Hem n Onc 8-8 (12)

Question 1

This patient presents with “B symptoms” (fever, night sweats, weight loss), signs of tumor lysis syndrome (oliguria), and a solitary jaw mass. This presentation, along with the results of the biopsy, suggest a diagnosis of Burkitt lymphoma, a lymphoma endemic to Africa and known to be associated with Epstein-Barr virus (EBV), which is a?

Answer 1

linear double-stranded DNA virus. The cytogenetic abnormality associated with Burkitt lymphoma is a t(8;14) translocation, in which the oncogene c-myc is placed under the expression of the immunoglobulin heavy-chain enhancer. In regions where the disease is endemic, children are typically infected with EBV by the age of 3 years, whereas infection typically occurs during adolescence in other regions.

Question 2

Since the Burkitt lymphoma tumor (like other aggressive lymphomas) exhibits a high mitotic index and has many apoptotic cells, the nuclear remnants are phagocytosed by macrophages. The phagocytes have abundant clear cytoplasm, creating the characteristic “starry sky” appearance, in which sheets of lymphocytes are interspersed with occasional macrophages, shown here.
The other viruses do not explain this patient’s symptoms:
An example of a circular partially double-stranded DNA virus is hepatitis B virus (HBV) which causes hepatitis.
Parvovirus B19 is?

Answer 2

a linear negative-sense single-stranded DNA virus that causes aplastic crises in sickle cell disease, erythema infectiosum (fifth disease) in children, and hydrops fetalis in fetuses.
Rotavirus is a linear positive-sense segmented double-stranded RNA virus that causes diarrhea in young children.
A linear positive-sense single-stranded RNA virus is hepatitis A. Individuals would likely present with gastrointestinal symptoms and will likely have had a history of recent travel.

Question 3

This patient presents with fever, hypotension (a common cause of syncope), dermatologic manifestations, and multisystem organ involvement. In this case, the lab values indicate hepatic, renal, and hematologic pathology. This clinical picture suggests a diagnosis of?

Answer 3

staphylococcal toxic shock syndrome. At least three of the following organ systems are typically involved:

Gastrointestinal (nausea/vomiting)
Muscular (myalgia with elevated creatine phosphokinase level)
Renal (elevated serum blood urea nitrogen and/or creatinine levels, or pyuria)
Hepatic (elevated aspartate aminotransferase, alanine aminotransferase, and/or bilirubin)
Hematologic (platelet count <100,000/mm3, leukocytosis)
Central nervous system (altered mentation/consciousness without focal findings).

Question 4

Disseminated intravascular coagulopathy (DIC) is often precipitated by gram-negative sepsis, but this patient’s lab values are inconsistent with DIC.
Hemolytic-uremic syndrome is seen in infants and children. It is characterized by a triad of hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia).
Rocky Mountain spotted fever (RMSF) usually causes a?

Answer 4

characteristic rash that involves the soles and palms. Symptoms include fever, headache, and muscle aches.

Stevens-Johnson syndrome is caused by a reaction to a medication or infection and manifests with a blistering rash on the skin.

Question 5

Staphylococcal toxic shock syndrome, caused by the massive cytokine release in response to exotoxin, may manifest systemically with?

Answer 5

fever and hypotension and involve multiple organ systems. Palmar/plantar desquamation is a hallmark feature, but it does not occur until approximately 2 weeks after onset.

Question 6

This patient received a bone marrow transplant, which puts her at risk for graft-versus-host disease. Graft-versus-host disease (GVHD) is a severe adverse immunologic reaction following this procedure, brought on by the reaction of donor T cells to recipient histoincompatible antigens. Cyclosporine is an ?

Answer 6

immunosuppressant and is often used in transplant recipients to control GVHD that may result from allogeneic bone transplant. The drug inhibits transcription of interleukin-2 and other cytokines important for T-lymphocyte activation, thus dampening the cell-mediated immune response. Cyclosporine has potential renal toxicity, which exacerbates this patient’s poor renal function, as evidenced by her high creatinine. Therefore, cyclosporine should be used with caution in this patient.

Question 7

Azathioprine is a prodrug for the immunosuppressant 6-mercaptopurine, but neither agent causes significant renal toxicity.
Dacluzimab is an interleukin-2 receptor antagonist and muromab-CD3 is a CD3 receptor antagonist. Neither causes marked renal impairment effects.
Mycophenolate is an IMPDH inhibitor preventing the synthesis of?

Answer 7

purines.

Like azathioprine, bone marrow suppression is the worrisome side effect, not renal toxicity.
Glucocorticosteroids like prednisone do not cause appreciable renal damage.

Question 8

This patient presents with complaints of fatigue, weight loss, and anorexia, along with a bulging mass extending from the left costal margin toward his right lower quadrant. The lymph node biopsy reveals a diffuse infiltrate of small, round, mature-appearing lymphocytes with minimal cytoplasm, which, along with his lymphadenopathy, is indicative of?

Answer 8

small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). The disease is a monoclonal B-lymphocyte neoplasm that affects the peripheral blood, bone marrow, and lymph nodes.

SLL-CLL is considered as one disease entity, with SLL representing disease restricted to tissues without blood involvement. Patients usually present with painless, generalized lymphadenopathy and splenomegaly and sometimes complain of fevers, night sweats, and weight loss.

Question 9

SLL can eventually transform to diffuse large B-cell lymphoma via the Richter process, but the morphology of the cells (large, basophilic cytoplasm, disorganized cell morphology) is not seen in this patient’s histologic slide.
Follicular lymphoma results in ?

Answer 9

nodular architecture but not diffuse growth of lymphocytes.
Infectious mononucleosis manifests with high fever, pharyngitis, and lymphadenopathy in adolescents and may lead to Burkitt lymphoma.

Question 10

This patient’s fatigue and pallor suggest anemia. His blood work demonstrates microcytic anemia (MCV < 80 fL) with basophilic stippling (RBCs with dark-purple, punctate inclusions). Together, these are highly suggestive of lead poisoning. His poor concentration and myalgias and his history of working in a shipyard further support the diagnosis of lead poisoning.

Lead poisoning inhibits?

Answer 10

aminolevulinic acid (ALA) dehydratase, an early enzyme in the hemoglobin synthesis pathway (shown above), resulting in the accumulation of ALA in the serum and urine. ALA synthase irreversibly catalyzes the first reaction of hemoglobin synthesis: glycine + succinyl-coenzyme A → ALA. This is the rate-limiting and committed step of heme synthesis (therefore, it would not cause accumulation of glycine or succinyl-coenzyme A).

Question 11

ALA dehydratase then catalyzes the second step in heme synthesis: 2 ALA → porphobilinogen (therefore, porphobilinogen levels would decrease [not increase] in lead poisoning). Elevated serum lead inhibits?

Answer 11

sulfhydryl-dependent enzymes, including ALA dehydratase (ferrochelatase, an enzyme later in the heme synthesis pathway, is also inactivated by high lead levels). Because ALA synthase’s action is irreversible, only ALA accumulates.
ALA is found only in the urine when blood lead levels are very high, so a thorough history and findings such as microcytic anemia and long-bone lead lines on X-ray are often more useful in making the diagnosis.
Uroporphyrinogen III levels increase in porphyria cutanea tarda.

Question 12

Prevalence is the measure of how commonly a disease or condition occurs in a population. In other words, prevalence is used as a way to describe how much of a disease is present in a population at a specific point in time. In this question we are asked to determine the prevalence of sickle cell disease in a specific population after 1 year. Let’s jot down some numbers. The initial prevalence is 10%; this means?

Answer 12

that of the total population there are (10% × 6000), or 600 cases of sickle cell disease. Over the course of the year there are 6 additional sickle cell births and 3 existing sickle cell patients who die, for a net gain of 3. Thus, in this population there are 603 sickle cell cases at the end of the year.

The total population also changes during the year. There are 100 births and 80 deaths, for a net gain of 20. Thus, the total population at the end of the year is 6020. Consequently, the prevalence in this population after one year is 603/6020, or 10.01%.

Question 13

If you chose 6/100 or 6/6020, then you are likely confusing prevalence with incidence. The incidence of sickle cell disease is calculated as the number of new cases (6 affected newborns) divided by the number of people at risk (100 newborns). Note that the denominator for incidence is only 100, because the original 6000 subjects were already genotyped and are not at risk.
The other choices are incorrect for various reasons:

3/6020 describes?

Answer 13

the net gain in the number of cases divided by the population at risk; it doesn’t take into account the initial 600 cases in the numerator.
603/6000 does not take into account the births and deaths that occurred during the year, which would affect the denominator.
606/6100 fails to reflect the deaths that occurred during the year, which would affect both the total number of cases and the population at the end of the year.

Question 14

HIV-positive patients who stop their HAART are at risk of developing viral rebound and AIDS-defining illness. This patient has the cutaneous lesions of Kaposi sarcoma, which are malignant proliferations of spindle cells and endothelial cells. Kaposi sarcoma arises in the setting of human herpes virus 8 infection in the immunocompromised host and is an AIDS-defining illness in patients with HIV infection.

Although cutaneous lesions are striking, lesions can appear in and affect any organ system in the body, most commonly?

Answer 14

the lungs, gastrointestinal tract, and biliary tree. Fifty percent of patients have gastrointestinal involvement, which often presents as mucosal bleeding leading to hematochezia, hematemesis, and/or melena (black stools).

Question 15

Note that severely immunocompromised patients may also develop bacillary angiomatosis, a severe consequence of Bartonella infection. The skin eruptions may look very much like Kaposi sarcoma, but there are several key differences. A biopsy will reveal Kaposi sarcoma to be a vascular tumor, whereas bacteria will be identified on a skin biopsy specimen from a patient with bacillary angiomatosis.
Staining with Warthin-Starry special stain highlights?

Answer 15

the bacterial colonies. Seizures in patients with HIV infection are not associated with Kaposi sarcoma, which very rarely manifests in the central nervous system. Although patients with HIV infection may have arthritis or bradycardia, arthritis and bradycardia are not caused by Kaposi sarcoma. Alopecia and excessive tearing are not associated with Kaposi sarcoma in the setting of HIV infection.

Question 16

The patient’s symptoms of fatigue, dizziness, and palpitations combined with a low hemoglobin points to a diagnosis of anemia. A major classification of anemia is based on the red blood cell size: macrocytic (>100 fL) or microcytic (<100 fL). As this patient’s RBC shows an MCV of 105.9, she has macrocytic anemia, specifically a megaloblastic anemia.

Megaloblastic anemia has two principal causes: vitamin B12 (cobalamin) deficiency and folate deficiency. This patient is eating very little, including only rice crackers, which are probably not fortified, so her megaloblastic anemia is most likely due to?

Answer 16

folate deficiency. Body stores of folate are minimal and can be depleted within a few months if intake is inadequate. Leafy green vegetables are a natural source of folate. In developed nations, flour is fortified with folate, which has dramatically decreased the incidence of folate deficiency, though it is still the most common vitamin deficiency in the United States.

Question 17

The tetrahydrofolate form of folate (folic acid) functions as an intermediate in the transfer of 1-carbon units, which is important for purine synthesis. Folate deficiency does not cause?

Answer 17

neurologic symptoms. Causes of folate deficiency include malnutrition (eg, alcoholism), malabsorption, antifolates (eg, methotrexate, trimethoprim, phenytoin), and increased requirement (eg, hemolytic anemia, pregnancy). Lab findings include increased homocysteine but normal methylmalonic acid levels, separating this from the megaloblastic anemia caused by vitamin B12 deficiency.

Question 18

Defects in the other processes listed are associated with different conditions:

A defect in heme synthesis is often due to lack of iron, since iron is the essential element of heme. A deficiency can lead to anemia.
Glutathione synthesis defects can result in increased susceptibility to oxidative stress, formation of Heinz bodies, and development of a normocytic (MCV between 70–100 fL), hemolytic anemia with characteristic “bite” cells.
Isomerization of methylmalonyl-CoA is a step in the process of forming succinyl-CoA, which is important for?

Answer 18

heme biosynthesis. Since vitamin B12 is a cofactor in this process, deficiency in B12 leads to deficiency in succinyl-CoA and DNA synthesis, resulting in macrocytic anemia.
Defects in synthesis of the spectrin-actin cytoskeleton due to mutations in the genes for these proteins result in reduced membrane stability and the loss of membrane fragments, resulting in anemia.
Problems with synthesis of β-globin chains can be caused by either β-thalassemia or sickle cell anemia.

Question 19

This patient presents with abdominal pain, new facial hair, and a 12-lb weight loss over the past month. Ultrasonogram shows masses in both ovaries, suggestive of malignancy. The ovaries are a potential site of visceral metastases of adenocarcinomas of the gastrointestinal tract (stomach, pancreas, and gallbladder) or the breast. The most common primary tumor site is the stomach. These metastases are often bilateral in the ovaries.

Krukenberg tumors are malignancies in the ovaries that are metastases from a primary tumor, usually located in ?

Answer 19

the gastrointestinal tract. Patients present with abdominal pain, as in this patient, as well as bloating and ascites. Occasionally, patients may also have hirsutism. Histologically, the overproduction of mucin pushes the nucleus to the side of the cell, producing the characteristic “signet ring” morphology of gastric cancer and Krukenberg tumor, as shown in this image.

Question 20

Omeprazole is a proton pump inhibitor that acts at the hydrogen ion pumps in the stomach. It is commonly used for gastroesophageal reflux disease and gastric/duodenal ulcers.
Albuterol is a bronchodilator that acts on?

Answer 20

the lung, but lung cancers rarely metastasize to the ovaries. Methimazole and acetylcysteine act on the thyroid and liver, respectively. Phenytoin is an antiepileptic drug that acts on the brain, but brain tumors are unlikely to spread to the ovaries.

Question 21

The patient presents with fatigue, arthritis, hyperpigmentation of the skin, as well as elevated liver enzymes. These signs and symptoms, combined with diabetes, make hereditary hemochromatosis a likely diagnosis. Hereditary hemochromatosis is an autosomal recessive condition that is most common in individuals of Northern European and Celtic descent. Hereditary hemochromatosis is caused by a mutation in the HFE gene. The mutated HFE protein decreases the affinity of the transferrin receptor for transferrin, leading to overactive intestinal and tissue iron uptake.

Hemochromatosis typically causes?

Answer 21

parenchymal end-organ damage in the liver (elevated LFTs), pancreas (increased blood glucose), and heart via excess iron deposition. Patients often present with “bronze diabetes” due to darker pigment secondary to increased melanin and iron deposition in the skin. Depending on the area of increased iron deposition, patients may also present with fatigue, arthralgias, impotence (in males), and ECG changes.
Lab studies in hemochromatosis show a decreased total iron-binding capacity (TIBC), since bloodstream transferrin is saturated in the iron overload state.

Question 22

Decreased serum ceruloplasmin levels are seen in patients with Wilson disease.
Patients typically present with chronic hepatitis, cirrhosis, tremor, personality changes, ataxia, and Kayser-Fleischer rings on ophthalmoscopic exam. On the other hand, ferritin and transferrin levels would be increased?

Answer 22

in this patient because of increased serum iron concentration.

Question 23

This patient is presenting with the signs and symptoms of pernicious anemia. This autoimmune condition is caused by the production of autoantibodies that lead to atrophic gastritis and intrinsic factor deficiency. With a deficiency in intrinsic factor levels, the body cannot properly absorb vitamin B12. Unlike folate deficiency, vitamin B12 deficiency can cause neurologic abnormalities such as ataxic gait, hyperreflexia, and loss of position and vibration sensation, as well as mental changes such as paranoia, dementia, or irritability (as seen in this patient). These abnormalities are due to vitamin B12’s involvement in myelin synthesis pathways.

Patients with vitamin B12 deficiency present ?

Answer 23

neurologically as having subacute combined degeneration involving the dorsal (sensory) and lateral (motor) columns of the spinal cord. These are all consistent with the patient’s history of unsteady gait, feeling more irritable than usual, positive extensor plantar reflex, and a positive Romberg test. The Romberg test is conducted by asking the patient to stand erect with feet together and eyes closed; the test is positive when the patient sways irregularly or even topples over, indicating neurologic abnormality.

Question 24

Furthermore, this patient exhibits signs and symptoms of anemia, including fatigue and conjunctival pallor. The peripheral blood smear will often show evidence of a megaloblastic anemia, including macrocytic RBCs and hypersegmented polymorphonuclear leukocytes (an elevated fraction of neutrophils having 6 or more lobes). Treatment involves vitamin B12 injections.

The other answer choices can be ruled out by their lack of neurologic symptoms. RBCs lacking central pallor (spherocytes) are seen in hereditary spherocytosis. RBC microcytosis (low mean corpuscular volume) and target cells (RBCs with a central density surrounded by a ring of pallor) can be seen?

Answer 24

in the thalassemias, among other conditions. (RBC microcytosis can also be seen in lead poisoning, and lead poisoning is associated with neuropathy; but lead poisoning is more common in children than adults.) And of course, sickle-shaped RBCs are a feature of sickle cell disease.