CNS Tumors
Schwannoma
CNS Tumors
A 26-year old femaleHeadache,vomiting, an epileptic attack, weakness of legs. Now drowsy. Two weeks before admission she gave her second birth.
CT and NMR revealed a huge parasagittal tumor (80x67x65 mm), enhanced by contrast, compressed corpus callosum and ventricles.