Neuropathology Flashcards

Question

A 58-year-old male presents with focal seizures anel is founel to have a large frontal lobe mass originating from the gray-white junction on MRI. The patient underwent a diagnostic biopsy of this lesion, and the specimen was CD45- nega tive, vimentin-positive, cytokeratin-AE1I3 positive, and ElvIA-negative. This is most consistent with which of the following neoplasms? A. Lymphoma B. Metastatic carcinoma C. Glioblastoma D. I-Iemangiopericytoma E. J'I'Ieningioma

Answer 1

A B **C** D E ## Footnote Glioblastoma multiforme exhibits staining for both vimentin and S-100. GBMs 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 exh ibits staining for epithelial membrane antigen (EMA) and cytokeratins, while lymphoma is CD45-positive, which distinguishes these neoplasms from GBM. GBM, however, occaSionally exhibits cross reactivity with some keratin stains (e.g., AE1I3). IIemangiopericytoma is vimentin-positive and ElvIA-negative; however, it does not exhibit AE1/3 cross-reactivity (Ellison , pp. 628- 632, 689-694, 732- 735, 745- 750; WHO, pp. 29- 39, 190, 198-203, 250-253).

Answer 2

A B **C** D E ## Footnote Meningothelial meningiomas exhibit sheets or 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 colJagen 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 chordonut (WHO, pp. 176-184; Ellison , pp. 703- 716).

Answer 3

**A** B C D E ## Footnote Papillary meningiomas are unique variants that exhibit a high nuclear-cytoplasmic ratio, prominent mitoses, metastasis throughout the CNS via CSF pathways, and occasional metastasis outside the CNS. Other meningioma variants are considered atypical if they exhibit prominent mitoses, increased cellularity, sheet-like growth patterns, and necrosis. Anaplastic meningiomas are frankly malignant lesions that exhibit prominent cellular pleomorphism and necrosis. Atypical and anaplastic meningiomas are more likely to exhibit local invasion and recur after resection; however, distant metastasis is usually confined to papillary meningiomas (Ellison, pp. 711- 715; WHO, pp.179-180).

Answer 4

A B C **D** E ## Footnote 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 in 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 mucopolysacchari doses and results from defective glycosaminoglycan (heparan sulfate) metabolism. Zellweger syndrome is a peroxisomal disorder that is associated with pachygyria, polymicrogyria, and various heterotopias (Ellison, pp. 93, 445 447,452 454,501-507;Me~tt,pp.539 540).

Answer 5

**A** B C D E ## Footnote Multiple sclerosis (MS) is classically associated with the I-ILA-DR2 allele, and I-ILA-DR15 is common in Northern Europeans with MS . The I-ILA alleles A3, B7, and DR3 are also overrepresented in the MS population. The incidence and prevalence of MS vary with latitude, increasing with 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 (Ellison, pp. 389- 404).

Answer 6

A **B** C D E ## Footnote I-Iemangiopericytoma 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 EMA, 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 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison, pp. 656-659, 691- 692,703- 716,732-735).

Answer 7

A B **C** D E ## Footnote I-Iemangiopericytoma 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 EMA, 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 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison, pp. 656-659, 691- 692,703- 716,732-735).

Answer 8

A B C **D** E ## Footnote I-Iemangiopericytoma 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 EMA, 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 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison, pp. 656-659, 691- 692,703- 716,732-735).

Answer 9

**A** B C D E ## Footnote I-Iemangiopericytoma 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 EMA, 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 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison, pp. 656-659, 691- 692,703- 716,732-735).

Answer 10

A B C D **E** ## Footnote I-Iemangiopericytoma 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 EMA, 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 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison, pp. 656-659, 691- 692,703- 716,732-735).

Answer 11

A B C **D** E ## Footnote Oligodendrogliomas are characterized by uniform cells, arranged 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 hete rozygosity on chromosome 1p and 19q and rarely contain ])53 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 (Ellison, pp . 641- 644; WHO, pp. 56- 64).

Answer 12

A B **C** D E ## Footnote Microscopically, acute cerebral infarcts (after 8 to 12 hours) exhibit neuronal eosinophilia, pylmosis, 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 pylmosis with vacuolation of the surrounding neuropil and a paucity of inflammation. This is most consistent with an acute cerebral infarction (Ellison, pp. 197-203, 627; WHO, p. 25).

Answer 13

A B **C** D E ## Footnote Acute spinal cord injury is characterized by 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 (Ellison, pp. 262-269).

Answer 14

A **B** C D E ## Footnote Monosomy 22 is by far the most common cytogenetic abnormality of meningiomas, and greater than 75% of all meningiomas exhibit loss of heterozygosity for chromosome 22q markers. Allelic losses of chromosomes 1p, 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 (Ellison, p. 715; Kaye and Laws, p. 78).

Answer 15

A B C D **E** ## Footnote Sturge-Weber syndrome (encephalotrigeminal angiomatosis) is a neurocutaneous disorder that occurs sporadically. The disorder is characterized by port wine stains i 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-\Veber syndrome develop epilepsy over time, and many exhibit progressive neurologic deficits such as hemiparesis, hemisensory loss, and homonymous hemianopsia. On 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 (Ellison, pp. 107-108).

Answer 16

A B C D **E** ## Footnote 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. :Microglial 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., CMV, HIV, arboviruses, polioviruses). The aggregation of microglia and macrophages around dying neurons is called "neuronophagia" (Ellison, pp. 273- 275, 277, 303-304, 319, 324).

Answer 17

A B C **D** E ## Footnote 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, progressive hearing loss, hepatosplenomegaly, and various degrees of mental retardation. Hurler syndrome (MPS I), not Hunter syndrome, is associated with corneal clouding (Ellison, pp. 445- 446)

Answer 18

A **B** C D E ## Footnote CNS metastatic lesions can occur anywhere but are typically located at the gray-white junction 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 can be firm, or they can 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 ~vIS plaques but can be observed with fulminant, acute plaques. Acute infarcts exhibit only slight blurring of the gray-white junction with dusky discoloration , often in major vascular territories (Ellison, pp. 197- 202,327- 334,389- 398,743- 750).

Answer 19

A B **C** D E ## Footnote 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 joints and cardiovascular system. Ouillain-Barre syndrome (OBS) is an acute ascending monophasic motor polyneuropathy that can involve the face , limbs, and even respiratory musculature. OBS is not typically associated with any sensory loss or ciliary paralYSiS, however (Ellison, pp. 342- 349; Merritt, pp. 613- 615)

Answer 20

A **B** C D ## Footnote Subependymal germinal matrix hemorrhage is usually observed in low-birth-weight premature infants and can result in intraventricular hemorrhage. The microcirculation of the peri ventricular matrix zone is extremely fragile and persists in the neonate until 34 weel(s of gestation. This microcirculation is prone to hemorrhage , with hypoxia and secondary failures of autoregulation. Choroid plexus hemorrhage is the most common cause of intraventricular hemorrhage in the term infant and can result in anything from minimal (asymptomatic) hemorrhage to massive intraventricular hemorrhage (Ellison, pp. 34-37).

Answer 21

**A** B C D ## Footnote Subependymal germinal matrix hemorrhage is usually observed in low-birth-weight premature infants and can result in intraventricular hemorrhage. The microcirculation of the peri ventricular matrix zone is extremely fragile and persists in the neonate until 34 weel(s of gestation. This microcirculation is prone to hemorrhage , with hypoxia and secondary failures of autoregulation. Choroid plexus hemorrhage is the most common cause of intraventricular hemorrhage in the term infant and can result in anything from minimal (asymptomatic) hemorrhage to massive intraventricular hemorrhage (Ellison, pp. 34-37).

Answer 22

A **B** C D E ## Footnote 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 (Ellison, pp. 29- 32, 62-68, 71-80,82-85,87-89).

Answer 23

A **B** C D E ## Footnote Pediatric patients with bacterial meningitis are usually due to infection by StreptococCllS pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS il1fhlellzae. The incidence of I-I . j'11fl'llellzae meningitis in the pediatric population has decreased significantly in the past decade because of the widespread use of the H. injl'llenzae B vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. 'Pnell11loniae or N. 11leningitidis. Meningitis in the elderly commonly results from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter (liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral abscesses in this population (Ellison, pp. 327- 330; Merritt, pp. 103-107)

Answer 24

**A** B C D E ## Footnote Pediatric patients with bacterial meningitis are usually due to infection by StreptococCllS pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS il1fhlellzae. The incidence of I-I . j'11fl'llellzae meningitis in the pediatric population has decreased significantly in the past decade because of the widespread use of the H. injl'llenzae B vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. 'Pnell11loniae or N. 11leningitidis. Meningitis in the elderly commonly results from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter (liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral abscesses in this population (Ellison, pp. 327- 330; Merritt, pp. 103-107)

Answer 25

A B **C** D E ## Footnote Pediatric patients with bacterial meningitis are usually due to infection by StreptococCllS pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS il1fhlellzae. The incidence of I-I . j'11fl'llellzae meningitis in the pediatric population has decreased significantly in the past decade because of the widespread use of the H. injl'llenzae B vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. 'Pnell11loniae or N. 11leningitidis. Meningitis in the elderly commonly results from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter (liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral abscesses in this population (Ellison, pp. 327- 330; Merritt, pp. 103-107)

Answer 26

A B C D **E** ## Footnote Pediatric patients with bacterial meningitis are usually due to infection by StreptococCllS pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS il1fhlellzae. The incidence of I-I . j'11fl'llellzae meningitis in the pediatric population has decreased significantly in the past decade because of the widespread use of the H. injl'llenzae B vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. 'Pnell11loniae or N. 11leningitidis. Meningitis in the elderly commonly results from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter (liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral abscesses in this population (Ellison, pp. 327- 330; Merritt, pp. 103-107)

Answer 27

A B C **D** E ## Footnote Pediatric patients with bacterial meningitis are usually due to infection by StreptococCllS pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS il1fhlellzae. The incidence of I-I . j'11fl'llellzae meningitis in the pediatric population has decreased significantly in the past decade because of the widespread use of the H. injl'llenzae B vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. 'Pnell11loniae or N. 11leningitidis. Meningitis in the elderly commonly results from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter (liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral abscesses in this population (Ellison, pp. 327- 330; Merritt, pp. 103-107)

Answer 28

A **B** C D E ## Footnote Ganglion cell tumors (gangliocytomas and gangliogliomas) are characterized by neoplastic ganglion cells, with or without a component of neoplastic glial tissue (usually with an astrocytic morphology). Neoplastic ganglion cells resemble normal neurons but are abnormally large and round, arranged in clusters, and contain an eccentric nucleus with a prominent nucleolus. The classic finding is binuclea tion, seen in one of the ganglion cells here, which never occurs in normal neurons. Gangliogliomas occasionally exhibit nuclear pleomorphism, but mitoses are absent. Ganglion cells exhibit immunoreactivity for synaptophysin and neurofilaments. J\'ledulloblastomas are characterized by 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 (Ellison, pp. 645- 647, 653- 657,667- 672; WHO, pp. 72- 77, 96- 98,129-137)

Answer 29

A **B** C D E ## Footnote Schwanllomas are characterized by compact arrangements of interwoven fascicl es 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 wavy nuclei arranged haphazardly within a mucoid matrLx with interspersed bundles of collagen ("shredded carrots" appearance). Fibrous meningiomas consist of spindle-shaped cells with inte rmixed collagen and lack a mucoid matrLx and Verocay bodies. Malignant nerve sheath tumors can also exhibit a fascicular pattern; however, this tumor is highly cellular and contains frequent mitoses and necrosis. The presence of Verocay bodies in this specimen is consistent with a schwannoma (Ellison, pp. 695- 702, 707, 715; WHO, pp. 164- 166, 172-174, 176- 184).

Answer 30

**A** B C D E ## Footnote Mature teratomas, the most common of which is the dermoid cyst depicted here , exhibit a mixture of ectodermal, mesodermal, and endodermal components. These neoplasms are well circumscribed and rarely associated with malignant transformation into carcinomas or sarcomas. Dermoid cysts are lined by squamous epitheliu111 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 keratini zed ghost cells, calCification, and cholesterol clefts (Ellison, pp. 683-684,724- 727,737- 739).

Answer 31

A B C D **E** ## Footnote 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 Klippel-Feil cases are associated with congenital elevation of the scapula, which is known as Sprengel's deformity. IGippel-Feil is also associated with diastema tomyelia, Chiari I malformations, basilar impression, and genitourinary abnormalities (Merritt, p. 490).

Answer 32

A B C **D** E ## Footnote Disjll.llction refers to the separation of superfiCial ectodenll from neural ectoderm during development. It is thought that premature disjunction allows cells of mesodermal origin to migrate between these two layers of ectoderm, which can lead to the formation of lipomas (Will

Answer 33

A B C D **E** ## Footnote Von Hippel-Lindau syndrome (VEL) is an autosomal dominant neurocutaneous disorder that is associated with chromosome 3p. VHL patients deve lop hemangioblastomas of the brainstem, cerebellum, and spinal cord. VHL is also associated with the development of retinal angiomas, paragangliomas, endolymphatic sac tumors, pheochromocytoma, epididymal cystadenoma, renal and pancreatic cysts, and renal cell carcinoma . The production of erythropoietin by hemangioblastomas can occur with VHL and result in polycythemia (Ellison, pp. 736- 738; WHO, pp. 223-226; Kaye and Laws, pp. 75- 76)

Answer 34

**A** B C D E ## Footnote 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 by the presence of swollen cortical neurons (ballooned neurons), gliosiS, and microvacuolation (Ellison, pp. 287- 289,512- 514).

Answer 35

A **B** C D E ## Footnote 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"). Sllbependymomas often exhibit microcysts; however, nuclear pleomorphism and mitoses are universally absent. Myxopapillary ependymomas claSSically exhibit collars of epithelioid cells surrounding pools of mucin with central blood vessels. Dysembryoplastic neuroepithelial tumor (D~TET) is a supratentorial cortical neoplasm of children and young adults that is usually located in the temporal lobe and presents with seizures. ;vIicroscopically, DNETs exhibit nodules of oligodendrocyte-like cells, mucinous cysts, and neurons that appear to "float" in the mucinous cysts (Ellison, pp. 651, 659- 661; WHO, pp. 78- 81, 103-106).

Answer 36

A B **C** D E ## Footnote Gliosarcoma is a variant of glioblastoma multifonne. 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). Malignant nerve sheath tumors also contain spindle-shaped neoplastic cells; 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 (Ellison, pp. 628-632, 682, 700- 702; WHO, pp. 42- 44)

Answer 37

A B C **D** E ## Footnote 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 (Ellison, pp. 667-672; WHO, pp. 129-137)

Answer 38

**A** B C D ## Footnote Neurofibromatosis type 1 (NF·l) is an autosomal dominant neurocutaneous disorder that localizes to chromo· some 17. The NF·l gene is very large and associated with a high spontaneous mutation rate. Approximately 50% of all NF·l cases are secondary to spontaneous mutations. NF·l is associated with 100% penetrance and variable expressivity. Tuberous sclerosis (TS) is also an autosomal dominant neurocutaneous disorder that is associated with a high spon· taneous mutation rate. TS can result from 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 (Kaye and Laws, pp. 69- 72, 75; WHO, pp. 216- 222; Ellison, pp. 695-697).

Answer 39

A **B** C D ## Footnote Neurofibromatosis type 1 (NF·l) is an autosomal dominant neurocutaneous disorder that localizes to chromo· some 17. The NF·l gene is very large and associated with a high spontaneous mutation rate. Approximately 50% of all NF·l cases are secondary to spontaneous mutations. NF·l is associated with 100% penetrance and variable expressivity. Tuberous sclerosis (TS) is also an autosomal dominant neurocutaneous disorder that is associated with a high spon· taneous mutation rate. TS can result from 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 (Kaye and Laws, pp. 69- 72, 75; WHO, pp. 216- 222; Ellison, pp. 695-697).

Answer 40

A **B** C D E ## Footnote 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 cOl11monly observed in chronic alcoholics and some patients with gastrointestinal disorders. Patients with Wernicl(e's encephalopathy exhibit ataxia, gaze pa lsies, confUSion, and apathy, which is often reversible with the administration of thiamine. The chronic form of the disease is Imown as I<,orsakoff's psychosis and is associated with retrograde and anterograde amnesia , with concomitant confabulation, usually irreversible (Ellison, pp. 415- 418).

Answer 41

A B **C** D ## Footnote Crouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoetlunoid 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 an autosomal dominant condition that involves premature closure of all cranial sutures. These patients have facies that resemble those of Crouzon's disease and also have a high incidence of hydrocephalus. Apert's syndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus (Will

Answer 42

A **B** C D ## Footnote Crouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoetlunoid 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 an autosomal dominant condition that involves premature closure of all cranial sutures. These patients have facies that resemble those of Crouzon's disease and also have a high incidence of hydrocephalus. Apert's syndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus (Will

Answer 43

A B **C** D ## Footnote Crouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoetlunoid 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 an autosomal dominant condition that involves premature closure of all cranial sutures. These patients have facies that resemble those of Crouzon's disease and also have a high incidence of hydrocephalus. Apert's syndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus (Will

Answer 44

A **B** C D E ## Footnote Oraniosynostosis refers to the premature closure of cranial sutures; this condition is often associated with Crouzon's disease and Apert's syndrome, although many 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) (Will

Answer 45

A B C D **E** ## Footnote Tuberous sclerosis (TS) often presents in 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 associated with the development of cortical tubers, which are firm, pale nodules that project 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 (Ellison, pp. 108-110; WHO, pp.227-230).

Answer 46

**A** B C D E ## Footnote 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 (Ellison, pp. 257-259).

Answer 47

A B C D **E** ## Footnote Diffuse axonal injury (DA1) 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. IvIicroscopically, DAl specimens exhibit prominent axonal spheroids, especially with silver stains. DAI varies in severity from minimal disturbances in level of consciousness to vegetative states with subsequent death (Ellison, pp. 249- 253).

Answer 48

**A** B C D E ## Footnote Cerebral aspergillosis is usually secondary to hematogenous dissemination from the lungs or local spread from the paranasal sinuses of Aspergillus fum:igatus or Aspergillus f/avus. Symptoms of cerebral aspergillosis are variable and include headache, seizures, cranial nerve palsies, hemiparesis, and elevated intracranial pressure. Aspergilltls has a tendency to exhibit prominent vascular invasion, with subsequent vascular thrombosis, infarction, and hemorrhage. Aspergilltls 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 cryptococcosis exhibits only a yeast form with CNS infections (Ellison, pp. 351-355, 357- 362).

Answer 49

A B C **D** E ## Footnote Amyotrophic lateral sclerosis (ALS) affects primarily the anterior and lateral corticospinal tracts of the spinal cord, as evidenced by the loss of myelinated a.'wns (as depicted in the specimen). Subacute combined degeneration (SACD) results from vitamin BI2 (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 dOl'sal 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 ata.\:ia (FA) is an autosomal recessive disorder that localizes to chromosome 9 and results in deterioration of the posterior columns, spinocerebellar tracts, Clarke's nucleus, and distal (thoracolumbar) corticospinal tracts (Ellison, pp. 344- 345, 417- 420,501-508,533- 534).

Answer 50

A **B** C D ## Footnote 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 lIsually exhibit a full recovery (10 to 20% have permanent neurologic deficits), and the disease course is generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in genetically 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 J\-IS 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 P-1b Betaserone), interferon p-1a (Avonex), and Copaxone are generally utilized to deCl'ease the frequency of MS attacl(s (Ellison, pp. 389- 404, 405-407; Merritt, pp. 151-153, 773-791; Greenberg, pp. 69-71).

Answer 51

A **B** C D ## Footnote 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 lIsually exhibit a full recovery (10 to 20% have permanent neurologic deficits), and the disease course is generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in genetically 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 J\-IS 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 P-1b Betaserone), interferon p-1a (Avonex), and Copaxone are generally utilized to deCl'ease the frequency of MS attacl(s (Ellison, pp. 389- 404, 405-407; Merritt, pp. 151-153, 773-791; Greenberg, pp. 69-71).

Answer 52

A B **C** D ## Footnote 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 lIsually exhibit a full recovery (10 to 20% have permanent neurologic deficits), and the disease course is generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in genetically 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 J\-IS 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 P-1b Betaserone), interferon p-1a (Avonex), and Copaxone are generally utilized to deCl'ease the frequency of MS attacl(s (Ellison, pp. 389- 404, 405-407; Merritt, pp. 151-153, 773-791; Greenberg, pp. 69-71).

Answer 53

A **B** C D ## Footnote 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 lIsually exhibit a full recovery (10 to 20% have permanent neurologic deficits), and the disease course is generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in genetically 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 J\-IS 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 P-1b Betaserone), interferon p-1a (Avonex), and Copaxone are generally utilized to deCl'ease the frequency of MS attacl(s (Ellison, pp. 389- 404, 405-407; Merritt, pp. 151-153, 773-791; Greenberg, pp. 69-71).

Answer 54

A **B** C D E ## Footnote CNS lymphoma is characterized by numerous malignant lymphocytes that tend to invade the walls of blood vessels. Lymphoma cells are prominent in the perivascular spaces, and they diffusely invade brain parenchyma toward the periphery of the lesion. More than 80% of these tumors are diffuse large B-cell lymphomas. The surrounding brain often exhibits reactive astrocytosis, which can resemble other inflammatory disorders. Interspersed 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-celllymphomas are positive for CD20 (Ellison, pp. 689-694; WHO, pp. 198- 203).

Answer 55

A B C **D** E ## Footnote Choroid plexus papillomas (CPPs) 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-100, 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 cyst wall are ciliated, and mucin-containing goblet cells may also be located within the epithelial layer (WHO, pp. 84-86, 180, 244-246; Ellison, pp. 685-688,713,724- 727,738-740).

Answer 56

A **B** C D E ## Footnote Paragangliomas usually arise from the cauda equina or jugular 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, neurofilamen t, and chromogranin immunostains. Sustentacular cells are S-IOO-positive. ll'lyxopapillary ependymomas can also originate frol11 the cauda equina region; however, they are GFAP-positive, whereas paragangliomas are GFAP-negative. Paragangliomas are WHO grade I lesions (Ellison, pp. 651, 658-659; WHO, pp. 78- 79, 112- 114).

Answer 57

A B C **D** E ## Footnote 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. J\Hcroscopically, fat embolism exhibits hemorrhagic lesions surrounding capillaries with signs of fibrinoid necrosis. Lipid globules can be demonstrated in necrotic regions with oil red o stains. Progressive multifocalleukoencephalopathy (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 exJ1ibits multiple petechial hemorrhages in both the cortical gray and deep white matter, which is most consistent with fat embolism (Ellison, pp. 254-256, 298- 300,454- 456).

Answer 58

**A** B C D E ## Footnote PTAH stains for collagen, while the Sudan, Weigert, and lvlm'chi are useful myelin stains (Wheater, pp. 102, 149, 309).

Answer 59

**A** B C D E ## Footnote 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 exJ1ibit epithelial differentiation and the presence of true gland-like canals. Ependymomas are GFAPpositive. The presence of numerous perivascular pseudorosettes in the above specimen is most consistent with an ependymoma (Ellison , pp. 645-651; WHO, pp. 72-77).

Answer 60

A B C D **E** ## Footnote 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 neoplasms, and embryonal neoplasms can also exhibit prominent melanin (Ellison, pp. 734-737).

Answer 61

A **B** C D E ## Footnote Hallervorden-Spatz disease (I-ISO) is an autosomal recessive disorder that presents with progressive gait disturbance, dystonia, dysarthria, and choreoathetosis in children and young adults. An adult variant of I-ISO presents with progressive cognitive decline and extrapyramidal signs. '1'2- weighted MRI exhibits prominent hypointensity within the globus pallidus in patients with HSO ("eye of the tiger" sign), which is secondary to the accumulation of iron pigment. Microscopically, HSO 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 (Ellison, pp. 134- 136,603-605).

Answer 62

A B C D **E**

Answer 63

A B **C** D E

Answer 64

A **B** C D E

Answer 65

**A** B C D E

Answer 66

A B C **D** E

Answer 67

A **B** C D E ## Footnote The ultrastructural homologue of the miniature endplate potential (MEPP) is the synaptic vesicle, which produces a MEPP after being released from the presynaptic terminal (Kandel, pp. 258-262).

Answer 68

**A** B C D E ## Footnote Note the presence of psammoma bodies intermingled with whorling meningothelial cells in this photomiCrograph, depicting a psammomatous meningioma (Ellison, pp.708-709).

Answer 69

A B C D **E** ## Footnote This photomicrograph depic ts a myxopapillary ependymoma with markedly thickened blood vessel walls and cells with a delicate fibrillary cytoplasm surrounding mucin-rich areas (Ellison, pp. 646-651).

Answer 70

A B C D **E** ## Footnote Anaplastic, rhabdOid, and papillary meningiomas are WHO grade III neoplasms and carry the worst prognosis, while atypical, chordoid, and clea r cell meningiomas are \\THO grade II variants. The best prognosis is seen with WHO grade I meningiomas, which include the psammomatous,angiomatous, microcystic, secretory, metaplastic, and lymphoplasmacytic variants (Ellison, pp. 709-712).

Answer 71

A B C D **E** ## Footnote Patients with homocystinuria (autosomal recessive, chromosome 21) have a variable onset and may present with a marfanoid habitus, codfish vertebrae (biconcave), eye anomalies (ectopia lentis, myopia , glaucoma, optic atrophy), mental retardation, seizures, behavioral disorders, and strokes (beginning at age 5 to 9 months). The pathophysiology includes intimal thickening and fibrosis of blood vessels, which may lead to arterial and venous thrombosis. It is the result of cystathionine ~-synthase deficiency, which leads to the accumulation of homocysteine and methionine. There is also impaired methylation of homocysteine to methionine from enzyme defiCiency or cofactor B1 2 deficiency. Treatment may include restriction of dietary methionine as well as pyridoxine, vitamin B12 , and cysteine supplements. Hypoxanthine-guanine phosphoribosyl transferase defiCiency results in Lesch-Nyhan syndrome, phenylalanine hydroxylase defiCiency results in phenyllcetonuria, and alpha-ketoacid dehydrogenase deficiency can produce maple syrup urine disease (Merritt, p. 256; Geyer, pp. 102- 106).

Answer 72

A B **C** D E ## Footnote Patients with homocystinuria (autosomal recessive, chromosome 21) have a variable onset and may present with a marfanoid habitus, codfish vertebrae (biconcave), eye anomalies (ectopia lentis, myopia , glaucoma, optic atrophy), mental retardation, seizures, behavioral disorders, and strokes (beginning at age 5 to 9 months). The pathophysiology includes intimal thickening and fibrosis of blood vessels, which may lead to arterial and venous thrombosis. It is the result of cystathionine ~-synthase deficiency, which leads to the accumulation of homocysteine and methionine. There is also impaired methylation of homocysteine to methionine from enzyme defiCiency or cofactor B1 2 deficiency. Treatment may include restriction of dietary methionine as well as pyridoxine, vitamin B12 , and cysteine supplements. Hypoxanthine-guanine phosphoribosyl transferase defiCiency results in Lesch-Nyhan syndrome, phenylalanine hydroxylase defiCiency results in phenyllcetonuria, and alpha-ketoacid dehydrogenase deficiency can produce maple syrup urine disease (Merritt, p. 256; Geyer, pp. 102- 106).

Answer 73

A B C D **E** ## Footnote Patients with homocystinuria (autosomal recessive, chromosome 21) have a variable onset and may present with a marfanoid habitus, codfish vertebrae (biconcave), eye anomalies (ectopia lentis, myopia , glaucoma, optic atrophy), mental retardation, seizures, behavioral disorders, and strokes (beginning at age 5 to 9 months). The pathophysiology includes intimal thickening and fibrosis of blood vessels, which may lead to arterial and venous thrombosis. It is the result of cystathionine ~-synthase deficiency, which leads to the accumulation of homocysteine and methionine. There is also impaired methylation of homocysteine to methionine from enzyme defiCiency or cofactor B1 2 deficiency. Treatment may include restriction of dietary methionine as well as pyridoxine, vitamin B12 , and cysteine supplements. Hypoxanthine-guanine phosphoribosyl transferase defiCiency results in Lesch-Nyhan syndrome, phenylalanine hydroxylase defiCiency results in phenyllcetonuria, and alpha-ketoacid dehydrogenase deficiency can produce maple syrup urine disease (Merritt, p. 256; Geyer, pp. 102- 106).

Answer 74

A B C **D** E ## Footnote Note the prominent pleomorphic astrocyte and oligodendrocytes with viral inclusions in this immunocompromised patient with PML. Patients with this disease present with focal neurologic deficits including dysarthria, limb weakness, visual disturbances, ataxia, personality changes, and occasionally seizures. PML usually progresses rapidly over the course of weeks to months, resulting in increasing neurologic impairment, coma, and death. Treatment of the underlying immunocompromised state can lead to remission (Ellison, pp. 298-300).

Answer 75

**A** B C D E ## Footnote Note the haphazardly arranged spindle cells with wavy nuclei and a prominent matrL'( of mucin and collagen in this photomicrograph depicting a neurofibroma (Ellison, pp.699- 701).

Answer 76

**A** B C D E ## Footnote Note the nests of chief cells (Zellballen) surrounded by a fibrovascular stroma and sustentacular cells in this photomicrograph depicting a paraganglioma of the tilum terminale. These neoplasms show immunoreactivity to synaptophysin and chrolllograninj ultrastructural examination reveals dense-core granules. Sustentacular cells are immunoreactive to S-100 protein (Ellison, pp. 658-659).

Answer 77

A **B** C D E ## Footnote Note the nests of chief cells (Zellballen) surrounded by a fibrovascular stroma and sustentacular cells in this photomicrograph depicting a paraganglioma of the tilum terminale. These neoplasms show immunoreactivity to synaptophysin and chrolllograninj ultrastructural examination reveals dense-core granules. Sustentacular cells are immunoreactive to S-100 protein (Ellison, pp. 658-659).

Answer 78

A B C D **E** ## Footnote Note the sheets of cells with uniform round nuclei, which is characteristic of central neurocytomas. These neoplasms most often show synaptophysin immunoreactivity, although a small astrocytic component is often present that is GFAP-positive. Ultrastructural features include dense-core and clear vesicles, microtubules, and intermediate filaments (Ellison, pp. 656-658; WHO, pp. 107-109).

Answer 79

A **B** C D E ## Footnote Subependymal germinal matrix hemorrhage (SEE) usually occurs in premature infants (less than 34 weeks' gestation) with low birth weight and is usually located adjacent to the head of the caudate nucleus or thalamus. SEE is the most common cause of intraventricular hemorrhage (IVI-I) in premature infants. Grade I SEE is confined to the germinal matrLx, grade 2 extends into the lateral ventricle from the germinalmatrLx, grade 3 consists of IVE with hydrocephalus, and grade IV involves extension into the brain parenchyma (Ellison, pp. 34-37).

Answer 80

A B **C** D E ## Footnote Laminar necrosis can be related to intrapartum difficulties, congenital heart disease, and vascular collapse in an infant. It often involves the depths of the sulci (as depicted here), and the necrosis can be in a laminar or pseudolaminar pattern (Ellison, pp. 37- 43).

Answer 81

A B C **D** E ## Footnote Note the absence of sulci and gyri along the cerebral convexities of this specimen depicting agyria, which results from abnormal cellular migration during embryologic development (Ellison, pp. 71- 76).

Answer 82

A B C **D** E ## Footnote Note the absence of sulci and gyri along the cerebral convexities of this specimen depicting agyria, which results from abnormal cellular migration during embryologic development (Ellison, pp. 71- 76).

Answer 83

A B C **D** E ## Footnote Note the prominent calcifications of residual neurons adjacent to a chronic infarct in this photomicrograph depicting siderocalcinosis (Ellison, pp. 190- 191)

Answer 84

A B C D **E** ## Footnote Note the prominent calcifications of residual neurons adjacent to a chronic infarct in this photomicrograph depicting siderocalcinosis (Ellison, pp. 190- 191)

Answer 85

**A** B C D E ## Footnote Note the presence of a prominent inflammatory infiltrate within the lumen of this blood vessel with concomitant vascular thrombosis in this photomicrograph depicting bacterial meningitis (Ellison, pp. 327-331).

Answer 86

A **B** C D E ## Footnote Note the presence of broad, nonseptate hyphae in this photomicrograph depicting mucormycosis, a fungal infection most often seen in diabetic patients with ketoacidosis. It most commonly enters the cranial cavity from the nasal mucosa via the cribriform plate. Mucormycosis is often fatal within a few days unless surgical debridement and antifungal therapy is initiated early (Ellison, pp. 353-355).

Answer 87

A B **C** D E ## Footnote Note the presence of broad, nonseptate hyphae in this photomicrograph depicting mucormycosis, a fungal infection most often seen in diabetic patients with ketoacidosis. It most commonly enters the cranial cavity from the nasal mucosa via the cribriform plate. Mucormycosis is often fatal within a few days unless surgical debridement and antifungal therapy is initiated early (Ellison, pp. 353-355).

Answer 88

A B **C** D E ## Footnote Note the presence of broad, nonseptate hyphae in this photomicrograph depicting mucormycosis, a fungal infection most often seen in diabetic patients with ketoacidosis. It most commonly enters the cranial cavity from the nasal mucosa via the cribriform plate. Mucormycosis is often fatal within a few days unless surgical debridement and antifungal therapy is initiated early (Ellison, pp. 353-355).

Answer 89

A B **C** D E ## Footnote Note the fascicular arrangement of these neoplastic cells that exhibit a high nuclear-cytoplasmic r and prominent mitosis in this photomicrograph depicting a malignant nerve sheath tumor (MNST). This neoplasm usually involves the trigeminal nerve intracranially but most often originates from the cervical or brachial plexi. MNST carries a poor prognosis, and approximately SO% of patients harboring this lesion have NFl (Ellison, pp. 700- 702).

Answer 90

A **B** C D E ## Footnote Note the fascicular arrangement of these neoplastic cells that exhibit a high nuclear-cytoplasmic r and prominent mitosis in this photomicrograph depicting a malignant nerve sheath tumor (MNST). This neoplasm usually involves the trigeminal nerve intracranially but most often originates from the cervical or brachial plexi. MNST carries a poor prognosis, and approximately SO% of patients harboring this lesion have NFl (Ellison, pp. 700- 702).

Answer 91

A B **C** ## Footnote The most common metastatic brain tumors originate from the lung, breast, skin, and kidney. Photomicrograph A depicts a lesion with an area of necrosis and branching as well as sharply angulated lobules, which is most consistent with metastatic breast carcinoma. Photomicrograph B depicts metastatic lung adenocarcinoma, which is thyroid transcription factor-l (TTF-l) positive, and thyroglobulin negative. Photomicrograph C shows a hypervascular tumor with lobules of clear cells, which is most consistent with renal cell carcinoma [EMA (+), CAM S.2 (+), CD 10 (+)] (Ellison, pp. 743-749; WHO, pp. 250-253).

Answer 92

**A** B C ## Footnote The most common metastatic brain tumors originate from the lung, breast, skin, and kidney. Photomicrograph A depicts a lesion with an area of necrosis and branching as well as sharply angulated lobules, which is most consistent with metastatic breast carcinoma. Photomicrograph B depicts metastatic lung adenocarcinoma, which is thyroid transcription factor-l (TTF-l) positive, and thyroglobulin negative. Photomicrograph C shows a hypervascular tumor with lobules of clear cells, which is most consistent with renal cell carcinoma [EMA (+), CAM S.2 (+), CD 10 (+)] (Ellison, pp. 743-749; WHO, pp. 250-253).

Answer 93

A **B** C ## Footnote The most common metastatic brain tumors originate from the lung, breast, skin, and kidney. Photomicrograph A depicts a lesion with an area of necrosis and branching as well as sharply angulated lobules, which is most consistent with metastatic breast carcinoma. Photomicrograph B depicts metastatic lung adenocarcinoma, which is thyroid transcription factor-l (TTF-l) positive, and thyroglobulin negative. Photomicrograph C shows a hypervascular tumor with lobules of clear cells, which is most consistent with renal cell carcinoma [EMA (+), CAM S.2 (+), CD 10 (+)] (Ellison, pp. 743-749; WHO, pp. 250-253).

Answer 94

A B C **D** E ## Footnote Note the areas of necrosis without intact cells or nuclei and the hyalinized, necrotic vessel in this photomicrograph depicting radiation necrosis (Ellison , p. 632; Berger, pp. 471-474; Greenberg, pp. 507-515).

Answer 95

A B C **D** E ## Footnote Note the prominent capsule and central purulent region in this gross section depicting a brain abscess. The central area of necrosis and surrounding capsule formation are characteristic features of the fourth stage of abscess formation (capsular stage). Refer to Table S.97-S.100A for a sumnulry of the stages of abscess formation (Ellison, pp. 330-336).

Answer 96

A **B** C D E ## Footnote Note the noncaseating sarcoid granuloma containing prominent epithelioid cells and multinucleated giant cells. Tuberculosis is associated with caseating granulomas, whereas MS plaques, paragangliomas, amputation neuromas, and acoustic neuromas are not associated with granuloma formation (Ellison, pp. 346-348).

Answer 97

A B **C** D E ## Footnote Note the noncaseating sarcoid granuloma containing prominent epithelioid cells and multinucleated giant cells. Tuberculosis is associated with caseating granulomas, whereas MS plaques, paragangliomas, amputation neuromas, and acoustic neuromas are not associated with granuloma formation (Ellison, pp. 346-348).

Answer 98

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 99

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 100

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 101

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 102

A **B** C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 103

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 104

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 105

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 106

**A** B C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 107

A **B** C D ## Footnote Patients with axonal neuropathies (most common) usually have symmetric distal sensory loss with weakness, atrophy, and loss of ankle jerks. Nerve conduction velocity (NCV) studies show mild slowing without conduction block or temporal dispersion as well as decreased amplitudes of compound motor action potentials (CMAP) and sensory nerve action potentials (SNAP). EJ\'IG studies show evidence of distal denervation. Demyelinating neuropathies typically present with sensory loss of larger fibers more than smaller fibers, and usually motor more than sensory involvement. NCV studies can show marked slowing, conduction block, temporal dispersion, prolonged F waves, and prolonged distal latencies with demyelinating diseases. EMG studies show denervation, based on chronicity. Of note, HIV-positive patients with neuropathy typically have a demyelinating process, whereas patients with AIDS rarely present with a demyelinating neuropathy but instead with an a:'Wnal neuropathy (Merritt, pp. 620- 624; Geyer, p. 164).

Answer 108

A **B** C D E ## Footnote Note the presence of hypocellularity, gliosis, demyelination, and a lack of inflammation in this photomicrograph depicting a chronic infarct (Ellison, pp. 197- 201)

Answer 109

A B **C** D E F ## Footnote Lewy bodies (E), the hallmark of Parkinson's disease, are intracellular cytoplasmic inclusions containing an eosinophilic core surrounded by a pale halo. They are predominantly found in the substantia nigra and consist of ubiquitin, neurofilaments, CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains; however, they are best identified with ubiquitin staining techniques. Hirano bodies (A) are eosinophilic cytoplasmic inclusions composed of actin and actin-associated proteins; they are particularly prominent in the CAl sector of the hippocampus in patients with Alzheimer's disease (AD) and Pick's disease. Neurofibrillary tangles (D) are intraneuronal inclusions composed of phosphorylated tau, which is a rnicrotubule-associated cytoskeletal protein. Phosphorylated tau forms helical filaments, which can be found within the neocortex and pyramidal cells of the hippocampus in patients with AD. The microscopic hallmark of Pick's disease is the Pick body (B), which is a spherical cytoplasmic inclusion (composed of phosphorylated tau) that is mildly basophilic and contains a well-demarcated margin. Negri bodies (C) are oval or round cytoplasmic inclusions that can be found throughout the CNS but are most prominent in Purkinje cells. The appearance of Negri bodies is similar to that of red blood cells (Ellison, pp. 288-289, 504, 513- 514, 552,556-559,570- 572).

Answer 110

**A** B C D E F ## Footnote Lewy bodies (E), the hallmark of Parkinson's disease, are intracellular cytoplasmic inclusions containing an eosinophilic core surrounded by a pale halo. They are predominantly found in the substantia nigra and consist of ubiquitin, neurofilaments, CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains; however, they are best identified with ubiquitin staining techniques. Hirano bodies (A) are eosinophilic cytoplasmic inclusions composed of actin and actin-associated proteins; they are particularly prominent in the CAl sector of the hippocampus in patients with Alzheimer's disease (AD) and Pick's disease. Neurofibrillary tangles (D) are intraneuronal inclusions composed of phosphorylated tau, which is a rnicrotubule-associated cytoskeletal protein. Phosphorylated tau forms helical filaments, which can be found within the neocortex and pyramidal cells of the hippocampus in patients with AD. The microscopic hallmark of Pick's disease is the Pick body (B), which is a spherical cytoplasmic inclusion (composed of phosphorylated tau) that is mildly basophilic and contains a well-demarcated margin. Negri bodies (C) are oval or round cytoplasmic inclusions that can be found throughout the CNS but are most prominent in Purkinje cells. The appearance of Negri bodies is similar to that of red blood cells (Ellison, pp. 288-289, 504, 513- 514, 552,556-559,570- 572).

Answer 111

A B C D **E** F ## Footnote Lewy bodies (E), the hallmark of Parkinson's disease, are intracellular cytoplasmic inclusions containing an eosinophilic core surrounded by a pale halo. They are predominantly found in the substantia nigra and consist of ubiquitin, neurofilaments, CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains; however, they are best identified with ubiquitin staining techniques. Hirano bodies (A) are eosinophilic cytoplasmic inclusions composed of actin and actin-associated proteins; they are particularly prominent in the CAl sector of the hippocampus in patients with Alzheimer's disease (AD) and Pick's disease. Neurofibrillary tangles (D) are intraneuronal inclusions composed of phosphorylated tau, which is a rnicrotubule-associated cytoskeletal protein. Phosphorylated tau forms helical filaments, which can be found within the neocortex and pyramidal cells of the hippocampus in patients with AD. The microscopic hallmark of Pick's disease is the Pick body (B), which is a spherical cytoplasmic inclusion (composed of phosphorylated tau) that is mildly basophilic and contains a well-demarcated margin. Negri bodies (C) are oval or round cytoplasmic inclusions that can be found throughout the CNS but are most prominent in Purkinje cells. The appearance of Negri bodies is similar to that of red blood cells (Ellison, pp. 288-289, 504, 513- 514, 552,556-559,570- 572).

Answer 112

A **B** C D E F ## Footnote Lewy bodies (E), the hallmark of Parkinson's disease, are intracellular cytoplasmic inclusions containing an eosinophilic core surrounded by a pale halo. They are predominantly found in the substantia nigra and consist of ubiquitin, neurofilaments, CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains; however, they are best identified with ubiquitin staining techniques. Hirano bodies (A) are eosinophilic cytoplasmic inclusions composed of actin and actin-associated proteins; they are particularly prominent in the CAl sector of the hippocampus in patients with Alzheimer's disease (AD) and Pick's disease. Neurofibrillary tangles (D) are intraneuronal inclusions composed of phosphorylated tau, which is a rnicrotubule-associated cytoskeletal protein. Phosphorylated tau forms helical filaments, which can be found within the neocortex and pyramidal cells of the hippocampus in patients with AD. The microscopic hallmark of Pick's disease is the Pick body (B), which is a spherical cytoplasmic inclusion (composed of phosphorylated tau) that is mildly basophilic and contains a well-demarcated margin. Negri bodies (C) are oval or round cytoplasmic inclusions that can be found throughout the CNS but are most prominent in Purkinje cells. The appearance of Negri bodies is similar to that of red blood cells (Ellison, pp. 288-289, 504, 513- 514, 552,556-559,570- 572).

Answer 113

A B C **D** E F ## Footnote Lewy bodies (E), the hallmark of Parkinson's disease, are intracellular cytoplasmic inclusions containing an eosinophilic core surrounded by a pale halo. They are predominantly found in the substantia nigra and consist of ubiquitin, neurofilaments, CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains; however, they are best identified with ubiquitin staining techniques. Hirano bodies (A) are eosinophilic cytoplasmic inclusions composed of actin and actin-associated proteins; they are particularly prominent in the CAl sector of the hippocampus in patients with Alzheimer's disease (AD) and Pick's disease. Neurofibrillary tangles (D) are intraneuronal inclusions composed of phosphorylated tau, which is a rnicrotubule-associated cytoskeletal protein. Phosphorylated tau forms helical filaments, which can be found within the neocortex and pyramidal cells of the hippocampus in patients with AD. The microscopic hallmark of Pick's disease is the Pick body (B), which is a spherical cytoplasmic inclusion (composed of phosphorylated tau) that is mildly basophilic and contains a well-demarcated margin. Negri bodies (C) are oval or round cytoplasmic inclusions that can be found throughout the CNS but are most prominent in Purkinje cells. The appearance of Negri bodies is similar to that of red blood cells (Ellison, pp. 288-289, 504, 513- 514, 552,556-559,570- 572).

Answer 114

A B C D E **F** ## Footnote Lewy bodies (E), the hallmark of Parkinson's disease, are intracellular cytoplasmic inclusions containing an eosinophilic core surrounded by a pale halo. They are predominantly found in the substantia nigra and consist of ubiquitin, neurofilaments, CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains; however, they are best identified with ubiquitin staining techniques. Hirano bodies (A) are eosinophilic cytoplasmic inclusions composed of actin and actin-associated proteins; they are particularly prominent in the CAl sector of the hippocampus in patients with Alzheimer's disease (AD) and Pick's disease. Neurofibrillary tangles (D) are intraneuronal inclusions composed of phosphorylated tau, which is a rnicrotubule-associated cytoskeletal protein. Phosphorylated tau forms helical filaments, which can be found within the neocortex and pyramidal cells of the hippocampus in patients with AD. The microscopic hallmark of Pick's disease is the Pick body (B), which is a spherical cytoplasmic inclusion (composed of phosphorylated tau) that is mildly basophilic and contains a well-demarcated margin. Negri bodies (C) are oval or round cytoplasmic inclusions that can be found throughout the CNS but are most prominent in Purkinje cells. The appearance of Negri bodies is similar to that of red blood cells (Ellison, pp. 288-289, 504, 513- 514, 552,556-559,570- 572).

Answer 115

A B **C** D E ## Footnote Neuroblastoma most commonly occurs in the first decade of life and can present with opsoclonus, myoclonus, and encephalopathy. This lesion most commonly originates from the adrenal glands (40% of neuroblastic tumors), followed by the abdominal (25%), thoracic (15%), cervical (5%), and pelvic sympathetic ganglia (5%); it is associated with amplification of the N-myc gene. The cerebral form tends to favor the frontoparietal lobes, although it is rare. Treatment typically includes surgical resection and radiation therapy to the tumor bed. Recurrence is frequent after excision (WHO, pp. 153- 161; Merritt, p. 330; Geyer, p. 146).

Answer 116

A **B** C D E ## Footnote Neuroblastoma most commonly occurs in the first decade of life and can present with opsoclonus, myoclonus, and encephalopathy. This lesion most commonly originates from the adrenal glands (40% of neuroblastic tumors), followed by the abdominal (25%), thoracic (15%), cervical (5%), and pelvic sympathetic ganglia (5%); it is associated with amplification of the N-myc gene. The cerebral form tends to favor the frontoparietal lobes, although it is rare. Treatment typically includes surgical resection and radiation therapy to the tumor bed. Recurrence is frequent after excision (WHO, pp. 153- 161; Merritt, p. 330; Geyer, p. 146).

Answer 117

**A** B C D E ## Footnote Neuroblastoma most commonly occurs in the first decade of life and can present with opsoclonus, myoclonus, and encephalopathy. This lesion most commonly originates from the adrenal glands (40% of neuroblastic tumors), followed by the abdominal (25%), thoracic (15%), cervical (5%), and pelvic sympathetic ganglia (5%); it is associated with amplification of the N-myc gene. The cerebral form tends to favor the frontoparietal lobes, although it is rare. Treatment typically includes surgical resection and radiation therapy to the tumor bed. Recurrence is frequent after excision (WHO, pp. 153- 161; Merritt, p. 330; Geyer, p. 146).

Answer 118

A B C D E **F** G H I

Answer 119

**A** B C D E F G H I

Answer 120

A **B** C D E F G H I

Answer 121

A B C D E F G **H** I

Answer 122

A B C **D** E F G H I

Answer 123

A B C **D** E F G H I

Answer 124

A B **C** D E F G H I

Answer 125

A B C D E F **G** H I

Answer 126

A B C **D** E F G H I

Answer 127

A B C D **E** ## Footnote Hypertrophied nerves may occur with neurofibromatosis, Refsum's disease, leprosy, hereditary sensory motor neuropathy (HSMN) III > II > I, acromegaly, neurofibromatosis, and amyloidosis. Hypertrophied nerves are not typically seen in patients with alcoholism (Merritt, p. 605).

Answer 128

**A** B C D E ## Footnote Note the prominent atrophy of the cerebellar vermis in this gross specimen depicting alcoholic cerebellar degeneration (Ellison, pp. 488- 489).

Answer 129

A B **C** D E ## Footnote Note the prominent epidermoid within the right cerebellopontine angle cistern in this gross specimen (Ellison, pp. 737- 739).

Answer 130

**A** B C D E ## Footnote Note the prominent spherules containing endospores in this photomicrograph depicting coccidioidomycosis. The spherules and enclosed endospores usually appear basophilic when stained with H&E but are better demonstrated by methenamine silver impregnation. Pulmonary infection can occur in the absence of underlying disease and is generally self-limiting, although there may be residual fibrosis and calcification. Coccidioidomycosis is most often associated with occupations involving exposures to large amounts of dust. Hematogenous spread is rare and is most often seen in patients with diabetes, immunosuppression, or pregnancy. CNS involvement is usually a late, terminal event (Ellison, pp. 362 363) .

Answer 131

**A** B C D E ## Footnote This gross section depicts prominent exudates along the cerebral convexities as well as focal areas of hemorrhage and thrombosed veins; these are characteristic of purulent meningitis (Ellison, pp. 328 330).

Answer 132

A B C **D** E ## Footnote Forms of fungi in CNS infection include yeasts (Blastomycosis, Ccmclida, Coccidioides, C,yptococcus, Histoplasma, Paracoccidioides, Sporotrichum, and Torulopsis) as well as branching septate (Aspergilllls, Cladosporium, FllSarillm) and nonseptate hyphae (MIlCor) and pseudohyphae, which are larger than yeasts but smaller than true hyphae (some Canclida species) (Ellison, pp. 351 354).

Answer 133

**A** B C D E ## Footnote Note the glomeruloid vascular proliferation in this photomicrograph depicting a glioblastoma (Ellison, p. 631)

Neuropathology Flashcards

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