Tumors Flashcards
(99 cards)
1
Q
In what general location of the brain are most adult brain tumors found vs. brain tumors in kids?
A
Adults - supratentorial
Kids - cerebellum and brainstem
2
Q
What are common brain tumors in adults vs. kids?
A
Adults - glioblastoma and meningioma
Kids - pilocytic astrocytoma and medulloblastoma
3
Q
True or False: brain tumors are the most common solid tumor in children
A
True; they are the second most common type of malignancy in children overall, after leukemia.
4
Q
What should be at the top of your list of differential diagnoses in an adult w/ new onset seizure?
A
brain tumor
common adult brain tumor: glioblastoma
5
Q
What are two characteristics features of a Grade IV tumor?
A
- vascular proliferation
- necrosis
6
Q
How are tumors graded using the four histological parameters of gliomas: atypia, mitoses, vascular proliferation, and necrosis?
A
one parameter: II (ex: atypia)
two parameters: III (ex: atypia and mitoses)
three/four parameters: IV
7
Q
Pilocytic astrocytomas are commonly found in which age group and what grade are they?
A
- children
- Grade I
8
Q
Glioblastomas are commonly found in which age group and what grade are they?
A
- adults
- Grade IV
9
Q
How are age of patient and tumor grade related in astrocytomas?
A
- the higher the patient age of typical onset, the higher the grade level of the tumor type
ex: Grade II 40’s and 50’s; Grade III 60’s
10
Q
Are astrocytomas usually white matter lesions or grey matter lesions?
A
White matter lesions
11
Q
What age group is most common for pilocytic astrocytomas?
A
-younger than 20 yrs old
first two decades, same as ependymomas
12
Q
What part of the brain is most common for pilocytic astrocytomas to be located?
A
- cerebellum
- posterior fossa
13
Q
What gene mutation predisposes patients to pilocytic astrocytomas?
A
NF1
-functional loss of neurofibromin in the tumor
14
Q
What is the gross appearance of a pilocytic astrocytoma?
A
- -well-circumscribed
- -cystic w/ a mural nodule
15
Q
What do the cells of a pilocytic astrocytoma look like?
A
–hair-like cells w/ long bipolar processes
16
Q
Do you typically see Rosenthal Fibers in a Pilocytic Astrocytoma?
A
Yes!
17
Q
Besides Rosenthal Fibers, what other structure do you see on histology of Pilocytic Astrocytomas?
A
Eosinophilic Granular Bodies (EGB’s)
18
Q
Are pilocytic astrocytomas GFAP positive or negative?
A
GFAP positive
19
Q
What is the most common primary brain neoplasm?
A
glioblastoma (Grade IV)
20
Q
What is a primary glioblastoma vs a secondary glioblastoma?
A
- primary glioblastomas appear as a new onset dz in older individuals
- secondary glioblastomas occur in younger pts as a results of progression of a lower-grade astrocytoma
21
Q
What genetic changes are seen in primary glioblastomas?
A
- mutations of PTEN suppressor gene
- deletions of chromosome 10
- amplification of EGFR oncogene
22
Q
What genetic changes are seen in secondary glioblastomas?
A
-mutations of p53
- point mutations of IDH1 and IDH2 (isocitrate dehydrogenase)
- -mutant form of IDH1 (R132H) has a better outcome than the wild type IDH1
23
Q
What is seen on imaging and morphology of a glioblastoma?
A
- -contrast ring-enhancing
- -central necrosis
- -crosses the corpus callosum
24
Q
What is seen on histology of glioblastomas?
A
- necrosis in a serpentine pattern in hypercellular areas
- pseudo palisading
- vascular/endothelial proliferation
- -VEGF production d/t hypoxia
- -glomeruloid bodies bulging into vascular lumen
25
Where in the brain do oligodendrogliomas (Grade II) usually occur?
- primarily in the cerebral hemispheres
| - predilection for white matter
26
What age group is most commonly affected by oligodendrogliomas?
-adults in their 50's and 60's
27
What is seen on morphology of oligodendrogliomas?
-calcification of the cortex in a gyriform distribution
28
What is seen on histology of oligodendrogliomas?
- perineuronal satellitosis (tumor cells collect around neurons)
- perivascular aggregation (chicken-wire pattern of vasculature, delicate anastamosing capillaries)
Note: remember oligodendrocytes look like "fried eggs" on H/E stains d/t the perinuclear halo artifacts
29
What is the most common gene mutation in oligodendrogliomas?
- -IDH1 and IDH2 (present in 90% of cases)
- --hold a favorable prognosis
--1p and 19q co-deletions (80% of cases)
30
What is notable about treatment of oligodendrogliomas with a 1p and 19q loss?
--consistent, long-lasting response to chemo and radiation
--tumors w/o the 1p and 19q loss appear to be resistant to chemo regimens
31
What are the characteristics of an anaplastic oligodendrogliomas (Grade III)?
- increased nucleus:cytoplasm ratio
- increased mitosis
- increased cellularity
- can be found in nodules within Grade II tumors
- poor prognosis (but still better than glioblastomas)
32
What age group is typically affected by ependymomas?
-younger than 20yrs old
| first two decades, same as pilocytic astrocytomas
33
What is the most common site in the brain for ependymomas?
-fourth ventricle (arising from the floor)
- spinal cord in adults
- -frequent w/ neurofibromatosis type 2 (NF2)
34
What is the gross morphology of ependymomas in the fourth ventricle?
- discrete
- exophytic
- enhancing
35
What is seen on histology of ependymomas?
- ependymal rosettes (true rosettes)
- perivascular rosettes
--true ependymal rosettes are more diagnostic (tubular structure w/ central canal)
36
What are the clinical features of ependymomas?
- hydrocephalus d/t 4th ventricle obstruction
- dissemination into the CSF (poor prognosis)
- 5yr survival in young children is less than 50%
37
What type of tumor is a medulloblastoma?
- malignant embryonal tumor in kids
- -neuroectoderm in origin; very poorly differentiated
-located exclusively in the cerebellum (midline)
38
What are the four groups of molecular alterations in medulloblastomas?
- WNT signaling pathway mutation (chr 6 monosomy)
- SHH signaling pathway mutation (MYC amplification)
- i17q w/ MYC (infants and young kids; worst outcome)
- i17q w/o MYC (poor prognosis)
39
Which molecular alteration in medulloblastoma has the best prognosis and which has the worst prognosis?
- WNT is best (90% 5yr survival rate)
| - i17q w/MYC amplification is the worst prognosis
40
What is a complication of rapid growth of a midline cerebellar medulloblastoma?
-hydrocephalus d/t occlusion of CSF flow
41
What do you seen on histology of a medulloblastoma?
- sheets of anaplastic cells
- abundant mitoses
- Homer Wright rosettes (neuropil in center)
42
What is a common complication of tumor cell dissemination into the CSF that can happen w/ a medulloblastoma?
-nodular masses, sometimes as far as the cauda equina
| aka "drop metastases
43
What is notable about the treatment of medulloblastomas?
-they are exquisitely radiosensitive
44
What tumor resembles a medulloblastoma that occurs in the cerebral hemispheres?
- CNS PNET
- -PRIMITIVE neuroectodermal tumor)
-poorly differentiated
45
Where in the brain do AT/RT (atypical teratoid/rhabdoid tumors) typically occur?
- posterior fossa
| - supratentorial
46
What types of cells comprise an AT/RT?
- divergent differentiation
- -epithelial
- -mesenchymal
- -neuronal
- -glial
- -rhabdoid
47
What proteins are present in rhabdoid cell cytoplasm that test positive in AT/RT's?
+epithelial membrane antigen (EMA)
+vimentin
+smooth muscle actin and keratins
NO desmin or myoglobin
48
What do rhabdoid cells look like on H and E stain?
- eosinophilic cytoplasm
- sharp borders
- eccentric nucleus
49
What is the most common genetic mutation in AT/RT (atypical teratoid/rhabdoid tumor)?
- mutation on chr 22 in 90% of cases
| - hSNF5/INI1 gene
50
What is the age most commonly affected by AT/RT's and what is the prognosis?
- nearly all tumors occur before the age of 5
| - most pts live less than 1yr after Dx
51
What is the most common CNS neoplasm in immunocompromised individuals, such as those with AIDS?
-Primary CNS lymphoma
52
True or False: primary CNS lymphoma often spreads outside of the CNS into LN's and bone marrow
False; and the converse is the same. Lymphomas arising outside the CNS rarely involve brain parenchyma.
53
What are the main locations of Primary CNS Lymphoma and the major cell type involved?
- multifocal
- periventricular spread is common
-usually B cells (CD20+) w/ high growth fraction
in immunocompromised, EBV is normally positive
54
Where do the tumor cells of a primary CNS lymphoma tend to accumulate?
-malignant cells infiltrate the brain parenchyma and accumulate around blood vessels
55
What is seen on a silver stain of Primary CNS lymphoma?
"hooping"
-cells are separated by reticulin
56
Where in the brain do primary germ cell tumors occur?
-along the midline
57
What ages and sex is most commonly affected by germ cell tumors in the brain?
- pineal location has a male predominance
- also occur in a suprasellar location
- 90% occur in those younger than 20yrs
58
What should be ruled out if a germ cell tumor is found in the brain?
-need to r/o metastasis from a gonadal germ cell tumor, since metastasis to the brain is common
59
What is a germ cell tumor's typical response to treatment?
- good response to radiation and chemo
| - alpha fetoprotein and hcg are used to track the tumor's response to treatment
60
What is the most common type of pineal tumor?
germinoma
61
What are two kinds of pineal parenchyma tumors?
Pineocytoma:
- neuronal differentiation,
- low grade, adults
Pineoblastoma:
- necrosis, mitoses, RB gene
- high grade, kids
- spreads throughout the CNS
62
When do meningiomas (Grade I) usually occur?
-occur after age 30
63
True or False: meningiomas commonly infiltrate the brain
False; they enlarge slowly and don't typically infiltrate the brain, but they will cause compression of it.
Meningiomas WILL penetrate BONE.
64
What is the common etiology of meningiomas?
radiation-induced from cancer treatment decades prior
65
What is the most common cytogenic abnormality in meningiomas?
- loss of 22q in 55% of cases
- -includes 22q12 (NF2) which codes for merlin
-tend to be higher grade tumors
66
What should be considered as a diagnosis in someone presenting with multiple meningiomas?
Neurofibromatosis Type 2
67
After NF2 gene, what is another cytogenic abnormality in meningiomas?
TRAF-7 (TNF receptor associated factor 7)
-tends to be lower grade tumors
68
What is the typical morphologic presentation of a meningioma?
- -rounded, well-defined mass with dural base
- -intraventricular or parasagittal
- -bosselated (bunches of balls like a blackberry)
- -contain calcified psammoma bodies
--or "en plaque" that spread like a sheet along dura
69
What is the cell of origin in meningiomas?
- arises from the meningothelial cells of the arachnoid
| - EMA+ (epithelial membrane antigen)
70
What is seen on histology of meningiomas?
- whorled clusters of monotonous cells
- psammoma bodies (calcification of nests of cells)
-the secretory type has PAS+ intracytoplasmic droplets
71
What are the characteristics of an Atypical Meningiomas (Grade II)?
- higher rate of recurrence
- may require radiation after surgery
- 4+ mitoses per 10 HPF
-"clear cell" and "choroid" are also in this category because they're more aggressive
72
What are the characteristics of an Anaplastic (malignant) meningioma (Grade III)?
-20+ mitoses per 10 HPF
Papillary Subtype:
-pleomorphic cells arranged around fibrovascular core
Rhabdoid Subtype:
-tumor cell sheets w/ hyaline eosinophilic cytoplasm
73
What type of hormone receptor is common for meningiomas to display and what is a consequence of this?
- 70% express progesterone receptors
| - may grow more rapidly during pregnancy
74
What type of cancer accounts for more than half of metastases to the brain?
- metastatic carcinomas
| - -most commonly lung and breast carcinomas
75
What is an example of a rare tumor that frequently metastasizes to the brain?
choriocarcinoma
76
What is an example of a very common cancer that rarely metastasizes to the brain?
prostate cancer
77
What part of the brain is a frequent site of metastasis?
meninges
Meningeal Carcinomatosis: tumor nodules studding the surface of the brain, spinal cord, and intradural nerve roots (most commonly associated w/ lung and breast CA)
78
What is the morphology of intraparenchymal metastases?
- form sharply demarcated masses
- occur at the grey to white junction
- often surrounded by edema
79
What are the characteristics of Subacute Cerebellar Degeneration (a paraneoplastic syndrome)?
- -gliosis, destruction of Purkinje cells
- -PCA-1 antibody
- -predominantly ovarian, uterine, or breast carcinoma
80
What are the characteristics of Limbic Encephalitis (a paraneoplastic syndrome)?
--ANNA-1 Ab (Anti-Hu) recognizes neuronal nuclei in CNS and PNS, most common from small cell lung CA
--NMDA receptor Ab cross reacts w/ hippocampus
--VGKC-complex Ab recognizes voltage-gated K+ channels; associated w/ peripheral neuropathy
81
True or False: symptoms of limbic encephalitis occur before any malignancy is suspected
True
Limbic encephalitis characterized by: subacute dementia, perivascular inflammatory cuffs, microglial nodules, neuronal loss, gliosis (most evident in anterior/medial temporal lobe)
82
What eye movement disorder may be found as a paraneoplastic syndrome?
--opsoclonus (uncontrolled, irregular, non-rhythmic eye mvmt)
--neuroblastoma in kids
83
What is Lambert-Eaton Myasthenic Syndrome (a paraneoplastic syndrome)?
--Ab's against voltage-gated Ca+ channels
84
What is the treatment for paraneoplastic syndromes?
- immunotherapy to remove the circulating Ab's
| - tumor removal
85
What are the associated features of Neurofibromatosis Type 1 (more common than Type 2)?
- pheochromocytoma
- cafe au lait spots
- optic nerve glioma
- pigmented nodules of the iris (Lisch nodules)
- neurofibromas of peripheral nerve
86
What are the associated neoplasms of Von Hippel-Lindau Disease (VHL)?
- pheochromocytoma
- renal cell carcinoma
- hemangioblastoma
- pancreatic endocrine neoplasm
87
What is the inheritance of Von Hippel-Lindau Disease?
autosomal dominant
- VHL chr3p25q3 (tumor suppressor gene) mutation
- -downregulates HIF-1, which regulations VEGF
- -regulates EPO (creates polycythemia)
88
What is the inheritance of Neurofibromatosis Type 1?
-autosomal dominant
89
What are the characteristics of Neurofibromatosis Type 2?
- B/L schwannomas of CN VIII
- multiple meningiomas
- multiple ependymomas
90
What are the characteristics of Cowden Syndrome?
- dysplastic gangliocytoma of the cerebellum
| - PTEN mutation causes PI3K/AKT signal pathway
91
What is Li-Fraumeni Syndrome?
- medulloblastomas
| - p53 mutations
92
What is Turcot Syndrome?
- medulloblastoma
- glioblastoma
- APC mutations or mismatch repair genes
93
What is Gorlin Syndrome?
- -medulloblastoma
| - -PTCH mutations (up-regulation of SHH pathway)
94
What is the inheritance of Tuberous Sclerosis and the neuro symptoms?
-autosomal dominant
- seizures (d/t cortical epileptogenic tubers)
- autism, mental retardation
95
What are the genes involved in Tuberous Sclerosis?
- TSC1 (chr 9q34 for hamartin)
| - TSC2 (chr 16q13.3 for tuberin)
96
What are the physical symptoms of Tuberous Sclerosis?
- benign hamartomas
- subependymal nodules ("candle-guttering")
- SEGA (subependymal giant cell astrocytomas)
- renal angiomyolipomas
- cardiac rhabdomyomas
- cutaneous lesions
- -Shagreen Patches (localized thickening)
- -Ash Leaf Patches (hypopigmented areas)
97
What are the characteristics of a Schwannoma (a peripheral nerve sheath tumor)?
- S100+
- acoustic neuroma of CN VIII ... tinnitus, hearing loss
- NF2 (loss of merlin)
- Antoni A areas: spindle cells, verocay bodies (palisading nuclei around nuclear free zones)
- Antoni B areas: hypocellular w/ myxoid EC matrix
98
Are the majority of Malignant Peripheral Nerve Sheath Tumors high grade or low grade?
- 85% are high grade
| - about 50% occur in NF1 pts
99
What is the "divergent differentiation" that is exhibited in malignant peripheral nerve sheath tumors?
- glandular, cartilaginous, osseous, rhabdomyoblastic morphology d/t differentiation in focal areas
- Triton Tumors exhibit rhabdomyoblastic areas
