Because Pathology Need Not Be the Root of All Suffering
The image is a microscopic section of the heart with an acute myocardial infarction. The cardiac myocytes have coagulative necrosis, with preservation of architecture but with loss of nuclear basophilia. Associated with the coagulative necrosis is a extensive neutrophilic infiltrate (see black arrows in image below).
The timing of the infarct would be around 2-3+ days.
Question 116
A 65-year-old male with a past medical history of hypertension, hyperlipidemia, and a 30 pack-year smoking history sustains an episode of chest pain while golfing with friends. He tells his friends that it feels like someone is standing on his chest and he clenches his fist in front of his chest when he does so. In addition to the pain, he is nauseous and sweating. They try to convince him to call an ambulance, but he refuses. The pain stops about 4 hours after it began. Three days later, his wife finds him dead in bed when she awakes. He had no complaints the night before. Of the following, which is most likely to be found at autopsy?
A. A ruptured ventricular aneurysm
B. A ruptured ventricular free wall
C. A ruptured interventricular septum
D. A ruptured papillary muscle
E. A ruptured coronary artery
Answer: B (a ruptured ventricular free wall).
Explanation: the symptoms are consistent with an acute coronary syndrome (i.e., pressure sensation in the chest associated with sweating and nausea). .He has several risk factors for coronary artery atherosclerosis, including his age, sex, and history of hypertension, hyperlipidemia, and smoking history. At three days, rupture of the myocardium can occur. The most common location is the free wall, which would lead to cardiac tamponade and a relatively quick death. Rupture of the interventricular septum and papillary muscle are much less common, and, while both are emergencies, the survival time would be expected to be longer and the patient would most likely be symptomatic. A ventricular aneurysm develops at >2 weeks after the myocardial infarct, and, because it is composed of scar tissue, does not commonly rupture. While a ruptured coronary artery could cause a hemopericardium and death, rupture of the coronary artery is not normally associated with an acute myocardial infarct.
Question 117
A 61-year-old male comes to the emergency room complaining of abdominal pain. He says that over the past 3 months, he has had abdominal pain which occurs 1-2 hours after eating, and then dissipates. Because of this pain, he has not wanted to eat, and has lost 20 lbs in that time frame. He has a 40 pack-year smoking history and hypertension. Of the following, what is the most likely diagnosis?
A. Acute mesenteric ischemia
B. Chronic mesenteric ischemia
C. Abdominal aortic aneurysm
D. Atypical acute myocardial infarct
E. Vasculitis
Answer: B (Chronic mesenteric ischemia)
Explanation: the history of abdominal pain occurring after eating a meal is characteristic of mesenteric ischemia. Because the disease process has been going on for some time, the best diagnosis would be chronic mesenteric ischemia. The pain occurs because atherosclerotic narrowing of the celiac artery or superior mesenteric artery or both blocks blood flow, and, when increased blood flow is needed to facilitate digestion, it does not develop and ischemia occurs. An abdominal aortic aneurysm can cause abdominal pain; however, not so consistently associated with meals. An atypical acute myocardial infarct should be considered when an older male (or female) with risk factors for atherosclerosis presents with abdominal pain, but the clinical presentation would be acute, nor chronic. Vasculitis can involve the celiac or mesenteric vessels; however, it would be much more rare than atherosclerosis.
Question 118
A 41-year-old male who has been diagnosed with hypertension for 2 years presents to his physician complaining of weakness, which he says comes and goes. Physical examination reveals a blood pressure of 152/81 mmHg, but is normal otherwise, including normal heart and lung sounds. Laboratory testing reveals an elevated concentration of sodium and a decreased concentration of potassium in the blood. A CT scan of the abdomen reveals a nodule in the right adrenal gland Additional laboratory testing would most likely reveal an elevated concentration of which of the following?
A. Aldosterone
B. ACTH
C. Epinephrine
D. Renin
E. Beta natriuretic peptide (BNP)
Answer: A (aldosterone)
Explanation: patients with an aldosterone-secreting adrenal adenoma (or, with adrenal cortical hyperplasia) can develop secondary hypertension. While patients can have only hypertension, they can also have hypernatremia and hypokalemia, which are associated with episodic weakness. In these individuals, laboratory testing would reveal an elevated concentration of aldosterone. Reninomas occur in the kidney and can be associated with hypertension. Pheochromocytomas occur as a nodule in the adrenal medulla and secrete catecholamines, but are not associated with hypernatremia or hypokalemia, and the hypertension and related symptoms are episodic. While Cushing syndrome is a cause of secondary hypertension, and with a pituitary adenoma, patients could have an increased concentration of ACTH, the patient has no other features of Cushing syndrome (e.g., thin skin, osteopenia, obesity, round facies).
QUESTION 113
A 67-year-old male with a past medical history of hypertension, hyperlipidemia, and a 30 pack-year smoking history is brought to the emergency room by ambulance, following an episode of chest pain occurring while golfing with friends, which started 6 hours ago. He describes the chest pain as though someone were standing on his chest and he clenches his fist in front of his chest when he does so. In addition to the pain, he is short of breath, nauseous, and sweating. He says that the pain extends to his left and right arm and jaw. His vital signs are BP of 164/96, heart rate of 104 bpm, and respiratory rate of 23 breaths per minute. Laboratory testing reveals an elevated troponin I upon admission. Of the following, which finding is most likely to be identified via physical examination?
A. A pleural rub
B. A pericardial friction rub
C. A systolic murmur
D. A diastolic murmur
E. Asymmetric pulses
Answer: C (a systolic murmur)
Explanation: the symptoms are consistent with an acute coronary syndrome (i.e., pressure sensation in the chest associated with sweating, nausea, and shortness of breath, and with the pain extending to the left arm, right arm, and jaw). The elevated troponin I indicates damage to the cardiac myocytes, which would be consistent with an acute myocardial infarct. With injury to the myocardium, papillary muscle dysfunction can occur, resulting in mitral insufficiency, which would be a systolic murmur. While a pericardial friction rub can occur in association with pericarditis due to an acute myocardial infarct, normally this requires at least around 1 day before it develops and would not be present at 6 hours.
QUESTION 114
A 51-year-old male with a past medical history of poorly-controlled hypertension for 10 years presents to the emergency room with complaints of a sharp tearing pain in his chest that radiates to his back. The blood pressure in his right and left arm are 151/91 and 149/90 respectively. Physical examination reveals no murmur. A chest x-ray reveals a widened mediastinum. He is told he needs emergent surgery; however, he refuses and leaves against medical advice. Given that he survives without surgery, of the following, which is most likely to develop as a result of his presenting condition?
A. Coarctation of the aorta
B. False aneurysm
C. A dilated left ventricle of the heart
D. Berry aneurysm
E. True aneurysm
Answer: B (False aneurysm)
Explanation: the clinical scenario is consistent with an aortic dissection, which most commonly occur in the background of hypertension. The absence of a murmur indicates that the dissection did not extend to the heart, as if it had done so, it would most likely have caused aortic insufficiency. Given that he survived, the aortic dissection was contained, but would have, on image, appeared as a bulge in the wall of the vessel–therefore, it would be a false aneurysm. As the intima and most of the media are on the lumen side of the hemorrhage, a true aneurysm would not develop. An aortic dissection does not normally cause coarctation of the aorta, and, with no aortic insufficiency, if would not cause a dilated left ventricle of the heart. A berry aneurysm occurs in the brain, and hypertension will contribute to its development, but berry aneurysms are not associated otherwise with aortic dissection.
QUESTION 115
A 63-year-old male comes to the emergency room complaining of abdominal pain. He says that over the past 2 months, he has had abdominal pain which occurs 1-2 hours after eating, and then dissipates. Because of this pain, he has not wanted to eat, and has lost 15 lbs in that time frame. He has a 30 pack-year smoking history and hypertension. Of the following, what other disease process is most likely to be identified?
A. Metastatic lung carcinoma
B. Berry aneurysm
C. Pheochromocytoma
D. Peripheral vascular disease
E. Early onset Alzheimer’s disease
Answer: D (peripheral vascular disease)
Explanation: the history of abdominal pain occurring after eating a meal is characteristic of mesenteric ischemia. Because the disease process has been going on for some time, the best diagnosis would be chronic mesenteric ischemia. Chronic mesenteric ischemia is most commonly due to atherosclerosis of the celiac artery, superior mesenteric artery or both. As atherosclerosis is a systemic disorder, in patients with one form of atherosclerosis, another form can often be found; thus, in a person with chronic mesenteric ischemia, of the choices, peripheral vascular disease, which is also most commonly due to atherosclerosis, would be the one most likely to be identified.
QUESTION 109
A 64-year-old female is brought to the emergency room by her family. She developed a severe substernal chest discomfort 4 hours ago that was not relieved with antacids. In addition to the pain, she is nauseous and sweating. She says that the pain extends into her left and right arm. Her vital signs are BP of 161/92, heart rate of 102 bpm, and respiratory rate of 21 breaths per minute. Laboratory testing reveals a normal troponin I upon admission, and a repeat troponin I at 3 hours later is also normal. Of the following, what is the most likely diagnosis?
A. Stable angina
B. Unstable angina
C. Variant angina
D. non-ST elevation myocardial infarct
E. ST elevation myocardial infarct
Answer: B (unstable angina)
Explanation: given the acute presentation and with no past history of similar symptoms, stable angina would not be the most likely diagnosis. While the symptoms have been on-going for 4 hours, the laboratory testing reveals no elevation of troponin I (and with the laboratory testing repeated 3 hours later) so there is no evidence of cardiac myocyte injury, as troponin I should have risen by this time, and thus, a non-ST or ST elevation myocardial infarct are not likely. Unstable angina is one form of acute coronary syndrome.
QUESTION 110
A 67-year-old female with a past medical history of hyperlipidemia, diabetes mellitus type II and a 40 pack-year smoking history is brought to the emergency room by her family. She developed a severe substernal chest discomfort 6 hours ago that was not relieved with antacids, and was described as being like someone standing on her chest. In addition to the pain, she is nauseous, sweating, and short of breath. She says that the pain extends to her jaw. Her vital signs are BP of 155/93, heart rate of 101 bpm, and respiratory rate of 20 breaths per minute. Laboratory testing reveals an elevated troponin I upon admission. Of the following, what is the most likely diagnosis?
A. Stable angina
B. Unstable angina
C. Acute myocardial infarct
D. Aortic dissection
E. Angiosarcoma of the heart
Answer: C (acute myocardial infarct)
Explanation: the symptoms are consistent with an acute coronary syndrome, with a pressure-like pain in the chest, which is associated with nausea, sweating, and shortness of breath, and with risk factors for coronary artery atherosclerosis, including her age, and history of hyperlipidemia, diabetes mellitus type II, and smoking history. The elevated troponin I indicates injury to cardiac myocytes, which rules out stable angina and unstable angina. The most likely diagnosis is an acute myocardial infarct (a form of acute coronary syndrome). While an aortic dissection can cause an elevated troponin I, given the lack of a past history of hypertension, and the nature of the chest pain, an acute myocardial infarct is more likely than an aortic dissection. An angiosarcoma of the heart would be very rare.
QUESTION 111
A 65-year-old female with a past medical history of hypertension and a 40 pack-year smoking history is brought to the emergency room by ambulance. She had developed a severe substernal chest discomfort 2 hours ago that was not relieved with antacids, and was described as being like someone standing on her chest. In addition to the pain, she is sweating and short of breath. She says that the pain extends to both her left and right arm. Her vital signs are BP of 162/90, heart rate of 103 bpm, and respiratory rate of 21 breaths per minute. Laboratory testing reveals an elevated troponin I upon admission. She sustains a cardiac arrest while in the emergency room. Of the following, what would an autopsy most likely identify in the myocardium?
A. Rupture of the free wall
B. Rupture of the interventricular septum
C. A large soft yellow discoloration
D. A large firm white discoloration
E. Grossly normal cardiac muscle
Answer: E (Grossly normal cardiac muscle)
Explanation: the symptoms are consistent with an acute coronary syndrome (i.e., pressure sensation in the chest associated with sweating and shortness of breath, and with the pain extending to the left and right arm). The elevated troponin I indicates damage to the cardiac myocytes, which would be consistent with an acute myocardial infarct. Her cause of death was a cardiac dysrhythmia. Ruptures occur around 1-3 days. A large soft yellow discoloration would be an acute infarct, with the yellow representing coagulative necrosis and neutrophilic infiltrate; however, to see a well-developed acute myocardial infarct, the time since the pain began would be around 1 day at least. A large firm white discoloration would be a remote myocardial infarct, and would indicate an age of 2 months or more.
QUESTION 112
A 63-year-old female with a past medical history of diabetes mellitus type II, hyperlipidemia, and a 30 pack-year smoking history is brought to the emergency room by ambulance. She developed a severe substernal chest discomfort 4 hours ago while playing cards with friends. She described the pain as being like someone was standing on her chest. In addition to the pain, she is short of breath and sweating. She says that the pain extends to her left arm. Her vital signs are BP of 149/90, heart rate of 102 bpm, and respiratory rate of 21 breaths per minute. Laboratory testing reveals an elevated troponin I upon admission. Of the following, which is most likely to be present in a coronary artery?
A. An atheroma, with a thin fibrous cap, that produces 75% stenosis
B. An atheroma, with a thick fibrous cap, that produces 75% stenosis
C. Marked focal neutrophilic infiltrate of the wall associated with fibrinoid necrosis
D. Focal granulomatous inflammation
E. Hemorrhage into an atheroma with rupture and resultant thrombosis of the lumen
Answer: E (hemorrhage into an atheroma with rupture and resultant thrombosis of the lumen)
Explanation: the symptoms are consistent with an acute coronary syndrome (i.e., pressure sensation in the chest associated with sweating and shortness of breath, and with the pain extending to the left arm). The elevated troponin I indicates damage to the cardiac myocytes, which would be consistent with an acute myocardial infarct. An acute coronary syndrome is caused by an acute change within an atheromatous plaque, such as hemorrhage, thrombosis, or both. E. describes an acute change. A and B do not describe an acute change. Both A and B would be associated with stable angina. A. describes a vulnerable plaque, which would be predisposed to rupture, but, which, as described, is not consistent with an acute change. Both C and D, forms of vasculitis, could cause an acute myocardial infarct; however, compared to an acute plaque change occurring in the background of coronary artery atherosclerosis, vasculitis of the coronary arteries is a rare cause of an acute myocardial infarct.
QUESTION 103
A 57-year-old male with a past history of treated hypertension for 15 years, diabetes mellitus type II, and a 20 pack-year smoking history presented to an acute care clinic complaining that over the past 6 months when climbing from the 1st floor to the 3rd floor at work by the stairwell, that he had developed a pressure-like sensation in his chest. Each episode lasted for about 5 minutes, and resolved shortly after he stopped climbing the stairs. Of the following, what is the most likely diagnosis?
A. Aortic dissection
B. Metastatic lung carcinoma
C. Stable angina
D. Unstable angina
E. Acute myocardial infarct
Answer: C (stable angina)
Explanation: the man has multiple risk factors for atherosclerosis (age, sex, hypertension, diabetes mellitus, and smoking history). Given the chronicity of the symptoms (i.e., occurring over a 6 month time period), aortic dissection, unstable angina, and acute myocardial infarct are all unlikely, as these are acute events. The symptoms are characteristic for stable angina, which is caused by coronary artery atherosclerosis. When the plaque reaches a critical degree of stenosis (70-75%), during exercise an adequate amount of blood to oxygenate the myocardium can no longer reach the heart, and chest pain occurs. While metastatic lung carcinoma, given the smoking history, is possible, compared to stable angina, would be a rare cause of such a clinical presentation.
QUESTION 104
A 52-year-old male with a past history of treated hypertension for 20 years, diabetes mellitus type II, and a 30 pack-year smoking history presented to an acute care clinic complaining that over the past 4 months when climbing from the 1st floor to the 4th floor at work by the stairwell, that he had developed a pressure-like sensation in his chest. Each episode lasted for about 5 minutes, and resolved shortly after he stopped climbing the stairs. Given that his heart is the source of his symptoms, of the following list of possible lesions of a coronary artery, what was the most likely source of the symptoms?
A. An atheroma producing 25% stenosis
B. An atheroma producing 50% stenosis
C. An atheroma producing 75% stenosis
D. A non-occlusive thromboembolus
E. A partial coronary artery dissection
Answer: C (an atheroma producing 75% stenosis)
Explanation: the symptoms, a pressure-like chest pain occurring during exertion and resolving at rest, in an older male with hypertension, diabetes mellitus, and a history of smoking, are consistent with stable angina. Stable angina is caused by a significantly stenotic atherosclerotic plaque. A 70-75% stenosis is considered significant; with less stenosis than this most often being asymptomatic. While a non-occlusive thromboembolus, such as from a mural thrombus after a myocardial infarct, or associated with a dilated cardiomyopathy could cause angina, it should present acutely, and be a sudden change. Coronary artery dissections are rare, and, while a partial dissection could cause stable angina (i.e., if the dissection occurred, then stopped, then resolved), it would be a very rare compared to atherosclerosis as a cause.
QUESTION 105
A 49-year-old male with a 40 pack-year smoking history presented to an acute care clinic complaining that over the past 6 months each time he has mowed the lawn that he developed a pressure-like sensation in his chest that occasionally was associated with some nausea. Each episode lasted for about 5 to 10 minutes, and resolved shortly after he stopped pushing the mower. His wife finally convinced him to see a doctor although he believes it was just bad heartburn. Given that his heart was the source of his symptoms, of the following, which was the initiating step in his disease process?
A. Necrosis of smooth muscle cells
B. Rupture of elastic lamina
C. Generation of reactive oxygen species
D. Endothelial dysfunction
E. Constriction of vaso vasorum
Answer: D (endothelial dysfunction)
Explanation: give a cardiac origin, the symptoms, a pressure-like chest pain occurring during exertion and resolving at rest, in an older male with hypertension, diabetes mellitus, and a history of smoking, are consistent with stable angina. The most common cause of stable angina is coronary artery atherosclerosis. The initiating step in coronary artery atherosclerosis is endothelial dysfunction, which can be induced by a variety of factors (i.e., cardiac risk factors). Once the endothelium becomes dysfunctional, it will promote thrombosis and allow attachment of white blood cells when it should not. White blood cells in the intima release reactive oxygen species and lead to oxidation of LDL, which accumulates in macrophages.
QUESTION 106
A 52-year-old male with a 30 pack-year smoking history and poorly-controlled hypertension presented to an acute care clinic complaining that over the past 3 months each time he has walked his dog at night that after 5 blocks, he developed a pressure-like sensation in his chest that occasionally was associated with some nausea. Each episode lasted for about 5 to 10 minutes, and resolved shortly after he stopped walking. Given that his heart was the source of his symptoms, of the following, which laboratory test is more likely to be elevated?
A. Troponin I
B. CK-MM
C. Erythrocyte sedimentation rate
D. ASO titer
E. Alanine aminotransferase
Answer: C (erythrocyte sedimentation rate)
Explanation: given a cardiac origin, the symptoms, a pressure-like chest pain occurring during exertion and resolving at rest, in an older male with hypertension and a history of smoking, are consistent with stable angina. The most common cause of stable angina is coronary artery atherosclerosis. In stable angina, there is no irreversible injury to cardiac myocytes, so troponin I and CK-MM (and CK-MB) should be within normal range. ASO titer (anti-streptolysin-O) is indicative of a previous Group A streptococcal infection, which is possible, but is not directly related to his disease process. Erythrocyte sedimentation rate is elevated in a variety of diseases, including coronary artery atherosclerosis. As a component of atherosclerosis is inflammation, and as ESR can be a marker for inflammation, ESR can be elevated; however, it is non-specific as a screening method for coronary artery disease.
QUESTION 107
A 54-year-old male with a past history of hypertension, diabetes mellitus type II and elevated cholesterol, presented to an acute care clinic complaining that over the past 6 months when taking the stairs to his 4th floor office, that he had developed a pressure-like sensation in his chest. Each episode lasted for about 5 minutes, and resolved shortly after he stopped climbing the stairs. Sometimes, the pain was associated with nausea, occasionally with some shortness of breath, and once, the pain radiated into his left arm. Of the following, which test would confirm the diagnosis?
A. CT scan of the chest
B. Echocardiogram
C. MRI of the back
D. Coronary artery angiogram
E. Lumbar puncture with culture
Answer: D (Coronary artery angiogram)
Explanation: the patient has several risk factors for coronary artery atherosclerosis, including age, sex, hypertension, diabetes mellitus, and hypercholesterolemia. The symptoms, given they occur with exertion and resolve within a few minutes, and can be associated with nausea, dyspnea, and radiation into the arm, are consistent with angina. A coronary artery angiogram would confirm the diagnosis.
QUESTION 108
A 58-year-old male presented to an acute care clinic complaining that he had developed a pressure-like sensation in his chest while playing basketball at the gym today with friends. The episode lasted for about 10 minutes, and was associated with some nausea and shortness of breath. The primary care physician determines that the patient’s heart is the source of the condition. Of the following, which condition would most likely be a risk factor for the patient’s disease process?
A. Chronic alcoholism
B. Metastatic tumor
C. High concentrations of HDL
D. Diabetes mellitus
E. Recurrent sinus infections
Answer: D (Diabetes mellitus)
Explanation: the symptoms are consistent with angina. The main cause of angina is coronary artery atherosclerosis. Major risk factors for coronary artery atherosclerosis include age >55 years in males, diabetes mellitus, hypertension, tobacco use, and hypercholesterolemia. Chronic alcoholism, metastatic tumor, high concentrations of HDL and recurrent sinus infections are not associated with coronary artery atherosclerosis. Low concentrations of HDL are a risk factor for atherosclerosis.
The image is liver. There is ballooning degeneration of hepatocytes (i.e., enlarged swollen hepatocytes). At the yellow arrow is bile (i.e., bile stasis) and at the black arrow is Mallory hyaline.
Steatosis of the liver–nearly every hepatocyte contains a large vacuole (macrovesicular steatosis). A common cause of steatosis of the liver is alcohol use. Other causes include obesity and diabetes mellitus. In the left upper quadrant is a portal tract.
QUESTION 89
A 5-year-old child is being seen by his pediatrician because his parents are concerned regarding his behavior during his first year of school. They are concerned that he has autism. Physical examination reveals large ears and large testicles. Of the following, what type of mutation or chromosomal abnormality underlines this child’s condition?
A. Point mutation
B. Frameshift mutation
C. Trinucleotide repeat
D. A trisomy
E. A monosomy
Answer: C (trinucleotide repeat)
Explanation: the large testicles are characteristic for Fragile X syndrome, in which patients can also have large ears, and which is a common cause of mental retardation, which can present as autism. Fragile X syndrome is due to CGG repeats.
QUESTION 90
A 19-year-old male who plays basketball for his college team is found dead in his dorm room by his roommate. He had an older brother who required a valve replacement and procedure on his aorta two years ago. Autopsy reveals an aortic dissection. A mutated gene for which of the following proteins was the most likely cause of his condition?
A. Elastin
B. Fibrillin
C. Keratin
D. Dystrophin
E. Titan
Answer: B (fibrillin)
Explanation: given that he plays basketball, the assumption can be made that he is tall. Marfan syndrome is autosomal dominant, so two affected brothers is very possible. Features of Marfan syndrome include dilation of the aortic valve ring and a myxomatous mitral valve (or, clinically, mitral valve prolapse, or floppy mitral valve), which would explain the brother’s recent medical procedure. The mutation in Marfan syndrome involves the gene for fibrillin-1. Fibrillin-1 forms a scaffold for tropoelastin, but the mutation is not in the elastin gene itself. Keratin is associated with epithelium and dystrophin and titan are found in the contractile apparatus in striated muscle.
QUESTION 91
A 25-year-old male suddenly becomes short of breath while watching television with friends. Shortly thereafter, he becomes unresponsive. An ambulance is called, but, upon arrival at the emergency room, he is pronounced dead. Autopsy identifies an aortic dissection as the cause of death. The pathologist makes a diagnosis of Marfan syndrome. Which of the following features might also be expected to occur in association with this condition?
A. Short fingers
B. Pes anserinus
C. Colonic adenocarcinoma
D. Hemorrhoids
E. Kyphoscoliosis
Answer: E (kyphoscoliosis)
Explanation: Marfan syndrome is characterized by long fingers (arachnodactyly) not short fingers. Colonic adenocarcinoma and hemorrhoids are not routinely associated with Marfan syndrome. Features of Marfan syndrome include aortic root dilation, myxomatous mitral valve, ectopia lentis, and tall stature. Patients can also have kyphoscoliosis. Pes anserinus is a normal anatomic structure.
QUESTION 92
Molecular analysis of a 10-year-old female, who was identified to have severe scoliosis, reveals a mutation in the gene for lysyl hydroxylase. Neither of her parents have a similar condition. Assuming L is for the normal allele and l is for the mutant allele, of the following, which combination best describes her parent’s genotype?
A. Father: LL; mother ll
B. Father: Ll; mother Ll
C. Father: LL; mother Ll
D. Father: LL; mother LL
Answer: B (Father Ll; mother Ll)
Explanation: the kyphoscoliotic variant of Ehlers-Danlos is due to a mutation in lysyl hydroxylase. This version of Ehlers-Danlos is autosomal recessive, so the patient’s genotype would be ll. To produce a child with an autosomal recessive disorder, when neither of the parent’s manifest the disease, both parents would have to be carriers of the mutation, so Ll.
QUESTION 93
A 24-year-old male is playing basketball with friends when he suddenly develops chest pain. His friends drive him to the emergency room, where he is admitted and diagnosed with a myocardial infarct due to a thrombus occurring in the background of severe coronary artery atherosclerosis. Although he knew about his underlying genetic disorder, he chose to ignore it and did not ever seek treatment. Of the following, what was the mode of inheritance for his underlying condition?
A. Autosomal dominant
B. Autosomal recessive
C. Co-dominant
D. X-linked
E. Mitochondrial
Answer: A (autosomal dominant)
Explanation: familial hypercholesterolemia is due to a mutation in the LDL receptor, which impairs the removal of LDL from the blood. Due to the high concentrations of LDL in the blood, these patients develop atherosclerosis at a young age, and, if untreated, often die of a myocardial infarct in their 20s. Familial hypercholesterolemia is autosomal dominant.
QUESTION 94
A 19-year-old male dies due to sepsis secondary to a pulmonary bacterial infection. At autopsy, sectioning of the lungs reveals plugging of the airways, dilation of airways, and an enlarged right ventricle with a thickened wall. Cultures of the lung grow Pseudomonas aeruginosa. Of the following, which is autopsy examination also likely to reveal?
A. Dilation of aortic root
B. Pancreatic islet metaplasia
C. Pancreatic acinar atrophy
D. Multiple liver hemangiomas
E. Patent ductus arteriosus
Answer: C (pancreatic acinar atrophy)
Explanation: the clinical features are consistent with cystic fibrosis. In cystic fibrosis, mucous in the airways becomes dehydrated, as sodium re-enters cells from the lumen, and water follows. The plugged airways will lead to dilation of the airways (bronchiectasis) and increased strain on the right side of the heart, leading to right ventricular hypertrophy and possible right sided heart failure (cor pulmonale). The changes thus described in the question stem indicate that the process was chronic and not just a one-time occurrence. Pseudomonas aeruginosa is commonly associated with cystic fibrosis, and, on culture, the colonies can be very mucoid in appearance. In addition to recurrent and chronic pulmonary infections, patients with cystic fibrosis also develop pancreatic insufficiency, due to the same changes in the lung (i.e., dehydration mucous leading to plugging of ducts). As the exocrine portion of the pancreas would be impaired from secreting proto-enzymes as normal, the cells would undergo atrophy. Dilation of the aortic root is associated with Marfan syndrome, which is not associated with recurrent pulmonary infections. Liver hemangiomas are associated with von Hippel-Lindau syndrome.
QUESTION 95
A 25-year-old male is seeing his physician because of an inability to have children. His wife of four years was evaluated by her obstetrician and no conditions that would contribute to infertility were identified. After a physical examination and appropriate imaging, the man is determined to have bilateral absence of the vas deferens, which was the cause of his infertility. Of the following, he most likely has a mutation of the gene for which protein?
A. Fibrillin
B. Collagen
C. Glucocerebrosidase
D. CF transmembrane conductance regulator
E. Acid lipase
Answer: D (CF transmembrane conductance regulator)
Explanation: while cystic fibrosis is best associated with recurrent pulmonary infections and pancreatic insufficiency, the number of mutations affecting the CFTR gene is high, and the possible phenotypes are numerous. Individuals with a mutation of the CFTR gene can survive into adulthood and be undiagnosed with the disease, until they present with infertility. In these individuals, bilateral absence of the vas deferens is a common finding.
QUESTION 96
A female neonate immediately after delivery is noted to have a distended abdomen. Forty-eight hours later, she has no passed meconium and has had an episode of bilious emesis. Of the following, what is a complication of her disease process that she will most likely develop during her lifetime?
A. Pancreatic adenocarcinoma
B. Congestive heart failure
C. Aortic dissection
D. Sinusitis
E. Glaucoma
Answer: D (sinusitis)
Explanation: the history presented is consistent with a meconium ileus, which is a complication of cystic fibrosis. The dehydrated secretions can cause plugging of the small intestine. With blockage of the small intestine, a neonate would not pass meconium and they could have bilious emesis. Of the conditions listed, sinusitis is most commonly associated with cystic fibrosis. Due to their production of secretions that are dehydrated, and therefore, thicker and more obstructing, patients with cystic fibrosis can develop pancreatic insufficiency, biliary plugging and eventual cirrhosis, and plugging of the upper respiratory tract, leading to sinusitis.
QUESTION 97
A 25-year-old male is visiting his primary care physician. He has a history of numerous pulmonary infections during his lifetime, several with Pseudomonas aeruginosa as the causative agent. He has also had numerous episodes of diarrhea when not following his prescribed diet and medication regimen. Laboratory testing has revealed elevated concentrations of ALT and AST, and his visit today is to repeat this testing. He is concerned that he may be developing cirrhosis. Of the following, what is the inheritance pattern for his condition?
A. Autosomal dominant
B. Autosomal recessive
C. Co-dominant
D. X-linked recessive
E. X-linked dominant
Answer: B (autosomal recessive)
Explanation: patients with cystic fibrosis often have recurrent and/or chronic pulmonary infections and most develop Pseudomonas aeruginosa. In addition, pancreatic insufficiency is a typical finding in these patients. Due to bile plugging, damage to the liver can occur, and can develop into cirrhosis. Cystic fibrosis is an autosomal recessive disorder.
QUESTION 98
A mother brings her child to an acute care clinic. Her and her husband delivered the child at home and have never sought medical care. The mother reports that she delivered a healthy baby boy, who was able to eat just fine; however, by about 6 months of age, her and her husband felt something was wrong. Six months later, she decided to bring her child to a doctor, as he had not talked and cannot walk. Physical examination reveals a normally developed child with pale hair and pale skin. Auscultation of the chest reveals no murmurs. Palpation of the abdomen reveals no hepatosplenomegaly. Of the following, a deficiency of which enzyme is the cause of this child’s clinical presentation?
A. CF transmembrane conductance regulator
B. Lysosomal glucosidase
C. Glucose-6-phosphatase
D. Glucocerebrosidase
E. Phenylalanine hydroxylase
Answer: E (phenylalanine hydroxylase)
Explanation: the clinical history is consistent with phenylketonuria. If untreated, the elevated concentration of phenylalanine hinders brain development, leading to mental retardation. Patients may never walk or talk. In addition, they can have decreased pigmentation of the hair and skin. The fact that the mother and her husband delivered at home and received no medical care is important, as, neonatal screening will normally detect patients with phenylketonuria, and a phenylalanine free diet can be started and the patients will develop normally. CF transmembrane conductance regulator is associated with cystic fibrosis, which is not associated with neurological conditions. Lysosomal glucosidase is deficient in Pompe’s disease, which affects the heart. Glucose-6-phosphatase is deficient in von Gierke’s disease, which primarily affects the liver and would be associated with hepatomegaly. Glucocerebrosidase is deficient in people with Gaucher disease, which, in most cases, does not involve the central nervous system, and is not associated with the decreased pigmentation.
QUESTION 99
A mother brings her 2-year-old son to an acute care clinic. She explains that she delivered her child at home and has never received medical care; however, her son has not gained weight as she expected, sometimes shakes, and has difficulty walking. Physical examination reveals an enlarged liver. A chest x-ray reveals a normal cardiac silhouette. Examination of the eyes reveals no abnormalities. Of the following, which enzyme is most likely deficient?
A. Glucose-6-phosphatase
B. Muscle phosphorylase
C. Lysosomal glucosidase
D. Galactose-1-phosphate uridyltransferase
Answer: A (glucose-6-phosphatase)
Explanation: a deficiency of glucose-6-phosphatase (von Gierke disease) leads to hypoglycemia, which can induce seizures, and can result in delayed motor development. Patients have hepatomegaly and failure to thrive. Muscle phosphorylase is deficient in McArdle disease, which usually presents in adulthood due to muscle weakness, muscle cramps, and exercise intolerance, and which involves the skeletal muscle only, and therefore would not be associated with hepatomegaly. Lysosomal glucosidase is deficient in Pompe disease, which characteristically affects the heart, causing cardiomegaly. A mild hepatomegaly can also be found in these patients. While deficiency of galactose-1-phosphate uridyltransferase is associated with hepatomegaly and can cause some neurologic changes, cataracts usually occur, and patients often have vomiting or diarrhea after drinking milk.
QUESTION 100
A mother brings her 6-month-old male infant to the pediatrician. She reports that over the past two months, she had had increasing difficulty feeding her baby, and, despite attempts, cannot get her child to stand; she also feels her child is more floppy than he should be. Physical examination reveals an enlarged liver. A chest x-ray reveals an enlarged cardiac silhouette. The child is <10% of age for height and weight. Of the following, what is the most likely enzyme deficiency?
A. Glucose-6-phosphatase
B. Muscle phosphorylase
C. Phenylalanine hydroxylase
D. Lysosomal glucosidase
E. Glucocerebrosidase
Answer: D (lysosomal glucosidase)
Explanation: in patients with deficient lysosomal glucosidase (Pompe disease), they can, when they present early, have liver enlargement, heart enlargement, and can present with feeding difficulties, failure to thrive, and can be hypotonic. Variable terms used for the enzyme are lysosomal glucosidase, α-1,4-glucosidase, and acid maltase). Glucose-6-phosphatase is deficient in von Gierke disease,which affects the liver and leads to hypoglycemia, but does not affect the heart. Phenylalanine hydroxylase has mostly neurological findings, and would not be associated with the heart and liver enlargement. Glucocerebrosidase in most cases does involve the liver, and can, in some cases, involve the central nervous system, but does not involve the heart.
QUESTION 101
A 12-year-old male is brought to the emergency room by his parents because of sudden onset of abdominal pain, which has not resolved over the two hours. Physical examination reveals rebound tenderness and guarding. An exploratory laparotomy reveals peritonitis associated with rupture of the descending colon. Two years ago, this child had emergent surgery to repair rupture of a mesenteric artery. The underlying genetic condition is due to a mutation in the gene for production of which type of collagen?
A. Type I
B. Type II
C. Type III
D. Type IV
Answer: C (Type III).
Explanation: this child has the vascular form of Ehlers-Danlos, which is characterized by rupture of vessels and of the colon. The wall of blood vessels and the colon contains a significant amount of type III collagen, and thus, abnormal type III collagen can predispose to rupture of these organs.
QUESTION 86
A researcher is working with gliomas in an attempt to understand the pathogenesis. One of her projects involves studying a mutated isocitrate dehydrogenase gene. Of the following, by which mechanism does this mutated gene promote neoplasia?
A. Production of 2-hydroxyglutarate
B. Production of a telomerase
C. Promotion of release of E2F
D. Over-production of bcl-2
E. Under-production of bcl-2
Answer: A (production of 2-hydroxyglutarate)
Explanation: mutated isocitrate dehydrogenase genes result in the production of an enzyme that catalyzes the formation of 2-hydroxyglutarate, which inhibits the TET2 family of of enzymes, leading to altered DNA methylation, which causes abnormal expression of genes. Mutated RB gene can result in abnormal release of E2F and promotion of the cell cycle. Over-production of bcl-2 would inhibit apoptosis by stabilizing the mitochondrial membrane, and under-production of bcl-2 could indirectly promote apoptosis and death of the neoplastic cells.
QUESTION 87
A medical student is on a 4th year pathology elective and is sitting at the microscope with their attending physician looking at a biopsy of a cervix. The pathologist points out areas of dysplasia to the medical student. The finding of which of the following features would indicate carcinoma was present within the areas of dysplasia?
A. Markedly increased number of mitotic figures
B. Increase in nuclear:cytoplasm ratio
C. Separate nests of squamous cells resembling the dysplastic cells, but in the dermis
D. Prominent new blood vessel formation
E. Dysplastic cells extending from the basement membrane to the apical surface
Answer: C (Separate nests of squamous cells resembling the dysplastic cells, but in the dermis)
Explanation: A, B, and E are found in areas of dysplasia, with the presence of these features increasing as dysplasia progresses from low grade to high grade. Separate nests of squamous cells resembling the dysplastic cells, but in the dermis would imply invasion, which is a feature of carcinoma. While angiogenesis is a component of neoplasia, the presence of angiogenesis alone would not allow for the diagnosis of neoplasia.
QUESTION 88
A pathologist is examining a prostate biopsy. Focally, within the biopsy is a small cluster of tissue characterized as small glands that are back-to-back, as opposed to the normal prostatic glandular tissue that is characterized by large glands with intervening space. The pathologist determines that the focus of cells is neoplastic. Of the following, what would be the best name for this focus of neoplastic cells?
A. Squamous cell carcinoma
B. Adenocarcinoma
C. Adenosarcoma
D. Leiomyosarcoma
E. Teratoma
Answer: B (adenocarcinoma)
Explanation: as the pathologist is looking at neoplastic glands, the neoplasm is a carcinoma (and not sarcoma, teratoma, lymphoma, or melanoma). As the neoplasm is derived from glands, the appropriate term is adenocarcinoma. Squamous cell carcinoma of the prostate would be rare, but could derive from squamous metaplasia, but the cells of origin are squamous cells.
QUESTION 74
A pathologist is examining a surgically removed mass under the microscope. Of the following, which feature would indicate the mass was malignant?
A. Necrosis
B. A high mitotic rate
C. Nuclear pleomorphism
D. Focal calcification
E. Invasion of surrounding tissue.
Answer: E (invasion of surrounding tissue)
Explanation: although necrosis, a high mitotic rate, and nuclear pleomorphism are commonly found in malignant neoplasms, they can also occasionally be identified in some benign tumors as well, and, as such, are not an absolute marker of malignancy (e.g., nodular fasciitis has a high mitotic rate and nuclear pleomorphism, and can be misdiagnosed as a sarcoma, but, is in fact a benign proliferation). Focal calcification, in areas of necrosis or areas of scarring can also occur in both tumor types. The two characteristic features that distinguish malignant tumors from benign tumors are the ability of malignant tumors to invade surrounding tissue and to metastasize to distant sites; and, of these two, the only one possessed by all malignant tumors is the ability to invade. Basal cell carcinoma of the skin, a malignant tumor, is locally invasive, but rarely metastasizes, and malignant neoplasms of the brain rarely metastasize. Drop metastases associated with a medulloblastoma are not technically metastatic.
QUESTION 75
Prior to an elective laparoscopic cholecystectomy, a 54-year-old male has a chest x-ray as part of his pre-operative work-up. The x-ray reveals a mass in the left lung, which is subsequently surgically excised. The pathologist examining the tissue notes it to be well-circumscribed, firm, and gray-white. Microscopically, he sees disorganizing but otherwise benign-appearing hyaline cartilage. Of the following, what is the best term to describe this mass?
A. Adenoma
B. Chondrosarcoma
C. Hamartoma
D. Choristoma
E. Hyalinoma
Answer: C (hamartoma)
Explanation: a disorganized collection of otherwise normal appearing tissue in an area where that tissue normally occurs is referred to as a hamartoma (cartilage is a normal component of the bronchi). A collection of benign appearing and normally developed cells at an abnormal location (e.g., a nest of adrenal gland cells in the cortex of the kidney), is termed a choristoma. An adenoma is a benign tumor derived from epithelial cells and a chondrosarcoma would be a malignant tumor derived from cartilage. The mass has no features of malignancy.
QUESTION 76
A pathologist is examining a repeat cervical biopsy from a 25-year-old female with a history of multiple sexual partners. She is positive for HPV16. Previous biopsies have revealed mild to moderate dysplasia. Of the following, which microscopic finding would indicate that carcinoma has developed within the dysplastic epithelium?
A. Marked disorganization of cellular maturation from basal to apical layers
B. Numerous mitotic figures throughout the epithelium
C. Hyperchromatic nuclei of various sizes throughout the epithelium
D. Sloughed outer layer of the epithelium
E. Nests of atypical epithelial cells within the superficial dermis
Answer: E (nests of atypical epithelial cells within the superficial dermis)
Explanation: nests of atypical epithelial cells within the superficial dermis would indicate invasion, which is a feature of carcinoma. A-C above, as they are confined to the epithelium are features of dysplasia and would not be indicative, by themself, of carcinoma.
QUESTION 77
A 23-year-old male develops abdominal pain. A CT scan reveals a mass in the liver. A surgical resection is performed. Microscopic examination of the mass by the pathologist reveals a diagnosis of metastatic osteosarcoma. Subsequently, radiologic examination of the right knee reveals a mass. Of the following, which route most likely allowed the neoplasm to spread from the knee to the liver?
A. Spread of tumor cells through the lymphatics
B. Spread of tumor cells through the blood
C. Spread of tumor cells along the surface of nerves
D. Invasion and growth along the lymphatics
E. Invasion and growth along the blood vessels
Answer: B (spread of tumor cells through the blood).
Explanation: While it is not absolute, sarcomas are most known for hematogenous spread. The tumor cells enter the blood vessels and are carried by the blood to distant sites where they implant and grow. Carcinomas are more commonly known for lymphatic spread. While tumors can grow along nerves, distant spread by growing along a nerve would not be a metastasis. Renal cell carcinoma and hepatocellular carcinoma are known for invading into and then growing along blood vessels, but spreading in this manner would not technically be a metastasis, since there is communication with the original tumor site.
QUESTION 78
A neuropathologist is examining a biopsy of a brain tumor at frozen section. Features consistent with a glioblastoma are identified. Molecular analysis of the tumor reveals over-expression of the PDGF gene. This molecular abnormality contributed to which of the following mechanisms by which this tumor developed?
A. Evasion of immune surveillance
B. Sustained angiogenesis
C. Evasion of apoptosis
D. Self-sufficiency for growth signals
E. Insensitivity to growth-inhibitory signals
Answer: D (self-sufficiency in growth signals)
Explanation: PDGF is platelet derived growth factor. In patients with glioblastoma, over-expression of the PDGF gene can occur, resulting in abnormal stimulation of the growth and division of the cell. The cells can grow and divide outside of the normal chain of events and therefore, have developed a self-sufficiency in their growth signals.
QUESTION 79
A young woman is diagnosed with breast cancer after a biopsy of a suspicious mass that had been detected by mammography. The pathologist confirmed the diagnosis of invasive ductal carcinoma and molecular analysis revealed that the tumor was HER2 positive. She received chemotherapy, including anti-HER2 antibodies. Her molecular abnormality contributed to which of the following mechanisms by which this tumor developed?
A. Evasion of immune surveillance
B. Sustained angiogenesis
C. Evasion of apoptosis
D. Self-sufficiency for growth signals
E. Insensitivity to growth-inhibitory signals
Answer: D (self-sufficiency in growth signals)
Explanation: HER2 (also referred to as ERBB2) is a member of the epidermal growth factor receptor family. A mutation in this receptor allowed the patient’s cells to be very sensitive to growth factors, and hence, the development of carcinoma occurred as there was uncontrolled cell growth. When the growth factor receptor is mutated and as a result more responsive to growth factor stimulation, the neoplastic cell has developed self-sufficiency for growth signals.
QUESTION 80
A large medical center that conducts molecular analyses of neoplasms for various small hospitals in the area, specializing in no specific tumor type, conducts a statistical analysis of their last 1000 tumors. Of the following, a mutation of which gene did they see most commonly?
A. ABL
B. MYC
C. ERBB1
D. RAS
E. PTEN
Answer: D (RAS)
Explanation: 30% of all tumors have a mutated RAS, and it is the most commonly identified mutation in human tumors in general. If the medical center had specialized in a specific tumor type, RAS may not have been the most commonly identified oncogene.
QUESTION 81
A 53-year-old male with a 45 pack-year smoking history is diagnosed with pancreatic adenocarcinoma during the work-up of prolonged and unexplained abdominal pain. Molecular analysis of the tumor reveals a mutated RAS gene. Of the following, what was the most likely mechanism by which this mutation contributed to the development of the tumor?
A. Pre-mature hydrolysis of ATP
B. Impaired hydrolysis of ATP
C. Pre-mature hydrolysis of GTP
D. Impaired hydrolysis of GTP
Answer: D (impaired hydrolysis of GTP)
Explanation: mutation of the RAS gene is commonly identified in a pancreatic adenocarcinomas. RAS is a signal transducing protein, a link between the growth factor receptor and the cascade of proteins (PI3K to AKT to mTOR or RAF to MAPK) that lead to activation of transcription factors in the nucleus. When RAS has GTP bound, it is active,and hydrolysis of the GTP inactivates RAS. So, impaired hydrolysis of the GTP would lead to prolonged activation of RAS and abnormal stimulus of nuclear transcription.
QUESTION 82
A pathologist is examining a tumor removed from the left testis of a young boy. Within the tumor, the pathologist identifies squamous epithelium overlying sebaceous glands, hyaline cartilage, neural tissue, and hepatocytes. Of the following, what is the correct name for this tumor?
A. Hamartoma
B. Carcinoma
C. Sarcoma
D. Teratoma
E. Choristoma
Answer: D (teratoma)
Explanation: teratomas, a form of germ cell tumor, have components derived from all three germ cell layers (ectoderm, mesoderm, and endoderm). The skin is derived from ectoderm, the neural tissue is derived from endoderm, and the hyaline cartilage is derived from mesoderm.
QUESTION 83
A pathologist is examining a malignant neoplasm of the lung. Molecular analysis reveals that the tumor has a mutation of the RB gene. Of which of the following mechanisms did the mutation present contribute to the development of the neoplasm?
A. Self-sufficiency in growth signals
B. Insensitivity to growth-inhibitory signals
C. Altered cellular metabolism
D. Evasion of apoptosis
E. Limitless replicative potential
Answer: B (insensitivity to growth inhibitory signals)
Explanation: RB is a tumor suppressor gene. Although it has other functions, when it is hypophosphorylated, the RB protein binds to E2F, which inhibits the transition from G1 to S. When hyperphosphorylation of RB occurs, through actions of Cyclin D/CDK4 and others, E2F is released and transcription occurs. Therefore, RB is growth inhibitory, and mutations to the RB gene will result in an insensitivity to growth inhibitory signals.
QUESTION 84
A researcher is studying the role of apoptosis in breast tissue following a period of lactation after the birth of a child. In their study, they wish to promote apoptosis in samples of lactating breast tissue to study its effects. Promotion of transcription of which of the following genes would best bring about their desired effects?
A. RB
B. Cyclin D
C. MYC
D. TP53
E. GADD45
Answer: D (TP53)
Explanation: the role of TP53 is to identify DNA damage, arrest the cell cycle at G1, trigger repair of the damaged DNA, and if repair is not possible, caused senescence or apoptosis of the cell. Of the genes listed, TP53 is the only one that plays a significant role in the promotion of apoptosis. GADD45 is a DNA repair gene. RB and Cyclin D control the transition from G1 to S.
QUESTION 85
A research oncologist is studying the Warburg effect in neoplastic cells obtained from an individual with small cell carcinoma of the lung. Given that the Warburg effect is present in this cell population, the breakdown of glucose to which of the following substances is expected to be greater than expected?
A. Lactose
B. Water and oxygen
C. Glycine
D. Reactive oxygen species
E. Triglycerides
Answer: A (lactose)
Explanation: in the Warburg effect, neoplastic cells preferentially breakdown glucose to lactose, even in the presence of sufficient oxygen (aerobic glycolysis). While this is an inefficient way to produce ATP, it is a good way to produce other substances required for growth (including proteins, lipids, and nucleic acids). Oxidative phosphorylation efficiently reduces glucose to water and oxygen, producing the maximum amount of ATP, but does not generate substances necessary for cellular growth. Other rapidly growing cells (e.g., during fetal develop) can also exhibit the Warburg effect, so it is not specific to cancer.