A 34-year-old man comes to the physician for evaluation of a rash on the elbows for several months. A biopsy of the affected area shows a thinned stratum granulosum as well as retained nuclei and spongiotic clusters of neutrophils in the stratum corneum. This patient's skin findings are most likely associated with which of the following conditions?
Q312
A 55-year-old male presents to his primary care physician with right upper quadrant pain that has progressed over the last three months with unexplained weakness and joint pains that have been "out of the ordinary" over the last year. On history, you note the patient lives a sedentary lifestyle, rarely leaves the house, has controlled diabetes diagnosed 15 years ago, and has documented cardiomyopathy. On physical exam the man appears non-toxic, sclera are icteric, cornea appear normal, generalized pain is elicited on palpation of the right upper quadrant, and skin appears quite bronzed on his extremities. What is this patient most at risk for ten to fifteen years later due to his underlying condition?
Q313
A 47-year-old woman comes to the physician for a 2-month history of fatigue, intermittent left-sided flank pain, and diffuse extremity pain. She was treated for a prolactinoma 5 years ago and has had recurrent antral and duodenal peptic ulcers despite medical therapy. Her only medication is omeprazole. Physical examination shows a moderately distended abdomen that is diffusely tender to palpation. There is mild left-sided costovertebral angle tenderness. Serum studies show a calcium of 12 mg/dL, phosphorus of 2 mg/dL, and parathyroid hormone level of 826 pg/mL. An ultrasound of the abdomen shows multiple kidney stones in the left ureteropelvic junction. This patient is most likely to have which of the following protein abnormalities?
Q314
A 51-year-old woman with Sjogren’s syndrome presents to her physician for suddenly developed palpitations. She feels more anxious than usual and has had difficulty sleeping well for the past 2 weeks. She has lost 2 kg (4.4 lb) since her last routine appointment 6 months ago. She also has had diarrhea and often feels like her heart is beating very quickly. On physical examination, her skin appears warm and moist. Her reflexes are hyperactive. Her thyroid is moderately enlarged and is non-tender. She has mild dry eyes and dry mouth. Her blood pressure is 136/88 mm Hg, pulse is 76/min, respirations are 17/min and temperature is 36.7°C (98.1°F). Which of the following pathologic findings is this patient likely to have?
Q315
An otherwise healthy 17-year-old girl comes to the physician because of multiple patches on her face, hands, abdomen, and feet that are lighter than the rest of her skin. The patches began to appear 3 years ago and have been gradually increasing in size since. There is no associated itchiness, redness, numbness, or pain. She emigrated from India 2 years ago. An image of the lesions on her face is shown. Which of the following is most likely involved in the pathogenesis of this patient's skin findings?
Q316
An investigator is studying the outcomes of a malaria outbreak in an endemic region of Africa. 500 men and 500 women with known malaria exposure are selected to participate in the study. Participants with G6PD deficiency are excluded from the study. The clinical records of the study subjects are reviewed and their peripheral blood smears are evaluated for the presence of Plasmodium trophozoites. Results show that 9% of the exposed population does not have clinical or laboratory evidence of malaria infection. Which of the following best explains the absence of infection seen in this subset of participants?
Q317
A 24-year-old Turkish female presents to your office for a routine examination. She recently started a new job and has been tired most of the time. She does not have any dizziness and has not lost consciousness. She follows a well-balanced diet and is not vegetarian. She recalls that other family members have had similar symptoms in the past. On physical exam her temperature is 99°F (37.2°C), blood pressure is 115/78 mmHg, pulse is 100/min, respirations are 22/min, and pulse oximetry is 99% on room air. On physical exam, you notice conjunctival pallor. Labs are obtained and the results are shown below:
Hemoglobin: 10.2 g/dL
Hematocrit: 34%
Leukocyte count: 5,000 cells/mm^3 with normal differential
Platelet count: 252,000/mm^3
Mean corpuscular hemoglobin concentration: 20.4%
Mean corpuscular volume: 65 µm^3
Peripheral blood smear is shown in the image provided. The cause of her anemia is most likely associated with which of the following?
Q318
A four-year-old boy is brought to his pediatrician by his mother for recurrent nosebleeds. The mother reports that the boy has had five nosebleeds within the past 2 weeks, each lasting between 15 and 20 minutes. The patient was born at term and has been hospitalized twice for pneumonia treatment. There is no family history of serious illness. The patient is at the 8th percentile for height and the 30th percentile for weight. Vital signs are within normal limits. Examination shows a small, thin child with two flat, dark brown areas of hyperpigmentation across the upper back and a similar discoloration on the left buttock. There is bilateral esotropia. Laboratory studies show a hemoglobin concentration of 9.3 g/dL, mean corpuscular volume of 107 μm3, leukocyte count of 3,800/mm3, and platelet count of 46,000/mm3. Which of the following is the most likely underlying cause of this patient's condition?
Q319
A 29-year-old woman presents with shortness of breath and chest pain for the past week. She says her chest pain is aggravated by deep breathing and she becomes short of breath while walking upstairs in her home. She also has been feeling feverish and fatigued for the past week, as well as pain in her wrists, hands, and left knee. Review of systems is significant for a 4.5 kg (10.0 lb) weight loss over the previous month. Past medical history consists of 2 spontaneous abortions, both of which occurred in the 1st trimester. On physical examination, there is a pink rash present over her face, which is aggravated by exposure to sunlight. There are decreased breath sounds on the right. A chest radiograph is performed which reveals evidence of a right pleural effusion. Serum ANA and anti-dsDNA autoantibodies are positive. Urinalysis is unremarkable. Errors with which of the following is most likely to lead to her disease?
Q320
A 51-year-old African American man presents to his primary care physician’s office for an annual visit. He has no major concerns and says that he has been healthy for the last year. His past medical history is significant for diabetes as well as long standing hypertension that has developed gradually since his 30's; however, he has refused to take any medications. Physical exam shows no abnormal findings. Routine laboratory testing reveals the following:
Serum creatinine concentration: 1.5 mg/dL
Blood urea nitrogen: 31 mg/dL
Based on these results, urine studies are conducted that reveal mild proteinuria of less than 1 g/day and no casts.
Which of the following is most likely associated with the cause of this patient's elevated creatinine?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 311: A 34-year-old man comes to the physician for evaluation of a rash on the elbows for several months. A biopsy of the affected area shows a thinned stratum granulosum as well as retained nuclei and spongiotic clusters of neutrophils in the stratum corneum. This patient's skin findings are most likely associated with which of the following conditions?
A. Hypersensitivity to gliadin
B. Hashimoto thyroiditis
C. Psoriasis (Correct Answer)
D. Insulin resistance
E. Infection with hepatitis C virus
Explanation: ***Psoriasis***
- The biopsy findings of a **thinned stratum granulosum**, **retained nuclei (parakeratosis)** and **spongiotic clusters of neutrophils in the stratum corneum (Munro microabscesses)** are characteristic histological features of psoriasis.
- Psoriasis often presents as **erythematous plaques with silvery scales**, commonly on extensor surfaces like the elbows, consistent with the patient's presentation.
*Hypersensitivity to gliadin*
- This is associated with **dermatitis herpetiformis**, which presents with intensely pruritic vesicles and bullae, typically on extensor surfaces, but has a different histopathological picture.
- Biopsy of dermatitis herpetiformis shows **subepidermal blistering** with **neutrophil and eosinophil infiltration**, and granular IgA deposition along the dermal papillae, not the findings described.
*Hashimoto thyroiditis*
- This is an **autoimmune disorder affecting the thyroid gland** and typically presents with symptoms of hypothyroidism, such as fatigue, weight gain, and cold intolerance.
- While autoimmune conditions can sometimes coexist, Hashimoto thyroiditis does not directly cause the *specific skin rash and biopsy findings* described in this patient.
*Insulin resistance*
- This condition is often associated with **acanthosis nigricans**, which presents as velvety, hyperpigmented plaques, typically in skin folds.
- The histological features of acanthosis nigricans show hyperkeratosis and papillomatosis, which are distinct from the findings of a thinned stratum granulosum and Munro microabscesses.
*Infection with hepatitis C virus*
- Hepatitis C infection can be associated with various dermatological manifestations, including **lichen planus**, **porphyria cutanea tarda**, and **leukocytoclastic vasculitis**.
- None of these associated skin conditions exhibit the specific biopsy findings of a thinned stratum granulosum and Munro microabscesses seen in this case.
Question 312: A 55-year-old male presents to his primary care physician with right upper quadrant pain that has progressed over the last three months with unexplained weakness and joint pains that have been "out of the ordinary" over the last year. On history, you note the patient lives a sedentary lifestyle, rarely leaves the house, has controlled diabetes diagnosed 15 years ago, and has documented cardiomyopathy. On physical exam the man appears non-toxic, sclera are icteric, cornea appear normal, generalized pain is elicited on palpation of the right upper quadrant, and skin appears quite bronzed on his extremities. What is this patient most at risk for ten to fifteen years later due to his underlying condition?
A. Pulmonary fibrosis
B. Movement disorders
C. Colonic adenocarcinoma
D. Hepatocellular carcinoma (Correct Answer)
E. Prostatic adenocarcinoma
Explanation: ***Hepatocellular carcinoma***
- The patient's presentation with **bronzed skin**, **diabetes**, **cardiomyopathy**, and **right upper quadrant pain** strongly suggests **hemochromatosis** due to iron overload.
- **Cirrhosis** is a common complication of iron overload in hemochromatosis, and **hepatocellular carcinoma** is a significant long-term risk for patients with cirrhosis.
*Pulmonary fibrosis*
- While chronic iron overload can affect various organs, **pulmonary fibrosis** is not a characteristic or common long-term complication of hemochromatosis.
- This condition is more typically associated with environmental exposures, autoimmune diseases, or idiopathic causes.
*Movement disorders*
- **Movement disorders** like Parkinsonism can be seen in other neurodegenerative conditions involving metal accumulation (e.g., Wilson's disease with copper), but it is not a primary or significant long-term complication of hemochromatosis.
- Neurological manifestations in hemochromatosis are rare and typically involve cognitive dysfunction rather than movement disorders.
*Colonic adenocarcinoma*
- While diabetes (a feature of hemochromatosis) is a mild risk factor for **colorectal cancer**, there is no direct strong link between **hemochromatosis** itself and a significantly increased risk of **colonic adenocarcinoma**.
- The primary cancer risk in hemochromatosis is associated with the **liver**.
*Prostatic adenocarcinoma*
- There is no established direct link or significantly increased risk of **prostatic adenocarcinoma** specifically due to **hemochromatosis**.
- General age-related risk factors would apply, but it's not a condition specifically exacerbated by iron overload.
Question 313: A 47-year-old woman comes to the physician for a 2-month history of fatigue, intermittent left-sided flank pain, and diffuse extremity pain. She was treated for a prolactinoma 5 years ago and has had recurrent antral and duodenal peptic ulcers despite medical therapy. Her only medication is omeprazole. Physical examination shows a moderately distended abdomen that is diffusely tender to palpation. There is mild left-sided costovertebral angle tenderness. Serum studies show a calcium of 12 mg/dL, phosphorus of 2 mg/dL, and parathyroid hormone level of 826 pg/mL. An ultrasound of the abdomen shows multiple kidney stones in the left ureteropelvic junction. This patient is most likely to have which of the following protein abnormalities?
A. Mutation of VHL tumor suppressor
B. Activation of RET proto-oncogene
C. Altered menin protein (Correct Answer)
D. Mutation in C-Kit protein
E. Altered merlin protein expression
Explanation: ***Altered menin protein***
- This patient presents with a **prolactinoma**, **recurrent peptic ulcers** (suggesting gastrinoma), and **hypercalcemia with elevated PTH** (indicating primary hyperparathyroidism). This triad of tumors (pituitary, parathyroid, and pancreatic/duodenal neuroendocrine tumors) is characteristic of **Multiple Endocrine Neoplasia type 1 (MEN1) syndrome**.
- **MEN1 syndrome** is caused by germline mutations in the *MEN1* gene, which encodes the **menin tumor suppressor protein**. An altered or dysfunctional menin protein leads to uncontrolled cell growth in these endocrine glands.
*Mutation of VHL tumor suppressor*
- Mutations in the **VHL (Von Hippel-Lindau) tumor suppressor gene** are associated with **Von Hippel-Lindau disease**.
- This syndrome is characterized by **hemangioblastomas** of the retina and CNS, **renal cell carcinoma**, **pheochromocytomas**, and pancreatic neuroendocrine tumors, which does not fit the patient's presentation.
*Activation of RET proto-oncogene*
- **Activating mutations in the RET proto-oncogene** are associated with **Multiple Endocrine Neoplasia type 2 (MEN2)** syndromes (MEN2A and MEN2B).
- These syndromes primarily involve **medullary thyroid carcinoma**, pheochromocytomas, and either primary hyperparathyroidism (MEN2A) or mucosal neuromas/Marfanoid habitus (MEN2B), none of which are present in this case.
*Mutation in C-Kit protein*
- Mutations in the **C-Kit protein** (encoded by the *KIT* gene) are primarily associated with certain types of **gastrointestinal stromal tumors (GISTs)** and **mastocytosis**.
- These conditions do not explain the pituitary adenoma, hyperparathyroidism, or the specific constellation of symptoms observed in the patient.
*Altered merlin protein expression*
- **Altered merlin protein expression** (encoded by the *NF2* gene) is characteristic of **Neurofibromatosis type 2 (NF2)**.
- NF2 is primarily associated with **bilateral vestibular schwannomas**, other schwannomas, meningiomas, and ependymomas, without the endocrine tumors seen in this patient.
Question 314: A 51-year-old woman with Sjogren’s syndrome presents to her physician for suddenly developed palpitations. She feels more anxious than usual and has had difficulty sleeping well for the past 2 weeks. She has lost 2 kg (4.4 lb) since her last routine appointment 6 months ago. She also has had diarrhea and often feels like her heart is beating very quickly. On physical examination, her skin appears warm and moist. Her reflexes are hyperactive. Her thyroid is moderately enlarged and is non-tender. She has mild dry eyes and dry mouth. Her blood pressure is 136/88 mm Hg, pulse is 76/min, respirations are 17/min and temperature is 36.7°C (98.1°F). Which of the following pathologic findings is this patient likely to have?
A. Lymphoma
B. Chronic lymphocytic thyroiditis (Correct Answer)
C. Silent thyroiditis
D. Fibrous thyroiditis
E. Granulomatous thyroiditis
Explanation: ***Chronic lymphocytic thyroiditis***
- This patient with **Sjogren's syndrome** (an autoimmune disease) presenting with hyperthyroidism most likely has **Hashimoto's thyroiditis** (chronic lymphocytic thyroiditis) in its early hyperthyroid phase, known as **"Hashitoxicosis"**.
- Patients with one autoimmune disease have an increased risk of developing other autoimmune conditions, and **Hashimoto's thyroiditis** frequently coexists with Sjogren's syndrome.
- The pathologic finding is **lymphocytic infiltration with germinal center formation** in the thyroid, along with destruction of thyroid follicles.
- Early in Hashimoto's disease, destruction of follicles releases stored thyroid hormone, causing **transient hyperthyroidism** before eventual progression to hypothyroidism.
- The **enlarged, non-tender thyroid** is characteristic of Hashimoto's thyroiditis.
*Lymphoma*
- While Sjogren's syndrome does increase the risk of **B-cell lymphoma** (particularly MALT lymphoma in salivary glands), this patient's presentation is classic for **hyperthyroidism from thyroiditis**, not lymphoma.
- Primary thyroid lymphoma typically presents as a **rapidly enlarging, firm thyroid mass** with **compressive symptoms** (dysphagia, dyspnea, hoarseness), which are absent here.
*Silent thyroiditis*
- Also called **painless thyroiditis** or **postpartum thyroiditis**, this involves transient thyroid inflammation with a hyperthyroid phase followed by hypothyroidism.
- While it can occur, the patient's **established autoimmune disease (Sjogren's syndrome)** makes **chronic lymphocytic thyroiditis (Hashimoto's)** a more likely underlying pathology, as these conditions frequently coexist.
- Silent thyroiditis is typically a **self-limited condition** without the chronic lymphocytic infiltration seen in Hashimoto's.
*Fibrous thyroiditis*
- **Riedel's thyroiditis** is a rare condition characterized by **dense fibrous tissue replacement** of the thyroid, often extending beyond the capsule to involve surrounding structures.
- It presents as a **hard, fixed, "woody" thyroid mass** and typically causes **hypothyroidism** due to thyroid destruction, not hyperthyroidism.
- The patient's **moderately enlarged, non-tender thyroid** does not fit this presentation.
*Granulomatous thyroiditis*
- **De Quervain's (subacute granulomatous) thyroiditis** typically follows a **viral upper respiratory infection** and presents with a **painful, tender thyroid gland** and systemic symptoms (fever, malaise).
- The pathologic finding is **granulomatous inflammation** with giant cells.
- The **absence of thyroid tenderness** and the presence of another autoimmune condition (Sjogren's) make chronic lymphocytic thyroiditis more likely than granulomatous thyroiditis.
Question 315: An otherwise healthy 17-year-old girl comes to the physician because of multiple patches on her face, hands, abdomen, and feet that are lighter than the rest of her skin. The patches began to appear 3 years ago and have been gradually increasing in size since. There is no associated itchiness, redness, numbness, or pain. She emigrated from India 2 years ago. An image of the lesions on her face is shown. Which of the following is most likely involved in the pathogenesis of this patient's skin findings?
A. Defective tuberin protein
B. Infection with Malassezia globosa
C. Infection with Mycobacterium leprae
D. Absence of tyrosinase activity
E. Autoimmune destruction of melanocytes (Correct Answer)
Explanation: ***Autoimmune destruction of melanocytes***
- The presentation of **multiple, gradually enlarging hypopigmented patches** on various body areas, particularly in an otherwise healthy individual, is highly suggestive of **vitiligo**.
- **Vitiligo** is an acquired depigmentation disorder resulting from the **autoimmune destruction of melanocytes**, leading to a complete absence of melanin in the affected areas.
*Defective tuberin protein*
- **Defective tuberin protein** is associated with **tuberous sclerosis**, a neurocutaneous syndrome.
- Skin manifestations of tuberous sclerosis include **ash-leaf spots** (hypopigmented macules), **facial angiofibromas**, and **Shagreen patches**, which are typically present from birth or early childhood and often associated with neurological symptoms.
*Infection with Malassezia globosa*
- **Malassezia globosa** causes **tinea versicolor** (pityriasis versicolor), a superficial fungal infection characterized by **hypopigmented or hyperpigmented patches** with fine scale.
- These lesions often occur on the trunk and proximal extremities and typically **fluoresce yellow-green** under Wood's lamp, which is not mentioned here.
*Infection with Mycobacterium leprae*
- **Mycobacterium leprae** causes **leprosy**, which can present with **hypopigmented macules** that are typically **anesthetic** (loss of sensation).
- While the patient is from an endemic area (India), the lack of **anesthesia**, associated neuropathic symptoms, or active inflammation makes leprosy less likely.
*Absence of tyrosinase activity*
- **Absence of tyrosinase activity** is characteristic of **oculocutaneous albinism**, a *genetic* condition leading to a *generalized lack of pigmentation* in the skin, hair, and eyes.
- This patient presents with *localized patches* of depigmentation that appeared at 14 years old, which is inconsistent with congenital albinism.
Question 316: An investigator is studying the outcomes of a malaria outbreak in an endemic region of Africa. 500 men and 500 women with known malaria exposure are selected to participate in the study. Participants with G6PD deficiency are excluded from the study. The clinical records of the study subjects are reviewed and their peripheral blood smears are evaluated for the presence of Plasmodium trophozoites. Results show that 9% of the exposed population does not have clinical or laboratory evidence of malaria infection. Which of the following best explains the absence of infection seen in this subset of participants?
A. Translocation of c-myc gene
B. Glutamic acid substitution in the β-globin chain (Correct Answer)
C. Inherited mutation affecting ribosome synthesis
D. Inherited defect in erythrocyte membrane ankyrin protein
E. Defective X-linked ALA synthase gene
Explanation: ***Glutamic acid substitution in the β-globin chain***
- This describes **sickle cell trait (heterozygous HbS)**, which confers significant protection against severe malaria, explaining the absence of infection despite exposure.
- Individuals with sickle cell trait have **abnormally shaped red blood cells** under low oxygen conditions, which are less hospitable for **Plasmodium falciparum** growth and are more rapidly cleared by the spleen.
*Translocation of c-myc gene*
- A **t(8;14) translocation of the c-myc gene** is characteristic of **Burkitt lymphoma**, a B-cell malignancy, and has no protective effect against malaria.
- This genetic alteration leads to overexpression of **c-myc**, a proto-oncogene, contributing to uncontrolled cell growth.
*Inherited mutation affecting ribosome synthesis*
- Defects in **ribosome synthesis** can lead to various **ribosomopathies**, affecting cell proliferation and function, but they are not known to provide protection against malaria.
- Such mutations often result in syndromes with **developmental abnormalities** or **bone marrow failure**.
*Inherited defect in erythrocyte membrane ankyrin protein*
- Defects in **ankyrin protein** are associated with **hereditary spherocytosis**, causing fragile, spherical red blood cells that are prematurely destroyed.
- While hereditary spherocytosis can reduce malaria severity, its role in preventing initial infection is less pronounced, and the question refers to absence of infection.
*Defective X-linked ALA synthase gene*
- A defective **X-linked ALA synthase gene** (ALAS2) is associated with **X-linked sideroblastic anemia**, causing impaired heme synthesis.
- This condition is characterized by **microcytic, hypochromic anemia** and iron overload in erythroid precursors, with no known protective effect against malaria.
Question 317: A 24-year-old Turkish female presents to your office for a routine examination. She recently started a new job and has been tired most of the time. She does not have any dizziness and has not lost consciousness. She follows a well-balanced diet and is not vegetarian. She recalls that other family members have had similar symptoms in the past. On physical exam her temperature is 99°F (37.2°C), blood pressure is 115/78 mmHg, pulse is 100/min, respirations are 22/min, and pulse oximetry is 99% on room air. On physical exam, you notice conjunctival pallor. Labs are obtained and the results are shown below:
Hemoglobin: 10.2 g/dL
Hematocrit: 34%
Leukocyte count: 5,000 cells/mm^3 with normal differential
Platelet count: 252,000/mm^3
Mean corpuscular hemoglobin concentration: 20.4%
Mean corpuscular volume: 65 µm^3
Peripheral blood smear is shown in the image provided. The cause of her anemia is most likely associated with which of the following?
A. Inhibition of ALA dehydratase
B. Blood loss
C. X-linked defect in ALA synthase
D. Malnutrition
E. Point mutation on chromosome 11 (Correct Answer)
Explanation: ***Point mutation on chromosome 11***
- This patient's presentation with a **microcytic, hypochromic anemia** (MCV 65 µm^3, MCHC 20.4%) and **family history of similar symptoms** in a person of **Turkish descent** strongly suggests **beta-thalassemia minor**. Beta-thalassemia is caused by **point mutations on chromosome 11** affecting the beta-globin gene.
- The **peripheral blood smear** would likely show **microcytic, hypochromic red blood cells**, which is characteristic of thalassemia.
*Inhibition of ALA dehydratase*
- Inhibition of **ALA dehydratase** is associated with **lead poisoning**, which typically presents with a **microcytic anemia**, but also includes symptoms like **abdominal pain**, **neuropathy**, and **basophilic stippling** on peripheral smear, which are not mentioned.
- While lead poisoning can cause microcytic anemia, the **familial aspect** and ethnic background point away from this being the primary cause.
*Blood loss*
- **Chronic blood loss** can cause **iron deficiency anemia**, which would present with **microcytic, hypochromic anemia**, but the provided history does not suggest any sources of chronic blood loss, and the patient reports a well-balanced diet.
- The **familial history** and **ethnic background** make a genetic cause like thalassemia more likely than uncomplicated iron deficiency from blood loss.
*X-linked defect in ALA synthase*
- An **X-linked defect in ALA synthase** is associated with **sideroblastic anemia**, which can also be **microcytic and hypochromic**, but specifically shows **ring sideroblasts** in the bone marrow and typically involves an **X-linked inheritance pattern**.
- While sideroblastic anemia can be genetic, thalassemia is far more common in populations like Turkish individuals experiencing microcytic anemia with a family history.
*Malnutrition*
- **Malnutrition**, particularly **iron deficiency**, can lead to **microcytic anemia**. However, the patient reports a **well-balanced diet** and is not vegetarian, making dietary iron deficiency less likely.
- The strong **familial component** and **ethnic background** are more indicative of a genetic disorder like thalassemia rather than simple nutritional deficiency.
Question 318: A four-year-old boy is brought to his pediatrician by his mother for recurrent nosebleeds. The mother reports that the boy has had five nosebleeds within the past 2 weeks, each lasting between 15 and 20 minutes. The patient was born at term and has been hospitalized twice for pneumonia treatment. There is no family history of serious illness. The patient is at the 8th percentile for height and the 30th percentile for weight. Vital signs are within normal limits. Examination shows a small, thin child with two flat, dark brown areas of hyperpigmentation across the upper back and a similar discoloration on the left buttock. There is bilateral esotropia. Laboratory studies show a hemoglobin concentration of 9.3 g/dL, mean corpuscular volume of 107 μm3, leukocyte count of 3,800/mm3, and platelet count of 46,000/mm3. Which of the following is the most likely underlying cause of this patient's condition?
A. Defect in DNA crosslink repair (Correct Answer)
B. Postviral autoimmune reaction
C. Parvovirus B19 infection
D. Recent history of NSAID use
E. Mutation in WAS protein
Explanation: **Defect in DNA crosslink repair**
- This constellation of symptoms, including **pancytopenia** (low hemoglobin, leukocytes, and platelets), **macrocytosis** (high MCV), **short stature**, recurrent infections, and **cafe-au-lait spots**, is highly suggestive of **Fanconi anemia**.
- **Fanconi anemia** is an autosomal recessive disorder caused by a defect in **DNA crosslink repair**, leading to increased chromosomal fragility and bone marrow failure.
*Postviral autoimmune reaction*
- While a postviral autoimmune reaction could cause pancytopenia, it typically does not present with the **congenital abnormalities** (short stature, cafe-au-lait spots, esotropia) seen in this patient.
- There is no direct evidence of a recent viral illness preceding the onset of pancytopenia in this case.
*Parvovirus B19 infection*
- **Parvovirus B19** can cause transient aplastic crisis, particularly in individuals with pre-existing hematological conditions, leading to severe anemia.
- However, it would not explain the **pancytopenia**, **macrocytosis**, and the characteristic **physical findings** like cafe-au-lait spots and short stature.
*Recent history of NSAID use*
- **NSAIDs** can cause various side effects, including gastrointestinal bleeding (exacerbating anemia) or rarely drug-induced aplastic anemia.
- However, NSAID use does not account for the **pancytopenia**, **macrocytosis**, recurrent infections, and the specific **congenital anomalies** noted.
*Mutation in WAS protein*
- A **mutation in the WAS protein** is responsible for **Wiskott-Aldrich syndrome**, which presents with recurrent infections, thrombocytopenia (leading to epistaxis), and eczema.
- This syndrome typically involves **micro-thrombocytopenia** (small platelets) and immunodeficiency, but it does not cause **macrocytosis**, pancytopenia beyond thrombocytopenia, or the skeletal/cutaneous abnormalities like cafe-au-lait spots.
Question 319: A 29-year-old woman presents with shortness of breath and chest pain for the past week. She says her chest pain is aggravated by deep breathing and she becomes short of breath while walking upstairs in her home. She also has been feeling feverish and fatigued for the past week, as well as pain in her wrists, hands, and left knee. Review of systems is significant for a 4.5 kg (10.0 lb) weight loss over the previous month. Past medical history consists of 2 spontaneous abortions, both of which occurred in the 1st trimester. On physical examination, there is a pink rash present over her face, which is aggravated by exposure to sunlight. There are decreased breath sounds on the right. A chest radiograph is performed which reveals evidence of a right pleural effusion. Serum ANA and anti-dsDNA autoantibodies are positive. Urinalysis is unremarkable. Errors with which of the following is most likely to lead to her disease?
A. Intrinsic pathway
B. Cytotoxic CD8+ T cells
C. Bcl-2 overexpression
D. Necrosis
E. Fas-FasL interaction (Correct Answer)
Explanation: ***Fas-FasL interaction***
- This patient presents with multiple symptoms suggestive of **systemic lupus erythematosus (SLE)**, including photosensitive rash, arthritis, serositis (pleural effusion), weight loss, recurrent spontaneous abortions, and positive ANA/anti-dsDNA.
- Genetic defects in the **Fas** or **Fas ligand (FasL) apoptotic pathway** are strongly associated with increased risk of autoimmunity, particularly SLE, as they impair the deletion of autoreactive lymphocytes.
*Intrinsic pathway*
- The intrinsic apoptotic pathway is primarily activated by intracellular stress and mitochondria-dependent signals.
- While essential for cell death, defects in the intrinsic pathway are not as specifically implicated in the pathogenesis of SLE as the Fas-FasL (extrinsic) pathway.
*Cytotoxic CD8+ T cells*
- **CD8+ T cells** are primarily involved in killing virally infected or cancerous cells and are crucial for cellular immunity.
- While involved in some autoimmune processes, their dysfunction is not the primary or most common error leading to the development of SLE, which is largely mediated by autoantibodies.
*Bcl-2 overexpression*
- **Bcl-2** is an anti-apoptotic protein, and its overexpression inhibits apoptosis.
- While Bcl-2 overexpression could theoretically prevent the deletion of autoreactive cells, specific defects in the direct Fas-FasL signaling pathway are more directly and commonly linked to the immune dysregulation seen in SLE.
*Necrosis*
- **Necrosis** is an uncontrolled form of cell death often associated with inflammation and tissue damage.
- While certainly present in tissues affected by SLE due to inflammation, necrosis itself is a consequence of the disease process, not an upstream error in cell death regulation that leads to the autoimmunity of SLE.
Question 320: A 51-year-old African American man presents to his primary care physician’s office for an annual visit. He has no major concerns and says that he has been healthy for the last year. His past medical history is significant for diabetes as well as long standing hypertension that has developed gradually since his 30's; however, he has refused to take any medications. Physical exam shows no abnormal findings. Routine laboratory testing reveals the following:
Serum creatinine concentration: 1.5 mg/dL
Blood urea nitrogen: 31 mg/dL
Based on these results, urine studies are conducted that reveal mild proteinuria of less than 1 g/day and no casts.
Which of the following is most likely associated with the cause of this patient's elevated creatinine?
A. String of beads on angiography
B. Kimmelstiel-Wilson lesions (Correct Answer)
C. Apple-green birefringent lesions
D. Renal cortex necrosis
E. Flea-bitten kidney
Explanation: **Kimmelstiel-Wilson lesions**
- The patient has a history of long-standing diabetes and hypertension, which are the primary risk factors for **diabetic nephropathy**.
- **Kimmelstiel-Wilson lesions** are nodular glomerulosclerosis pathognomonic for **diabetic nephropathy**, characterized by hyaline nodules in the mesangium.
- This is the most likely cause given the combination of diabetes, mild proteinuria (<1 g/day), and chronic renal insufficiency.
*String of beads on angiography*
- This finding is characteristic of **fibromuscular dysplasia**, a non-inflammatory vascular disease that can cause **renal artery stenosis**.
- While renal artery stenosis can cause hypertension and renal impairment, the patient's long-standing diabetes and gradual progression make diabetic nephropathy a more probable cause.
*Apple-green birefringent lesions*
- This describes the characteristic staining of **amyloid deposits** with **Congo red stain** under polarized light.
- While amyloidosis can cause renal failure with proteinuria, it is less common than diabetic nephropathy in a patient with long-standing diabetes and the typical presentation described.
*Renal cortex necrosis*
- This is a rare and severe form of **acute kidney injury** often associated with conditions like severe sepsis, obstetric complications, or disseminated intravascular coagulation.
- The patient's history of gradual onset hypertension and diabetes, along with mild proteinuria and elevated creatinine, points to a chronic rather than acute process.
*Flea-bitten kidney*
- This describes the gross appearance of kidneys in **malignant hypertension**, showing petechial hemorrhages on the renal surface.
- While the patient has long-standing hypertension, the presentation suggests chronic kidney disease from diabetic nephropathy rather than acute malignant hypertension, which would present with markedly elevated blood pressure and acute kidney injury.