37-year-old man comes to the emergency department due to blood-tinged vomiting and abdominal discomfort.  Six months ago, he lost his job as an investment banker and began drinking large amounts of whiskey on a daily basis.  He has since been hospitalized several times with alcohol intoxication.  His temperature is 36.7 C (98 F), blood pressure is 110/70 mm Hg, pulse is 84/min, and respirations are 18/min.  Physical examination shows a firm, enlarged liver.  Peripheral blood smear results show neutrophils with 6-8 nuclear lobes.  Which of the following is the most likely explanation for this patient’s abnormal hematologic findings?

A 60-year-old African-American female is evaluated for fatigue.  Past surgical history includes mitral valve repair with a mechanical valve due to severe mitral insufficiency.  She has 30-pack year history of smoking and occasionally drinks alcohol.  Examination shows pallor.  Laboratory studies show the following:

Complete blood count

Hemoglobin	9.0 g/L
Reticulocytes	6.8%
Platelets	218,000/mm3
Leukocyte count	4,500/mm3

Serum chemistries are within normal limits.  Her peripheral smear shows red blood cell fragments, “burr cells,” and “helmet cells”.  Which of the following is the most likely cause of her condition?

A 43-year-old man comes to the hospital due to recurrent episodes of fever and sore throat despite multiple antibiotic courses.  For the past several months, he has also felt “run down” and fatigued all the time.  His wife adds that he bruises easily and has had bleeding gums on several occasions.  Temperature is 37.8 C (100.2 F).  On physical examination, he has mucosal pallor, pharyngeal erythema, and multiple ecchymoses on his extremities.  Peripheral blood smear is shown in the image below:

Which of the following chromosomal abnormalities is most likely present in the affected cells?

A 5-week-old boy is brought to the emergency department after having tonic-clonic movements of his left upper and lower extremity that lasted approximately 3 minutes.  The patient was born at 38 weeks gestation to a 23-year-old primigravid woman.  The mother received normal prenatal care, took prenatal vitamins, and had a healthy diet during pregnancy.  The infant’s newborn screen was positive for cystic fibrosis, and confirmatory testing is pending.  The infant has been breastfeeding exclusively.  He has never taken any medications and has received no vaccinations.  On examination, the infant is postictal.  A CT scan of the head shows a right-sided intracranial hemorrhage.  Which of the following is the most likely cause of this infant’s presentation?

A 28-year-old previously healthy man comes to the office due to episodic fevers, night sweats, and weight loss for several months.  He emigrated from Kenya with his family at age 14.  He does not use tobacco, alcohol, or illicit drugs.  The patient works as a driving instructor and volunteers at a homeless shelter.  His temperature is 37.2 C (99 F).  Physical examination is normal with the exception of cervical lymphadenopathy.  A lymph node biopsy is performed, and histopathologic findings are shown in the image below.

Which of the following is the most likely diagnosis?

A 23-year-old African American man comes to the emergency department due to back and lower extremity pain for 2 days.  He has had several similar episodes over the last 15 years that have required hospitalization.  His pain is not responsive to over-the-counter analgesics, and review of his prior records shows that he has needed treatment with opioids for adequate pain relief.  The patient does not use tobacco, alcohol, or illicit drugs.  On physical examination, he has scleral icterus and tenderness over his lower back and long bones of his thighs.  Laboratory evaluation shows a hemoglobin level of 6.7 g/dL.

Item 1 of 2

Histopathologic evaluation of this patient’s spleen is most likely to reveal which of the following?

Item 2 of 2

The patient is admitted to the hospital and receives opioid analgesics and intravenous fluids.  He has no evidence of active infection.  His hemoglobin electrophoresis results are consistent with sickle cell disease (hemoglobin SS).  Further laboratory evaluation shows a mean corpuscular volume of 113 µm³ and a reticulocyte index of 1.5, which is low given the patient’s severe anemia.  Which of the following is the most likely cause of this patient’s macrocytosis?

A 34-year-old man with an unremarkable past medical history is evaluated for an enlarged lymph node in his anterior cervical chain that measures 4 cm in diameter.  The patient first felt the lymph node several weeks ago and states that it has been steadily increasing in size.  He is concerned about whether or not he “has cancer.”  The patient is referred to a specialist for surgical removal of the enlarged node.  Biopsy reveals abnormal lymph node architecture and numerous lymphocytes.  Which of the following, if present, would be most consistent with malignancy in this patient?

An 8-year-old boy comes to the office due to a mass in the right mandible.  His family first noticed it a few months ago, and it has grown rapidly.  He has had no fevers, chills, cough, or weight loss.  The patient and his family recently immigrated to the United States from East Africa.  He has no known medical problems.  Temperature is 37 C (98.6 F).  Physical examination shows a large tumor on the right mandible with palpable regional lymphadenopathy.  A biopsy of the lesion is performed.  Histopathologic examination shows a diffuse infiltrate of lymphoid cells with numerous mitotic figures; interspersed macrophages with clear cytoplasm are also seen.  These lymphoid cells most likely have a chromosomal translocation that directly alters which of the following processes?

A 70-year-old female presents to your office complaining of easy fatigability, exertional dyspnea and weight loss.  She also complains of frequent falls.  Physical examination reveals symmetrically decreased vibratory sensation to the lower extremities.  Her hemoglobin is 7.8 g/dL and a peripheral blood smear shows hypersegmented neutrophils.  Which of the following is the best treatment for this patient?

A 42-year-old man is hospitalized due to fever and persistent sore throat.  Temperature is 38.3 C (100.9 F), blood pressure is 120/80 mm Hg, pulse is 94/min, and respirations are 16/min.  There are several bruises on his trunk, and blood oozes from his intravenous catheter venipuncture sites.  Blood fibrinogen level is 110 mg/dL (normal: 150-400).  Bone marrow aspirate shows a predominance of immature myeloid cells with numerous azurophilic, needle-shaped cytoplasmic granules.  Chromosomal analysis of these immature cells is most likely to show which of the following abnormalities?

A 22-year-old woman comes to the emergency department due to a nosebleed.  She had a similar episode yesterday, but the bleeding stopped with prolonged local pressure.  On review of systems, the patient has also had easy bruising for the past several months.  She has no significant past medical history and takes no medications.  On physical examination, her heart and lungs appear normal.  The liver span is 8 cm and the spleen is not palpable.  There are scattered ecchymoses over her arms and legs.  Laboratory results are as follows:

HIV and hepatitis C tests are negative.  Which of the following is the most likely primary mechanism causing this patient’s condition?

A 35-year-old woman comes to the physician complaining of weakness, fatigue, and pallor.  She denies heavy menses or melena.  Physical examination is unremarkable except for conjunctival pallor.  Laboratory results are as follows:

Iron studies and serum B₁₂ and folic acid levels are within normal limits.  Bone marrow biopsy shows absence of erythroid precursors but preserved myeloid and megakaryocytic elements.  Further workup would most likely show which of the following?

A 24-year-old woman, gravida 1 para 0, at 28 weeks gestation comes to the labor and delivery unit due to intense abdominal pain, vaginal bleeding, and absent fetal movement.  Temperature is 36.7 C (98.1 F), blood pressure is 170/96 mm Hg, pulse is 108/min, and respirations are 22/min.  Pulse oximetry shows 98% on room air.  Physical examination shows a tense abdomen and a firm, tender uterus.  Ultrasound shows a hematoma between the placenta and the uterine wall and no fetal cardiac activity.  Laboratory results are as follows:

The patient is hospitalized for further management.  Once hospitalized, she begins to experience bleeding from her gums and intravenous catheter sites.  Blood is also noted in the urinary catheter.  Vital signs are unchanged, and she reports no shortness of breath.  Which of the following is the most likely underlying cause of this patient’s hospital symptoms?

A 52-year-old man comes to the office due to a progressively enlarging neck mass, fatigue, and weight loss over the past 2 months.  Physical examination shows enlarged, firm, and nontender cervical lymph nodes.  The patient also has enlarged tonsils, bilateral axillary lymphadenopathy, and splenomegaly.  Excisional lymph node biopsy reveals diffuse sheets of atypical, large B cells that have replaced the normal tissue architecture.  In situ hybridization of the tissue specimen is positive for Epstein-Barr virus.  Which of the following risk factors is most strongly associated with development of this patient’s condition?

A 34-year-old obese man presents to your office complaining of fatigue, daytime sleepiness and occasional headaches.  When you inquire about his sleeping habits, he reports that he sleeps in a separate room from his wife because she finds his snoring annoying.  On physical examination, his blood pressure is 160/90 mmHg and his heart rate is 80/min.  His abdomen is soft and non-tender, his liver span is 9 cm, and his spleen is not palpable.  Laboratory findings are:

Decreased oxygen delivery to which of the following organs is responsible for his increased hematocrit?

A 67-year-old woman is evaluated for worsening fatigue and exertional dyspnea.  She has no prior medical conditions and takes no medications.  The patient does not use tobacco, alcohol, or illicit drugs and consumes a balanced diet.  Vital signs are within normal limits.  Physical examination is notable for mucosal pallor.  Stool testing for occult blood is negative.  Laboratory studies reveal that hemoglobin is 6.7 g/dL, white blood cell count is 35,000/mm³, and platelets are 45,000/mm³.  Peripheral blood flow cytometry of the white blood cell population is shown below.

Which of the following is the most likely diagnosis?

A 42-year-old previously healthy woman comes to the office due to fever and sore throat.  She has no cough.  Physical examination shows tonsillar exudate and a nontender cervical lymph node that measures 3.5 cm in diameter.  Oral antibiotic therapy is started and on a follow-up visit a week later, the patient reports that her symptoms have resolved.  The previously enlarged cervical lymph node has decreased slightly in size.  On several follow-up visits over the following year, the patient remains asymptomatic and the size of the lymph node fluctuates but does not disappear completely.  Referral to a surgeon is made and excisional biopsy of the lymph node is performed.  Which of the following is the most likely diagnosis?

 46-year-old smoker presents to your office with a three week history of low-grade fever, weakness and neck swelling. Biopsy of the affected tissue reveals the following histologic findings:

An abnormality in which of the following tissues is most likely responsible for this patient’s symptoms?

A 15-year-old boy is brought to the emergency department due to progressive shortness of breath.  The patient has no chronic medical conditions.  Temperature is 37.1 C (98.8 F), pulse is 130/min, and respirations are 32/min.  Pulse oximetry is 94% on room air.  Lung examination demonstrates diffusely diminished breath sounds.  Clusters of enlarged cervical lymph nodes are palpable bilaterally.  A large mediastinal mass is visualized on chest x-ray.  The leukocyte count is elevated, and a peripheral blood smear shows abnormal white blood cells, as shown in the image below:

Specialized staining shows the cells are positive for terminal deoxynucleotidyl transferase (TdT) and CD3; they are negative for CD19 and myeloperoxidase (MPO).  Which of the following is the most likely diagnosis?

A 7-year-old boy comes to the office for follow-up.  A week ago, the patient began having episodes of bloody diarrhea that have since resolved.  His current laboratory studies show elevated blood urea nitrogen and serum creatinine levels.  Complete blood count reveals anemia and thrombocytopenia.  Coagulation studies are within normal limits.  His peripheral blood smear is shown in the image below.

Which of the following is the most likely cause of this patient’s anemia?

A 30-year-old man comes to the emergency department due to rapidly increasing abdominal distention and anorexia.  The patient has a history of HIV infection and intravenous drug use.  CT scan of the abdomen shows ascites and a large mass involving the small intestine.  Biopsy of the mass reveals sheets of uniform, round, medium-sized tumor cells with basophilic cytoplasm and a very high rate of proliferation and apoptosis.  Which of the following infectious agents is most closely associated with the development of this patient’s condition?

A 53-year-old man comes to the physician due to frequent headaches and dizziness.  He has a history of hypertension and peptic ulcer disease.  His medications include daily chlorthalidone and antacids as needed.  The patient’s temperature is 37 C (98.6 F), blood pressure is 146/92 mm Hg, pulse is 89/min, and respirations are 16/min.  His BMI is 26 kg/m².  Physical examination shows facial plethora and moderate splenomegaly.  Laboratory results are as follows:

This patient most likely has a mutation in which of the following types of proteins?

A 35-year-old woman comes to the office due to reduced energy and fatigue.  She reports heavy menstrual bleeding over the past 6 months.  The patient is found to have hypochromic microcytic anemia.  Iron supplementation is prescribed.  A week later, a peripheral blood smear shows numerous enlarged red blood cells that have a bluish hue on Wright-Giemsa staining.  The bluish color of these red blood cells is best explained by the presence of which of the following?

A 64-year-old man is brought to the hospital by ambulance after being found unresponsive by his brother.  Despite resuscitative efforts, he dies shortly thereafter.  The family reports that the patient had 2 months of progressive fatigue and an unintentional weight loss prior to the episode.  Autopsy examination reveals a massive pulmonary embolus, and a cross-section of the liver shows the following:

Genomic analysis of the hepatic lesions demonstrates intranuclear fragments of foreign DNA.  These fragments most likely belong to which of the following pathogens?

A 53-year-old woman comes to the office due to aching pain in her legs.  She is a hair stylist and has cut down on her work hours due to the discomfort.  The patient has a history of migraine and untreated chronic hepatitis C.  She smokes a pack of cigarettes daily but does not use alcohol or recreational drugs.  Physical examination findings are shown in the image below.

An abnormality affecting which of the following is the most likely cause of this patient’s symptoms?

A 65-year-old man comes to the office due to 4 months of worsening fatigue.  The patient feels tired with simple household chores.  He has a 15-pack-year smoking history and drinks 2 or 3 beers daily.  Temperature is 37 C (98.6 F), blood pressure is 134/86 mm Hg, and pulse is 76/min.  Physical examination reveals a late systolic ejection murmur with a soft S2.  The lungs are clear to auscultation.  The abdomen is soft and nontender with no hepatosplenomegaly.  There are no focal neurological deficits.  Laboratory testing reveals hemoglobin is 9 g/dL and mean corpuscular volume is 93 µm³.  Peripheral blood smear is shown below:

Which of the following best explains the observed erythrocyte findings in this patient?

A 20-year-old man is evaluated for recurrent episodes of jaundice.  He was separated from his parents at a young age and is unaware of his family medical history.  The patient resided in several foster homes throughout his childhood but currently lives alone.  Temperature is 36.7 C (98.1 F), blood pressure is 120/80 mm Hg, and pulse is 72/min.  Physical examination shows pallor, icterus, and mild splenomegaly.  There is no lymphadenopathy or hepatomegaly.  The remainder of the physical examination is normal.  Laboratory results are as follows:

When the patient’s red blood cells are incubated in a hypotonic saline solution, hemoglobin is released.  The control sample does not release hemoglobin.  This patient is at greatest risk for developing which of the following complications?

A 6-year-old boy is brought to the clinic due to recurrent nosebleeds over the last couple of weeks.  The patient has no chronic medical conditions and takes no medications.  Vital signs are normal.  On physical examination, there is conjunctival pallor.  The nares have dried, crusted blood with no active bleeding.  The oropharynx is clear.  Neck examination shows enlarged, palpable lymph nodes bilaterally.  Cardiopulmonary examination is unremarkable.  The abdomen is soft and nontender, with the liver measuring 4 cm below the costal margin.  There are scattered petechiae along the trunk.  Complete blood count is as follows:

Flow cytometry of the peripheral blood demonstrates a distinct population of cells that express terminal deoxynucleotidyl transferase (TdT), CD10, and CD19.  Myeloperoxidase (MPO) is negative.  Which of the following is the most likely diagnosis?

A 60-year-old man is being evaluated due to nontender cervical lymphadenopathy that he first noticed while shaving.  A biopsy is performed, and microscopy findings are shown in the image below:

Further analysis would most likely demonstrate which of the following?