Pathology Final

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30. A 39-year-old man goes to the physician because he has experienced diminished libido for the past 4 months. Review of systems indicates that he has had frequent headaches over the past 2 months. On physical examination, he has gynecomastia bilaterally, normal-sized testes in the scrotum, and difficulty with peripheral vision. His visual acuity is 20/20 bilaterally. Laboratory findings show Na+, 141 mmol/L; K+, 4.1 mmol/L; Cl-, 102 mmol/L; CO2, 25 mmol/L; glucose, 75 mg/dL; and creatinine, 1.2 mg/dL. Which of the following neoplasms is most likely to be diagnosed? (A) Adenophypophyseal adenoma (B) Carcinoid tumor (C) Medullary carcinoma (D) Pheochromocytoma (E) Renal cell carcinoma (F) Small-cell anaplastic carcinoma

(A) Adenophypophyseal adenoma

29. A 42-year-old woman has had increasing weakness, nausea, vomiting, watery diarrhea, and a 5-kg weight loss over the past 7 months. She has generalized muscle weakness, muscle wasting, and increased skin pigmentation on physical examination. After an upper respiratory tract infection lasting 1 week, she develops abdominal pain and faintness and lapses into a coma. On admission to the hospital, her temperature is 36.9ºC, pulse is 83/min, respirations are 17/min and shallow, and blood pressure is 80/40 mm Hg. Laboratory findings show hemoglobin, 13.6 g/dL; hematocrit, 43.8%; WBC count, 5420/mm3; Na+, 129 mmol/L; K+, 3.5 mmol/L; Cl-, 95 mmol/L; CO2, 23 mmol/L; glucose, 48 mg/dL; and creatinine, 0.6 mg/dL. Atrophy of which of the following tissues is most likely to be present? (A) Adrenal cortex (B) Islets of Langerhans (C) Hypothalamus (D) Parafollicular cells (E) Pineal gland (F) Thyroid epithelium

(A) Adrenal cortex

14. A 50-year-old woman has a 20-year history of Crohn disease. Over the past 14 months, she has had increasing fatigue with worsening peripheral edema. On physical examination, she has pitting edema to her knees. Laboratory studies show hemoglobin, 13.2 g/dL; hematocrit, 40.1%; platelet count, 203,000/mm3; and WBC count, 7470/mm3. Serum urea nitrogen is 35 mg/dL, and creatinine is 3.8 mg/dL. Urinalysis shows proteinuria without hematuria, glucosuria, or ketonuria. A renal biopsy specimen shows deposits of amorphous pink material in glomeruli, aterioles, and peritubular interstitium. By electron microscopy, these pink deposits are composed of nonbranching 7.5- to 10-nm fibrils. A Congo Red Stain is positive and shows apple green birefringence. Which of the following proteins is most likely to form these fibrils? (A) Amyloid-associated (B) Amyloid precursor protein (C) Atrial natriuretic peptide (D) Β2-microglobulin (E) Calcitonin (F) Lambda light chain (G) Transthyretin

(A) Amyloid-associated

4. A 24-year-old, previously healthy man who smokes one pack of cigarettes per day and who works as a histotechnologist has developed a cough with bloody sputum over the past 2 days. He has increasing lethargy and nausea. A chest radiograph shows diffuse infiltrates most pronounced in the lower lobes. Laboratory findings show hemoglobin, 13.7 g/dL; hematocrit, 40.6%; MCV, 91 µm3; platelet count, 361,000/mm3; WBC count, 7385/mm3; Na+, 144 mmol/L; K-, 4.3 mmol/L; Cl-, 1-3 mmol/L; CO2, 26 mmol/L; creatinine, 3.8 mg/dL; urea nitrogen, 36 mg/dL; and glucose, 75 mg/dL. An abdominal ultrasound scan shows normal-sized kidneys. A renal biopsy specimen shows a crescentic glomerulonephritis. Which of the following mechanisms most likely produced this patient's pulmonary disease? (A) Antibody directed against basement membrane collagen (B) Apoptosis induced by CD8+ lymphocytes (C) Complement activation by circulating antigen-antibody complexes (D) Macrophage activation by CD4+ lymphocytes (E) Release of inflammatory mediators from mast cells

(A) Antibody directed against basement membrane collagen

60. A 43-year-old woman has had increasing difficulty swallowing over the past year. She notices that her hands turn white and are painful on exposure to the cold. She remarks, "I may be getting older, but at least I don't have any wrinkles on my face or hands yet." On physical examination, her temperature is 37ºC, pulse is 68/min, respirations are 14/min, and blood pressure is 115/75 mm Hg. The skin of her face and hands appears taut and shiny. A punch biopsy specimen of the skin of the hand shows dermal collagenous fibrosis and focal calcification. She receives yearly esophageal dilation for the next 20 years, during which time she receives no serious illnesses. Which of the following serologic test results is most likely to be positive? (A) Anticentromere antibody (B) Anti-DNA topoisomerase antibody (C) Antigliadin antibody (D) Antimicrosomal antibody (E) Antimitochondrial antibody (F) ANCA

(A) Anticentromere antibody

13. A 75-year-old woman has had a constant, dull pain in her back that has persisted for more than a month. She is in no acute distress. On physical examination, there are no abnormal findings. Laboratory findings include serum Na+, 141 mmol/L; K+, 4.4 mmol/L; Cl-, 103 mmol/L; CO2, 28 mmol/L; glucose, 101 mg/dL; creatinine, 0.9 mg/dL; urea nitrogen, 17 mg/dL; total protein, 6.8 g/dL; albumin, 4.2 g/dL; total bilirubin, 0.8 mg/dL; AST, 25 U/L; ALT, 29 U/L; calcium, 10.8 mg/dL; phosphorus, 2.3 mg/dL; and alkaline phosphatase, 228 U/L. Parathormone-related peptide is increased. What is the most likely diagnosis? (A) Bone metastases (B) Chondrosarcoma (C) Chronic cholecystitis (D) Osteoarthritis (E) Osteoporosis (F) Paget disease of bone

(A) Bone metastases

35. A 10-year-old girl has a respiratory tract infection and is treated with trimethoprim-sulfamethoxazole. Three days later, she develops a sore throat, malaise, fever, and a macular skin rash on the trunk and extremities. Some of the skin lesions have a central raised area of more pronounced erythema. Within a few days, there are erosions of the oral mucosa and small blisters developing on purpuric skin macules. The blisters enlarge slightly and then show epidermal detachment. The total body surface area involved with blistering and detachment is less than 10%. This disease process is most likely mediated by what inflammatory cell type? (A) CD8+ lymphocytes (B) Eosinophils (C) Langerhans cells (D) Macrophages (E) Neutrophils (F) Natural killer cells

(A) CD8+ lymphocytes

7. A 40-year-old man has been taking daily insulin injections for the past 25 years. When he does not arrive at work, a friend visits his house and finds him on the floor in an obtunded state. He is taken to the hospital by ambulance. On admission to the hospital, he cannot be aroused. He is afebrile, with a pulse of 90/min, respirations of 17/min, and blood pressure of 90/60 mm Hg. Laboratory studies show a hemoglobin A1c concentration of 8.9%, serum glucose level of 11 mg/dL, and serum osmolality of 295 mOsm/kg. Urinalysis shows 4+ ketonuria with a specific gravity of 1.010. Which of the following statements best characterizes these findings? (A) He is in poor glycemic control, and has had an insulin overdose (B) He is in good glycemic control, but has developed ketoacidosis (C) He is in poor glycemic control, and is not taking his insulin (D) He is in good glycemic control, but has not eaten food recently (E) He is in poor glycemic control, and has developed a hyperosmolar coma

(A) He is in poor glycemic control, and has had an insulin overdose

65. A 43-year-old woman has had easy fatigability along with pain and stiffness of both wrist joints and other small joints of the hands for the past 7 years. The stiffness is marked in the morning and abates as the day goes by. X-rays of her hands reveal narrowing of the proximal interphalangeal and metacarpophalangeal joint spaces from synovitis and erosion of the cartilage. Laboratory tests show Hgb 8.4 g/dL, Hct 23.5, MCV 65 fL, and MCH 23 pg. Her peripheral blood smear shows hypochromic, microcytic red blood cells. Her serum iron and iron binding capacity levels are low and the ferritin level elevated. A high level of which of the following is most likely related to the causation of anemia in this woman? (A) C-reactive protein (B) GM-CSF (C) Hepcidin (D) IgG (E) IL-1β

(A) Hepcidin

41. For the past month, a 33-year-old woman has had burning epigastric pain and nausea and vomiting. An upper gastrointestinal endoscopic study shows multiple 1-cm shallow gastric antral and proximal duodenal ulcerations. She is treated with omeprazole and improves. One year later, she has an episode of severe, colicky lower abdominal pain and hematuria and passes a calcium oxalate calculus. She notes galactorrhea 1 month later, and over the next 2 months ceases to menstruate. She is given a dopamine agonist and improves. Laboratory findings show Na+, 140 mmol/L; K+, 4 mmol/L; Cl-, 101 mmol/L; Co2, 25 mmol/L; calcium, 11.1 mg/dL; phosphorus, 2.4 mg/dL; and creatinine, 1.1 mg/dL. Which of the following gene mutations with associated neoplasms is most likely to develop in this patient? (A) MENI—islet cell adenoma (B) RET—medullary carcinoma (C) BCL6—non-Hodgkin lymphoma (D) APC—osteoma (E) RET—pheochromocytoma (F) VHL—renal cell carcinoma

(A) MENI—islet cell adenoma

18. Over the past 6 months, a 42-year-old man has experienced increasing fatigue and a 6-kg weight gain, predominantly in a truncal distribution. On physical examination, his temperature is 37.1°C, pulse is 77/min, respirations are 14/min, and blood pressure is 165/105 mm Hg. He exhibits proximal muscle weakness. Laboratory findings include a fasting serum glucose level of 155 mg/dL, an 8:00 A.M. serum cortisol level that is elevated at 54 µg/dL, and an elevated serum corticotrophin level at 63 pg/mL. His serum cortisol level does not decrease with a low dose of dexamethasone, but decreases by 70% with a high dose. What test would be most helpful in establishing his diagnosis? (A) MRI of the brain (B) Abdominal CT scan of the adrenals (C) Serum assay for glycosylated hemoglobin (D) Biopsy of the gastrocnemius (E) Assay for urinary catecholamine metabolites

(A) MRI of the brain

72. A 12-year-old boy develops fever, accompanied by occasional headaches, malaise, fatigue, and nausea after being bitten by a dog. One day later, he experiences episodes of rigidity, hallucinations, breathe holding, and difficulty swallowing because of uncontrollable oral secretions. Dr. Louis Pasteur is called upon. "The death of this child appearing to be inevitable, I decided, not without lively and sore anxiety, as may well be believed, to try...the method which I had found constantly successful with dogs. Consequently, 60 hours after the bites [the child] was inoculated under a fold of skin with half a syringeful of the spinal cord of a rabbit. In the following days, fresh inoculations were made. I thus made 13 inoculations." The boy survived. Which of the following pathologic findings is most characteristic of the boy's disease? (A) Anterior horn cell loss (B) Gummatous necrosis (C) Multinucleated giant cells (D) Necrotizing vasculitis (E) Negri bodies (F) Pseudocysts with bradyzoites (G) Spongiform encephalopathy

(A) Negri bodies

66. A 70-year-old man has had increasing exercise intolerance and difficulty breathing for the past year. His family has noted memory loss and decreased ability to perform activities of daily living for the past 2 years. On physical examination, his temperature is 37.1°C, pulse is 70/min, respirations are 18/min, and blood pressure is 140/80 mm Hg. On auscultation of the chest, rales are audible in the lung bases, and there is a diastolic murmur. He has a marked decrease in sensation to light touch and pinprick over the lower extremities. His gait is ataxic, with the feet widely spaced. He cannot name any of three objects after 3 minutes. He thinks he is an astronaut returned from Mars. An echocardiogram shows aortic, regurgitation with a widened aortic root and arch. MRI of the brain shows mild diffuse cortical atrophy and meningeal thickening. Infection with what organism would most likely produce these findings? (A) Borrelia burgdorferi (B) Coxackiervirus B (C) HIV (D) Mycobacterium leprae (E) Mycobacterium tuberculosis (F) Treponema pallidum (G) West Nile virus

(A) Treponema pallidum

6. A 58-year-old man reports increasing malaise over the past 8 months. He recently developed a cough productive of yellowish sputum, and a sputum culture grew Streptococcus pneumoniae. On physical examination, he has no lymphadenopathy or hepatosplenomegaly. Laboratory studies show serum creatinine, 4 mg/dL; urea nitrogen, 38 mg/dL; total protein, 9.3 g/dL; albumin, 4.1 g/dL; and alkaline phosphatase, 297 U/L. The finding on serum protein electrophoresis is shown in the figure. Which of the following laboratory findings is most likely to be reported? (A) TdT+ circulating blasts (B) Bence Jones proteinuria (C) Bone marrow karyotype with t(8;14) (D) Reactive amyloidosis (E) Hematocrit of 62%

(B) Bence Jones proteinuria

38. A 4-year-old girl has become increasingly listless over the past year. The child is at the 35th percentile for height and weight. On physical examination, there is pubic hair and clitoral and breast enlargement. There is no hepatomegaly, splenomegaly, or lymphadenopathy. The neurologic examination is unremarkable. Laboratory findings show hemoglobin, 13.7 g/dL; hematocrit, 41.8%; WBC count, 7120/mm3; Na+, 128 mmol/L; K+, 4.8 mmol/L; Cl-, 99 mmol/L; CO2, 21 mmol/L; glucose, 69 mg/dL; and creatinine, 0.5 mg/dL, and ACTH of 95 pg/mL with loss of diurnal rhythm of secretion. What disease process is most likely associated with these findings? (A) Anaplastic carcinoma of the thyroid (B) Bilateral adrenal hyperplasia (C) Islet cell adenoma (D) Medullary carcinoma of the thyroid (E) Neuroblastoma of the adrenal (F) Pituitary microadenoma (G) Suprasellar craniopharyngioma

(B) Bilateral adrenal hyperplasia

50. A 25-hear-old man has had increasingly frequent infections over the past 5 years. His most recent respiratory infection was due to Streptococcus pneumoniae. He now has watery diarrhea. On physical examination, he is below ideal weight. There is a vesicular rash in the T10 dermatomal distribution on the left side. Laboratory findings include hemoglobin, 14.3 g/dL; hematocrit, 43.2%; platelet count, 290,600/mm3; and WBC count, 7200/mm3 with 55% segmented neutrophils, 2% bands, 35% lymphocytes, 6% monocytes, and 2% eosinophils. Quantitative immunoglobulins include IgA of 22 mg/dL, IgG of 175 mg/dL, and IgM of 40 mg/dL. Lymphocyte subsets by flow cytometry show CD4+ cells (absolute) of 630/µL, CD8+ cells (absolute) of 785/µL, B cells of 280/µL, and T cells of 2010/µL. A stool culture is negative for bacterial pathogens, but a stool culture for ova and parasites shows Giardia lamblia cysts. What is the most likely diagnosis? (A) Chronic granulomatous disease (B) Common variable immunodeficiency (C) Hyper-IgM syndrome (D) Leukocyte adhesion deficiency (E) Severe combined immunodeficiency

(B) Common variable immunodeficiency

16. A 68-year-old man has had increasing dyspnea with cough productive of frothy sputum for the past 5 months. On physical examination, he is afebrile, and his blood pressure is 165/100 mm Hg. There is dullness to percussion at lung bases. He has pitting edema of the ankles. A chest radiograph shows blunting of costophrenic recesses bilaterally and cardiomegaly with prominent right and left heart borders. A right thoracentesis is performed, and 300 mL of straw-colored fluid is removed. Laboratory studies on this fluid show total protein of 2.2 g/dL (serum is 6.5 g/dL), glucose of 45 mg/dL (serum is 75 mg/dL), lactate dehydrogenase of 200 U/L (serum is 420 U/L), pH 7.2, and cell count of 100/mm3 mononuclear leukocytes, and no red blood cells. What condition does he most likely have? (A) Cavitary tuberculosis (B) Congestive heart failure (C) Malignant mesothelioma (D) Non-Hodgkin lymphoma (E) Pneumococcal pneumonia

(B) Congestive heart failure

14. A 17-year-old girl has had frequent nosebleeds since childhood. Her gums bleed easily, even with routine tooth brushing. She has experienced menorrhagia since menarche at age 14. On physical examination, there are no abnormal findings. Laboratory studies show hemoglobin, 14.1 g/dL; hematocrit, 42.5%; MCV, 90 µm3; platelet count, 277,400/mm3; and WBC count, 5920/mm3. Her platelets fail to aggregate in response to ADP, collagen, epinephrine, and thrombin. The ristocetin agglutination test result is normal. There is a deficiency of glycoprotein IIb/IIIa. Prothrombin time is 12 seconds, and partial thromboplastin time is 28 seconds. What is the most likely diagnosis? (A) Disseminated intravascular coagulation (B) Glanzmann thrombasthenia (C) Immune thrombocytopenic purpura (D) Vitamin C deficiency (E) Von Willebrand disease

(B) Glanzmann thrombasthenia

28. A 59-year-old man comes to the physician seeking a prescription for sildenafil after seeing television advertisements regarding erectile dysfunction. He is 168 cm (5 ft 6 in) tall and weighs 93 kg (body mass index 33). On physical examination, there are bilateral carotid bruits and a midline palpable abdominal pulsatile mass. Decreased hair is noted over the lower extremities, and a 1-cm shallow ulceration is present in the skin over the right first metatarsal head. He has decreased sensation to light touch and pinprick in the lower extremities. Laboratory findings include hemoglobin, 12.9 g/dL; hematocrit, 42%; WBC count, 8950/mm3; Na+, 140 mmol/L; K+, 4.2 mmol/L; Cl-, 105 mmol/L; CO2, 26 mmol/L; glucose, 144 mg/dL; and creatinine, 1.7 mg/dL. Which of the following laboratory findings is most likely to be present in this man? (A) Plasma ACTH 119 pg/mL (B) Hemoglobin A1c 8.8% (C) Plasma homocysteine 23 µmol/L (D) Cerebrospinal fluid oligoclonal IgG bands (E) Serum anti-parietal cell antibodies

(B) Hemoglobin A1c 8.8%

12. Several children 6 to 10 years old in the same community have been reported by a local physician to have similar symptoms. They are all doing poorly in school, which has been attributed to behavioral problems. Their parents state that these children have poor appetites, complain of nausea, and have frequent headaches. On physical examination, they have decreased sensation to touch over the lower extremities. They exhibit loss of fine motor control of movement and have a slightly ataxic gait. A representative CBC shows hemoglobin count of 282,300/mm3, and WBC count of 4745/mm3. Examination of the peripheral blood smear shows basophilic stippling of the RBCs. Serum chemistries show Na+, 144 mmol/L; K+, 4.4 mmol/L; Cl-, 105 mmol/L; CO2, 26 mmol/L; glucose, 69 mmol/L; creatinine, 1.4 mg/dL; calcium, 7.7 mg/dL; total protein, 6.6 g/dL; albumin, 4.3 g/dL; AST, 43 U/L; ALT, 28 U/L; alkaline phosphate, 189 U/L; and total bilirubin, 1.1 mg/dL. Excessive chronic ingestion of which of the following substances is most likely to explain these findings? (A) Fluoride (B) Lead (C) Methanol (D) Monosodium glutamate (E) Vitamin A (F) Zinc

(B) Lead

61. A 56-year-old man has had increasing lower leg swelling during the past 6 months. Also, he has had so much difficulty breathing at night that he sleeps propped up on two pillows. On physical examination, his temperature is 37.1°C, pulse is 80/min, respirations are 17/min, and blood pressure is 110/70 mm Hg. On auscultation of the chest, bilateral crackles are audible at the lung bases. The liver span is increased. There is 2+ pitting edema to the thighs. Laboratory findings show hemoglobin, 13.4 g/dL; hematocrit, 40.2%; MCV, 88 µm3; platelet count, 229,300/mm3; and WBC count, 6715/mm3. He develops an acute psychosis 1 year later. He dies of aspiration pneumonia. At autopsy, there is anterior vermian atrophy and petechial hemorrhages with brown discoloration in the periaqueductal gray matter and shrunken mamillary bodies. A chronic deficiency of which of the following vitamins would most likely explain these findings? (A) Vitamin A (retinoic acid) (B) Vitamin B1 (thiamine) (C) Vitamin B2 (riboflavin) (D) Vitamin B3 (niacin) (E) Vitamin B12 (cobalamin) (F) Vitamin C (ascorbic acid) (G) Vitamin D (cholecalciferol) (H) Vitamin E (α-tocopherol)

(B) Vitamin B1 (thiamine)

16. A 30-year-old man visits the physician because he has had joint pain in the right hip and left elbow and a headache for the past week. One month ago, he had similar pain in the left hip and knee, which slowly resolved. He remembers having a ringlike skin rash on his left thigh several months ago after a tick bite. On physical examination, there is joint tenderness, but no swelling or deformity of the right hip and left elbow. His heart rate is slightly irregular. What infectious agent is most likely to produce these findings? (A) Streptococcus pyogenes (B) Staphylococcus aureus (C) Borrelia burgdorferi (D) Mycobacterium tuberculosis (E) Parvovirus B19 (F) Yersinia enterocolitica

(C) Borrelia burgdorferi

3. A 68-year-old man has had worsening dyspnea and orthopnea for the past 3 years with increased production of frothy sputum. On examination, crackles are ausculated at lung bases. A chest radiograph shows bilateral interstitial infiltrates, distinct Kerley B lines, and a prominent left heart border. Laboratory studies show Na+, 135 mmol/L; K+, 3.8 mmol/L; Cl-, 99 mmol/L; CO2, 25 mmol/L; glucose, 76 mg/dL; creatinine, 1.5 mg/dL; and urea nitrogen, 30 mg/dL. Fractional excretion of sodium is less than 1%. Plasma rennin, aldosterone, and antidiuretic hormone levels are all increased. Brain-type natriuretic peptide (BNP) is 200 pg/mL (normal<100 pg/mL). What is the most likely diagnosis? (A) Addison disease (B) Chronic glomerulonephritis (C) Congestive heart failure (D) Conn syndrome (E) Pulmonary fibrosis (F) SIADH

(C) Congestive heart failure

58. A 29-year-old man sees his physician because of burning pain on urination that has persisted for 3 days. There is a urethral discharge. A sample of the exudate is positive by ELISA for Chlamydia trachomatis. The man has increasing stiffness of the knees and ankles and lower back pain 3 weeks later. A radiograph of the lumber spine shows narrowing with sclerosis of the sacroiliac joints. One month later, he develops painful erythema of the penile glans, and the conjunctivae are red. A follow-up examination shows a slightly irregular heart rate and a murmur suggestive of aortic regurgitation. The back pain continues off and on for 5 more months. Which of the following test results is most likely to be positive? (A) ANCA (B) ANA (C) HLA-B27 antigen (D) Lyme disease (E) Purified protein derivative (F) Rapid plasma reagin (G) Rheumatoid factor (H) U1-RNP

(C) HLA-B27 antigen

2. A 29-year-old woman has had fatigue with dizziness for the past 5 months. On physical examination, she has an erythematous malar rash. She has no lymphadenopathy, but there is a palpable spleen tip. She is afebrile. Laboratory studies show hemoglobin, 8.9 g/dL; hematocrit, 27.8%; MCV, 103 µm3; RBC distribution width index, 22; WBC count, 8560/mm3; platelet count, 222,000/mm3; and reticulocyte count, 3.3%. The peripheral blood smear shows polychromasia, but no schistocytes. Her serum total bilirubin is 3.2 mg/dL with direct bilirubin 0.8 mg/dL, and haptoglobin is 5 mg/dL. Antinuclear antibody and anti-double-stranded DNA tests are positive. What additional laboratory test finding is she most likely to have? (A) D-dimer 10 µg/mL (B) Increased RBC osmotic fragility (C) Positive Coombs test (D) Serum cobalamin (vitamin B12) 50 pg/mL (E) Serum ferritin 240 ng/mL

(C) Positive Coombs test

57. A 37-year-old primigravida at 30 weeks' gestation has noted increasing pedal edema for the past 2 weeks. During the past week, she has developed headaches and confusion, and she has decreased urine output. She exhibited seizure activity and then lapsed into a coma. On physical examination, her temperature is 36.8ºC, pulse is 82/min, respirations are 18/min, and blood pressure is 145/95 mm Hg. Her heart rate is regular, and lung fields are clear. The abdomen is soft, and bowel sounds are present. There is pitting edema to the thighs. No vaginal bleeding is noted, and the cervix is not effaced. Laboratory findings show hemoglobin, 11.9 g/dL; hematocrit, 35.8%; platelet count, 73,000/mm3; WBC count, 8180/mm3; glucose, 151 mg/dL; total protein, 6.6 g/dL; albumin, 3.2 g/dL; total bilirubin, 2.3 mg/dL; AST, 78 U/L; ALT, 93 U/L; alkaline phosphatase, 253 U/L; and prothrombin time, 32 seconds. Urinalysis shows specific gravity of 1.024, pH 6, 4+ proteinuria, 1+ glucosuria, and no blood. An ultrasound examination shows a viable 30-week fetus. What condition is most likely present in this patient? (A) Abruptio placentae (B) Budd-Chiari syndrome (C) Dilated cardiomyopathy (D) HELLP syndrome (E) Hydatidiform mole (F) Reye syndrome (G) Sheehan syndrome

(D) HELLP syndrome

1. A 47-year-old white man has had increasing orthopnea and worsening pedal edema for the past 3 years. He complains of worsening arthritis involving his hands, knees, hips, and elbows. On physical examination, he has decreased range of motion of the lower legs, but no apparent joint deformities, warmth, or swelling. There is a brownish hue to his skin, although it is winter, and he rarely goes outdoors. Laboratory findings show hemoglobin, 13.7 g/dL; hematocrit, 40.8%; MCV, 90 µm3; platelet count, 213,500/mm3; WBC count, 6690/mm3; Na+, 141 mmol/L; K+, 4.2 mmol/L; Cl-, 101 mmol/L; CO2, 24 mmol/L; glucose, 201 mg/dL; creatinine, 1.2 mg/dL; and calcium, 8.2 mg/dL. Which of the following underlying diseases most likely explains these findings? (A) β-Thalassemia minor (B) Diabetes mellitus type 1 (C) Familial hypercholesterolemia (D) Hereditary hemochromatosis (E) Rheumatoid arthritis

(D) Hereditary hemochromatosis

8. A 31-year-old woman has experienced menorrhagia for the past year. She has developed easy bruisability to her skin, even with minor trauma, over the past month. She has multiple contusions of varying ages seen over her torso and extremities on physical examination. She has no difficulty with movement. No neurologic deficits are noted. Prothrombin time is 12.5 seconds, and partial thromboplastin time is 27 seconds. Hemoglobin is 13.3 g/dL, hematocrit is 42.1%, MCV is 95 µm3, platelet count is 25,000/mm3, and WBC count is 7500/mm3. A bone marrow biopsy specimen shows increased numbers of megakaryocytes. What is the most likely diagnosis? (A) Acute promyelocytic leukemia (B) Antiphospholipid syndrome (C) Hemophilia A (D) Immune thrombocytopenic purpura (E) Von Willebrand disease

(D) Immune thrombocytopenic purpura

10. A 54-year-old man has had nausea for the past 6 months, but he does not report hematemesis. He has increasing malaise. On physical examination, he has decreased sensation to pinprick and light touch over the lower extremities bilaterally. He exhibits mild ataxia when walking. An upper gastrointestinal endoscopy study shows the absence of gastric rugal folds, but no ulceration or mass. Which of the following laboratory findings is most likely to be reported? (A) Positive anti-Smith antibody (B) Deficiency of factor V (C) Positive Helicobacter pylori antibody (D) MCV 125 µm3 (E) Urine glucose 4+

(D) MCV 125 µm3

20. A 38-year-old woman has had malaise and arthralgias for the past 14 months. Over the past month, she has developed areas of purpura on the distal extremities. On physical examination, her temperature is 37ºC, pulse is 81/min, respirations are 14/min, and blood pressure is 140/90 mm Hg. She has scleral icterus and 1- to 3-cm areas of reddish purple discoloration on her skin. Several of these areas show focal ulceration. Laboratory findings show total protein, 7.1 g/dL; albumin, 3.3 g/dL; AST, 87 U/L; ALT, 95 U/L; alkaline phosphatase, 80 U/L; total bilirubin, 4 mg/dL; and direct bilirubin, 3.1 mg/dL. Serologic test results are positive for anti-HCV and negative for anti-HBs and IgM anti-HAV. Urinalysis shows 4+ proteinuria and 1+ hematuria. CT scan of the abdomen shows a small amount of ascites, mild hepatomegaly, and no splenomegaly or lymphadenopathy. A biopsy specimen of an ulcerated skin lesion shows leukocytoclastic vasculitis involving the upper dermis. What is the most likely diagnosis? (A) Autoimmune hemolytic anemia (B) Hepatocellular carcinoma (C) Hereditary hemochromatosis (D) Mixed cryoglobulinemia (E) Multiple myeloma

(D) Mixed cryoglobulinemia

24. Over the past 2 years, a 44-year-old man has noticed a decline in the dexterity of his right hand in his work as an auto mechanic. His right hand strength is weaker than the left. He experienced painful burning sensations in the left upper extremity 1 year ago. He has been bothered by decreased visual acuity in the left eye for the past month. He is insensitive to heat, and on taking a hot shower, his vision worsens. On physical examination, he is afebrile, and his blood pressure is normal. Motor strength in the right extremity is 4/5, but 5/5 elsewhere. Vision is 20/100 in the left eye and 20/40 in the right eye. One year later, he reports chronic constipation and urinary urgency, hesitancy, and incontinence. An MR image of the brain is shown in the figure. What is the most likely diagnosis? (A) Diabetes mellitus (B) Graves disease (C) HIV infection (D) Multiple sclerosis (E) Myasthenia gravis (F) Systemic lupus erythematosus

(D) Multiple sclerosis

34. A 14-year-old girl who has been in foster care for the past 11 years has not been with one caregiver for more than 1 year at a time. She is brought to the physician by the most recent caregiver, who obtained custody of the child 1 week ago. On physical examination, there are ecchymoses of the trunk, extremities, and gingiva hyperkeratotic, popular rash, with 0.4-cm lesions ringed by hemorrhage, is present in a similar distribution. The child has pain on the movement of the arms and legs. There is abnormal depression of the sternum with prominence of the ribs and the costochondral junctions. Radiographs of the arms and legs show bowing of the long bones and widening of the metaphyses, with normal calcification. There is a right femoral subperiosteal hematoma. No fractures are noted. CBC shows hemoglobin of 10.8 g/dL, hematocrit of 32.4%, MCV of 77 µm3, platelet count of 201,300/mm3, and WBC count of 5730/mm3. What most likely explains these findings? (A) CFTR gene mutation (B) Inhibitor of procoagulant factor VIII (C) Collagen gene mutation (D) Vitamin C deficiency (E) Multiple blunt trauma

(D) Vitamin C deficiency

20. A 39-year-old man experiences sudden onset of a severe headache. Physical examination shows no localizing neurologic signs and no organomegaly. A stool sample is positive for occult blood. Areas of purpura appear on the skin of his extremities. Laboratory studies show hemoglobin of 9.6 g/dL, hematocrit of 28.9%, platelet count of 26,400/mm3, and WBC count of 75,000/mm3. The peripheral blood smear has the appearance shown in the figure; schistocytes also are seen. The plasma D-dimer level (fibrin degradation products), prothrombin time, and partial thromboplastin time are all elevated. Cytogenetic analysis of cells from a bone marrow biopsy specimen is most likely to yield what karyotypic abnormality? (A) t(8;21) (B) t(9;22) (C) t(14;18) (D) t(15;17) (E) t(8;14)

(D) t(15;17)

13. A 45-year-old, previously healthy woman has had a chronic nonproductive cough for the past 2 months. During the past 3 weeks, she has had increasing dyspnea and arthralgias. One week ago, her cough was productive of blood-streaked sputum. She does not smoke. Physical examination shows temperature of 37.5ºC, pulse of 77/min, respirations of 17/min, and blood pressure of 140/90 mm Hg. On auscultation, bilateral crackles are audible in the lungs. A chest radiograph shows bilateral nodular and cavitary infiltrates, but there are no masses. Laboratory findings show hemoglobin, 11.7 g/dL; hematocrit, 35.2%; platelet count, 217,000/mm3; WBC count, 6330/mm3, serum glucose, 72 mg/dL; creatinine, 2.6 mg/dL; and urea nitrogen, 25 mg/dL. Urinalysis shows specific gravity of 1.017, pH 6.5, 1+ proteinuria, 2+ hematuria, and now glucose or ketones. A transbronchial biopsy specimen shows necrotizing granulomatous vasculitis of the alveolar capillaries and small peripheral pulmonary arteries. A rental biopsy specimen shows a crescentic glomerulonephritis. Which of the following serologic test results is most likely to be positive? (A) Anti-DNA topoisomerase I (B) Anti-glomerular basement membrane antibody (C) Anti-Jo-1 antibody (D) Antimitochondrial antibody (E) C-ANCA (F) ANA (G) Antiribonucleoprotein antibody

(E) C-ANCA

7. A 20-year-old man has sudden onset of severe abdominal and back pain and dyspnea. His medical history indicates similar episodes over a 12-year period. He had osteomyelitis of the left hip 1 year ago; the bone culture was positive for Salmonella enteritidis. On physical examination, his lungs are clear to auscultation, but he has tachycardia. Palpation of the abdomen reveals diffuse tenderness with rigidity of abdominal musculature, but no apparent masses. CT scan of the chest shows prominent pulmonary veins, but no infiltrates. Abdominal CT scan shows the presence of multiple 0.5- to 1-cm stones in the gallbladder, a very small spleen, and prominent hepatic veins. An abdominal radiograph shows no free air. CBC shows hemoglobin of 10.2 g/dL, hematocrit of 30.9%, MCV of 99 m3, RDW of 22, platelet count of 189,300/mm3, and WBC count of 6230/mm3. What additional laboratory test finding is most likely to be reported? (A) Amylase 694 U/L (B) Positive anticardiolipin antibody (C) Calcium 12.3 mg/dL (D) Ferritin 710 ng/mL (E) Haptoglobin 1 mg/dL

(E) Haptoglobin 1 mg/dL

17. A 9-year-old girl has become increasingly listless over the past year. On physical examination, she has pitting edema to the thighs, muscle wasting, a protuberant abdomen with a fluid wave, areas of scaling skin with decreased pigmentation, and patches of hair that are irregularly pigmented. No ecchymoses are noted. She is 75% of ideal body weight, but her height is normal. Which of the following laboratory findings is most likely to be present? (A) Hyperhomocysteinemia (B) Hyperuricemia (C) Hypercalcemia (D) Hypoprothrombinemia (E) Hypoalbuminemia (F) Hypoinsulinemia

(E) Hypoalbuminemia

48. A 41-year-old woman has had headaches with blurred vision for the past 3 days. Over the past day, she has developed increasing mental confusion. On admission to the hospital, her temperature is 37.9ºC, pulse is 104/min, respirations are 25/min, and blood pressure is 70/40 mm Hg. On physical examination, she has petechial hemorrhages over her arms and trunk. A stool sample is positive for occult blood. Laboratory findings show hemoglobin of 9.1 g/dL, hematocrit of 27.2%, MCV of 92 µm3, RDW of 19%, platelet count of 8900/mm3, and WBC count of 8950/mm3. The peripheral blood smear shows schistocytes. A serum electrolyte panel shows Na+, 147 mmol/L; K+, 5 mmol/L; Cl-, 105 mmol/L; CO2, 26 mmol/L; creatinine, 3.3 mg/dL; urea nitrogen, 32 mg/dL; and glucose, 80 mg/dL. Ultra-large multimers of von Willebrand factor are present in plasma. What therapy should she receive emergently? (A) 2 U of packed RBCs (B) 6-pack of platelets (C) Dobutamine (D) Exploratory laparotomy (E) Plasmapheresis (F) Prednisone

(E) Plasmapheresis

19. A 51-year-old man has had increasing lethargy over the past year. On physical examination, his temperature is 37ºC, pulse is 80/min, respirations are 15/min, and blood pressure is 145/90 mm Hg. He has deformity with increased size, and there is decreased range of motion of the first three metacarpophalangeal (MCP) joints on the right and the second two MCP joints on the left. There is a 2-cm, firm, painless nodule over the left olecranon bursa. A similar 1-cm nodule is palpated in the helix of the right ear, and another 1.5 cm nodule is palpable over the right Achilles tendon. Urinalysis shows specific gravity of 1.012, pH 5.5, 1+ hematuria, 1+ proteinuria, and no glucose. The serum urea nitrogen level is 31 mg/dL, and the creatinine is 3.2 mg/dL. The total serum cholesterol is 222 mg/dL. Aspiration of material from the nodule at the left elbow is performed. Which of the following types of crystals is most likely to be seen microscopically in this aspirate? (A) Calcium pyrophosphate dihydrate (B) Cholesterol (C) Cystine (D) Hydroxyapatite (E) Sodium urate

(E) Sodium urate

36. Within the past 24 hours, a 26-year-old, previously healthy woman has developed a high fever and generalized diffuse erythematosus macular rash resembling a sunburn. She is menstruating, and her menstrual cycles are regular. She has nausea, vomiting, abdominal pain, diarrhea, myalgias, sore throat, headache, and dizziness. On physical examination, her temperature is 39.4ºC, pulse is 101/min, respirations are 18/min, and blood pressure is 90/40 mm Hg. She has oropharyngeal and conjunctival hyperemia. The vaginal mucosa is erythematosus. A tampon is present in the vaginal vault. She is disoriented, but there are no neurologic deficits. Laboratory findings show hemoglobin, 13.5 g/dL; hematocrit, 41.4%; platelet count, 100,000/mm3; WBC count, 11,200/mm3; glucose, 70 mg/dL; creatinine, 2.5 mg/dL; total bilirubin, 2.4 mg/dL; AST, 82 U/L; and ALT, 29 U/L. A chest radiograph shows no abnormal findings. She receives supportive therapy of nafcillin with clindamycin and improves, but skin and mucous membrane desquamation is noted 10 days later. These findings are most likely produced by an exotonin elaborated by which of the following organisms? (A) Bacillus anthracis (B) Clostridium perfringens (C) Enterococcus (D) Listeria monocytogenes (E) Staphylococcus aureus (F) Vibrio cholerae

(E) Staphylococcus aureus

47. A 29-year-old man has had a low-grade fever for the past 2 weeks. He has had increasing fatigue and a 2-kg weight loss during this time. On physical examination, his temperature is 37.5ºC, pulse is 80/min, respirations are 17/min, and blood pressure is 150/70 mm Hg. His spleen tip is palpable, and there is left upper quadrant tenderness. There is bilateral costovertebral angle tenderness. A diastolic murmur is heard at the left sternal border. Subungual hemorrhages are noted on the digits of his hands. A needle track is present in the left antecubital fossa. Laboratory findings show hemoglobin, 13.6 g/dL; hematocrit, 41.8%; platelet count, 228,000/mm3; WBC count, 11,200/mm3; glucose, 66 mg/dL; AST, 101 U/L; ALT, 28 U/L; alkaline phosphatase, 89 U/L; amylase, 45 U/L; and total bilirubin, 0.9 mg/dL. Urinalysis shows 1+ hematuria, and WBCs and WBC casts. A chest radiograph shows a 3-cm nodule with an air-fluid level in the right upper lobe. What organism is most likely to be cultured from his blood? (A) Candida albicans (B) Cryptococcus neoformans (C) Escherichia coli (D) Listeria monocytogenes (E) Staphylococcus aureus (F) Streptococcus pyogenes (G) Yersinia enterocolitica

(E) Staphylococcus aureus

15. A 41-year-old woman has had increasing lethargy and weakness over the past 3 years. She complains of being cold most of the time and wears a sweater in the summer. One year ago, she had menorrhagia, but now she has oligomenorrhea. She has difficulty concentrating, and her memory is poor. She has chronic constipation. On physical examination, her temperature is 35.5°C, pulse is 54/min, respirations are 13/min, and blood pressure is 110/70 mm Hg. She has alopecia, and her skin appears coarse and dry. Her face, hands, and feet appear puffy, with a doughlike consistency to the skin. Laboratory findings show hemoglobin, 13.8 g/dL; hematocrit, 41.5%; AST, 26 U/L; ALT, 21 U/L; total bilirubin, 1 mg/dL; Na+, 140 mmol/L; K+, 4.1 mmol/L; Cl-, 99 mmol/L; CO2, 25 mmol/L; glucose, 73 mg/dL; and creatinine, 1.1 mg/dL. Which of the following serologic test findings is most likely to be positive? (A) Anticentromere antibody (B) Anti-DNA topoisomerase antibody (C) Antimitochondrial antibody (D) Antinuclear antibody (E) Antiribonucleoprotein antibody (F) Anti-thyroid peroxidase antibody

(F) Anti-thyroid peroxidase antibody

2. A 34-year-old woman has had increasing lethargy for the past 8 months. During this time, she has experienced increased sensitivity to sunlight, and now rarely goes outdoors during the day. She has pain in her hands, elbows, knees, and feed, and muscle aches in her arms and legs. She has had increasing dyspnea for the past week. Physical examination shows no joint deformities, swelling, or redness. On auscultation of the chest, a friction rub is audible. A chest radiograph shows bilateral pleural effusions. Laboratory findings show hemoglobin, 11.6 mg/dL; hematocrit, 34.3%; MCV, 84 µm3; platelet count, 133,400/mm3; WBC count, 4610/mm3; Na+, 140 mmol/L; K+, 4 mmol/L; Cl-, 99 mmol/L; CO2, 25 mmol/L; glucose, 80 mg/dL; creatinine, 2.4 mg/dL; and calcium, 7.9 mg/dL. Which of the following additional laboratory tests would be most helpful to diagnose her underlying condition? (A) Acetylcholine receptor antibody (B) Anti-DNA topoisomerase antibody (C) Anti-glomerular basement membrane antibody (D) Antimicrosomal antibody (E) Antimitochondrial antibody (F) Antinuclear antibody

(F) Antinuclear antibody

5. A 56-year-old man has noticed increasing abdominal girth and decreased libido for the past 7 months. Physical examination shows an enlarged abdomen with a fluid wave, but no tenderness or masses; the spleen tip is palpable. Bibasilar crackles are audible on the auscultation of the chest. There is 1+ pitting edema to the knees. The testes are smaller than normal, but without masses. Laboratory findings show hemoglobin, 12.2 g/dL; hematocrit, 36.9%; MCV, 103 µm3; platelet count, 189,400/mm3; WBC count, 5762/mm3; Na+, 138 mmol/L; K+, 3.9 mmol/L; Cl-, 98 mmol/L; CO2, 24 mmol/L; creatinine, 1.1 mg/dL; glucose, 88 mg/dL; total protein, 5.7 g/dL; albumin, 2.7 g/dL; AST, 167 U/L; ALT, 69 U/L; alkaline phosphatase, 48 U/L; total bilirubin, 1.5 mg/dL; and prothrombin time, 23 seconds. What is the most likely diagnosis? (A) Adrenal atrophy (B) Aortic valvular stenosis (C) Autoimmune gastritis (D) Chronic glomerulonephritis (E) Hypertrophic cardiomyopathy (F) Micronodular cirrhosis

(F) Micronodular cirrhosis

8. A 24-year-old woman has developed right-sided facial pain over the past 24 hours. During that time, she has become lethargic and obtunded. Her medical history shows a 5-kg weight loss over the past 6 months, despite increasing caloric intake. On physical examination, there is swelling with marked tenderness over the right maxilla, exophthalmos on the right side, diffuse abdominal pain, poor skin turgor, and dry mucous membranes. Her temperature is 37.7ºC. She has tachycardia, but no murmurs, and tachypnea; the lung fields are clear. Laboratory findings show hemoglobin, 13.1 g/dL; hematocrit, 39.4%; Na+, 131 mmol/L; K+, 4.6 mmol/L; Cl-, 92 mmol/L; CO2, 9 mmol/L; glucose, 481 mg/dL; and creatinine, 1 mg/dL. An arterial blood gas measurement shows pH 7.2, Po2 98 mm Hg, Pco2 28 mm Hg, and HCO-3 10 mmol/L. Fine-needle aspiration of the right maxillary region is performed. What organism is most likely to be present in this aspirate? (A) Actinomyces israelii (B) Bacillus anthracis (C) Cytomegalovirus (D) Clostridium perfringens (E) Cryptococcus neoformans (F) Mucor circinelloides (G) Pseudomonas aeruginosa

(F) Mucor circinelloides

19. A 35-year-old woman has had a low-grade fever and worsening nonproductive cough and dyspnea for the past 2 years. On examination, she has breath sounds in all lung fields. A chest radiograph shows prominent hilar lymphadenopathy and increased interstitial lung markings. An arterial blood gas shows pH 7.45, PO2 83 mm Hg, PCO2 30 mm Hg, and HCO3- 20 mEq/L. Pulmonary function tests show total lung capacity 3 L (60% of predicted), FEV1 2.5 (66% of predicted), and DCLO 10 mL/min/mm Hg (50% of predicted). Her pulmonary compliance is reduced. Lunch biopsy shows non-necrotizing granulomas. Special stains show no micro-organism. What is the most likely diagnosis? (A) α1-antitrypsin deficiency (B) Adult respiratory distress syndrome (C) Chronic bronchitis (D) Goodpasture syndrome (E) Nonatopic asthma (F) Sarcoidosis

(F) Sarcoidosis

21. The prenatal course of a 25-year-old primigravida is uncomplicated. She gives birth to a 4500-g boy whose Apgar scores are 8 and 10 at 1 minute and 5 minutes. Shortly after birth, he develops irritability with seizure activity. On examination the infant is normally developed with no abnormalities. The lungs are clear to auscultation. Laboratory studies show serum Na+, 145 mmol/L; K+, 4.2 mmol/L; Cl-, 99 mmol/L; CO2, 25 mmol/L; urea nitrogen, 0.4 mg/dL; and glucose, 18 mg/dL. Which of the following pathologic findings is most likely to be present in the pancreas of this infant? (A) Acute pancreatitis (B) Amyloid deposition (C) Adenocarcinoma (D) Chronic pancreatitis (E) Fatty replacement (F) Insulitis (G) Islet hyperplasia (H) Pseudocyst

(G) Islet hyperplasia

41. A 25 year old man has complained of headaches for the past 5 months. During that time, family members noticed that he was not as mentally sharp as he has been in the past and that he has become more emotionally labile. Over a 2 week period, he has a generalized seizure, followed by three more seizures. On physical examination, there is no papilledema or movement disorder. CT scan of the head shows a 2-cm mass in the right frontal lobe. A stereotactic biopsy specimen of this lesion shows only gliosis and evidence of recent and remote hemorrhage. The mass is removed and histologic examination shows a conglomerate of various-sized tortuous vessels surrounded by gliosis. What is the most likely diagnosis? A. Arteriovenous malformation B. Organizing abscess C Angiosarcoma D Prior head trauma E. Ruptured saccular aneurysm F. Multiple sclerosis plaque

A. Arteriovenous malformation

4. A 72 year old man with diabetes mellitus has had stepwise cognitive decline for the past 5 years. There is an acute even, such as loss of consciousness or confusion, followed by worsening ability to perform activities of daily living. On physical examination, he has mild right hemiparesis, ataxia, and dysarthria. Which of the following pathologic findings is most likely to be present and numerous in this man? A. Lacune B. Lew bodies C. Neuritic plaques D. Neurofibrillary tangles E. Pick bodies F. Plaques of demyelination

A. Lacune

18. A 38 year old woman who fell to the ground and hit her head is taken to the emergency department. There are no remarkable findings on physical examination. CT scan of the head shows no hemorrhage or fracture, but there is a 5-cm mass beneath dura that compresses the underlying left super-olateral parietal lobe. The mass is surgically removed. Histologic analysis shows elongated cells with pale, oblong nuclei and pink cytoplasm with occasional Psammoma bodies. What is the most likely diagnosis? A. Meningioma B Tuberculoma C. Medulloblastoma D. Schwannoma E. Ependymoma

A. Meningioma

15. An 18 year old university student has had decreased vision on the left for 6 months. On physical examination, there is papilledema on the right. She has 14 scattered, 2-to5-cm flat, hyperpigmented skin lesions with irregular borders on the extremities and torso. CT scan of the head shows no intracranial hemorrhage and no edema or midline shift, but there is a mass in the region of the right optic nerve. An optic nerve glioma is excised. Eight months later, she returns for a follow up examination, and a mass is palpated on the right wrist. Histologic examination of the mass is most likely to show which of the following neoplasms? A. Schwannoma B. Lipoma C. Fibrosarcoma D. Meningioma E. Hemangioma

A. Schwannoma

63. A 60 year old woman had problems related to movement for 5 years. Physical examination showed cogwheel rigidity of limbs and a festinating gait, which she had difficulty performing activities of daily living and showed marked cognitive decline. She died of aspiration pneumonia. Autopsy findings include mild cerebral atrophy and loss of substantia nigra pigmentation. Microscopically, there is loss of pigmented neurons, and the remaining substantia nigra neurons and cortical neurons show spheroidal, intraneuronal, cytoplasmic and eosinophilic inclusions. Immunohistochemical staining for which of the following proteins is most likely to be positive in these inclusions? A. α-Synuclein B. Amyloid precursor protein C. Apolipoprotein E D. Huntingtin E. Presenilin F. Tau protein

A. α-Synuclein

60. A 46 year old woman has had increasing weakness and loss of sedation in the lower extremities for the past 5 months. She comes to the physician because she has been unable to walk without assistance for the past week. On physical examination, there is 4/5 motor strength in the right lower extremity and 3/5 motor strength in the left lower extremity. There is bilateral loss of sensation to light touch from the lateral midthigh distally. MRI of the spine shows a 1X4 cm lesion in the filum terminale. The mass is removed. Microscopically, the mass is composed of cuboidal cells around papillary cores in a myxoid background. Which of the following was most likely present in this patient? A. Choroid plexus papilloma B. Ependymoma C. Meningioma D. Metastatic transitional cell carcinoma E. Neurofibroma F. Pilocytic astrocytoma G. Schwannoma

B. Ependymoma

14. A 19 year old snow boarder wearing protective equipment consisting of a baseball cap, baggy shorts and a letterman's jacket flew off a jump and hit a tree. He was initially unconscious, and then "came to" and wanted to try another run, but his friends though it best to call for help. On the way to the emergency department, he became comatose. Physical examination shows left papilledema. Skull radiographs show a linear fracture of the left temporoparietal region. A serum drug screen is positive for cannabinoids. This clinical picture is most consistent with which of the following lesions? A. Contusion of frontal lobes B. Epidural hematoma C. Ruptured berry aneurysm D. Acute leptomeningitis E. Acute subdural hematoma

B. Epidural hematoma

29. A 26 year old man states that 3 years ago he experienced Paresthesias of his left arm and had difficulty walking, but these problems diminished. During the past year, he developed difficulty seeing form his left eye. Six months ago, he had difficulty writing with this right hand. On physical examination, there is decreased visual acuity on the left and no pailledema and no retinal lesions. There is decreased motor strength and decreased sensation in the right hand and forearm. MRI of the brain shows focal areas of brightness in periventricular white matter and in the left optic nerve. A lumbar puncture is performed. What finding is most likely to be present on examination of the CSF? A. Cryptococcal antigen B. Oligoclonal bands of immunoglobulins C. Malignant cells D. Xanthochromia E. Antitreponemal antibodies

B. Oligoclonal bands of immunoglobulins

46. A 48 year old man has noticed speech difficulties for 2 months. On physical examination, he has weakness on the left side. MRI of the brain shows a large, irregular, 6-cm mass in the centrum semiovale of the right cerebral hemisphere that extends across the corpus callosum. Stereotactic biopsy of the mass shows areas of necrosis surrounded by nuclear pseudopalisading. The neoplastic cells within the mass are hyperchromatic. Which of the following neoplasms is most likely to be present in this patient? A. Medulloblastoma B. Glioblastoma C. Metastatic lung carcinoma D. Malignant melanoma E. Cystic astrocytoma

B. Glioblastoma

49. A 5 year old boy has been irritable for the past 2 days and has complained of an earache for the past 5 days. On physical examination, he has a temperature of 39.1C. Laboratory examination of the CSF from a lumbar puncture shows numerous neutrophils, slightly increased protein level and decreased glucose concentration. On Gram staining of the CSF, which of the following is most likely to be seen microscopically? A. No organisms B. Gram-positive cocci C. gram-negative diplococci D. Short Gram-positive rods E. Gram-negative bacilli

B. Gram-positive cocci

5. A 40 year old, previously healthy man is brought to the emergency department after sudden onset of a grand mal seizure. Physical examination yields no remarkable findings except for a 1-Cm, darkly pigmented skin lesion on the upper back. CT scan of the head shows five sharply circumscribed, 1-to2.4-cm mass lesions located in the cerebral hemispheres at the gray-white junction of the parietal and frontal lobes. What is the most likely diagnosis? A. AIDS B. Metastases C. Infective endocarditis D. Neurofibromatosis type 1 E. Cysticercosis

B. Metastases

12. A 45 year old, previously healthy man has developed headaches over the past month. There are no remarkable findings on physical examination. A cerebral angiogram shows a 7-mm saccular aneurysm at the trifurcation of the right middle cerebral artery. Which of the following is most likely to result from this lesion? A. Epidural hematoma B. Subarachnoid hemorrhage C. Subdural hematoma D. Cerebellar tonsillar herniation E. Hydrocephalus

B. Subarachnoid hemorrhage

28. In the past 3 months, a 79 year old man has had several episodes of sudden dysarthria, a feeling of weakness in his hands and dizziness. These episodes usually last lest than 1 hour and then he feels fine. Today, he suddenly lost consciousness while walking to the bathroom in his house and fell to the floor. On regaining consciousness several minutes later, he was unable to move his right arm or to speak clearly. Which of the following findings in the brain best explains this patient's symptoms? A. Frontal lobe astrocytoma B. Subdural hematoma C. Cerebral atherosclerosis D. Arteriovenous malformation E. Meningoencephalitis

C. Cerebral atherosclerosis

6. A 25 year old, previously healthy woman has acute onset of confusion and disorientation followed by a generalized tonic-clonic seizure. On admission to the hospital, she is afebrile and her blood pressure is 110/65mm Hg. No papilledema is observed. Serum and urine drug screening results are negative. CT scan of the head shows a 3-cm recent hemorrhage in the left temporal lobe. A lumbar puncture is done, and the CSF shows only a few mononuclear cells and normal glucose and protein levels. Infection with which of the following organisms is the most likely cause of her disease? A. Cytomegalovirus B. Neisseria meningitides C. Herpes simplex virus D. Eastern equine encephalitis virus E. Aspergillus niger

C. Herpes simplex virus

9. A 69 year old woman with a 7 year history of progressive dementia dies of bronchopneumonia. At autopsy, there is cerebral atrophy in a predominantly frontal and parietal lobe distribution. Microscopic examination of the brain shows numerous neuritic plaques in the hippocampus, amygdala, and neocortex. Congo red staining shows amyloid in the media of the small peripheral cerebral arteries. Which of the following conditions is likely to be the most important factor in the development of her disease? A. HLA-DR3/DR4 B. Expansion of CAG repeats on chromosome 4p16 C. Inheritance of the e4 allele at the ApoE4 gene D. Inheritance of a mutant prion gene E. Deficiency of thiamine

C. Inheritance of the e4 allele at the ApoE4 gene

61. A 52 year old woman has had malaise for the past 6 months. On physical examination, there are no remarkable findings. Laboratory studies show hemoglobin, 9.3g/dL;hematocrit, 27.9%;platelet count, 549,000/mm³; and WBC count, 282,000/mm³ with 64% segmented neutrophils, 10% bands, 3% metamyelocytes, 2% myelocytes, 2% lymphocytes, 1% monocytes, 9% eosinophils and 9% basophils. She undergoes chemotherapy. Two months later, she develops neurologic deficits with ataxia, motor weakness in the right arm, difficulty swallowing and sensory changes in the left leg. MRI of the brain shows irregular areas of increased attenuation in white matter of the cerebral hemispheres and the cerebellum. A stereotaxic biopsy specimen shows perivascular chronic inflammation, marked gliosis, large reactive astrocytes with bizarre nuclei, and intranuclear inclusions within oligodendroglia. What infection most likely caused these findings? A. Cytomegalovirus B. Herpes simplex virus C. JC papovavirus D. Rabies virus E. Rubeola virus F. West Nile virus

C. JC papovavirus

45. A 41 year old woman has had diminished hearing for the last 4 months. On physical examination, she has decreased hearing on the left. Sound lateralizes to the right ear on the Weber tuning fork test. CT scan of the head shows a sharply circumscribed, 4-cm mass adjacent to the left pons that extends toward the left inferior cerebellar hemisphere. What neoplasm is most likely to be present in this patient? A. Meningioma B Astrocytoma C. Schwannoma D Medulloblastoma E. Ependymoma

C. Schwannoma

1. A 46 year old man who is an intravenous drug user is admitted to the hospital because he has had increasing headache and high fever for the past 24 hours. On physical examination, his temperature is 38.4C, pulse is 85/min, respirations are 18/min, and blood pressure is 125/85mm Hg. CT scan of the head shows no mass lesion or midline shift. A lumbar puncture is performed. The CSF shows an increased protein concentration and a decreased glucose level. Which of the following infectious agents is most likely to produce these findings? A. JC papovavirus B. Mycobacterium tuberculosis C. Staphylococcus aureus D. Herpes simplex virus E. Toxoplasma gondii

C. Staphylococcus aureus

33. While working at her desk as an accountant, a 50 year old woman develops a sudden, severe headache and is taken to the emergency department. On examination, she has nuchal rigidity. A lumbar puncture is done; the CSF shows numerous RBC's, no neutrophils, a few mononuclear cells, and a normal glucose level. The Gram stain result is negative. Which of the following events has most likely occurred? A. Middle cerebral artery thromboembolism B. Tear of subdural bridging veins C. ruptured intracranial berry aneurysm D. Bleeding from cerebral amyloid angiopathy E. Hypertensive basal ganglia hemorrhage

C. ruptured intracranial berry aneurysm

4. A 12-year-old boy has had worsening problems with joint mobility involving his arms and legs, particularly his knees and ankles, for the past 6 years. He has been receiving therapy for this condition. His grandfather had a similar condition and died at age 25. On physical examination, he has no visible petechiae or areas of purpura. Laboratory studies show that prothrombin time is 12 seconds, and partial thromboplastin time is 52 seconds. After addition of an equivalent aliquot of normal plasma, the partial thromboplastin time is 30 seconds. Hemoglobin is 12.9 g/dL, platelet count is 238,500/mm3, and WBC count is 6620/mm3. His platelet function studies are normal. What is the most likely inheritance pattern for his condition? (A) Confined placental mosaicism (B) Autosomal recessive mutation (C) Autosomal dominant mutation (D) X-linked mutation (E) Germline mutation

D) X-linked mutation

27. A 43 year old, previously healthy woman has had a headache and fever for the past 2 weeks. She recently had a severe respiratory tract infection. On physical examination, her temperature is 38.3C. There is no papilledema. She has no loss of sensation or motor function, but there is decreased vision in the left half of her visual fields. CT scan of the head shows a sharply demarcated, 3-cm, ring-enhancing lesion in the right occipital region. A lumbar puncture is done, and laboratory analysis of the CSF shows a cell count of four lymphocytes and eight neutrophils and increased protein and normal glucose levels. What is the most likely diagnosis? A. Glioblastoma multiforme B. Multiple sclerosis C. Subacute infarction D. Cerebral abscess E. Metastatic carcinoma

D. Cerebral abscess

24. A fetus is stillborn at 34 weeks gestation to a 33 year old woman, G3, P2, whose two previous pregnancies resulted in normal term infants. On examination, the fetus is observed to be hydropic. Autopsy of the fetus shows marked organomegaly, and the brain has extensive necrosis in a periventricular pattern, with focal calcifications. What congenital infection is most likely to produce these findings? A. Listeria monocytogenes B. HIV C. Herpes simplex virus D. Cytomegalovirus E. Group B streptococcus

D. Cytomegalovirus

54. An 83 year old woman slips in the bathtub in her home and falls backward, striking her head. She is taken to the emergency department, where examination shows a 3-cm, reddish, slightly swollen are over the occiput. She is arousable but somnolent. There are no motor or sensory deficits. There is no papilledema. CT scan of the head is performed. Acute hemorrhage in which of the following locations is most likely to be seen? A. Basis pontis B. Cerebral ventricle C. Epidural space D. Inferior frontal lobe E. Putamen F. Sella turcica

D. Inferior frontal lobe

62. A 39 year old man who has been HIV-positive for at least 8 years has received no antiretroviral therapy. He has had left-sided weakness for the past month. He sees the physician 1 day after experiencing a generalized seizure. On physical examination, he is afebrile. There is 4/5 motor strength in the left upper extremity. CT scan of the head shows no intracranial hemorrhage, but there is a midline shift. MRI of the brain shows a 4-cm mass in the region of the putamen near the right internal capsule, a 3-cm mass in the right centrum semiovale, and a 1-cm mass near the splenium of the corpus callosum. These masses are circumscribed and solid. CSF from a lumbar puncture shows an elevated protein concentration and a normal glucose level. Cytologic examination shows large cells with large nuclei and scant cytoplasm that mark with CD19, but not with GFAP or cytokeratin. What is the most likely diagnosis? A. Cytomegalovirus B. Glioblastoma multiforme C. Kaposi sarcoma D. Large B-cell lymphoma E. Progressive multifocal leukoencephalopathy F. Toxoplasmosis

D. Large B-cell lymphoma

16. A 62 year old man has had increasing difficulty with voluntary movements because of muscular rigidity. On physical examination, he has difficulty initiating movement, but he can keep moving if he follows someone walking ahead of him. He has an expressionless facies. When he is sitting, his hands have a "pill-rolling" tremor. Which pathologic finding in the brain is most likely to be present? A. Hippocampal neurofibrillary tangles B. Neuronal loss with gliosis in caudate C. Hemosiderosis and gliosis of mammillary bodies D. Loss of pigmented neurons in substantia nigra E. Alzheimer type II gliosis in basal ganglia

D. Loss of pigmented neurons in substantia nigra

35. A 5 year old boy has complained of headaches for the past week. His gait has become ataxic. After sudden onset of vomiting, he is brought to the emergency department, where he becomes comatose. On physical examination, he is afebrile. CT scan of the head shows the presence of a 4-cm mass in the cerebellar vermis and dilation of the cerebral ventricles. A lumbar puncture is done. Cytologic examination of the CSF shows small cells with dark blue nuclei and scant cytoplasm. What neoplasm would most likely explain these findings? A. Schwannoma B. Ependymom C. Glioblastoma multiforme D. Medulloblastoma E. Metastatic carcinoma

D. Medulloblastoma

34. A 20 year old, HIV-positive man has had a decreased level of consciousness for the past week. He now experiences a seizure. On physical examination, his temperature is 37.6C. MRI of the brain shows several 1-to3-cm, ring-enhancing lesions in the cerebral gray matter bilaterally. A stereotaxic biopsy is performed. What pathologic finding is most likely to be present on microscopic examination of the biopsy specimen? A. Large atypical lymphocytes B. Budding cells with pseudohyphae C. Spongiform encephalopathy D. Toxoplasma pseudocysts E. Metastatic squamous cell carcinoma

D. Toxoplasma pseudocysts

13. A 55 year old man dies of aspiration pneumonia after a 6 year illness, characterized by progressive, symmetric muscular weakness. At autopsy, the brain and spinal cord appear normal on gross examination. Microscopic sections show gliosis in the motor cortex, pallor of the lateral corticospinal tracts and neuronal loss in the anterior horns of the spinal cord. What is the most likely underlying cause of death? A. Becker muscular dystrophy B. Neurofibromatosis type 3 C. Guillain-Barre syndrome D. Creutzfeldt-Jakob disease E. Amyotrophic lateral sclerosis

E. Amyotrophic lateral sclerosis

11. A previously healthy 26 year old medical student has headaches for several weeks. She has increasing malaise. Physical examination yields no remarkable findings. CT scan of the head shows no abnormalities. A lumbar puncture yields clear, colorless CSF with a normal opening pressure. Laboratory analysis of the CSF shows a normal glucose concentration and a minimal increased protein level. A few lymphocytes are present, but there are no neutrophils. A Gram stain and India ink preparation of the CSF are negative. Her condition gradually improves over the next several months. Serum serologic tests are most likely to show an elevated titer of antibodies to which of the following infectious agents? A. Toxoplasma gondii B. Listeria monocytogenes C. Cryptococcus neoformans D. Neisseria meningitides E. Echovirus

E. Echovirus

56. A 4 year old girl developed clumsiness and difficulty ambulating over 6 months. On physical examination, she showed difficulty with balance while walking, dysarthria, poor hand coordination, absent deep tendon reflexes and a bilateral Babinski sign. Light touch and vibratory sensation were greatly diminished. There was no muscular weakness. Over the next 5 years, she developed congestive heart failure from hypertrophic cardiomyopathy. She also had hyperglycemia. At autopsy, there was increased perinuclear iron deposition within cardiac myocytes. Which of the following genetic abnormalities with trinucleotide repeat expansions was most likely present in this patient? A. CAG repeats in the huntington gene B. CAG repeats in the spinocerebellar ataxia 7 gene C. CGG repeats in the FMR1 gene D. CTG repeats in the dystrophila myotonia-protein kinase gene E. GAA repeats in the frataxin gene

E. GAA repeats in the frataxin gene

8. A 53 year old man with a lengthy history of chronic alcoholism has had an increasingly clouded sensorium over the past 2 days. On physical examination, he has a flapping tremor of his outstretched hands. MRI of the brain shows no abnormalities. At autopsy, microscopic examination of his brain shows increased numbers of neocortical and basal ganglia astrocytes with pale, swollen nuclei (Alzheimer type II cells). Which of the following laboratory findings is most likely to be associated with these findings? A. Hyponatremia B. Hypoglycemia C. Elevated hemoglobin A₁c level D. Elevated carboxyhemoglobin level E. Hyperammonemia

E. Hyperammonemia

19. A 47 year old woman is brought to the physician by family members, who report that she has become more forgetful in the past few months. She is emotionally labile and often cries. She is disturbed and depressed by these developments because her mother died a few years after experiencing the same symptoms. On physical examination, she has some choreiform movements of her extremities. Which of the following laboratory findings is most likely to be present? A. Decreased level of hexosaminidase A enzyme B. Mutation in presenilin genes C. Extra chromosome 21 D. Abnormal prion protein E. Increased CAG repeats

E. Increased CAG repeats

3. A 49 year old man with an acute psychosis is being examined by a nurse practitioner. The man tells her that he has a lengthy history of chronic alcoholism. He has difficulty performing a finger-to-nose test, and there is paralysis of the lateral rectus muscles. A deficiency of which of the following nutrients is most likely to produce these findings? A. Folate B. Niacin C. Cobalamin D. Pyridoxine E. Thiamine

E. Thiamine

40. A 56 year old man sees his physician after a single episode of grand mal seizure. On physical examination, he is afebrile and normotensive. Motor strength is intact and there is no loss of sensation. Cranial nerves are intact. His mental function is not diminished. Brain MRI shows three solid, 1-to3-cm mass lesions, without ring enhancement or surrounding edema, located at the gray-white junction in the right and left frontal lobes. The cerebral ventricles appear normal in size. What is the most likely diagnosis? A. Glioblastoma multiforme B. Hemangioblastoma C. Medulloblastoma D. Meningioma E. Metastatic carcinoma F. Non-Hodgkin Lymphoma G. Oligodendroglioma H. Schwannoma

E. Metastatic carcinoma

2. The family of a 63 year old woman noticed that she has become more forgetful over a period of 6 weeks. One month later, the woman has difficulty ambulating and is unable to care for herself. On physical examination, she has myoclonus. She is afebrile. CT scan of the head shows minimal cerebral atrophy, which is nearly consistent for age. An EEG shows low-amplitude, show background activity with periodic complexes and occasional repetitive sharp waves with intervals of 0.5 to 1 second. Which of the following histologic abnormalities is most likely to be found in the cerebral cortex? A. Numerous neuritic plauques B. Plaques of demyelination C. Lewy bodies D. Microglial nodules E. Spongiform encephalopathy

E. Spongiform encephalopathy

10. A 72 year old woman trips on a toy truck left at the top of a flight of stairs by a grandchild and falls down the stairs. She does not lose consciousness. About 36 hours later, she develops a headache and confusion and is taken to the emergency department. On physical examination, she is conscious and has a scalp contusion on the occiput. What is the most likely location of an intracranial hemorrhage in this patient? A. Pontine B. Subarachnoid C. Basal ganglia D. Epidural E. Subdural

E. Subdural

57. A 63 year old man had increasing irritability over 3 years. He spent a lot of time wandering about his neighborhood, complaining to the neighbors about everything. He had no memory loss and was always able to find his way home. The neighbors were pleased when he developed aphasia. On physical examination, there were no motor or sensory deficits and no gain disturbances or tremor. MRI of the brain showed bilateral marked temporal and frontal lobe gyral atrophy. He died of pneumonia 1 year later. At autopsy, the frontal cortex microscopically shows extensive neuronal loss and some remaining nerons show intracytoplasmic, faintly eosinophilic, rounded inclusions that stain immunohistochemically for tau protein. What is the most likely diagnosis? A. Alzheimer disease B. Huntington disease C. Leigh disease D. Multiple system atrophy E. Parkinson disease F. Pick disease G. Vascular dementia

F. Pick disease

59. A 40 year old man, who rarely had headaches, now has been experiencing headaches for the past 6 months. He comes to the physician because of a seizure that occurred 1 day ago. On physical examination, there are no remarkable findings. MRI of the brain shows a solitary, circumscribed 3-cm mass in the right parietal centrum semiovale. The mass has small cysts and area of calcification and hemorrhage. Neurosurgery is performed, and the mass is removed. Microscopically, the mass consists of sheets of cells with round nuclei that have granular chromatin. The cells have a moderate amount of clear cytoplasm. These cells mark with FGAP by immunohistochemical staining. The patient receives adjuvant radiation and chemotherapy and there is no recurrence. Which of the following neoplasms was most likely present in this patient? A. Astrocytoma B. Diffuse large B-cell lymphoma C. Germ cell tumor D. Glioblastoma multiforme E. MEdulloblastoma F. Metastatic renal cell carcinoma G. Oligodendroglioma

G. Oligodendroglioma


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