A 36-year-old man presents to his primary care physician with increasing fatigue. He says that the fatigue started after he returned from vacation in South America 4 weeks ago and thinks that it may be related to an infection he got while abroad. He does not know the name of the infection but says that he went to a local clinic for treatment and was given an antibiotic. Since then, he has noticed that he is no longer able to perform his job as a contractor who renovates old homes because he feels short of breath after just a few minutes of work. Furthermore, he says that he has been experiencing prolonged nosebleeds that never occurred prior to this episode. He denies any neurologic symptoms. His past medical history is significant for alcoholic hepatitis secondary to alcohol abuse 3 years prior. Physical exam reveals conjunctival pallor as well as petechiae. Which of the following findings is associated with the most likely cause of this patient's symptoms?
Q52
A 16-year-old male presents to the emergency department with a hematoma after falling during gym class. He claims that he has a history of prolonged nosebleeds and bruising/bleeding after minor injuries. Physical exam is unrevealing other than the hematoma. Labs are obtained showing an increased bleeding time and an abnormal ristocetin cofactor assay. Coagulation assays reveal an increased partial thromboplastin time (PTT) but a normal prothrombin time (PT). The patient is given desmopressin and is asked to avoid aspirin. Which of the following findings is most likely directly involved in the etiology of this patient's presentation?
Q53
A 66-year-old man is admitted to the medical floor after being diagnosed with community-acquired pneumonia. He has been in good health except for the use of steroids for the past 6 months for ulcerative colitis. The patient is started on the empiric therapy with ceftriaxone for the management of pneumonia. After 10 days of treatment in the hospital, he becomes tachypneic with a decreased level of consciousness. He develops generalized pustular eruptions all over his trunk. The temperature is 40.8°C (105.4°F), and the white blood cell count is 19,000/mm3. The gram stain of an aspirate shows many budding yeasts and neutrophils. A culture of the skin specimen is positive for Candida albicans. The nitroblue tetrazolium test is normal. What is the most likely condition related to his signs and symptoms?
Q54
A 24-year-old healthy male presents to the emergency room complaining of severe abdominal pain. He reports that he was playing rugby for his college team when he was tackled on his left side by a member of the opposing team. He is currently experiencing severe left upper abdominal pain and left shoulder pain. A review of his medical record reveals that he was seen by his primary care physician two weeks ago for mononucleosis. His temperature is 99°F (37.2°C), blood pressure is 90/50 mmHg, pulse is 130/min, and respirations are 26/min. He becomes increasingly lethargic over the course of the examination. He demonstrates exquisite tenderness to palpation over the left 8th, 9th, and 10th ribs as well as rebound tenderness in the abdomen. He is eventually stabilized and undergoes definitive operative management. After this patient recovers, which of the following is most likely to be found on a peripheral blood smear in this patient?
Q55
A 25-year-old man comes to the physician for the evaluation of recurrent episodes of nosebleeds over the past 6 months. The nosebleeds occur spontaneously and stop after 10 minutes after pinching the nose at the nostrils. He has no history of serious illness except for prolonged bleeding following wisdom teeth extraction 2 years ago. He does not smoke or drink alcohol. He takes no medications. Vital signs are within normal limits. Examination of the nose shows no abnormalities. There are several bruises on the lower extremities. The remainder of the examination shows no abnormalities. Laboratory studies show:
Hemoglobin 15 g/dL
Leukocyte count 6,000/mm3
Platelet count 220,000/mm3
Bleeding time 9 minutes
Prothrombin time 13 sec
Partial thromboplastin time 55 sec
Which of the following is the most likely diagnosis?
Q56
A mother brings her 6-year-old daughter in to the pediatrician’s clinic for a wellness visit. The mother has a history of von Willebrand’s disease (vWD) and is concerned that her daughter may be affected as well. The mother tells you that she has noticed that her daughter bruises very easily, and her bruises typically are visible for a longer period of time than those of her brother. She denies any personal history of blood clots in her past, but she says that her mother has had to be treated for pulmonary embolism in the recent past. Her birth history is significant for preeclampsia, preterm birth at 32 weeks, a NICU stay of two and a half weeks, and retinopathy of prematurity. She currently eats a diet full of green vegetables, fruits, and french fries. Her vital signs include: temperature, 36.7°C (98.0°F); blood pressure, 106/54 mm Hg; heart rate, 111/min; and respiratory, rate 23/min. On physical examination, her pulses are bounding, complexion is pale, scattered bruises throughout all extremities that are specifically scattered around the knees and elbows. After ordering a coagulation panel, which of the following would one expect to see in the lab panel of a patient with vWD?
Q57
A 27-year-old woman presented to the clinic with recurrent abdominal swelling and stunted growth relative to her siblings. She has a history of multiple blood transfusions in her childhood. She has a family history of jaundice in her father who was operated on for multiple gallbladder stones. The physical examination reveals a pale, icteric, small and short-statured young lady. On abdominal examination, the spleen was enlarged by 6 cm below the right costal margin, but the liver was not palpable. The ultrasound of the abdomen reveals multiple gallbladder stones. The laboratory test results are as follows:
Hb 9 g/dL
Hct 27%
WBC 6,200/mm3
Platelets 200,000/mm3
MCV 75 um3
MCHC 37 gm/dL
Reticulocytes 6.5%
A peripheral blood smear is presented in the image. The direct Coombs test was negative. The osmotic fragility test was increased. What is the most likely cause of her condition?
Q58
A 9-year-old boy is brought to the physician by his mother because of a 3-day history of fever and bleeding after brushing his teeth. His mother also reports that her son has asked to be picked up early from soccer practice the past few days because of fatigue. He appears pale and ill. His temperature is 38.3°C (101.1°F), pulse is 115/min, and blood pressure is 100/60 mm Hg. The lungs are clear to auscultation. Examination shows a soft, nontender abdomen with no organomegaly. There are several spots of subcutaneous bleeding on the abdomen and shins. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?
Q59
A 46-year-old woman presents to your office with oral lesions as shown in Image A. On examination, you find that her back has flaccid bullae that spread when you apply lateral pressure with your fingertips. This patient most likely has autoantibodies directed against which of the following?
Q60
A 12-year-old boy is found on a routine auditory screening to have mild high frequency hearing impairment. On exam, he has no ear pain, no focal neurological deficits, and no cardiac murmurs. He has not had any recent illness. Laboratory studies show:
Serum:
Creatinine: 0.7 mg/dl
Protein: 3.8 g/dl
Antistreptolysin O titer: 60 Todd units (12-166 normal range)
Urinalysis:
Microscopic heme
Protein: 4+
RBCs: 6/hpf
A kidney biopsy is taken. Which of the following findings is most characteristic of this patient’s disease?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 51: A 36-year-old man presents to his primary care physician with increasing fatigue. He says that the fatigue started after he returned from vacation in South America 4 weeks ago and thinks that it may be related to an infection he got while abroad. He does not know the name of the infection but says that he went to a local clinic for treatment and was given an antibiotic. Since then, he has noticed that he is no longer able to perform his job as a contractor who renovates old homes because he feels short of breath after just a few minutes of work. Furthermore, he says that he has been experiencing prolonged nosebleeds that never occurred prior to this episode. He denies any neurologic symptoms. His past medical history is significant for alcoholic hepatitis secondary to alcohol abuse 3 years prior. Physical exam reveals conjunctival pallor as well as petechiae. Which of the following findings is associated with the most likely cause of this patient's symptoms?
A. Hypersegmented neutrophils
B. Hypocellular bone marrow with fatty infiltration (Correct Answer)
C. Schistocytes on peripheral blood smear
D. Low circulating levels of erythropoietin
E. Dense lines in the metaphysis of long bones
Explanation: ***Hypocellular bone marrow with fatty infiltration***
- The patient's history of **fatigue**, **shortness of breath**, **prolonged nosebleeds**, **conjunctival pallor**, and **petechiae** suggests **pancytopenia**, a hallmark of **aplastic anemia**.
- Aplastic anemia is characterized by a **hypocellular bone marrow** with significant **fatty infiltration**, replacing hematopoietic tissue.
- The history of antibiotic treatment abroad (possibly chloramphenicol) combined with the patient's symptoms points to **drug-induced aplastic anemia**.
*Hypersegmented neutrophils*
- **Hypersegmented neutrophils** are characteristic of **megaloblastic anemias**, such as those caused by **vitamin B12 deficiency** or **folate deficiency**.
- This patient's symptoms are more indicative of bone marrow failure rather than a maturation defect in myeloid cells.
*Schistocytes on peripheral blood smear*
- **Schistocytes** are fragmented red blood cells seen in **microangiopathic hemolytic anemias** (e.g., TTP, HUS, DIC) or mechanical hemolysis.
- While hemolysis can cause anemia, it does not explain the concurrent **thrombocytopenia** (leading to nosebleeds and petechiae) seen in this patient.
*Low circulating levels of erythropoietin*
- **Low erythropoietin** levels are typically seen in **anemia of chronic kidney disease**, where the kidneys fail to produce adequate erythropoietin to stimulate red blood cell production.
- This patient's presentation with significant bleeding issues and pancytopenia points away from kidney-related anemia.
*Dense lines in the metaphysis of long bones*
- **Dense lines in the metaphysis of long bones** are characteristic of **lead poisoning**, which can cause **anemia** and **fatigue**.
- However, lead poisoning does not typically cause the prominent bleeding symptoms (nosebleeds, petechiae) or pancytopenia seen in this patient.
- While the patient's occupation renovating old homes suggests potential lead exposure, the clinical picture is more consistent with aplastic anemia.
Question 52: A 16-year-old male presents to the emergency department with a hematoma after falling during gym class. He claims that he has a history of prolonged nosebleeds and bruising/bleeding after minor injuries. Physical exam is unrevealing other than the hematoma. Labs are obtained showing an increased bleeding time and an abnormal ristocetin cofactor assay. Coagulation assays reveal an increased partial thromboplastin time (PTT) but a normal prothrombin time (PT). The patient is given desmopressin and is asked to avoid aspirin. Which of the following findings is most likely directly involved in the etiology of this patient's presentation?
A. Decreased levels or dysfunction of von Willebrand factor (Correct Answer)
B. Decreased levels of factor IX
C. Decreased platelet count
D. Decreased plasma fibrinogen
E. Decreased activity of ADAMTS13
Explanation: ***Decreased levels or dysfunction of von Willebrand factor***
- The patient's presentation with mucosal bleeding (nosebleeds), easy bruising, prolonged **bleeding time**, increased **PTT**, and abnormal **ristocetin cofactor assay** is characteristic of **von Willebrand disease (vWD)**.
- The **direct etiology** is a deficiency or dysfunction of **von Willebrand factor (vWF)**, which serves two critical functions: mediating platelet adhesion to damaged endothelium and stabilizing factor VIII in circulation.
- The abnormal **ristocetin cofactor assay** specifically tests vWF function and is diagnostic for vWD.
- Treatment with **desmopressin (DDAVP)** stimulates release of stored vWF, confirming the diagnosis.
*Decreased levels of factor VIII*
- While factor VIII levels are indeed **secondarily decreased** in vWD due to loss of vWF's stabilizing effect, this is a **consequence** rather than the direct etiologic defect.
- Factor VIII deficiency alone (hemophilia A) would cause prolonged PTT and bleeding, but would not cause prolonged bleeding time or abnormal ristocetin cofactor assay, as these specifically reflect platelet function and vWF activity.
*Decreased levels of factor IX*
- This causes **hemophilia B**, characterized by prolonged **PTT** and bleeding into joints and muscles.
- However, hemophilia B would not cause prolonged **bleeding time** or abnormal **ristocetin cofactor assay**, which indicate platelet dysfunction specific to vWD.
*Decreased platelet count*
- Thrombocytopenia causes prolonged **bleeding time** and mucocutaneous bleeding, but typically does not affect **PTT**.
- The abnormal **ristocetin cofactor assay** indicates a qualitative platelet function defect (inability to aggregate with ristocetin due to absent vWF), not simply low platelet numbers.
*Decreased activity of ADAMTS13*
- This enzyme cleaves ultra-large vWF multimers; its deficiency causes **Thrombotic Thrombocytopenic Purpura (TTP)**.
- TTP presents with thrombotic microangiopathy, hemolytic anemia, thrombocytopenia, renal failure, and neurological symptoms - not the bleeding diathesis seen here.
- This patient's presentation indicates **insufficient** vWF function, not excessive vWF activity.
Question 53: A 66-year-old man is admitted to the medical floor after being diagnosed with community-acquired pneumonia. He has been in good health except for the use of steroids for the past 6 months for ulcerative colitis. The patient is started on the empiric therapy with ceftriaxone for the management of pneumonia. After 10 days of treatment in the hospital, he becomes tachypneic with a decreased level of consciousness. He develops generalized pustular eruptions all over his trunk. The temperature is 40.8°C (105.4°F), and the white blood cell count is 19,000/mm3. The gram stain of an aspirate shows many budding yeasts and neutrophils. A culture of the skin specimen is positive for Candida albicans. The nitroblue tetrazolium test is normal. What is the most likely condition related to his signs and symptoms?
A. X-linked agammaglobulinemia
B. Leukocyte adhesion deficiency-1
C. Myeloperoxidase deficiency (Correct Answer)
D. Chronic granulomatous disease
E. Chediak-Higashi syndrome
Explanation: ***Myeloperoxidase deficiency***
- This deficiency impairs the ability of **neutrophils** to produce hypochlorous acid (via the myeloperoxidase-H₂O₂-halide system), a potent antimicrobial agent, leading to increased susceptibility to fungal infections, especially *Candida* species.
- The patient's presentation with **systemic candidiasis** (budding yeasts on gram stain, positive culture), high fever, and pustular eruptions in the setting of immunosuppression (steroid use) is consistent with this diagnosis.
- The **normal nitroblue tetrazolium (NBT) test** is the key finding that rules out chronic granulomatous disease and points toward myeloperoxidase deficiency, as MPO deficiency has normal NADPH oxidase function (which NBT tests) but impaired downstream killing via hypochlorous acid.
- While MPO deficiency is often asymptomatic, severe infections can occur, particularly in patients with additional risk factors such as prolonged steroid use.
*X-linked agammaglobulinemia*
- This condition is characterized by a defect in **B cell development** (BTK gene mutation), leading to absent or very low immunoglobulins and recurrent bacterial infections (particularly encapsulated organisms), not primarily fungal infections.
- Patients typically present with recurrent sinopulmonary infections in infancy and early childhood, which doesn't fit this clinical picture of a 66-year-old with disseminated candidiasis.
*Leukocyte adhesion deficiency-1*
- This disorder involves a defect in **integrin expression** (CD18 deficiency), impairing leukocyte adhesion, migration, and chemotaxis, causing recurrent bacterial infections, impaired wound healing, and delayed umbilical cord separation.
- Presents in early childhood, not adulthood, and is not primarily associated with systemic candidiasis.
*Chronic granulomatous disease*
- This condition results from a defect in **NADPH oxidase**, impairing the neutrophil's respiratory burst and ability to produce reactive oxygen species, leading to recurrent infections with catalase-positive organisms (e.g., *Staphylococcus aureus*, *Aspergillus*, *Serratia*, *Burkholderia*).
- The **nitroblue tetrazolium (NBT) test would be abnormal** (fails to reduce NBT dye, remains colorless) in CGD, but it was stated as **normal** in this patient, effectively ruling out this diagnosis.
*Chediak-Higashi syndrome*
- This is a rare, autosomal recessive disorder caused by **LYST gene mutation**, characterized by defective lysosomal trafficking, leading to giant cytoplasmic granules in leukocytes.
- Clinical features include **immunodeficiency**, partial oculocutaneous albinism, progressive neurological dysfunction, and bleeding tendency.
- While associated with recurrent pyogenic infections, the characteristic albinism and neurological features are absent in this case.
Question 54: A 24-year-old healthy male presents to the emergency room complaining of severe abdominal pain. He reports that he was playing rugby for his college team when he was tackled on his left side by a member of the opposing team. He is currently experiencing severe left upper abdominal pain and left shoulder pain. A review of his medical record reveals that he was seen by his primary care physician two weeks ago for mononucleosis. His temperature is 99°F (37.2°C), blood pressure is 90/50 mmHg, pulse is 130/min, and respirations are 26/min. He becomes increasingly lethargic over the course of the examination. He demonstrates exquisite tenderness to palpation over the left 8th, 9th, and 10th ribs as well as rebound tenderness in the abdomen. He is eventually stabilized and undergoes definitive operative management. After this patient recovers, which of the following is most likely to be found on a peripheral blood smear in this patient?
A. Basophilic stippling
B. Erythrocytes lacking central pallor
C. Erythrocyte fragments
D. Basophilic nuclear remnants (Correct Answer)
E. Inclusions of denatured hemoglobin
Explanation: ***Basophilic nuclear remnants***
- The patient's history of **mononucleosis**, severe left upper abdominal pain, left shoulder pain (Kehr's sign), and signs of hypovolemic shock (hypotension, tachycardia) following trauma strongly suggest a **splenic rupture**.
- After a **splenectomy** (implied by "definitive operative management" for a ruptured spleen), the spleen's function of removing abnormal red blood cells and inclusions is lost, leading to the persistence of **Howell-Jolly bodies** (basophilic nuclear remnants) on a peripheral blood smear.
*Basophilic stippling*
- This indicates the presence of **ribosomal precipitates** in red blood cells, commonly associated with conditions like **lead poisoning** or **thalassemia**.
- It is not a typical finding after splenectomy or as a direct consequence of splenic rupture.
*Erythrocytes lacking central pallor*
- This describes **spherocytes**, which are red blood cells that have lost their biconcave shape and are often seen in conditions like **hereditary spherocytosis** or **autoimmune hemolytic anemia**.
- While the spleen typically removes spherocytes, their presence without central pallor isn't the most specific finding post-splenectomy in a previously healthy individual.
*Erythrocyte fragments*
- These are also known as **schistocytes** and indicate **microangiopathic hemolytic anemia (MAHA)**, commonly seen in conditions like DIC, TTP, HUS, or mechanical heart valve hemolysis.
- While trauma can potentially lead to some fragmentation, it is not the most characteristic finding following a splenic rupture and subsequent splenectomy.
*Inclusions of denatured hemoglobin*
- This describes **Heinz bodies**, which are formed when hemoglobin is denatured and precipitates within red blood cells, typical of **G6PD deficiency** or unstable hemoglobin variants.
- Although the spleen normally removes cells containing Heinz bodies, they are not the primary or most common finding after splenectomy in a patient without a pre-existing hemoglobinopathy.
Question 55: A 25-year-old man comes to the physician for the evaluation of recurrent episodes of nosebleeds over the past 6 months. The nosebleeds occur spontaneously and stop after 10 minutes after pinching the nose at the nostrils. He has no history of serious illness except for prolonged bleeding following wisdom teeth extraction 2 years ago. He does not smoke or drink alcohol. He takes no medications. Vital signs are within normal limits. Examination of the nose shows no abnormalities. There are several bruises on the lower extremities. The remainder of the examination shows no abnormalities. Laboratory studies show:
Hemoglobin 15 g/dL
Leukocyte count 6,000/mm3
Platelet count 220,000/mm3
Bleeding time 9 minutes
Prothrombin time 13 sec
Partial thromboplastin time 55 sec
Which of the following is the most likely diagnosis?
A. Von Willebrand disease (Correct Answer)
B. Bernard-Soulier Syndrome
C. Hemophilia A
D. Factor X deficiency
E. Wiskott-Aldrich syndrome
Explanation: ***Von Willebrand disease***
- This patient presents with a history consistent with a **primary hemostasis disorder** (recurrent nosebleeds, prolonged bleeding after tooth extraction, easy bruising) and laboratory findings of a **prolonged bleeding time** and a **prolonged PTT**.
- Von Willebrand disease is the most common inherited bleeding disorder, characterized by a deficiency or dysfunction of **von Willebrand factor (vWF)**, which is crucial for platelet adhesion and also stabilizes factor VIII.
*Bernard-Soulier Syndrome*
- This syndrome is characterized by a defect in the **GP-Ib/IX/V receptor complex** on platelets, leading to impaired platelet adhesion and **thrombocytopenia**.
- While it presents with mucocutaneous bleeding and prolonged bleeding time, the platelet count in this patient is normal, making Bernard-Soulier Syndrome less likely.
*Hemophilia A*
- Hemophilia A is an **X-linked recessive disorder** caused by a deficiency of **Factor VIII**, leading to a prolonged PTT but typically a **normal bleeding time** and platelet count.
- While the PTT is prolonged in this case, the significant history of mucocutaneous bleeding and prolonged bleeding time points away from hemophilia A.
*Factor X deficiency*
- Factor X is involved in both the intrinsic and extrinsic coagulation pathways, so its deficiency would lead to **prolonged PT and PTT**.
- In this case, only the PTT is prolonged, and the PT is normal, making Factor X deficiency an unlikely diagnosis.
*Wiskott-Aldrich syndrome*
- This is an **X-linked recessive immunodeficiency disorder** characterized by **thrombocytopenia** (small platelets), eczema, and recurrent infections.
- While bleeding is a feature due to thrombocytopenia, the platelet count in this patient is normal, ruling out Wiskott-Aldrich syndrome.
Question 56: A mother brings her 6-year-old daughter in to the pediatrician’s clinic for a wellness visit. The mother has a history of von Willebrand’s disease (vWD) and is concerned that her daughter may be affected as well. The mother tells you that she has noticed that her daughter bruises very easily, and her bruises typically are visible for a longer period of time than those of her brother. She denies any personal history of blood clots in her past, but she says that her mother has had to be treated for pulmonary embolism in the recent past. Her birth history is significant for preeclampsia, preterm birth at 32 weeks, a NICU stay of two and a half weeks, and retinopathy of prematurity. She currently eats a diet full of green vegetables, fruits, and french fries. Her vital signs include: temperature, 36.7°C (98.0°F); blood pressure, 106/54 mm Hg; heart rate, 111/min; and respiratory, rate 23/min. On physical examination, her pulses are bounding, complexion is pale, scattered bruises throughout all extremities that are specifically scattered around the knees and elbows. After ordering a coagulation panel, which of the following would one expect to see in the lab panel of a patient with vWD?
A. Elevated platelet count
B. Prolonged PT
C. Normal bleeding time
D. Decreased factor IX
E. Prolonged PTT (Correct Answer)
Explanation: ***Prolonged PTT***
- **Von Willebrand factor (vWF)** stabilizes **Factor VIII**, and in vWD, reduced vWF levels lead to lower Factor VIII activity, which is reflected as a **prolonged PTT**.
- The coagulation cascade components associated with PTT (intrinsic and common pathways) are affected due to the impaired function or deficiency of vWF.
*Elevated platelet count*
- **Platelet count** is typically **normal** in vWD, as the disorder primarily affects platelet function and adhesion, not platelet production.
- Thrombocytosis is not characteristic of vWD and would suggest other primary hematologic conditions.
*Prolonged PT*
- The **prothrombin time (PT)** measures the extrinsic and common pathways of coagulation, which are typically **unaffected** in vWD.
- PT prolongation would suggest deficiencies in factors VII, X, V, or prothrombin.
*Normal bleeding time*
- **Bleeding time** is typically **prolonged** in vWD because vWF is crucial for platelet adhesion to the subendothelium and platelet plug formation.
- A normal bleeding time would argue against a platelet function disorder like vWD.
*Decreased factor IX*
- **Factor IX** deficiency is associated with **Hemophilia B**, a separate X-linked coagulopathy, and is not directly affected in vWD.
- While vWD involves coagulation factor deficiencies, the primary factor stabilized by vWF is Factor VIII, not Factor IX.
Question 57: A 27-year-old woman presented to the clinic with recurrent abdominal swelling and stunted growth relative to her siblings. She has a history of multiple blood transfusions in her childhood. She has a family history of jaundice in her father who was operated on for multiple gallbladder stones. The physical examination reveals a pale, icteric, small and short-statured young lady. On abdominal examination, the spleen was enlarged by 6 cm below the right costal margin, but the liver was not palpable. The ultrasound of the abdomen reveals multiple gallbladder stones. The laboratory test results are as follows:
Hb 9 g/dL
Hct 27%
WBC 6,200/mm3
Platelets 200,000/mm3
MCV 75 um3
MCHC 37 gm/dL
Reticulocytes 6.5%
A peripheral blood smear is presented in the image. The direct Coombs test was negative. The osmotic fragility test was increased. What is the most likely cause of her condition?
A. Anemia of chronic disease
B. Aplastic anemia
C. Blood loss
D. Vitamin B12 deficiency
E. Hereditary spherocytosis (Correct Answer)
Explanation: ***Hereditary spherocytosis***
- The patient's history of **recurrent abdominal swelling**, **stunted growth**, prior **multiple blood transfusions**, **family history of jaundice** and gallbladder stones, along with current findings of **palpable splenomegaly**, **increased osmotic fragility test**, and **elevated MCHC (37 g/dL)** with **spherocytes** on peripheral smear, all point to hereditary spherocytosis.
- **Hereditary spherocytosis** is caused by defects in red blood cell membrane proteins (spectrin, ankyrin, band 3), leading to fragile, spherical red blood cells that lose membrane surface area and are prematurely destroyed in the spleen, resulting in **hemolytic anemia**, **splenomegaly**, **jaundice**, and increased risk of **pigment gallstones** from chronic hemolysis.
- The **elevated MCHC** (concentration of hemoglobin) and **reduced MCV** (75 fL) reflect the spherical shape with decreased surface area-to-volume ratio characteristic of spherocytes.
- **Increased osmotic fragility test** is pathognomonic for hereditary spherocytosis, as spherocytes lyse more readily in hypotonic solutions.
*Anemia of chronic disease*
- This typically presents as **normocytic, normochromic anemia** or **microcytic, hypochromic anemia** with **low reticulocyte count**, elevated ferritin, and low transferrin saturation.
- The patient's **elevated reticulocyte count (6.5%)**, evidence of significant hemolysis (jaundice, splenomegaly, gallstones), **elevated MCHC**, and **increased osmotic fragility** are inconsistent with anemia of chronic disease.
*Aplastic anemia*
- Characterized by **pancytopenia** (low red blood cells, white blood cells, and platelets) due to bone marrow failure with **low reticulocyte count**.
- The patient has **normal white blood cell and platelet counts**, along with **elevated reticulocytes (6.5%)**, which is contrary to aplastic anemia where reticulocytes would be markedly decreased.
*Blood loss*
- Acute blood loss would present with **normocytic, normochromic anemia** and eventually an **elevated reticulocyte count**. Chronic blood loss leads to **iron deficiency anemia** (microcytic, hypochromic with **low MCHC**).
- The patient's presentation includes significant **signs of hemolysis** (jaundice, splenomegaly, pigment gallstones), **elevated MCHC**, and **increased osmotic fragility test**, which are not features of anemia due to blood loss.
*Vitamin B12 deficiency*
- This causes **megaloblastic anemia**, characterized by **macrocytic red blood cells (MCV >100 fL)**, hypersegmented neutrophils, and **low reticulocyte count**.
- The patient's **MCV is 75 fL (microcytic)**, she has an **elevated reticulocyte count (6.5%)**, and **elevated MCHC**, all contradicting B12 deficiency.
Question 58: A 9-year-old boy is brought to the physician by his mother because of a 3-day history of fever and bleeding after brushing his teeth. His mother also reports that her son has asked to be picked up early from soccer practice the past few days because of fatigue. He appears pale and ill. His temperature is 38.3°C (101.1°F), pulse is 115/min, and blood pressure is 100/60 mm Hg. The lungs are clear to auscultation. Examination shows a soft, nontender abdomen with no organomegaly. There are several spots of subcutaneous bleeding on the abdomen and shins. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?
A. Infiltration of the marrow with collagen and fibrous tissue
B. Normocellular bone marrow
C. Hypercellular, dysplastic bone marrow with ringed sideroblasts
D. Sheets of abnormal plasma cells
E. Hypocellular fat-filled marrow with RBCs of normal morphology (Correct Answer)
Explanation: ***Hypocellular fat-filled marrow with RBCs of normal morphology***
- The patient presents with **pancytopenia** (anemia, leukopenia, thrombocytopenia) and a very low **reticulocyte count**, indicating severe bone marrow failure.
- A **hypocellular, fat-filled marrow** with normal RBC morphology is characteristic of **aplastic anemia**, which fits the clinical picture of fatigue, bleeding, and pallor due to suppressed hematopoiesis.
*Infiltration of the marrow with collagen and fibrous tissue*
- This finding is typical of **myelofibrosis**, which usually presents with **splenomegaly** due to extramedullary hematopoiesis and often **leukoerythroblastosis** in the peripheral blood.
- The patient's abdomen is soft with **no organomegaly**, and the blood counts do not suggest myelofibrosis.
*Normocellular bone marrow*
- A **normocellular marrow** would not explain the severe pancytopenia seen in this patient; it suggests adequate cell production, which is clearly lacking here.
- While other conditions can cause pancytopenia due to peripheral destruction, the **low reticulocyte count** points to a production problem in the bone marrow.
*Hypercellular, dysplastic bone marrow with ringed sideroblasts*
- This describes features of **myelodysplastic syndrome (MDS)**, which can cause pancytopenia and often presents with **dysplastic changes** in blood cells.
- While MDS can occur in children, the sudden onset and severe pancytopenia, coupled with the absence of specific dysplastic features mentioned, make aplastic anemia more likely.
*Sheets of abnormal plasma cells*
- **Sheets of abnormal plasma cells** are seen in **multiple myeloma**, a malignancy typically affecting older adults and associated with **bone pain**, hypercalcemia, renal failure, and **monoclonal gammopathy**.
- This diagnosis is highly unlikely in a 9-year-old boy with these symptoms.
Question 59: A 46-year-old woman presents to your office with oral lesions as shown in Image A. On examination, you find that her back has flaccid bullae that spread when you apply lateral pressure with your fingertips. This patient most likely has autoantibodies directed against which of the following?
A. Type VII collagen
B. Lamina densa
C. Hemidesmosomes
D. Lamina lucida
E. Desmosomes (Correct Answer)
Explanation: ***Desmosomes***
- The presence of **flaccid bullae**, a positive **Nikolsky sign (spread with lateral pressure)**, and **oral lesions** are characteristic features of **pemphigus vulgaris**.
- **Pemphigus vulgaris** is an autoimmune disease where autoantibodies target **desmogleins 1 and 3**, which are components of desmosomes, leading to the loss of cell-to-cell adhesion within the epidermis.
*Type VII collagen*
- Autoantibodies against **type VII collagen** are associated with **epidermolysis bullosa acquisita**, which typically presents with **tense bullae** and scarring, unlike the flaccid bullae seen here.
- This condition involves the **dermal-epidermal junction**, leading to subepidermal blistering.
*Lamina densa*
- The **lamina densa** is a component of the **basement membrane zone**, and antibodies targeting it are characteristic of certain types of **bullous pemphigoid** or some forms of **epidermolysis bullosa**.
- However, typical bullous pemphigoid presents with **tense bullae** and, unlike pemphigus, usually spares the oral mucosa.
*Hemidesmosomes*
- Autoantibodies targeting **hemidesmosomes** (specifically **BP180 and BP230 antigens**) are typical of **bullous pemphigoid**, which is characterized by **tense bullae** and often pruritus.
- These antibodies lead to blistering at the **dermal-epidermal junction**, but the bullae are typically firm and do not show a positive Nikolsky sign.
*Lamina lucida*
- The **lamina lucida** is another component of the **basement membrane zone** where blistering occurs in some autoimmune bullous diseases, specifically **bullous pemphigoid**.
- However, the clinical presentation of flaccid bullae with oral involvement and a positive Nikolsky sign strongly points away from bullous pemphigoid and towards pemphigus vulgaris, which primarily involves intercellular adhesion.
Question 60: A 12-year-old boy is found on a routine auditory screening to have mild high frequency hearing impairment. On exam, he has no ear pain, no focal neurological deficits, and no cardiac murmurs. He has not had any recent illness. Laboratory studies show:
Serum:
Creatinine: 0.7 mg/dl
Protein: 3.8 g/dl
Antistreptolysin O titer: 60 Todd units (12-166 normal range)
Urinalysis:
Microscopic heme
Protein: 4+
RBCs: 6/hpf
A kidney biopsy is taken. Which of the following findings is most characteristic of this patient’s disease?
A. Thickened “tram-track” appearance of basement membrane on electron microscopy
B. “Spike and dome” appearance on electron microscopy
C. Crescent-moon shapes on light microscopy
D. Large eosinophilic nodular lesions on light microscopy
E. “Basket-weave” pattern of basement membrane on electron microscopy (Correct Answer)
Explanation: ***“Basket-weave” pattern of basement membrane on electron microscopy***
- The combination of **Sensorineural hearing loss**, **microscopic hematuria**, and **proteinuria** in a young boy is highly suggestive of **Alport syndrome**.
- **Alport syndrome** is characterized by mutations in genes encoding **Type IV collagen**, leading to characteristic ultrastructural changes in the glomerular basement membrane, including splitting and thinning, which gives it a **"basket-weave" appearance** on electron microscopy.
*Thickened “tram-track” appearance of basement membrane on electron microscopy*
- This finding is characteristic of **dense deposit disease** (also known as C3 glomerulopathy), where dense deposits within the glomerular basement membrane lead to a unique pattern.
- While dense deposit disease can cause hematuria and proteinuria, it is not typically associated with the high-frequency hearing loss seen in this patient.
*“Spike and dome” appearance on electron microscopy*
- This is a classic finding in **membranous nephropathy**, due to subepithelial immune deposits and new basement membrane material forming around them.
- Membranous nephropathy typically presents with **nephrotic syndrome** in adults and is not associated with hearing impairment.
*Crescent-moon shapes on light microscopy*
- **Crescent formation** is characteristic of rapidly progressive glomerulonephritis (RPGN), indicating severe glomerular injury and often associated with systemic vasculitis or anti-GBM disease.
- While RPGN can cause hematuria and proteinuria, the clinical presentation with hearing loss is not typical, and the underlying pathology is different.
*Large eosinophilic nodular lesions on light microscopy*
- This describes the **Kimmelstiel-Wilson lesions** seen in **diabetic nephropathy**, which are pathognomonic for this condition.
- Diabetic nephropathy is a complication of long-standing diabetes and is not consistent with the patient's age or clinical presentation.
