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NMSP Exam I > Chapter 28: Tumors > Flashcards

Chapter 28: Tumors Flashcards

1
Q

Which grade of tumor is considered infiltrative? aka what stage does a tumor become infiltrative?

A

Grade II

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2
Q

In which decade of life are Grade II, III, and IV Astrocytomas found?

A
  • Grade II: usually 3rd-4th decase
  • Grade III: usually 5th decade
  • Grade IV: usually 6th decade and beyond
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3
Q

Pilocytic Astrocytomas generally occur during what decades of life?

Where in brain do they typically occur?

A
  • First 2 decades of life
  • Cerebellum and floor/walls of 3rd ventricle, optic nerves, spinal cord, and occasionally cerebral hemispheres
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4
Q

What grade of tumor is a Pilocytic Astrocytoma?

A
  • I/IV
  • Benign
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5
Q

What are the distinguishing morphological characteristics of Pilocytic Astrocytomas?

A

- Well-circumscribed, often CYSTIC w/ a mural nodule

- Biphasic pattern (alternating loose and compact regions of tumor growth)

  • Hair-like cells w/ long bipolar processes
  • Rosenthal fibers
  • Eosinophilic granular bodies (EGBs) (mark of slow growing tumors)
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6
Q

Which disease predisposes patients to Pilocytic Astrocytomas and due to what?

A

NF-1 due to functional loss of neurofibromin

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7
Q

Alterations in what signaling pathway have been found in Pilocytic Astrocytomas?

A

BRAF signaling pathway

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8
Q

Which brain tumor appears as a cystic mass with a mural nodule?

A

Pilocystic astrocytoma

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9
Q

Which 3 tumors are part of the Glioma family?

A
  • Astrocytoma
  • Oligodendroglioma
  • Ependymomas
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10
Q

Most common presenting signs and symptoms of Infiltrating Astrocytomas?

A

Seizures, headaches, and focal neurologic deficits related to the site of involvement

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11
Q

Which type of infiltrating astrocytoma belongs to the Grade II-IV designation?

A

Grade II: diffuse astrocytoma

Grade III: anaplastic astrocytoma

Grade IV: glioblastoma (this is malignant)

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12
Q

what is the mutant protein that causes 90% of cases of infiltrating astrocytomas?

A

IDH1 R132H mutant protein IHC

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13
Q

Among the higher grade astrocytomas (grades II-IV), presence of what mutation is associated with a better outcome?

A

Mutant form of IDH1

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14
Q

what is the gross appearance of an infiltrative astrocytoma?

A

there is blurring of the corticomedullary junction

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15
Q

Tumor where the predominant neoplastic astrocyte has a brightly eosinophilic cell body from which emanante abundant, stout processes describes what?

A

Gemistocytic astrocytoma

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16
Q

What are the 3 histology hallmarks of glioblastoma?

A

Pseudo-palisading: tumor cells collecting along the edges of necrotic regions

Necrosis: serpentine

Vascular/endothelial proliferation

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17
Q

Necrosis in glioblastoma often occurs in a ________ pattern in areas of hypercellularity

A

Serpentine

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18
Q

Which additional features differentiate a glioblastoma from anaplastic astrocytomas?

A

Necrosis and vascular (glomeruloid type)/endothelial cell proliferation

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19
Q

What characteristic of Glioblastomas is seen on MRI?

A

Contrast ring-enhancing, hypodense central necrosis

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20
Q

Which tumor often crosses the corpus callosum and produces a “butterfly” appearance

A

Glioblastoma

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21
Q

Contrast ring enhancing lesions, with hypodense central necrosis is characteristic of what kind of tumor?

A

Glioblastoma

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22
Q

Which tumor is most often found in the temporal lobe in children and young adults, usually with a history of seizures?

A

Pleomorphic Xanthoastrocytoma

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23
Q

What distinguishes a Pleomorphic Xanthoastrocytoma from more malignant types?

What is the grade and prognosis of this tumor?

A
  • Abundant reticulin deposits, absence of necrosis and mitotic activity
  • Grade II/IV w/ 5-year survival rate of 80%
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24
Q

What is the most common Brainstem Glioma?

A

Intrinsic pontine glioma

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25
Q

What is the prognosis of Intrinsic Pontine Gliomas?

A

Aggressive and short survival (most common brainstem gliomas)

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26
Q

When are Oligodendrogliomas most commonly seen (decades)?

How are they graded?

A
  • Most common in fourth and fifth decades
  • Grade II/IV
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27
Q

Where in the brain are Oligodendrogliomas most often seen?

A

Cerebral hemispheres w/ predilection for white matter

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28
Q

What are the most common mutations seen in Oligodendrogliomas; which have a better prognosis?

A
  • IDH1 and IDH2 (better prognosis)
  • 1p19q loss (favorable prognosis)
  • CDKN2A
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29
Q

What are the distinguishing morphological characteristics of Oligodendrogliomas?

A
  • CALCIFICATION
  • Perinuclear halos, “fried eggs” and delicate anastomosing capillaries, “chicken wire”
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30
Q

Which features distinguish an Anaplastic Oligodendroglioma (III/IV) from an Oligodendroglioma?

A

Vascular hypertrophy, necrosis, and nuclear anaplasia

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31
Q

During which decades of life are Ependymomas most commonly seen and where are they most commonly located?

A
  • First 2 decades
  • Fourth ventricle = most common site
  • Spinal cord = most common for adults
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32
Q

When Ependymomas occurs in adults they are most often associated with what other condition; due to what mutation?

A

NF2 – due to mutation on chromosome 22

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33
Q

Which chromosome is the NF2 gene found on?

A

Chromosome 22

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34
Q

Well circumscribed tumors in the brain that often have cysts, focal hemorrhage, and calcification generally describes?

A

Oligodendrogliomas

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35
Q

A tumor displaying uniform populations of cells w/ round or oval nuclei w/ abundant clumped chromatin and the appearance of perivascular rosettes is often what type?

A

Ependymoma

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36
Q

Which rosette type found in ependymomas are more diagnostic?

A

Ependymal rosettes (true rosettes) = MORE diagnostic than perivascular rosettes

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37
Q

What is the grade for most Ependymomas?

A

Grade II/IV

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38
Q

Which tumor type is often found in the filum terminale of the spinal cord?

A

Myxopapillary ependymomas

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39
Q

What is a frequent clinical manifestation of posterior fossa ependymomas?

A

Hydrocephalus (non-communicating) secondary to progressive obstruction of the 4th ventricle

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40
Q

Which location of ependymomas have the worst overall prognosis in children?

A
  • Posteior fossa = worst overall prognosis; 5 year survival is 50%
  • Completely resected supratentorial and spinal types are better
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41
Q

what are the three different types of ependymomas?

A
  • anaplastic ependymoma
  • mxyopapillary ependymoma
  • subependymoma
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42
Q

what grade is given to subependymoma and where are they located?

A
  • grade I/ IV
  • located in the lateral or 4th ventricle
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43
Q

how do subependymomas present? What can subependymomas lead to?

A
  • usually asymptomatic, incidental finding
  • can lead to obstructive hydrocephalus
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44
Q

what are the morphological features suggestive of a subependymoma?

A

clusters of nuclei in a dense fibrillary background suggestive of subependymoma

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45
Q

what are the morphological features of a myxopapillary ependymoma?

A

blue myxoid material in core of papillary structures

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46
Q

Homer-Wright rosettes are most often seen with what 2 brain tumors?

A

1) Medulloblastoma
2) Neuroblastoma

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47
Q

Choroid plexus papillomas are most often found where in children and adults?

A
  • In children – lateral ventricles
  • In adults – fourth ventricle
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48
Q

Who is most often affected by Non-neoplastic Colloid Cysts of the 3rd Ventricle?

What is the clinical manifestation?

A
  • Young adults
  • Found attached to roof of 3rd ventricle, can obstruct foramina of Monro = non-communicating hydrocephalus
  • Can be rapidly fatal
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49
Q

What is an important clinical symptom of Colloid Cysts of the 3rd Ventricle?

A

Headache, sometimes positional (worse when standing up)

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50
Q

What is the most common neuronal type of tumor in the CNS?

Common activating mutation?

A
  • Gangliogliomas
  • Mutations in BRAF
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51
Q

Gangliomas are typically ________ lesions that present with ______

A

Gangliomas are typically superficial lesions that present with seizures

52
Q

Gangliogliomas are most commonly found in the _______ lobe and have a _____ component

A

Gangliogliomas are most commonly found in the temporal lobe and have a cystic component

53
Q

what is a rare, benign (WHO Grade I) tumor often associated with epilepsy?

A

Dysembryoplastic neuroepithelial tumor (DNET)

54
Q

where are dysembryoplastic neuroepithelial tumors (DNETs) most likely to be found? How do they appear?

A
  • superficial temporal lobes
  • multiple discrete mucin-rich intracortical nodules of small oligodendrocyte-like cells
55
Q

What is the most common malignant embryonal CNS tumor in children?

A

Medulloblastoma (IV/IV)

56
Q

Medulloblastomas are often located where?

A

Midline of the Cerebellum

57
Q

Medulloblastomas that occur in older children tend to have what genetic mutations?

A
  • Mutations in WNT signaling pathway
  • Monosomy of chromosome 6
  • Nuclear expression of β-catenin
58
Q

What is the prognosis of the WNT type of medulloblastomas?

A

Best prognosis: with 90% 5-year survival

59
Q

Medulloblastomas with the second best prognosis, behind the WNT type, tend to occur in infants-young children and are associated with what mutations?

A
  • Mutations in SHH pathway
  • May also have MYCN amplification
60
Q

Group 3 medulloblastomas (worst prognosis) tend to occur in infants-young children and are associated with what mutations?

A
  • MYC amplification
  • Isochromosome 17 (i17q)
61
Q

What are the mutations associated with group 4 Medulloblastomas and what is the prognosis?

A
  • i17q cytogenic alterations, classic or large cell histology
  • WITHOUT MYC amplification
  • Sometimes with MYCN amplification
  • Intermediate prognosis, in general i17q signals a worse prognosis
62
Q

Which variant of medulloblastomas is characterized by areas of stromal response marked by collagen and reticulin deposition that form pale islands with more neuropil and neuronal markers?

A

Nodular desmoplastic type

63
Q

What is a common complication due to Medulloblastomas propensity to form linear chains and infiltrate?

A
  • May infiltrate cerebral cortex and penetrate the pia, spreading into subarachnoid space
  • Dissemination through CSF is common complication, giving rise to nodular masses some distance from the priamry tumor (i.e., as far as the cauda equina) – Drop Metastases
64
Q

How well do Medulloblastomas respond to treatment?

A
  • Exquisitely radiosensitive
  • Total excision and irradiation, 5 year survival of 100%
65
Q

What are CNS supratentorial primitive neuroectodermal tumors (CNS PNET)?

A

A distinct type of tumor that is poorly differentiated and resembling a medulloblastoma

66
Q

Atypical Teratoid/Rhabdoid Tumors are most commonly seen in whom and where are they seen in the brain?

Benign or malignant?

A
  • Highly malignant tumor (grade IV) of young children (most often before age 3)
  • Posterior fossa and supratentorial compartments
67
Q

Which chromosome is most often altered in Atypical teratoid/Rhaboid tumors and is considered a hallmark; what specific gene?

A
  • Chromosome 22
  • hSNF5/INI1
  • Deletion of the locus and loss of nuclear staining for INI1 protein seen in majority
68
Q

Cytoplasm of rhaboid cells found in Rhaboid tumors is immunoreactive for what?

A
  • Epithelial membrane antigen (EMA)
  • Vimentin

*Other markers may include: smooth muscle actin and keratins

69
Q

What is the most common CNS neoplasm in immunosuppressed patients, such as those with AIDS or following transplantation?

A

Primary CNS lymphoma

70
Q

Vast majority of primary brain lymphomas are of _____origin (immune cell)

A

B-cell CD20+

71
Q

In the setting of immunosuppression, the cells in nearly all primary brain lymphomas are latently infected by which virus?

In the setting of organ transplantation, may be associated with a systemic what?

A
  • Epstein-Barr virus
  • Systemic post-transcriptional lymphoproliferative disorder
72
Q

When not associated with immunosuppression, primary CNS lymphomas show a phenotype typical of __________ differentiation

A

Postgerminal center B-cell differentiation

73
Q

What is the morphology of the lesions associated with Primary CNS Lymphomas?

Which stain shows their characteristic pattern?

A
  • Frequently mutliple and often involve deep gray matter as well as white matter and cortex; accumulate around vessels
  • Reticulin + silver stain show infiltrating cells separated from one another in a pattern called “hooping.”
74
Q

Primary brain germ cell tumors occur along where?

Most commonly in what locations?

A
  • Along the MIDLINE!
  • Most commonly in the pineal (male predominance) and suprasellar regions
75
Q

During what decades do the majority of Primary Brain Germ Cell tumors occur and who is affected the most?

A
  • 90% during first 2 decades
  • Japanese have highest incidence
76
Q

Germ cell tumors in the pineal region show a strong predominance in which sex?

A

Males

77
Q

Which markers of CNS germ cell tumors may be helpful in assisting with diagnosis and tracking response to therapy?

A
  • α-fetoprotein
  • β- hCG
78
Q

Metastasis of which type of germ cell tumor to the CNS is common?

What is the significance of this in regards to classifying the tumor?

A

Gonadal germ cell tumors

*Why the presence of a non-CNS primary tumor must be excluded before a diagnosis of primary germ cell tumor of the CNS is made!

79
Q

The tumor that is histologically similar to a seminoma in the testis is referred to what in the CNS?

A

Germinoma

80
Q

What is the response of primary brain germ cell tumors to radiation therapy/chemotherapy?

A

Good response

81
Q

Differentiate Pineocytomas from Pineoblastomas in regards to grade and and who they most commonly affect.

A
  • Pineocytomas = LOW grade and more common in adults
  • Pineoblastomas = HIGH grade and more common in kids
82
Q

Pineoblastomas occur with increased frequency in individuals with which germ line mutations?

A

Germ line mutations in RB

83
Q

What is the most common pineal tumor?

A

Germinoma

84
Q

What is a risk factor for the development of Meningiomas?

A

Prior radiation therapy to the head and neck, typically decades earlier

85
Q

What is the severity of Meningiomas, who are they commonly seen in and where are they found?

A
  • Benign tumors of adults
  • Usually attached to the dura; found along any of the external surfaces of the brain as well as ventricular system
86
Q

What is the most common cytogenic abnormality seen in Meningiomas?

A
  • Loss of chromosome 22, especially the long arm (22q)
  • Including the region that harbors the NF2 gene, which encodes the protein merlin
87
Q

Higher grade Meningiomas are associated with what mutations?

A

NF2 mutations, loss of chromosome 22, and evidence of chromosomal instability

88
Q

What is the most common mutation seen in Meningiomas without NF2 mutations?

What is the histologic grade of this type?

A
  • TNF-receptor associated 7 (TRAF7)
  • Lower histologic grade
89
Q

Which tumors are often seen growing en plaque, in which the tumor spreads in a sheet like fashion along the surface of the dura?

A

Meningiomas

90
Q

Which tumor of the CNS is characterized by whorled clusters of monotonous cells; psammoma bodies?

A

Meningioma

91
Q

Which subtype of Meningiomas has PAS+ intracytoplasmic droplets?

Is associated with mutations in what genes?

A
  • Secretory subtype
  • TRAF7 and KLF4 genes
92
Q

What is the typical patient presentation for a Meningioma?

A

Present with vague non-localizing signs and symptoms or with focal findings due to compression of underlying brain

93
Q

Which receptors may be expressed by Meningiomas and which patient population can this potentially affect?

A
  • Progesterone and Estrogen receptors
  • Pregnancy increases symptomatic presentation NOT incidence
94
Q

What are the 5 most common primary sites for potential metastasis to the brain?

A
  1. Lung
  2. Breast
  3. Skin (melanoma)
  4. Kidney
  5. GI
95
Q

Which rare tumor has a high likelihood of metastasing to the brain?

A

Choriocarcinomas

96
Q

Where in the CNS is a frequent site of involvement for metastatic disease?

A
  • Meninges
  • Intraparenchymal = Gray/White junction
97
Q

Meningeal carcinomatosis with tumor nodules studding the surface of the brain, spinal cord, and intradural nerve roots is most commonly associated with carcinoma of the _______ and _______.

A

Lung and Breast

98
Q

What are the common histologic findings of metastases to the CNS?

A

Nodules of tumor, often with central areas of necrosis, surrounded by reactive gliosis

99
Q

Subacute cerebellar degeneration (paraneoplastic syndrome) is associated with destruction of which structures?

Which antibody?

Which cancers?

A
  • Destruction of Purkinje cells, gliosis, and a mild chronic inflammatory cell infiltrate
  • PCA-1 antibody (anti-Yo)
  • Women w/ ovarian, uterine, or breast carcinoma
100
Q

Which antibody is most commonly associated with small cell carcinoma of the lung and may cause limbic encephalitis (paraneoplastic)?

A

ANNA-1 antibody (anti-Hu) recognized neuronal nuclei in the CNS and PNS

101
Q

Which antibody is most commonly associated with ovarian teratomas and may cause limbic encephalitis (paraneoplastic)?

A

NMDA receptor antibody cross-reacts with hippocampal neurons

102
Q

Which antibody is most commonly associated with peripheral neuropathy and may cause limbic encephalitis (paraneoplastic)?

A

VGKC-complex antibody: voltage-gated potassium channel

103
Q

What is an important consideration in regards to limbic encephalitis and malignancy?

A

The syndrome appears before any malignancy is suspected

104
Q

Opsoclonus (eye movement disorder) in children is most commonly associated with what malignancy?

A

Neuroblastoma

105
Q

Lambert-Eaton myasthenic syndrome is caused by antibodies against?

A

Voltage-gated calcium channels in the presynaptic elements of the NMJ

106
Q

What is the treatment for some of the paraneoplastic syndromes and in general which are the best responders?

A
  • Immunotherapy (removal of circulating antibodies and immunosuppression)
  • Those with plasma membrane-reactive antibodies (i.e., VGKC and NMDAR) respond better
107
Q

Cowden syndrome is associated with what tumor; due to what mutation?

A
  • Dysplastic gangliogliocytoma of the cerebellum (Lhermitte-Duclos disease)
  • Mutations in PTEN resulting in PI3K/AKT signaling pathway activity
108
Q

Li-Fraumeni syndrome is associated with what tumor; due to what mutation?

A
  • Medulloblastomas
  • Mutations in TP53
109
Q

Turcot syndrome is associated with what tumor; due to what mutation?

A
  • Medulloblastoma or Glioblastoma
  • Mutations in APC or mismatch repair genes
110
Q

Gorlin syndrome is associated with what tumor; due to what mutation?

A
  • Medulloblastoma
  • Mutations in PTCH gene – upregulation of SHH signaling pathways
111
Q

What is the inheritance pattern for Tuberous Sclerosis Complex?

A

Autosomal Dominant

112
Q

Tuberous Sclerosis Complex is characterized by the development of what?

Most frequent clinical manifestations are?

A
  • Development of hamartomas and benign neoplasms involving the brain and other tissues
  • Seizures, autism, and mental retardation
113
Q

What are the 2 tuberous sclerosis locuses; associated chromosome; and protein each encodes

Which is more commonly mutated?

A
  • TSC1 on chromosome 9q34 encodes hamartin
  • TSC2 on chromosome 16p13.3 encodes tuberin = Most commonly mutated
114
Q

Which tumors are associated with the Tuberous Sclerosis Complex?

A
  • Renal angiomyolipomas
  • Cardiac rhabdomyomas
  • Giant-cell astrocytomas
115
Q

What are the cutaneous lesions associated with the Tuberous Sclerosis Complex?

A
  • Shagreen patches (localized cutaneous thickenings)
  • Ash-leaf patches (hypopigmented areas)
116
Q

What is the function of the proteins hamartin and tuberin produced by the tuberous sclerosis genes?

How does dysregulation of these proteins lead to the histological characterstics of tumors associated w/ tuberous sclerosis?

A
  • Inhibit the kinase mTOR
  • mTOR is key regulator of protein synthesis and other aspects of anabolic metabolism, including control of cell size

*Tumors associated w/ tuberous sclerosis are remarkable for having voluminous amounts of cytoplasm!

117
Q

Multiple drop like masses associated with clusters of large tumor cells beneath the ventricular surface that buldge into the ventricular system and are known as candle-guttering is associated with?

A

Tuberous sclerosis – giant cell astrocytomas

118
Q

Von Hippel-Lindau Disease is associated with the development of which malignancies?

A
  • Hemangioblastomas of the CNS (cerebellum and retina)
  • Renal cell carcinoma
  • Pheochromocytoma
119
Q

What is the inheritance pattern of Von Hippel-Lindau disease; which gene and chromosome are involved?

What is the function of the protein associated with this gene?

A
  • AD
  • VHL = tumor suppressor gene on chromosome 3p25.3
  • VHL is component of ubiquitin ligase complex that down-regulates HIF-1 –> involved in expression of VEGF and erythropoietin
120
Q

What is responsible for the polycythemia observed in hemangioblastomas associated with Von Hippel-Lindau Disease?

A

VHL is involved in regulating expression of erythropoietin —> Polycythemia

121
Q

What is the mnemonic using VHL for Von Hippel-Lindau Disease?

A
  • V = VHL gene
  • H = Hemangioblastoma
  • L = Lots of catecholamines = pheochromocytoma

*VHL = 3 letters = RCC (renal cell carcinoma)

*VHL = 3 letters = chromosome 3

122
Q

Metastasis to the brain by what malignancy does not follow the general rule of having the boundary between tumor and brain parenchuma being well-defined microscopically?

A

Melanoma

123
Q

Which CNS tumor is characterized as highly vascular and occuring as a mural nodule associated with a large fluid-filled cyst?

A

Hemangioblastomas

124
Q

Which stain for hemangioblastomas?

A

Inhibin

125
Q

NF1 is more common and is characterized by which malignancies and other findings?

A
  • Neurofibromas of peripheral nerve
  • Gliomas of optic nerve
  • Pigmented nodules of the iris (L**isch nodules)
  • Cutaneous hyperpigmented macules (cafe au lait spots)
126
Q

NF2 is most commonly characterized by which malignancies?

A
  • Bilateral schwannomas of CN VIII
  • Multiple meningiomas
  • Gliomas may also occur and are typically ependymomas of the spinal cord

NMSP Exam I (11 decks)

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