A 19-year-old male from rural West Virginia presents to his family medicine doctor to discuss why he is having trouble getting his wife pregnant. On exam, he is 6 feet 2 inches with a frail frame and broad hips for a male his size. He is noted to have mild gynecomastia, no facial hair, and small, underdeveloped testes. He claims that although he has a lower libido than most of his friends, he does have unprotected sex with his wife. His past medical history is notable for developmental delay and difficulties in school. What is the most likely chromosomal abnormality in this patient?
Q92
A 42-year-old woman comes to the physician because of a 2-month history of progressive muscular weakness. She has had difficulty climbing stairs, getting up from chairs, and brushing her hair. Her vital signs are within normal limits. Muscle strength is 2/5 with flexion of the hips and 3/5 with abduction of the shoulders. She is unable to stand up from her chair without the use of her arms for support. Laboratory studies show elevations in leukocyte count, erythrocyte sedimentation rate, and creatine kinase concentration. Histological evaluation of a biopsy specimen of the deltoid muscle is most likely to show which of the following?
Q93
A 20-year-old man presents with a painless neck mass that has gradually increased in size. The mass is anteromedial to the right sternocleidomastoid muscle and has been present for 3 years. The mass increased in size and became more tender following an upper respiratory infection. An ultrasound of the neck identifies a single, round cystic mass with uniform, low echogenicity, and no internal septations. A contrast-enhanced CT scan of the neck shows a homogeneous mass with low attenuation centrally and with smooth rim enhancement. Which of the following is the most likely diagnosis?
Q94
A 55-year-old male presents with left hip pain and stiffness. Radiographs are shown in Figures A and B. Serum alkaline phosphatase levels are elevated. A biopsy of the left femur is performed and shown in Figure C. Which of the following cells are initially responsible for this condition?
Q95
Following a recent myocardial infarction, a 60-year-old woman has been started on multiple medications at the time of discharge from the hospital. After 10 days of discharge, she presents to the emergency department with a history of fever, headache, and dark colored urine for 2 days. Her husband mentions that she has not passed urine for the last 24 hours. Her physical examination shows significant pallor, and multiple petechiae are present all over her limbs. Her vital signs include: temperature 38.9°C (102.0°F), pulse rate 94/min, blood pressure 124/82 mm Hg, and respiratory rate 16/min. Her sensorium is altered with the absence of spontaneous speech and spontaneous movements. She responds inappropriately to verbal stimuli. Her laboratory results show the presence of anemia and thrombocytopenia. Examination of peripheral blood smear shows the presence of schistocytes. Serum creatinine is 2 mg/dL. Serum levels of fibrinogen, fibrin monomers, fibrin degradation products and D-dimers are normal. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are normal. Which is the most likely treatment for this patient’s condition?
Q96
A 39-year-old man presents to the emergency department with the complaint of ‘cola-colored’ urine that he noticed this morning. Additionally, he complains of malaise and reports that he has not been able to be productive at work since last week. Lab results revealed a hemoglobin of 6.7 g/dL, leukocyte total count of 1,000 cells/mm3, and a reticulocyte count of 6%. Coomb test is negative and flow cytometry shows CD55/CD59-negative red blood cells. Concerned about the results of his complete blood count, his physician explains the diagnosis to the patient. Which of the following sets of events best describes the mechanism underlying the development of neutropenia?
Q97
A 35-year-old man presents with large tense blisters on the flexor surfaces of the upper extremities and trunk. The histologic findings show subepidermal blisters with an eosinophil-rich infiltrate. What is the most likely underlying pathology?
Q98
A 29-year-old woman comes to the office with the complaints of severe bleeding after a dental extraction which required local hemostatic therapy. She has a long-term excessive menstrual bleeding and iron-deficiency anemia that required treatment with iron supplement since the age of 17. In addition, she states that her mother also has a history of frequent nosebleeds. The vital signs include: pulse rate 107/min, respiratory rate 17/min, temperature 37.2°C (99.0°F), and blood pressure 90/60 mm Hg. Her physical exam shows generalized pallor.
The complete blood count results are as follows:
Hemoglobin 10.7 g/dL
Hematocrit 41%
Leukocyte count 8,000/mm3
Neutrophils 54%
Bands 3%
Eosinophils 1%
Basophils 0%
Lymphocytes 32%
Monocytes 2%
Mean corpuscular hemoglobin 25.4 pg/cell
Mean corpuscular hemoglobin concentration 31% Hb/cell
Mean corpuscular volume 76 μm3
Platelet count 380,000/mm³
The coagulation test results are as follows:
Partial thromboplastin time (activated) 48.0 s
Prothrombin time 14.0 s
International normalized ratio 0.9
What is the most likely diagnosis?
Q99
A 24-year-old woman presents with blisters and erosions on her upper face, chest, and back. The blisters have erythema, scales, and crust formation. Examination shows oromucosal involvement. Histopathologic evaluation reveals a tombstone arrangement at the base of the blister. What is the most likely cause for the patient's condition?
Q100
A 32-year-old man comes to the physician because of a 3-week history of cough, weight loss, and night sweats. He migrated from Sri Lanka 6 months ago. He appears emaciated. His temperature is 38.1°C (100.5°F). Physical examination shows enlargement of the right supraclavicular lymph node. Chest and abdominal examination show no abnormalities. An interferon-gamma assay is positive. A biopsy specimen of the cervical lymph node is most likely to show the causal organism in which of the following locations?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 91: A 19-year-old male from rural West Virginia presents to his family medicine doctor to discuss why he is having trouble getting his wife pregnant. On exam, he is 6 feet 2 inches with a frail frame and broad hips for a male his size. He is noted to have mild gynecomastia, no facial hair, and small, underdeveloped testes. He claims that although he has a lower libido than most of his friends, he does have unprotected sex with his wife. His past medical history is notable for developmental delay and difficulties in school. What is the most likely chromosomal abnormality in this patient?
A. Trisomy 13
B. 45: XO
C. Trisomy 21
D. 47: XYY
E. 47: XXY (Correct Answer)
Explanation: ***47: XXY***
- The patient's presentation with **infertility**, small testes, **gynecomastia**, eunuchoid body habitus (tall, frail frame, broad hips), lack of facial hair, and **developmental delay** are classic features of **Klinefelter syndrome (47, XXY)**.
- This chromosomal abnormality leads to primary **hypogonadism** due to the presence of an extra X chromosome in males.
*Trisomy 13*
- Trisomy 13, or **Patau syndrome**, is characterized by severe developmental anomalies, including **cleft lip and palate**, polydactyly, and severe neurological defects.
- Infants with Trisomy 13 rarely survive beyond the first year and do not present with the described signs of hypogonadism or gynecomastia in adolescence.
*45: XO*
- **45, XO** or **Turner syndrome** affects females and is characterized by **short stature**, primary amenorrhea, webbed neck, and **gonadal dysgenesis (streak gonads)**.
- This karyotype is incompatible with a male phenotype and the symptoms described.
*Trisomy 21*
- Trisomy 21, or **Down syndrome**, is associated with distinct facial features, intellectual disability, and congenital heart defects.
- While individuals with Down syndrome may have fertility issues, they do not typically present with the specific combination of **gynecomastia**, eunuchoid habitus, and **small testes** seen in this patient.
*47: XYY*
- **47, XYY syndrome** is associated with increased height and potentially some learning difficulties, but typically does not cause the significant **hypogonadism**, **gynecomastia**, or **small testes** seen in this patient.
- Men with 47, XYY usually have normal sexual development and fertility, though some may experience learning disabilities or behavioral problems.
Question 92: A 42-year-old woman comes to the physician because of a 2-month history of progressive muscular weakness. She has had difficulty climbing stairs, getting up from chairs, and brushing her hair. Her vital signs are within normal limits. Muscle strength is 2/5 with flexion of the hips and 3/5 with abduction of the shoulders. She is unable to stand up from her chair without the use of her arms for support. Laboratory studies show elevations in leukocyte count, erythrocyte sedimentation rate, and creatine kinase concentration. Histological evaluation of a biopsy specimen of the deltoid muscle is most likely to show which of the following?
A. Muscle fiber necrosis with rare inflammatory cells
B. Perimysial inflammation with perivascular CD4+ T lymphocytic infiltration
C. Sarcoplasmic rimmed vacuoles with CD8+ lymphocytic infiltration
D. Sarcolemmal MHC-I overexpression with CD8+ lymphocytic infiltration (Correct Answer)
E. Relative atrophy of type II muscle fibers with hypertrophy of type I muscle fibers
Explanation: ***Sarcolemmal MHC-I overexpression with CD8+ lymphocytic infiltration***
- This finding is characteristic of **polymyositis**, an inflammatory myopathy presenting with **progressive, proximal muscle weakness**, elevated **creatine kinase**, and inflammation.
- The **MHC-I overexpression** on the sarcolemma makes muscle fibers susceptible to destruction by activated cytotoxic **CD8+ T cells**, leading to necrosis and weakness.
*Muscle fiber necrosis with rare inflammatory cells*
- While muscle fiber necrosis is present in inflammatory myopathies, the description of **rare inflammatory cells** is inconsistent with the significant inflammation seen in polymyositis.
- This pattern might suggest other myopathies, such as toxic myopathies or muscular dystrophies, rather than a primary inflammatory process.
*Perimysial inflammation with perivascular CD4+ T lymphocytic infiltration*
- This histological pattern is highly suggestive of **dermatomyositis**, not polymyositis.
- In dermatomyositis, inflammation primarily involves the **perivascular spaces** and **perimysium**, and **CD4+ T cells** are the predominant infiltrating lymphocytes.
*Sarcoplasmic rimmed vacuoles with CD8+ lymphocytic infiltration*
- This finding is characteristic of **inclusion body myositis (IBM)**, which typically presents in older individuals (>50 years) with **asymmetric distal and proximal weakness**.
- The presence of **rimmed vacuoles** containing protein aggregates is a hallmark of IBM, differentiating it from polymyositis.
*Relative atrophy of type II muscle fibers with hypertrophy of type I muscle fibers*
- This pattern of muscle fiber atrophy and hypertrophy is more characteristic of **disuse atrophy**, **steroid-induced myopathy**, or other **neurogenic conditions**, not inflammatory myopathies like polymyositis.
- Polymyositis involves inflammatory cell infiltration and necrosis, affecting various fiber types.
Question 93: A 20-year-old man presents with a painless neck mass that has gradually increased in size. The mass is anteromedial to the right sternocleidomastoid muscle and has been present for 3 years. The mass increased in size and became more tender following an upper respiratory infection. An ultrasound of the neck identifies a single, round cystic mass with uniform, low echogenicity, and no internal septations. A contrast-enhanced CT scan of the neck shows a homogeneous mass with low attenuation centrally and with smooth rim enhancement. Which of the following is the most likely diagnosis?
A. First branchial cleft cyst
B. Sternomastoid tumor
C. Second branchial cleft cyst (Correct Answer)
D. Ectopic thyroid tissue
E. Cervical lymphadenopathy
Explanation: **Second branchial cleft cyst**
- The **location** (anteromedial to the sternocleidomastoid muscle), **painless** nature, and history of **gradual enlargement** becoming tender after an URI are classic presentations.
- **Imaging findings** (single, round cystic mass with uniform low echogenicity on ultrasound; homogeneous mass with low attenuation centrally and smooth rim enhancement on CT) are highly characteristic of an infected branchial cleft cyst.
*First branchial cleft cyst*
- Typically presents with a mass located near the **external auditory canal** or **angle of the mandible**, often causing otorrhea or recurrent infections.
- The presented mass is in a different anatomical location, **anteromedial** to the sternocleidomastoid.
*Sternomastoid tumor*
- This condition usually presents as a **fibrotic mass** within the sternocleidomastoid muscle in **neonates or infants**, associated with **congenital muscular torticollis**.
- The patient's age (20 years old) and the **cystic nature** of the mass make this diagnosis unlikely.
*Ectopic thyroid tissue*
- While possible in the neck, ectopic thyroid tissue would typically present as a **solid mass** and would show **iodine uptake** on nuclear imaging, not a cystic appearance on ultrasound and CT.
- It is more commonly located in the **midline** of the neck (e.g., lingual thyroid) rather than anteromedial to the sternocleidomastoid.
*Cervical lymphadenopathy*
- Enlarged lymph nodes typically present with **multiple, often tender, solid masses** or a single mass with typical lymph node morphology (e.g., hilar fat, oval shape), especially after an infection.
- The **cystic nature** described by imaging, with uniform low echogenicity and rim enhancement, is not typical for uncomplicated lymphadenopathy.
Question 94: A 55-year-old male presents with left hip pain and stiffness. Radiographs are shown in Figures A and B. Serum alkaline phosphatase levels are elevated. A biopsy of the left femur is performed and shown in Figure C. Which of the following cells are initially responsible for this condition?
A. T-Cells
B. Fibroblasts
C. Osteoblasts
D. Osteoclasts (Correct Answer)
E. Neutrophils
Explanation: ***Osteoclasts***
- The presented images and elevated **alkaline phosphatase** strongly suggest **Paget's disease of bone**, which is characterized by abnormal bone remodeling initially driven by excessive osteoclastic activity.
- In Paget's disease, the initial phase involves a chaotic increase in **osteoclast** number and activity, leading to focal areas of excessive bone resorption.
*T-Cells*
- **T-cells** are primarily involved in immune responses and cell-mediated immunity rather than direct bone remodeling in Paget's disease.
- While immune factors may play a role in the pathogenesis of Paget's disease, **T-cells** are not the primary cells responsible for the initial destructive phase.
*Fibroblasts*
- **Fibroblasts** are connective tissue cells involved in producing collagen and extracellular matrix, important for tissue repair and scarring.
- They are not the main cells responsible for the initial abnormal bone resorption observed in Paget's disease.
*Osteoblasts*
- **Osteoblasts** are bone-forming cells responsible for synthesizing and depositing new bone matrix.
- In Paget's disease, osteoblastic activity is increased in a compensatory and disorganized manner following the initial osteoclastic hyperactivity, but they are not the cells _initially_ responsible for the condition.
*Neutrophils*
- **Neutrophils** are a type of white blood cell primarily involved in acute inflammatory responses to infections.
- They have no direct role in the primary pathogenesis of Paget's disease of bone.
Question 95: Following a recent myocardial infarction, a 60-year-old woman has been started on multiple medications at the time of discharge from the hospital. After 10 days of discharge, she presents to the emergency department with a history of fever, headache, and dark colored urine for 2 days. Her husband mentions that she has not passed urine for the last 24 hours. Her physical examination shows significant pallor, and multiple petechiae are present all over her limbs. Her vital signs include: temperature 38.9°C (102.0°F), pulse rate 94/min, blood pressure 124/82 mm Hg, and respiratory rate 16/min. Her sensorium is altered with the absence of spontaneous speech and spontaneous movements. She responds inappropriately to verbal stimuli. Her laboratory results show the presence of anemia and thrombocytopenia. Examination of peripheral blood smear shows the presence of schistocytes. Serum creatinine is 2 mg/dL. Serum levels of fibrinogen, fibrin monomers, fibrin degradation products and D-dimers are normal. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are normal. Which is the most likely treatment for this patient’s condition?
A. Renal dialysis
B. Platelet transfusion
C. Rehydration
D. Plasma exchange (Correct Answer)
E. Intravenous immunoglobulin
Explanation: ***Plasma exchange***
- The patient's presentation with **fever, altered mental status, renal failure, microangiopathic hemolytic anemia (schistocytes, anemia), and thrombocytopenia** is characteristic of **Thrombotic Thrombocytopenic Purpura (TTP)**.
- **Plasma exchange (plasmapheresis)** is the mainstay of TTP treatment, as it removes inhibiting antibodies against **ADAMTS13** and replaces functional ADAMTS13.
*Renal dialysis*
- While the patient has **acute kidney injury (creatinine 2 mg/dL)** and **anuria**, dialysis is a supportive measure for renal failure, not a definitive treatment for the underlying TTP.
- Addressing the primary cause (TTP) with plasma exchange will be crucial in potentially reversing the renal damage.
*Platelet transfusion*
- Platelet transfusions are generally **contraindicated in TTP** because they can worsen thrombosis by providing more substrate for platelet aggregation in the presence of severe ADAMTS13 deficiency.
- They should only be considered if there is life-threatening hemorrhage and the benefits outweigh the risks.
*Rehydration*
- While the patient is anuric, rehydration alone will not address the **microangiopathic hemolytic anemia, thrombocytopenia, fever, or neurological symptoms** caused by TTP.
- Overzealous rehydration could also exacerbate fluid overload in a patient with acute kidney injury.
*Intravenous immunoglobulin*
- **Intravenous immunoglobulin (IVIg)** is not a primary treatment for TTP. While it might be used in some autoimmune conditions, its role in TTP is limited and not supported as a first-line therapy.
- The immediate and critical need for TTP is the removal of autoantibodies and replacement of ADAMTS13, which IVIg does not directly achieve.
Question 96: A 39-year-old man presents to the emergency department with the complaint of ‘cola-colored’ urine that he noticed this morning. Additionally, he complains of malaise and reports that he has not been able to be productive at work since last week. Lab results revealed a hemoglobin of 6.7 g/dL, leukocyte total count of 1,000 cells/mm3, and a reticulocyte count of 6%. Coomb test is negative and flow cytometry shows CD55/CD59-negative red blood cells. Concerned about the results of his complete blood count, his physician explains the diagnosis to the patient. Which of the following sets of events best describes the mechanism underlying the development of neutropenia?
A. ↑ release of neutrophils in the bone marrow, ↑ destruction of neutrophils, and ↑ activation of neutrophil adhesion molecules
B. ↓ activation of neutrophil adhesion molecules and ↓ production of neutrophils in the bone marrow
C. ↑ activation of neutrophil adhesion molecules, ↓ destruction of neutrophils, and ↓ production of neutrophils in the bone marrow
D. ↑ activation of neutrophil adhesion molecules, ↓ release of neutrophils in the bone marrow, and ↑ destruction of neutrophils
E. ↓ production of neutrophils in the bone marrow, ↑ destruction of neutrophils, and ↑ activation of neutrophil adhesion molecules (Correct Answer)
Explanation: ***↓ production of neutrophils in the bone marrow, ↑ destruction of neutrophils, and ↑ activation of neutrophil adhesion molecules***
- **Paroxysmal nocturnal hemoglobinuria (PNH)**, indicated by the **CD55/CD59-negative red blood cells** and **cola-colored urine (hemoglobinuria)**, is characterized by a defect in **hematopoietic stem cells** in the **bone marrow**, leading to the **decreased production of all myeloid cell lines**, including neutrophils.
- The deficiency of **glycosylphosphatidylinositol-anchored proteins (GPI-APs)**, specifically **CD55** and **CD59**, on the surface of neutrophils in PNH makes them susceptible to **complement-mediated destruction**, and their increased activation of adhesion molecules can paradoxically lead to their sequestration or increased clearance.
*↑ release of neutrophils in the bone marrow, ↑ destruction of neutrophils, and ↑ activation of neutrophil adhesion molecules*
- **Neutropenia** (low leukocyte count) is due to a **decreased production** and/or **increased destruction**, not increased release, of neutrophils from the bone marrow.
- While increased destruction and activation of adhesion molecules can contribute to neutropenia, the initial step in PNH is impaired production.
*↓ activation of neutrophil adhesion molecules and ↓ production of neutrophils in the bone marrow*
- While **decreased production of neutrophils** in the bone marrow correctly describes a component of neutropenia in PNH, **decreased activation of neutrophil adhesion molecules** is not a feature; instead, there is often paradoxically increased activation leading to sequestration.
- Reduced adhesion molecule activation would typically lead to impaired margination and increased circulating neutrophils (leukocytosis) in the setting of inflammation, not neutropenia.
*↑ activation of neutrophil adhesion molecules, ↓ destruction of neutrophils, and ↓ production of neutrophils in the bone marrow*
- In PNH, the neutrophils are actually highly susceptible to **complement-mediated destruction** due to the lack of complement-inhibiting proteins like CD55 and CD59, hence there is **increased destruction**, not decreased.
- While **decreased production** and **increased activation of adhesion molecules** may contribute, the statement incorrectly suggests decreased destruction.
*↑ activation of neutrophil adhesion molecules, ↓ release of neutrophils in the bone marrow, and ↑ destruction of neutrophils*
- Although there is **increased destruction** and **increased activation of neutrophil adhesion molecules**, the primary issue is **decreased production** of neutrophils from the bone marrow, not specifically decreased release of adequately produced cells.
- The underlying **hematopoietic stem cell defect** results in a failure to generate sufficient neutrophils in the first place.
Question 97: A 35-year-old man presents with large tense blisters on the flexor surfaces of the upper extremities and trunk. The histologic findings show subepidermal blisters with an eosinophil-rich infiltrate. What is the most likely underlying pathology?
A. Linear band of IgA in the basement membrane
B. Autoantibodies to desmoglein 3
C. Autoantibodies to desmoglein 1
D. Linear band of immunoglobulin G (IgG) in the epidermal basement membrane (Correct Answer)
E. Granular deposits of immunoglobulin A (IgA) in the dermal papilla
Explanation: ***Linear band of immunoglobulin G (IgG) in the epidermal basement membrane***
- This finding, specifically targeting **hemidesmosomes** in the **dermal-epidermal junction**, is characteristic of **bullous pemphigoid**.
- The clinical presentation of **large, tense blisters** on flexor surfaces and the histological finding of **subepidermal blisters** with an **eosinophil-rich infiltrate** are classic for bullous pemphigoid.
*Linear band of IgA in the basement membrane*
- This describes **linear IgA bullous dermatosis**, which typically presents with an **annular or rosette-like pattern of blisters** and is less common than bullous pemphigoid.
- While it also involves subepidermal blistering, the immune reactant is IgA, not IgG, and the morphology of the lesions is often distinct.
*Autoantibodies to desmoglein 3*
- **Autoantibodies to desmoglein 3** are characteristic of **pemphigus vulgaris**, which typically presents with **flaccid blisters** and **mucosal involvement**.
- Histologically, pemphigus vulgaris shows **intraepidermal blistering** (acantholysis), not subepidermal.
*Autoantibodies to desmoglein 1*
- **Autoantibodies to desmoglein 1** are primarily associated with **pemphigus foliaceus** (superficial form) or sometimes **pemphigus vulgaris**, particularly when combined with desmoglein 3 antibodies.
- Pemphigus foliaceus presents with **superficial erosions and crusts**, not large tense blisters, and it is also an intraepidermal blistering disease.
*Granular deposits of immunoglobulin A (IgA) in the dermal papilla*
- This finding is pathognomonic for **dermatitis herpetiformis**, an intensely pruritic condition characterized by **grouped vesicles and urticarial plaques**, often on extensor surfaces.
- The blisters in dermatitis herpetiformis are typically small, not large and tense, and the immune mechanism involves IgA interacting with transglutaminase.
Question 98: A 29-year-old woman comes to the office with the complaints of severe bleeding after a dental extraction which required local hemostatic therapy. She has a long-term excessive menstrual bleeding and iron-deficiency anemia that required treatment with iron supplement since the age of 17. In addition, she states that her mother also has a history of frequent nosebleeds. The vital signs include: pulse rate 107/min, respiratory rate 17/min, temperature 37.2°C (99.0°F), and blood pressure 90/60 mm Hg. Her physical exam shows generalized pallor.
The complete blood count results are as follows:
Hemoglobin 10.7 g/dL
Hematocrit 41%
Leukocyte count 8,000/mm3
Neutrophils 54%
Bands 3%
Eosinophils 1%
Basophils 0%
Lymphocytes 32%
Monocytes 2%
Mean corpuscular hemoglobin 25.4 pg/cell
Mean corpuscular hemoglobin concentration 31% Hb/cell
Mean corpuscular volume 76 μm3
Platelet count 380,000/mm³
The coagulation test results are as follows:
Partial thromboplastin time (activated) 48.0 s
Prothrombin time 14.0 s
International normalized ratio 0.9
What is the most likely diagnosis?
A. Von Willebrand disease (Correct Answer)
B. Systemic lupus erythematosus
C. Sideroblastic anemia
D. Congenital thrombocytopenia
E. Hemophilia A
Explanation: ***Von Willebrand disease***
- This condition presents with a history of **excessive bleeding** from mucous membranes, menorrhagia, and prolonged bleeding after dental extraction, all indicative of a **primary hemostasis defect**.
- The elevated **aPTT (48.0s)** along with normal PT and platelet count, coupled with a family history of frequent nosebleeds, strongly suggests von Willebrand disease, which affects both platelet adhesion and factor VIII activity.
*Systemic lupus erythematosus*
- This is an **autoimmune disorder** that can cause various manifestations, but **bleeding disorders** are typically due to **immune thrombocytopenia** or acquired coagulopathies, neither of which is directly supported by the normal platelet count or specific coagulation profile (normal PT/INR).
- While it can cause anemia, the **microcytic anemia** presented is better explained by iron deficiency secondary to chronic blood loss.
*Sideroblastic anemia*
- This is a type of **microcytic hypochromic anemia** characterized by a defect in **heme synthesis**, leading to iron accumulation in mitochondria.
- It does not typically present with bleeding disorders or an elevated aPTT, making it an unlikely cause of the patient's primary bleeding complaints.
*Congenital thrombocytopenia*
- This condition involves a chronically **low platelet count**, which would lead to bleeding symptoms similar to this patient's.
- However, the patient's **platelet count is normal at 380,000/mm³**, ruling out a primary platelet deficiency.
*Hemophilia A*
- Hemophilia A is an **X-linked recessive disorder** primarily affecting males, characterized by a deficiency of **Factor VIII**, leading to prolonged aPTT.
- While it explains the elevated aPTT, the patient is female, and the predominant mucous membrane bleeding (menorrhagia, dental extraction bleeding) is more typical of **platelet function defects or von Willebrand disease** than the deep tissue or joint bleeds seen in hemophilia.
Question 99: A 24-year-old woman presents with blisters and erosions on her upper face, chest, and back. The blisters have erythema, scales, and crust formation. Examination shows oromucosal involvement. Histopathologic evaluation reveals a tombstone arrangement at the base of the blister. What is the most likely cause for the patient's condition?
A. Pemphigus foliaceus
B. Pemphigus vulgaris (Correct Answer)
C. Linear immunoglobulin A (IgA) disease (LAD)
D. Dermatitis herpetiformis
E. Bullous pemphigoid
Explanation: ***Pemphigus vulgaris***
- The presence of widespread **blisters and erosions**, particularly with **oromucosal involvement**, is highly characteristic of pemphigus vulgaris. The **tombstone arrangement** on histopathology, indicative of **acantholysis** above the basal layer, further supports this diagnosis.
- Unlike **pemphigus foliaceus**, pemphigus vulgaris typically involves **mucous membranes** and presents with deeper, flaccid blisters that rupture easily, leading to erosions.
*Pemphigus foliaceus*
- This condition primarily affects the **superficial epidermis**, resulting in **superficial blisters, erosions, and scaling**, often on the face and trunk.
- A key differentiating feature is the **absence of mucosal involvement** in pemphigus foliaceus, which is present in this patient.
*Linear immunoglobulin A (IgA) disease (LAD)*
- LAD presents with tense bullae often in an **annular or rosette pattern**, and can involve mucous membranes, but the histopathology shows a **subepidermal blister** with a linear IgA deposit along the basement membrane zone.
- The "tombstone arrangement" with intraepidermal acantholysis is not a feature of LAD, which points away from this diagnosis.
*Dermatitis herpetiformis*
- This condition typically presents with intensely **pruritic vesicles and papules**, primarily on extensor surfaces (e.g., elbows, knees, buttocks), and is strongly associated with **celiac disease**.
- Histopathology reveals **subepidermal vesicles with neutrophils** at the dermal papillae, and **granular IgA deposits** in the dermal papillae, which is different from the described intraepidermal blistering.
*Bullous pemphigoid*
- Bullous pemphigoid is characterized by **tense bullae** on an erythematous or urticarial base, typically affecting the **flexural surfaces** and trunk in elderly patients.
- Histopathologically, it shows **subepidermal blistering** with a linear deposition of IgG and C3 along the basement membrane zone, which differs from the intraepidermal acantholysis seen in this patient.
Question 100: A 32-year-old man comes to the physician because of a 3-week history of cough, weight loss, and night sweats. He migrated from Sri Lanka 6 months ago. He appears emaciated. His temperature is 38.1°C (100.5°F). Physical examination shows enlargement of the right supraclavicular lymph node. Chest and abdominal examination show no abnormalities. An interferon-gamma assay is positive. A biopsy specimen of the cervical lymph node is most likely to show the causal organism in which of the following locations?
A. Mantle zone
B. Medullary sinus
C. Germinal center
D. Subcapsular sinus
E. Paracortex (Correct Answer)
Explanation: ***Paracortex***
- The patient's symptoms (cough, weight loss, night sweats, fever), recent migration from an endemic area (Sri Lanka), **supraclavicular lymphadenopathy**, and positive **interferon-gamma release assay (IGRA)** strongly suggest **tuberculosis**.
- In tuberculous lymphadenitis, **caseating granulomas** containing *Mycobacterium tuberculosis* organisms characteristically form in the **paracortex** (T-cell zone).
- The **paracortex** is where **cell-mediated immunity** occurs, with T cells interacting with infected macrophages and dendritic cells to form the **epithelioid granulomas** with **Langhans giant cells** that are pathognomonic for TB.
- The organisms are found within these **granulomas**, which predominantly occur in the paracortical (interfollicular) region.
*Mantle zone*
- The **mantle zone** primarily contains **naïve B cells** surrounding germinal centers.
- This is a B-cell area not typically involved in granuloma formation or mycobacterial infection.
*Germinal center*
- **Germinal centers** are sites of B cell proliferation, somatic hypermutation, and antibody class switching.
- TB is a disease of **cell-mediated immunity** (T cells and macrophages), not humoral immunity, so granulomas do not form in germinal centers.
*Medullary sinus*
- The **medullary sinuses** are channels in the medulla of the lymph node through which lymph flows toward the efferent lymphatic vessels.
- While macrophages line these sinuses and may contain some organisms in acute infections, the characteristic **caseating granulomas** of chronic tuberculous lymphadenitis form in the **paracortex**, not in the sinuses.
*Subcapsular sinus*
- The **subcapsular sinus** is the initial entry point for afferent lymph into the lymph node.
- While this is where pathogens first enter, chronic granulomatous infections like TB develop their characteristic pathology deeper in the node, specifically in the **paracortex** where T-cell-mediated granuloma formation occurs.
