Hematology & oncology Clinical Case / MCQS / Uworld for Usmle step 2 / case 9

Hematology & oncology Clinical Case  / MCQS / Uworld for Usmle step 2 / case 9 with answer and explanation and references and Educational objective

A 7-year-old Caucasian boy is brought to your office for a routine check-up. He underwent splenectomy one year ago for persistent anemia and jaundice. He has received pneumococcal vaccination and takes penicillin prophylaxis. His uncle underwent splenectomy for "some blood disorder" in his childhood. His blood hemoglobin level is 11.5 mg/dL and MCV is 90 fL. Blood smear demonstrates occasional red blood cells with single, round, blue inclusions on Wright stain. The latter finding is most likely related to:

 

A. Hemoglobin precipitation . B. Low reticulocyte count . C. Penicillin therapy . D. Mechanical RBC damage . E. Splenectomy  .

 

Answer : E

Explanation:

This patient has Howell-Jolly bodies on his peripheral blood smear. These bodies are nuclear remnants within red blood cells (RBCs) that are typically removed by the spleen. They are evident on peripheral blood smear as single, round, blue inclusions on Wright stain. The presence of Howell-Jolly bodies usually indicates physical absence of the spleen or functional hyposplenism due to splenic autoinfarction, infiltrative disorders of  the spleen, or splenic congestion. This patient's surgical splenectomy was most likely performed as treatment for hereditary spherocytosis .

(Choice A) Hemoglobin precipitation is seen in glucose-6-phosphate dehydrogenase (G6PD) deficiency. In this disease, hemoglobin becomes oxidized and forms insoluble precipitants called Heinz bodies. They appear in RBCs on peripheral smear after staining with a dye such as crystal violet.

(Choice B) A low reticulocyte count indicates decreased production of RBCs. This can be due to a number of causes, including iron deficiency, folate or 812 deficiencies, cancer chemotherapy, infection, or aplastic anemia. On peripheral smear, reticulocytes have a slightly bluish tint and stain with methylene blue. This patient's blood smear does not suggest decreased reticulocyte production.

(Choice C) The main side effect of penicillin administration is allergic reaction. Penicillin and other beta-lactam antibiotics have been associated with autoimmune hemolytic anemia, but Howell-Jolly bodies are not seen with immune-mediated hemolysis.

(Choice D) Mechanical red blood cell damage occurs when RBCs shear on a foreign object within the vascular system. The classic example is RBC shearing on artificial heart valves, but mechanical RBC damage can occur with catheters and other intravascular devices. Schistocytes (fragmented RBCs) will be seen on the peripheral blood smear.

Educational Objective:

Howell-Jolly bodies are nuclear remnants within red blood cells typically removed by the spleen. Their presence strongly suggests physical or functional hyposplenism.

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Hematology & oncology Clinical Case / MCQS / Uworld for Usmle step 2 / case 8

 Hematology & oncology Clinical Case  / MCQS / Uworld for Usmle step 2 / case 8 with answer and explanation and references and Educational objective

A 16 year-old-girl with hereditary spherocytosis is scheduled for a splenectomy. She was previously managed with folate therapy and occasional blood transfusions, but her anemia became refractory to medical management alone. Before the operation, she is told that she will have an enhanced risk of developing pneumococcal sepsis. She then asks, "How long will this risk last?" What is the best response to her question?

 

A. 2 weeks B. Up to 6 months C. Up to 2 years D. Up to 10 years E. More than 10 years

 

Answer : E

Explanation:

Hereditary spherocytosis is an autosomal dominant disorder. It is characterized by a lack of spectrin in the red cell membrane, which causes the cells to become spheres, instead of being normal, flexible and durable biconcave discs. The poorly flexible spherical cells are thus unable to pass through the small fenestrations in the splenic red pulp, and hemolysis takes place when the red cells are trapped within the spleen.

 

The treatment for most patients involves supportive care with oral folic acid and blood transfusions during periods of extreme anemia. Splenectomy is considered if patients have moderate to severe spherocytosis, or are refractory to medical management. The benefits of splenectomy must be balanced against the immediate and long-term risks of the procedure. Life-threatening anemia and the need for regular transfusions may be abolished by splenectomy, although a mild degree of anemia usually persists. Immediate risks (e.g. , hemorrhage, postoperative infection, injury to nearby organs) are infrequent. The most feared long-term complication is overwhelming sepsis with encapsulated

bacteria, most commonly Streptococcus pneumoniae.

 

Studies have shown that the risk for pneumococcal sepsis is present up to 30 years and probably longer after splenectomy. To decrease this risk, current recommendations call for the administration of anti-pneumococcal, Haemophilus, and meningococcal vaccines several weeks before the operation, and daily oral penicillin prophylaxis for three to five years following splenectomy or until adulthood (for pediatric patients). In view of reported deaths from sepsis up to 30 years or more after splenectomy, a case can be made for lifetime penicillin prophylaxis. Alternatively, antibiotics can be made available at home for immediate treatment of any significant fever.

Educational Objective:

Studies have shown that the risk for sepsis is present up to 30 years and probably longer after splenectomy. Current recommendations state that patients should receive anti-pneumococcal, Haemophilus, and meningococcal vaccines several weeks before the operation, and daily oral penicillin prophylaxis for three to five years following splenectomy.

 

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Hematology & oncology Clinical Case / MCQS / Uworld for Usmle step 2 / case 7

 Hematology & oncology Clinical Case  / MCQS / Uworld for Usmle step 2 / case7 with answer and explanation and references and Educational objective

A 34-year-old man is brought to the emergency department due to several hours of confusion. His wife reports that he has had fever. malaise. and cough for the past 2 days. A year ago, the patient required prolonged hospitalization and extensive surgery for multiple gunshot wounds to the abdomen. He takes no medications regularly and has no other medical problems. The patient does not use tobacco, alcohol, or illicit drugs.

He has no history of recent travel. Temperature is 40.5 C (104.9 F), blood pressure is 80/50 mm Hg. pulse is 11 0/min, and respirations are 32/min. Mucous membranes are moist and no cervical lymphadenopathy is present. Dullness to percussion and crackles over the left lower chest are present. Cardiovascular examination reveals normal first and second heart sounds and bounding peripheral pulses. The abdomen has several well-healed surgical scars. Intravenous fluids and broad-spectrum antibiotics are initiated. The next day, blood cultures show gram-positive cocci. Which of the following is the most likely underlying mechanism leading to this patient's clinical presentation?

 

A Complement deficiency . B. Destruction of CD4+ cells . C. Immunoglobulin A deficiency . D. Impaired antibody-facilitated phagocytosis . E. Impaired B cell isotype switching . F. Impaired chemotaxis . G. Impaired oxidative burst .

 

Answer : D

Explanation :

This patient likely had a splenectomy during his operation for multiple gunshot wounds to the abdomen. He now has high fever, hypotension, tachypnea, and tachycardia in the setting of bacteremia with gram-positive cocci, suggesting an overwhelming Streptococcus pneumoniae infection.

Encapsulated organisms such as S pneumoniae, Haemophilus influenzae, and Neisseria meningitidis have a polysaccharide exterior that conceals antigenic epitopes and resists innate phagocytosis. Therefore, these pathogens are largely eliminated via the humoral immune response with antibody-mediated phagocytosis (opsonization) and antibody-mediated complement activation. Much of this is dependent on splenic macrophages and the generation of splenic opsonizing antibodies. As such, patients with asplenia are at high risk for fulminant infection with encapsulated organisms. These patients should be immunized with pneumococcal, meningococcal, and H influenzae type B vaccines and take oral antibiotics early in the course of any febrile illness.

(Choice A) Deficiencies of the complement system can be inherited or acquired (eg, systemic lupus erythematosus, antiphospholipid antibody syndrome) and can increase risk of infection with encapsulated bacteria (classic complement pathway). However, such deficiencies are rare, and splenectomy is far more likely to be the cause of this patient's bloodstream infection given his history of multiple abdominal gunshot wounds.

(Choice B) CD4+ lymphocyte cells are destroyed by HIV, and patients are at increased risk of infection with a wide range of pathogenic organisms (including encapsulated bacteria). However, this patient is more likely to have asplenia with defects in antibody  production and antibody-mediated phagocytosis

(Choices C and E) Impaired 8 cell isotype switching is seen in some patients with common variable immunodeficiency. They have normal 8 cell numbers but significantly reduced lg subtypes. Patients with common variable immunodeficiency are at risk for

recurrent infections (eg, sinopulmonary, gastrointestinal) and autoimmune disease. Patients with lgA deficiency are often asymptomatic and rapid, fulminant infection is uncommon. This patient is far more likely to have had a splenectomy.

(Choice F) Chemotaxis is impaired in patients with leukocyte adhesion deficiency. Patients with this condition have recurrent bacterial infections, primarily of the skin and mucosa.

(Choice G) Patients with chronic granulomatous disease have impaired oxidative burst and often present with recurrent bacterial or fungal infections due to catalase-producing organisms (eg, Aspergillus nidu/ans, Staphylococcus aureus). Host response against pneumococci (catalase-negative) is not affected by oxidative burst deficiency.

Educational objective:

Patients with asplenia are at risk for fulminant infection with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae) due to deficits in antibody response and antibody-mediated phagocytosis/complement activation.

  

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Hematology & oncology Clinical Case / MCQS / Uworld for Usmle step 2 / case 6

 Hematology & oncology Clinical Case  / MCQS / Uworld for Usmle step 2 / case 6 with answer and explanation and references and Educational objective 

A 7-year-old boy is brought to the physician by his mother because of bleeding gums for the past 3 months. The mother reports that he regularly brushes his teeth and visits a dentist twice per year. Examination at his most recent dentist visit 6 months ago was normal. The patient also complains of easy fatigability and a pounding sensation in his ears. He has no other medical problems and takes no medication. Physical examination shows that he is at the 5th percentile for height and 25th percentile for weight for his age. His thumbs are slightly bent, and several areas of hypopigmentation are noted on his skin. Laboratory findings reveal:

 

WBC count                3000/mm3

Hemoglobin               7.8 g/dL

RBC count                 3 million/mm3

MCV                          112 fL

Platelet count            40,000/mm3

 

Which of the following is the most likely cause of this patient's condition?

A. Chromosomal breaks . B. RBC enzyme deficiency . C. Congenital infection . D. Benzene exposure . E. Thymic tumor . F. Cobalamin deficiency .

 

Answer : A

Explanation:

Acquired Causes of Aplastic Anemia

Drugs (e.g., NSAIDs, sulfonamides,etc.)

Toxic chemicals (e.g., benzene, glue,etc.)

Idiopathic

Viral infections (e.g., HIV, EBV, etc.)

Immune disorders

Thymoma

This patient presents with symptoms and laboratory values consistent with aplastic anemia, which can be acquired or congenital as shown above. Congenital causes are more common in children, and Fanconi anemia (FA) is the most common congenital cause. It is an autosomal recessive or X-linked disorder associated with the clinical manifestations summarized below. Most patients with FA are diagnosed by the age of 16 years and have a predisposition for developing cancer. Numerous genes, all believed to involve DNA repair, have been implicated.

 

Location	Clinical Manifestations of Fanconi Anemia
Bone marrow	Aplastic anemia and progressive bone marrow failure
Appearance	Short stature, microcephaly, abnormal thumbs, and Hypogonadism
Skin	Hypopigmented/hyperpigmented areas, cafe au lait spots, and large freckles
Eyes/ears	Strabismus, low-set ears, and middle ear abnormalities (e.g., hemorrhage, incomplete development, chronic infections,deafness, etc.)

 

Diagnosis of FA is made by chromosomal breaks on genetic analysis combined with the clinical findings. This patient likely has bleeding secondary to thrombocytopenia, fatigue from macrocytic anemia, and pounding in his ears from possible conduction defects or chronic hemorrhage. The definitive treatment for aplastic anemia is hematopoietic stem cell transplantation.

 

(Choice B) The most common RBC enzyme deficiency causing anemia is glucose-6-phosphate dehydrogenase (G6PD) deficiency. In affected patients, oxidant drugs (e.g., antimalarials and sulfas) and infection can cause episodic hemolysis.

 

(Choice C) The TORCH (toxoplasmosis, other infections [e.g., syphilis), rubella, cytomegalovirus, and herpes simplex) infections are known to cause significant neonatal and perinatal morbidity and mortality. They commonly cause growth restriction but not chronic pancytopenia, which is seen in this patient.

 

(Choice D) Benzene is an industrial chemical known to cause aplastic anemia. Based on this patient's history, there is no reason to suspect that he has been exposed to benzene. Furthermore, benzene exposure does not explain his skin changes.

 

(Choice E) Approximately 5%-15% of the patients with thymic tumors have pure red cell aplasia. This finding is most common in older women. This patient does not have an isolated red cell aplasia because he is also thrombocytopenic.

 

(Choice F) Autoimmune pernicious anemia due to anti-intrinsic factor autoantibodies is the leading cause of cobalamin deficiency. However, this patient is somewhat young to have pernicious anemia.

 

Educational objective:

 

Fanconi anemia is an autosomal recessive disorder that causes congenital marrow failure, poor growth, morphologic abnormalities, and usually macrocytic anemia.

 

References: 1.   Fanconi anemia and its diagnosis 2.    X-linked inheritance of Fanconi anemia complementation group B New links : 1.   Fanconi anemia and its diagnosis 1.   2. X-linked inheritance of Fanconi anemia complementation group B

 

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Hematology & oncology Clinical Case / MCQS / Uworld for Usmle step 2 / case 5

  Hematology & oncology Clinical Case  / MCQS / Uworld for Usmle step 2 / case 5 with answer and explanation and references and Educational objective

A 2 and a half-year-old child is brought to the office for the evaluation of easy bruising, nosebleeds, and decreased activity over the past week. He had an upper respiratory infection that was treated with an antibiotic 2 weeks ago. On examination, he is well-developed, seems well-nourished, anicteric, and pale. Pertinent findings include some small palpable posterior cervical lymph nodes, sinus tachycardia, a grade I/VI systolic ejection murmur, ecchymoses on his left shoulder and both lower extremities, and petechiae over his extremities and groin. There is no hepatosplenomegaly. The laboratory findings are as follows:

 

Hemoglobin                7.9 g/dL

Hematocrit                  24%

Platelet count             12,000/mm3

WBC                           3,000/mm3

Reticulocyte count      0.5%

A bone marrow biopsy reveal a markedly hypocellular marrow with decreased megakaryocytes and precursors of the erythroid and myeloid cell lines. What is the most likely diagnosis?

 

A.  Acquired aplastic anemia . B.  Fanconi's anemia . C.  Diamond-Biackfan anemia . D.  Transient erythroblastopenia . E.  Acute myeloid leukemia .

 

Answer : A

Explanation:

Acquired aplastic anemia results from an injury to the bone marrow by radiation, drugs (chemotherapy or antibiotics such as chloramphenicol), insecticides, toxins (benzene, carbon tetrachloride), or infections. Signs and symptoms include pallor, fatigue, weakness, loss of appetite, easy bruising, petechiae, mucosal hemorrhage, and fever. Laboratory evaluation demonstrates a normocytic or macrocytic anemia, leukopenia, reticulocytopenia, and thrombocytopenia. A bone marrow biopsy is essential to make the diagnosis; it typically shows profound hypocellularity with a decrease in all cell lines and fatty infiltration of the marrow.

 

(Choice B) Classically, patients with Fanconi's anemia have pancytopenia and characteristic congenital anomalies, such as hyperpigmentation on the trunk, neck and intertriginous areas and/or cafe-au-lait spots, short stature, upper limb abnormalities, hypogonadism, skeletal anomalies, eye or eyelid changes, and renal malformations. Blood counts start to decrease between 4 and 12 years of age, and the initial manifestation is usually thrombocytopenia, followed by neutropenia, then anemia.

(Choice C) Diamond-Biackfan anemia (DBA), or congenital pure red cell aplasia, presents in the first 3 months of life with pallor and poor feeding. CBC reveals a normocytic or macrocytic anemia with reticulocytopenia. WBC and platelet counts are normal.

(Choice D) Transient erythroblastopenia of childhood (TEC) is an acquired red cell aplasia which occurs in healthy children between 6 months and 5 years old. There is a gradual onset of symptoms such as pallor and decreased activity. The physical examination is unremarkable except for pallor and tachycardia. The typical laboratory findings are normocytic normochromic anemia, with hemoglobin levels ranging from 3 to 8 g/dl , and an extremely low reticulocyte count.

(Choice E) Bone marrow infiltration due to leukemia results in pancytopenia by crowding out the normal bone marrow elements. Patients present with lethargy (from anemia), bruising and bleeding (from thrombocytopenia), and unexplained fever. They may also complain of bone pain or present with a limp. CBC shows pancytopenia or anemia, thrombocytopenia and leukocytosis. Acute myeloid leukemia is more common in adults.

In this case, the classic presentation after an upper respiratory infection, as well as the absence of other features of leukemia (normal bone marrow), makes acquired aplastic anemia the best answer.

Educational Objective:

Aplastic anemia should be suspected in any patient with pancytopenia following drug intake, exposure to toxins or viral infections.

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