A 47-year-old woman presents for a routine wellness checkup. She complains of general fatigue and lethargy for the past 6 months. She does not have a significant past medical history and is currently not taking any medications. The patient reports that she drinks “socially” approx. 6 nights a week. She says she also enjoys a “nightcap,” which is 1–2 glasses of wine before bed every night. She denies any history of drug use or smoking. The patient is afebrile, and her vital signs are within normal limits. A physical examination reveals pallor of the mucous membranes. Her laboratory findings are significant for a mean corpuscular volume of 72 fL, leukocyte count of 5,300/mL, hemoglobin of 11.0 g/dL, and platelet count of 420,000/mL.
Which of the following is the most likely cause of this patient’s thrombocytosis?
Q212
A 25-year-old woman comes to the physician because of recurrent episodes of reddish discoloration of her urine. She also has a 3-month history of intermittent abdominal pain, yellowish discoloration of the skin and eyes, and fatigue. Physical examination shows pallor and scleral icterus. The spleen is not palpable. Her hemoglobin concentration is 7.8 g/dL, leukocyte count is 2,000/mm3, and platelet count is 80,000/mm3. Serum LDH and unconjugated bilirubin concentrations are elevated. Addition of a serum containing anti-human globulins to a blood sample shows no agglutination. A urine dipstick shows blood; urinalysis shows no RBCs. A CT scan of the abdomen shows a thrombus in a distal branch of the superior mesenteric vein. Which of the following is the most likely cause of this patient's condition?
Q213
A 15-year-old girl presents with menorrhagia for the last 4 months. The patient’s mother says that she just started getting her period 4 months ago, which have been heavy and prolonged. The patient does recall getting a tooth extracted 3 years ago that was complicated by persistent bleeding afterward. She has no other significant past medical history and takes no current medications. Her vital signs include: blood pressure 118/76 mm Hg, respirations 17/min, pulse 64/min, temperature 36.7°C (98.0°F). Physical examination is unremarkable. Which of the following laboratory tests is most likely to be of the greatest diagnostic value in the workup of this patient?
Q214
A 22-year-old man comes to the physician because of several episodes of painless bloody urine over the past 6 months. The episodes are not related to physical activity. He has had frequent nosebleeds since early childhood and an episode of heavy bleeding after a tooth extraction one year ago. He smokes one pack of cigarettes daily. He drinks 1 to 2 beers on social occasions. He appears pale. His vital signs are within normal limits. Physical examination shows several small hematomas in different stages of healing over his arms and legs. Examination of the extremities shows decreased passive range of motion with crepitus in both ankles. His abdomen is soft and nontender. Laboratory studies show:
Hemoglobin 9.5 mg/dL
Leukocyte count 5000/mm3
Platelet count 240,000/mm3
Bleeding time 5 minutes
Prothrombin time 14 seconds
Partial thromboplastin time 68 seconds
Urine
RBC 30–40/hpf
RBC casts negative
WBC none
Protein negative
An x-ray of the pelvis shows no abnormalities. Further evaluation of this patient is most likely to show which of the following findings?
Q215
A 17-year-old boy is brought to the physician because of swelling of his face and legs for 5 days. He immigrated to the United States from Korea with his family 10 years ago. He has been healthy except for an episode of sore throat 2 weeks ago. His younger sister has type 1 diabetes mellitus. His temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 145/87 mm Hg. Examination shows periorbital edema and 3+ pitting edema of the lower extremities. Laboratory studies show:
Hemoglobin 13.9 g/dL
Leukocyte count 8,100/mm3
Serum
Glucose 78 mg/dL
Albumin 2.4 g/dL
Hepatitis B surface antigen positive
Hepatitis B surface antibody negative
Complement C4 decreased
Urine
Blood negative
Protein 4+
Glucose negative
Protein/creatinine ratio 8.1 (N ≤ 0.2)
Further evaluation is most likely to show which of the following additional findings?
Q216
A 17-year-old boy is brought to the physician with complaints of an ataxic gait and hearing deficits for the past few days. His parents also reported a history of tonic gaze deviation on the right side and the spontaneous remission of a similar episode 6 months ago. His temperature is 37°C (98.6°F), pulse is 88/min, and respirations are 20/min. On physical examination, no abnormality is found, but evoked potential tests are abnormal. Magnetic resonance imaging of the head shows multiple lesions with high T2 signal intensity and one large white matter lesion showing contrast enhancement. His laboratory studies show:
Hemoglobin 12.9 g/dL
CSF leukocyte count 1000/μL
CSF gamma globulin 15.4% (normal 7–14%)
Erythrocyte sedimentation rate 16 mm/h
Which of the following most likely explains the mechanism of this condition?
Q217
An investigator studying immune-mediated pulmonary damage performs an autopsy on a bilateral lung transplant recipient who died of hypercapnic respiratory failure. The patient underwent lung transplantation for idiopathic pulmonary fibrosis. Microscopic examination of the lung shows diffuse eosinophilic scarring of the terminal and respiratory bronchioles and near-complete luminal obliteration by polypoidal plugs of granulation tissue. Examination of the skin shows no abnormalities. The findings in this patient are most consistent with which of the following conditions?
Q218
A 45-year-old woman with β-thalassemia major comes to the physician with a 1-week history of fatigue. She receives approximately 8 blood transfusions per year; her last transfusion was 1 month ago. Examination shows conjunctival pallor. Her hemoglobin level is 6.5 mg/dL. Microscopic evaluation of a liver biopsy specimen in this patient would most likely show which of the following?
Q219
A 29-year-old woman presents to the office with the complaint of a tingling sensation over her face and distal parts of her lower limbs. Three weeks ago, she had an episode of bloody diarrhea and was successfully treated with erythromycin. She is a full-time radiology technician. Currently, she takes oral contraceptives and zopiclone (1 mg) at bedtime. Her blood pressure is 100/80 mm Hg, her heart rate is 91/min, her respiratory rate is 15/min, and her temperature is 36.7°C (98.0°F). Neurological examination reveals loss of all sensation over the face and in the distal part of her lower limbs. Strength in calf flexor and extensor muscles is diminished bilaterally (4/5 on all of the muscle groups). Deep tendon reflexes are 1+ in the knees and 1+ in the ankles. Plantar reflexes are flexor. What is the most probable mechanism of the pathological findings in this patient?
Q220
A 22-year-old man has had dyspnea and hemoptysis for the past week. He has no known sick contacts. There is no personal or family history of serious illness. He takes no medications. His temperature is 37°C (98.6°F), pulse is 82/min, respirations are 22/min, and blood pressure is 152/90 mm Hg. Examination shows inspiratory crackles at both lung bases. The remainder of the examination shows no abnormalities. His hemoglobin is 14.2 g/dL, leukocyte count is 10,300/mm3, and platelet count is 205,000/mm3. Urinalysis shows a proteinuria of 2+, 70 RBC/hpf, and 1–2 WBC/hpf. Chest x-ray shows pulmonary infiltrates. Further evaluation is most likely to show which of the following findings?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 211: A 47-year-old woman presents for a routine wellness checkup. She complains of general fatigue and lethargy for the past 6 months. She does not have a significant past medical history and is currently not taking any medications. The patient reports that she drinks “socially” approx. 6 nights a week. She says she also enjoys a “nightcap,” which is 1–2 glasses of wine before bed every night. She denies any history of drug use or smoking. The patient is afebrile, and her vital signs are within normal limits. A physical examination reveals pallor of the mucous membranes. Her laboratory findings are significant for a mean corpuscular volume of 72 fL, leukocyte count of 5,300/mL, hemoglobin of 11.0 g/dL, and platelet count of 420,000/mL.
Which of the following is the most likely cause of this patient’s thrombocytosis?
A. Iron deficiency anemia (Correct Answer)
B. Essential thrombocytosis
C. Aplastic anemia
D. Chronic alcohol abuse
E. Chronic myelogenous leukemia (CML)
Explanation: ***Iron deficiency anemia***
- The patient presents with **microcytic anemia** (MCV 72 fL, Hb 11.0 g/dL) and **pallor**, which are classic signs of iron deficiency.
- **Iron deficiency** is a common cause of **secondary thrombocytosis**, as iron plays a role in platelet production and maturation.
*Essential thrombocytosis*
- This is a **myeloproliferative neoplasm** characterized by significantly elevated platelet counts, usually much higher than 420,000/mL (often > 600,000/mL).
- While it causes thrombocytosis, it typically doesn't present with microcytic anemia unless there's a co-existing iron deficiency, which is the primary finding here.
*Aplastic anemia*
- **Aplastic anemia** would present with **pancytopenia** (low red blood cells, white blood cells, and platelets), which is not consistent with the patient's elevated platelet count and normal leukocyte count.
- The patient's presentation of fatigue and pallor would likely be more severe due to significant anemia, and thrombocytosis would not be present.
*Chronic alcohol abuse*
- **Chronic alcohol abuse** typically causes **macrocytic anemia** (elevated MCV) due to folate deficiency or direct bone marrow toxicity, not microcytic anemia.
- While it can sometimes lead to thrombocytopenia, it is not a direct cause of robust thrombocytosis, especially in the context of microcytic anemia.
*Chronic myelogenous leukemia (CML)*
- CML is a **myeloproliferative neoplasm** characterized by the **Philadelphia chromosome (BCR-ABL1 fusion gene)**, leading to a significant increase in **granulocytes** (leukocytosis) and often thrombocytosis.
- Although thrombocytosis can occur, the primary hallmark is significant leukocytosis, which is not seen here (leukocyte count is normal), and the anemia would typically be normocytic or even macrocytic if folate deficient.
Question 212: A 25-year-old woman comes to the physician because of recurrent episodes of reddish discoloration of her urine. She also has a 3-month history of intermittent abdominal pain, yellowish discoloration of the skin and eyes, and fatigue. Physical examination shows pallor and scleral icterus. The spleen is not palpable. Her hemoglobin concentration is 7.8 g/dL, leukocyte count is 2,000/mm3, and platelet count is 80,000/mm3. Serum LDH and unconjugated bilirubin concentrations are elevated. Addition of a serum containing anti-human globulins to a blood sample shows no agglutination. A urine dipstick shows blood; urinalysis shows no RBCs. A CT scan of the abdomen shows a thrombus in a distal branch of the superior mesenteric vein. Which of the following is the most likely cause of this patient's condition?
A. Activation and consumption of platelets and coagulation factors
B. Absence of protective factors against destruction by complement (Correct Answer)
C. Replacement of a single amino acid in a β-globin chain
D. Formation of IgG antibodies against glycoprotein IIb/IIIa
E. Endothelial cell dysfunction from bacterial toxin production
Explanation: ***Absence of protective factors against destruction by complement***
- The patient's presentation is **classic for Paroxysmal Nocturnal Hemoglobinuria (PNH)**: hemoglobinuria (positive urine dipstick with no RBCs), intravascular hemolysis (elevated LDH/unconjugated bilirubin), pancytopenia, negative Coombs test, and venous thrombosis.
- PNH is caused by an acquired **PIGA gene mutation** leading to deficiency of **GPI-anchored proteins CD55 and CD59** on hematopoietic cells.
- Without these complement regulatory proteins, red blood cells undergo uncontrolled **complement-mediated hemolysis**, and platelet activation leads to thrombotic complications.
*Activation and consumption of platelets and coagulation factors*
- This describes **Disseminated Intravascular Coagulation (DIC)**, which presents with both bleeding and thrombosis, prolonged PT/aPTT, decreased fibrinogen, and elevated D-dimer.
- While PNH can cause thrombosis, the primary pathophysiology is complement dysregulation, not consumption coagulopathy. The negative Coombs test, hemoglobinuria pattern, and pancytopenia point to PNH rather than DIC.
*Replacement of a single amino acid in a β-globin chain*
- This describes **sickle cell disease** (glutamic acid → valine substitution in β-globin), causing RBC sickling under hypoxic conditions.
- Sickle cell typically presents with painful vaso-occlusive crises, acute chest syndrome, and splenic sequestration. The hemoglobinuria without RBCs, pancytopenia, and mesenteric vein thrombosis are characteristic of PNH, not sickle cell disease.
*Formation of IgG antibodies against glycoprotein IIb/IIIa*
- This describes **Immune Thrombocytopenic Purpura (ITP)**, characterized by isolated thrombocytopenia with mucocutaneous bleeding.
- ITP does not cause hemolytic anemia, leukopenia, hemoglobinuria, or thrombosis—features central to this patient's presentation.
*Endothelial cell dysfunction from bacterial toxin production*
- This describes **Hemolytic Uremic Syndrome (HUS)**, typically caused by Shiga toxin-producing E. coli, presenting with the classic triad: microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
- HUS features schistocytes on blood smear and renal failure, not pancytopenia or the typical venous thrombosis pattern seen in PNH.
Question 213: A 15-year-old girl presents with menorrhagia for the last 4 months. The patient’s mother says that she just started getting her period 4 months ago, which have been heavy and prolonged. The patient does recall getting a tooth extracted 3 years ago that was complicated by persistent bleeding afterward. She has no other significant past medical history and takes no current medications. Her vital signs include: blood pressure 118/76 mm Hg, respirations 17/min, pulse 64/min, temperature 36.7°C (98.0°F). Physical examination is unremarkable. Which of the following laboratory tests is most likely to be of the greatest diagnostic value in the workup of this patient?
A. Anti-cardiolipin antibodies
B. Prothrombin time (PT)
C. Factor IX assay
D. Ro/La autoantibodies
E. Partial thromboplastin time (PTT) (Correct Answer)
Explanation: ***Partial thromboplastin time (PTT)***
- The patient's history of **menorrhagia** and **post-extraction bleeding** suggests an underlying **bleeding disorder**, most likely **von Willebrand disease** (most common inherited bleeding disorder) or a **coagulation factor deficiency**.
- Among the available options, **PTT is the best screening test** as it assesses the **intrinsic and common coagulation pathways** (Factors XII, XI, IX, VIII, X, V, II, I).
- PTT can detect **hemophilia A and B** (Factor VIII or IX deficiency) and **severe von Willebrand disease** (Type 3 or severe Type 1, where Factor VIII is significantly reduced).
- **Important limitation:** PTT may be **normal in mild to moderate von Willebrand disease** (Type 1), which is the most common type. If PTT is normal but clinical suspicion remains high, specific **von Willebrand factor testing** (vWF antigen, vWF activity, Factor VIII) should be performed.
- PTT is preferred over more specific factor assays as an initial screening test to guide further workup.
*Anti-cardiolipin antibodies*
- These antibodies are associated with **antiphospholipid syndrome**, which causes **hypercoagulability and thrombosis**, not bleeding.
- While antiphospholipid syndrome can cause a paradoxically prolonged PTT in vitro, it does not explain the bleeding symptoms in this patient.
*Prothrombin time (PT)*
- PT measures the **extrinsic and common coagulation pathways** (Factors VII, X, V, II, I).
- **Menorrhagia with mucocutaneous bleeding** is more characteristic of **intrinsic pathway defects** (detected by PTT) or **platelet disorders**, not extrinsic pathway defects.
- Isolated extrinsic pathway deficiencies (Factor VII) are rare and typically cause post-surgical bleeding rather than menorrhagia.
*Factor IX assay*
- A Factor IX assay specifically diagnoses **hemophilia B**.
- However, hemophilia B is **X-linked recessive** and would be extremely rare in a female (requires homozygosity or X-inactivation).
- **PTT should be performed first** as a screening test; if prolonged, specific factor assays (including Factor IX) can then be ordered to identify the exact deficiency.
*Ro/La autoantibodies*
- These autoantibodies are associated with **Sjögren's syndrome** and **systemic lupus erythematosus (SLE)**.
- While SLE can cause bleeding due to **thrombocytopenia** or **acquired coagulation factor deficiencies**, Ro/La antibodies themselves are not directly linked to bleeding disorders and would not be the initial diagnostic test for this presentation.
Question 214: A 22-year-old man comes to the physician because of several episodes of painless bloody urine over the past 6 months. The episodes are not related to physical activity. He has had frequent nosebleeds since early childhood and an episode of heavy bleeding after a tooth extraction one year ago. He smokes one pack of cigarettes daily. He drinks 1 to 2 beers on social occasions. He appears pale. His vital signs are within normal limits. Physical examination shows several small hematomas in different stages of healing over his arms and legs. Examination of the extremities shows decreased passive range of motion with crepitus in both ankles. His abdomen is soft and nontender. Laboratory studies show:
Hemoglobin 9.5 mg/dL
Leukocyte count 5000/mm3
Platelet count 240,000/mm3
Bleeding time 5 minutes
Prothrombin time 14 seconds
Partial thromboplastin time 68 seconds
Urine
RBC 30–40/hpf
RBC casts negative
WBC none
Protein negative
An x-ray of the pelvis shows no abnormalities. Further evaluation of this patient is most likely to show which of the following findings?
A. Nephrolithiasis
B. Palpable spleen below the left costal margin
C. Intraarticular iron deposition (Correct Answer)
D. Hemosiderin-laden alveolar macrophages
E. Evasive behavior when asked about the hematomas
Explanation: ***Intraarticular iron deposition***
- The patient's history of **painless hematuria**, **recurrent epistaxis**, prolonged bleeding after tooth extraction, and multiple hematomas, combined with **prolonged PTT** and normal platelet count/bleeding time, strongly suggests **Hemophilia A or B**.
- In such clotting disorders, **recurrent hemarthroses (joint bleeding)** lead to **hemosiderin deposition** and subsequent joint damage, explaining the decreased range of motion and crepitus in the ankles.
*Nephrolithiasis*
- While nephrolithiasis can cause **hematuria**, it typically presents with **flank pain** radiating to the groin, which is not mentioned here.
- It does not explain the widespread bleeding tendencies (nosebleeds, post-extraction bleeding, hematomas) or the prolonged PTT.
*Palpable spleen below the left costal margin*
- **Splenomegaly** can be seen in various hematological disorders, but it is not a direct or common complication of hemophilia itself.
- The patient's symptoms primarily point to a coagulation defect, not a condition directly causing splenomegaly.
*Hemosiderin-laden alveolar macrophages*
- These "heart failure cells" are typically seen in conditions like **pulmonary hypertension** or **congestive heart failure** leading to extravasation of red blood cells into the alveoli.
- There is no clinical evidence (e.g., respiratory symptoms, cardiac findings) in the patient's presentation to suggest such pulmonary pathology.
*Evasive behavior when asked about the hematomas*
- This option refers to a psychological or social finding which is not directly related to the underlying medical pathology suggested by the constellation of severe bleeding symptoms and lab findings.
- While possible in cases of abuse, it would not explain the other specific bleeding manifestations (epistaxis, post-extraction bleeding, hematuria) and the abnormal PTT.
Question 215: A 17-year-old boy is brought to the physician because of swelling of his face and legs for 5 days. He immigrated to the United States from Korea with his family 10 years ago. He has been healthy except for an episode of sore throat 2 weeks ago. His younger sister has type 1 diabetes mellitus. His temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 145/87 mm Hg. Examination shows periorbital edema and 3+ pitting edema of the lower extremities. Laboratory studies show:
Hemoglobin 13.9 g/dL
Leukocyte count 8,100/mm3
Serum
Glucose 78 mg/dL
Albumin 2.4 g/dL
Hepatitis B surface antigen positive
Hepatitis B surface antibody negative
Complement C4 decreased
Urine
Blood negative
Protein 4+
Glucose negative
Protein/creatinine ratio 8.1 (N ≤ 0.2)
Further evaluation is most likely to show which of the following additional findings?
A. Increased IgA levels in serum
B. Normal-appearing glomeruli on renal biopsy
C. Subepithelial deposits on renal biopsy (Correct Answer)
D. Antineutrophil cytoplasmic antibody level in serum
E. Eosinophilic nodules on renal biopsy
Explanation: ***Subepithelial deposits on renal biopsy***
- The patient presents with **nephrotic syndrome** (edema, proteinuria, hypoalbuminemia), a history of **hepatitis B infection** (HBsAg positive), and decreased **complement C4** levels. These findings are highly suggestive of **membranous nephropathy**, which is characterized by **subepithelial immune complex deposits**.
- **Membranous nephropathy** is a common cause of nephrotic syndrome in adults and can be secondary to infections like **hepatitis B**, systemic lupus erythematosus, or certain medications.
*Increased IgA levels in serum*
- **Increased IgA levels** are characteristic of **IgA nephropathy**, which typically presents with recurrent episodes of **hematuria**, often following an upper respiratory infection.
- While there was a sore throat, the dominant presentation here is **nephrotic syndrome** with significant proteinuria and **hypocomplementemia**, which is not typical for IgA nephropathy.
*Normal-appearing glomeruli on renal biopsy*
- In cases of significant proteinuria and nephrotic syndrome, it is highly unlikely for the glomeruli to appear **normal** on biopsy.
- Conditions causing nephrotic syndrome, such as **minimal change disease**, do show normal glomeruli on light microscopy, but this patient's presentation with **Hepatitis B** and **hypocomplementemia** points away from minimal change disease.
*Antineutrophil cytoplasmic antibody level in serum*
- **Antineutrophil cytoplasmic antibodies (ANCAs)** are associated with **vasculitic diseases** such as granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss).
- These conditions typically present with **rapidly progressive glomerulonephritis** and systemic vasculitis, which is different from the predominant nephrotic syndrome seen in this patient.
*Eosinophilic nodules on renal biopsy*
- **Eosinophilic nodules**, also known as **Kimmelstiel-Wilson lesions**, are characteristic findings in **diabetic nephropathy**.
- Although the patient's sister has type 1 diabetes, there is no indication that the patient himself has diabetes (normal serum glucose), making this finding unlikely.
Question 216: A 17-year-old boy is brought to the physician with complaints of an ataxic gait and hearing deficits for the past few days. His parents also reported a history of tonic gaze deviation on the right side and the spontaneous remission of a similar episode 6 months ago. His temperature is 37°C (98.6°F), pulse is 88/min, and respirations are 20/min. On physical examination, no abnormality is found, but evoked potential tests are abnormal. Magnetic resonance imaging of the head shows multiple lesions with high T2 signal intensity and one large white matter lesion showing contrast enhancement. His laboratory studies show:
Hemoglobin 12.9 g/dL
CSF leukocyte count 1000/μL
CSF gamma globulin 15.4% (normal 7–14%)
Erythrocyte sedimentation rate 16 mm/h
Which of the following most likely explains the mechanism of this condition?
A. Type IV hypersensitivity (Correct Answer)
B. Type II hypersensitivity
C. Type V hypersensitivity
D. Type I hypersensitivity
E. Type III hypersensitivity
Explanation: ***Type IV hypersensitivity***
- The constellation of **ataxic gait**, **hearing deficits**, **tonic gaze deviation**, **remitting-relapsing episodes**, **abnormal evoked potentials**, and **MRI findings** (multiple lesions, contrast enhancement) is highly suggestive of **multiple sclerosis (MS)**.
- MS is primarily mediated by **T-cells** reacting against **myelin antigens** in the central nervous system, classifying it as a **Type IV (delayed-type) hypersensitivity reaction**.
*Type II hypersensitivity*
- This type involves **antibodies binding to antigens on cell surfaces** or in the extracellular matrix, leading to cell destruction, functional changes, or inflammation.
- Conditions like **Goodpasture syndrome** or **autoimmune hemolytic anemia** are examples, which do not fit the neurological presentation and demyelinating pathology described.
*Type V hypersensitivity*
- This is a variant of **Type II hypersensitivity** where antibodies bind to and **stimulate cell surface receptors**, rather than destroying them.
- **Graves' disease**, where antibodies activate TSH receptors, is a classic example; it does not involve T-cell mediated demyelination.
*Type I hypersensitivity*
- This is an **immediate hypersensitivity reaction** mediated by **IgE antibodies** binding to mast cells and basophils, leading to mediator release upon allergen exposure.
- It's associated with allergic reactions like **anaphylaxis** or **asthma** and doesn't explain the chronic demyelinating process seen in the patient.
*Type III hypersensitivity*
- This type involves the formation of **immune complexes** (antigen-antibody complexes) that deposit in tissues, leading to inflammation and tissue damage.
- Diseases like **systemic lupus erythematosus** or **serum sickness** are examples, which typically present with systemic inflammation and vasculitis, not primary demyelination.
Question 217: An investigator studying immune-mediated pulmonary damage performs an autopsy on a bilateral lung transplant recipient who died of hypercapnic respiratory failure. The patient underwent lung transplantation for idiopathic pulmonary fibrosis. Microscopic examination of the lung shows diffuse eosinophilic scarring of the terminal and respiratory bronchioles and near-complete luminal obliteration by polypoidal plugs of granulation tissue. Examination of the skin shows no abnormalities. The findings in this patient are most consistent with which of the following conditions?
A. Acute graft rejection
B. Recurrence of primary disease
C. Transfusion-related acute lung injury
D. Chronic graft rejection (Correct Answer)
E. Acute graft-versus-host disease
Explanation: ***Chronic graft rejection***
- Chronic rejection in lung transplant recipients classically manifests as **bronchiolitis obliterans**, characterized by diffuse **eosinophilic scarring** and **luminal obliteration** of small airways by polypoidal granulation tissue.
- This process leads to irreversible airflow obstruction and progressive respiratory failure, which aligns with the patient's death from **hypercapnic respiratory failure**.
*Acute graft rejection*
- Acute graft rejection typically presents with perivascular and interstitial mononuclear infiltrates, not necessarily diffuse eosinophilic scarring or luminal obliteration of bronchioles.
- While it can cause respiratory decline, the described microscopic features are more characteristic of a chronic process.
*Recurrence of primary disease*
- **Idiopathic pulmonary fibrosis** is characterized by usual interstitial pneumonia (UIP) pattern with patchy interstitial fibrosis, honeycombing, and fibroblast foci, which is distinct from the described bronchiolar scarring and obliteration.
- While IPF can recur, the histological findings described are not typical for recurrent IPF but rather for chronic rejection.
*Transfusion-related acute lung injury*
- **TRALI** is an acute lung injury reaction to blood products, usually occurring within 6 hours of transfusion, and is characterized by non-cardiogenic pulmonary edema.
- The described pathology of chronic scarring and obliteration is not consistent with the acute inflammatory and edematous changes seen in TRALI.
*Acute graft-versus-host disease*
- **Acute GVHD** primarily affects the skin, liver, and gastrointestinal tract; lung involvement is rare and typically presents as a diffuse interstitial pneumonitis.
- The absence of skin abnormalities and the specific bronchiolar pathology described do not fit the typical presentation of acute GVHD.
Question 218: A 45-year-old woman with β-thalassemia major comes to the physician with a 1-week history of fatigue. She receives approximately 8 blood transfusions per year; her last transfusion was 1 month ago. Examination shows conjunctival pallor. Her hemoglobin level is 6.5 mg/dL. Microscopic evaluation of a liver biopsy specimen in this patient would most likely show which of the following?
A. Cytoplasmic pink-staining granules that stain positive with PAS
B. Macrophages with yellow-brown, lipid-containing granules
C. Extracellular deposition of pink-staining proteins
D. Cytoplasmic brown-pigmented granules that stain positive for S-100
E. Macrophages with cytoplasmic golden-brown granules that stain positive with Prussian blue (Correct Answer)
Explanation: ***Macrophages with cytoplasmic golden-brown granules that stain positive with Prussian blue***
- The patient's history of **β-thalassemia major** and frequent **blood transfusions** (8 per year) strongly suggests **secondary hemochromatosis** (transfusional hemosiderosis). Iron overload results from the chronic transfusion of red blood cells, as the body has no physiological mechanism for actively excreting excess iron.
- **Hemosiderin** is an iron-storage complex formed in macrophages (Kupffer cells in the liver) and hepatocytes. On histological examination, hemosiderin appears as **golden-brown cytoplasmic granules** on routine H&E staining and stains **blue with Prussian blue stain** (Perls' stain), which is the definitive test for iron.
- Chronic iron overload can lead to liver fibrosis, cirrhosis, and hepatic dysfunction if untreated.
*Cytoplasmic pink-staining granules that stain positive with PAS*
- This description is characteristic of **glycogen storage diseases** or some lysosomal storage disorders, such as **Pompe disease** (lysosomal glycogen accumulation).
- These conditions involve **carbohydrate accumulation**, not iron overload, and are not directly related to chronic blood transfusions.
*Macrophages with yellow-brown, lipid-containing granules*
- This description is indicative of **lipofuscin**, a "wear-and-tear" pigment that accumulates in aging or atrophying cells, particularly in the heart, liver, and brain.
- While lipofuscin is a yellow-brown pigment, it is **lipid-derived** and does not stain for iron (Prussian blue negative), thus differing from hemosiderin associated with iron overload.
*Extracellular deposition of pink-staining proteins*
- This suggests **amyloidosis**, a condition characterized by the deposition of **abnormal protein fibrils** in extracellular spaces. Amyloid typically stains pink with **hematoxylin and eosin (H&E)** and shows apple-green birefringence under polarized light with **Congo red stain**.
- Amyloidosis is not the primary consequence of iron overload from chronic transfusions.
*Cytoplasmic brown-pigmented granules that stain positive for S-100*
- **S-100 protein** is a marker for cells of neural crest origin, such as Schwann cells, melanocytes, and some dendritic cells (e.g., Langerhans cells). The presence of **brown-pigmented granules** could suggest conditions like **melanin accumulation** or certain **tumors involving melanocytes** (e.g., melanoma).
- This finding is unrelated to the iron overload pathology seen in β-thalassemia patients receiving multiple transfusions.
Question 219: A 29-year-old woman presents to the office with the complaint of a tingling sensation over her face and distal parts of her lower limbs. Three weeks ago, she had an episode of bloody diarrhea and was successfully treated with erythromycin. She is a full-time radiology technician. Currently, she takes oral contraceptives and zopiclone (1 mg) at bedtime. Her blood pressure is 100/80 mm Hg, her heart rate is 91/min, her respiratory rate is 15/min, and her temperature is 36.7°C (98.0°F). Neurological examination reveals loss of all sensation over the face and in the distal part of her lower limbs. Strength in calf flexor and extensor muscles is diminished bilaterally (4/5 on all of the muscle groups). Deep tendon reflexes are 1+ in the knees and 1+ in the ankles. Plantar reflexes are flexor. What is the most probable mechanism of the pathological findings in this patient?
A. Failure of Schwann cells to produce myelin
B. Direct damage to myelin caused by diarrhea causing organism
C. Granulomatous alteration of the vessels supplying peripheral nerves
D. Antibody-mediated destruction of peripheral myelin by cytotoxic cells (Correct Answer)
E. Radiation-induced oxidative stress in the neurons of dorsal ganglia
Explanation: ***Antibody-mediated destruction of peripheral myelin by cytotoxic cells***
- The patient's symptoms (tingling, facial numbness, distal limb weakness, and reduced reflexes) after a **bloody diarrhea** episode strongly suggest **Guillain-Barré Syndrome (GBS)**, which is an **autoimmune demyelinating polyneuropathy**.
- GBS often follows infections (like *Campylobacter jejuni*, which causes bloody diarrhea) where the immune system produces **antibodies** that cross-react with **peripheral myelin components** (molecular mimicry), leading to its destruction by cytotoxic cells.
*Failure of Schwann cells to produce myelin*
- This mechanism is characteristic of certain **hereditary demyelinating neuropathies** or conditions affecting Schwann cell function developmentally.
- It does not explain the acute onset following an infection, which is typical for post-infectious autoimmune neuropathies like GBS.
*Direct damage to myelin caused by diarrhea causing organism*
- While infections can trigger neuropathies, **direct damage** to myelin by the pathogen itself is rare in GBS.
- The primary mechanism in GBS is an **immune-mediated attack**, not direct microbial destruction of neural tissue.
*Granulomatous alteration of the vessels supplying peripheral nerves*
- **Granulomatous vasculitis** affecting peripheral nerve vessels is characteristic of conditions like **vasculitic neuropathy**.
- This mechanism typically involves inflammation and damage to the blood vessels, leading to nerve ischemia, which differs from the immune-mediated demyelination seen in GBS.
*Radiation-induced oxidative stress in the neurons of dorsal ganglia*
- Radiation-induced nerve damage would be related to her occupation but typically manifests in areas exposed to **high-dose radiation** and is usually chronic.
- It would not explain the acute, ascending pattern of sensory and motor deficits following a gastrointestinal infection.
Question 220: A 22-year-old man has had dyspnea and hemoptysis for the past week. He has no known sick contacts. There is no personal or family history of serious illness. He takes no medications. His temperature is 37°C (98.6°F), pulse is 82/min, respirations are 22/min, and blood pressure is 152/90 mm Hg. Examination shows inspiratory crackles at both lung bases. The remainder of the examination shows no abnormalities. His hemoglobin is 14.2 g/dL, leukocyte count is 10,300/mm3, and platelet count is 205,000/mm3. Urinalysis shows a proteinuria of 2+, 70 RBC/hpf, and 1–2 WBC/hpf. Chest x-ray shows pulmonary infiltrates. Further evaluation is most likely to show which of the following findings?
A. Increased serum IgA titers
B. Increased anti-GBM antibody titers (Correct Answer)
C. Increased c-ANCA titers
D. Increased anti-dsDNA antibody titers
E. Increased p-ANCA titers
Explanation: ***Increased anti-GBM antibody titers***
- The patient's presentation with **hemoptysis** (pulmonary involvement) and **renal symptoms** (proteinuria, hematuria) suggests a **pulmonary-renal syndrome**.
- **Increased anti-GBM antibody titers** are characteristic of **Goodpasture syndrome**, which classically presents with rapidly progressive glomerulonephritis and pulmonary hemorrhage due to antibodies targeting the alpha-3 chain of type IV collagen in the glomerular and alveolar basement membranes.
*Increased serum IgA titers*
- While seen in **IgA nephropathy** (Berger's disease), this condition primarily causes **renal disease** and typically does not present with significant **pulmonary hemorrhage**.
- IgA nephropathy is also more commonly associated with gross hematuria following an upper respiratory infection, which is not the primary feature here.
*Increased c-ANCA titers*
- Increased **c-ANCA (PR3-ANCA)** titers are associated with **Granulomatosis with Polyangiitis (GPA)**, which can also cause pulmonary-renal syndrome.
- However, GPA more often involves **upper and lower airway inflammation** (e.g., sinusitis, otitis) and can present with **granulomatous inflammation**, which are not specified in this case.
*Increased anti-dsDNA antibody titers*
- **Anti-dsDNA antibodies** are a hallmark of **Systemic Lupus Erythematosus (SLE)**, which can cause glomerulonephritis (lupus nephritis) and pulmonary manifestations (e.g., pleurisy, pneumonitis).
- However, SLE typically presents with a broader range of systemic symptoms like **arthralgias, skin rashes (malar rash)**, and serositis, which are absent in this acute presentation.
*Increased p-ANCA titers*
- **Increased p-ANCA (MPO-ANCA)** titers are associated with **Microscopic Polyangiitis (MPA)** and **Eosinophilic Granulomatosis with Polyangiitis (EGPA)**, both of which can cause pulmonary-renal syndrome.
- While MPA is a possibility, Goodpasture syndrome is a more direct fit for the sudden onset of **hemoptysis** and **glomerulonephritis** specifically targeting basement membranes.
