A 50-year-old woman with a history of systemic lupus erythematosus is admitted with fever, chills, vomiting, and burning pain when urinating.  Temperature is 39.3 C (102.7 F), blood pressure is 80/50 mm Hg, pulse is 120/min, and respirations are 20/min.  On examination, costovertebral angle tenderness is present.  The patient is given intravenous antibiotics.  Over the next several hours, she has decreased urine output despite aggressive intravenous hydration.  Blood is oozing around the central venous catheter.  Laboratory results are as follows:

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

A 9-year-old girl is brought to the emergency department due to prolonged epistaxis.  The girl says that she picked her nose immediately before the bleeding started.  Her parents decided to bring her to the emergency department after the epistaxis persisted for 20 minutes despite constant compression of the nasal alae.  The patient has had frequent nosebleeds that often last >10 minutes.  Her family history is significant for a grandfather who had an unspecified bleeding disorder.  Given the history of prolonged, recurrent nosebleeds, laboratory tests are ordered, and results are as follows:

Which of the following is the most likely diagnosis?

A 32-year-old woman experiences 3 episodes of deep venous thrombosis in a 6-year period.  She has a history of pulmonary embolism as well.  The patient’s partial thromboplastin time (PTT) is within normal limits, and remains unchanged when activated protein C is added to her plasma.  The most likely cause of this patient’s problem is:

A 23-year-old man comes to the office due to a left-sided jaw mass that has rapidly enlarged over the past several weeks.  The patient is an immigrant from East Africa.  He has no known medical problems and takes no medications.  Temperature is 37.1 C (98.8 F).  Physical examination shows a large left-sided tumor on his jaw with associated lymphadenopathy but no erythema or warmth.  The rest of the examination is unremarkable.  HIV testing is negative.  The lesion is biopsied, and numerous mitotic figures and apoptotic bodies are observed on histopathologic examination.  Which of the following genetic features is most likely to be present in the abnormal tissue?

A 68-year-old man comes to the office due to severe fatigue for the last few months.  He has also had 6.8-kg (15-lb) of unintentional weight loss over the same period.  The patient has no significant medical history and has not seen a physician in many years.  He takes no medications and does not use tobacco, alcohol, or illicit drugs.  Physical examination shows mucosal pallor with no scleral icterus.  The lungs are clear on auscultation, and heart sounds are normal.  Abdominal examination shows mild hepatomegaly and a markedly enlarged spleen.  Stool guaiac testing is negative.  Laboratory results show pancytopenia, and peripheral blood smear is shown below.

Bone marrow aspiration is attempted but yields no marrow, and a bone marrow biopsy is subsequently performed.  Which of the following findings is most likely to be observed in this patient’s bone marrow?

A 28-year-old man starts taking a prophylactic medication before leaving on a business trip to Costa Rica.  Five days later, he comes to the emergency department due to jaundice and dark urine.  Laboratory results are as follows:

A peripheral smear shows red blood cells with dark inclusions when stained with crystal violet, a supravital stain.  This patient’s condition most likely demonstrates which of the following inheritance patterns?

A 20-year-old man is brought to the emergency department due to fever, headache, and neck pain for the last day.  He has no significant medical history.  Temperature is 38.7 C (101.7 F), blood pressure is 120/72 mm Hg, pulse is 112/min, and respirations are 26/min.  There is neck stiffness and a petechial rash on the trunk.  Cerebrospinal fluid (CSF) analysis reveals the following:

CSF gram stain shows gram-negative diplococci.  In the emergency department, the patient’s hemodynamic status deteriorates rapidly.  Blood pressure drops to 80/50 mm Hg, and the venous access sites are oozing blood.  Which of the following findings is most likely to be seen on this patient’s peripheral blood smear?

A 23-year-old man comes to the emergency department due to 4 days of cramping abdominal pain.  He has been feeling weak for the past 2 weeks.  The patient tried over-the-counter antacids without relief.  He is an industrial laborer with no significant medical history or known allergies.  The patient lives in Massachusetts.  The patient’s parents have hypertension, and his siblings are healthy.  Temperature is 37.1 C (98.8 F).  Physical examination is unremarkable.  The patient’s peripheral blood smear is shown in the image below:

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

A 9-year-old boy with beta-thalassemia major is brought to the office for a routine red blood cell transfusion.  He was diagnosed at age 6 months and has since received numerous blood transfusions.  The patient has tolerated each transfusion well with no immediate reactions.  Vital signs are normal.  On physical examination, the patient has mild frontal bossing, hepatosplenomegaly, and jaundice.  A recent liver biopsy showed Kupffer cells containing coarse, yellow-brown cytoplasmic granules.  The granules are most likely composed of which of the following?

A 26-year-old woman is found to have a single amino acid substitution (glutamine for arginine) near the protein C cleavage site in her coagulation factor V gene product.  The patient is at greatest risk for developing which of the following conditions?

A 40-year-old man with end-stage renal disease due to type 1 diabetes mellitus is hospitalized for initiation of hemodialysis.  A tunneled dialysis catheter is inserted into the right internal jugular vein.  Before he is able to undergo dialysis treatment, the patient develops bleeding around the catheter exit site that is difficult to control.  He has not been treated recently with anticoagulants.  Further evaluation of this patient would most likely show which of the following laboratory abnormalities?

A 32-year-old man comes to the office due to progressive fatigue, easy bruising, and recurring episodes of gum bleeding.  Physical examination shows several ecchymoses in his lower extremities.  Laboratory studies are as follows:

Bone marrow biopsy is performed and fluorescence in situ hybridization studies reveal a balanced translocation between the long arms of chromosomes 15 and 17.  Which of the following proteins is most likely to be abnormal in the hematopoietic cells of this patient?

A 5-year-old boy is brought to the office by his parents who say that he “looks yellow” and has been uncharacteristically tired lately.  He has had upper respiratory tract infection symptoms for the past 3 days, including cough, rhinorrhea, sneezing, and sore throat.  The parents say that “a lot of kids at daycare have been sick lately.”  The patient has no prior medical problems.  He is consistently at the 50th percentile for height and weight.  He takes no medications, and his immunizations are up to date.  Pallor, scleral icterus, and palpable splenomegaly are seen on examination.  Laboratory results are as follows:

The patient recovers spontaneously after a few weeks.  Peripheral smear of the boy’s blood after recovery is shown in the exhibit.  Which of the following is the most likely cause of this patient’s condition?

A 57-year-old male presents to your office complaining of fatigue and low energy.  He also notes experiencing intermittent back pain that responds to ibuprofen.  He has no significant past medical history.  His family history is significant for his father dying of a heart attack at age 60.  Fecal occult blood testing is negative.  Laboratory studies reveal:

Plasma protein electrophoresis reveals a high peak corresponding to gamma-globulins.  The most likely diagnosis is:

A 3-year-old boy comes to the emergency department for evaluation of oral bleeding that began 1 hour after a tooth extraction.  The bleeding has persisted for approximately 30 minutes despite application of constant pressure with gauze.  He has no significant past medical or surgical history.  The patient takes no medications, and his vaccinations are up to date.  Blood pressure is 90/60 mm Hg and pulse is 100/min.  On physical examination, he has slow oozing of blood at the site of the dental extraction.  Family history is significant for a maternal uncle who suffered from recurrent bleeding into his joints.  Which of the following is most likely to be abnormal in this patient?

A 12-year-old boy is brought to the emergency room due to high fever, chest pains, and dyspnea.  Medical history is significant for 2 prior hospitalizations for abdominal pain that resolved with analgesics and hydration.  Evaluation today shows a hematocrit of 23% and reticulocyte count of 9%.  Several hours after being admitted to the hospital, the patient dies.  At autopsy, the spleen is small and firm.  This patient’s autopsy finding is most likely related to which of the following?

A 67-year-old man comes to the office due to severe fatigue for the past several months.  The patient cannot eat as much as he used to and has lost nearly 10 kg (22 lb) in the past 6 months.  Physical examination shows mucosal pallor, hepatomegaly, and massive splenomegaly.  Further evaluation reveals a gain-of-function mutation of a non-receptor tyrosine kinase protein in hematopoietic cells, leading to persistent activation of signal transducers and activators of transcription (STAT) proteins.  This patient is most likely suffering from which of the following disorders?

A 28-year-old woman comes to the office after finding a lump in her right breast.  Her mother died from ovarian cancer at age 34 and her maternal aunt died from breast cancer at age 32.  After an appropriate workup, the patient is diagnosed with breast cancer.  This patient most likely inherited a mutation in a gene normally responsible for which of the following processes?

A research scientist injects hepatocellular carcinoma cells into the liver parenchyma of an experimental guinea pig.  Serial observations show that the tumor cells progressively proliferate and invade the liver parenchyma to form a large mass.  After some time, malignant cells begin to penetrate the vascular basement membrane to gain access to the circulation.  During the process of basement membrane invasion, expression of which of the following substances is most likely to be increased in the tumor cells?

A 56-year-old man is evaluated for increased fatigability.  His past medical history is significant for diabetes mellitus, osteoarthritis, and severe aortic stenosis that required aortic valve replacement.  His peripheral blood smear is shown on the slide below.

Which of the following laboratory findings is most likely to be seen in this patient?

A 15-year-old boy is brought to the emergency department due to hemoptysis.  He has a history of amputation of the right lower extremity due to bone cancer.  Chest imaging reveals a lung mass.  Excisional biopsy of the mass shows sheets of uniform, round, small cells slightly larger than lymphocytes with scant, clear cytoplasm.  The cellular deposits are interrupted by vascular fibrous septa, with areas of hemorrhage and an abrupt transition from viable to necrotic cells.  A representative sample is shown in the image below.

Which of the following is the most likely diagnosis?

A 55-year-old man undergoing evaluation for fatigue and exertional dyspnea is diagnosed with macrocytic anemia.  Upper gastrointestinal endoscopy is consistent with atrophic gastritis.  He is prescribed intramuscular cyanocobalamin, with the resulting changes shown in the graph below:

The blue curve most likely corresponds to which of the following parameters?

An 18-year-old man is evaluated due to 3 months of lower extremity pain.  The pain is persistent and present both day and night.  He has no fever, chills, or history of leg trauma.  Imaging shows an expansile lesion of the distal femur.  Surgical resection is performed, and the specimen is shown below.

Mutations involving which of the following genes are most likely present in this patient?