Tumors Flashcards
Incidence
- 10-17 per 100,000 people, more than double the number of cases of Hodgkin’s disease, and over
half the number of cases of melanoma - 50 - 75% – primary tumors
- 25 - 50% – metastastic tumors (stats vary depending upon source)
- Children:
- Cancer is #2 cause of death
- Of cancers, #1 Brain tumors (20%), #2 Leukemias
- 70% in posterior fossa
- Adults, 70% above tentorium
Unique Characteristics of brain tumors
- more difficult to tell benign from malignant; some tumors that look
benign act malignant - difficult to completely resect glial tumors without serious neurological effects
- if brain tumors occur in a vital location, does not matter if it is benign
or malignant - rarely get mets outside the CNS, can seed along the spinal cord and
lead to leptomeninigitis
Primary Brain Tumors: Clinical presentation:
depends upon location and rate of growth, can be focal or generalized
Generalized: due to increased ICP, can present with headache, nausea and vomiting, sixth nerve palsy; on physical exam will see papilledema if have increased ICP
Focal: hemiparesis, aphasia, seizures
-tumors in the ventricles (especially posterior fossa ependymomas) present with hydrocephalus
Primary Brain Tumors: Diagnosis and Risk Factors
only necessary test – MRI with contrast; CT can miss some lesions
Normally blood vessels in CNS (blood-brain barrier) will not accept contrast from peripheral circulation so
no contrast would go through. With high grade tumor, new blood vessels form which are leaky and contrast can
pass through. These lesions called contrast enhancing.
Risk Factors: only unequivocal risk factor is ionizing radiation
Gliomas
- Used to think these tumors were derived from their specific mature cell types in the CNS
(astrocyte->astrocytoma, oligodenodrocytes ->oligodendroglioma, ependymal cells->ependymoma,
etc) - Now, the tumors are thought to originate from progenitor cells that preferentially
differentiate down one of the cellular lineages
Gliomas: Astrocytomas include variety of tumors
ytomas include variety of tumors. WHO histologic grading for astrocytomas, I-IV:
I: well-differentiated - pilocytic astrocytoma
II: diffuse growth of well-differentiated astrocytes - diffuse astrocytoma
III: Anaplastic features (pleomorphism, increased mitoses) - anaplastic astrocytoma
IV: undifferentiated with vascular proliferation and necrosis - glioblastoma (formerly
known as glioblastoma multiforme or GBM).
Gliomas: Astrocytoma: Infiltrating astrocytomas
- Account for 80% of primary brain tumors
- spectrum of tumors from diffuse astrocytoma (grade II/IV) to anaplastic
astrocytomas (grade III/IV) to glioblastoma (grade IV/IV) - some tumors progress from low grade to glioblastoma
- occurs due to ordered accumulation of mutations
- see uniform sequence of tissue changes which meet the histologic criteria of malignancy
- most common mutations are affect p53 and overexpression of platelet derived growth factor
Gliomas: Astrocytoma: Infiltrating astrocytomas: Diffuse astrocytoma (II/IV):
- Most initially occur as low-grade tumors in younger adults, may
present with a seizure, HA, focal neurologic deficits. - Histologically: increase in number of glial cells, variable nuclear
pleomorphism, GFAP-positive astrocytic processes give a fibrillary background - Transition between neoplastic and normal tissue is indistinct
- Median survival: 5 years
- May recur as high-grade tumor
Gliomas: Astrocytoma: Infiltrating astrocytomas: Anaplastic astrocytoma (III/IV):
- Have regions that are more densely cellular with greater nuclear pleomorphism,
mitotic figures - MRI: non-enhancing lesion, may not be seen on CT
- Treatment: surgical resection but often cannot be resected due to size &
location. Radiation is most effective nonsurgical treatment - Median survival: ~ 2 years, most tumors progress to high-grade
Gliomas: Astrocytoma: Infiltrating astrocytomas: Glioblastoma
- high grade end of spectrum of astrocytomas, most atypical & mitotically active
- Primary
▪ Most common type
▪ New onset disease in older people - Secondary
▪ Younger patients
4
▪ Due to progression of a lower grade astrocytoma - Four molecular subtypes: (most affect two cancer hallmarks: sustained proliferative signaling and
evasion of growth suppressors) - Histology: characteristically have necrosis & vascular proliferation, get
pseudopalisading - MRI shows a contrast enhancing lesion (usually ring enhancing)
- treatment: surgery, radiation, chemotherapy
- uniformly fatal, survival ~15 mos, 25% alive at 2 years, shorter survival in older patients
Gliomas: Astrocytoma: Non-infiltrating Astrocytomas: Pilocytic astrocytoma (I/IV)
- occurs in kids & young adults
- relatively benign behavior
- occur in cerebellum, third ventricle
- often cystic, occurs as mural nodule
- Histology: cells with hair-like processes, eosinophilic fibers (Rosenthal
fibers) - Grow very slowly, recurrence often involves cyst enlargement rather than growth of solid component
- survival - patients have survived >40 years past incomplete excision
Gliomas: Oligodendroglioma
- most occur in adults, 4th
–5
th decades - relatively rare, slow growing
- occur mostly in cerebral hemispheres
- can result in bleeding
- Histology: sheets of regular cells with spherical nuclei, surrounded by clear
halo of cytoplasm (poached egg appearance) - calcifications - 90% of oligodendrogliomas
- Genetics:
o Mutations in IDH1 and IDH2 (90% of tumors
o Co-deletions in chromosome 1p and 19q (80% of tumors) - median long-term survival-approx 5 - 10 years
- treatment: surgery, radiation & chemotherapy, depending upon presentation
Gliomas: Ependymoma
- most often tumor of children & young adults
- Occur most often in ependymal-lined ventricular system
- Children and young adults: 4
th ventricle - Adults: spinal cord is most common location
- present with hydrocephalus, get CSF dissemination
- Histology: histologically are benign in appearance, occur as masses of small dark cells, variably
dense fibrillary background between nuclei, form perivascular pseudorosettes - Genetics: spinal cord ependymomas most commonly show a
mutation in NF2 gene on chromosome 22, supratentorial ependymomas show
alterations in chromosome 9 - prognosis: posterior fossa lesions ~ 5 years; resected supratentorial and spinal
cord lesions have a better prognosis - subtypes: myxopapillary ependymoma: occurs in fillum terminale of spinal
cord, can be difficult to resect, due to location, so recurrence is likely
Gliomas: Choroid plexus papillomas
- most common in children, in lateral ventricle
- in adults – fourth ventricle
- papillary growth with connective tissue stalk
- microscopically look just like normal choroid plexus
- present with hydrocephalus
Gliomas: Colloid cyst of third ventricle
- Young adults
- Attached to roof of the ventricle
- Can obstruct the foramina of Monro
- Can cause hydrocephalus
- Can be rapidly fatal
- Clinical: may complain of positional headache
Embryonal Tumors OR Primitive Neuroectodermal Tumors (PNET): Medulloblastoma
- WHO Grade IV/IV
- Highly malignant tumor of children
- Occurs in midline of the cerebellum – rapid growth may result in hydrocephalus
- Histology: Small round blue cell tumor, rosettes or perivascular pseudorosettes
- Molecular genetics: 4 groups
- Commonly get dissemination through the CSF – can spread down the spine even to the cauda
equina called “drop” metastasis - Very radiosensitive tumor
- 5-year survival with complete excision & radiation: 75%
Embryonal Tumors OR Primitive Neuroectodermal Tumors (PNET): CNS supratentorial primitive neuroectodermal tumors (CNS PNET)
- Children
- Occur in cerebral hemispheres
- Resemble medulloblastoma in histology and poor degree
of differentiation but differ in location - Genetically distinct from medulloblastoma
Other Lesions: Primary Brain Lymphoma
- Comprises 1% or less of all primary brain tumors
- Most common CNS neoplasm in immunosuppressed patients
- Patients get multiple tumor masses within the brain, rarely spreads to lymph nodes or outside
the brain - If patient has non-CNS lymphoma rarely involves brain parenchyma – although can spread to
CSF - Majority are B cell lymphomas,
a. In immunosuppressed, contain EBV genes (think AIDS, transplantation)
b. If not associated with immunosuppression, then phenotype is typical of postgerminal
center B cell differentiation - Aggressive disease, no role for resection, do not respond as well to chemotherapy
- Median survival- 4-5 years
Other Lesions: Metastatic Tumors
- Most common sites: lung, breast, skin (melanoma), kidney, & GI tract
(Lots of bad stuff kills glia) - Usually occur as multiples masses
- Treatment may improve quality of remaining life
Other Lesions: Meningiomas
- Most are WHO Grade I/IV, overwhelming majority of meningiomas are
benign, few are III or IV/IV
7 - Actually, not true brain tumors, arise from meningothelial cells of the
arachnoid - Constitute 20% of “brain tumors”
- Majority are found in adults as asymptomatic tumors discovered incidentally at autopsy
- Can present as headache or with neurologic sx
- Multiple meningiomas are found in patients with neurofibromatosis type 2 (NF2)
- Dural-based tumor
- Common sites
a. Parasagittal aspect of the brain convexity
b. Dura over the lateral convexity
c. Wing of the sphenoid
d. Olfactory groove
e. Sella turcica
f. Foramen magnum - MRI –
a. See adjacent to bone & have “dural tail” which indicates tumor is anchored to the
dura
b. Contrast-enhancing lesion - Histology – have many patterns of growth
a. Syncytial – Whorls of bland cells
b. Psammomatous – Psammoma bodies - Genetics: most common is loss of chromosome 22, deletions include NF2 gene (codes for
merlin [restricts cell-surface expression of growth factor receptors]) - If occur as small lesion, can just be followed
- Surgery is “definitive therapy,” although even with complete resection,
20% recur - Prior RT is a risk factor
Other Lesions: Craniopharyngioma
– Usually suprasellar arising in pituitary stalk
– Arise from remnants of Rathke’s pouch
– Bimodal age distribution: 5 – 15 yrs and > 65 yrs
– 5 – 10% of brain tumors in children
– Slow growing, benign, malignant transformation to squamous cell cancer is very rare
– Solid or mixed solid and cystic
– Two histologic types:
a. Adamantinomatous
– Children
– Stratified squamous epithelium in nests or chords
– Spongy reticulum
– Calcifications
– Lamellar keratin formation
– Cysts with thick brownish-yellow fluid contents
b. Papillary
– Adults
– Solid sheets and papillae lined by squamous epithelium
– No keratin, calcifications or cysts
– Clinical
a. Visual symptoms from pressure on optic chiasm
b. Children: growth retardation 2° pituitary hypofunction and GH def’cy
c. Headache
– Treatment – surgery and / or radiation therapy
Peripheral Nerve Sheath Tumors: Schwannoma
- Often arise directly from peripheral nerves, attached to but do not invade the nerve
- Commonly seen at cerebellopontine angle where attached to vestibular
branch of 8th nerve - called acoustic neuroma - Patients present with tinnitus and hearing loss
- Outside the dura they are commonly found associated with large nerves
- Associated with neurofibromatosis type 2 (NF2)
- See as well-circumscribed, encapsulated mass attached to nerve, but can be separated from
the nerve - Shows mixture of 2 growth patterns
- Antoni A: more cellular area with dense masses of nuclear
palisading called Verocay bodies - Antoni B: less cellular area, more myxoid
- Completely benign lesions – surgical removal is curative
- Genetics – inactivating mutations in NF2 gene on chromosome 22
Peripheral Nerve Sheath Tumors: Neurofibroma
- Benign spindle cell lesions which occur in three forms:
1. Superficial cutaneous: skin or peripheral nerve - sporadic or associated with NFI
- never turn malignant
2. Diffuse: large plaque-like elevation of skin, NF1-associated
3. Plexiform: - only in patients with NF1
- significant potential for malignant transformation to Malignant
Peripheral Nerve Sheath Tumor (MPNST) - occurs associated with large nerves, cannot be
separated from the nerve - Histology: Admixed
1. Neoplastic Schwann cells
2. Perineurial-like cells
3. Mast cells
4. CD34+ spindle cells
5. Fibroblasts
Familial Tumor Syndromes: Neurofibromatosis: NF Type 1
- AD
- Get multiple neurofibromas: superficial cutaneous, diffuse & plexiform
- Get gliomas of optic nerve
- Pigmented nodules of iris (Lisch nodules)
- Café au lait spots – brown spots on skin
- Genetics: NF1 gene neurofibromin, tumor suppressor,
chromosome 17 - One of the more common genetic disorders
- Increased propensity for neurofibromas to undergo malignant
transformation
