INBR 7 - Neuropathology Flashcards

Question

``` 25. Tn. X, 58 tahun dibawa dengan kejang focal dan ditemukan massa lobe frontal besar yang berasal dari pertemuan abu-abu-putih berdasarkan hasil MRI. Pasien menjalani biopsi diagnostik, dan spesimen-nya adalah CD45-negatif, vimentin-positif, sitokeratin-AE1/3 positif dan EMA-Negatif. Temuan ini paling konsisten dengan neoplasma yang mana? A. Limpoma B. Karsinoma Metastatik C. Glioblastoma D. Hemangiopersitoma E. Meningioma ```

Answer 1

C. Glioblastoma mul tifonne exhibits · staining for both vimentin and S-100. GBfl'ls are usually focally positive for GFAP as well . With small tissue biopsies, it can be difficult to distinguish GBM from metastatic carcinoma and lymphoma.Metastatic carcinoma exhibits staining for epithelial membrane antigen ( EMA) and cytokeratins, while lymphoma is CD4S-positive, which distinguishes these neoplasms from GBM. However, occasionally exhibits cross reactivity with some keratin stains (e.g. , AE l/3 ). Hemangiopericytoma is vimentin-positive and EMA negative; however, it does not exh ibit AE l/3 cross-reactivity

Answer 2

C. Meningothelial meningiomas exhibit sheets o r lobules of cells with oval nuclei and indistinct cell borders. Rudimentary whorls are often present. Fibrous meningiomas exhibit streaming of elongated (spindle-shaped) nuclei with prominent surrounding collagen deposition. Transitional meningiomas contain elements of both meningothelial and fibrous variants. Transitional variants exhibit whorls or lobules as well as a fascicular (streaming) pattern of neoplastic cells, as depicted here. Secretory meningiomas can exhibit a transitional or meningothelial pattern; however, many cells contain prominent eosinophilic (PAS-positive) globules. Chordoid meningiomas exhibit columns of cells surrounded by a mucoid matrix, thus resembling a chordoma

Answer 3

A. Papillary meningiomas are unique variants that exhibit a high nuclear-cytoplasmic ratio, prominent mitoses, metastasis throughout the C S via CSF pathways, and occasional metastasis outside the CNS. Other meningioma variants are considered atypical if they exhibit prominem mitoses , increased cellularity, sheet-like growth patterns. and necrosis. Anaplastic meningiomas are frankly mali

Answer 4

D. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results in the loss of upper and lower motor neurons. Although the cause of ALS is unknown, 5 to 10% of all cases of ALS are inherited i n an autosomal dominant fashion. Approximately 25% of these familial cases of ALS are secondary to mutations of the copper/zinc superoxide dismutase (SOD1) gene located on chromosome 21q. Refsum's disease results from deficiencies of the enzyme phytanoyl CoA hydroxylase, which results in the accumulation of phytanic acid. Clinical manifestations of Refsum's disease include ataxia, peripheral neuropathy, and retinitis pigmentosa. Sanfilippo syndrome is one of the mucopolysaccharidoses and results from defective glucosaminoglycan (heparan sulfate) metabolism. Zellweger syndrome is a peroxisomal disorder that is associated with pachygyria, polymicrogyria, and various heterotopias

Answer 5

A. Multiple sclerosis ( MS ) is classically associated with the HLA-DR2 allele, and HLA-D R 1 S is common in Northern Europeans with MS . The HLA alleles A3, B7, and DR3 are also overrepresented in the MS population. The incidence and prevalence of MS vary with latitude, increasing wi th greater distance from the equator. If, however, an individual migrates to a higher-risk latitude after the teen years, that individual's risk of developing MS is no greater than the risk associated with the original region

Answer 6

B. Hemangiopericytoma is vimentinpositive, with focal reactivity to CD34 as well. The sustentacular cell of paragangliomas exhibits immunoreactivity for S-100, while chief cells exhibit chromogranin-A and synaptophysin positivity. Meningiomas are vimentin positive, with occasional focal reactivity for EM.A, S 100, and cytokeratins. Notably, meningiomas are GFAP-negative. Central neurocytoma exhibits immunoreactivity for synaptophysin, GFAP, and neurofilament proteins. Primary CNS T-cell lymphomas are CD 4 5- and CD 3-positive, while B cell lymphomas usually show immunoreactivity to CD 79a and CD 20

Answer 7

C. Hemangiopericytoma is vimentinpositive, with focal reactivity to CD34 as well. The sustentacular cell of paragangliomas exhibits immunoreactivity for S-100, while chief cells exhibit chromogranin-A and synaptophysin positivity. Meningiomas are vimentin positive, with occasional focal reactivity for EM.A, S 100, and cytokeratins. Notably, meningiomas are GFAP-negative. Central neurocytoma exhibits immunoreactivity for synaptophysin, GFAP, and neurofilament proteins. Primary CNS T-cell lymphomas are CD 4 5- and CD 3-positive, while B cell lymphomas usually show immunoreactivity to CD 79a and CD 20

Answer 8

D. Hemangiopericytoma is vimentinpositive, with focal reactivity to CD34 as well. The sustentacular cell of paragangliomas exhibits immunoreactivity for S-100, while chief cells exhibit chromogranin-A and synaptophysin positivity. Meningiomas are vimentin positive, with occasional focal reactivity for EM.A, S 100, and cytokeratins. Notably, meningiomas are GFAP-negative. Central neurocytoma exhibits immunoreactivity for synaptophysin, GFAP, and neurofilament proteins. Primary CNS T-cell lymphomas are CD 4 5- and CD 3-positive, while B cell lymphomas usually show immunoreactivity to CD 79a and CD 20

Answer 9

A. Hemangiopericytoma is vimentinpositive, with focal reactivity to CD34 as well. The sustentacular cell of paragangliomas exhibits immunoreactivity for S-100, while chief cells exhibit chromogranin-A and synaptophysin positivity. Meningiomas are vimentin positive, with occasional focal reactivity for EM.A, S 100, and cytokeratins. Notably, meningiomas are GFAP-negative. Central neurocytoma exhibits immunoreactivity for synaptophysin, GFAP, and neurofilament proteins. Primary CNS T-cell lymphomas are CD 4 5- and CD 3-positive, while B cell lymphomas usually show immunoreactivity to CD 79a and CD 20

Answer 10

E. Hemangiopericytoma is vimentinpositive, with focal reactivity to CD34 as well. The sustentacular cell of paragangliomas exhibits immunoreactivity for S-100, while chief cells exhibit chromogranin-A and synaptophysin positivity. Meningiomas are vimentin positive, with occasional focal reactivity for EM.A, S 100, and cytokeratins. Notably, meningiomas are GFAP-negative. Central neurocytoma exhibits immunoreactivity for synaptophysin, GFAP, and neurofilament proteins. Primary CNS T-cell lymphomas are CD 4 5- and CD 3-positive, while B cell lymphomas usually show immunoreactivity to CD 79a and CD 20

Answer 11

D. Oligodendrogliomas are characterized by uniform cells. arr:mgecl back to back, and interspersed prominent branching capillaries ( "chicken-wire" vasculature). Artifactual clearing of the cytoplasm ("fried-egg" appearance), as depicted here. results from delayed formalin fixation and is not always observed. The neoplastic cells of oligodendrogliomas contain monomorphic round nuclei. Oligodendrogliomas frequently exhibit loss of heterozygosity on chromosome 1p and 1 9q and rare contain p53 mutations . Very few cells in these neoplasms exhibit immunoreactivity for GFAP. Clear cell meningiomas resemble oligodendrogliomas microscopically, but like other meningiomas, clear cell meningiomas contain bands of collagen. They also lack the chicken-wire vasculature of oligodendrogliomas

Answer 12

C. Microscopically, acute cerebral infarcts (after 8 to 12 hours) exhibit neuronal eosinophilia, pyknosis, and vacuolation of the neuropil. Subacute infarcts (2 to 4 days) also exhibit neuronal eosinophilia; however, they may also contain neutrophil infiltrates, occasional necrotic microvessels, and scattered foamy histiocytes. Chronic infarcts exhibit foamy macrophages, reactive astrocytosis, thin-walled blood vessels (neovascularization), and ferrugination of residual neurons surrounding a cystic (acellular) cavity. Gemistocytic astrocytomas exhibit large plump eosinophilic cells with glassy cytoplasm and are hypercellular. Viral encephalitis can exhibit neuronal eosinophilia, especially in the early stages; however, inclusion bodies are usually observed in conjunction with prominent lymphocytic infiltrates. Bacterial meningitis exhibits prominent infiltrates of neutrophils and lymphocytes, often with infiltration of leptomeningeal and cortical vessels. The above photomicrograph illustrates neuronal eosinophilia and pyknosis with vacuolation of the surrounding neuropil and a paucity of inflammation. This is most consistent with an acute cerebral infarction

Answer 13

C . Acute spinal cord injury i s characterized b y axonal swellings (spheroids), hemorrhagic necrosis of gray and white matter, and variable amounts of surrounding edema. Over the following weeks there is infiltration of macrophages and a gradual removal of myelin and neuronal debris. Posttraumatic syrinx formation, or cavitation, is a relatively late feature of spinal cord injury, often occurring months to years after the original injury. The gray matter often shows prominent fibroblastic proliferation and associated collagenous fibrosis, as well as hyaline thickening of small blood vessels

Answer 14

B. Monosomy 22 is by far the most common cytogenetic abnormality of meningiomas, and greater than 75% of all meningiomas exhibit loss of heterozygosite· for chromosome 22q markers. Allelic losses of chromosomes 1 p , 10, and 14q are associated with progression to more aggressive meningiomas (atypical and anaplastic ) . Despite the occurrence of (multiple) meningiomas with Nf-2. Which also localizes to chromosome 22, the tumor suppressor gene that is responsible for tumorigenesis with meningiomas in patients without neurofibromatosis is separate from the NF-2 gene locus

Answer 15

E. Sturge-Weber svndrome ( encephalotrigeminal angiomatosis) is a neurocutaneous disorder that occurs sporadically. The disorder is characterized by port wine stains in the distribution of the sensory fibers of the trigeminal nerve, with associated ocular angiomas and leptomeningeal venous angiomas of the ipsilateral cerebral hemisphere. Occasionally the cerebral hemispheres are involved bilaterally. Most patients with Sturge-Weber syndrome develop epilepsy over time, and many exhibit progressive neurologic deficits such as hemiparesis, hemisensory loss, and homonymous hemianopsia. O n microscopic analysis, there is widespread gliosis and dystrophic calcification of the involved brain parenchyma, with iron and calcium deposition in large, tortuous meningeal vessels. The treatment of this disorder is largely symptomatic

Answer 16

E. This photomicrograph depicts a microglial nodule. Microglia typically have rod-shaped nuclei and are CD68-positive. Microglia proliferate in many chronic CNS infections and viral encephalitides. IV!icroglial nodules sometimes contain neurons with viral inclusion bodies, and they are commonly observed with neurosyphilis, toxoplasmosis, and many different viral infections of the CNS (e.g. , C.tl-fV, I-IIV, arboviruses, polioviruses) . The aggregation of microgl ia and macrophages around dying neurons is called "neuronophagia"

Answer 17

D. Hunter syndrome is a lysosomal disorder that results from deficiencies of the enzyme iduronate sulfatase . It is inherited in an X-linked recessive fashion and usually presents in the first 2 to 4 years of life. Clinical findings of Hunter syndrome include delayed growth (short stature) , coarse facial features, joint stiffness, macrocephaly, progressi,·e hearing loss, hepatosplenomegaly, and various degrees of mental retardation. H u rler syndrome (MPS I ) , not Hunter syndrome, is associated with corneal clouding

Answer 18

B. CNS metastatic lesions can occur anywhere but are typically located at the gray-white j unction of the cerebral hemispheres. This H&E photomicrograph depicts a malignant metastatic melanoma characterized by areas of hemorrhage, prominent nucleoli (dark spot inside nucleus ) , and some tumor cells containing melanin pigment (brown ) . Grossly, metastases c a n be firm, or they c a n exhibit a soft, necrotic central region. Hemorrhage is often associated with metastatic melanoma, renal cell carcinoma, or choriocarcinoma. Metastases rarely involve the brainstem or spinal cord. Intracranial abscesses can also occur at the gray-white junction as a result of hematogenous spread. and they usually occur in the MCA distribution. Grossly. abscesses usually exhibit a well-defined capsule that is thicker toward the cortical surface and thinner toward the deep surface. The center of a brain abscess contains purulent, necrotic debris. MS plaques are well demarcated gray areas of discoloration that commonly occur at the lateral angles of the lateral ventricles. Foci of cavitation are rare with IllS plaques but can be observed with fulminant, acute plaques cure infarcts exhibit only slight blurring of the gray-white junction "·ith dusky discoloration, often in m ajor vascular territories

Answer 19

C. Diphtheria infections can result in paralysis of accommodation (ciliary ganglion ) , followed by facial and oropharyngeal paralysis with preservation of extraocular movements. The fifth to eighth week of the illness is associated with an ascending sensorimotor polyneuropathy in approximately 20% of all cases; this results in a mild to severe paralysis. The disease course is shortened by early treatment with antitoxin and antibiotics, and the majority of patients eventually make a full recovery. Symptoms of neurosarcoidosis include cranial nerve palsies (facial weakness, hearing loss, vertigo, optic atrophy), hypopituitarism, hydrocephalus, and ataxia. Neurosyphilis is associated with cranial nerve palsies, hydrocephalus, arteritis, seizures, and eventually psychosis and cognitive decline. Lyme disease results in an enlarging maculopapular rash with · central clearing (erythema chronicum migrans) , followed by the development of axonal neuropathies, lymphocytic meningitis, encephalopathy, polyradiculitis, and cranial nerve palsies. Lyme disease can also affect the j oints and cardiovascular system. Guillain-Barre syndrome (GBS) is an acute ascending monophasic motor polyneuropathy that can involve the face, limbs, and even respiratory musculature. GBS is not typically associated with any sensory loss or ciliarv paralysis, however

Answer 20

B. Subependymal germinal matrix hemorrhage i s usually observed in low-birth-weight premature infants and can result in intraventricular hemorrhage. The microcirculation of the periventricular matrix zone is extremely fragile and persists in the neonate until 34 weeks of gestation. This microcirculation is prone to hemorrhage, with hypoxia and secondary failures of autoregulation. Choroid plexus hemorrhage is the most common cause of i ntraventricular hemorrhage in the term infant and can result in anything from minimal (asymptomatic) hemorrhage to massive intraventricular hemorrhage

Answer 21

A. Subependymal germinal matrix hemorrhage i s usually observed in low-birth-weight premature infants and can result in intraventricular hemorrhage. The microcirculation of the periventricular matrix zone is extremely fragile and persists in the neonate until 34 weeks of gestation. This microcirculation is prone to hemorrhage, with hypoxia and secondary failures of autoregulation. Choroid plexus hemorrhage is the most common cause of i ntraventricular hemorrhage in the term infant and can result in anything from minimal (asymptomatic) hemorrhage to massive intraventricular hemorrhage

Answer 22

B. Disorders of abnormal neuronal migration include agyria, pachygyria, polymicrogyria, cortical dysplasia, and focal and diffuse heterotopias. Schizencephaly and porencephaly are fetal hypoxic-ischemic lesions, and holoprosencephaly results from a failure of the normal growth and cleavage of the prosencephalic vesicles

Answer 23

B. Pediatric patients with bacterial meningitis are usually due to infection by Streptococcus pnewno n iae, Neisseria meningitidis, or Haemophilus illfluenzae. The incidence of H. irifluenzae meningitis in rhe pediatric population has decreased significantly in the past decade because of the widespread use of the H. influensae B vaccination. Bacterial meningitis in the adult population 110 Intensive Neurosurgery Board Review is usually secondary to infection by S. pneumoniae or N. meningitidis . Meningitis in the elderly commonly results from S. pneumoniae and gram-negative rods. Listeria monocytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter clivasus and Proteus mirabilis-related meningitis are associated with the development of concomitant cerebral abscesses in this population

Answer 24

A. Pediatric patients with bacterial meningitis are usually due to infection by Streptococcus pnewno n iae, Neisseria meningitidis, or Haemophilus illfluenzae. The incidence of H. irifluenzae meningitis in rhe pediatric population has decreased significantly in the past decade because of the widespread use of the H. influensae B vaccination. Bacterial meningitis in the adult population 110 Intensive Neurosurgery Board Review is usually secondary to infection by S. pneumoniae or N. meningitidis . Meningitis in the elderly commonly results from S. pneumoniae and gram-negative rods. Listeria monocytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter clivasus and Proteus mirabilis-related meningitis are associated with the development of concomitant cerebral abscesses in this population

Answer 25

C. Pediatric patients with bacterial meningitis are usually due to infection by Streptococcus pnewno n iae, Neisseria meningitidis, or Haemophilus illfluenzae. The incidence of H. irifluenzae meningitis in rhe pediatric population has decreased significantly in the past decade because of the widespread use of the H. influensae B vaccination. Bacterial meningitis in the adult population 110 Intensive Neurosurgery Board Review is usually secondary to infection by S. pneumoniae or N. meningitidis . Meningitis in the elderly commonly results from S. pneumoniae and gram-negative rods. Listeria monocytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter clivasus and Proteus mirabilis-related meningitis are associated with the development of concomitant cerebral abscesses in this population

Answer 26

E. Pediatric patients with bacterial meningitis are usually due to infection by Streptococcus pnewno n iae, Neisseria meningitidis, or Haemophilus illfluenzae. The incidence of H. irifluenzae meningitis in rhe pediatric population has decreased significantly in the past decade because of the widespread use of the H. influensae B vaccination. Bacterial meningitis in the adult population 110 Intensive Neurosurgery Board Review is usually secondary to infection by S. pneumoniae or N. meningitidis . Meningitis in the elderly commonly results from S. pneumoniae and gram-negative rods. Listeria monocytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter clivasus and Proteus mirabilis-related meningitis are associated with the development of concomitant cerebral abscesses in this population

Answer 27

D. Pediatric patients with bacterial meningitis are usually due to infection by Streptococcus pnewno n iae, Neisseria meningitidis, or Haemophilus illfluenzae. The incidence of H. irifluenzae meningitis in rhe pediatric population has decreased significantly in the past decade because of the widespread use of the H. influensae B vaccination. Bacterial meningitis in the adult population 110 Intensive Neurosurgery Board Review is usually secondary to infection by S. pneumoniae or N. meningitidis . Meningitis in the elderly commonly results from S. pneumoniae and gram-negative rods. Listeria monocytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter clivasus and Proteus mirabilis-related meningitis are associated with the development of concomitant cerebral abscesses in this population

Answer 28

B. Ganglion cell tumors (gangliocytomas and gangliogliomas) are characterized by neoplastic ganglion cells, with or without a component of neoplastic glial tissue ( usuallv with an astrocytic morphology) . Neoplastic ganglion cells resemble normal neurons but are abnormallv large and round, arranged in clusters, and contain a n eccentric nucleus with a prominent nucleolus . The classic finding is binucleation, seen in one of the ganglion cells here, which never occurs in normal neurons. Gangliogliomas occasionally exhibit nuclear pleomorphism , but mitoses are absent. Gangl ion cells exhibit immunoreactivity for synaptophysin and neurofilaments. Medulloblastomas are characterized bv a uniform population of small blue cells with hyperchromatic nuclei , minimal cytoplasm, mitoses, and occasional foci of necrosis. Central neurocytoma consists of uniform round cells with few mitoses. Ependymomas also contain uniform cells with round nuclei that often form pseudorosettes and rarely form true ( ependymal) rosettes

Answer 29

B. Schwannomas are characterized b y compact arrangements of interwoven fascicles of cells (Antoni A areas) and spindle-shaped cells arranged in a loose myxoid stroma (Antoni B areas ) . The Antoni A areas often exhibit sequential palisading nuclei (Verocay bodies), shown here. Thickened blood vessels with hyaline walls may be seen. Neurofibromas are characterized by spindle-shaped cells with wal)' nuclei arranged haphazardly within a mucoid matrix with interspersed bundles of collagen ( "shredded carrots" appearance ) . Fibrous meningiomas consist of spindle-shaped cells with intermixed colla,gen and lack a mucoid matrix and \'erocay bodies. Malignant nerve sheath tumors can also exhibit a fascicular pattern; however, this tumor is highlv cellular and contains frequent mitoses and necrosis. The presence of Verocay bodies in this specimen is consistent with a schwannoma

Answer 30

D. Mature teratomas, the most common of which is the dermoid cyst depicted here, exhibit a mixture of ectodermal, mesoderm and endodermal components. These neoplasms are well circumscribed and rarely associated with malignant transformation into carcinomas or sarcomas. Dermoid cysts are lined by squamous epithelium and contain adnexal structures such as sebaceous glands (shown in this example). Craniopharyngiomas (adamantinomatous) are characterized by collections of squamous cells with intermingled clusters of keratinized ghost cells, calcification, and cholesterol clefts

Answer 31

E. Klippel-Feil anomaly results from the failure of cervical vertebral (somite) segmentation. Klippel-Feil anomaly is classically associated with the triad of short neck, low posterior hairline, and limited cervical motion. Approximately one-third of all Klippei-Feil cases are associated with congenital elevation of the scapula, which is known as Sprengel's deformity. Klippel-Feil is also associated with diastematomyelia, Chiari I malformations, basilar impression, and genitourinary abnormalities

Answer 32

D. Disjunction refers t o the separation o f superficial ectoderm from ne_ural ectoderm during development. It is thought that premature disjunction allows cells of mesodermal origin to migrate between these two layers of ecroderm, which can lead to the formation of lipomas

Answer 33

E. Von Hippel-Linclau syndrome (VHL) is an autosomal dominant neurocutaneous disorder that is associated with chromosome 3p. VHL patiems develop hemangioblastomas of the brainstem, cerebellum, and spinal cord. VHL is also associated with the developmen t of retinal angiomas, paragangliomas, endolymphatic sac tumors, pheochromocYtoma, epididymal cystade.wma, renal and pancreatic cysts, and renal cell carcinoma. The production of erythropoietin by hemangioblastomas can occur with VIIL and result in polycythemia

Answer 34

A. The Lewy body is an intracellular neuronal inclusion characterized by the presence of a hyaline eosinophilic core and a pale halo. Lewy bodies are observed within the substantia nigra in Parkinson's disease and within the cerebral cortex in certain forms of dementia ( e.g. , "dementia with Lewy bodies" ) . Rabies encephalitis is characterized by the presence of Negri bodies. which are intracellular inclusions resembling red blood cells. and Babes' nodules, which are clusters of microglia. Corticobasal degeneration is characterized b y the presence of s11•ollen cortical neurons ( ballooned neurons), gliosis. and microvacuolation

Answer 35

B. Subependymomas are characterized by the presence of clusters of cells with round nuclei and interspersed regions of very low cellularity ( "islands of blue in a sea of pink " ) . Subependymomas often exhibit microcysts; however. nuclear pleomorphism and mitoses are universally absent. Ependnnomas classically exhibit collars of epithelioid cells surrounding pools of mucin with central blood vessels. Dysembryoplastic neuroepithelial tumor (DNET) is a supratentorial cortical neoplasm of children and young adults that is usually located in the temporal lobe and presents with seizures. Microscopically, DNETs exhibit nodules of oligodendrocyte-like cells, mucinous cysts, and neurons that appear to "float" in the mucinous cysts

Answer 36

C. Gliosarcoma is a variant of glioblastoma multiforme. The presenting features, demographic characteristics, cytogenetic changes, and prognosis of the gliosarcoma (Feigin tumor) are all similar to that of the glioblastoma. Microscopically, the gliosarcoma consists of two distinct cell populations: sarcomatous areas containing spindle-shaped cells arranged in a streaming fashion (left photomicrograph) and areas of conventional glioblastoma ( right photomicrograph ) . lvlalignant nerve sheath tumors also contain spindle-shaped neoplastic cellst however, areas of conventional glioblastoma are not observed. Embryonal carcinoma exhibits large cells with slight pleomorphism arranged in solid, glandular, papillary, or cribriform patterns. Spindle-shaped cells are absent in embryonal carcinoma

Answer 37

D. This photomicrograph illustrates a medulloblastoma. which is characterized by a population of undifferentiated cells with hyperchromatic nuclei and minimal cytoplasm. Medulloblastomas exhibit prominent mitoses, with focal regions of necrosis and apoptosis. Occasionally cells may form rosettes that lack a central canal or blood vessel ( HomerWright rosettes). Medulloblastomas often spread throughout the CNS via CSF pathways. Approximately 50% of all medulloblastomas present in children less than 10 years of age; they are usually located in the cerebellar vermis in children. Therefore this tumor could lead to ataxia and hydrocephalus, which is consistent with answer D

Answer 38

A. Neurofibromatosis type 1 ( N F - 1 ) is an autosomal dominant neurocutaneous disorder that localizes to chromosome 1 7 . The NF-1 gene is very large and associated with a high spontaneous mutation rate. Approximately 50% of all NF-1 cases are secondary to spontaneous mutations. NF-1 is associated with 100% penetrance and variable expressivity. Tuberous sclerosis ( T S ) is also an autosomal domi nant neurocutaneous disorder that is associated with a high spontaneous mutation rate. TS can result irom mutations at two different loci, one located on chromosome 9 and the other on chromosome 11 . Tuberous sclerosis is associated with approximately 80% penetrance and variable expressivity

Answer 39

B. Neurofibromatosis type 1 ( N F - 1 ) is an autosomal dominant neurocutaneous disorder that localizes to chromosome 1 7 . The NF-1 gene is very large and associated with a high spontaneous mutation rate. Approximately 50% of all NF-1 cases are secondary to spontaneous mutations. NF-1 is associated with 100% penetrance and variable expressivity. Tuberous sclerosis ( T S ) is also an autosomal domi nant neurocutaneous disorder that is associated with a high spontaneous mutation rate. TS can result irom mutations at two different loci, one located on chromosome 9 and the other on chromosome 11 . Tuberous sclerosis is associated with approximately 80% penetrance and variable expressivity

Answer 40

B. This gross specimen exhibits bilateral petechial hemorrhages within the mamillary bodies. which is associated with Wernicke's encephalopathy. Wernicke's encephalopathy is associated with thiamine deficiency and is commonly observed in chronic alcoholics and some patients with gastrointestinal disorders. Patients with Wernicke's encephalopathy exhibit ataxia, gaze palsies, confusion, and apathy, which is often reversible with the administration of thiamine. The chronic form of the disease is known as Korsakoff's psychosis and is associated with retrograde and anterograde amnesia, with concomitant confabulation, usually irreversible

Answer 41

C. Crouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoethmoid synostosis. Patients with Crouzon's disease have a high incidence of hydrocephalus ; however, the vast majority achieve normal IQ's with adequate treatment of the hydrocephalus. Facial features of Crouzon's disease include proptosis. maxillary hypoplasia, and a "parrot's beak" nose . Apert's syndrome is a n autosomal dominant condition that iiwolves premature closure of all cranial sutures. These patients ha\•e facies that resemble those of Crouzon's disease and also have a high incidence of hydrocephalus. Apert's svndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus

Answer 42

B. Crouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoethmoid synostosis. Patients with Crouzon's disease have a high incidence of hydrocephalus ; however, the vast majority achieve normal IQ's with adequate treatment of the hydrocephalus. Facial features of Crouzon's disease include proptosis. maxillary hypoplasia, and a "parrot's beak" nose . Apert's syndrome is a n autosomal dominant condition that iiwolves premature closure of all cranial sutures. These patients ha\•e facies that resemble those of Crouzon's disease and also have a high incidence of hydrocephalus. Apert's svndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus

Answer 43

C. Crouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoethmoid synostosis. Patients with Crouzon's disease have a high incidence of hydrocephalus ; however, the vast majority achieve normal IQ's with adequate treatment of the hydrocephalus. Facial features of Crouzon's disease include proptosis. maxillary hypoplasia, and a "parrot's beak" nose . Apert's syndrome is a n autosomal dominant condition that iiwolves premature closure of all cranial sutures. These patients ha\•e facies that resemble those of Crouzon's disease and also have a high incidence of hydrocephalus. Apert's svndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus

Answer 44

B. Craniosynostosis refers to the premature closure of cranial sutures; this condition is often associated with Crouzon's disease and Apert's syndrome, although manv cases are isolated and sporadic as well. Many cases of craniosynostosis are associated with mutations of the fibroblast growth factor receptor gene. Craniosynostosis is more common in males, and isolated sagittal synostosis (scaphocephaly) accounts for approximately 50% of all cases ( most common type of synostosis)

Answer 45

E. Tuberous sclerosis (TS) often presents i n children between the ages of 1 and 6 months with seizures, which usually consists of infantile spasms. Approximately 90% of all patients with TS experience seizures, and the vast majority also exhibit various degrees of mental retardation. TS is as ociated with the development of cortical tubers, which are firm, pale nodules that proj ect from the cortical surface. as depicted in this gross specimen. TS is also associated with subependymal nodules and the development of subependymal giant cell astrocytoma

Answer 46

A. Prolonged elevations in intracranial pressure can result in various herniation syndromes. Transtentorial herniation of the uncus through the tentorial incisura can result in compression of the ipsilateral oculomotor nerve. midbrain , and ipsilateral posterior cerebral artery, with subsequent infarction. Prolonged herniation can result in the development of hemorrhagic necrosis within the pons and midbrain (Duret hemorrhages) as a consequence of penetrating arteriolar compression and ischemia. This gross specimen illustrates transtentorial herniation of the uncus, with notable indentation of the surrounding cerebrum by the tentorium cerebelli

Answer 47

E. Diffuse axonal injury (DAI) results from acceleration/ deceleration injuries of the brain . DAI can exhibit prominent petechial hemorrhages within the corpus callosum, interventricular septum, dorsolateral brainstem , superior cerebellar peduncles, and parasagittal deep white matter on gross specimens. lllicroscopically, DAI specimens exhibit prominent axonal spheroids, especially with silver stains. DAI varies in severity from minimal diswrbances in level of consciousness to vegetative states with subsequent death

Answer 48

A. Cerebral aspergillosis is usuallY secondary to hematogenous dissemination from the lungs or local spread from the paranasal sinuses of Aspergillus fu m igaws or Aspergillus flavus. Symptoms of cerebral aspergillosis are variable and include headache, seizures, cranial nerve palsies, hemiparesis, and elevated intracranial pressure. Aspergillus has a tendency to exhibit prominent vascular invasion, with subsequent vascular thrombosis, infarction, and hemorrhage. Aspergillus is characterized by septate hYphae that are readily demonstrated on silver stains. In contrast, mucormycosis exhibits broad nonseptate hyphae, candidiasis exhibits budding yeasts and pseudohyphae, and crvptococcosis exhibits only a yeast form with CNS infections

Answer 49

D . Amyotrophic lateral sclerosis (ALS) affects primarily the anterior and la teral corticospinal tracts of the spinal cord, as evidenced by the loss of myelinated axons (as depicted in the specimen). Subacute combined degeneration (SACD) results from vitamin B12 (cobalamin) deficiency and exhibits symmetric demyelination in the posterior and lateral columns of the spinal cord. In severe cases of SACD, the anterior columns can also be involved. Tabes dorsalis results from chronic inflammation of the dorsal roots and dorsal root ganglia and is usually observed 15 to 20 years after initial infection with syphilis. The posterior columns are primarily affected in tabes dorsalis. Friedreich's ataxia ( FA ) is an autosomal recessive disorder that localizes to chromosome 9 and results in deterioration of the posterior columns. sri nocerebellar tracts, C larke's nucleus, and distal (thoracolumbar) corticospinal tracts

Answer 50

B. Acute disseminated encephalomyelitis (ADEM) also known as postinfectious encephalomyelitis, is a monophasic demyelinating disorder. that usually follows a viral infection or vaccination (especially rabies vaccine). ADEM results from T -cell autoimmune attacks against myelin basic protein and usually presents with fever, headache, nuchal rigidity, and focal neurologic deficits. ADEM is characterized by perivenular inflammation and demyelination on microscopic analysis. Patients with ADEM usually exhibit a full recovery ( 1 0 to 20% have permanent neurologic deficits) , and the disease course i s generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in geneticllllY susceptible animals after immunization with myelin basic protein. EAE is actually the animal model of ADEM, although there is a chronic relapsing form of the disease that resembles .MS and has provided much of the immunologic information that there is about MS in humans. MS is typically a chronic relapsing/remitting demyelinating disorder that affects adults between the third to fifth decades of life and is more common in women than men . Approximately 85% of acute MS exacerbations improve with the administration of IV methylprednisolone. Acute MS plaques can exhibit perivascular inflammation; however, arterioles are involved ( as well as venules) . Interferon 13 - 1 b Betaserone), interferon 13 - 1 a (Avonex) , and Copaxone are generally utilized to decrease the frequency of MS attacks

Answer 51

B. Acute disseminated encephalomyelitis (ADEM) also known as postinfectious encephalomyelitis, is a monophasic demyelinating disorder. that usually follows a viral infection or vaccination (especially rabies vaccine). ADEM results from T -cell autoimmune attacks against myelin basic protein and usually presents with fever, headache, nuchal rigidity, and focal neurologic deficits. ADEM is characterized by perivenular inflammation and demyelination on microscopic analysis. Patients with ADEM usually exhibit a full recovery ( 1 0 to 20% have permanent neurologic deficits) , and the disease course i s generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in geneticllllY susceptible animals after immunization with myelin basic protein. EAE is actually the animal model of ADEM, although there is a chronic relapsing form of the disease that resembles .MS and has provided much of the immunologic information that there is about MS in humans. MS is typically a chronic relapsing/remitting demyelinating disorder that affects adults between the third to fifth decades of life and is more common in women than men . Approximately 85% of acute MS exacerbations improve with the administration of IV methylprednisolone. Acute MS plaques can exhibit perivascular inflammation; however, arterioles are involved ( as well as venules) . Interferon 13 - 1 b Betaserone), interferon 13 - 1 a (Avonex) , and Copaxone are generally utilized to decrease the frequency of MS attacks

Answer 52

C. Acute disseminated encephalomyelitis (ADEM) also known as postinfectious encephalomyelitis, is a monophasic demyelinating disorder. that usually follows a viral infection or vaccination (especially rabies vaccine). ADEM results from T -cell autoimmune attacks against myelin basic protein and usually presents with fever, headache, nuchal rigidity, and focal neurologic deficits. ADEM is characterized by perivenular inflammation and demyelination on microscopic analysis. Patients with ADEM usually exhibit a full recovery ( 1 0 to 20% have permanent neurologic deficits) , and the disease course i s generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in geneticllllY susceptible animals after immunization with myelin basic protein. EAE is actually the animal model of ADEM, although there is a chronic relapsing form of the disease that resembles .MS and has provided much of the immunologic information that there is about MS in humans. MS is typically a chronic relapsing/remitting demyelinating disorder that affects adults between the third to fifth decades of life and is more common in women than men . Approximately 85% of acute MS exacerbations improve with the administration of IV methylprednisolone. Acute MS plaques can exhibit perivascular inflammation; however, arterioles are involved ( as well as venules) . Interferon 13 - 1 b Betaserone), interferon 13 - 1 a (Avonex) , and Copaxone are generally utilized to decrease the frequency of MS attacks

Answer 53

B. Acute disseminated encephalomyelitis (ADEM) also known as postinfectious encephalomyelitis, is a monophasic demyelinating disorder. that usually follows a viral infection or vaccination (especially rabies vaccine). ADEM results from T -cell autoimmune attacks against myelin basic protein and usually presents with fever, headache, nuchal rigidity, and focal neurologic deficits. ADEM is characterized by perivenular inflammation and demyelination on microscopic analysis. Patients with ADEM usually exhibit a full recovery ( 1 0 to 20% have permanent neurologic deficits) , and the disease course i s generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in geneticllllY susceptible animals after immunization with myelin basic protein. EAE is actually the animal model of ADEM, although there is a chronic relapsing form of the disease that resembles .MS and has provided much of the immunologic information that there is about MS in humans. MS is typically a chronic relapsing/remitting demyelinating disorder that affects adults between the third to fifth decades of life and is more common in women than men . Approximately 85% of acute MS exacerbations improve with the administration of IV methylprednisolone. Acute MS plaques can exhibit perivascular inflammation; however, arterioles are involved ( as well as venules) . Interferon 13 - 1 b Betaserone), interferon 13 - 1 a (Avonex) , and Copaxone are generally utilized to decrease the frequency of MS attacks

Answer 54

B. CNS lymphoma i s diaracterizecl b y numerous malignant lymphocytes that tend to invade the walls of blood vessels. Lymphoma cells are prominent i n the perivascular spaces, and they diffusely invade brain parenchyma toward the periphery of the lesion. J\tore than 80% of these tumors are diffuse large B-cell lymphomas. The surrounding brain often exhibits reactive astrocytosis, which can resemble other inflammatory disorders. I nterspersed small reactive (nonneoplastic) lymphocytes are usually observed as well and provide contrast to the larger, polymorphous malignant lymphocytes, which facilitates distinguishing lymphoma from other inflammatory conditions. B-cell lymphomas are positive for CD20

Answer 55

D. Choroid plexus papillomas ( C PPs) exhibit a columnar epithelium with an underlying fibrovascular network and prominent papillary projections. CPPs exhibit slight nuclear crowding and loss of the normal "cobblestone" surface, which differentiates them from normal choroid plexus. CPPs are generally positive for S - 1 00 , transthyretin, and cytokeratin. Papillary meningiomas are aggressive tumors that exhibit prominent mitoses, a high nuclear-cytoplasmic ratio, and poorly defined papillary structures. Papillary craniopharyngiomas are composed of papillae of squamous cells without fibrovascular cores. Colloid cysts are lined by a single layer of columnar cells . Many of the cells of a colloid cvst wall are ciliated, and mucin-containing goblet cells maY also be located within the epithelial layer

Answer 56

B. Paragangliomas usually arise from the cauda equina or j ugular bulb (glomus jugulare tumors) and consist of lobules of chief cells (Zellballen) surrounded by a single layer of sustentacular cells. Chief cells are labeled with synaptophysin, neurofilament, and chromogranin immunostains. Sustentacular cells are S-100-positive. Myxopapillary ependymomas can also originate from the cauda equina region; however, they are GFAP-positive, whereas paragangliomas are GFAP-negative. Paragangliomas are WHO grade I lesions

Answer 57

D. Fat embolism is usually observed in trauma patients with multisystem injuries and is often associated with long bone fractures. Grossly, fat embolism is characterized by multiple petechial hemorrhages that affect both the gray and white matter of the cerebral hemispheres diffusely, with concomitant regions of perivascular (gray) discoloration. Mlicroscopically, fat embolism exhibits hemorrhagic lesions surrounding capillaries with signs of fibrinoid necrosis. Lipid globules can be demonstrated in necrotic regions with oil red 0 stains. Progressive multifocal leukoencephalopathy (PML) results from JC virus (polyomavirus) reactivation in the CNS of immunocompromised patients. PML exhibits foci of gray discoloration with regions of necrosis and cavitation, primarily in the deep white matter. AdrenoleukodystrophY is characterized by extensive white matter demyelination with sparing of the subcortical U fibers, and involves the parietooccipital regions more extensively than the frontotemporal region. This specimen exhibits multiple petechial hemorrhages in both the cortical gray and deep white matter, which is most consistent with fat embolism

Answer 58

A. PTAH stains for collagen, while the Sudan, Weigert, and Marchi are useful myelin stains

Answer 59

A. Ependymomas are characterized by the presence of uniform cells with round nuclei, mild nuclear pleomorphism, and indistinct cytoplasmic borders. Pseudorosettes ( With a central blood vessel) are commonly observed in ependymomas; however, true rosettes with a central lumen ( shown in the mid-upper portion of the picture) are less frequent. Some ependymomas exhibit epithelial differentiation and the presence of true gland-like canals . Ependymomas are GFAPpositive. The presence of numerous perivaskular pseudorosettes in the above specimen is most consistent with an ependymoma

Answer 60

E. Melanocytes are present within the leptomeninges of the CNS and can lead to the formation of malignant melanoma, diffuse melanosis, and melanocytomas. All of these neoplasms exhibit prominent melanin. Occasionally, schwannomas, ependymomas, pineal neoplasm. and embryonal neoplasms can also exhibit prominent melanin

Answer 61

B. Hallervorden-Spatz disease (HSD) is an autosomal recessive disorder that presents with progressive gait disturbance, dystonia, dysarthria, and choreoathetosis in children and young adults. An adult variant of HSD presents with progressive cognitive dec l i ne and extrapyramidal signs. T2- weighted MRI exhibits prominent hypointensity within the globus pallid us i n patients with HSD ("eye of the tiger" sign ) , which is secondary to the accumulation o f iron pigment. Microscopically, HSD is characterized by the presence of gliosis, axonal spheroids, and occasional Lewy bodies and neurofibrillary tangles within the globus pallidus and substantia nigra (pars reticulata). Wilson's disease (hepatolenticular degeneration) is also characterized by abnormalities of the pallidum; however, prominent iron deposition is not observed

Answer 62

C. Neurocysticercosis results from ingestion of the larval form of Taenia so/iwn . These larvae migrate throughout the body and can involve the eyes, liver, brain, lung, and skeletal muscle. Grossly, neurocysticcrcosis exhibits the presence of a variable number of cysts that usually involve the cortical gray matter. Viable cysts are often 1 to 2 cm in diameter; they become fibrotic and calcified with degeneration . Occasionally a prominent scolex is observed within the viable cysts

Answer 63

E . Paget's disease is characterized by initial excessive bone resorption bv osteoclasts, followed by the progressive deposition of disorganized vascular bone. Paget's disease can involve any bone in the body and can exhibit neurologic symptoms by neural compression, fracture/dislocations, hemorrhage, vascular insufficiency ("steal" phenomena), and malignant degeneration into osteogenic sarcoma or fibrosarcoma with local invasion. Common neurologic symptoms associated with Paget's disease include cranial nerve palsies (optic atrophy, trigeminal neuralgia, facial paralysis, hearing loss ) , entrapment neuropathies, hypopituitarism, myeloradiculopathy, and brainstem compression

Answer 64

D. Alzheimer type I I astrocytes exhibit an enlarged vesicular nucleus with peripheral chromatin and minimal cytoplasm . Alzheimer type II astrocytes can be observed in the caudate, putamen, thalamus, hypothalamus, and brainstem of patients with Wilson's disease and acquired hepatic encephalopathy

Answer 65

A. Neuronophagia ( the aggregation o f macrophages and microglia around dying neurons ) is classically associated with polio virus infections of the CNS; however, it can also be observed with other CNS viral infection

Answer 66

D. Chordomas usually arise within the sacrum or clivus and are characterized microscopically by the presence of cells with prominent vacuolated cytoplasm (physaliphorous cells) surrounded by a mucinous matrix

Answer 67

E. Glioblastomas generally exhibit widespread reactivity for vimentin and focal reactivity for GFAP and S- 100; they are not reactive with cytokeratin markers such as epithelial membrane antigen (EMA). An exception to this is cytokeratin AEl/3, which is occasionally cross-reactive with glioblastomas

Answer 68

B. Pleomorphic xanthoastrocytoma (PXA) is a WHO grade II lesion that is usually located superficially in the cerebrum of children and young adults. I t has variable biologic behavior. Some may progress to become aggressive neoplasms, which behave like glioblastomas, whereas others have a more favorable prognosis, carrying a 70% 10-year survival rate. PX.As exhibits promi nent cytologic pleomorphism, with occasional nuclear hyperchromasia and atypical nuclei. Many of the neoplastic cells with PXA contain prominent eosinophilic cytoplasm, but groups of undifferentiated cells may also be found. Cytoplasmic lipid accumulation is found with variable frequency in some cells, which often appear xanthomatous or Vacuolated. Unlike most gliomas , they are often surrounded by dense pericellular reticulin. l"vfitoses and necrosis are rarely observed, and PX.A is generally GFAP- and S-100-positive. PXA can be differentiated from a glioblastoma by the presence of extensive reticulin deposition, intracellular eosinophilic accumulations, and the lack of mitotic figures, neovascularization, and necrosis

Answer 69

D. Duchenne muscular dystrophy results from the complete absence of the protein dystrophin, which is encoded by a gene located on chromosome Xp2 1 . Duchenne muscular dystrophy exhi.bits X-linked recessive inheritance

Answer 70

D. Giant cell arteritis (GCA) occurs almost exclusively in the elderly and is associated with polymyalgia rheumatica, fever, malaise, weakness, and visual loss. The ESR is elevated in approximately 95% of all cases of GCA. Temporal arterv biopsy is often diagnostic for GCA; however, skip lesions can occur with involved arteries, which can lead to false-negative biopsies. Microscopicallv, GCA is characterized by prominent granulomatous inflammation of arterial walls, marked intimal hyperplasia, and frequent multinucleated giant cells, as depicted in this example

Answer 71

D . Dermatomyositis is an inflammatory disorder of the muscles and skin that has been associated with infections, vaccinations, pothyroiclism, sarcoidosis, and systemic malignancy (11% of all cases ) . DermatomYositis results primarily from B-cell infiltration of the perimysium and blood vessels, with concomitant immunoglobulin deposition that can result in vasculitis. Muscle fiber degeneration occurs in a perifascicular pattern with dermatomyositis; cutaneous findings include scaly macules of the extensor surfaces of the fingers (Gottron sign) and a rash of the eyelids (heliotrope), nose, and cheeks. T-cell infiltration of muscle fibers with subsequent muscle fiber necrosis is a characteristic of polymyositis

Answer 72

C. The white matter exhibits prominent demyelination with relative sparing of the subcortical U fibers, which is characteristic of several leukodystrophies, including metachromatic leukodystrophy

Answer 73

A. Pituitary adenomas usuallv consist of minimally atypical monomorphic cells, which can be arranged in sheets as well as in acinar, papillary, or trabecular patterns. The cells occasionally form perivascular pseudorosettes. Cytologic pleomorphism and mitoses are infrequently observed in pituitary adenomas

Answer 74

A . Tay-Sachs disease is a metabolic disorder that results from a deficiency (or absence) of the lysosomal enzyme

Answer 75

A. Glioblastoma multiforme (GBM) can occur de novo without any prior evidence of neoplasia or secondarily as a result of anaplastic progression from low-grade astrocytomas. There are many cytogenetic differences between primarv (de novo) and secondary GBMs. Secondary GBMs are associated with p53 gene mutations ( chromosome 17) , CDK4 gene amplification. and loss o f heterozygosity ( LOH) of chromosomes lJq ( Rb ) . 9p. and 19q. Epidermal growth factor receptor ( EG F R ) and MDM2 gene amplifications are more common,- associated with de novo GBMs. The most frequent ahnormality. associated with the progression of malignant asrrocytoma overall is LOH on chromosome 10

Answer 76

D. Approximately 80% of all glioblastomas exhibit gains of part or all of chromosome 7. Other common nonrandom cytogenetic aberrations of glioblastoma multiforme include the loss of chromosome 10 (60%), deletion or rearrangements of chromosome 9p (35%), and the acquisition of double minute chromosomes (33%) . LOH involving various alleles on chromosome 1 7 (22%), chromosome 22 (19%), and chromosome 13 (14%) has also been observed regularly in glioblastoma karyotypes