Neuropathology Flashcards

Question

Rickets A. Thiamine B. Niacin C. VitaminB12 D. VitaminA E. VitaminD

Answer 1

A. Thiamine B. Niacin C. VitaminB12 D. VitaminA **E. VitaminD**

Answer 2

A. Thiamine B. Niacin **C. VitaminB12** D. VitaminA E. VitaminD

Answer 3

A. Thiamine B. Niacin **C. VitaminB12** D. VitaminA E. VitaminD

Answer 4

**A. Thiamine** B. Niacin C. VitaminB12 D. VitaminA E. VitaminD ## Footnote Diets heavy in corn lack t ryptophan that is used to synthesize niacin (B); niacin de ciency causes pellagra—dermat it is, diarrhea, and dementia. Diets heavy in re ned rice are more likely to lack su cient thiamine (A). Thiamine de ciency is associated with Wernicke’s encephalopathy and Korsako ’s psychosis, as seen in chronic alcoholism, and is also associated with beriberi— characterized by peripheral polyneuropathy, demyelinat ion, and autonomic dysfunction. Vitamin A (D) toxicit y m ay cause cerebral edema w ith a pseudotumor presentation. Pernicious anemia can lead to a vitamin B12 (C) de ciency with megaloblast ic anemia and subacute combined degenerat ion of the spinal cord. Vitamin D de ciency (E) causes rickets, which is associated with decreased parathyroid hormone and brit tle bones.3

Answer 5

**A. All exhibit a di use histologic pattern.** B. Meningeal lesions are more common in primary lymphomas. C. Most are of T cell lineage. D. Parenchymal lesions are more common in secondary lymphomas. E. They are radioresistant. ## Footnote Meningeal in ltration is the most common lesion in secondary lymphomas (B is false), and parenchymal lesions are the most common lesion in primary lymphomas (D is false). Most are of B cell lineage and are radiosensitive (Cand E are false). Nodular lymphomas are not seen in the central nervous system (CNS); all show a di use histology (A is true).

Answer 6

**A. Cortical arteriovenous malformations** B. Facialnevus C. Intracortical calci cation D. Meningeal angioma E. Seizures ## Footnote Sturge-Weber syndrome is characterized by a usually unilateral port-wine nevus (B) that typically involves the orbit or upper eyelid, unilateral menin- geal angioma (D), calci cations con ned to the second and third layers of c e r e b r a l c o r t e x ( C) , a n d s e i z u r e a c t i v i t y ( E ) . T h e a b n o r m a l m e n i n g e a l v e s s e l s are typically veins and are not well-visualized on angiography—a feature that is not consistent with arteriovenous malformations. Arteriovenous malfor- mations (AVMs) are not characteristic of the Sturge-Weber syndrome (A).

Answer 7

A. Demyelination occurs **B. Lumbar levels are most severely affected** C. Lesions may occur in the medulla D. Vacuolar distention of myelin sheaths occurs E. Wallerian degeneration occurs ## Footnote The demyelination (A), spongiosis (D), and gliosis seen in vitamin B12 de ciency are most common at lower cervical and thoracic levels (Bis false)

Answer 8

A. Bacterial infection **B. Demyelination** C. Increased numbers of oligodendroglial cells D. Intense in ammatory in ltrate E. Shrunken oligodendroglial nuclei at the periphery of the lesion ## Footnote Progressive multifocal leukoencephalopathy is caused by a papovavirus (no- tably the JCvirus; A is false). Lesions occur mainly in the white matter and consistoffociofmyelinandoligodendroglialcelllosswithminimalin amma- tory in ltrate (Cand D are false). Hyperchromatic enlarged oligodendroglial nuclei are found at the margin of the lesions (E is false). Demyelination is present (B); some early cases were thought to represent atypical MS.1

Answer 9

A. I, II, III B. I, III C. II, IV D. IV **E. Alloftheabove** ## Footnote v o n H i p p e l - L i n d a u ( V H L) d i s e a s e i s a n a u t o s o m a l d o m i n a n t d i s o r d e r l i n k e d t o t h e VHLgene on chromosome 3—a tumor suppressor gene. The disease is associated with hemangioblastomas of the brain and spinal cord (II), retinal hemangio- blastomas, renal cell carcinomas and renal cysts (III, IV), pheochromocytoma, pancreatic tumors and cysts, hepatic cysts (I), and polycythemia vera

Answer 10

A. Neurofibroma **B. Schwannoma** C. Both D. Neither ## Footnote Schwannomas (B) are characterized by a biphasic cellular pattern composed of compact spindle cells (Antoni Aareas) and loosely arranged stellate cells (An- toni Bareas). Also seen are Verocay bodies, which result from the palisading of elongated nuclei alternating with anuclear brillar material.

Answer 11

A. Neurofibroma **B. Schwannoma** C. Both D. Neither ## Footnote Schwannomas (B) are characterized by a biphasic cellular pattern composed of compact spindle cells (Antoni Aareas) and loosely arranged stellate cells (An- toni Bareas). Also seen are Verocay bodies, which result from the palisading of elongated nuclei alternating with anuclear brillar material.

Answer 12

A. Neurofibroma **B. Schwannoma** C. Both D. Neither ## Footnote Schwannomas (B) are characterized by a biphasic cellular pattern composed of compact spindle cells (Antoni Aareas) and loosely arranged stellate cells (An- toni Bareas). Also seen are Verocay bodies, which result from the palisading of elongated nuclei alternating with anuclear brillar material.

Answer 13

**A. Neurofibroma** B. Schwannoma C. Both D. Neither ## Footnote Neuro bromas (A) incorporate the parent nerve and hence have axons in their midst. The plexiform type is considered pathognomonic for neuro bromatosis type 1

Answer 14

**A. Neurofibroma** B. Schwannoma C. Both D. Neither ## Footnote Neuro bromas (A) incorporate the parent nerve and hence have axons in their midst. The plexiform type is considered pathognomonic for neuro bromatosis type 1

Answer 15

A. Breast **B. Choriocarcinoma** C. Gastrointestinal (GI) tract D. Ovarian E. Prostate ## Footnote Of these choices, choriocarcinoma (B) has the greatest tendency to hem- orrhage. Hemorrhage is also common in melanoma, renal cell carcinoma, colorectal carcinoma (C), and lung carcinoma. Cancers of breast origin (A) are unlikely to hemorrhage.

Answer 16

A. 12–24 hours B. Days 1–2 **C. Days 5–7** D. Days 10–20 E. More than 3 months ## Footnote Macrophages begin to arrive on day 3; by day 5–7 (C)

Answer 17

A. 12–24 hours B. Days 1–2 C. Days 5–7 D. Days 10–20 **E. More than 3 months** ## Footnote gem- istocytic astrocytes begin to appear at the periphery of the lesion, and en- hancement begins to occur on contrasted images. Fibrillary astrocytes do not appear at the periphery of the lesion for more than 3 months (E)

Answer 18

A. 12–24 hours B. Days 1–2 C. Days 5–7 **D. Days 10–20** E. More than 3 months ## Footnote lipid-laden macrophages become apparent.Between days 10 and 20 (D)

Answer 19

A. 12–24 hours **B. Days 1–2** C. Days 5–7 D. Days 10–20 E. More than 3 months ## Footnote Polymorphonuclear (PMN) leu- kocytes begin to accumulate 24 hours after the insult and PMN accumulation peaks at 48 hours (B)

Answer 20

**A. 12–24 hours** B. Days 1–2 C. Days 5–7 D. Days 10–20 E. More than 3 months ## Footnote Irreversible ischemic injury is evident at the cellular level within 6 hours with microvacuolization of the cells and cytoplasmic bulging. Neuronal necrosis becomes apparent within 12–24 hours (A)

Answer 21

A. Endothelial proliferation B. Gliosis localized to the globus pallidus and hippocampus C. Gliosis localized to the white matter **D. Alzheimer’stypeIIastrocytes** E. Loss of oligodendroglial cells ## Footnote Acquired hepatocerebral degeneration is associated with gliosis with a predi- lection for the cortex (C is false). It tends to spare the hippocampus, globus pallidus, and deep folia of the cerebellar cortex (B is false). Widespread hy- perplasia of protoplasmic astrocytes (Alzheimer’s type II astrocytes) is visible in the deep layers of the cerebral and cerebellar cortex and in deep nuclear structures (D)

Answer 22

A. Alcoholism B. Severe burns C. Rapid correction of hyponatremia D. Serum hyperosmolarity **E. VitaminAexcess** ## Footnote “The outstanding characteristic of CPM is its invariable association with some other serious, often life threatening disease.” Central pontine myelinolysis is an acute demyelinating condition of the brainstem that has been attributed to rapid correction of hyponatremia. The disorder has been associated with alcoholism (A), severe burns (B), and serum hyperosmolarity (D). The common pathway of all of these disease processes seems to involve either the rapid correction of hyponatremia (C) or severe acute hyperosmolarity (D) (as in burn victims). Vitamin A excess has not been associated with central pontine myelinolysis (E is false)

Answer 23

**A. I, II, III** B. I, III C. II, IV D. IV E. Alloftheabove ## Footnote Rosenthal bers, eosinophilic masses observed in astrocytic processes, are associated with pilocytic astrocytomas (III, neoplastic), astrocytosis (I), and Alexander’s disease (II, nonneoplastic). Pick’s disease (IV) is associated with Pick bodies, which are round, intracytoplasmic eosinophilic inclusions that are positive with silver stains and with antibodies to tau

Answer 24

A. Acousticneuromas B. Café-au-lait spots C. Cutaneous neuro bromatosis **D. Lisch nodules** E. Plexiform neuro bromas ## Footnote Neuro bromas (E) and café-au-lait spots (B) occur less commonly in neuro- bromatosis type 2 (NF-2) than in NF-1. Bilateral acoustic neuromas (A) are the hallmark of NF-2. Lisch nodules (D) are rare in NF-2.

Answer 25

**A. Thiamine de ciency** B. Asterixis C. Alzheimer’stypeIIastrocytes D. Increased serum ammonia ## Footnote Asterixis (B) can appear in a variety of metabolic encephalopathies but is most common in hepatic encephalopathy. The serum ammonia (D) level usually exceeds 200 mg/dL. The most striking neuropathologic nding in pa- tients who die in a state of hepatic encephalopathy is the presence of a large amount of large protoplasmic astrocytes with glycogen-containing inclu- sions. These Alzheimerʼs type II astrocytes (C) can be found throughout the deep cerebral cortex, lenticular nuclei, thalamus, substantia nigra, cerebellar cortex, red, dentate, and pontine nuclei. Thiamine de ciency is not associated with hepatic encephalopathy

Answer 26

**A. III** B. V C. VII D. IX E. XII ## Footnote The motor nuclei of cranial nerves V (B), VII (C), IX (D), and XII (E) as well as the motor cortex may be a ected.

Answer 27

A. Arteriovenous malformations B. Capillary telangiectasias **C. Cavernous malformations** D. Cryptic arteriovenous malformations E. Venous angiomas ## Footnote Cavernous malformations (cavernous hemangiomas [C]) are composed of large, thin-walled vessels without interposed brain parenchyma. Typically AVMs (Aand D) traverse disordered brain tissue that lies between the abnor- mal vessels. Capillary telangiectasias (B) contain intervening brain paren- chyma; so do developmental venous anomalies (venous angiomas [E]

Answer 28

A. Microtubules B. Oxidative phosphorylation C. Transcription D. Translation **E. Turnaround transport** ## Footnote in particular. End-organ glycosylation may disrupt turn- around transport (E), as seen in diabetes.

Answer 29

**A. Microtubules** B. Oxidative phosphorylation C. Transcription D. Translation E. Turnaround transport ## Footnote This question focuses on causes of toxic neuropathies. Both vincristine and v i n b l a s t i n e i n t e r f e r e w i t h m i c r o t u b u l e ( A) f u n c t i o n , a l t h o u g h t h r o u g h s l i g h t l y di erent mechanisms.

Answer 30

A. Microtubules B. Oxidative phosphorylation C. Transcription **D. Translation** E. Turnaround transport ## Footnote Mercury inactivates sulfhydryl groups of enzymes interfering with cellular metabolism and function— translation (D),

Answer 31

A. Microtubules B. Oxidative phosphorylation **C. Transcription** D. Translation E. Turnaround transport ## Footnote Actinomycin D is an antibiotic produced by streptomyces that is used in cancer therapy. Its phenoxazone ring intercolates with DNA and interferes with DNA transcription (C).

Answer 32

A. Microtubules **B. Oxidative phosphorylation** C. Transcription D. Translation E. Turnaround transport ## Footnote Dinitrophenol is thought to disrupt oxidative phos- phorylation (B).

Answer 33

**A. Microtubules** B. Oxidative phosphorylation C. Transcription D. Translation E. Turnaround transport ## Footnote This quest ion focuses on causes of toxic neuropathies. Both vincristine and vinblastine interfere with microtubule (A) funct ion, although through slightly di erent mechanisms. Dinit rophenol is thought to disrupt oxidative phosphorylation (B). Act inomycin D is an antibiotic produced by streptomyces that is used in cancer therapy. Its phenoxazone ring intercolates with DNA and interferes with DNA transcription (C). Mercury inact ivates sulfhydryl groups of enzymes interfering with cellular metabolism and function— translation (D), in part icular. End-organ glycosylation may disrupt turnaround transport (E), as seen in diabetes

Answer 34

A. Choriocarcinomas **B. Glomus jugulare tumors** C. Oligodendrogliomas D. Pineocytomas E. Pleomorphic xanthoastrocytomas ## Footnote Glomus jugulare tumors (B) originate from foci of paraganglionic tissue around the jugular bulb (they are paragangliomas of the glomus jugulare). These invasive tumors contain neurosecretory granules similar to those in the carotid body. Some of them produce clinically detectable amounts of catecholamine. The most common paraganglioma is that of the adrenal gland and goes by another name: pheochromocytoma. None of the other options listed are known to secrete catecholamines.

Answer 35

A. Basophilic B. CalledCowdrytypeBbodies C. Found in neurons only **D. Intranuclear** E. Only evident several weeks after the infection ## Footnote The viral inclusions of herpes simplex type 1 (Cowdry type A) are dense, in- tranuclear, eosinophilic bodies found in neurons, astrocytes, and oligoden- drocytes. They are more likely to be found early in the course of the disease

Answer 36

**A. Endodermal sinus tumors** B. Choriocarcinomas C. Germinomas D. Pineoblastomas E. Teratomas ## Footnote High levels of human chorionic gonadotrophin (HCG) are associated with choriocarcinomas (B), and high levels of a-fetoprotein (AFP) are associated with endodermal sinus tumors (yolk sac tumors [A]). Fifteen percent of germinomas (C) may be associated with increased HCG. Embryonal carcino- mas will show elevations in both AFP and HCG. Teratomas (E) may cause a rise in serum CEAlevels

Answer 37

A. Lobar, putamen, cerebellum, thalamus, pons **B. Putamen, lobar, thalamus, cerebellum, pons** C. Putamen, thalamus, pons, lobar, cerebellum D. Thalamus, cerebellum, lobar, putamen, pons E. Thalamus, lobar, putamen, cerebellum, pons ## Footnote The most common sites of hypertensive cerebral hemorrhage are (1) puta- men and internal capsule (50%); (2) lobar hemorrhages of the central white matter of the temporal, parietal, or frontal lobes; (3) thalamus; (4) cerebellar hemisphere; and (5) pons

Answer 38

A. Breast B. Choriocarcinoma **C. Lung** D. Lymphoma E. Prostate ## Footnote Lung (C) metastasis is the most common intracranial metastatic tumor.

Answer 39

A. Breast **B. Choriocarcinoma** C. Lung D. Lymphoma E. Prostate ## Footnote Choriocarcinoma (B) has the greatest propensity to hemorrhage.

Answer 40

A. Breast B. Choriocarcinoma C. Lung **D. Lymphoma** E. Prostate ## Footnote Secondary (metastatic) CNS lymphoma (D) tends to involve the meninges, while primary CNS lymphoma tends to involve the parenchyma. Of the options listed,

Answer 41

A. Breast B. Choriocarcinoma C. Lung D. Lymphoma **E. Prostate** ## Footnote prostate (E) has the lowest propensity to metastasize to brain.

Answer 42

**A. Presynaptic inhibition at the neuromuscular junction** B. Inhibition of Renshaw cells C. Postsynaptic inhibition ## Footnote Both botulism and Eaton-Lambert syndrome cause presynaptic inhibition at the neuromuscular junction (A)

Answer 43

A. Presynaptic inhibition at the neuromuscular junction B. Inhibition of Renshaw cells **C. Postsynaptic inhibition** ## Footnote Myasthenia gravis is caused by antibodies to acetycholine receptors located on the postsynaptic end-plate (C).

Answer 44

**A. Presynaptic inhibition at the neuromuscular junction** B. Inhibition of Renshaw cells C. Postsynaptic inhibition

Answer 45

A. Presynaptic inhibition at the neuromuscular junction **B. Inhibition of Renshaw cells** C. Postsynaptic inhibition ## Footnote albeit via di erent mechanisms. Botuli- num toxin prevents binding of synaptic vesicles to the presynaptic membrane inhibiting acetylcholine release. Eaton-Lambert syndrome is caused by anti- bodies directed against voltage-gated calcium channels located at the presyn- aptic terminal; interference with these voltage-gated Ca21 channels causes decreased release of ACh quanta, as synaptic vesicle binding is a calcium- dependent process. Tetanus toxin causes excitation of agonist and antago- nist muscles by inhibiting the release of glycine from Renshaw cells (B) (similar to strychnine poisoning)

Answer 46

A. Acousticneuromas B. Cortical calci cation **C. Giant-cell astrocytomas** D. Opticgliomas E. Renalcysts ## Footnote Tuberous sclerosis is an autosomal dominant condition localized to chromo- som es 9 and 16 that is associated w ith a classic triad of m ental retardation, sei- zures, and adenoma sebaceum. Subependymal giant-cell astrocytomas (C) are present in 15%of cases. Acoustic neuromas (A) are associated with NF-2. Cortical calci cations (B) are associated with Sturge-Weber syndrome.Optic gliomas (D) are associated with NF-1.Renal cysts (E) are associated with VHL disease

Answer 47

**A. Choriocarcinoma** B. Embryonal carcinoma C. Endodermal sinus tumor D. Germinoma E. Teratoma ## Footnote High levels of human chorionic gonadotrophin (HCG) are associated with choriocarcinomas (A), and high levels of a-fetoprotein (AFP) are associated with endodermal sinus tumors (yolk sac tumors [C]). Fifteen percent of germinomas (D) may be associated with increased HCG. Embryonal carci- nomas (B) will show elevations in both AFP and HCG. Teratomas (E) may cause a rise in serum carcinoembryonic antigen levels.

Answer 48

A. Acidophilic pituitary adenoma **B. Basophilic pituitary adenoma** C. Chromophobic pituitary adenoma D. Ectopic source of adrenocorticotropic hormone (ACTH) E. Nonfunctioning pituitary adenoma ## Footnote Cushing’s disease is hypercortisolemia caused by an ACTH-secreting pituitary tumor (D is false). Cushing’s syndrome is a hypercortisol state that may be due to a variety of causes. Acidophilic (A) pituitary cells may produce prolactin, growth hormone, or FSH/LH. Basophilic (B) pituitary cells may produce ACTH or TSH. Therefore, Cushing’s disease, by de nition, is most often associated with a basophilic pituitary adenoma (B).

Answer 49

A. Fabry’s disease B. Gaucher’s disease **C. Niemann-Pick disease** D. Sandho ’s disease E. Tay-Sachs disease ## Footnote Niemann-Pickdisease(C)iscausedbysphingomyelinasede ciencywithan accumulation of sphingomyelin and cholesterol. Supranuclear paresis of ver- tical gaze is highly characteristic of this disease.

Answer 50

A. Fabry’s disease B. Gaucher’s disease C. Niemann-Pick disease **D. Sandho ’s disease** E. Tay-Sachs disease ## Footnote Sandho ’s disease (D) is caused by hexosaminidase A and B de ciency with accumulation of GM2 gangliosides

Answer 51

A. Fabry’s disease **B. Gaucher’s disease** C. Niemann-Pick disease D. Sandho ’s disease E. Tay-Sachs disease ## Footnote Gaucher’s disease (B) is caused by a glucocerebrosidase de ciency with accumulation of glucocerebrosides.

Answer 52

A. Fabry’s disease B. Gaucher’s disease C. Niemann-Pick disease D. Sandho ’s disease **E. Tay-Sachs disease** ## Footnote Tay-Sachs disease (E) is caused by a de ciency of hexosaminidase A with accumulation of GM2 gangliosides

Answer 53

**A. Fabry’s disease** B. Gaucher’s disease C. Niemann-Pick disease D. Sandho ’s disease E. Tay-Sachs disease ## Footnote The ve options listed are sphingolipidoses, lysosomal storage disorders that r e s u l t i n a b n o r m a l a c c u m u l a t i o n o f l i p i d s . Al l o f t h e c h o i c e s a r e i n h e r i t e d i n a n autosomal recessive fashion except for Fabry’s disease (A), which is X-linked recessive.

Answer 54

**A. Fabry’s disease** B. Gaucher’s disease C. Niemann-Pick disease D. Sandho ’s disease E. Tay-Sachs disease

Answer 55

A. Fabry’s disease B. Gaucher’s disease C. Niemann-Pick disease **D. Sandho ’s disease** E. Tay-Sachs disease ## Footnote Tay-Sachs (E) and Sandho ’s disease (D) are the two GM2 ganglio- sidoses, and both have cherry-red spots in the macula as a prominent feature.

Answer 56

A. Fabry’s disease B. Gaucher’s disease **C. Niemann-Pick disease** D. Sandho ’s disease E. Tay-Sachs disease

Answer 57

**A. Fabry’s disease** B. Gaucher’s disease C. Niemann-Pick disease D. Sandho ’s disease E. Tay-Sachs disease

Answer 58

**A. Fabry’s disease** B. Gaucher’s disease C. Niemann-Pick disease D. Sandho ’s disease E. Tay-Sachs disease

Answer 59

A. Fabry’s disease B. Gaucher’s disease C. Niemann-Pick disease D. Sandho ’s disease **E. Tay-Sachs disease**

Answer 60

A. Hunter’s syndrome (MPSII) **B. Hurler’s syndrome (MPS I H)** C. Morquio’s syndrome (MPSIV) D. San lippo’ssyndrome(MPSIII) E. Scheie’s syndrome (MPSIS) ## Footnote Hurler’s syndrome (B) is caused by an a-L-iduronidase de ciency with heparan and dermatan sulfate excretion in the urine.

Answer 61

A. Hunter’s syndrome (MPSII) B. Hurler’s syndrome (MPS I H) **C. Morquio’s syndrome (MPSIV)** D. San lippo’ssyndrome(MPSIII) E. Scheie’s syndrome (MPSIS) ## Footnote Morquio’s syn- drome (C) is caused by b-galactosidase and galactose-6-sulfatase de ciency with keratin excretion in the urine. Ligamentous laxity, skeletal deformities, and atlantoaxial subluxation are characteristic.

Answer 62

A. Hunter’s syndrome (MPSII) B. Hurler’s syndrome (MPS I H) C. Morquio’s syndrome (MPSIV) **D. San lippo’ssyndrome(MPSIII)** E. Scheie’s syndrome (MPSIS) ## Footnote San lippo’s syndrome (D) is caused by sulfamidase de ciency with heparan excretion in the urine

Answer 63

**A. Hunter’s syndrome (MPSII)** B. Hurler’s syndrome (MPS I H) C. Morquio’s syndrome (MPSIV) D. San lippo’ssyndrome(MPSIII) E. Scheie’s syndrome (MPSIS) ## Footnote The options listed are mucopolysaccharidoses (MPS), which produce lipid accumulation in the lysosomes of the gray matter and polysaccharide accumulation in connective tissue. All of these options are inherited in an autosomal recessive fashion, with the exception of Hunter’s syndrome (A), which is inherited in an X-linked recessive fashion. Hunter’s syndrome (A) is caused by a de ciency of iduronidase sulfatase with heparan and dermatan excretion in the urine—skin pebbling and peripheral nerve entrapment are common.

Answer 64

A. Hunter’s syndrome (MPSII) B. Hurler’s syndrome (MPS I H) C. Morquio’s syndrome (MPSIV) D. San lippo’ssyndrome(MPSIII) **E. Scheie’s syndrome (MPSIS)** ## Footnote .Scheie’s syndrome (E) is a milder form of Hurler’s disease that is also caused by a de ciency of a-L-iduronidase. It is characterized by normal intelligence.

Answer 65

A. Adrenoleukodystrophy B. Alexander’s disease C. Canavan’s disease **D. Krabbe’s disease** E. Metachromatic leukodystrophy ## Footnote Krabbe’s disease (D) is an autosomal recessive disorder of the enzyme b-galactosidase with accumulation of galactocerebroside as well as psychosine, which is toxic for oligodendroglial cells. In Krabbe’s disease, there is vacuolization of the white matter with sparing of subcortical U- bers.

Answer 66

**A. Adrenoleukodystrophy** B. Alexander’s disease C. Canavan’s disease D. Krabbe’s disease E. Metachromatic leukodystrophy ## Footnote Adrenoleukodystrophy (A) is an X-linked recessive disorder result- ing from abnormal lipid oxidation in peroxisomes leading to accumulation of long-chain fatty acids accompanied by adrenal insu ciency.

Answer 67

A. Adrenoleukodystrophy **B. Alexander’s disease** C. Canavan’s disease D. Krabbe’s disease E. Metachromatic leukodystrophy ## Footnote Alexander’s disease (B) is a sporadically inherited disease resulting from a defect in the GFAPgene.Psychomotor retardation and seizures are common,and Rosenthal bers are present on histologic sections.

Answer 68

A. Adrenoleukodystrophy B. Alexander’s disease C. Canavan’s disease D. Krabbe’s disease **E. Metachromatic leukodystrophy**

Answer 69

**A. Adrenoleukodystrophy** B. Alexander’s disease C. Canavan’s disease D. Krabbe’s disease E. Metachromatic leukodystrophy ## Footnote Adrenoleukodystrophy (A) is an X-linked recessive disorder result- ing from abnormal lipid oxidation in peroxisomes leading to accumulation of long-chain fatty acids accompanied by adrenal insu ciency.

Answer 70

A. Adrenoleukodystrophy B. Alexander’s disease C. Canavan’s disease **D. Krabbe’s disease** E. Metachromatic leukodystrophy

Answer 71

**A. Adrenoleukodystrophy** B. Alexander’s disease C. Canavan’s disease D. Krabbe’s disease E. Metachromatic leukodystrophy

Answer 72

A. Alzheimer’s type II astrocytes B. Atrophy and brownish discoloration of the globus pallidus and putamen **C. Autosomal dominant trait** D. Decreased serum ceruloplasmin E. Decreased serum copper ## Footnote Wilson’s disease is transmitted as an autosomal recessive trait (Cis false), and involves the ATP7B gene, which causes two disturbances of copper metabolism. There is reduced incorporation of copper into ceruloplasmin, and there is reduction in biliary excretion of copper. Decreased serum cop- per levels (E), decreased serum ceruloplasmin levels (D), and increased urinary excretion of copper are typical laboratory ndings. Cavitation and discoloration (B) of the lentiform nuclei (hence, “hepatolenticular degen- eration”) are typical on pathologic examination. There is marked hyperplasia of protoplasmic astrocytes (Alzheimer’s type II astrocytes [A]) in both corti- cal and subcortical structures

Answer 73

A. Idiopathic Parkinson’s disease B. Shy-Drager syndrome **C. Both** D. Neither ## Footnote Both idiopathic Parkinson’s disease (A) and the Shy-Drager syndrome (a form of striatonigral degeneration [B]) are characterized by loss of cells in the zona compacta of the substantia nigra,

Answer 74

A. Idiopathic Parkinson’s disease **B. Shy-Drager syndrome** C. Both D. Neither ## Footnote Shy-Drager syndrome (B), signi cant cell loss in the putamen and the intermediolateral column is also found. Lewy bodies are not found in the Shy-Drager syndrome (B). Patients with this syndrome su er from parkinsonian symptoms and orthostatic hypotension.5

Answer 75

**A. Idiopathic Parkinson’s disease** B. Shy-Drager syndrome C. Both D. Neither ## Footnote Shy-Drager syndrome (B), signi cant cell loss in the putamen and the intermediolateral column is also found. Lewy bodies are not found in the Shy-Drager syndrome (B). Patients with this syndrome su er from parkinsonian symptoms and orthostatic hypotension.5

Answer 76

A. Idiopathic Parkinson’s disease **B. Shy-Drager syndrome** C. Both D. Neither ## Footnote Shy-Drager syndrome (B), signi cant cell loss in the putamen and the intermediolateral column is also found. Lewy bodies are not found in the Shy-Drager syndrome (B). Patients with this syndrome su er from parkinsonian symptoms and orthostatic hypotension.5

Answer 77

**A. Dementia** B. In ammatory polymyositis C. Lymphoma D. Myelopathy E. Toxoplasmosis ## Footnote D e m e n t i a ( A) , c h a r a c t e r i z e d b y c o g n i t i v e d y s f u n c t i o n , b e h a v i o r a l d i s t u r b a n c e , and motor impairment, occurs in one-third to two-thirds of patients with AIDS. Myelopathy (D) occurs in less than 10%, in ammatory polymyositis (B) in 20%, toxoplasmosis (E) in 10%, and lymphoma (C) in 5%of AIDS patients

Answer 78

A. Adenoma sebaceum **B. Renalcellcarcinoma** C. Rhabdomyomasoftheheart D. Subependymal giant-cell astrocytoma E. Subungual bromas ## Footnote The triad of adenoma sebaceum (A) (actually angio bromas), epilepsy, and mental retardation characterizes tuberous sclerosis. Although benign tumors (angiomyolipomas) of the kidney and other organs are seen, renal cell car- cinomas (B) are not (renal cell carcinoma is associated with VHL). Rhabdo- myomas of the heart (C), subependymal giant-cell astrocytoma (D), and subungual bromas (E) are all seen in tuberous sclerosis.

Answer 79

A. Axillary freckling **B. Café-au-lait macules** C. Neuro bromasoftheiris D. Optic gliomas E. Sphenoid dysplasia ## Footnote Neuro bromatosistype1(NFofvonRecklinghausen,peripheralorclassicNF) is an autosomal dominant disorder localized to chromosome 17 (neuro bro- min gene) characterized by areas of skin hyperpigmentation and cutaneous and subcutaneous neuro bromas. Café-au-lait spots (B) are present on the skin, and the presence of six or more . 1.5 cm lesions is indicative of the diagnosis. The presence of axillary freckling (A) in conjunction with café-au- lait macules is nearly pathognomonic of NF-1. NF-1 is also associated with the growth of multiple peripheral neuro bromas, bone cysts, scoliosis, sphenoid dysplasia (E), and optic glioma (D) formation. The Lisch nodules of NF-1 represent hamartomas of the iris, not neuro bromas of the iris (Cis false)

Answer 80

A. Amyloid b protein is the major protein seen B. Aneurysmal dilations are seen in involved vessels **C. It occurs primarily in vessels of deep nuclear structures of the brain** D. It occurs primarily in patients over 70 years of age E. Ayellow-green dichromism is seen under polarized light when the amyloid is stained with Congo red ## Footnote Cerebral amyloid angiopathy is con ned to intracranial arteries and arterioles in the leptomeninges and super cial cortex (Cis false). The other responses are true statements regarding amyloid angiopathy

Answer 81

A. Increased cerebrospinal uid (CSF) protein at 5 weeks after onset of illness **B. Lymphocytic pleocytosis in 90%of patients** C. NormalCSFpressures D. Perivascular lymphocytic and in ammatory cell in ltrate E. Perivenular and segmental demyelination ## Footnote The CSF in Guillain-Barré syndrome is under normal pressure (C), is acel- lular in 90%of patients (B is false), and demonstrates an increased protein level that peaks at 4 to 6 weeks after onset (A). Presence of a perivascular lymphocytic in ammatory in ltrate (D) and perivenular and segmental demyelination (E) are characteristic ndings

Answer 82

A. Rarely multiple B. Associated with immunosuppression in older men **C. Associated with immunosuppression in younger men** D. Resistant to steroids ## Footnote This is lymphoma with di use perivascular lymphocytic in ltration into the Virchow-Robin space around a blood vessel. Such lymphomas are often multiple (A is false), respond initially to steroids (D is false), but invariably recur, and are associated with immunosuppression in younger men (C). They also occur in immunocompetent males over 60 years

Answer 83

A. Hirano bodies **B. Inclusion bodies of herpes simplex virus-1 (HSV-1)** C. Lewybodies D. Pick bodies E. Rabies ## Footnote This hematoxylin and eosin H&E-stained section represents HSV-1 encepha- litis (B) and shows lymphocytic perivascular cu ng on the main slide. The inset at the top right of the image shows a Cowdry type A body, the eosino- philic intranuclear inclusion with a surrounding halo typical for HSV-1

Answer 84

A. Hirano bodies **B. Inclusion bodies of subacute sclerosing panencephalitis (SSPE)** C. Lewybodies D. Pick bodies E. Rabies ## Footnote This H&E-stained section is an example of subacute sclerosing panencepha- litis (B) as is seen sometimes following measles infection (1 in 1,000 cases). The inclusion bodies of HSV (dense, eosinophilic, and surrounded by a clear halo) and SSPE are intranuclear. The inclusion bodies seen in the other responses are intracytoplasmic. Smaller eosinophilic intracytoplasmic inclu- sions may also be seen in SSPE

Answer 85

A. Inclusion bodies of HSV-1 B. Lewybodies **C. Pick bodies** D. Rabies E. Inclusion bodies of SSPE ## Footnote This silver stain shows an example of Pick bodies (C), rounded intracytoplas- micmasses.OnH&Estaining,itmightbedi culttodistinguishcorticalPick bodies from cortical Lewy bodies (B), both of which would appear as round eosinophilic intracytoplasmic inclusions. Lewy bodies of the brainstem and nucleus basalis typically have a halo,which can help with the distinction.Pick bodies are marked with silver stains (Lewy bodies are not). Pick bodies are immunopositive with anti-tau antibodies

Answer 86

A. Inclusion bodies of HSV-1 **B. Lewybodies** C. Pick bodies D. Rabies E. Inclusion bodies of SSPE ## Footnote Th i s i s a n H &E- s t a i n e d s e c t i o n s h o w i n g a n e x a m p l e o f a Le w y b o d y ( n e u r o n a l intracytoplasmic inclusion with an eosinophilic core surrounded by a clear halo [B]), which can be seen in the neurons of the substantia nigra in Parkinson’s disease patients

Answer 87

A. Ganglioglioma **B. Hepatic encephalopathy** C. H S V- 1 D. Parkinson’s disease E. Normalcortex ## Footnote This H&E-stained section shows an example of Alzheimer’s type II astrocytes, large vesicular nuclei,and little visible cytoplasm.These reactive protoplasmic astrocytes are found in hepatic encephalopathy (B) and Wilson’s disease

Answer 88

A. Fibrillary astrocytoma **B. Gemistocytic astrocytoma** C. Glioblastoma multiforme D. Hem angioblastom a E. Oligodendroglioma ## Footnote This H&E-stained section shows an example of a gemistocytic astrocytoma (B). The cells of this variant of astrocytoma have prominent eosinophilic cyto- plasm,short processes,and eccentricnuclei(comprised ofgemistocyticastro- cytes). Gemistocytic astrocytes can be seen in the setting of reactive gliosis, but the crowding and overlapping of cells in this slide support the diagnosis of neoplasm. Gemistocytic astrocytomas tend to behave more aggressively than other WHO grade II astrocytomas; for this reason, gemistocytic astrocytomas are sometimes graded WHO grade III because of gemistocytic features

Answer 89

A. Aneurysmal subarachnoid hemorrhage B. Bacterial meningitis C. Contusion **D. H S V- 1** E. Subdural hematoma ## Footnote The hemorrhagic appearance of the medial temporal lobe is characteristic of HSV-1 (D)

Answer 90

A. AIDS encephalopathy B. Giant-cell glioblastoma multiforme (GBM) C. Hem angioblastom a D. Creutzfeldt-Jakob disease **E. Progressive multifocal leukoencephalopathy** ## Footnote This H&E-stained section is an example of progressive multifocal encepha- lopathy (E, associated with the JC virus and an immunocompromised state). Demyelination and oligodendroglial cell loss are seen. Residual oligo- dendroglial nuclei (arrows) are large and bizarre

Answer 91

A. AIDS encephalopathy B. Giant-cell GBM C. Hem angioblastom a **D. Creutzfeldt-Jakob disease** E. Progressive multifocal leukoencephalopathy ## Footnote This is a representative H&E-stained section from a patient with Creutzfeldt- Jakob disease (D), a prion disease causing vacuolization and spongiform changes

Answer 92

A. Metastatic disease **B. Neuro bromatosis type 1 (NF-1)** C. NF-2 D. Tuberous sclerosis E. von Hippel-Lindau disease ## Footnote The iris hamartomas (Lisch nodules) of NF-1 (B) are seen in this photograph.

Answer 93

**A. HIV encephalopathy** B. Giant-cell GBM C. Hem angioblastom a D. Creutzfeldt-Jakob disease E. Progressive multifocal leukoencephalopathy ## Footnote This Luxolfast blue H&E-stained section is an example ofHIVencephalopathy (A). Microglial nodules with foci of demyelination, neuronal loss, and reac- tive astrocytosis are typical. The characteristic multinucleated giant cell is seen here

Answer 94

A. Anaplastic astrocytoma B. Ependymoma **C. Ganglioglioma** D. Meningioma E. Oligodendroglioma ## Footnote This is an H&E-stained section from a ganglioglioma (C),which contains both neoplastic neurons and ganglion cells. The nding of abnormal ganglion cells (including binucleate forms) is key to the diagnosis of ganglioglioma

Answer 95

A. Anaplastic astrocytoma B. Meningioma C. Normal pituitary gland **D. Oligodendroglioma** E. Pituitary adenoma ## Footnote This is an H&E-stained section of an oligodendroglioma (D). 1p and 19q co-deletions in these tumors are associated with improved progression-free and overall survival. A characteristic “chicken wire” vascular pattern and a monotonous “fried egg” nuclear array are seen

Answer 96

A. Choroid plexus papilloma B. Ependymoma **C. Medulloblastoma** D. Meningioma E. Pituitary adenoma ## Footnote This H&E-stained sections shows dense, hyperchromatic cells that are radially arranged in Homer-Wright rosettes with central granulo brillar material. These ndings are most consistent with a primitive neuroectodermal tumor (medulloblastoma [C]), neuroblastoma, etc.)

Answer 97

A. Choroid plexus papilloma B. Craniopharyngioma C. Hem angioblastom a D. Metastatic tumor **E. Myxopapillary ependymoma** ## Footnote This H&E-stained section of a myxopapillary ependymoma (E) shows cohesive ependymal cells terminating around perivascular accumulations of mucinous material. Myxopapillary ependymomas tend to occur at the lum (conus medullaris

Answer 98

A. Choroid plexus papilloma **B. Craniopharyngioma** C. Hem angioblastom a D. Metastatic tumor E. Myxopapillary ependymoma ## Footnote Question 122 shows an H&E-stained section from a craniopharyngioma (B) that demonstrates an adamantinomatous pattern with a basal layer of colum- nar cells separated by loosely arranged stellate cells. Palisading epithelial cells with keratinization and calci cation are prominent. The papillary variant is more often seen in adults and contains papillae of well-di erentiated squa- mous epithelium (not pictured here)

Answer 99

A. Choroid plexus papilloma B. Craniopharyngioma **C. Hem angioblastom a** D. Metastatic tumor E. Myxopapillary ependymoma ## Footnote An H&E-stained section of hemangioblastoma (C) is pictured here. They are most commonly found in the posterior fossa, and 60%present as a cyst with a mural nodule. Multiple hemangioblastoma are associated with VHL. On H&E staining they are di cult to distinguish from renal cell carcinoma (particularly problematic in VHLpatients who are at risk for renal cell carci- noma also). The diagnostic distinction can be made by immunohistochemis- try. Vacuolated “stromal” cells in a complex capillary network are seen in this photomicrograph

Answer 100

A. Butter yglioma B. Carbon monoxide poisoning C. Fatemboli **D. Lipoma** E. Lipofuscin deposition ## Footnote This gross anatomical specimen shows an example of a lipoma (D) of the corpus callosum

Answer 101

**A. Carbon monoxide poisoning** B. Fatemboli C. Hallervorden-Spatz disease D. Miliary tuberculosis E. Wilson’s disease ## Footnote This gross anatomic specimen shows selective necrosis of the globus pallidus, most consistent with carbon monoxide poisoning (A)

Answer 102

A. Ependymoma **B. Glioblastoma** C. Medulloblastoma D. Meningioma E. Schwannoma ## Footnote This is an H&E-stained section showing a section representative of glioblas- toma (B). Either microvascular proliferation or necrosis is required for an astrocytic tumor to qualify as glioblastoma (WHO grade IV). Necrosis with pseudopalisading is well illustrated in this photomicrograph

Answer 103

A. Metastatic disease B. NF-1 C. NF-2 **D. Tuberous sclerosis** E. von Hippel-Lindau disease ## Footnote The adenoma sebaceum of tuberous sclerosis (D) is seen in this photograph. Tuberous sclerosis is an autosomal dominant condition linked to chromo- somes 9 and 16 characterized by the classic triad of adenoma sebaceum, seizures, and mental retardation. Patients with tuberous sclerosis are prone to develop cortical tubers, subependymal giant cell astrocytomas, cardiac rhabdomyoma, retinal hamartoma, and renal angiomyolipoma.

Answer 104

A. Anaplastic astrocytoma B. Medulloblastoma **C. Meningioma** D. Metastatic tumor E. Oligodendroglioma ## Footnote This H&E-stained photomicrograph is an example of a meningotheliomatous (syncytial) type of meningioma (C). Apsammoma body is noted as well

Answer 105

A. Glioblastoma B. Malignant peripheral nerve sheath tumor **C. Meningioma** D. Neurofibroma E. Schwannoma ## Footnote This H&E-stained section is another example of meningioma (C). Note the prominent whorls

Answer 106

A. Glioblastoma B. Malignant peripheral nerve sheath tumor C. Meningioma **D. Neurofibroma** E. Schwannoma ## Footnote This is an H&E-stained section of a neuro broma (D). Bundles of elongated Schwann cells with characteristic wavy nuclei in a loose mucinous or collag- enous matrix are features of the neuro broma

Answer 107

A. Glioblastoma **B. Malignant peripheral nerve sheath tumor** C. Meningioma D. Neurofibroma E. Schwannoma ## Footnote Malignant peripheral nerve sheath tumors (B) are composed of spindle cells in fascicles with occasional mitoses and foci of necrosis (H&E).

Answer 108

A. Glioblastoma B. Malignant peripheral nerve sheath tumor C. Meningioma D. Neurofibroma **E. Schwannoma** ## Footnote This H&E-stained section shows Verocay bodies, palisading elongated nuclei en- circling anuclear brillary material, which are hallmarks of schwannomas (E).

Answer 109

A. Filum terminale B. Kidney **C. Notochord** D. Pituitary E. von Hippel-Lindau disease ## Footnote This H&E-stained section shows “physaliphorous” or “bubbly” cells surround- ing pools of mucin, consistent with the diagnosis of chordoma. Chordomas are thought to arise from notochord (C) remnants, usually occurring in the clivus or sacrum.3

Answer 110

A. Alzheimer’s disease B. H S V- 1 **C. Huntington’s disease** D. Parkinson’s disease E. Pickʼs disease ## Footnote Huntington’s disease (C) is an autosomal dominant hereditary movement disorder that localizes to chromosome 4 and involves a CAG trinucleotide repeat. The clinical syndrome involves choreiform movements of the trunk and upper limbs with subcortical dementia. Atrophy of the head of the caudate with “boxcar”ventricles is characteristic and can be seen in this gross pathologic specimen.1,3

Answer 111

A. Bacterial meningitis B. Candidiasis **C. Neuritic plaques** D. Neuro brillary tangles E. Pick bodies ## Footnote Neuritic (“senile”) plaques (composed of degenerating nerve cell processes surrounding a central core of amyloid composed of b/A4 protein, double ar- rows [C]) and neuro brillary tangles (single arrows [D]) are seen (silver stain).3

Answer 112

A. Acute disseminated encephalomyelitis B. Adrenoleukodystrophy **C. Alexander’s disease** D. Krabbe’s disease E. Metachromatic leukodystrophy ## Footnote Alexander’s disease (C) is one of the leukodystrophies and is caused by a defect in the GFAP gene leading to hemispheric demyelination and mitochon- drial dysfunction. Numerous Rosenthal bers (eosinophilic material in cell processes, likely from GFAP degradation products) in areas of astrocytosis are noted (H&E). Alexander’s disease is an example of a nonneoplastic process where Rosenthal bers may occur.

Answer 113

A. Amyloid angiopathy B. Duret’s hemorrhage C. Glioblastoma **D. Hypertensive hemorrhage** E. Melanoma ## Footnote Amassive basal ganglia hypertensive hemorrhage (D) is noted on this gross pathologic specimen

Answer 114

**A. Central neurocytoma** B. Colloid cysts C. Glioblastoma D. Hem angioblastom a E. Schwannoma ## Footnote A dense array of uniform undi erentiated cells with small blue nuclei and perinuclear halos is found in central neurocytomas (A). The ndings are similar to oligodendrogliomas and can be di cult to di erentiate on H&E staining.Centralneurocytomasstainwithsynaptophysinandneuron-speci c enolase (NSE).

Answer 115

A. Amyotrophic lateral sclerosis **B. Friedreich’s ataxia** C. Multiple sclerosis D. Radiation myelopathy E. Subacute combined degeneration ## Footnote This Luxol fast blue stain shows demyelination of the posterior columns and ventral spinocerebellar tracts. Corticospinal tracts are also a ected

Answer 116

A. Amyotrophic lateral sclerosis B. Friedreich’s ataxia C. Multiple sclerosis D. Radiation myelopathy **E. Subacute combined degeneration** ## Footnote This Luxol fast blue stain reveals a spongiform and gliotic appearance of the cord primarily a ecting the posterior and lateral columns consistent with subacute combined degeneration (E). Subacute combined degeneration occurs in the setting of vitamin B12 de ciency and leads to impaired proprioceptive sense and paraplegia

Answer 117

A. Amyotrophic lateral sclerosis B. Friedreich’s ataxia C. Multiple sclerosis **D. Radiation myelopathy** E. Subacute combined degeneration ## Footnote There is an irregular area of coagulative necrosis involving both gray and white matter consistent with radiation myelopathy (D).

Answer 118

A. Amyotrophic lateral sclerosis B. Friedreich’s ataxia **C. Multiple sclerosis** D. Radiation myelopathy E. Subacute combined degeneration ## Footnote Well-de ned plaques are seen involving both gray and white matter in this Luxolfastbluestainedsection.These ndingssupportadiagnosisofmultiple sclerosis (C).

Answer 119

**A. Amyotrophic lateral sclerosis** B. Friedreich’s ataxia C. Multiple sclerosis D. Radiation myelopathy E. Subacute combined degeneration ## Footnote This photomicrograph of a Luxol fast blue stained section shows degeneration of the anterior horn and corticospinal tracts, consistent with amyotrophic lateral sclerosis (A).

Answer 120

A. Gliomatosis cerebri B. Huntington’s disease C. Krabbe’s disease D. Multiple sclerosis **E. Tuberous sclerosis** ## Footnote Cortical tubers are seen in the frontal and temporal lobes of this gross pathologic specimen as seen in . 95%of patients with tuberous sclerosis (D). Tuberous sclerosis is an autosomal dominant condition linked to chro- mosomes 9 and 16 characterized by the classic triad of adenoma sebaceum, seizures, and mental retardation. Patients with tuberous sclerosis are prone to develop cortical tubers, subependymal giant cell astrocytomas, cardiac rhabdomyoma, retinal hamartoma, and renal angiomyolipoma.

Answer 121

A. Choroid plexus papilloma **B. Ependymoma** C. Lymphoma D. Medulloblastoma E. Meningioma ## Footnote The histologic appearance of ependymomas is highly variable. Acellular vari- ety with sheetlike growth of oval to polygonal cells arranged in a perivascular pseudorosette is illustrated (H&E). Ependymomas are CNS neoplasms that resemblethestructureofthebrain’sependyma.Themostde nitiveevidence of ependymoma is the presence of true rosettes, also called “Flexner- Wintersteiner rosettes.” Most ependymomas contain perivascular pseudo- rosettes involving tumor cells surrounding an endothelial-lined lumen (as seen here). Ependymomas tend to stain for GFAP and vimentin, particularly in the perivascular pseudorosettes. On electron microscopy extensive surface microvilli forming both intra- and extracellular lumens can be seen.

Answer 122

A. Chordoma B. Dermoid C. Metastatic tumor D. Myxopapillary ependymoma **E. Teratoma** ## Footnote Teratomas are the most di erentiated of the germ cell neoplasms and contain elements of all three germ layers: ectoderm, mesoderm, and endoderm. Ca r t i l a g e , m u c i n - p r o d u c i n g e p i t h e l i u m , a n d i m m a t u r e s p i n d l e c e l l s t r o m a a r e all part of this immature teratoma (E)—a low-grade malignancy (H&E)

Answer 123

A. Advanced age and lobar hemorrhages B. Alcoholism and prone to falls **C. Port-wine nevus on the face** D. Retinalhamartomas E. Subungual bromas ## Footnote Atrophy of the hemisphere and leptomeningeal venous angioma are present in this specimen with Sturge-Weber syndrome. Sturge-Weber syndrome is characterized by a usually unilateral port-wine nevus (C) that typically in- volves the orbit or upper eyelid, unilateral meningeal angioma, calci cations con ned to the second and third layers of cerebral cortex, and seizure activity. Advanced age and lobar hemorrhage (A) are associated with amyloid angi- opathy. Retinal hamartomas (D) and subungual bromas (E) are associated with tuberous sclerosis. Choice B, alcoholism and prone to falls, would be a better answer if the gross specimen showed cerebellar atrophy

Answer 124

**A. Acousticneuroma** B. Anaplastic astrocytoma C. Medulloblastoma D. Melanoma E. Meningioma ## Footnote This low-power view (H&E) shows dense Antoni Aareas (with compact spin- dle cells) and looser Antoni Bareas (with stellate cells) consistent with acous- tic neuroma (schwannoma)

Answer 125

A. Carbon monoxide poisoning B. Cerebral contusions C. Herpes encephalitis D. Meningeal carcinomatosis **E. Melanoma** ## Footnote Melanoma (E) tends to be composed of cells with epitheloid or spindle cell con gurations. Epitheloid cells with melanin inclusions are seen in this H&E-stained section, consistent with the diagnosis of melanoma. Primary CNS melanomas are more likely to be pigmented than metastatic melano- mas, which tend to be amelanotic. Amelanotic metastatic melanomas may be di cult to distinguish from metastatic carcinoma, but this distinction can be made with immunohistochemical stains. The presence of ducts or glands rules out melanoma

Answer 126

A. Acousticneuroma **B. Anaplastic astrocytoma** C. Medulloblastoma D. Melanoma E. Meningioma ## Footnote The anaplastic astrocytoma (B, WHO grade III) is a di use tumor with low to moderate cell density and moderate pleomorphism. There may be focal areas of increased cell density and increased pleomorphism; however, it must not contain areas of microvascular proliferation or necrosis (if either of these features are present, the diagnosis is glioblastoma—WHO grade IV). This H&E-stained section shows cellular pleomorphism, hypercellularity, and mitotic activity consistent with the diagnosis of anaplastic astrocytoma

Answer 127

A. Anaplastic astrocytoma B. Infarct C. Metachromatic leukodystrophy **D. Multiple sclerosis** E. Radiation necrosis ## Footnote This gross anatomical specimen shows a periventricular demyelinating plaque. This nding is consistent with the diagnosis of multiple sclerosis (D)

Answer 128

A. Anaplastic astrocytoma B. Infarct **C. Metachromatic leukodystrophy** D. Multiple sclerosis E. Radiation necrosis ## Footnote Metachromatic leukodystrophy (C) is caused by a de ciency of arylsulfatase Aleading to the accumulation of sulfatides in lysosomes. Inheritance is auto- somalrecessive—itisthemostcommonoftheleukodystrophies.Largecon u- ent areas of demyelination with U- ber sparing are seen in the H&E-stained photomicrograph and are typical of metachromatic leukodystrophy

Answer 129

**A. Epidermoid** B. Lipoma C. Metastatic tumor D. Multiple sclerosis E. Teratoma ## Footnote A large cerebellopontine angle epidermoid (A) with white aky, keratinous debris is illustrated in this gross specimen. Epidermoid cysts consist of a cyst wallmadeupofstrati edsquamousepitheliumwithoutglandularstructures. The cyst contains desquamated keratin. Dermoid cysts can be distinguished histopathologically from epidermoid cysts based on the presence of hair follicles, adnexal glands, and the beginnings of papillary dermis formation in dermoid cysts. Some authors argue that dermoid cysts may represent benign teratom as.

Answer 130

A. Astrocytoma **B. Lymphoma** C. Melanoma D. Oligodendroglioma E. Pituitary adenoma ## Footnote This is an example of lymphoma (B) with di use perivascular lymphocytic in ltration into the Virchow-Robin space around a blood vessel. Such lym- phomas are often multiple, respond initially to steroids, but invariably recur, and are associated with immunosuppression in younger men.They also occur in immunocompetent males over age 60 years

Answer 131

A. Meningioma B. Neurfibroma **C. Pilocytic astrocytoma** D. Pleomorphic xanthoastrocytoma E. Schwannoma ## Footnote Compact fascicles of elongated cells and spongiform foci with stellate forms and microcystic change are noted in this example of pilocytic astrocytoma (C).

Answer 132

A. Aneurysmal subarachnoid hemorrhage B. Bacterial meningitis **C. Contusion** D. H S V- 1 E. Subdural hematoma ## Footnote Extensive bilateral contrecoup contusions of the orbital surfaces and frontal poles are illustrated in this gross pathologic specimen

Answer 133

**A. Amyloid angiopathy** B. Arteriovenous malformation C. Capillary telangiectasia D. Embolism E. Venousangioma ## Footnote The arterioles of the leptomeninges and super cial cortex are dilated, and amorphous material in ltrates the wall in this H&E-stained section from a patient with amyloid angiopathy (A).

Answer 134

A. Alzheimer’s disease B. Astrocytoma C. Huntington’s disease D. Krabbe’s disease **E. Pick’s disease** ## Footnote Pickʼs disease (E) is a form of cerebral degeneration characterized by atrophy of the frontal and temporal lobes involving both the gray and white matter (lobar atrophy). Selective atrophy of the frontal and temporal lobes consistent with Pickʼs disease is noted in this gross pathologic specimen. In Alzheimer’s disease (A), atrophy is more mild and di use. Huntington’s disease (C) is associated with atrophy of the caudate

Answer 135

A. Astrocytoma B. Glioblastoma **C. Hem angioblastom a** D. Medulloblastoma E. Metastasis ## Footnote Hemangioblastoma (C) accounts for ~10% of posterior fossa tumors. The majority of hemangioblastomas are cystic with a mural nodule. In this gross specimen, a vascular mural nodule in the left cerebellar hemisphere and an associated cyst (midline) are consistent with the diagnosis of cerebellar hemangioblastoma.

Answer 136

A. Astrocytoma B. Glioblastoma C. Neuro broma **D. Pituitary adenoma** E. Schwannoma ## Footnote This H&E-stained section shows an example of a pituitary adenoma (D). The normal acinar, heterogeneous appearance of the pituitary is replaced by a di use sheet of polygonal cells.2,3

Answer 137

A. Dejerine-Sottas disease B. Krabbe’s disease C. Metachromatic leukodystrophy **D. Normal peripheral nerve** E. Charcot-Marie-Tooth disease ## Footnote Asection from normal sural nerve is illustrated

Answer 138

**A. Cysticercosis** B. Hemangioblastoma C. Juvenile pilocytic astrocytoma D. Renalcellcarcinoma E. Toxoplasmosis ## Footnote The lesion seen here is an example of cysticercosis (A). This specimen was excised from the fourth ventricle. The other responses are incorrect

Answer 139

**A. Arsenic toxicity** B. Lead toxicity C. Manganese toxicity D. Mercury toxicity ## Footnote Arsenic toxicity (A) is associated with insecticides and is manifested in its acute form by encephalopathy, peripheral neuropathy, abdominal pain, nau- s e a , v o m i t i n g , d i a r r h e a , a n d s h o c k .

Answer 140

**A. Arsenic toxicity** B. Lead toxicity C. Manganese toxicity D. Mercury toxicity ## Footnote Arsenictoxicity(chronic) Ch r o n i c a r s e n i c t o x i c i t y ( A) c a u s e s m a l a i s e , Mees’ transverse white lines on the ngernails, and increased pigmentation and hyperkeratosis of the palms and soles.

Answer 141

A. Arsenic toxicity **B. Lead toxicity** C. Manganese toxicity D. Mercury toxicity ## Footnote Lead poisoning (B) in children causes irritability, seizures, abdominal pain, ataxia, and coma.

Answer 142

A. Arsenic toxicity **B. Lead toxicity** C. Manganese toxicity D. Mercury toxicity ## Footnote In adults, lead poisoning (B) causes a pure motor demyelinating polyneuropathy often asso- ciated with wrist drop, anemia, and a gingival lead line.

Answer 143

A. Arsenic toxicity B. Lead toxicity C. Manganese toxicity **D. Mercury toxicity** ## Footnote Mercury poisoning (D) is associated with sh ingestion and expo- sure to felt hat dyes. Mercury poisoning leads to psychological dysfunction, tremor, movement disorders, peripheral neuropathy, and cerebellar signs.

Answer 144

A. Arsenic toxicity B. Lead toxicity **C. Manganese toxicity** D. Mercury toxicity ## Footnote Manganese toxicity (C) occurs in miners and causes Parkinson’s type symptoms that typically re- spond to levodopa. Neuronal loss and gliosis are observed in the pallidum and striatum.

Answer 145

A. Herpes zoster virus has been implicated in the pathogenesis. **B. It is often periventricular and brightly enhancing.** C. Steroid therapy should be initiated immediately. D. It is typically of T cell lineage. E. It is an unlikely diagnosis in immunocompromised patients. ## Footnote Primary CNS lymphoma is usually of B cell origin (D is false) and tends to occur in a periventricular location (B). Primary CNS lymphoma is more common in immunocompromised patients (E is false), and Epstein- Barr virus has been implicated in the pathophysiology of the disease in immunocompromised patients (A is false). Generally, an e ort is made to withhold steroid treatment until a tissue diagnosis is made, as steroids can decrease the diagnostic yield of tissue biopsy (Cis false).

Answer 146

A. Centralneurocytoma **B. Dysembryoplastic neuroepithelial tumor** C. Lymphoma D. Meningioma E. Schwannoma ## Footnote This H&E-stained section is an example ofdysembryoplastic neuroepithelial tumor (B). Note the “ oating neuron” in a microcyst surrounded by smaller neurocytic cells. The other answer choices are incorrect

Answer 147

A. Chromosome 10 deletions (PTEN) B. Epidermal growth factor receptor (EGFR) ampli cation C. p53 deletion D. None of the above E. Alloftheabove **F. AandB** G. BandC ## Footnote Primary glioblastomas are thought to arise de novo without any history of a prior known lower grade tumor. Primary glioblastomas tend to have normal p53 genes (C), overexpression of the epidermal growth factor receptor (EGFR [B]), and partial deletions of chromosome 10 near the phosphatase and tensin homologue (PTEN) gene (A). Secondary glioblastomas tend to lack overexpression of EGFR, but typically have a loss of heterozygosity of chromosome 17p leading to decreased p53 (C)

Answer 148

A. Chondrosarcoma B. Chordoma C. Glioblastoma **D. Gliosarcoma** E. Schwannoma ## Footnote This H&E-stained photomicrograph shows an example of gliosarcoma (D) with a mosaic pattern of sarcomatous and gliomatous foci. Cells in the glial portion tend to be GFAP positive, while cells in the sarcomatous areas tend to be GFAP negative.

Answer 149

A. Chromosome 3 B. Chromosome 10 C. Chromosome 17 **D. Chromosome 22** E. Alloftheabove ## Footnote At least half of all meningiomas have deletions or mutations involving chro- mosome 22 (D) involving the NF-2 gene. A wide variety of genetic aberra- tions have been described in meningiomas, but a reliable pattern has yet to be identi ed

Answer 150

A. Epithelial membrane antigen (EMA) B. Vimentin C. Progesterone receptor **D. Alloftheabove** E. None of the above ## Footnote Meningiomas tend to be strongly immunopositive for the intermediate la- mentproteinvimentin(B),whichisare ectionofthemesenchymalcharacter of meningiomas. This is not particularly useful diagnostically as other tumors in the di erential are often vimentin positive, such as metastatic carcinoma, glioma, melanoma, schwannoma, and hemangioblastoma. The epithelial nature of meningiomas is re ected by their immunopositivity to EMA (A), which helps to rule out schwannomas, melanomas, and hemangioblastomas. The vast majority of meningiomas show progesterone receptor (C) immu- nopositivity in their nuclei, but this tends not to be helpful diagnostically. The correct answer is D, all of the above

Answer 151

**A. Diffuse deposits of b-amyloid are sometimes present.** B. Lewybodiesareprominent. C. N-acetylaspartate content in the putamen and pallidum is increased. D. The clinical syndrome is present in up to one-half of professional boxers. E. There is a reduced incidence of cavum septum pellucidum in this disorder. ## Footnote Dementia pugilistica, or “punch-drunk” encephalopathy, is a clinical syn- drome characterized by dysarthric speech, slowness in thinking, and forget- fulness,along with slow,sti movements and a wide-based gait.Alarge series found that the syndrome occurs in approximately 17%of professional boxers (D is false), although radiographic changes may occur in up to one-half of boxers. Radiographic ndings include ventricular dilatation, sulcal widening, and an increased incidence of cavum septum pellucidum (E is false). Dif- fuse deposition of b-amyloid (A) is a not uncommon nding in the brains of patients with dementia pugilistica. Lewy bodies are not present, however (B is false). MRI spectroscopy reveals decreased levels of N-acetylaspartate in the putamen and pallidum that may be a result of neuronal loss in these regions (Cis false).

Answer 152

**A. Age , 3 years at diagnosis** B. Desmoplastic subtype on histology C. Extensive nodularity on histology D. Less than 1.5 cm2 postoperative residual tumor E. Nuclear positivity for b-catenin ## Footnote Medulloblastomas are the most common malignant brain tumor in children. High-risk patients are currently de ned as children with more than 1.5 cm2 postoperative tumor residual (D), those presenting at , 3 years of age (A), and those with metastases. Desmoplastic medulloblastoma (B) and medul- loblastoma with extensive nodularity (C) are thought to have a better prog- nosis. Large-cell and anaplastic medulloblastoma are associated with a poor prognosis. Nuclear positivity for b-catenin (E) is a marker of Wnt pathway activation, which has been associated with a better prognosis. High expres- sion of the myc and erbB2 oncogenes is associated with worse outcomes.

Answer 153

A. They are usually lled with keratin. B. They tend to be dorsally located. **C. They tend to occur in the midline.** D. Alloftheabove E. None of the above ## Footnote The lesion seen here is an example of a neurenteric cyst. Neurenteric cysts likely represent developmental abnormalities involving entrapment of devel- oping foregut tissue in the developing leptomeninges. They have a columnar epithelium that usually produces a mucinous (PAS positive) material into the cyst lumen (A is false). Typically they occur ventrally (B is false), in the midline (C).