Pathology/ Histology Flashcards

Question

The lesion shown in this image is best classified as a(n): A. Craniopharyngioma B. Colloid cyst C. Dermoid cyst D. Endodermal cyst E. Epidermoid cyst

Answer 1

C. Dermoid cyst ## Footnote The cyst lining is characterized by squamous epithelium and shows evidence of skin adnexal structures in the cyst wall that may include structures such as sebaceous glands, apocrine glands, hair, or eccrine glands. These findings are consistent with a dermoid cyst.

Answer 2

B. Chondrosarcoma ## Footnote The tumor shown in the image accompanying the question is marked by a malignant spindled cell component next to an atypical cartilaginous component, consistent with a chondrosarcoma.

Answer 3

C. Most pontine tumors have high-grade histology. ## Footnote The axial T2 and contrast-enhanced T1-weighted images demonstrate a nonenhancing, infiltrative, expansile lesion involving the pons, most compatible with a diffuse infiltrative pontine glioma. These lesions are more common in children than in adults. Histologically, they may originate from astrocytes, oligodendrocytes, or ependymal cells, but the great majority (95%) are astrocytic. Most brainstem gliomas arise in the pons, and most pontine tumors have a high-grade histology, being either anaplastic astrocytomas or glioblastomas. In contrast, tumors arising in the tectum and cervicomedullary junction as well as those that are cystic or exophytic usually are low grade. Enhancement is variable. Prognosis usually is poor, even for presumed low-grade histologies. (A) Diffuse intrinsic pontine gliomas are aggressive lesions, but they rarely metastasize to distant sites. Instead, they tend to infiltrate along anatomic fiber tracts and can extend cranially to involve the midbrain and thalami. (B) Hydrocephalus is a late complication of diffuse intrinsic pontine gliomas, and is more commonly seen in tectal lesions. (D) Calcifications are unusual in diffuse intrinsic pontine gliomas.

Answer 4

E. Osteosarcoma ## Footnote The malignant tumor shown in the image accompanying the question is marked by bone formation (the dark purple material). Osteosarcoma is the best diagnosis for this tumor. These lesions rarely may represent a primary tumor arising in the meninges or skull or distant metastatic disease. (A) Chondrosarcomas contain atypical cartilage within the tumor. (B) Glial fibrillary acidic protein (GFAP) negativity rules out a gliosarcoma. (C) Hemangiopericytomas often are malignant meningeal tumors that lack bone formation. (D) Metaplastic meningiomas are benign tumors marked by meningothelial cells intermixed with benign mesenchymal tissue such as bone or cartilage.

Answer 5

C. 12 hours ## Footnote The earliest changes indicating ischemic damage are apparent in neuronal cells at 12 to 24 hours after the precipitating event. The cells shrink in size, acquire cytoplasmic hypereosinophilia, and show nuclei shrinkage (the “red and dead” look).

Answer 6

B. Filum terminale ## Footnote The tumor shown in the image accompanying the question represents a paraganglioma, which generally is marked by cells arranged in loose nests (zellballen). The nests of cells are delimited by spindled, S-100–positive staining sustentacular cells. The tumor cells in the nests stain with neural markers such as chromogranin and neuronspecific enolase. In the central nervous system, paragangliomas most commonly arise in the spinal cord region.

Answer 7

E. CD138 ## Footnote The lesion shown in the image accompanying the question is composed of plasma cells and represents a plasma cell dyscrasia. CD138 is an antibody that targets plasma cells. These lesions typically demonstrate evidence of monoclonality with either kappa or lambda immunostaining.

Answer 8

A. Cerebellopontine angle ## Footnote This simple squamous epithelial-lined cyst represents an epidermoid cyst. It lacks the adnexal structures that mark a dermoid cyst. Epidermoid cysts most commonly arise in the cerebellopontine angle region.

Answer 9

A. Epidural space ## Footnote Over 90% of epidural hemorrhages are associated with a skull fracture and are associated with a torn middle meningeal artery. Less commonly, epidural hemorrhages result from a dural sinus tear or a tear in the middle meningeal vein.

Answer 10

A. 2 hours ## Footnote Usually within 2 hours of diffuse axonal injury, axonal swelling can be visualized with β-amyloid precursor protein immunostaining.

Answer 11

A. Dermatomyositis ## Footnote The biopsy shown in the image accompanying the question demonstrates predominantly perivascular-based chronic inflammation and atrophy around the perimeter of the muscle fascicles (perifascicular atrophy). Perifascicular atrophy in the setting of an inflammatory myopathy is highly suggestive of dermatomyositis.

Answer 12

B. Dystrophin ## Footnote The clinical history is suggestive of Duchenne muscular dystrophy. The biopsy is marked by a prominent variation in muscle fiber size with increased endomysial fibrosis. One would anticipate an absence of membrane staining with dystrophin antibody in this case.

Answer 13

A. Arachnoid cyst ## Footnote The cyst shown is lined by a thin layer of meningothelial cells or arachnoid cap cells, consistent with an arachnoid cyst.

Answer 14

E. No available therapies ## Footnote The pathological findings shown in the image accompanying the question are consistent with inclusion body myositis. The biopsy shows inflammation, a variation in muscle fiber size, and rimmed vacuoles (vacuoles with basophilic granularity). Currently, there is no known effective treatment for inclusion body myositis.

Answer 15

E. Ryanodine receptor gene mutation ## Footnote The findings in the biopsy illustrate a core myopathy, one of the congenital myopathies marked by a focal decrease in oxidative activity as manifested by the staining pattern. The condition generally is inherited as an autosomal dominant condition and is associated with mutations in the ryanodine receptor gene. There is an association of this condition with malignant hyperthermia.

Answer 16

A. Acid maltase deficiency ## Footnote Glycogen-filled vacuoles suggest a glycogen storage disease. Acid maltase deficiency is the only one of the glycogenoses that is lysosomal associated and stains with acid phosphatase (a lysosomal associated enzyme).

Answer 17

C. Kappa light chain protein ## Footnote Most of the amyloid encountered in the brain is β-amyloid. Less commonly, other proteins may arrange themselves in a β-pleated sheet configuration to form amyloid. Kappa light chain protein is unlikely to deposit in the brain. (A) Cystatin C is a serum indicator of kidney function and may be involved in Alzheimer amyloid. (B) Gelsolin is a regulator of actin filament assembly/disassembly and is associated with β-amyloid formation in the brain. (D) Prion protein causes spongiform encephalopathy

Answer 18

D. HTT gene ## Footnote The trinucleotide repeat in the HTT gene that encodes the huntingtin protein is associated with Huntington disease. The normal CAG repeat length is up to 35 repeats, whereas in Huntington disease, there are 36 or more repeats. (A, B) Ataxin-2 and CACNA1A gene repeats are associated with forms of hereditary spinocerebellar ataxia. (C) Chorein gene alterations are associated with a rare condition known as neuroacanthocytosis. (E) The myotonin gene is implicated in myotonic dystrophy.

Answer 19

A. Alzheimer disease ## Footnote The globular, extracellular structures highlighted with the silver stain represent senile plaques and are associated most classically with Alzheimer disease. Current pathological diagnostic criteria rely on plaque and neurofibrillary tangle counts as well as an assessment of the distribution of amyloid deposition. Plaques are composed variably of neuritic processes (highlighted with the silver stain), amyloid, and associated microglial cells.

Answer 20

D. Tau ## Footnote The dark-staining, elongated structures located within the cytoplasm of neurons represent neurofibrillary tangles. They can be highlighted with tau immunostaining. (A) α-synuclein is a good stain to highlight Lewy bodies. (B, E) Congo red and thioflavin S stains highlight amyloid.

Answer 21

D. Lymphoma ## Footnote Lymphomas often are B cell in origin and are identified by white blood cells with angiocentric growth patterns forming perivascular cuffs by tumor cells. (A) Germinomas show large, epithelioid cells with abundant PAS-positive cytoplasm. The cells have irregular nuclei that may have prominent nests of lymphocytes with occasional granulomatous inflammation. (B) Ependymomas classically have dark, small nuclei with perivascular and true rosettes. (C) Chordomas characteristically are described by physaliphorous cells and represent a remnant of the nucleus pulposus. (E) Hemangioblastomas have numerous capillary channels lined by a single layer of endothelium surrounded by reticulin.

Answer 22

D. Froin syndrome ## Footnote Froin syndrome is stagnation of the cerebrospinal fluid (CSF) from an inflammatory or neoplastic lesion, causing increased exudation from the tumor itself and activation of coagulation factors. (A) A positive Queckenstedt test is a failure of jugular vein compression to increase CSF pressure, which it will normally do in the absence of a block of the venous outflow. (B) Coup de poignard of Michon is sudden excruciating back pain with subarachnoid hemorrhage in patients with a spinal vascular malformation. (C) A positive Froment sign (during an evaluation of the ulnar nerve) occurs when a patient is unable to grasp a sheet of paper between his thumb and extended index finger and will instead pinch the paper, as the action of the weak adductor pollicis (ulnar innervated) is substituted for the action of the strong flexor pollicis longus (anterior interosseous innervated). (E) FoixAlajouanine is an acute/subacute neurologic deterioration without hemorrhage in patients with a spinal vascular malformation.

Answer 23

D. Seizure ## Footnote The epithelial-lined cyst shown in the image accompanying the question represents a colloid cyst. Seizures are not an expected presenting symptom. (A, B, E) Headaches, incontinence, and even sudden death can occur with the development of hydrocephalus secondary to colloid cysts, especially if a “ball-valving” phenomenon occurs.

Answer 24

A. β-amyloid ## Footnote β-amyloid is the best and most specific stain for the type of amyloid that accumulates in patients with Alzheimer disease. (B) Luxol fast blue is a myelin stain. (C) Mucicarmine stains mucin such as in an adenocarcinoma. (D) Prussian blue is an iron stain. (E) Trichrome highlights connective tissue and collagen.

Answer 25

B. Cavernous malformation ## Footnote Cavernous malformations appear on MRI with hemosiderin and a “popcorn-like” appearance, with irregular thick- and thin-walled sinusoidal vascular channels without intervening neural parenchyma, large feeding arteries, or draining veins. (A) Microscopically, capillary telangiectasias have slightly enlarged capillaries with low flow and intervening neural tissue. (C) Venous malformations (venous angiomas, also known as developmental venous anomalies) are abnormal veins draining normal brain. They often present as a starburst pattern (caput medusa on angiogram) and are associated with cavernomas. (D) Arteriovenous malformations appear as tangles of abnormal vessels of various diameters separated by gliotic tissue without an intervening capillary bed. There may be evidence of prior hemorrhage. (E) Dural arteriovenous fistulas are true arteriovenous shunts within the leaflets of the dura matter and usually are found adjacent to dural sinuses.

Answer 26

D. Sporadically with no obvious genetic ## Footnote Sturge-Weber disease has no known genetic transmission and is characterized by a facial nevus in the ophthalmic division of the trigeminal nerve, along with leptomeningeal venous angiomas and intracortical tram-track calcifications.

Answer 27

A. SNCA ## Footnote The neuron displayed with the eosinophilic cytoplasmic inclusion also has brown melanin pigment in its cytoplasm, with these components representing a Lewy body. α-synuclein (encoded by the SCNA gene) is the best stain for highlighting Lewy bodies. The most common gene to be affected in familial cases of Parkinson disease is the SCNA gene. Less commonly, alterations in the various PARK genes have been described in the disease.

Answer 28

A. L-iduronidase ## Footnote The described patient has Hurler syndrome. (B) Iduronate sulfatase deficiency (Hunter syndrome) causes symptoms similar to those seen in Hurler syndrome, except that Hunter syndrome is milder, without mental retardation, with minimal corneal involvement, slower progressing, and with a life span into adulthood. (C) Galactose 6-sulfatase and β-galactosidase deficiencies (Morquio syndrome) are inherited in an autosomal recessive manner and are characterized by severe skeletal abnormalities, ligamentous laxity, dwarfism, myelopathy, and a lack of mental retardation. (D) Sulfatase B deficiency (Maroteaux-Lamy) presents with carpal tunnel syndrome, valvular heart disease, and without mental retardation. (E) β-glucuronidase deficiency is inherited in an autosomal recessive manner and is characterized by moderate mental retardation, corneal clouding, hydrocephalus, hepatosplenomegaly, and various bony changes.

Answer 29

A. Low posterior hairline, brevicollis, and decreased neck motion ## Footnote Klippel-Feil syndrome is a congenital fusion of two or more cervical vertebrae due to the failure of normal segmentation of cervical somites that is characterized by a low posterior hairline, shortened neck, and limitations in neck motion. The condition also can be associated with scoliosis, torticollis, pterygium colli (neck webbing), and Sprengel deformity (inability to raise the scapula). (B) Sebaceous adenomas, mental retardation, and seizures represent a triad associated with tuberous sclerosis. (C) Anorectal malformation, anterior sacral defects, and presacral masses are seen in the Currarino triad, which typically presents with constipation secondary to the anorectal malformation. (D) Dementia, urinary incontinence, and gait instability are seen in conjunction with normal pressure hydrocephalus.

Answer 30

D. Amyotrophic lateral sclerosis ## Footnote Axonal spheroids are seen in amyotrophic lateral sclerosis, diffuse axonal injury, and HallervordenSpatz disease.

Answer 31

C. Myxopapillary ependymoma ## Footnote The findings are most consistent with a myxopapillary ependymoma (WHO grade I). (A, D, E) These tumor types often are in the differential diagnosis due to location rather than histomorphology. (B) Metastatic adenocarcinomas also can be mucin positive but would be unusual in such a young patient and are generally glial fibrillary acidic protein negative.

Answer 32

A. Basal ganglia ## Footnote PANK2 gene mutations are associated with neuronal degeneration with brain iron accumulation (formerly known as Hallervorden-Spatz disease). The increased iron accumulation preferentially deposits in the basal ganglia region and is accompanied by neuronal loss and gliosis.

Answer 33

C. CA1 and CA4 ## Footnote In hippocampal sclerosis, the most severely involved areas are the CA1 and CA4 regions; however, neuronal loss may be present in any of the hippocampal regions.

Answer 34

B. Dysautonomia ## Footnote Dysautonomia is a feature present in multisystem atrophy in both the parkinsonian and cerebellar predominant types. The cerebellar type usually presents with gait and limb ataxia, dysarthria, and oculomotor disturbances. It is marked by atrophy of and loss of neurons in the cerebellum, middle cerebellar peduncles, and pons. Ubiquitin and tau immunoreactive glial cytoplasmic inclusions may be seen.

Answer 35

D. SOD1 ## Footnote Ten percent of patients with amyotrophic lateral sclerosis have an autosomal dominant pattern of familial disease. Twenty percent of familial cases are due to a mutation in the gene encoding the Cu/Zn superoxide dismutase 1 protein on chromosome 21. Less commonly, familial cases have been associated with mutations in the TARDBP gene on chromosome 1.

Answer 36

A. Cytomegalovirus infection ## Footnote The occasional large cells marked by prominent intranuclear inclusions are suggestive of a viral infection (e.g., cytomegalovirus). A few of the large cells also have small, brightly eosinophilic cytoplasmic inclusions as well, which sometimes can be encountered with cytomegalovirus infection.

Answer 37

C. Radiation effects ## Footnote The thickened or sclerosed appearance of the blood vessels in this case is typical of the vascular changes observed following radiation therapy. Sometimes these changes are accompanied by chronic inflammatory cells and necrosis of the adjacent tissue with infiltration by macrophages.

Answer 38

B. Fourth ventricle ## Footnote The low-grade tumor shown in the image accompanying the question is marked by loose aggregates of tumor cell nuclei with intervening hypocellular zones. Microcysts frequently are present in this tumor. These pathological findings are consistent with a subependymoma (WHO grade I). Although they can arise in the spinal cord, the fourth ventricle is a more common site.

Answer 39

C. Tuberous sclerosis ## Footnote As its name suggests, large astrocytic cells compose this intraventricular subependymal giant cell astrocytoma. This tumor sometimes is associated with tuberous sclerosis along with subependymal hamartomas and cortical tubers.

Answer 40

A. ATRX protein staining ## Footnote Oligodendrogliomas generally show retention of ATRX protein staining (in contrast to a subset of diffuse astrocytomas).

Answer 41

D. Deletion on chromosome 1p ## Footnote Prognosis for anaplastic oligodendrogliomas is best predicted by looking for large deletions on chromosomes 1p and 19q. The deletions are thought by many to be part of the definition of these tumors. Although high mitotic count and cell proliferation indices and necrosis are associated with higher grade oligodendrogliomas, the chromosome deletions are more predictive of chemoresponsiveness and outcome.

Answer 42

B. IDH-1 ## Footnote IDH-1 antibody does not stain reactive or inflammatory lesions including gliosis. A subset of diffuse or fibrillary astrocytomas and most oligodendrogliomas stain with IDH-1 antibody. (A, E) GFAP and S-100 antibodies stain astrocytes in both processes. (C) More cells stain with Ki-67, a cell proliferation marker in astrocytomas versus gliosis; however, there is significant overlap in the ranges of observed labeling indices with Ki-67 in both processes, so it has little value unless the labeling index is moderately high. (D) Only widespread positivity with p53 antibody would be useful in indicating a tumor, as low levels of staining may be seen in both processes and is nonspecific.

Answer 43

D. B12 ## Footnote A deficiency in vitamin B12 (cobalamin) can result in degeneration of the posterior columns of the spinal cord, referred to as subacute combined degeneration. The lateral columns of the upper thoracic and lower cervical spinal cord also may be involved. (A) Vitamin B1 (thiamine) deficiency can lead to Wernicke encephalopathy, Korsakoff psychosis, or Beriberi. (B) Vitamin B2 (riboflavin) deficiency can cause stomatitis and a red, scaly rash. (C) Vitamin B6 (pyridoxine) deficiency is associated with isoniazid and hydralazine use, and causes lower limb paresthesias, pain, and weakness. (E) Vitamin C deficiency results in scurvy, with early symptoms of malaise, lethargy, and painful gums.

Answer 44

A. BRAF ## Footnote This astrocytic tumor is marked by the presence of clustered eosinophilic material known as eosinophilic granular bodies. This finding is suggestive of a pilocytic astrocytoma, which sometimes is associated with BRAF gene alterations. (B–D) Alterations in these genes generally are not encountered in pilocytic astrocytomas and are more common in diffuse or fibrillary astrocytomas.

Answer 45

A. Associated with focal cortical dysplasia ## Footnote The image accompanying the question presents a WHO grade I dysembryoplastic neuroepithelial tumor. These tumors are associated with chronic epilepsy and most frequently arise in the temporal lobe. Ki-67 indices are typically low, often less than 5%. The tumor has a blistered appearance grossly. It often is associated with adjacent cortical architectural disorganization (focal cortical dysplasia).

Answer 46

A. Ependymoma ## Footnote True rosettes (tumor cells arranged around a central lumen) are characteristic of an ependymoma. (C, E) Rosettes and perivascular pseudorosettes are not typical features of myxopapillary ependymomas and subependymomas. (D) Retinoblastomas of the eye contain similar true rosettes (FlexnerWintersteiner rosettes).

Answer 47

A. Streptococcus species ## Footnote Streptococcus species are the most common pathogens found in brain abscesses across all ages and typically stem from adjacent sinus or ear infections. (B, E) Staphylococcus species and enteric bacilli are common pathogens in brain abscesses due to trauma. (C, D) Bacteroides and Proteus species are common pathogens in brain abscesses in neonates, along with Citrobacter species and gramnegative bacilli.

Answer 48

D. Adjacent sinus or ear infections ## Footnote Adjacent sinus or ear infections account for about 40% of brain abscesses due to the ability of pathogens to spread along valveless venous channels that are the cranial sinuses. (E) Hematogenous spread from distant infections accounts for about 30% of brain abscesses. Hematogenous spread of pathogens tends to produce abscesses in the middle cerebral artery territory and often causes multiple abscesses.

Answer 49

C. Grade III ## Footnote An astrocytoma with necrosis, vascular proliferation, and moderate pleomorphism is WHO grade IV.

Answer 50

D. P53 protein mutation ## Footnote The p53 tumor suppressor protein is encoded by the TP53 gene on chromosome 17, and mutations result in Li-Fraumeni syndrome. Individuals with Li-Fraumeni syndrome are at risk for developing a variety of tumors throughout their bodies, including primitive neuroectodermal tumors and astrocytomas in the brain, breast cancer, and soft tissue and bone sarcomas. (A) Turcot syndrome has been linked to gene mutations in the MLH1, MSH2, MSH6, and PMS2 genes and predisposes individuals to medulloblastomas and glioblastomas. (B) Merlin protein is a tumor suppressor protein encoded by the neurofibromin 2 gene on chromosome 22. Mutations in merlin are seen in individuals with neurofibromatosis type 2, which is associated with bilateral acoustic neuromas, meningiomas, astrocytomas, and ependymomas. (C) The neurofibromin 1 protein is mutated in individuals with neurofibromatosis type 1. This chromosome 17 abnormality predisposes possessors to optic gliomas, astrocytomas, and neurofibromas. (E) The von Hippel–Lindau tumor suppressor gene mutation (chromosome 3) is seen in von Hippel–Lindau disease and results in an increased risk for developing hemangioblastomas and endolymphatic sac tumors.

Answer 51

E. Synaptophysin ## Footnote Central neurocytomas most commonly arise in the lateral ventricles and demonstrate diffuse, strong immunoreactivity with synaptophysin antibodies, consistent with their neural lineage. (A) CD34 is a vascular marker. (B) Epithelial membrane antigen stains carcinomas and meningiomas. (C, D) Glial fibrillary acidic protein and S-100 protein stain astrocytic tumors, among others.

Answer 52

E. WHO grade III anaplastic astrocytoma ## Footnote Ki-67 is a cell proliferation marker that stains a nuclear protein that is produced during the proliferative phases of the cell cycle. Staining results typically are reported as a percentage of positive staining tumor cells in the area of the tumor with the most staining (labeling index). The rate of cell proliferation is more than what would be expected in a WHO grade I or II neoplasm and is most consistent with a higher grade neoplasm.

Answer 53

B. WHO grade II ## Footnote This tumor represents a pleomorphic xanthoastrocytoma. It is one of the few astrocytic tumors that has a rich connective tissue matrix that can be highlighted with a reticulin stain. Despite the cellularity and marked atypia of the tumor cells in this neoplasm, the majority of these tumors are considered to be WHO grade II neoplasms. Rare WHO grade III pleomorphic xanthoastrocytomas are marked by increased mitotic activity or necrosis.

Answer 54

E. Sturge-Weber syndrome ## Footnote The photomicrograph shown in the image accompanying the question demonstrates some surface cortex on the right and a proliferation of blood vessels in the meninges (angiomatosis). The history and pathological image are suggestive of Sturge-Weber syndrome. (A) There are no tumor cells between the blood vessels, as one would encounter in an angiomatous meningioma.

Answer 55

D. Nasal glioma ## Footnote The presence of ectopic neural/brain tissue in the nasal area is referred to as a nasal glioma, even though it is not really a glioma in the traditional sense. The usual differential diagnosis with the described lesion is encephalocele if the lesion is connected to the brain itself. Angiofibromas meningiomas, and pituitary adenomas occasionally can arise as masses in the nasal cavity but look very different histologically

Answer 56

D. Atypical teratoid/rhabdoid tumor ## Footnote Atypical teratoid/rhabdoid tumors are associated with INI1 and chromosome 22 abnormalities and stain positively for vimentin, epithelial membrane antigen, and glial fibrillary acidic protein, among others. (A) Chromosomal deletions in chromosome 17p and not 22 are seen with medulloblastomas and other primitive neuroectodermal tumors. (B) The most common chromosomal changes in ependymomas are amplification of chromosome 1q and loss of chromosomes 6q, 17p, and 22q, with chromosome 1q amplification being most likely to lead to intracranial tumor recurrence. (C) Astrocytomas can be associated with a variety of syndromes and their associated chromosomal changes, including neurofibromatosis types 1 and 2, tuberous sclerosis, retinoblastoma, Li-Fraumeni, and Turcot syndromes. (E) Chromosome 22 abnormalities can be seen with schwannomas, but INI1 mutations are not seen.

Answer 57

E. Thiamine deficiency ## Footnote The changes described are associated with thiamine deficiency and Wernicke-Korsakoff syndrome. The brownish discoloration of the mammillary bodies is due to small hemorrhages.

Answer 58

D. Syringobulbia ## Footnote A glial-lined cavitation in the brainstem area is referred to as syringobulbia. In the spinal cord, a comparable lesion is called syringomyelia. (A) Diplomyelia refers to duplication of spinal cord segments. (B) Hydromyelia is a dilation of the central spinal canal. (C) Iniencephaly refers to failure of closure of the posterior vertebral arches of the rostral cervical vertebrae and usually is associated with abnormalities of the brainstem.

Answer 59

B. Hemorrhagic infarct ## Footnote The acute angle branching hyphae shown in the image accompanying the question are consistent with Aspergillus. Aspergillus tends to be angioinvasive, and consequently presents most commonly with hemorrhagic infarcts. Less commonly, one can encounter an abscess or meningitis with Aspergillus.

Answer 60

D. Open neural tube defect ## Footnote Elevated amniotic fluid levels of α-fetoprotein and acetylcholinesterase are associated with open neural tube defects (i.e., defects in which there is a lack of skin covering exposed meninges or central neuroglial tissue). The risk of such defects can be reduced with adequate maternal folate consumption.

Answer 61

C. Germinoma ## Footnote The pineal region is a common location for germinomas. In addition to Parinaud (dorsal midbrain) syndrome, precocious puberty and other endocrine manifestations commonly are associated with this malignant neoplasm. Histologically, the classic findings with germinomas are aggregates of nonneoplastic lymphocytes (small dark blue cells) and large tumor cells with abundant cytoplasm, large nuclei, and prominent nucleoli.

Answer 62

B. Hemangioblastoma ## Footnote A WHO grade I tumor, hemangioblastoma is commonly seen in the cerebellum as a brightly enhancing mass associated with a cystic component. Histologically, these tumors are rich in capillaries (hence their name despite their histogenesis remaining unknown), with intervening large “epithelioid” cells with foamy cytoplasm and hyperchromatic nuclei called stromal cells.

Answer 63

C. Prematurity ## Footnote Germinal matrix hemorrhage is associated strongly with prematurity and results from the increased susceptibility of these patients to hypoxia/ ischemia. Germinal matrix hemorrhage can extend into the ventricles, leading to intraventricular hemorrhage, which is associated with serious sequelae.

Answer 64

D. Glioblastoma, WHO grade IV ## Footnote The microphotograph accompanying the question shows a hypercellular neoplasm with characteristic pale areas of necrosis surrounded by viable tumor cells. This type of necrosis is called pseudopalisading necrosis and is characteristic of glioblastomas (WHO grade IV) and other high-grade lesions.

Answer 65

B. Schwannoma ## Footnote Antoni A (compact spindled areas) and Antoni B (loosely organized and less cellular areas of mucinous stroma and fibrillary collagen) areas are typical of schwannomas. (A) Neurofibromas often stain with neurofilament and have axons coursing through them. (C) Malignant peripheral nerve sheath tumors often involve multiple fascicles and are characterized by uniform spindle cells with hyperchromatic nuclei arranged in fascicles. Necrosis and a high mitotic index are seen.

Answer 66

A. Alzheimer disease ## Footnote Pathological findings in Alzheimer disease include deposition of extracellular β-amyloid in neuritic plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau and ubiquitin proteins. (B) Pick disease (frontotemporal dementia) is characterized by tauopathy (a neuronal/glial inclusion of tau). (C) CreutzfeldtJakob disease is associated with abnormal prion PrPSc, and has the classic findings of 14-3-3 protein in the cerebrospinal fluid and periodic sharp waves and spikes on electroencephalography. (D) Dementia with Lewy bodies has eosinophilic intracytoplasmic neuronal inclusions (Lewy bodies) that contain α-synuclein and tau proteins. (E) Huntington disease is due to a CAG trinucleotide repeat on chromosome 4 and is not associated with intra- or extracellular inclusion bodies.

Answer 67

A. Putamen ## Footnote The basal ganglia are the most common site of hypertensive hemorrhage. Of the basal ganglia, the putamen is the most common location for hypertension-related hemorrhage. This is followed by the thalamus, the pons, and the dentate nuclei of the cerebellum. Lobar hemorrhages can occur with hypertension in the subcortical white matter, but they more often are associated with amyloidosis in the elderly.

Answer 68

B. Chromosomes 1p and 19q co-deletion ## Footnote The histopathological features in this case are of an oligodendroglioma. Tumor cells have round, uniform nuclei with an artifactual perinuclear halo. Branching, delicate blood vessels are present within the tumor. Most oligodendrogliomas show a codeletion of the short arm of chromosome 1 (1p) and long arm of chromosome 19 (19q). The presence of this co-deletion is associated with a better response to chemotherapy and longer survival.

Answer 69

B. Angiocentric glioma ## Footnote Angiocentric gliomas are rare, low-grade lesions most commonly seen in the temporal lobe in young patients with chronic epilepsy. The tumor, as shown in the image accompanying the question, is marked by perivascular pseudorosette-like structures. Ependymomas also may have similar rosette structures but are predominantly intraventricular in location.

Answer 70

D. Neuroblastoma ## Footnote Homer-Wright rosettes lack a central canal or capillary and are seen classically in neuroblastomas, medulloblastomas, primitive neuroectodermal tumors (PNETs), and retinoblastomas. Their lumens contain dense neuropil. Flexner-Wintersteiner rosettes are seen classically in retinoblastomas but also occur in pineoblastomas. They have no fiberrich neuropil in their centers and resemble photoreceptor rods/cones ultrastructurally. (A) Ependymal rosettes form central lumens, whereas pseudorosettes form zones of fibrillary processes around blood vessels. Pseudorosettes are seen much more commonly in ependymomas and are more sensitive for a diagnosis of ependymoma than true rosettes. (C) Pineocytomatous/neurocytic rosettes are seen in pineocytomas/central neurocytomas and are similar to Homer-Wright rosettes but are larger and more regular

Answer 71

E. Papillary and rhabdoid ## Footnote Meningothelial, transitional, and fibrous are the most common meningioma subtypes. Clear cell, chordoid, and atypical meningiomas are WHO grade II. Atypical meningiomas are characterized by increased mitotic activity (four or more mitotic figures per high power microscopic field), brain invasion, or a tumor with three or more other worrisome features (e.g., patternless/sheet-like growth patterns, hypercellularity, small cell change, necrosis, and prominent nucleation). Anaplastic meningiomas are grade III, characterized by obvious malignant features resembling carcinoma/ melanoma or high-grade sarcoma or mitotic activity in excess of 19 mitotic figures per 10 high power fields. Papillary and rhabdoid tumors also are considered WHO grade III.

Answer 72

C. Pilocytic astrocytoma ## Footnote The most common histological type of optic pathway/hypothalamic glioma in the pediatric population is pilocytic astrocytoma, which comprises the majority of prechiasmatic tumors. Other common tumor types are low-grade fibrillary astrocytoma, ganglioglioma, and, rarely, malignant glioma.

Answer 73

C. Cytomegalovirus infection ## Footnote Neurons infected by cytomegalovirus show large intranuclear eosinophilic inclusions known as Cowdry A (or just Cowdry) bodies. Smaller cytoplasmic inclusions also can be present in infected cells.

Answer 74

E. Oligodendroglioma ## Footnote Oligodendrogliomas have a “chicken wire” vasculature with a delicate network of branching capillaries, whereas the “fried egg” appearance is an artifactual perinuclear clear space following delayed formalin fixation (thus not seen in frozen sections). (A) Germinomas have sheets of large cells with round nuclei, distinct cell borders, and often are infiltrated with lymphocytes. (B) Ependymomas often show rosettes or perivascular pseudorosettes. (C) Pleomorphic xanthoastrocytomas are described by their large cells with abundant intracytoplasmic vacuoles due to lipid accumulation.

Answer 75

A. Streptococcus species ## Footnote Sixty percent of cerebral abscesses are polymicrobial. Streptococcus species are the most frequent organisms found, with 33 to 50% of abscesses being anaerobic or microaerophilic. Streptococcus milleri can be seen in frontoethmoidal sinusitis. (B) Escherichia coli abscesses are seen in neonates and following brain surgery. (C) Bacteroides is a common abscess former from otitis media/mastoiditis. (D) Actinomyces abscesses can be seen with odontogenic sources. (E) Staphylococcus epidermidis abscesses can be seen after neurosurgical procedures

Answer 76

E. Pilocytic astrocytoma ## Footnote The microphotograph shows the classic “biphasic” pattern of a pilocytic astrocytoma. Compacted eosinophilic areas (center) contrast with loose, microcystic zones (sides). Rosenthal fibers (not shown) also are frequently seen.

Answer 77

A. Glioblastoma

Answer 78

D. Metastatic carcinoma

Answer 79

C. Mitotic activity

Answer 80

B. Low-grade diffuse astrocytoma

Answer 81

E. Small cell

Answer 82

B. Gemistocytic astrocytoma

Answer 83

D. Pilocytic astrocytoma

Answer 84

D. Prior surgery

Answer 85

E. Prion disease

Answer 86

E. Nocardia asteroides

Answer 87

E. Toxoplasmosis

Answer 88

E. Respiratory tract

Answer 89

D. Metastatic melanoma

Answer 90

A. Abscess

Answer 91

C. Smith-Lemli-Opitz syndrome

Answer 92

E. Organizing subdural hemorrhage

Answer 93

D. Schwannoma

Answer 94

B. Neurofibroma

Answer 95

E. Viral infection

Answer 96

E. Cryptococcus

Answer 97

A. Cowden disease

Answer 98

B. Ganglioglioma

Answer 99

A. Choroid plexus epithelium

Answer 100

D. Transthyretin

Answer 101

A. Caudate nucleus

Answer 102

A. Chordoid meningioma

Answer 103

B. Brain invasion

Answer 104

C. Embolization effect

Answer 105

D. Progesterone receptors and EMA

Answer 106

D. Hemangiopericytoma (solitary fibrous tumor)

Answer 107

C. Inhibin

Answer 108

C. Intravascular lymphoma

Answer 109

C. HIV infection

Answer 110

B. Medulloblastoma

Answer 111

A. Germinoma

Answer 112

D. Pineocytoma

Answer 113

D. Neurofibromatosis type 2

Answer 114

B. Liponeurocytoma

Answer 115

D. Rosette-forming glioneuronal tumor of the fourth ventricle

Answer 116

A. Associated with gelastic epilepsy

Answer 117

B. INI-1 loss

Answer 118

A. Chordoid glioma

Answer 119

E. Zellweger syndrome

Answer 120

A. Cardiac myxoma

Answer 121

B. CHMP2B protein mutation

Answer 122

D. Pick disease

Answer 123

D. Degeneration of anterior horn cells and corticospinal tracts

Answer 124

D. Trypanosomiasis

Answer 125

C. Friedreich ataxia

Answer 126

D. Motor vehicle accident

Answer 127

C. Ragged red fibers

Answer 128

E. Mucopolysaccharidoses

Answer 129

C. Optic nerves and chiasm

Answer 130

B. Gaucher disease

Answer 131

B. Neuronal ceroid lipofuscinosis

Answer 132

A. Sphingomyelinase; sphingomyelin

Answer 133

E. Wilson disease

Answer 134

B. Homocystinuria

Answer 135

A. Fabry disease

Answer 136

B. Dandy-Walker malformation

Answer 137

C. Periventricular leukomalacia

Answer 138

E. Zellweger syndrome

Answer 139

A. Lissencephaly

Answer 140

C. Rhabdomyolysis

Answer 141

A. Abnormal dystrophin, fatty/fibrous infiltration, and no necrosis

Answer 142

E. Medium range

Answer 143

E. Tuberculosis