IV. N UTRITION — A NSWERS 31 IV-4. The answer is C. (Chap. 78) Treating patients with severe anorexia nervosa (Ͻ75% of expected body weight) requires careful medical and psychiatric care. Patients with such severe weight deficits should be hospitalized, at which time a program of nutritional res- toration with oral feeding with food or liquid supplements can be undertaken. However, much support and education are required to reassure the patient that the weight gain will not be permitted to get “out of control.” Psychiatric treatment focuses on emotional support and improving self-esteem. Complications of re-feeding can be as severe as congestive heart failure; abnormal liver function tests and low levels of magnesium and phosphate have been reported. Tricyclic antidepressants are contraindicated due to the possibility of prolongation of the QT interval in the setting of abnormal electrolyte levels. No psycho- tropic medicine has been shown to be beneficial in this disorder. IV-5. The answer is E. (Chap. 77. Heymsfield et al, JAMA 282:1568– 1575, 1999.) Studying mutations in obese rodents has provided important insights into the mechanism of obesity in humans. Genetically obese (ob/ob) mice have a mutation in the gene that encodes the peptide leptin. Leptin is normally secreted by adipose (fat) cells and acts through the hypothalamus to provide a homeostat for adipose energy stores. Patients who are leptin deficient develop severe obesity, insulin resistance, and hyperphagia as well as overly efficient metabolism. Although high leptin levels in mice are associated with decreased food intake and increased energy expenditure, patients with common obesity do not re- spond significantly to administration of recombinant leptin. Most obese people do have increased leptin levels and do not have mutations of either leptin or its receptor. Therefore, it is not surprising that administering leptin to such individuals has no benefit. Typical obese people may have “leptin resistance.” IV-6. The answer is A. (Chap. 77, Connolly et al, N Engl J Med 337:581 – 588, 1997.) Although it may be tempting to use drugs to help a severely overweight person lose weight, such an approach is rarely effective. Leptin therapy is not effective in people with a nongenetic cause of obesity. Several amphetamine-type drugs such as phentermine can cause modest weight loss over a short period of time, but rebound weight gain is typically seen upon discontinuation of the agent. Serotonin uptake inhibitors such as fenfluramine also have modest efficacy and perhaps potentiate the weight loss effect of phentermine. However, dual treatment with both these agents yields a twentyfold increase in the like- lihood of severe pulmonary hypertension and valvular heart disease. Modest weight loss has been described with the new central neurotransmitter uptake inhibitor, sibutramine, and with an inhibitor of intestinal lipase, orlistat. Since most obese individuals are euthy- roid, thyroid hormone replacement has little role in treatment of overweight patients. IV-7. The answer is D. (Chap. 74) A normal person stores about 15 kg of energy as fat, 6 kg as muscle, and 0.4 kg as glycogen. During the first 24 h of starvation, energy needs can be met by the conversion of liver stores of glycogen to glucose. During prolonged starvation, body fat is converted into fatty acid–derived ketones. Normal-weight individ- uals can fast for 2 months, while obese individuals can fast for many more months. How- ever, the response to acute illness such as surgical trauma or sepsis includes a promotion of hypermetabolism in which skeletal muscle and viscera undergo proteolysis to provide the amino acid substrates required for gluconeogenesis. Such rapid proteolysis is promoted by high levels of circulating catecholamines, glucagon, and cortisol, as well as cytokines such as tumor necrosis factor and interleukins 1 and 6. If the starvation process is pro- longed, severe protein-calorie malnutrition can be associated with decreased cardiac and renal function, fluid retention, intestinal mucosal atrophy, and loss of cell-mediated im- mune functions. IV-8. The answer is A. (Chap. 74) Nutritional assessment should be undertaken in any pa- tient with a debilitating chronic illness or in homeless individuals. The conditions that promote involuntary diet restriction such as drug abuse, chronic alcoholism, or many psychiatric disorders are often associated with malnutrition. Severe malnutrition, defined IV. N UTRITION — A NSWERS 32 as Ͻ70% of ideal body weight, causes diminution of skeletal protein and is evidenced by decreased temporal and proximal extremity muscle mass. Decreased body fat stores are indicated by a decrease in skin-fold thickness (the so-called pinch test). Evidence of vi- tamin deficiency may abound, including bruising due to vitamin C deficiency or coarse skin with “goose bumps” due to vitamin A deficiency. Vitamin deficiency can cause oph- thalmoplegia, confabulation, cerebeller gait, and peripheral neuropathy. While levels of serum immunoglobulins, granulocytes, and monocytes are generally well preserved, lym- phopenia, which can be promoted by chronic alcoholism or other chronic infections such as HIV, is the most common hematologic abnormality. Patients may often display anergy in skin testing. More common than the microcytic red cells in iron deficiency is the mac- rocytosis of coexistent vitamin B deficiency. 12 IV-9. The answer is B. (Chap. 75) Thiamine (or vitamin B ), when metabolized to thiamine 1 pyrophosphate, is the coenzyme required for proper energy-producing metabolism of branched-chain amino acids. Thiamine may also play a role in peripheral nerve conduction. Deficiency of this vitamin produces anorexia, irritability, apathy, generalized weakness, as well as pain and numbness in the extremities due to peripheral neuropathy. Vitamin B deficiency may also present with central nervous system problems, especially with the 1 syndrome known as Wernicke’s encephalopathy, which consists of horizontal nystagmus, ophthalmoplegia due to weakness of one or more extraocular muscles, cerebellar ataxia, and mental impairment. Thiamine should be given prophylactically to all chronic alcoholic patients in the emergency room to prevent precipitation of thiamine deficiency after ad- ministration of glucose-containing fluids. Unlike in vitamin B deficiency, joint position 12 sense is usually maintained in patients with thiamine deficiency. IV-10. The answer is D. (Chap. 75) The amino acid tryptophan is converted to the niacin derivatives nicotinic acid and nicotinamide, coenzymes required for numerous oxidative and reductive enzymes. Niacin deficiency causes pellagra, which is a complicated syn- drome involving loss of appetite, weakness, irritability, abdominal pain, bright red tongue and stomatitis, and a skin rash characterized by pigmentation and scaling, particularly in areas exposed to sunlight. Pellagra can be seen in those whose diet consists primarily of corn in parts of China, Africa, and India; in chronic alcoholics; in those with congenital defects of tryptophan absorption; and in patients with carcinoid syndrome, in which there is an increased conversion of tryptophan into serotonin. IV-11. The answer is C. (Chap. 75) Certain medications, including isoniazid used for tuber- culosis, L -dopa used for Parkinson’s disease, and penicillamine used for scleroderma, promote vitamin B (pyridoxine) deficiency by reacting with a carbonyl group on 5-pyr- 6 idoxal phosphate, which is a cofactor for a host of enzymes involved in amino acid me- tabolism. Foods that contain vitamin B include legumes, nuts, wheat bran, and meat. 6 Vitamin B deficiency produces seborrheic dermatitis, glossitis, stomatitis, and cheliosis 6 (also seen in other vitamin B deficiencies). A microcytic, hypochromic anemia may also result from the fact that the first enzyme in heme synthesis (amino-levulonic synthetase) requires pyridoxal phosphate as a cofactor. However, vitamin B is also necessary for the 6 conversion of homocysteine to cystathionine. Consequently, deficiency of this vitamin could produce an increased risk of cardiovascular disease due to the resultant hyperho- mocystinemia. IV-12. The answer is D. (Chap. 75) Scurvy develops when the body pool of vitamin C drops to Ͻ33 mg/d and the plasma levels drop to Ͻ11 mg/L. Vitamin C is a cofactor for many enzymes involved in connective tissue metabolism and cross-linking. Consequently, the symptoms of vitamin C deficiency reflect diminished formation of connective tissue com- ponents such as skin and gums. Impaired connective tissue formation presents with pete- chiae, ecchymoses, and perifollicular hemorrhages in the skin; bleeding gums; and bleed- ing into the joints, peritoneal cavity, pericardium, and adrenal glands. The symptoms of scurvy improve within a few days after administration of vitamin C. Whether or not vitamin IV. N UTRITION — A NSWERS 33 C supplementation can prevent cancer due to its effect on the prevention of converting nitrate to carcinogenic nitrosamines is controversial. IV-13. The answer is A. (Chap. 75) Vitamin A intoxication may occur in those who ingest Ͼ15 mg/d of vitamin A for a period of several months (lower amounts in children). Manifestations of vitamin A intoxication include dry skin, cheliosis, glossitis, vomiting, alopecia, bone pain, hypercalcemia, lymph node enlargement, or hyperlipidemia. Patients will also develop amenorrhea and features of pseudotumor cerebri with increased intra- cranial pressure and papilledema. Liver fibrosis and bone demineralization have also been described. Patients with liver disease, alcoholics, and the elderly are more prone to this problem, in addition to those who ingest megadoses of vitamins. Vitamin A overload is teratogenic and has been associated with spontaneous abortions. IV-14. The answer is C. (Chap. 76. Heyland et al, JAMA 280:2013 – 2019, 1998.) Nutritional support is risky, depending on the route used, and is expensive. Although nutritional support has been proposed in many situations, it has been proved beneficial through the use of prospective, randomized clinical trials in a subset. Compared with other preoperative patients, only those presurgical patients who have severe protein-calorie malnutrition ben- efit from parenteral nutrition. Critically ill patients, patients undergoing bone marrow trans- plantation, and those with liver failure, pancreatitis, and severe inflammatory bowel disease have all been shown to benefit from nutritional support. Patients with cancer cachexia probably achieve no net benefit, except for those about to undergo cancer surgery who have severe protein-calorie malnutrition. IV-15. The answer is A. (Chaps. 43, 74) Involuntary weight loss is almost always due to a serious condition. The three mechanisms of weight loss are increased energy expenditure (relatively rare), loss of energy in stool or urine, and decreased food intake. In young persons the most likely causes of weight loss are diabetes, hyperthyroidism, anorexia nervosa, and infection (particularly with HIV). In older persons cancer is the most likely cause of weight loss, with psychiatric illness, including Alzheimer’s disease and depres- sion, being the second most important cause. A simple round of screening tests is rec- ommended during the initial evaluation of a patient with significant weight loss. In the current case, the normal CBC and negative stool for occult blood loss suggest that upper or lower gastrointestinal endoscopy probably would not be useful. Since this patient has normal electrolytes, Addison’s disease is also less likely, making the short ACTH test an inappropriate initial diagnostic study. Since the patient has no fever, blood cultures or bone marrow biopsy cultures are not likely to be revealing. Serum protein electrophoresis would be appropriate in the setting of anemia or abnormal protein excretion on urinalysis. An abdominal CT, which will provide a reasonable initial screen for pancreatic or gynecologic malignancies, is probably the best initial test in the case of occult weight loss in an older individual. IV-16. The answer is C. (Chap. 77) Menstrual abnormalities are often associated with obesity in women. The excessive number of adipocytes allows increased peripheral conversion of the excess levels of androgen to estrogen. There is a decreased level of sex hormone – binding globulin. Such endocrinologic abnormalities are frequently associated with the polycystic ovarian syndrome (PCOS). PCOS, which includes anovulation and hyperan- drogenism, is also found in many nonobese women, but many PCOS patients also have insulin resistance, suggesting a link between these two problems. Moreover, the increased incidence of endometrial cancer in obese women is believed to be due to the increased conversion of androstenedione to estrogen, high levels of which promote the proliferation of cells that line the uterine cavity. IV-17. The answer is E. (Chap. 78) Patients with anorexia nervosa who develop severe mal- nourishment may develop a host of endocrinopathies. First, amenorrhea is very common and is attributed to a failure of the body weight – sensitive hypothalamus to elaborate IV. N UTRITION — A NSWERS 34 normal amounts of gonadotropin-releasing hormone (GnRH). The mechanism of hypo- thalamic-mediated GnRH lack may be the low leptin level in these adipocyte-poor indi- viduals. Although serum cortisol levels are generally elevated, anorexic patients do not display features of hypercortisolism. As might be expected, the thyroid function test pattern in patients with anorexia nervosa resembles the euthyroid sick syndrome in which thyrox- ine (T ) and triidothyronine levels are in the low or low-normal range, reverse T is ele- 4 4 vated, and the thyroid stimulating hormone is low or partially suppressed. While levels of the stress-related growth hormone are elevated, hepatically produced insulin-like growth factor secretion is depressed. Some of these abnormalities, particularly decreased sex ster- oids and elevated cortisol, in combination with nutritional deficiencies can lead to severe osteoporosis. IV-18. The answer is E. (Chap. 73) In order to maintain a stable weight, energy intake must match energy output. For an average healthy male, this requires about 2800 kcal/d; this varies upward if the individual is quite active. Moreover, in times of stress, much greater needs must be met. The stress of severe trauma, burn, or hyperthyroidism (if severe) can essentially double the resting energy requirement. Fever itself increases energy require- ments by 10 to 15% per degree above normal. IV-19. The answer is B. (Chap. 74) The laboratory assessment of a patient’s nutritional status could include measurement of serum albumin, a hepatically synthesized protein with a half-life of 2 to 3 weeks. Increased extracellular volume or acute stresses such as trauma or surgery could, via tumor necrosis factor, depress the albumin level and give a false impression of chronic malnutrition. The measurement of shorter-lived “visceral” proteins (e.g., transferrin, prealbumin, or fibronectin) has been considered as an alternative to al- bumin, but their levels are also affected by acute inflammation. Hepatic diseases such as cirrhosis can lead to a low albumin synthesis, even in the face of adequate nutrition. Similarly, the loss of gut protein due an inflammatory condition such as Crohn’s colitis can lower the serum albumin. IV-20. The answer is D. (Chap. 76) Total parenteral nutrition (TPN) may be life-saving, but it is expensive, can be logistically difficult, and is associated with several complications, including infection due to the presence of a central venous catheter and anatomic issues related to the catheter itself. Moreover, there are a myriad potential metabolic problems such as immediate fluid overload, hyperglycemia, hypokalemia, or hyperphosphatemia. After TPN has proceeded for several weeks, patients may experience congestive heart failure, refeeding edema, or electrolyte/acid-base imbalances, particularly hyperosmolar nonketotic hyperglycemia coma. Once long-term TPN has been successful in converting the patient to an anabolic state, deficiencies of micronutrients, vitamins, and trace minerals (e.g., zinc, copper, selenium) may develop. Close monitoring and inclusion of essential “extras” in the TPN formula can avoid most of these complications. 35 V. ONCOLOGY AND HEMATOLOGY QUESTIONS DIRECTIONS: Each question below contains five suggested responses. Choose the one best response to each question. V-1. Which of the following statements concerning the musculoskeletal abnormalities in patients with sickle cell disease is correct? (A) Hand-foot syndrome characterized by diffuse swelling, tenderness, and warmth of the hands and feet in children under the age of 5 leads to chronic disability in about 10% of patients. (B) Acute arthritis seen in patients with sickle cell cri- sis is often associated with high white cell counts in joint effusions. (C) The bone pain in sickle cell crisis is due to bone and bone marrow infarction. (D) Acute gouty arthritis is common in patients with sickle cell disease. (E) Total hip replacement is contraindicated in patients with sickle cell anemia who sustain avascular ne- crosis of the femoral head. V-2. A 70-year-old man of Irish descent returns to his phy- sician for a routine check of his blood pressure. He is a vigorous, retired executive who except for mild hyperten- sion is healthy. After his examination, as he is getting dressed, he states that his wife has been nagging him to mention a spot on his nose (as shown in Plate P). He is certain that this lesion, which has been present for several years, is of no significance. The most likely diagnosis for this lesion is (A) dermal nevus (B) sebaceous hyperplasia (C) clear cell acanthoma (D) xanthoma (E) basal cell carcinoma V-3. A 52-year-old woman sees her physician for an “in- surance physical.” Physical examination reveals only a pigmented lesion (as shown in Plate Q) present on one foot. The woman states that the lesion apparently was present at birth and does not itch or bleed; it is, however, not as homogeneous in color as it used to be. Which of the following statements about the condition described is true? V-3. (Continued) (A) Bleeding and tenderness would be the first signs of malignant degeneration. (B) It is unlikely that the lesion, present since birth, is malignant. (C) The diagnostic procedure of choice is an incisional biopsy of this lesion. (D) Change in color of the lesion is a suspicious sign for potential malignancy. (E) Early diagnosis of this lesion would not affect prognosis. V-4. A 58-year-old man presents with fatigue. His physical examination is normal except for the presence of spleno- megaly. CBC discloses hematocrit, 29%; platelet count, 90,000/ ␮ L; WBC, 2700/ ␮ L; and an essentially normal red cell morphology (differential 12% monocytes, 12% gran- ulocytes, and 76% lymphocytes). A bone marrow aspirate and biopsy were performed. The aspirate was dry and the biopsy is pending. Based on the available information, the most likely diagnosis in this case is (A) chronic lymphocytic leukemia (CLL) (B) hairy cell leukemia (C) chronic myeloid leukemia (CML) (D) myelofibrosis (E) multiple myeloma V-5. A 58-year-old chronic alcoholic and heavy smoker presents with a 3-cm, firm, right midcervical neck mass. An excisional biopsy reveals squamous cell carcinoma. Which of the following is the most appropriate approach at this time? (A) Bronchoscopy, esophagoscopy, and laryngoscopy (B) CT of the neck (C) CT of the brain (D) Neck dissection (E) Radiation therapy V-6. A 28-year-old man with newly diagnosed acute my- elogenous leukemia spikes a temperature to 38.7ЊC Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use. V. O NCOLOGY A ND H EMATOLOGY — Q UESTIONS 36 V-6. (Continued) V-9. (Continued) (101.7ЊF) on the sixth day of induction therapy. He feels well and has no physical complaints. His only medicine is intravenous cytosine arabinoside, 140 mg every 12 h. Physical examination is unrevealing. His white blood count is 900/ ␮ L, of which 10% are granulocytes and the rest mostly lymphocytes; platelet count is 24,000/ ␮ L. Findings on chest x-ray and urinalysis are normal. After obtaining appropriate cultures, the man’s physi- cian should (A) observe closely for the development of a clinically evident source of fever (B) begin antibiotic therapy with gentamicin and mez- locillin (C) begin granulocyte transfusion and antibiotic ther- apy with gentamicin and mezlocillin (D) begin gammaglobulin treatment and antibiotic ther- apy with gentamicin and mezlocillin (E) begin antibiotic therapy with amphotericin, genta- micin, and mezlocillin V-7. Coumarin-induced skin necrosis is occasionally as- sociated with the institution of oral anticoagulants in pa- tients with (A) antithrombin III deficiency (B) protein C deficiency (C) factor VIII deficiency (D) plasminogen deficiency (E) dysfibrinogenemias V-8. A 55-year-old woman presents to the emergency de- partment because her family notes that she has yellow skin. The patient has lost 7 kg (15 lbs) over the past 3 months but states that this is because she has been dieting in preparation for her daughter’s wedding. Her past med- ical history is significant only for vitiligo. Her physical examination is unremarkable except for the presence of scleral icterus and a yellow tinge to the skin. Laboratory evaluation reveals hematocrit of 17%, WBC count of 2500/ ␮ L, and platelet count of 70,000/ ␮ L. Serum chem- istries are normal except for direct bilirubin of 51 ␮ mol/ L (3 mg/dL) and indirect bilirubin of 12 ␮ mol/L (0.7 mg/ dL). The patient’s reticulocyte count is 3%. MCV is 108 fL. Which one of the following additional laboratory findings would most likely be associated with this pa- tient’s clinical syndrome? (A) Clonal chromosomal abnormalities on karyotypic analysis of the bone marrow (B) Positive direct Coombs’ test (C) Extrahepatic biliary obstruction (D) Decreased gastric fluid pH (E) Antiparietal cell antibody V-9. A 43-year-old woman was diagnosed as having an infiltrating ductal carcinoma of the right breast when she was 41. The lesion was 3 cm in diameter. Lymph node examination was negative. Estrogen and progesterone re- ceptors were negative. She underwent a lumpectomy, fol- lowed by radiation therapy to the breast and chest wall, followed by six cycles of cyclophosphamide plus doxo- rubicin chemotherapy. At this time she feels well but has two 2-cm nodules in each lung on chest radiography. These were not present on prior chest radiographs. In dis- cussing the situation with the patient, which of the follow- ing statements is correct? (A) These nodules are a late manifestation of cyclo- phosphamide toxicity. (B) Tamoxifen therapy should be employed at this time. (C) Autologous bone marrow transplantation offers this patient the best chance for long-term disease- free survival. (D) An antibody to the erbB2 proto-oncogene may im- prove the response to chemotherapy. (E) The patient has a median survival of approxi- mately 6 to 12 months. V-10. A 27-year-old woman presents with stage II (breast and lymph node involvement) right breast cancer. Her family history is markedly positive for other tumors. One of her sisters developed an osteogenic sarcoma at age 17, her brother was diagnosed with acute leukemia at age 5, her mother died of breast cancer, and she has two uncles with soft-tissue sarcomas, both developing this disease when in their thirties. This patient’s peripheral blood lym- phocytes would be most likely to reveal which of the fol- lowing abnormalities? (A) Retinoblastoma gene mutation (B) p53 gene mutation (C) Translocation between chromosomes 9 and 22 (D) Translocation between chromosomes 8 and 14 (E) Mutations of epidermal growth factor receptor gene V-11. A patient with a myelodysplastic syndrome (sub- type, refractory anemia with ringed sideroblasts) has been transfusion-dependent for the past 2 years. The patient has received a total of 50 units of packed red blood cells. His physical examination is normal except for hyperpigmen- tation. Laboratory evaluation reveals mild glucose intol- erance. A trial of erythropoietin was unsuccessful. Which of the following would be the most important therapeutic approach at this time? (A) Granulocyte colony-stimulating factor (G-CSF) (B) Phlebotomy (C) Ascorbic acid (D) Desferrioxamine (E) Hypertransfusion (maintain hematocrit at 40%) V. O NCOLOGY A ND H EMATOLOGY — Q UESTIONS 37 V-16. (Continued)V-12. A 26-year-old woman has painful mouth ulcers. Six weeks ago, she was started on propylthiouracil for hyper- thyroidism. She is afebrile, and physical examination is unremarkable except for several small oral aphthous ul- cers. White blood cell count is 200/ ␮ L (15% neutrophils, 80% lymphocytes, 5% monocytes); hemoglobin concen- tration, hematocrit, and platelet count are normal. The woman’s physician should stop the prophylthiouracil and (A) schedule a follow-up outpatient appointment (B) arrange for HLA typing of her siblings in prepara- tion for bone marrow transplantation (C) prescribe oral prednisone, 1 mg/kg (D) hospitalize her for broad-spectrum antibiotic ther- apy (E) hospitalize her for white blood cell transfusion V-13. An 18-year-old black man undergoing a physical ex- amination prior to playing college sports is found to have a normal CBC except that the MCV is 72 fL. Subsequent testing reveals a normal metabisulfite test and a normal hemoglobin electrophoresis. Which of the following con- ditions most likely accounts for these findings? (A) Hemoglobin E trait (B) Sickle C disease (C) Sickle ␤ thalassemia (D) ␤ -thalassemia trait (E) ␣ -thalassemia trait V-14. A 30-year-old black woman with long-standing sickle cell anemia presents with severe pain in the chest and abdomen ϳ1 week after having an upper respiratory infection. No intrathoracic or intraabdominal pathology was immediately obvious on routine physical examination and laboratory evaluation. The most appropriate therapeu- tic intervention at this point is (A) hypertransfusion (B) hydration and narcotic analgesia (C) hydroxyurea (D) broad-spectrum antibiotics (E) exploratory laparotomy V-15. In persons who have chronic myelogenous leuke- mia, the translocation that accounts for the Philadelphia chromosome most commonly is found in (A) all cells of the body (B) all three hematopoietic cell lines but not in nonhe- matopoietic cells (C) all cells of the granulocytic cell line but not in nongranulocytic cells (D) all bone marrow stem cells but not in mature cells (E) all bone marrow stem cells and certain mature granulocytes V-16. Which of the following statements describes the re- lationship between testicular tumors and serum markers? (A) Pure seminomas produce ␣ -fetoprotein (AFP) or ␤ -human chorionic gonadotropin ( ␤ -hCG) in Ͼ90% of cases. (B) More than 40% of nonseminomatous germ cell tu- mors produce no cell markers. (C) Both ␤ -hCG and AFP should be measured in fol- lowing the progress of a tumor. (D) Measurement of tumor markers the day following surgery for localized disease is useful in determin- ing completeness of the resection. (E) ␤ -hCG is limited in its usefulness as a marker, be- cause it is identical to human luteinizing hormone. V-17. A 45-year-old man presents with fatigue. Two years ago the patient received six cycles of combination chemo- therapy (each cycle consisted of cyclophosphamide, dox- orubicin, vincristine, and prednisone) for non-Hodgkin’s lymphoma in chest and abdominal sites. The patient en- tered complete remission and has been followed expec- tantly since that point. His last prior visit was 3 months ago at which time he had no evidence of recurrent lym- phoma, felt well, and had a normal laboratory examina- tion. At this time his physical examination is remarkable for a purple discoloration of the fingertips, ears, and nose. The patient is somewhat pale. There is no evidence for peripheral lymphadenopathy. Laboratory studies include the following: white count 10,000/ ␮ L (differential 60% neutrophils, 10% bands, 10% lymphocytes, 10% mono- cytes, 3% eosinophils, 1% basophils, 2% metamyelocytes, 1% myelocytes, and 1% nucleated red blood cell), he- matocrit 28% and platelet count 300,000/ ␮ L. The follow- ing results are also found: MCV 98 fL, lactic dehydro- genase 6.8 ␮ kat/L (400 U/L), total bilirubin 51 ␮ mol/L (3.0 mg/dL), and direct bilirubin 5.1 ␮ mol/L (0.3 mg/dL). Review of the peripheral blood smear reveals clumped red cells. A routine direct Coombs’ test is negative. Addi- tional laboratory testing would most likely reveal (A) positive direct Coombs’ test (using anti-IgG anti- sera) if specimen is processed without allowing cooling (B) positive indirect Coombs’ test detected with anti- IgG antibodies (C) circulating antibodies against Epstein-Barr virus (D) circulating antibodies against fetal red blood cells (E) circulating antibodies against Mycoplasma pneu- moniae V-18. A 70-year-old man presents with back pain and fa- tigue. Workup reveals hematocrit of 30%, white blood cell count of 3.5/mL, and platelet count of 220,000/mL. Serum calcium and serum creatinine are normal. However, serum protein electrophoresis reveals a monoclonal protein of 42 g/L (4.2 g/dL), proved to be IgG-κ based on immunoelectrophoresis. Bone marrow examination dis- V. O NCOLOGY A ND H EMATOLOGY — Q UESTIONS 38 V-18. (Continued) V-20. (Continued) closes sheets of dysplastic plasma cells, and skeletal sur- vey reveals multiple osteolytic legions in the skull and spine. The patient is started on melphalan, prednisone, and erythropoietin. Which of the following would be most rea- sonable to add to the patient’s therapeutic regimen at this time? (A) G-CSF (B) Anti-interleukin (IL)6 antibodies (C) Pamidronate (D) Fludarabine (E) Doxorubicin V-19. A 25-year-old, previously healthy woman presents with jaundice, confusion, and fever. Initial physical ex- amination is unremarkable except for scattered petechiae on the lower extremities, scleral icterus, and disorientation on mental status examination. Laboratory examination discloses the following: hematocrit, 27%; white cell count, 12,000/ ␮ L; platelet count, 10,000/ ␮ L; bilirubin, 85 ␮ mol/ L (5 mg/dL); direct bilirubin, 10 ␮ mol/L (0.6 mg/ dL); urea nitrogen, 21 mmol/L (60 mg/dL); creatinine, 400 ␮ mol/L (4.5 mg/dL). Red blood cell smear discloses fragmented red blood cells and nucleated red blood cells. Prothrombin, thrombin, and partial thromboplastin times are all normal. The most effective and appropriate therapeutic maneu- ver is likely to be (A) plasmapheresis (B) administration of aspirin (C) administration of high-dose glucocorticoids (D) administration of high-dose glucocorticoids plus cyclophosphamide (E) splenectomy V-20. A 38-year-old woman presents with redness and burning in the distal extremities. She has no other com- plaints. She has never been pregnant. Physical examina- tion is normal except for redness of the fingertips and splenomegaly. Laboratory examination reveals hematocrit 40%, WBC count 9000 with a normal differential, and platelet count of 950,000/ ␮ L. Other laboratory studies in- clude reticulocyte count of 1%, bone marrow examination that discloses a hypercellular marrow with megakaryocy- tic hyperplasia and hyperlobated megakaryocytes, absent collagen deposition, and the presence of normal amounts of bone marrow iron. Cytogenetic studies reveal a normal female karyotype. A red cell mass study is normal. Which of the following statements concerning the patient’s con- dition is true? (A) Observation is indicated. (B) Splenectomy should be performed. (C) Oral administration of chlorambucil, 0.4 mg/kg daily for 5 days, should begin. (D) Aspirin, 2 tablets every 6 h, should be adminis- tered. (E) Hydroxyurea, 1000 mg daily orally, is indicated. V-21. A 42-year-old woman presents with epistaxis and gum bleeding. Physical examination is remarkable for a temperature of 38ЊC (100.4ЊF) and petechiae on the lower extremities. Laboratory evaluation includes a hematocrit of 29%, platelet count of 15,000/ ␮ L, and WBC of 2100/ ␮ L (differential including 22% blasts, 30% promyelo- cytes, 20% lymphocytes, 10% monocytes, 2% myelocy- tes, and 3% metamyelocytes). PT is 15 s and PTT is 55 s. Bone marrow examination discloses a hypercellular marrow infiltrated with myeloblasts and heavily granu- lated promyelocytes. Myeloperoxidase stain of a bone marrow aspirate smear is markedly positive and demon- strates numerous intracellular rodlike forms. The patient is begun on all-trans retinoic acid. Which of the following is the most likely complication of this therapy? (A) Worsening of disseminated intravascular coagulop- athy (B) Infection during neutropenia (C) Respiratory distress (D) Uric acid nephropathy (E) Mucositis V-22. Which of the following statements regarding toxic effects of chemotherapy is correct? (A) Anthracyclines are relatively nonmyelosuppressive. (B) Vincristine is a relatively weak myelosuppressive agent and can be administered during periods of low blood counts. (C) Cisplatin-induced nausea and vomiting are mild. (D) The use of bleomycin has been associated with secondary leukemia. (E) Cisplatin can produce hypercalcemia by imparing renal excretion. V-23. A 45-year-old man develops leukocytosis and fa- tigue. Workup reveals infiltration of the bone marrow with lymphoblasts. A sample of bone marrow is also sent for immunologic and cytogenetic analysis. Which of the fol- lowing findings would be associated with the best prog- nosis? (A) Common acute lymphocytic leukemia antigen (CALLA) CD10 positivity, normal cytogenetics (B) CALLA CD10 positivity, t(9;22) (C) Surface immunoglobulin positivity, t(8;14) (D) My10 (CD34) positivity, normal cytogenetics (E) My7 (CD13) positivity, t(4;11) translocation V-24. Two years ago a 68-year-old man was found to have a prostate nodule on routine examination. Biopsy revealed V. O NCOLOGY A ND H EMATOLOGY — Q UESTIONS 39 V-24. (Continued) poorly differentiated prostatic adenocarcinoma; staging studies failed to reveal any evidence of extraprostatic spread. Because of a desire to maintain potency, the pa- tient opted for radiation therapy as primary treatment. Ex- cept for requiring lower extremity revascularization for intractable claudication, he did well until recently, when he developed pain in his right hip. Prostate specific anti- gen was elevated. Bone scan revealed areas of positive uptake in the pelvis and ribs (not present on the original staging study). The patient expresses a desire not to have a bilateral orchiectomy, “unless it would significantly im- prove my quality of life or survival compared with other therapies.” The most appropriate strategy at this point is to (A) biopsy one of the bony lesions (B) administer cisplatin and 5-fluorouracil (C) administer leuprolide and flutamide (D) administer diethylstilbestrol (DES) at low dose (E) perform an orchiectomy V-25. A 72-year-old man with known benign prostatic hy- pertrophy develops fever and flank pain. He rapidly be- comes very ill. He presents to the emergency room with a blood pressure of 80/40 mmHg, heart rate of 120, and a temperature of 39.5ЊC (103ЊF). His urine shows numer- ous white cells. His laboratory examination is remarkable for a white count of 2000, hematocrit of 28%, and platelet count of 10,000. The PT and PTT are elevated. The most appropriate way to deal with this patient’s coagulopathy is (A) intravenous ⑀ -aminocaproic acid (B) intravenous heparin (C) platelets and fresh-frozen plasma (D) antithrombin 3 concentrates (E) intravenous antibiotics V-26. A 65-year-old woman presents with bleeding gums. Except for the presence of petechiae on the ankles, the physical examination is unremarkable. The white blood cell count is 500/ ␮ L with 10% neutrophils, the hematocrit is 25%, and the platelet count is 10,000/ ␮ L. Examination of a bone marrow biopsy reveals a cellularity of 10%. The few cells available for scrutiny do not reveal any mor- phologic abnormalities. The patient has no history of re- cent drug ingestion or hepatitis and has never experienced any similar problems. The most appropriate therapy for this patient would be (A) prednisone (B) low-dose ara-C (C) plasmapheresis (D) antithymocyte globulin, cyclosporine, methylpred- nisone, and G-CSF (E) G-CSF, erythropoietin, and IL-11 V-27. A patient being treated for refractory anemia has required monthly transfusions of 2 units of packed red blood cells over the past several months. Three days after receiving 2 units of packed red blood cells for a hematocrit of 22%, the patient’s hematocrit was 27%. One week after the transfusion the hematocrit is 22%; the patient feels ill, has a low-grade fever, and is mildly jaundiced. Which of the following statements about this situation is incorrect? (A) This problem is probably due to autoantibodies. (B) Intravascular hemolysis has probably occurred. (C) The Rh status of donor and recipient should be re- checked. (D) If the patient is Rh-positive, one should look for anti-Kell or anti-Duffy antibodies in the patient’s serum. (E) A positive direct Coombs’ test is unlikely. V-28. Intravenous aprotinin is given to patients undergo- ing cardiac surgery to reduce blood loss. The mechanism of action is (A) primary inhibition of fibrinolysis (prevents dissolu- tion of formed clots) (B) prevention of activation of the clotting cascade (C) prevention of activation of the clotting cascade and inhibition of fibrinolysis (D) enhancement of platelet activity (E) enhancement of platelet activity and inhibition of activation of the clotting cascade V-29. Which of the following statements regarding ovar- ian cancer is correct? (A) A surgical debulking procedure is unhelpful. (B) Nulliparity is a risk factor. (C) A history of cervical cancer is a risk factor. (D) Stromal cell and germ cell tumors of the ovary are the most common histologic subtypes. (E) Histologic grade is not an important prognostic factor. V-30. A 65-year-old woman on hemodialysis for chronic renal failure requires an urgent dental extraction for an abscessed tooth. Of the following, the most appropriate agent to administer to reduce the risk of significant bleed- ing would be (A) desmopressin (B) conjugated estrogen (C) erythropoietin (D) fresh-frozen plasma (E) ⑀ -Aminocaproic acid V-31. A 70-year-old woman is well except for a history of hypertension. On a routine physical examination, com- plete blood count and serum chemistry analysis are all normal except for total protein, which is 80 g/L (8.0 g/ V. O NCOLOGY A ND H EMATOLOGY — Q UESTIONS 41 V-37. (Continued) V-40. (Continued) ity from colorectal cancer in annually screened persons. (D) Present American Cancer Society recommenda- tions include Hemoccult screening beginning at age 50 and sigmoidoscopic examination every 3 to 5 years beginning at age 50 for persons at average risk. (E) Rehydration of Hemoccult slides has no effect on the positivity rate. V-38. A 53-year-old man with rectal bleeding was found to have adenocarcinoma 2 cm below the peritoneal re- flection. After a negative metastatic workup, the patient underwent resection of the tumor with primary reanasto- mosis. Pathologic examination revealed a moderately well-differentiated adenocarcinoma of the rectum with 2 of 10 adjacent lymph nodes that contained cancer. The patient has no other medical problems. Optimal therapy at this point should include (A) pelvic radiation therapy alone (B) a chemotherapy regimen containing 5-fluorouracil (5-FU) (C) a combination of pelvic irradiation and a chemo- therapy regimen containing 5-FU (D) a chemotherapy regimen containing 5-FU plus lev- amisole (E) observation alone V-39. A 36-year-old woman presents with a firm painless mass in her right thigh just superior to her knee. A CT scan reveals a 4- by 5-cm solid mass attached to the mus- cle. You refer the patient to a surgeon, who performs an incisional biopsy. The pathology indicates high-grade fi- brosarcoma with several mitoses per 10 high-power fields. The most appropriate management at this point is (A) observation (B) radiation therapy (C) chemotherapy with a doxorubicin-containing regi- men (D) radiation therapy plus chemotherapy with a doxo- rubicin-containing regimen (E) complete excision of the mass V-40. A 50-year-old man with a history of organomegaly and an elevated hematocrit without an apparent secondary cause was well until the sudden onset of pain in the right upper quadrant. On examination the patient is afebrile and has clear lungs, normal cardiac function, an abdominal fluid wave, splenomegaly, and a markedly enlarged liver with a palpable, very tender edge. Liver function tests are normal except for mild elevation of hepatic transminases. Which of the following is the most appropriate procedure for the purposes of establishing a diagnosis? (A) CT scan of the liver (B) Abdominal ultrasound (C) Radionuclide liver-spleen scan (D) Hepatic venography (E) Paracentesis V-41. A 65-year-old man with long-standing, stable bi- opsy-proven postnecrotic cirrhosis develops abdominal pain in the right upper quadrant and abdominal swelling. He is afebrile. Palmar erythema, spider telangiectasias, and mild jaundice are noted on physical examination. His abdomen is distended, shifting dullness is present, a ten- der, firm liver edge is felt 3 finger-breadths below the right costal margin, and a spleen tip is palpable. A faint bruit is heard over the liver. Laboratory values include the fol- lowing: Hematocrit: 34% White blood cell count: 4300/ ␮ L Platelet count: 104,000/ ␮ L Serum albumin: 26 g/L (2.6 g/dL) Serum globulins: 46 g/L (4.6 g/dL) Alkaline phosphatase: 8.0 ␮ kat/L (480 U/L) Paracentesis reveals blood-tinged fluid. The serum marker most specifically associated with this man’s con- dition is (A) antinuclear antibody (B) ␣ fetoprotein (C) antimitochondrial antibody (D) 5′-nucleotidase (E) chorionic gonadotropin V-42. A 68-year-old man is undergoing adjuvant chemo- therapy for completely resected colon cancer that involved several pericolonic lymph nodes at the time of his surgical resection. He calls the internist covering for his primary oncologist with a complaint of a few days of diarrhea. He tells the physician that he has experienced approximately three to five loose watery stools per day over the past few days. He is mildly light-headed when walking around. The patient should be told to (A) take loperimide and increase oral fluid intake (B) begin metronidazole for presumed Clostridium dif- ficile colitis (C) begin therapy with octreotide (D) come to the clinic or emergency room for evalua- tion (E) begin loperimide and metronidazole and increase fluid intake V-43. A 73-year-old woman with known myelodysplastic syndrome and chronic anemia has required multiple trans- [...]... in non-small cell lung cancer V-47 A 43-year-old woman presents with a hematocrit of 25 %, an MCV of 101, reticulocyte count of 1 .2% , platelet V-47 (Continued) count of 25 ,000/␮L, and white count of 23 00/␮L with 25 % neutrophils Non-Hodgkin’s lymphoma was diagnosed 6 years ago At that time she presented with diffuse large cell lymphoma in abdominal and cervical lymph nodes She underwent six cycles of cyclophosphamide,... fungal infection of the chest V-60 The most common cause of high serum calcium in a patient with a known cancer is (A) ectopic production of parathyroid hormone (B) direct destruction of bone by tumor cells (C) local production of tumor necrosis factor and IL-6 by bony metastasis (D) high levels of 1 ,25 -hydroxyvitamin D (E) production of parathyroid hormone – like substance V-61 A 35-year-old man with... dysarthria, and past-pointing on finger-tonose testing She also has an unsteady gait MRI reveals atrophy of both lobes of the cerebellum Serologic evaluation reveals the presence of anti-Yo antibody Which of the following is the most likely cause of this clinical syndrome? (A) Non-small cell cancer of the lung (B) Small cell cancer of the lung V-58 (C) (D) (E) (Continued) Breast cancer Non-Hodgkin’s lymphoma... cytarabine, and cisplatin V-56 A 5 2- year-old man noted a pigmented lesion in the area of his left flank Excisional biopsy revealed a malignant melanoma 2. 5 mm in thickness The patient then underwent a definitive resection of the tumor with 2- cm margins that were not involved Chest x-ray and liver function tests are normal The patient should receive (A) (B) (C) (D) (E) interferon-␣ interleukin -2 dacarbazine dacarbazine... antigen (PSA) Beta human chorionic gonadotropin (␤-hCG) Carcinoembryonic antigen (CEA) CA- 125 CA1 9-9 V-83 Which of the following is likely to be a neoplasm of T-lymphocyte lineage? (A) (B) (C) (D) (E) Chronic lymphocytic leukemia Follicular lymphomas Burkitt’s lymphoma Mycosis fungoides Small lymphocytic (well-differentiated) lymphomas V-84 A 29 -year-old woman undergoing an infertility workup presents... chromosome is present in about 25 to 33% of adults with ALL but only in 3 – 5% of children Rearrangements involving the MLL gene on chromosome 11q23, such as the t(4;11) translocation, are about equally common in both age groups The so-called tel-1-CBF␣ fusion mRNA created when there is a t( 12; 21) chromosomal translocation (often occult on routine karyotype analysis) is present in 22 % of children and almost... one of the four ␣-globin genes is deleted Such persons have no hematologic abnormalities Persons with deletion of two of the four ␣-chain genes (␣-thalassemia trait) tend to have microcytic and slightly hypochromic red cells without significant hemolysis or anemia Hemoglobin electrophoresis may be normal or may reveal a decreased amount of hemoglobin A2 Deletion of three of the four ␣-chain genes, so-called... blood reveals that most of the cells express the CD20, CD23, and CD5 antigens A CT scan of the chest, abdomen, and the pelvis discloses multiple 1- to 2- cm lymph nodes in the peri-aortic area The most appropriate therapy at this time is (A) (B) (C) (D) (E) observation intravenous gammaglobulin chlorambucil chlorambucil and prednisone fludarabine V-63 A 65-year-old man presents because of fatigue He has no... basis of a non-BRCA-1 or -BRCA -2 mutation If the affected relative is positive for one of these mutations, then given the autosomal dominant inheritance pattern, the sibling has a 50% chance to carry this mutation in the germline and thereby have a very high risk for developing breast or ovarian cancer If the affected sister had a sample of blood sent for germline sequencing of BRCA-1 and BRCA -2 genes... tested for presence of BRCA-1 or BRCA -2 mutation (B) recommend that the patient be tested for the presence of BRCA-1 or BRCA -2 mutation (C) recommend bilateral simple mastectomies (D) recommend bilateral total mastectomies (E) recommend annual mammographic screening V-55 A 4 2- year-old man is admitted to the hospital with a fever Eight days ago he received his third cycle of cyclophosphamide, doxorubicin, . in non-small cell lung cancer. V-47. A 43-year-old woman presents with a hematocrit of 25 %, an MCV of 101, reticulocyte count of 1 .2% , platelet count of 25 ,000/ ␮ L, and white count of 23 00/ ␮ L. An antibody to the erbB2 proto-oncogene may im- prove the response to chemotherapy. (E) The patient has a median survival of approxi- mately 6 to 12 months. V-10. A 27 -year-old woman presents with. O NCOLOGY A ND H EMATOLOGY — Q UESTIONS 45 V-61. (Continued) V-64. (Continued) (E) placement of a CT-guided catheter for percutane- ous drainage of the abdominal abscess V- 62. A 70-year-old woman presents to her