A 35-year-old woman with no significant past medical, past surgical, family or social history presents to clinic with a recently identified area of flat, intact, pigmented skin. The patient believes that this is a large freckle, and she states that it becomes darker during the summer when she is outdoors. On physical examination, you measure the lesion to be 6 mm in diameter. Which of the following is the best descriptor of this patient’s skin finding?
Q2
A 68-year-old male is brought to his primary care physician by his wife who is concerned that the patient seems more confused and irritable than usual. Three months ago, she started noticing that he appeared confused while doing simple tasks and seemed to be off balance. He has fallen several times over that time period. She has also noticed that if he is startled by one of their grandchildren, his arm starts to twitch uncontrollably. His past medical history is notable for transient ischemic attacks, hypertension, and hyperlipidemia. He takes aspirin, enalapril, hydrochlorothiazide, and rosuvastatin. He has a 30 pack-year smoking history. His family history is notable for Alzheimer’s disease in his mother and maternal uncle. His temperature is 98.6°F (37°C), blood pressure is 130/70 mmHg, pulse is 95/min, and respirations are 16/min. Physical examination reveals dysmetria and an ataxic gait. This patient’s condition is most strongly associated with which of the following findings on brain autopsy?
Q3
Two weeks after undergoing low anterior resection for rectal cancer, a 52-year-old man comes to the physician because of swelling in both feet. He has not had any fever, chills, or shortness of breath. His temperature is 36°C (96.8°F) and pulse is 88/min. Physical examination shows a normal thyroid and no jugular venous distention. Examination of the lower extremities shows bilateral non-pitting edema that extends from the feet to the lower thigh, with deep flexion creases. His skin is warm and dry, and there is no erythema or rash. Microscopic examination of the interstitial space in this patient's lower extremities would be most likely to show the presence of which of the following?
Q4
A 35-year-old nulligravid woman and her 33-year-old husband come to the physician for genetic counseling prior to conception. The husband has had severe psoriasis since adolescence that is now well-controlled under combination treatment with UV light therapy and etanercept. His father and two brothers also have this condition, and the couple wants to know how likely it is that their child will have psoriasis. The inheritance pattern of this patient's illness is most similar to which of the following conditions?
Q5
A 5-year-old girl accompanied by her mother presents to the emergency department after suffering a fall on the elementary school playground. Her mother reports that a child on the playground pushed her daughter who fell on her right side, after which she screamed and was found clutching her right leg. The girl's past medical history is significant for a fracture of the left femur and right radius over the past 2 years and an auditory deficit requiring hearing aid use starting 6 months ago. Inspection reveals a relatively short girl in moderate distress. She has brown opalescent teeth. She refuses to bear weight on her right lower extremity. Radiography of the right lower extremity reveals a femoral midshaft fracture. Which of the following is the most likely etiology of the patient's condition?
Q6
An investigator is attempting to develop a blood test to diagnose sporadic Creutzfeldt-Jakob disease (CJD). She has collected several tissue samples from adults who were diagnosed with CJD. After performing a comprehensive tissue analysis, she has identified two amino acid sequences on the affected proteins that are highly consistent across samples. She then creates antibodies that are highly specific to those amino acid sequences and is interested in using those antibodies to identify similar sequences in individuals suspected of having CJD. Which of the following tests would be most helpful in identifying these individuals?
Q7
A 48-year-old man is brought to the emergency department with a stab wound to his chest. The wound is treated in the emergency room. Three months later he develops a firm 4 x 3 cm nodular mass with intact epithelium over the site of the chest wound. On local examination, the scar is firm, non-tender, and there is no erythema. The mass is excised and microscopic examination reveals fibroblasts with plentiful collagen. Which of the following processes is most likely related to the series of events mentioned above?
Q8
A 35-year-old woman is involved in a car accident and presents with an open fracture of the left femur and severe bleeding from the left femoral artery. No past medical history or current medications. Her blood pressure is 90/60 mm Hg, pulse is 110/min, and respirations are 21/min. On physical examination, the patient is lethargic, confused, and poorly responds to commands. Peripheral pulses are 1+ in the left lower extremity below the level of the knee and 2+ elsewhere. When she arrives at the hospital, a stat hemoglobin level shows 6 g/dL. Which of the following is most correct about the patient’s condition?
Q9
A 35-year-old man is brought to the emergency room after suffering a catastrophic fall while skiing during a training session. He was found unconscious by the aeromedical emergency services team, who established an airway and cervical spine control measures. Upon arrival at the emergency department, ventilatory support is started followed by an evaluation of the patient by the neurosurgical team. His blood pressure is 210/125 mm Hg, the heart rate is 55/min, and the respiratory rate is 15/min with a Cheyne-Stokes breathing pattern. Neurological examination shows a Glasgow Coma Score of 4/15, with dilated, fixed pupils and a decerebrate posture. An MRI of the brain shows diffuse axonal injury to the brain with severe cerebral edema, multiple frontal and occipital lobe contusions and multiple flame-shaped hemorrhages in the brainstem. Despite the medical team efforts, the patient dies 24 hours later. What would be the most likely type of herniation found at this patient’s autopsy?
Q10
A newborn male is evaluated in the hospital nursery two hours after birth. The patient was born at 39 weeks of gestation to a 30-year-old primigravid via vaginal delivery. The patient’s mother received routine prenatal care, and the pregnancy was uncomplicated. The patient’s anatomy ultrasound at 20 weeks of gestation was unremarkable. The patient’s mother denies any family history of genetic diseases. The patient’s Apgar scores were notable for poor muscle tone at both one and five minutes of life. The patient’s birth weight is 2.6 kg (5 lb 11 oz), which is at the 5th percentile. His height and head circumference are in the 15th and 3rd percentile, respectively. On physical exam, the patient has a wide nasal bridge, downslanting palpebral fissures, and widely spaced eyes. He has good respiratory effort with a high-pitched cry. This patient is most likely to have experienced a deletion on which of the following chromosomes?
General Pathology US Medical PG Practice Questions and MCQs
Question 1: A 35-year-old woman with no significant past medical, past surgical, family or social history presents to clinic with a recently identified area of flat, intact, pigmented skin. The patient believes that this is a large freckle, and she states that it becomes darker during the summer when she is outdoors. On physical examination, you measure the lesion to be 6 mm in diameter. Which of the following is the best descriptor of this patient’s skin finding?
A. Wheal
B. Papule
C. Ulcer
D. Plaque
E. Macule (Correct Answer)
Explanation: ***Macule***
- A **macule** is a **flat, discolored lesion** that is less than 1 cm in diameter, which fits the description of a **flat, pigmented skin area** that is 6 mm in diameter.
- The darkening of the lesion with sun exposure is characteristic of a **freckle**, which is a type of macule caused by increased melanin production without an increase in melanocyte numbers.
*Wheal*
- A **wheal** is a **transient, elevated lesion** caused by dermal edema, typically seen in allergic reactions like hives.
- This patient's lesion is described as a **flat, pigmented area**, not an elevated, transient swelling.
*Papule*
- A **papule** is a **solid, elevated lesion** that is less than 1 cm in diameter.
- The patient's skin finding is explicitly described as **flat** and intact, not elevated.
*Ulcer*
- An **ulcer** is a **loss of epidermis and dermis**, resulting in an open sore; it is not a flat, intact pigmented lesion.
- The description of the lesion as **intact** rules out an ulcer, which involves a break in the skin surface.
*Plaque*
- A **plaque** is a **flat-topped, elevated lesion** that is larger than 1 cm in diameter.
- While flat-topped, a plaque is **elevated**, and the patient's lesion is described as **flat**, not elevated.
Question 2: A 68-year-old male is brought to his primary care physician by his wife who is concerned that the patient seems more confused and irritable than usual. Three months ago, she started noticing that he appeared confused while doing simple tasks and seemed to be off balance. He has fallen several times over that time period. She has also noticed that if he is startled by one of their grandchildren, his arm starts to twitch uncontrollably. His past medical history is notable for transient ischemic attacks, hypertension, and hyperlipidemia. He takes aspirin, enalapril, hydrochlorothiazide, and rosuvastatin. He has a 30 pack-year smoking history. His family history is notable for Alzheimer’s disease in his mother and maternal uncle. His temperature is 98.6°F (37°C), blood pressure is 130/70 mmHg, pulse is 95/min, and respirations are 16/min. Physical examination reveals dysmetria and an ataxic gait. This patient’s condition is most strongly associated with which of the following findings on brain autopsy?
A. Intracellular rounded hyperphosphorylated tau
B. Extracellular accumulation of amyloid beta
C. Multifocal ischemic changes
D. Accumulations of beta-pleated sheets (Correct Answer)
E. Intracellular aggregates of alpha-synuclein
Explanation: ***Accumulations of beta-pleated sheets***
- This patient's presentation with **rapidly progressive dementia**, confusion, ataxia, **myoclonus** (twitching arm when startled), and falls, without significant family history of early-onset Alzheimer's, strongly points towards **Creutzfeldt-Jakob disease (CJD)**.
- CJD is characterized pathologically by the accumulation of abnormally folded **prion proteins (PrPSc)**, which form **beta-pleated sheets** and cause spongiform changes in the brain.
*Intracellular rounded hyperphosphorylated tau*
- This finding is characteristic of **Alzheimer's disease (neurofibrillary tangles)**, which typically presents with a more gradual onset of memory loss and cognitive decline, rather than the rapid progression, prominent motor symptoms (ataxia, myoclonus), and falls seen in this patient.
- While there is a family history of Alzheimer's, the **rapid progression** and specific neurological signs make CJD a more likely diagnosis in this case.
*Extracellular accumulation of amyloid beta*
- This describes **amyloid plaques**, another hallmark of **Alzheimer's disease**.
- Similar to tau pathology, this finding would be more consistent with a gradual, progressive memory impairment, and less with the pronounced and rapid neurological deficits observed.
*Multifocal ischemic changes*
- While the patient has vascular risk factors (**hypertension, hyperlipidemia, TIA history, smoking**), multifocal ischemic changes (as seen in **vascular dementia**) usually lead to a stepwise cognitive decline and may cause focal neurological deficits, but typically do not present with the characteristic myoclonus and rapidly progressive ataxia seen here.
- The constellation of symptoms is more indicative of a **prion disease** than purely vascular dementia.
*Intracellular aggregates of alpha-synuclein*
- This pathology is characteristic of **Lewy body dementia** or **Parkinson's disease dementia**.
- Symptoms would include progressive cognitive decline, **fluctuating cognition**, prominent **visual hallucinations**, and parkinsonism. While some motor symptoms like falls are present, the myoclonus and rapid progression make CJD a more fitting diagnosis.
Question 3: Two weeks after undergoing low anterior resection for rectal cancer, a 52-year-old man comes to the physician because of swelling in both feet. He has not had any fever, chills, or shortness of breath. His temperature is 36°C (96.8°F) and pulse is 88/min. Physical examination shows a normal thyroid and no jugular venous distention. Examination of the lower extremities shows bilateral non-pitting edema that extends from the feet to the lower thigh, with deep flexion creases. His skin is warm and dry, and there is no erythema or rash. Microscopic examination of the interstitial space in this patient's lower extremities would be most likely to show the presence of which of the following?
A. Neutrophilic, protein-rich fluid
B. Lymphocytic, hemosiderin-rich fluid
C. Lipid-rich, protein-rich fluid (Correct Answer)
D. Protein-rich, glycosaminoglycan-rich fluid
E. Acellular, protein-poor fluid
Explanation: ***Lipid-rich, protein-rich fluid***
- The presentation of bilateral non-pitting edema extending to the thigh, with deep flexion creases, in a patient post-**low anterior resection** for rectal cancer, strongly suggests **lymphedema**.
- Lymphedema results from impaired lymphatic drainage, leading to the accumulation of **protein-rich fluid**, **macromolecules**, and **adipose tissue** in the interstitial space, which eventually becomes lipid-rich due to chronic inflammation and fibroblasts stimulating adipogenesis.
*Neutrophilic, protein-rich fluid*
- This description is characteristic of **inflammatory edema** or **purulent exudate**, typically seen in infections.
- The patient's lack of fever, chills, erythema, or warmth makes an infectious or acute inflammatory process unlikely.
*Lymphocytic, hemosiderin-rich fluid*
- **Hemosiderin deposits** are indicative of chronic **venous insufficiency** or recurrent hemorrhages, leading to red blood cell extravasation and breakdown.
- While lymphocytes can be present in chronic inflammation, the primary issue here is lymphatic obstruction, not venous stasis or bleeding.
*Protein-rich, glycosaminoglycan-rich fluid*
- While lymphedema is indeed **protein-rich**, the primary accumulation in mature lymphedema involves **adipose tissue** and fibrosis.
- **Glycosaminoglycans** accumulate significantly in conditions like **myxedema** (hypothyroidism), which was ruled out by the normal thyroid examination.
*Acellular, protein-poor fluid*
- This describes a **transudate**, typically seen in conditions like **heart failure**, **liver cirrhosis**, or **nephrotic syndrome** where there's an imbalance of hydrostatic and oncotic pressures.
- The edema in this case is **non-pitting**, suggesting a higher protein content and tissue changes characteristic of lymphatic dysfunction, not systemic fluid overload leading to protein-poor fluid.
Question 4: A 35-year-old nulligravid woman and her 33-year-old husband come to the physician for genetic counseling prior to conception. The husband has had severe psoriasis since adolescence that is now well-controlled under combination treatment with UV light therapy and etanercept. His father and two brothers also have this condition, and the couple wants to know how likely it is that their child will have psoriasis. The inheritance pattern of this patient's illness is most similar to which of the following conditions?
A. Alport syndrome
B. Schizophrenia (Correct Answer)
C. Familial hypercholesterolemia
D. Alpha thalassemia minor
E. Oculocutaneous albinism
Explanation: ***Schizophrenia***
- Psoriasis exhibits a **complex, multifactorial inheritance pattern**, influenced by multiple genes and environmental factors, similar to **schizophrenia**.
- No single gene dictates its expression, leading to variable penetrance and a risk that is higher in first-degree relatives but not Mendelian.
*Alport syndrome*
- This is an **X-linked dominant genetic disorder** primarily affecting the kidneys, ears, and eyes, characterized by a clear Mendelian inheritance pattern.
- The inheritance pattern in **Alport syndrome** is distinct and follows predictable ratios based on sex and parental genotypes.
*Familial hypercholesterolemia*
- This condition is inherited in an **autosomal dominant** manner, meaning a single copy of the mutated gene is sufficient to cause the disease, resulting in high penetrance.
- Its inheritance pattern is **monogenic** and follows a clear Mendelian 50% risk for offspring of an affected individual.
*Alpha thalassemia minor*
- This is an **autosomal recessive** condition, where affected individuals inherit two copies of the mutated gene (one from each parent).
- While it has a genetic basis, it is a **monogenic disorder** with a well-defined recessive inheritance, unlike the complex inheritance of psoriasis.
*Oculocutaneous albinism*
- This is typically an **autosomal recessive disorder** characterized by a significant reduction or absence of melanin production in the skin, hair, and eyes.
- Like alpha thalassemia minor, it is a **monogenic disorder** with a clear Mendelian recessive inheritance.
Question 5: A 5-year-old girl accompanied by her mother presents to the emergency department after suffering a fall on the elementary school playground. Her mother reports that a child on the playground pushed her daughter who fell on her right side, after which she screamed and was found clutching her right leg. The girl's past medical history is significant for a fracture of the left femur and right radius over the past 2 years and an auditory deficit requiring hearing aid use starting 6 months ago. Inspection reveals a relatively short girl in moderate distress. She has brown opalescent teeth. She refuses to bear weight on her right lower extremity. Radiography of the right lower extremity reveals a femoral midshaft fracture. Which of the following is the most likely etiology of the patient's condition?
A. Decreased cystathionine beta synthase activity
B. Vitamin D deficiency
C. Fibrillin gene defect
D. Defective type I collagen production (Correct Answer)
E. Type III collagen gene defect
Explanation: **Defective type I collagen production**
- The patient's history of **recurrent fractures** from minor trauma, **auditory deficit**, and **brown opalescent teeth** (dentinogenesis imperfecta) are classic manifestations of **osteogenesis imperfecta**, a genetic disorder characterized by **defective type I collagen production**.
- **Type I collagen** is a major component of bone, dentin, and the sclera, and its deficiency leads to brittle bones, hearing loss due to ossicle abnormalities, and dental defects.
*Decreased cystathionine beta synthase activity*
- This condition describes **homocystinuria**, which can present with skeletal abnormalities and developmental delays.
- However, typical features include **marfanoid habitus**, **lens luxation**, and **thromboembolic events**, which are not reported in this patient.
*Vitamin D deficiency*
- **Vitamin D deficiency** leads to **rickets** in children, characterized by bone pain, muscle weakness, and skeletal deformities but typically presents with **bowing of legs**, **rachitic rosary**, and **craniotabes**, not recurrent fractures from minor trauma or opalescent teeth.
- While it weakens bones, the constellation of symptoms here, especially dental and auditory deficits, points away from simple vitamin D deficiency.
*Fibrillin gene defect*
- A **fibrillin gene defect** is characteristic of **Marfan syndrome**, which presents with **long limbs**, **arachnodactyly**, **lens luxation**, and **aortic root dilation**.
- While it involves connective tissue, it does not typically cause the bone fragility and dental findings seen in this patient.
*Type III collagen gene defect*
- A **type III collagen gene defect** is associated with **Ehlers-Danlos syndrome, vascular type**, which features **easy bruising**, **fragile blood vessels**, and **organ rupture**.
- This condition leads to hypermobility and skin hyperextensibility, but not the specific combination of brittle bones, hearing loss, and dental defects seen in this patient.
Question 6: An investigator is attempting to develop a blood test to diagnose sporadic Creutzfeldt-Jakob disease (CJD). She has collected several tissue samples from adults who were diagnosed with CJD. After performing a comprehensive tissue analysis, she has identified two amino acid sequences on the affected proteins that are highly consistent across samples. She then creates antibodies that are highly specific to those amino acid sequences and is interested in using those antibodies to identify similar sequences in individuals suspected of having CJD. Which of the following tests would be most helpful in identifying these individuals?
A. Western blot (Correct Answer)
B. Northern blot
C. Southwestern blot
D. Polymerase chain reaction
E. Southern blot
Explanation: ***Western blot***
- A **Western blot** (also known as protein immunoblot) is used to detect **specific proteins** in a sample of tissue homogenate or extract.
- The scenario describes identifying **amino acid sequences** (protein markers) in affected individuals using **specific antibodies**, which is precisely the principle of a Western blot.
*Northern blot*
- A **Northern blot** is used to detect **specific RNA sequences** in a sample.
- This technique is not applicable here as the investigator is targeting **protein sequences**, not RNA.
*Southwestern blot*
- A **Southwestern blot** is used to detect and characterize **DNA-binding proteins**.
- This method is not relevant because the goal is to identify specific **protein sequences** associated with CJD, not proteins that bind to DNA.
*Polymerase chain reaction*
- **Polymerase chain reaction (PCR)** is a molecular biology technique used to **amplify specific DNA sequences**.
- While fundamental in molecular diagnostics, PCR does not directly detect **proteins** and is therefore not the appropriate assay for the described purpose.
*Southern blot*
- A **Southern blot** is a laboratory method used to detect **specific DNA sequences** in DNA samples.
- This technique focuses on DNA, whereas the investigator is looking to identify specific **protein sequences** using antibodies.
Question 7: A 48-year-old man is brought to the emergency department with a stab wound to his chest. The wound is treated in the emergency room. Three months later he develops a firm 4 x 3 cm nodular mass with intact epithelium over the site of the chest wound. On local examination, the scar is firm, non-tender, and there is no erythema. The mass is excised and microscopic examination reveals fibroblasts with plentiful collagen. Which of the following processes is most likely related to the series of events mentioned above?
A. Development of a fibrosarcoma
B. Foreign body response from suturing
C. Staphylococcal wound infection
D. Poor wound healing from diabetes mellitus
E. Keloid scar formation (Correct Answer)
Explanation: ***Keloid scar formation***
- A **keloid** is a raised, firm, nodular scar that extends beyond the original wound boundaries and is characterized by excessive collagen deposition from **fibroblasts**.
- The delayed presentation (3 months), firm nature, absence of inflammation (no erythema, non-tender), and microscopic findings of fibroblasts with plentiful collagen are classic features of a keloid.
*Development of a fibrosarcoma*
- A fibrosarcoma is a **malignant tumor** of fibroblasts, which would typically present with more aggressive growth, often pain, and possibly ulceration, none of which are described.
- While composed of fibroblasts, fibrosarcomas exhibit **cellular atypia**, mitotic activity, and invasion, which are not mentioned in the microscopic description.
*Foreign body response from suturing*
- A foreign body response usually involves a **granulomatous inflammation** around foreign material, such as suture remnants.
- The microscopic description of "fibroblasts with plentiful collagen" without mention of inflammatory cells or foreign bodies makes this less likely.
*Staphylococcal wound infection*
- A **bacterial infection** would typically present with signs of acute inflammation such as erythema, warmth, pain, and possibly pus, shortly after the wound.
- The mass is described as non-tender with no erythema, and the 3-month delay makes an active infection less probable.
*Poor wound healing from diabetes mellitus*
- Poor wound healing in diabetes often manifests as **delayed closure**, chronic ulcers, and increased susceptibility to infection, rather than an overgrowth of fibrous tissue in the form of a nodular mass.
- While diabetes can affect wound healing, the specific description of a firm, nodular mass with excessive collagen points away from typical diabetic wound complications.
Question 8: A 35-year-old woman is involved in a car accident and presents with an open fracture of the left femur and severe bleeding from the left femoral artery. No past medical history or current medications. Her blood pressure is 90/60 mm Hg, pulse is 110/min, and respirations are 21/min. On physical examination, the patient is lethargic, confused, and poorly responds to commands. Peripheral pulses are 1+ in the left lower extremity below the level of the knee and 2+ elsewhere. When she arrives at the hospital, a stat hemoglobin level shows 6 g/dL. Which of the following is most correct about the patient’s condition?
A. This patient’s laboratory findings will likely demonstrate a normocytic anemia (Correct Answer)
B. Hemoglobin concentration will be significantly decreased immediately after the acute bleeding begins
C. This patient will likely be diagnosed with iron deficiency anemia
D. Hematocrit is expected to accurately reflect the degree of blood loss immediately after acute hemorrhage
E. Her reticulocyte count is expected to be elevated at this time
Explanation: ***This patient's laboratory findings will likely demonstrate a normocytic anemia***
- In cases of **acute blood loss**, both plasma and red blood cells are lost proportionally, leading to **normocytic, normochromic anemia** as the body has not yet had time to alter red blood cell production
- The MCV (mean corpuscular volume) remains **normal (80-100 fL)** until chronic compensatory mechanisms develop
- This distinguishes acute hemorrhage from chronic blood loss, which can eventually lead to **microcytic anemia** due to iron depletion
*Hematocrit is expected to accurately reflect the degree of blood loss immediately after acute hemorrhage*
- **Immediately after acute hemorrhage**, both red blood cells and plasma are lost proportionally, so the **hematocrit initially remains relatively unchanged** despite significant blood volume loss
- The hematocrit **drops hours later** as fluid shifts from the interstitial space into the vascular compartment to restore blood volume, diluting the remaining red blood cells
- This patient's low hemoglobin at hospital arrival reflects this compensatory hemodilution process
*Hemoglobin concentration will be significantly decreased immediately after the acute bleeding begins*
- While the patient is actively bleeding, the **hemoglobin concentration may not immediately decrease** because red blood cells and plasma are lost together in proportion
- The apparent drop in hemoglobin becomes more pronounced as the body **replenishes plasma volume** through fluid shifts or after **intravenous fluid administration**, diluting the remaining red cell mass
- The hemoglobin of 6 g/dL at hospital arrival reflects fluid shifts that have already occurred
*Her reticulocyte count is expected to be elevated at this time*
- The bone marrow requires **3-5 days to mount a reticulocytosis** in response to acute blood loss and increased erythropoietin production
- At hospital arrival shortly after the accident, the **reticulocyte count will be normal** as insufficient time has passed for bone marrow response
- An elevated reticulocyte count would be expected **several days after the hemorrhage**, not acutely
*This patient will likely be diagnosed with iron deficiency anemia*
- **Iron deficiency anemia** is a **chronic condition** characterized by **microcytic, hypochromic red blood cells** due to prolonged iron loss or inadequate dietary intake
- Acute blood loss, as seen in this trauma case, causes **normocytic anemia** with normal MCV and MCH
- Iron deficiency could develop weeks to months later if iron stores become depleted without supplementation
Question 9: A 35-year-old man is brought to the emergency room after suffering a catastrophic fall while skiing during a training session. He was found unconscious by the aeromedical emergency services team, who established an airway and cervical spine control measures. Upon arrival at the emergency department, ventilatory support is started followed by an evaluation of the patient by the neurosurgical team. His blood pressure is 210/125 mm Hg, the heart rate is 55/min, and the respiratory rate is 15/min with a Cheyne-Stokes breathing pattern. Neurological examination shows a Glasgow Coma Score of 4/15, with dilated, fixed pupils and a decerebrate posture. An MRI of the brain shows diffuse axonal injury to the brain with severe cerebral edema, multiple frontal and occipital lobe contusions and multiple flame-shaped hemorrhages in the brainstem. Despite the medical team efforts, the patient dies 24 hours later. What would be the most likely type of herniation found at this patient’s autopsy?
A. Upward cerebellar herniation
B. Uncal herniation
C. Central herniation (Correct Answer)
D. Downward cerebellar herniation
E. Subfalcine herniation
Explanation: ***Central herniation***
- The presence of **Cushing's triad** (hypertension, bradycardia, irregular respirations like Cheyne-Stokes), **dilated fixed pupils**, and **decerebrate posturing** in a patient with severe diffuse cerebral edema and brainstem hemorrhages, indicates significant downward displacement of the diencephalon and midbrain through the tentorial notch.
- **Flame-shaped hemorrhages in the brainstem** (Duret hemorrhages) are a classic pathological finding associated with central or transtentorial herniation due to stretching and rupture of small perforating arteries as the brainstem is displaced.
*Upward cerebellar herniation*
- This type of herniation involves the upward displacement of the **cerebellum** and **brainstem** through the tentorial notch, often due to an infratentorial mass.
- It typically presents with **hydrocephalus**, oculomotor nerve palsies, and respiratory compromise, which are not the primary neurological signs described here.
*Uncal herniation*
- **Uncal herniation** specifically involves the medial temporal lobe (uncus) compressing the **ipsilateral oculomotor nerve (CN III)**, leading to a **dilated pupil** on one side, followed by hemiparesis.
- While a dilated pupil is present, the bilateral fixed pupils, decerebrate posturing, and diffuse brainstem involvement suggest a more widespread herniation pattern than just uncal.
*Downward cerebellar herniation*
- Also known as **tonsillar herniation**, this involves the **cerebellar tonsils** descending through the **foramen magnum**, compressing the medulla.
- This typically causes **respiratory arrest**, bradycardia, and flaccid paralysis; the clinical picture of decerebrate posturing and Duret hemorrhages points away from primary tonsillar herniation.
*Subfalcine herniation*
- **Subfalcine herniation** involves the cingulate gyrus displacing under the **falx cerebri**.
- This type of herniation often presents with **contralateral leg weakness** and can compress the anterior cerebral artery, but it does not directly cause the severe brainstem signs seen in this patient.
Question 10: A newborn male is evaluated in the hospital nursery two hours after birth. The patient was born at 39 weeks of gestation to a 30-year-old primigravid via vaginal delivery. The patient’s mother received routine prenatal care, and the pregnancy was uncomplicated. The patient’s anatomy ultrasound at 20 weeks of gestation was unremarkable. The patient’s mother denies any family history of genetic diseases. The patient’s Apgar scores were notable for poor muscle tone at both one and five minutes of life. The patient’s birth weight is 2.6 kg (5 lb 11 oz), which is at the 5th percentile. His height and head circumference are in the 15th and 3rd percentile, respectively. On physical exam, the patient has a wide nasal bridge, downslanting palpebral fissures, and widely spaced eyes. He has good respiratory effort with a high-pitched cry. This patient is most likely to have experienced a deletion on which of the following chromosomes?
A. 4p
B. 5q
C. 7q
D. 15q
E. 5p (Correct Answer)
Explanation: ***5p***
- The constellation of findings, including **low birth weight**, **microcephaly**, **hypotonia**, **widely spaced eyes**, **downslanting palpebral fissures**, **wide nasal bridge**, and a **high-pitched cry**, is highly characteristic of **Cri-du-chat syndrome**.
- **Cri-du-chat syndrome** is caused by a **deletion of the short arm of chromosome 5 (5p)**.
*4p*
- A deletion on **4p** is associated with **Wolf-Hirschhorn syndrome**, which presents with **microcephaly**, a distinct **"Greek helmet" facial appearance**, and often severe intellectual disability, which are not perfectly aligned with all features described.
- While there can be overlapping features like growth restriction and developmental delay, the specific craniofacial features and the characteristic cry of Cri-du-chat are not typical for Wolf-Hirschhorn syndrome.
*5q*
- A deletion on **5q** is associated with various conditions, including some forms of **myelodysplastic syndromes** (particularly 5q- syndrome), which are hematologic disorders and not typically presenting with the described birth defects.
- While deletions can occur on the long arm of chromosome 5, they do not cause Cri-du-chat syndrome; that is specifically a 5p deletion.
*7q*
- Deletions on **7q** are associated with conditions like **Williams syndrome** (a microdeletion on 7q11.23, characterized by "elfin" facies, supravalvular aortic stenosis, and unique personality traits) or **Silver-Russell syndrome** (associated with some 7q deletions, causing growth restriction and characteristic facial features).
- The described presentation does not match the typical features of conditions linked to 7q deletions.
*15q*
- Deletions on **15q** are linked to conditions such as **Prader-Willi syndrome** (paternal deletion of 15q11-q13, causing hypotonia, feeding difficulties in infancy followed by hyperphagia, and intellectual disability) and **Angelman syndrome** (maternal deletion or mutation on 15q11-q13, presenting with severe intellectual disability, ataxia, and inappropriate laughter).
- The clinical features presented do not align with the characteristic presentation of either Prader-Willi or Angelman syndrome.
Question 11: A 3-year-old boy presents to a geneticist for generalized developmental delay. Upon presentation he is found to have a distinctive facial structure with prominent epicanthal folds and macroglossia. Further physical examination reveals a simian crease on his palms bilaterally. Based on these findings, the physician strongly suspects Down syndrome and obtains a karyotype. Surprisingly the karyotype shows 46 chromosomes with two normal appearing alleles of chromosome 21. Further examination with fluorescent probes reveals a third copy of chromosome 21 genes that have been incorporated into another chromosome. What is the name of this mechanism of Down syndrome inheritance?
A. Robertsonian translocation (Correct Answer)
B. Nondisjunction
C. Anticipation
D. Imprinting
E. Mosaicism
Explanation: ***Robertsonian translocation***
- A Robertsonian translocation involves two **acrocentric chromosomes** (chromosomes 13, 14, 15, 21, 22) that fuse at their centromeres, with loss of their short arms, resulting in a single, large **derivative chromosome**.
- In this case, while the karyotype shows 46 chromosomes, the presence of a third copy of chromosome 21 genes incorporated into another chromosome, likely through the fusion of chromosome 21 with another acrocentric chromosome, leads to **trisomy 21** phenotype even though the total chromosome count is normal.
*Nondisjunction*
- **Nondisjunction** refers to the failure of homologous chromosomes or sister chromatids to separate during meiosis or mitosis, leading to an abnormal number of chromosomes (e.g., three separate copies of chromosome 21 in **trisomy 21**).
- This mechanism would typically result in a karyotype of **47,XX,+21** or **47,XY,+21** and would not explain the finding of 46 chromosomes with a third copy of chromosome 21 genes incorporated into another chromosome.
*Anticipation*
- **Anticipation** is a phenomenon in which the severity of a genetic disorder increases and/or the age of onset decreases in succeeding generations.
- This mechanism is characteristic of certain **trinucleotide repeat disorders** like Huntington's disease or myotonic dystrophy and does not explain the genetic findings associated with Down syndrome.
*Imprinting*
- **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a parent-of-origin specific manner, meaning only the allele inherited from either the mother or the father is expressed.
- While important for some genetic disorders (e.g., Prader-Willi or Angelman syndromes), imprinting does not explain the presence of an extra copy of chromosome 21 genetic material leading to Down syndrome.
*Mosaicism*
- **Mosaicism** occurs when an individual has two or more genetically distinct cell lines originating from a single zygote, often due to a **nondisjunction event** during early postzygotic mitotic divisions.
- While mosaic Down syndrome can occur, it would typically present with some cells having **trisomy 21** (47,XX,+21) and other cells being normal (46,XX), not with 46 chromosomes and an extra set of chromosome 21 genes translocated onto another chromosome.
Question 12: A 3500-g (7 lb 11 oz) healthy female newborn is delivered at 38 weeks' gestation. Chorionic villus sampling (CVS) in the first trimester showed a trisomy of chromosome 21 but the pregnancy was otherwise uncomplicated. Physical examination of the newborn is normal. Chromosomal analysis at birth shows a 46, XX karyotype. Which of the following is the most likely explanation for the prenatal chromosomal abnormality?
A. Incomplete penetrance
B. Placental mosaicism (Correct Answer)
C. Phenotypic pleiotropy
D. Variable expressivity
E. Uniparental disomy
Explanation: ***Placental mosaicism***
- **Placental mosaicism** occurs when the chromosomal abnormality (e.g., trisomy 21) is present in the placenta but not in the fetus.
- This can lead to a false positive result on **chorionic villus sampling (CVS)** if the sampled tissue from the placenta contains the abnormal cells, while the fetus is truly euploid.
*Incomplete penetrance*
- **Incomplete penetrance** refers to a situation where individuals with a specific genotype do not always express the associated phenotype.
- This concept applies to single-gene disorders, not to a resolution of a **chromosomal abnormality** found during prenatal testing.
*Phenotypic pleiotropy*
- **Phenotypic pleiotropy** describes when a single gene mutation affects multiple, seemingly unrelated phenotypic traits.
- It does not explain a discrepancy between a prenatal chromosomal finding and a normal postnatal karyotype.
*Variable expressivity*
- **Variable expressivity** describes the range of signs and symptoms that can occur in different people with the same genetic condition.
- While it explains differing severity of a genetic disorder, it does not account for a complete resolution of a **chromosomal abnormality** from a trisomy to a normal karyotype.
*Uniparental disomy*
- **Uniparental disomy** occurs when an individual receives both copies of a chromosome from one parent and none from the other.
- While it can be associated with certain genetic disorders, it does not explain a situation where a prenatal trisomy completely resolves to a normal diploid karyotype.
Question 13: A 10-year-old boy is brought to a pediatrician by his mother for evaluation of fever, malaise, and rash with severe itching all over his body for the past 5 days. His immunization history is unavailable. His vital signs include: pulse 110/min, temperature 37.8°C (100.0°F), and respiratory rate 26/min. On examination of the skin, diffuse peeling vesicular lesions involving the arms and chest are observed. The pediatrician diagnoses the boy with chickenpox and reassures the mother. A few days later the boy returns to the clinic for a follow-up with his mother. The skin lesions have healed and there are scars. The formation of these scars is best described by which of the following statements?
A. The scars are permanent and remain for life in all cases.
B. The lesions now have progressed on to chronic inflammation.
C. The scars represent complete resolution of acute inflammation.
D. Neutrophils, plasma cells, and macrophages are the predominant cells in these lesions.
E. It is a part of the healing process of acute inflammation. (Correct Answer)
Explanation: ***It is a part of the healing process of acute inflammation.***
- The formation of scars after chickenpox reflects the body's attempt to repair tissue damage from the **vesicular lesions**, a direct consequence of the acute inflammatory response.
- Varicella-zoster virus (chickenpox) causes skin lesions that lead to localized tissue destruction, and subsequent **fibrosis** and scar formation are part of the normal healing with tissue repair.
*The scars are permanent and remain for life in all cases.*
- While many chickenpox scars are permanent, their **visibility and persistence can vary**, and some may fade significantly over time or with treatment.
- The depth and severity of the original lesion, as well as individual healing factors, influence the **permanence of the scar**.
*The lesions now have progressed on to chronic inflammation.*
- Scars indicate the **resolution of acute inflammation** and subsequent repair, not a progression to chronic inflammation.
- **Chronic inflammation** would involve ongoing active inflammation and tissue destruction, which is not characteristic of healed chickenpox scars.
*The scars represent complete resolution of acute inflammation.*
- While scars do represent the resolution of active inflammation, they signify **repair by fibrosis** rather than a "complete resolution" where the tissue returns to its original state.
- **Complete resolution** would imply restitution ad integrum (returning to normal tissue structure) without any residual scarring.
*Neutrophils, plasma cells, and macrophages are the predominant cells in these lesions.*
- These cells are characteristic of **active acute or chronic inflammatory processes**, not healed scars.
- Scars primarily consist of **collagen deposits** laid down by fibroblasts, with a much-reduced presence of inflammatory cells.
Question 14: A 62-year-old woman with type 2 diabetes mellitus comes to the physician because of a 1-year history of progressively worsening paresthesias in her upper limbs. She has accidentally burned her fingers on hot dishes several times. She was involved in a motor vehicle collision 3 years ago. Neurologic examination shows absent temperature sensation with normal fine touch sensation over the upper extremities and chest. Without treatment, this patient is at increased risk of developing which of the following?
A. Decreased Mini-Mental State Examination score
B. Drooping of the eyelid
C. Absent anal wink reflex
D. Absent knee-jerk reflex
E. Exaggerated biceps reflex (Correct Answer)
Explanation: ***Exaggerated biceps reflex***
- This patient presents with **syringomyelia**, characterized by a **cape-like distribution of dissociated sensory loss** (absent pain/temperature sensation with preserved fine touch over the upper extremities and chest), likely post-traumatic from the motor vehicle collision 3 years ago.
- As the syrinx expands, it can extend laterally to involve the **lateral corticospinal tracts**, leading to **upper motor neuron signs** including hyperreflexia in the upper limbs.
- While early syringomyelia may cause lower motor neuron signs (from anterior horn cell damage), progressive expansion of the cavity can result in exaggerated reflexes as corticospinal pathways are compromised.
*Decreased Mini-Mental State Examination score*
- This score assesses **cognitive function** and is not affected by syringomyelia, which primarily impacts **spinal cord tracts**.
- Syringomyelia does not cause dementia or cognitive decline.
*Drooping of the eyelid*
- **Ptosis** (drooping eyelid) can occur if the syrinx extends to **C8-T1** and damages sympathetic fibers in the **intermediolateral cell column**, causing Horner's syndrome.
- However, this is a less common complication compared to motor changes, and the clinical scenario doesn't suggest extension to this level yet.
*Absent anal wink reflex*
- The anal wink reflex tests the integrity of the **S2-S4 spinal segments** and **pudendal nerve**.
- Syringomyelia typically affects the **cervical or thoracic spine**, and the described presentation shows no evidence of lumbosacral involvement.
*Absent knee-jerk reflex*
- The knee-jerk reflex tests the **L2-L4 spinal segments**.
- The patient's sensory loss is confined to the upper extremities and chest, indicating a **cervical/upper thoracic syrinx** that would not directly affect lumbar reflexes.
Question 15: An 80-year-old woman is brought to the physician by her 2 daughters for worsening memory loss. They report that their mother is increasingly forgetful about recent conversations and events. She is unable to remember her appointments and commitments she has made. 3 years ago, the patient was moved into an elder care facility because she was often getting lost on her way home and forgetting to take her medications. The patient reports that she is very socially active at her new home and has long conversations with the other residents about her adventures as an air hostess during her youth. Which of the following cerebral pathologies is most likely present in this patient?
A. Lewy bodies
B. Lacunar infarcts
C. Intracytoplasmic vacuoles
D. Neurofibrillary tangles (Correct Answer)
E. Demyelination
Explanation: ***Neurofibrillary tangles***
- The patient's presentation with **progressive memory loss** affecting recent events, getting lost, and forgetting medications, while largely preserving long-term memory (recalling youth as an air hostess and engaging in conversations), is highly characteristic of **Alzheimer's disease**.
- **Neurofibrillary tangles**, composed of hyperphosphorylated tau protein, along with **amyloid plaques**, are the hallmark pathological findings in Alzheimer's disease.
*Lewy bodies*
- **Lewy bodies** are characteristic of **Lewy body dementia** or Parkinson's disease with dementia, which typically present with prominent **fluctuations in cognition**, recurrent **visual hallucinations**, and parkinsonism.
- While memory loss can occur, the dominant features in this case point away from Lewy body pathology.
*Lacunar infarcts*
- **Lacunar infarcts** are associated with **vascular dementia**, which often presents with a more **step-wise decline** in cognitive function, focal neurological deficits, and evidence of cerebrovascular disease on imaging.
- The patient's gradual and progressive memory loss is less typical of lacunar infarcts as the primary cause.
*Intracytoplasmic vacuoles*
- **Intracytoplasmic vacuoles** are characteristic of **Creutzfeldt-Jakob disease** (spongiform encephalopathy), which is a rapidly progressive and fatal neurodegenerative disorder with distinct neurological symptoms such as myoclonus and ataxia, not fitting this patient's profile.
- The disease course is typically much faster than the 3-year progression described.
*Demyelination*
- **Demyelination** is the hallmark of conditions like **multiple sclerosis**, which primarily affects younger individuals and typically presents with a range of neurological deficits, including motor, sensory, and visual disturbances, that often relapse and remit.
- It does not typically present as a primary, progressive memory disorder in an 80-year-old in this manner.
Question 16: A 17-year-old boy comes to the physician because of a nonpruritic rash on his chest for 1 week. He returned from a trip to Puerto Rico 10 days ago. He started using a new laundry detergent after returning. He has type 1 diabetes mellitus controlled with insulin. His mother has Hashimoto thyroiditis, and his sister has severe facial acne. Examination of the skin shows multiple, nontender, round, hypopigmented macules on the chest and trunk. There is fine scaling when the lesions are scraped with a spatula. Which of the following is the most likely underlying mechanism of this patient's symptoms?
A. Increased sebum production
B. Infection with Trichophyton rubrum
C. Increased growth of Malassezia globosa (Correct Answer)
D. Antigen uptake by Langerhans cells
E. Autoimmune destruction of melanocytes
Explanation: ***Increased growth of Malassezia globosa***
- The clinical presentation of **hypopigmented macules with fine scaling** on the chest and trunk, especially in a young male who recently traveled to a tropical climate (Puerto Rico), is highly characteristic of **tinea versicolor**.
- Tinea versicolor is caused by an overgrowth of **Malassezia species** (primarily *M. globosa*), a commensal yeast that thrives in warm, humid conditions and is often associated with oily skin, leading to dyspigmentation and scaling due to interference with melanin production.
*Increased sebum production*
- While increased sebum production can contribute to a favorable environment for fungal growth, it is the underlying mechanism for conditions like **acne vulgaris** and **seborrheic dermatitis**, which present differently (e.g., comedones, inflammatory papules, erythema, greasy scales).
- This patient's rash is specifically described as hypopigmented macules with fine scaling, not inflammatory papules or pustules typical of acne, nor the greasy scales of seborrheic dermatitis.
*Infection with Trichophyton rubrum*
- **Trichophyton rubrum** is a dermatophyte commonly responsible for **tinea corporis** (ringworm of the body), **tinea pedis** (athlete's foot), and **tinea cruris** (jock itch), which typically present as **erythematous, annular, itchy lesions with raised borders**.
- The rash described here (hypopigmented, nonpruritic macules) does not fit the typical presentation of dermatophyte infections caused by *Trichophyton rubrum*.
*Antigen uptake by Langerhans cells*
- **Antigen uptake by Langerhans cells** is a crucial step in the pathogenesis of **allergic contact dermatitis**, where the skin reacts to an external allergen after sensitization, mediated by a **Type IV hypersensitivity reaction**.
- While the patient used a new laundry detergent, the rash's appearance (**hypopigmented macules with fine scaling**) is incongruent with contact dermatitis, which usually presents as an **erythematous, pruritic, vesicular, or eczematous rash** in the contact area.
*Autoimmune destruction of melanocytes*
- **Autoimmune destruction of melanocytes** is the underlying mechanism for **vitiligo**, an autoimmune condition characterized by **well-demarcated, completely depigmented patches** of skin.
- The lesions in this patient are described as **hypopigmented** (reduced pigmentation), not completely depigmented, and show **fine scaling**, which is not a feature of vitiligo.
Question 17: A 65-year-old man with no significant medical history begins to have memory loss and personality changes. Rapidly, over the next few months his symptoms increase in severity. He experiences a rapid mental deterioration associated with sudden, jerking movements, particularly in response to being startled. He has gait disturbances as well. Eventually, he lapses into a coma and dies approximately ten months after the onset of symptoms. Which of the following would most likely be seen on autopsy of the brain in this patient?
A. Neurofibrillary tangles
B. Amyloid plaques
C. Spongiform changes (Correct Answer)
D. Vascular lesions
E. Lewy bodies
Explanation: ***Spongiform changes***
- This patient's **rapidly progressive dementia**, associated with **myoclonus (jerking movements)** and **gait disturbances**, culminating in death within months, is highly suggestive of **Creutzfeldt-Jakob disease (CJD)**.
- CJD is characterized by the accumulation of abnormally folded prion proteins (PrPSc), leading to **spongiform degeneration** (vacuolation) of neurons and neuropil, **neuronal loss**, and **astrogliosis** in the brain.
*Neurofibrillary tangles*
- **Neurofibrillary tangles**, composed primarily of hyperphosphorylated **tau protein**, are a hallmark of **Alzheimer's disease**.
- Alzheimer's disease typically has a much **slower progression** over several years, unlike the rapid deterioration seen in this patient.
*Amyloid plaques*
- **Amyloid plaques**, formed by the extracellular deposition of **beta-amyloid protein**, are also characteristic features of **Alzheimer's disease**.
- Like neurofibrillary tangles, amyloid plaques are associated with a chronic, progressive course of dementia, not the **rapidly fatal trajectory** described.
*Vascular lesions*
- **Vascular lesions**, such as infarcts or hemorrhages, are the underlying pathology in **vascular dementia**.
- While vascular dementia can cause cognitive decline, its presentation often involves **step-wise deterioration** and may be associated with focal neurological deficits, which are not the primary features here.
*Lewy bodies*
- **Lewy bodies**, which are intracellular cytoplasmic inclusions of **alpha-synuclein protein**, are characteristic of **Lewy body dementia** and **Parkinson's disease**.
- Lewy body dementia presents with fluctuating cognition, visual hallucinations, and parkinsonism, but typically does not show the **rapid progression** and prominent myoclonus seen in CJD.
