Clinical Review

CASE 1: Preterm labor with cervical changes

Ms. M, a 42-year-old woman pregnant with her second child, begins having contractions at 30 weeks’ gestation. Examination reveals that her cervix is dilated 2 cm and effaced 50%. She is given subcutaneous terbutaline to suppress her contractions. Thirty minutes later, she complains of shortness of breath and chest pain. An electrocardiogram reveals depression of the ST segment, and a chest radiograph shows mild pulmonary edema.

How should her symptoms be managed?

Preterm labor precedes delivery in about 50% of preterm births. Approximately 33% of women who have preterm labor will experience spontaneous resolution, and more than 50% of women who have preterm labor will deliver at term. Although the use of tocolytic therapy has proved to be effective at temporarily ­suppressing uterine activity, it has not been shown to delay delivery for more than a few hours or days.¹

The American College of Obstetricians and Gynecologists (ACOG) recommends the use of tocolytics only when a delay in labor for approximately 48 hours would improve outcome. Therefore, tocolytic therapy should be reserved for the following circumstances:

• to stop the progress of labor long enough to administer antenatal corticosteroid therapy
• to prolong pregnancy when there is an underlying self-limiting condition that can cause labor, such as pyelonephritis
• to provide time for safe transport to a facility with a higher level of neonatal care.²

Tocolytics are generally not indicated before the fetus is viable, although we lack data from randomized, controlled trials to support a specific recommendation. The approach is clearer when the fetus is near the upper limits of viability. Most studies suggest that 34 weeks’ gestation is the threshold at which the perinatal morbidity and mortality associated with delivery are too low to justify the cost and potential complications of tocolysis.³

Women who experience preterm labor without cervical changes generally should not be treated with tocolytics.² Contraindications to tocolytic therapy include:

• lethal fetal anomaly
• nonreassuring fetal status
• maternal disease
• maternal hemorrhage with hemodynamic instability.

Beta-adrenergic agonists carry many risks

These agents have been studied in several randomized, controlled trials. Although ritodrine was approved as tocolytic therapy by the US Food and Drug Administration (FDA), it has since been removed from the US market. Terbutaline is still available but lacks FDA approval as a tocolytic.

Maternal side effects associated with beta-adrenergic agonists are thought to arise from stimulation of the beta-1 and beta-2 adrenergic receptors. Stimulation of the former increases maternal heart rate and stroke volume, whereas stimulation of the beta-2 adrenergic receptors causes the relaxation of smooth muscle, including the muscles of the myometrium, blood vessels, and bronchial tree. The resulting symptoms may include maternal tachycardia, cardiac arrhythmias, palpitations, and metabolic aberrations (including hyperglycemia, hypokalemia, and hypotension). Common symptoms associated with the administration of a beta-adrenergic agonist include tremor, shortness of breath, and chest discomfort.⁴ Although pulmonary edema and myocardial ischemia are uncommon, they can occur even when there is no history of underlying maternal disease.

Terbutaline has been linked to maternal deaths

Sixteen maternal deaths were reported following initial marketing of terbutaline in 1976 until 2009. Three of the 16 cases involved outpatient use of terbutaline administered by a subcutaneous pump, and nine cases involved use of oral terbutaline alone or in addition to subcutaneous or IV terbutaline. In addition, 12 cases of serious maternal cardiovascular events were reported in association with terbutaline. These events included cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia.

Because of these events, the FDA issued a black box warning for terbutaline that prohibits its use in the treatment of preterm labor for longer than 48 to 72 hours in the inpatient or outpatient setting because of the potential for serious maternal heart problems and death.⁵ Oral terbutaline should be avoided entirely in the prevention and treatment of preterm labor. However, the use of terbutaline for the management of acute tachysystole with an abnormal fetal heart-rate (FHR) pattern remains a reasonable course of treatment.⁶

Fetal tachycardia is the most common side effect of beta-adrenergic receptor agonists. For this reason, use of these drugs is not recommended when changes in FHR may be the first sign of fetal compromise, such as in patients with hemorrhage or infection. Neonatal hypoglycemia may also occur if maternal hyperglycemia is not controlled.⁷

Case 1 Resolved

Terbutaline is discontinued, and the patient’s pulmonary edema is treated with a single dose of furosemide. Electrolyte abnormalities resolve with discontinuation of medication. The patient stabilizes. Once her cardiorespiratory status improves, her contractions lessen and the cervix remains unchanged. She requires no further tocolysis and is discharged home. She presents again at 38 weeks in spontaneous labor.

CASE 2: Preterm labor treated with indomethacin

Ms. J, age 23, is 26 weeks’ pregnant with her first child. When she experienced preterm labor at 24.5 weeks’ gestation, she was given indomethacin. Now, ultrasonographic imaging reveals decreased amniotic fluid volume.

How should she be managed?

Indomethacin is a cyclooxygenase (COX) inhibitor. These drugs reduce prostaglandin production through the general inhibition of cyclooxygenase or by a specific receptor.⁸ Indomethacin is the most commonly used tocolytic in this class. It is a nonspecific COX inhibitor, as opposed to a COX-2 inhibitor. The latter has been associated with serious adverse outcomes in the nonobstetric population. COX-2 inhibitors now carry a black box warning or are no longer available.

Maternal contraindications for COX inhibitors include asthma, bleeding disorders, and significant renal dysfunction.

Although maternal side effects with COX inhibitors are usually mild, fetal side effects may be serious enough to cause perinatal morbidity or death.⁹

How indomethacin can lead to oligohydramnios

Maternal administration of indomethacin or ibuprofen can reduce fetal urine output and decrease the volume of amniotic fluid. In most cases, oligohydramnios occurs when indomethacin or ibuprofen has been given for more than 72 hours. For this reason, long-term use of a COX inhibitor should be accompanied by frequent monitoring of amniotic fluid volume by ultrasonography.

The most serious fetal complication associated with prolonged indomethacin administration (longer than 72 hours) is premature constriction of the ductus arteriosus. Ductal constriction appears to be contingent on gestational age. It has been described as early as 24 weeks’ gestation but is most common after 31 or 32 weeks. Therefore, indomethacin is not recommended for use after 32 weeks’ gestation.¹⁰

CASE 2 Resolved

The indomethacin is discontinued as soon as the decreased amniotic fluid is noted. The fluid volume returns to normal over the next 3 to 5 days. Because of the early gestational age, nifedipine is given to suppress contractions, and the patient has no further complications.

CASE 3: Preterm labor and magnesium intoxication

Ms. K experiences contractions and rapid cervical change at 32 weeks’ gestation. She is given magnesium for the preterm labor and fetal neuroprophylaxis, with nifedipine, a calcium-channel blocker, added as second-line tocolysis. Approximately 8 hours later, she reports difficulty breathing and moving.

How should her obstetrician proceed?

Calcium-channel blockers such as nifedipine are used for acute and maintenance tocolysis. This class of drugs is often selected for its relative ease of use and safety, as it has few maternal and fetal side effects. However, concomitant use of a calcium-channel blocker and magnesium sulfate can sometimes lead to neuromuscular blockade and significant respiratory depression, even necessitating mechanical ventilation.⁹ Treatment of these effects includes IV administration of 10% calcium gluconate (5–10 mEq), which usually reverses respiratory depression and heart block caused by magnesium intoxication. In extreme cases, peritoneal dialysis or hemodialysis may be required.

CASE 3 Resolved

The patient is given 10% calcium gluconate in the dosage described above, and she stabilizes. However, her contractions continue and she delivers at 32 weeks’ gestation. The infant does well in the NICU.

CASE 4: Preterm labor in a woman with kidney dysfunction

Ms. F, age 40, presents at 30 weeks’ gestation with regular contractions and cervical dilation of more than 3 cm. She also reports a history of kidney disease.

What steps are recommended prior to the initiation of magnesium therapy?

Magnesium sulfate has been used for more than 40 years to treat preterm labor and is still considered a first-line therapy in many centers. Although maternal side effects usually are mild, an adverse event may occur if the patient is not monitored carefully. An absence of deep-tendon reflexes should alert the clinician that magnesium levels need to be measured. Reflexes usually are lost at a serum level of 10 mEq/L or higher. When the magnesium level exceeds 13 mEq/L, cardiac arrest is a risk. IV calcium should be administered immediately in such patients.

Magnesium should be used with caution in patients with myocardial compromise. Because magnesium is eliminated by the kidneys, women with impaired renal function may experience magnesium toxicity at normal doses. If a patient has a creatinine level above 1 mg/dL, consider alternative treatment for her preterm labor. If magnesium is given, the normal loading dose (4–6 g) is appropriate, but the maintenance dose should be reduced.¹¹

Fetal effects of magnesium sulfate

Recent studies indicate that predelivery magnesium may offer fetal neuroprotection. The minimum duration of administration for such neuroprotection is unknown but is less than 24 hours.⁸

Although magnesium can alter FHR patterns slightly, these changes are not clinically significant. Magnesium can also cause mild neonatal suppression at the time of delivery, but its effects quickly resolve with appropriate neonatal resuscitation. Long-term (>5 days) therapy is not recommended.

In May 2013, the FDA issued a warning about the risk of neonatal complications with long-term maternal magnesium administration. These complications include osteopenia, low calcium, and bone fracture. The pregnancy category for magnesium sulfate will be changed from “A” to “D” because of these teratogenic effects.¹²

CASE 4 Resolved

Because magnesium is mainly cleared by renal excretion, the clinician administers the medication with caution in this patient with reduced renal function. The clinician administers the same 4- to 6-g bolus that would be given a patient with normal kidney function, but the maintenance dose is reduced to 1 g. Magnesium levels are obtained every 12 hours or when clinically indicated.

Bottom line: Be ready to act

The short-term use of tocolytic therapy usually is not associated with maternal or fetal complications. After initial administration, maintenance tocolytic therapy probably does not prolong gestation.

Given the potential for harm without additional fetal benefit associated with extended therapy, I recommend that clinicians follow current clinical guidelines from ACOG for use of tocolytic agents. In the process, be vigilant for complications and be ready to act appropriately. Keep maternal and fetal conditions in mind when selecting a tocolytic agent.

CASE 1: Preterm labor with cervical changes

Ms. M, a 42-year-old woman pregnant with her second child, begins having contractions at 30 weeks’ gestation. Examination reveals that her cervix is dilated 2 cm and effaced 50%. She is given subcutaneous terbutaline to suppress her contractions. Thirty minutes later, she complains of shortness of breath and chest pain. An electrocardiogram reveals depression of the ST segment, and a chest radiograph shows mild pulmonary edema.

How should her symptoms be managed?

Preterm labor precedes delivery in about 50% of preterm births. Approximately 33% of women who have preterm labor will experience spontaneous resolution, and more than 50% of women who have preterm labor will deliver at term. Although the use of tocolytic therapy has proved to be effective at temporarily ­suppressing uterine activity, it has not been shown to delay delivery for more than a few hours or days.¹

The American College of Obstetricians and Gynecologists (ACOG) recommends the use of tocolytics only when a delay in labor for approximately 48 hours would improve outcome. Therefore, tocolytic therapy should be reserved for the following circumstances:

• to stop the progress of labor long enough to administer antenatal corticosteroid therapy
• to prolong pregnancy when there is an underlying self-limiting condition that can cause labor, such as pyelonephritis
• to provide time for safe transport to a facility with a higher level of neonatal care.²

Tocolytics are generally not indicated before the fetus is viable, although we lack data from randomized, controlled trials to support a specific recommendation. The approach is clearer when the fetus is near the upper limits of viability. Most studies suggest that 34 weeks’ gestation is the threshold at which the perinatal morbidity and mortality associated with delivery are too low to justify the cost and potential complications of tocolysis.³

Women who experience preterm labor without cervical changes generally should not be treated with tocolytics.² Contraindications to tocolytic therapy include:

• lethal fetal anomaly
• nonreassuring fetal status
• maternal disease
• maternal hemorrhage with hemodynamic instability.

Beta-adrenergic agonists carry many risks

These agents have been studied in several randomized, controlled trials. Although ritodrine was approved as tocolytic therapy by the US Food and Drug Administration (FDA), it has since been removed from the US market. Terbutaline is still available but lacks FDA approval as a tocolytic.

Maternal side effects associated with beta-adrenergic agonists are thought to arise from stimulation of the beta-1 and beta-2 adrenergic receptors. Stimulation of the former increases maternal heart rate and stroke volume, whereas stimulation of the beta-2 adrenergic receptors causes the relaxation of smooth muscle, including the muscles of the myometrium, blood vessels, and bronchial tree. The resulting symptoms may include maternal tachycardia, cardiac arrhythmias, palpitations, and metabolic aberrations (including hyperglycemia, hypokalemia, and hypotension). Common symptoms associated with the administration of a beta-adrenergic agonist include tremor, shortness of breath, and chest discomfort.⁴ Although pulmonary edema and myocardial ischemia are uncommon, they can occur even when there is no history of underlying maternal disease.

Terbutaline has been linked to maternal deaths

Sixteen maternal deaths were reported following initial marketing of terbutaline in 1976 until 2009. Three of the 16 cases involved outpatient use of terbutaline administered by a subcutaneous pump, and nine cases involved use of oral terbutaline alone or in addition to subcutaneous or IV terbutaline. In addition, 12 cases of serious maternal cardiovascular events were reported in association with terbutaline. These events included cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia.

Because of these events, the FDA issued a black box warning for terbutaline that prohibits its use in the treatment of preterm labor for longer than 48 to 72 hours in the inpatient or outpatient setting because of the potential for serious maternal heart problems and death.⁵ Oral terbutaline should be avoided entirely in the prevention and treatment of preterm labor. However, the use of terbutaline for the management of acute tachysystole with an abnormal fetal heart-rate (FHR) pattern remains a reasonable course of treatment.⁶

Fetal tachycardia is the most common side effect of beta-adrenergic receptor agonists. For this reason, use of these drugs is not recommended when changes in FHR may be the first sign of fetal compromise, such as in patients with hemorrhage or infection. Neonatal hypoglycemia may also occur if maternal hyperglycemia is not controlled.⁷

Case 1 Resolved

Terbutaline is discontinued, and the patient’s pulmonary edema is treated with a single dose of furosemide. Electrolyte abnormalities resolve with discontinuation of medication. The patient stabilizes. Once her cardiorespiratory status improves, her contractions lessen and the cervix remains unchanged. She requires no further tocolysis and is discharged home. She presents again at 38 weeks in spontaneous labor.

CASE 2: Preterm labor treated with indomethacin

Ms. J, age 23, is 26 weeks’ pregnant with her first child. When she experienced preterm labor at 24.5 weeks’ gestation, she was given indomethacin. Now, ultrasonographic imaging reveals decreased amniotic fluid volume.

How should she be managed?

Indomethacin is a cyclooxygenase (COX) inhibitor. These drugs reduce prostaglandin production through the general inhibition of cyclooxygenase or by a specific receptor.⁸ Indomethacin is the most commonly used tocolytic in this class. It is a nonspecific COX inhibitor, as opposed to a COX-2 inhibitor. The latter has been associated with serious adverse outcomes in the nonobstetric population. COX-2 inhibitors now carry a black box warning or are no longer available.

Maternal contraindications for COX inhibitors include asthma, bleeding disorders, and significant renal dysfunction.

Although maternal side effects with COX inhibitors are usually mild, fetal side effects may be serious enough to cause perinatal morbidity or death.⁹

How indomethacin can lead to oligohydramnios

Maternal administration of indomethacin or ibuprofen can reduce fetal urine output and decrease the volume of amniotic fluid. In most cases, oligohydramnios occurs when indomethacin or ibuprofen has been given for more than 72 hours. For this reason, long-term use of a COX inhibitor should be accompanied by frequent monitoring of amniotic fluid volume by ultrasonography.

The most serious fetal complication associated with prolonged indomethacin administration (longer than 72 hours) is premature constriction of the ductus arteriosus. Ductal constriction appears to be contingent on gestational age. It has been described as early as 24 weeks’ gestation but is most common after 31 or 32 weeks. Therefore, indomethacin is not recommended for use after 32 weeks’ gestation.¹⁰

CASE 2 Resolved

The indomethacin is discontinued as soon as the decreased amniotic fluid is noted. The fluid volume returns to normal over the next 3 to 5 days. Because of the early gestational age, nifedipine is given to suppress contractions, and the patient has no further complications.

CASE 3: Preterm labor and magnesium intoxication

Ms. K experiences contractions and rapid cervical change at 32 weeks’ gestation. She is given magnesium for the preterm labor and fetal neuroprophylaxis, with nifedipine, a calcium-channel blocker, added as second-line tocolysis. Approximately 8 hours later, she reports difficulty breathing and moving.

How should her obstetrician proceed?

Calcium-channel blockers such as nifedipine are used for acute and maintenance tocolysis. This class of drugs is often selected for its relative ease of use and safety, as it has few maternal and fetal side effects. However, concomitant use of a calcium-channel blocker and magnesium sulfate can sometimes lead to neuromuscular blockade and significant respiratory depression, even necessitating mechanical ventilation.⁹ Treatment of these effects includes IV administration of 10% calcium gluconate (5–10 mEq), which usually reverses respiratory depression and heart block caused by magnesium intoxication. In extreme cases, peritoneal dialysis or hemodialysis may be required.

CASE 3 Resolved

The patient is given 10% calcium gluconate in the dosage described above, and she stabilizes. However, her contractions continue and she delivers at 32 weeks’ gestation. The infant does well in the NICU.

CASE 4: Preterm labor in a woman with kidney dysfunction

Ms. F, age 40, presents at 30 weeks’ gestation with regular contractions and cervical dilation of more than 3 cm. She also reports a history of kidney disease.

What steps are recommended prior to the initiation of magnesium therapy?

Magnesium sulfate has been used for more than 40 years to treat preterm labor and is still considered a first-line therapy in many centers. Although maternal side effects usually are mild, an adverse event may occur if the patient is not monitored carefully. An absence of deep-tendon reflexes should alert the clinician that magnesium levels need to be measured. Reflexes usually are lost at a serum level of 10 mEq/L or higher. When the magnesium level exceeds 13 mEq/L, cardiac arrest is a risk. IV calcium should be administered immediately in such patients.

Magnesium should be used with caution in patients with myocardial compromise. Because magnesium is eliminated by the kidneys, women with impaired renal function may experience magnesium toxicity at normal doses. If a patient has a creatinine level above 1 mg/dL, consider alternative treatment for her preterm labor. If magnesium is given, the normal loading dose (4–6 g) is appropriate, but the maintenance dose should be reduced.¹¹

Fetal effects of magnesium sulfate

Recent studies indicate that predelivery magnesium may offer fetal neuroprotection. The minimum duration of administration for such neuroprotection is unknown but is less than 24 hours.⁸

Although magnesium can alter FHR patterns slightly, these changes are not clinically significant. Magnesium can also cause mild neonatal suppression at the time of delivery, but its effects quickly resolve with appropriate neonatal resuscitation. Long-term (>5 days) therapy is not recommended.

In May 2013, the FDA issued a warning about the risk of neonatal complications with long-term maternal magnesium administration. These complications include osteopenia, low calcium, and bone fracture. The pregnancy category for magnesium sulfate will be changed from “A” to “D” because of these teratogenic effects.¹²

CASE 4 Resolved

Because magnesium is mainly cleared by renal excretion, the clinician administers the medication with caution in this patient with reduced renal function. The clinician administers the same 4- to 6-g bolus that would be given a patient with normal kidney function, but the maintenance dose is reduced to 1 g. Magnesium levels are obtained every 12 hours or when clinically indicated.

Bottom line: Be ready to act

The short-term use of tocolytic therapy usually is not associated with maternal or fetal complications. After initial administration, maintenance tocolytic therapy probably does not prolong gestation.

Given the potential for harm without additional fetal benefit associated with extended therapy, I recommend that clinicians follow current clinical guidelines from ACOG for use of tocolytic agents. In the process, be vigilant for complications and be ready to act appropriately. Keep maternal and fetal conditions in mind when selecting a tocolytic agent.

CASE 1: Preterm labor with cervical changes

Ms. M, a 42-year-old woman pregnant with her second child, begins having contractions at 30 weeks’ gestation. Examination reveals that her cervix is dilated 2 cm and effaced 50%. She is given subcutaneous terbutaline to suppress her contractions. Thirty minutes later, she complains of shortness of breath and chest pain. An electrocardiogram reveals depression of the ST segment, and a chest radiograph shows mild pulmonary edema.

How should her symptoms be managed?

Preterm labor precedes delivery in about 50% of preterm births. Approximately 33% of women who have preterm labor will experience spontaneous resolution, and more than 50% of women who have preterm labor will deliver at term. Although the use of tocolytic therapy has proved to be effective at temporarily ­suppressing uterine activity, it has not been shown to delay delivery for more than a few hours or days.¹

The American College of Obstetricians and Gynecologists (ACOG) recommends the use of tocolytics only when a delay in labor for approximately 48 hours would improve outcome. Therefore, tocolytic therapy should be reserved for the following circumstances:

• to stop the progress of labor long enough to administer antenatal corticosteroid therapy
• to prolong pregnancy when there is an underlying self-limiting condition that can cause labor, such as pyelonephritis
• to provide time for safe transport to a facility with a higher level of neonatal care.²

Tocolytics are generally not indicated before the fetus is viable, although we lack data from randomized, controlled trials to support a specific recommendation. The approach is clearer when the fetus is near the upper limits of viability. Most studies suggest that 34 weeks’ gestation is the threshold at which the perinatal morbidity and mortality associated with delivery are too low to justify the cost and potential complications of tocolysis.³

Women who experience preterm labor without cervical changes generally should not be treated with tocolytics.² Contraindications to tocolytic therapy include:

• lethal fetal anomaly
• nonreassuring fetal status
• maternal disease
• maternal hemorrhage with hemodynamic instability.

Beta-adrenergic agonists carry many risks

These agents have been studied in several randomized, controlled trials. Although ritodrine was approved as tocolytic therapy by the US Food and Drug Administration (FDA), it has since been removed from the US market. Terbutaline is still available but lacks FDA approval as a tocolytic.

Maternal side effects associated with beta-adrenergic agonists are thought to arise from stimulation of the beta-1 and beta-2 adrenergic receptors. Stimulation of the former increases maternal heart rate and stroke volume, whereas stimulation of the beta-2 adrenergic receptors causes the relaxation of smooth muscle, including the muscles of the myometrium, blood vessels, and bronchial tree. The resulting symptoms may include maternal tachycardia, cardiac arrhythmias, palpitations, and metabolic aberrations (including hyperglycemia, hypokalemia, and hypotension). Common symptoms associated with the administration of a beta-adrenergic agonist include tremor, shortness of breath, and chest discomfort.⁴ Although pulmonary edema and myocardial ischemia are uncommon, they can occur even when there is no history of underlying maternal disease.

Terbutaline has been linked to maternal deaths

Sixteen maternal deaths were reported following initial marketing of terbutaline in 1976 until 2009. Three of the 16 cases involved outpatient use of terbutaline administered by a subcutaneous pump, and nine cases involved use of oral terbutaline alone or in addition to subcutaneous or IV terbutaline. In addition, 12 cases of serious maternal cardiovascular events were reported in association with terbutaline. These events included cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia.

Because of these events, the FDA issued a black box warning for terbutaline that prohibits its use in the treatment of preterm labor for longer than 48 to 72 hours in the inpatient or outpatient setting because of the potential for serious maternal heart problems and death.⁵ Oral terbutaline should be avoided entirely in the prevention and treatment of preterm labor. However, the use of terbutaline for the management of acute tachysystole with an abnormal fetal heart-rate (FHR) pattern remains a reasonable course of treatment.⁶

Fetal tachycardia is the most common side effect of beta-adrenergic receptor agonists. For this reason, use of these drugs is not recommended when changes in FHR may be the first sign of fetal compromise, such as in patients with hemorrhage or infection. Neonatal hypoglycemia may also occur if maternal hyperglycemia is not controlled.⁷

Case 1 Resolved

Terbutaline is discontinued, and the patient’s pulmonary edema is treated with a single dose of furosemide. Electrolyte abnormalities resolve with discontinuation of medication. The patient stabilizes. Once her cardiorespiratory status improves, her contractions lessen and the cervix remains unchanged. She requires no further tocolysis and is discharged home. She presents again at 38 weeks in spontaneous labor.

CASE 2: Preterm labor treated with indomethacin

Ms. J, age 23, is 26 weeks’ pregnant with her first child. When she experienced preterm labor at 24.5 weeks’ gestation, she was given indomethacin. Now, ultrasonographic imaging reveals decreased amniotic fluid volume.

How should she be managed?

Indomethacin is a cyclooxygenase (COX) inhibitor. These drugs reduce prostaglandin production through the general inhibition of cyclooxygenase or by a specific receptor.⁸ Indomethacin is the most commonly used tocolytic in this class. It is a nonspecific COX inhibitor, as opposed to a COX-2 inhibitor. The latter has been associated with serious adverse outcomes in the nonobstetric population. COX-2 inhibitors now carry a black box warning or are no longer available.

Maternal contraindications for COX inhibitors include asthma, bleeding disorders, and significant renal dysfunction.

Although maternal side effects with COX inhibitors are usually mild, fetal side effects may be serious enough to cause perinatal morbidity or death.⁹

How indomethacin can lead to oligohydramnios

Maternal administration of indomethacin or ibuprofen can reduce fetal urine output and decrease the volume of amniotic fluid. In most cases, oligohydramnios occurs when indomethacin or ibuprofen has been given for more than 72 hours. For this reason, long-term use of a COX inhibitor should be accompanied by frequent monitoring of amniotic fluid volume by ultrasonography.

The most serious fetal complication associated with prolonged indomethacin administration (longer than 72 hours) is premature constriction of the ductus arteriosus. Ductal constriction appears to be contingent on gestational age. It has been described as early as 24 weeks’ gestation but is most common after 31 or 32 weeks. Therefore, indomethacin is not recommended for use after 32 weeks’ gestation.¹⁰

CASE 2 Resolved

The indomethacin is discontinued as soon as the decreased amniotic fluid is noted. The fluid volume returns to normal over the next 3 to 5 days. Because of the early gestational age, nifedipine is given to suppress contractions, and the patient has no further complications.

CASE 3: Preterm labor and magnesium intoxication

Ms. K experiences contractions and rapid cervical change at 32 weeks’ gestation. She is given magnesium for the preterm labor and fetal neuroprophylaxis, with nifedipine, a calcium-channel blocker, added as second-line tocolysis. Approximately 8 hours later, she reports difficulty breathing and moving.

How should her obstetrician proceed?

Calcium-channel blockers such as nifedipine are used for acute and maintenance tocolysis. This class of drugs is often selected for its relative ease of use and safety, as it has few maternal and fetal side effects. However, concomitant use of a calcium-channel blocker and magnesium sulfate can sometimes lead to neuromuscular blockade and significant respiratory depression, even necessitating mechanical ventilation.⁹ Treatment of these effects includes IV administration of 10% calcium gluconate (5–10 mEq), which usually reverses respiratory depression and heart block caused by magnesium intoxication. In extreme cases, peritoneal dialysis or hemodialysis may be required.

CASE 3 Resolved

The patient is given 10% calcium gluconate in the dosage described above, and she stabilizes. However, her contractions continue and she delivers at 32 weeks’ gestation. The infant does well in the NICU.

CASE 4: Preterm labor in a woman with kidney dysfunction

Ms. F, age 40, presents at 30 weeks’ gestation with regular contractions and cervical dilation of more than 3 cm. She also reports a history of kidney disease.

What steps are recommended prior to the initiation of magnesium therapy?

Magnesium sulfate has been used for more than 40 years to treat preterm labor and is still considered a first-line therapy in many centers. Although maternal side effects usually are mild, an adverse event may occur if the patient is not monitored carefully. An absence of deep-tendon reflexes should alert the clinician that magnesium levels need to be measured. Reflexes usually are lost at a serum level of 10 mEq/L or higher. When the magnesium level exceeds 13 mEq/L, cardiac arrest is a risk. IV calcium should be administered immediately in such patients.

Magnesium should be used with caution in patients with myocardial compromise. Because magnesium is eliminated by the kidneys, women with impaired renal function may experience magnesium toxicity at normal doses. If a patient has a creatinine level above 1 mg/dL, consider alternative treatment for her preterm labor. If magnesium is given, the normal loading dose (4–6 g) is appropriate, but the maintenance dose should be reduced.¹¹

Fetal effects of magnesium sulfate

Recent studies indicate that predelivery magnesium may offer fetal neuroprotection. The minimum duration of administration for such neuroprotection is unknown but is less than 24 hours.⁸

Although magnesium can alter FHR patterns slightly, these changes are not clinically significant. Magnesium can also cause mild neonatal suppression at the time of delivery, but its effects quickly resolve with appropriate neonatal resuscitation. Long-term (>5 days) therapy is not recommended.

In May 2013, the FDA issued a warning about the risk of neonatal complications with long-term maternal magnesium administration. These complications include osteopenia, low calcium, and bone fracture. The pregnancy category for magnesium sulfate will be changed from “A” to “D” because of these teratogenic effects.¹²

CASE 4 Resolved

Because magnesium is mainly cleared by renal excretion, the clinician administers the medication with caution in this patient with reduced renal function. The clinician administers the same 4- to 6-g bolus that would be given a patient with normal kidney function, but the maintenance dose is reduced to 1 g. Magnesium levels are obtained every 12 hours or when clinically indicated.

Bottom line: Be ready to act

The short-term use of tocolytic therapy usually is not associated with maternal or fetal complications. After initial administration, maintenance tocolytic therapy probably does not prolong gestation.

Given the potential for harm without additional fetal benefit associated with extended therapy, I recommend that clinicians follow current clinical guidelines from ACOG for use of tocolytic agents. In the process, be vigilant for complications and be ready to act appropriately. Keep maternal and fetal conditions in mind when selecting a tocolytic agent.

A girl, age 13 years, 4 months, presented to her primary care provider’s office for a well visit. Among her concerns, she mentioned a “bump” she had had on her right leg “for the past six months, maybe longer.” The area felt irritated when touched or when the patient “ran too much.” She had seen no change in the bump since she first noticed it. The patient knew of no trauma or other preceding factors. She denied any fever or warmth, redness, or ecchymosis to the area.

Medical history was unremarkable except for familial short stature and myopia. The patient was the fifth of eight children born to nonconsanguinous parents. She denied any surgical history or hospitalizations and was premenarcheal. She was up to date on all age-appropriate vaccines, with her meningococcal vaccine administered at that visit.

The patient’s blood pressure was 99/58 mm Hg with an apical pulse rate of 82 beats/min. Her growth parameters were following her curve. Her height was 55” (0.3 percentile); weight, 81 lb (7.5 percentile); and BMI, 18.8 (48.6 percentile).

The physical exam was normal with the exception of the musculoskeletal exam. Examination of the lower extremities revealed a palpable, 4 cm x 5 cm lesion at the right distal medial thigh just proximal to the knee. The lesion could not be visualized but on palpation was tender and firm. There was some question as to whether the lesion itself or inflamed soft tissue overlying the lesion was mobile. No overlying warmth, induration, erythema, or ecchymosis was noted.

Passive and active range of motion was intact at the hip and knee. No lesions to the upper extremities were evident, and no scoliosis was seen.

Blood work was done to rule out certain diagnoses. Results from a complete blood count with differential, lactate dehydrogenase (LDH), parathyroid hormone, lipid profiles, thyroid function, and a comprehensive metabolic profile were unremarkable. A low level of vitamin D 25-OH was detected: 21.7 ng/mL (normal range, 32 to 100 ng/mL).

Distal femur x-rays with posteroanterior, lateral, and oblique views were ordered. The imaging revealed a 3 cm x 3 cm lesion projecting from the “distal, somewhat medial” femur, which was diagnosed as a benign femoral osteochondroma. Significant inflammation to the surrounding soft-tissue structures was observed. A questionable old fracture of the osteochondroma was noted. The remaining bony structures and joints appeared normal.

An ultrasound of the lesion was also ordered to investigate soft-tissue swelling. This revealed a hypoechoic collar around the distal end of the osteochondroma, which could represent a fluid collection, hematoma from trauma, or bursitis. The soft tissues were deemed normal.

Because of the extent of inflammation, the radiologist recommended MRI without contrast to rule out bursitis or trauma to the osteochondroma.

DISCUSSION
Osteochondromas, which may be present in up to 3% of the general population, are the most common benign bone tumors.^1-3 An osteochondroma is a cartilage-capped bony projection that arises on the external surface of the bone; it contains a marrow cavity that is continuous with the underlying bone.^2,4 The majority of osteochondromas are solitary, accounting for perhaps 85% to 90% of all such lesions, and they are typically nonhereditary; the remaining 10% to 15% of osteochondromas are hereditary multiple osteochondromas or exostoses^1,2 (see “Definition of Multiple Exostoses Syndrome”^2,5,6,7).

Most lesions are painless and slow growing, and they usually occur in children and adolescents.² They typically stop growing at skeletal maturity with the closure of the growth plates.^3,8,9 There is no predilection for males or females in single lesions.²

Solitary osteochondromas typically appear in the lower extremities and at long tubular bone metaphyses,^1-3,10 especially on the femur, humerus, tibia, spine, and hip. Any part of the skeleton can be affected, but 30% of lesions occur on the femur and 40% at either the proximal metaphysis of the tibia or the distal metaphysis of the femur.^2,11

Most osteochondromas are asymptomatic and are found incidentally.^1,3 However, some patients present with local pain as a result of irritation to adjacent structures, limitation of joint motion, growth disturbance, or fracture of the pedicle.^3,4,9,11,12 A very small proportion of patients (no more than 1%) with solitary osteochondromas experience malignant transformation.^2,3,6,7 No particular blood work is recommended for patients with solitary osteochondromas.²

Differential Diagnosis
In addition to osteochondromas, several other lesions should be considered in the patient with musculoskeletal lesions (see Table 1^5,6,13-19).

Cartilaginous tumors. Chondrosarcomas are malignant cartilaginous tumors.^20-22 They commonly affect long bones, including the humerus and femur, and some flat bones, such as the pelvic bones.^13,22 They are most commonly seen in adults, and have no predisposition by gender.¹³

Chondrosarcomas can be primary (ie, arising de novo) or secondary (developing on preexisting benign cartilaginous neoplasms, including osteochondromas). The majority of chondrosarcomas are slow growing, and they rarely metastasize. It is difficult to differentiate between a benign lesion (such as an osteochondroma) and a chondrosarcoma by either histology or radiology. However, reliable predictors for malignancy include size exceeding 5 cm and location in the axial skeleton.²⁰

Bone tumors.Osteosarcomas are the most common malignant bone tumors in children and adolescents, with 400 to 560 US patients in this age-group diagnosed each year.^14-16 Osteosarcomas are uncommon in children younger than 10; their incidence peaks during the early teenage years (median peak age, 16), then declines rapidly among older patients. They are more common in males than females.¹⁵

Osteosarcomas commonly develop during periods of rapid bone turnover, such as the adolescent growth spurt. Common sites include the distal femur, proximal humerus, and proximal tibia,^15,16 particularly near the knee.¹³ Usually, osteosarcomas present with nonspecific symptoms, including strain-related pain of several months’ duration, which may disrupt sleep.¹⁶ Laboratory findings in affected patients may include elevations in LDH, alkaline phosphatase, and/or ESR.^15,23

Physical exam reveals a visible or palpable mass in the affected area, along with decreased joint motion; localized warmth or erythema may also be present. Late signs of osteosarcoma include weight loss, general malaise, and fever. First-line imaging for the patient with a suspected osteosarcoma is x-ray, which will show ill-defined borders, osteoblastic and/or osteolytic features, and an associated soft tissue mass. Advanced imaging, such as MRI, is warranted.¹⁶

Ewing sarcoma, the second most common bone tumor in children and adolescents, is an aggressive form of childhood cancer.^14,18 Approximately 25% of all Ewing sarcomas arise in soft tissues rather than bones.¹⁸ They are more common in whites than in other ethnic groups and have a slight male predominance.^13,18 The median age at diagnosis is 15.¹³ The most common presenting symptoms are tumor related, such as pain or a noticeable mass. While x-rays are usually ordered first, MRI is preferred.¹⁸

Soft tissue tumors and masses.Rhabdomyosarcomas are malignancies that account for more than half of the soft tissue sarcomas in children and adolescents. Less than one-fifth of cases occur in the extremities, and most occur in children younger than 10. These lesions have a slight male predominance and are more common in whites than in other patients.^14,17,24

Approximately 6% of childhood soft tissue tumors are adipose tissue tumors, which may be benign (eg, lipomas) or malignant (eg, liposarcomas). Lipomas in children account for nearly 4% of all soft tissue tumors and can be classified as superficial (which are often diagnosed clinically) or deep (frequently requiring imaging).²⁵

Lymphomaaccounts for 7% of cancers in US children and adolescents and more than 25% of newly diagnosed cancers in patients between 15 and 19, making it the most common malignancy in adolescents and the third most common in children.^26,27 Non-Hodgkin lymphoma is the fourth leading type of malignancy in US adolescents.²⁷ Rarely, lymphomas present with primary event soft tissue involvement.²⁸

Myositis ossificans (MO) is a rare benign disorder involving formation of heterotrophic bone in skeletal muscles and soft tissues.²⁹ Though possible in patients of any age, MO is most commonly seen in adolescents and young adults. Often the result of soft tissue injury (in which case it is referred to as myositis ossificans circumscripta or traumatic), MO develops in areas that are exposed to trauma, such as the anterior thighs or arms. Lesions can be diagnosed via plain x-ray or CT, although MRI and ultrasound can also be useful evaluation tools.^17,29,30

Because MO circumscripta typically presents as a painful soft tissue mass, it can be mistaken for a soft tissue sarcoma or an osteosarcoma; radiologic evaluation is required to make the proper diagnosis. Less common forms of MO are myositis ossificans progressiva and myositis ossificans without a history of trauma.²⁹

Ollier diseaseis a rare, nonfamilial disorder characterized by multiple enchondromas (or enchondromatoses), which are distributed asymmetrically with areas of dysplastic cartilage. Enchondromas are benign cartilage tumors that frequently affect long tubular bones along the metaphyses in proximity to the growth plate. The enchondromas result in significant growth abnormalities. About one in 1 million people are diagnosed yearly.^5,19 (Similarly, Maffucci syndrome is represented by multiple enchondromas in association with hemangiomas.⁵)

Ollier disease typically manifests during childhood⁵ with bone swelling, local pain, and palpable bony masses, which are often associated with bone deformities.¹⁹ Patients generally present with an asymmetric shortening of one extremity and the appearance of palpable bony masses on their fingers or toes, which may or may not be associated with pathologic fractures.^5,19 In 20% to 50% of patients with Ollier disease, enchondromas are at risk for malignant transformation into chondrosarcomas.⁵

Vascular malformations. Certain abnormalities of vascular development cause birthmarks and abnormalities of varying degree in underlying tissues.³¹ They are usually present at birth and grow proportionally to the child’s growth.^25,31 However, they can also be seen in later childhood and adolescence.

Radiologic Investigation
Plain radiography of the affected area is the first-line radiologic study to be performed.¹³ While most osteochondromas can be diagnosed by plain x-ray, cross-sectional imaging via CT or MRI is recommended in lesions with certain characteristics, such as a broad stalk or location in the axial skeleton. Because MRI involves no radiation exposure, it is a particularly good diagnostic tool for children.³²

Ultrasound is a good imaging method for evaluating for complications of osteochondromas, including bursa formation or vascular compromise.³²

Treatment and Management
Although usually asymptomatic, osteochondroma can trigger some significant symptoms. Osteochondromas are at risk for fracture and can cause body deformities, mechanical joint problems, weakness of the affected limb, numbness, vascular compression, aneurysm, arterial thrombosis, venous thrombosis, pain, acute ischemia, and nerve compression. Clinical signs of malignant transformation include pain, swelling, and increased lesion size.²

Surgical excision is recommended but should be delayed until after the patient has reached skeletal maturity in order to decrease the risk for recurrence.³³

Patient Education and Follow-up
In addition to explaining appropriate pain management (eg, NSAIDs), it is especially important for the pediatric NP or PA to encourage the patient with a solitary osteochondroma to follow up with the pediatric orthopedic surgeon. Reasons include the need to monitor growth of the lesion (which is likely to continue in a patient who has not yet reached skeletal maturity) and assess for associated functional or joint problems. Patients should also be advised to seek the specialist’s attention if such problems develop or if pain increases.

Generally, the pediatric clinician should be sufficiently informed to answer questions about this condition from the patient or family. Any follow-up laboratory work recommended by the specialist can also be performed by the pediatric NP or PA.

OUTCOME FOR THE CASE PATIENT
MRI without contrast, as recommended by the radiologist to rule out a bursa or trauma to the osteochondroma, was considered an important part of the follow-up plan. As the patient had not yet reached skeletal maturity, she was referred to a pediatric orthopedic surgeon for possible excision of the lesion, due to its size and the pain associated with running or other exertion.

CONCLUSION
Solitary osteochondromas are the most common benign bone tumors. Although they are generally asymptomatic, pain and other symptoms can arise as a result of irritation to the adjacent structures. In this case, the patient’s chief complaint was an irritating “bump” that she had had on her right leg for at least six months.

Generally, follow-up monitoring of the osteochondroma and orthopedic follow-up care are warranted, at least until the patient reaches skeletal maturity. At that point, surgical excision of the lesion is recommended.            

REFERENCES
1. Florez B, Mönckeberg J, Castillo G, Beguiristain J. Solitary osteochondroma long-term follow-up. J Pediatr Orthop B. 2008;17:91-94.

2. Kitsoulis P, Galani V, Stefanaki K, et al. Osteochondromas: review of the clinical, radiological and pathological features. In Vivo. 2008;22:633-646.

3. Ramos-Pascua LR, Sánchez-Herráez S, Alonso-Barrio JA, Alonso-León A. Solitary proximal end of femur osteochondroma: an indication and result of the en bloc resection without hip luxation [in Spanish]. Rev Esp Cir Ortop Traumatol. 2012;56:24-31.

4. Payne WT, Merrell G. Benign bony and soft tissue tumors of the hand. J Hand Surg. 2010;35:1901-1910.

5. Pannier S, Legeai-Mallet L. Hereditary multiple exostoses and enchondromatosis. Best Pract Res Clin Rheumatol. 2008;22:45-54.

6. Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008;3(3).

7. Staals EL, Bacchini P, Mercuri M, Bertoni F. Dedifferentiated chondrosarcomas arising in preexisting osteochondromas. J Bone Joint Surg Am. 2007;89:987-993.

8. Singh R, Jain M, Siwach R, et al. Large para-articular osteochondroma of the knee joint: a case report. Acta Orthop Traumatol Turc. 2012;46:139-143.

9. Lee JY, Lee S, Joo KB, et al. Intraarticular osteochondroma of shoulder: a case report. Clin Imaging. 2013;37:379-381.

10. Kim Y-C, Ahn JH, Lee JW. Osteochondroma of the distal tibia complicated by a tibialis posterior tendon tear. J Foot Ankle Surg. 2012;51: 660-663.

11. Allagui M, Amara K, Aloui I, et al. Historical giant near-circumferential osteochondroma of the proximal humerus. J Shoulder Elbow Surg. 2010;19:e12-e15.

12.
Li M, Luettringhaus T, Walker KR, Cole PA. Operative treatment of femoral neck osteochondroma through a digastric approach in a pediatric patient: a case report and review of the literature. J Pediatr Orthop B. 2012;21:230-234.

13. Hogendoorn PC, Athanasou N, Bielack S, et al; ESMO/EUROBONET Working Group. Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 suppl 5:v204-v213.

14. Arndt CAS, Rose PS, Folpe AL, Laack NN. Common musculoskeletal tumors of childhood and adolescence. Mayo Clin Proc. 2012;87:475-487.

15. Ta HT, Dass CR, Choong PF, Dunstan DE. Osteosarcoma treatment: state of the art. Cancer Metastasis Rev. 2009;28:247-263.

16. Messerschmitt PJ, Garcia RM, Abdul-Karim FW, et al. Osteosarcoma. J Am Acad Orthop Surg. 2009;17:515-527.

17. Laffan EE, Ngan B-Y, Navarro OM. Pediatric soft-tissue tumors and pseudotumors: MR imaging features with pathologic correlation: Part 2. Tumors of fibroblastic/myofibroblastic, so-called fibrohistiocytic, muscular, lymphomatous, neurogenic, hair matrix, and uncertain origin. Radiographics. 2009;29:e36.

18. Balamuth NJ, Womer RB. Ewing’s sarcoma. Lancet Oncol. 2010;11(2):184.

19. D’Angelo L, Massimi L, Narducci A, Di Rocco C. Ollier disease. Childs Nerv Syst. 2009;25:647-653.

20. Gelderblom H, Hogendoorn PC, Dijkstra SD, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13:320-329.

21. Nosratzehi T, Pakfetrat A. Chondrosarcoma. Zahedan J Res Med Sci. 2013;15:64-64.

22. Prado FO, Nishimoto IN, Perez DE, et al. Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral Maxillofacial Surg. 2009;47:555-557.

23. Kim HJ, Chalmers PN, Morris CD. Pediatric osteogenic sarcoma. Curr Opin Pediatr. 2010;22:61-66.

24. Sultan I, Qaddoumi I, Yaser S, et al. Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol. 2009;27:3391-3397.

25. Navarro OM, Laffan EE, Ngan B-Y. Pediatric soft-tissue tumors and pseudo-tumors: MR imaging features with pathologic correlation: Part 1. Imaging approach, pseudotumors, vascular lesions, and adipocytic tumors. Radiographics. 2009;29:887-906.

26. Gross TG, Termuhlen AM. Pediatric non-Hodgkin lymphoma. Curr Hematol Malig Rep. 2008;3:167-173.

27. Hochberg J, Waxman IM, Kelly KM, et al. Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma: state of the science. Br J Haematol. 2009;144:24-40.

28. Derenzini E, Casadei B, Pellegrini C, et al. Non-Hodgkin lymphomas presenting as soft tissue masses: A single center experience and meta-analysis of the published series. Clin Lymphoma Myeloma Leuk. 2012 Dec 12. [Epub ahead of print]

29. Micheli A, Trapani S, Brizzi I, et al. Myositis ossificans circumscripta: a paediatric case and review of the literature. Eur J Pediatr. 2009;168:523-529.

30. McKenzie G, Raby N, Ritchie D. Non-neoplastic soft-tissue masses. Br J Radiol. 2009;82:775-785.

31. Buckmiller LM, Richter GT, Suen JY. Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Dis. 2010;16:405-418.

32. Khanna G, Bennett DL. Pediatric bone lesions: beyond the plain radiographic evaluation. Semin Roentgenol. 2012;47:90-99.

33.
Rijal L, Nepal P, Baral S, et al. Solitary diaphyseal exostosis of femur, how common is it? Eur J Orthop Surg Traumatol. 2011;21:363-365.

A girl, age 13 years, 4 months, presented to her primary care provider’s office for a well visit. Among her concerns, she mentioned a “bump” she had had on her right leg “for the past six months, maybe longer.” The area felt irritated when touched or when the patient “ran too much.” She had seen no change in the bump since she first noticed it. The patient knew of no trauma or other preceding factors. She denied any fever or warmth, redness, or ecchymosis to the area.

Medical history was unremarkable except for familial short stature and myopia. The patient was the fifth of eight children born to nonconsanguinous parents. She denied any surgical history or hospitalizations and was premenarcheal. She was up to date on all age-appropriate vaccines, with her meningococcal vaccine administered at that visit.

The patient’s blood pressure was 99/58 mm Hg with an apical pulse rate of 82 beats/min. Her growth parameters were following her curve. Her height was 55” (0.3 percentile); weight, 81 lb (7.5 percentile); and BMI, 18.8 (48.6 percentile).

The physical exam was normal with the exception of the musculoskeletal exam. Examination of the lower extremities revealed a palpable, 4 cm x 5 cm lesion at the right distal medial thigh just proximal to the knee. The lesion could not be visualized but on palpation was tender and firm. There was some question as to whether the lesion itself or inflamed soft tissue overlying the lesion was mobile. No overlying warmth, induration, erythema, or ecchymosis was noted.

Passive and active range of motion was intact at the hip and knee. No lesions to the upper extremities were evident, and no scoliosis was seen.

Blood work was done to rule out certain diagnoses. Results from a complete blood count with differential, lactate dehydrogenase (LDH), parathyroid hormone, lipid profiles, thyroid function, and a comprehensive metabolic profile were unremarkable. A low level of vitamin D 25-OH was detected: 21.7 ng/mL (normal range, 32 to 100 ng/mL).

Distal femur x-rays with posteroanterior, lateral, and oblique views were ordered. The imaging revealed a 3 cm x 3 cm lesion projecting from the “distal, somewhat medial” femur, which was diagnosed as a benign femoral osteochondroma. Significant inflammation to the surrounding soft-tissue structures was observed. A questionable old fracture of the osteochondroma was noted. The remaining bony structures and joints appeared normal.

An ultrasound of the lesion was also ordered to investigate soft-tissue swelling. This revealed a hypoechoic collar around the distal end of the osteochondroma, which could represent a fluid collection, hematoma from trauma, or bursitis. The soft tissues were deemed normal.

Because of the extent of inflammation, the radiologist recommended MRI without contrast to rule out bursitis or trauma to the osteochondroma.

DISCUSSION
Osteochondromas, which may be present in up to 3% of the general population, are the most common benign bone tumors.^1-3 An osteochondroma is a cartilage-capped bony projection that arises on the external surface of the bone; it contains a marrow cavity that is continuous with the underlying bone.^2,4 The majority of osteochondromas are solitary, accounting for perhaps 85% to 90% of all such lesions, and they are typically nonhereditary; the remaining 10% to 15% of osteochondromas are hereditary multiple osteochondromas or exostoses^1,2 (see “Definition of Multiple Exostoses Syndrome”^2,5,6,7).

Most lesions are painless and slow growing, and they usually occur in children and adolescents.² They typically stop growing at skeletal maturity with the closure of the growth plates.^3,8,9 There is no predilection for males or females in single lesions.²

Solitary osteochondromas typically appear in the lower extremities and at long tubular bone metaphyses,^1-3,10 especially on the femur, humerus, tibia, spine, and hip. Any part of the skeleton can be affected, but 30% of lesions occur on the femur and 40% at either the proximal metaphysis of the tibia or the distal metaphysis of the femur.^2,11

Most osteochondromas are asymptomatic and are found incidentally.^1,3 However, some patients present with local pain as a result of irritation to adjacent structures, limitation of joint motion, growth disturbance, or fracture of the pedicle.^3,4,9,11,12 A very small proportion of patients (no more than 1%) with solitary osteochondromas experience malignant transformation.^2,3,6,7 No particular blood work is recommended for patients with solitary osteochondromas.²

Differential Diagnosis
In addition to osteochondromas, several other lesions should be considered in the patient with musculoskeletal lesions (see Table 1^5,6,13-19).

Cartilaginous tumors. Chondrosarcomas are malignant cartilaginous tumors.^20-22 They commonly affect long bones, including the humerus and femur, and some flat bones, such as the pelvic bones.^13,22 They are most commonly seen in adults, and have no predisposition by gender.¹³

Chondrosarcomas can be primary (ie, arising de novo) or secondary (developing on preexisting benign cartilaginous neoplasms, including osteochondromas). The majority of chondrosarcomas are slow growing, and they rarely metastasize. It is difficult to differentiate between a benign lesion (such as an osteochondroma) and a chondrosarcoma by either histology or radiology. However, reliable predictors for malignancy include size exceeding 5 cm and location in the axial skeleton.²⁰

Bone tumors.Osteosarcomas are the most common malignant bone tumors in children and adolescents, with 400 to 560 US patients in this age-group diagnosed each year.^14-16 Osteosarcomas are uncommon in children younger than 10; their incidence peaks during the early teenage years (median peak age, 16), then declines rapidly among older patients. They are more common in males than females.¹⁵

Osteosarcomas commonly develop during periods of rapid bone turnover, such as the adolescent growth spurt. Common sites include the distal femur, proximal humerus, and proximal tibia,^15,16 particularly near the knee.¹³ Usually, osteosarcomas present with nonspecific symptoms, including strain-related pain of several months’ duration, which may disrupt sleep.¹⁶ Laboratory findings in affected patients may include elevations in LDH, alkaline phosphatase, and/or ESR.^15,23

Physical exam reveals a visible or palpable mass in the affected area, along with decreased joint motion; localized warmth or erythema may also be present. Late signs of osteosarcoma include weight loss, general malaise, and fever. First-line imaging for the patient with a suspected osteosarcoma is x-ray, which will show ill-defined borders, osteoblastic and/or osteolytic features, and an associated soft tissue mass. Advanced imaging, such as MRI, is warranted.¹⁶

Ewing sarcoma, the second most common bone tumor in children and adolescents, is an aggressive form of childhood cancer.^14,18 Approximately 25% of all Ewing sarcomas arise in soft tissues rather than bones.¹⁸ They are more common in whites than in other ethnic groups and have a slight male predominance.^13,18 The median age at diagnosis is 15.¹³ The most common presenting symptoms are tumor related, such as pain or a noticeable mass. While x-rays are usually ordered first, MRI is preferred.¹⁸

Soft tissue tumors and masses.Rhabdomyosarcomas are malignancies that account for more than half of the soft tissue sarcomas in children and adolescents. Less than one-fifth of cases occur in the extremities, and most occur in children younger than 10. These lesions have a slight male predominance and are more common in whites than in other patients.^14,17,24

Approximately 6% of childhood soft tissue tumors are adipose tissue tumors, which may be benign (eg, lipomas) or malignant (eg, liposarcomas). Lipomas in children account for nearly 4% of all soft tissue tumors and can be classified as superficial (which are often diagnosed clinically) or deep (frequently requiring imaging).²⁵

Lymphomaaccounts for 7% of cancers in US children and adolescents and more than 25% of newly diagnosed cancers in patients between 15 and 19, making it the most common malignancy in adolescents and the third most common in children.^26,27 Non-Hodgkin lymphoma is the fourth leading type of malignancy in US adolescents.²⁷ Rarely, lymphomas present with primary event soft tissue involvement.²⁸

Myositis ossificans (MO) is a rare benign disorder involving formation of heterotrophic bone in skeletal muscles and soft tissues.²⁹ Though possible in patients of any age, MO is most commonly seen in adolescents and young adults. Often the result of soft tissue injury (in which case it is referred to as myositis ossificans circumscripta or traumatic), MO develops in areas that are exposed to trauma, such as the anterior thighs or arms. Lesions can be diagnosed via plain x-ray or CT, although MRI and ultrasound can also be useful evaluation tools.^17,29,30

Because MO circumscripta typically presents as a painful soft tissue mass, it can be mistaken for a soft tissue sarcoma or an osteosarcoma; radiologic evaluation is required to make the proper diagnosis. Less common forms of MO are myositis ossificans progressiva and myositis ossificans without a history of trauma.²⁹

Ollier diseaseis a rare, nonfamilial disorder characterized by multiple enchondromas (or enchondromatoses), which are distributed asymmetrically with areas of dysplastic cartilage. Enchondromas are benign cartilage tumors that frequently affect long tubular bones along the metaphyses in proximity to the growth plate. The enchondromas result in significant growth abnormalities. About one in 1 million people are diagnosed yearly.^5,19 (Similarly, Maffucci syndrome is represented by multiple enchondromas in association with hemangiomas.⁵)

Ollier disease typically manifests during childhood⁵ with bone swelling, local pain, and palpable bony masses, which are often associated with bone deformities.¹⁹ Patients generally present with an asymmetric shortening of one extremity and the appearance of palpable bony masses on their fingers or toes, which may or may not be associated with pathologic fractures.^5,19 In 20% to 50% of patients with Ollier disease, enchondromas are at risk for malignant transformation into chondrosarcomas.⁵

Vascular malformations. Certain abnormalities of vascular development cause birthmarks and abnormalities of varying degree in underlying tissues.³¹ They are usually present at birth and grow proportionally to the child’s growth.^25,31 However, they can also be seen in later childhood and adolescence.

Radiologic Investigation
Plain radiography of the affected area is the first-line radiologic study to be performed.¹³ While most osteochondromas can be diagnosed by plain x-ray, cross-sectional imaging via CT or MRI is recommended in lesions with certain characteristics, such as a broad stalk or location in the axial skeleton. Because MRI involves no radiation exposure, it is a particularly good diagnostic tool for children.³²

Ultrasound is a good imaging method for evaluating for complications of osteochondromas, including bursa formation or vascular compromise.³²

Treatment and Management
Although usually asymptomatic, osteochondroma can trigger some significant symptoms. Osteochondromas are at risk for fracture and can cause body deformities, mechanical joint problems, weakness of the affected limb, numbness, vascular compression, aneurysm, arterial thrombosis, venous thrombosis, pain, acute ischemia, and nerve compression. Clinical signs of malignant transformation include pain, swelling, and increased lesion size.²

Surgical excision is recommended but should be delayed until after the patient has reached skeletal maturity in order to decrease the risk for recurrence.³³

Patient Education and Follow-up
In addition to explaining appropriate pain management (eg, NSAIDs), it is especially important for the pediatric NP or PA to encourage the patient with a solitary osteochondroma to follow up with the pediatric orthopedic surgeon. Reasons include the need to monitor growth of the lesion (which is likely to continue in a patient who has not yet reached skeletal maturity) and assess for associated functional or joint problems. Patients should also be advised to seek the specialist’s attention if such problems develop or if pain increases.

Generally, the pediatric clinician should be sufficiently informed to answer questions about this condition from the patient or family. Any follow-up laboratory work recommended by the specialist can also be performed by the pediatric NP or PA.

OUTCOME FOR THE CASE PATIENT
MRI without contrast, as recommended by the radiologist to rule out a bursa or trauma to the osteochondroma, was considered an important part of the follow-up plan. As the patient had not yet reached skeletal maturity, she was referred to a pediatric orthopedic surgeon for possible excision of the lesion, due to its size and the pain associated with running or other exertion.

CONCLUSION
Solitary osteochondromas are the most common benign bone tumors. Although they are generally asymptomatic, pain and other symptoms can arise as a result of irritation to the adjacent structures. In this case, the patient’s chief complaint was an irritating “bump” that she had had on her right leg for at least six months.

Generally, follow-up monitoring of the osteochondroma and orthopedic follow-up care are warranted, at least until the patient reaches skeletal maturity. At that point, surgical excision of the lesion is recommended.            

REFERENCES
1. Florez B, Mönckeberg J, Castillo G, Beguiristain J. Solitary osteochondroma long-term follow-up. J Pediatr Orthop B. 2008;17:91-94.

2. Kitsoulis P, Galani V, Stefanaki K, et al. Osteochondromas: review of the clinical, radiological and pathological features. In Vivo. 2008;22:633-646.

3. Ramos-Pascua LR, Sánchez-Herráez S, Alonso-Barrio JA, Alonso-León A. Solitary proximal end of femur osteochondroma: an indication and result of the en bloc resection without hip luxation [in Spanish]. Rev Esp Cir Ortop Traumatol. 2012;56:24-31.

4. Payne WT, Merrell G. Benign bony and soft tissue tumors of the hand. J Hand Surg. 2010;35:1901-1910.

5. Pannier S, Legeai-Mallet L. Hereditary multiple exostoses and enchondromatosis. Best Pract Res Clin Rheumatol. 2008;22:45-54.

6. Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008;3(3).

7. Staals EL, Bacchini P, Mercuri M, Bertoni F. Dedifferentiated chondrosarcomas arising in preexisting osteochondromas. J Bone Joint Surg Am. 2007;89:987-993.

8. Singh R, Jain M, Siwach R, et al. Large para-articular osteochondroma of the knee joint: a case report. Acta Orthop Traumatol Turc. 2012;46:139-143.

9. Lee JY, Lee S, Joo KB, et al. Intraarticular osteochondroma of shoulder: a case report. Clin Imaging. 2013;37:379-381.

10. Kim Y-C, Ahn JH, Lee JW. Osteochondroma of the distal tibia complicated by a tibialis posterior tendon tear. J Foot Ankle Surg. 2012;51: 660-663.

11. Allagui M, Amara K, Aloui I, et al. Historical giant near-circumferential osteochondroma of the proximal humerus. J Shoulder Elbow Surg. 2010;19:e12-e15.

12.
Li M, Luettringhaus T, Walker KR, Cole PA. Operative treatment of femoral neck osteochondroma through a digastric approach in a pediatric patient: a case report and review of the literature. J Pediatr Orthop B. 2012;21:230-234.

13. Hogendoorn PC, Athanasou N, Bielack S, et al; ESMO/EUROBONET Working Group. Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 suppl 5:v204-v213.

14. Arndt CAS, Rose PS, Folpe AL, Laack NN. Common musculoskeletal tumors of childhood and adolescence. Mayo Clin Proc. 2012;87:475-487.

15. Ta HT, Dass CR, Choong PF, Dunstan DE. Osteosarcoma treatment: state of the art. Cancer Metastasis Rev. 2009;28:247-263.

16. Messerschmitt PJ, Garcia RM, Abdul-Karim FW, et al. Osteosarcoma. J Am Acad Orthop Surg. 2009;17:515-527.

17. Laffan EE, Ngan B-Y, Navarro OM. Pediatric soft-tissue tumors and pseudotumors: MR imaging features with pathologic correlation: Part 2. Tumors of fibroblastic/myofibroblastic, so-called fibrohistiocytic, muscular, lymphomatous, neurogenic, hair matrix, and uncertain origin. Radiographics. 2009;29:e36.

18. Balamuth NJ, Womer RB. Ewing’s sarcoma. Lancet Oncol. 2010;11(2):184.

19. D’Angelo L, Massimi L, Narducci A, Di Rocco C. Ollier disease. Childs Nerv Syst. 2009;25:647-653.

20. Gelderblom H, Hogendoorn PC, Dijkstra SD, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13:320-329.

21. Nosratzehi T, Pakfetrat A. Chondrosarcoma. Zahedan J Res Med Sci. 2013;15:64-64.

22. Prado FO, Nishimoto IN, Perez DE, et al. Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral Maxillofacial Surg. 2009;47:555-557.

23. Kim HJ, Chalmers PN, Morris CD. Pediatric osteogenic sarcoma. Curr Opin Pediatr. 2010;22:61-66.

24. Sultan I, Qaddoumi I, Yaser S, et al. Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol. 2009;27:3391-3397.

25. Navarro OM, Laffan EE, Ngan B-Y. Pediatric soft-tissue tumors and pseudo-tumors: MR imaging features with pathologic correlation: Part 1. Imaging approach, pseudotumors, vascular lesions, and adipocytic tumors. Radiographics. 2009;29:887-906.

26. Gross TG, Termuhlen AM. Pediatric non-Hodgkin lymphoma. Curr Hematol Malig Rep. 2008;3:167-173.

27. Hochberg J, Waxman IM, Kelly KM, et al. Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma: state of the science. Br J Haematol. 2009;144:24-40.

28. Derenzini E, Casadei B, Pellegrini C, et al. Non-Hodgkin lymphomas presenting as soft tissue masses: A single center experience and meta-analysis of the published series. Clin Lymphoma Myeloma Leuk. 2012 Dec 12. [Epub ahead of print]

29. Micheli A, Trapani S, Brizzi I, et al. Myositis ossificans circumscripta: a paediatric case and review of the literature. Eur J Pediatr. 2009;168:523-529.

30. McKenzie G, Raby N, Ritchie D. Non-neoplastic soft-tissue masses. Br J Radiol. 2009;82:775-785.

31. Buckmiller LM, Richter GT, Suen JY. Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Dis. 2010;16:405-418.

32. Khanna G, Bennett DL. Pediatric bone lesions: beyond the plain radiographic evaluation. Semin Roentgenol. 2012;47:90-99.

33.
Rijal L, Nepal P, Baral S, et al. Solitary diaphyseal exostosis of femur, how common is it? Eur J Orthop Surg Traumatol. 2011;21:363-365.

A girl, age 13 years, 4 months, presented to her primary care provider’s office for a well visit. Among her concerns, she mentioned a “bump” she had had on her right leg “for the past six months, maybe longer.” The area felt irritated when touched or when the patient “ran too much.” She had seen no change in the bump since she first noticed it. The patient knew of no trauma or other preceding factors. She denied any fever or warmth, redness, or ecchymosis to the area.

Medical history was unremarkable except for familial short stature and myopia. The patient was the fifth of eight children born to nonconsanguinous parents. She denied any surgical history or hospitalizations and was premenarcheal. She was up to date on all age-appropriate vaccines, with her meningococcal vaccine administered at that visit.

The patient’s blood pressure was 99/58 mm Hg with an apical pulse rate of 82 beats/min. Her growth parameters were following her curve. Her height was 55” (0.3 percentile); weight, 81 lb (7.5 percentile); and BMI, 18.8 (48.6 percentile).

The physical exam was normal with the exception of the musculoskeletal exam. Examination of the lower extremities revealed a palpable, 4 cm x 5 cm lesion at the right distal medial thigh just proximal to the knee. The lesion could not be visualized but on palpation was tender and firm. There was some question as to whether the lesion itself or inflamed soft tissue overlying the lesion was mobile. No overlying warmth, induration, erythema, or ecchymosis was noted.

Passive and active range of motion was intact at the hip and knee. No lesions to the upper extremities were evident, and no scoliosis was seen.

Blood work was done to rule out certain diagnoses. Results from a complete blood count with differential, lactate dehydrogenase (LDH), parathyroid hormone, lipid profiles, thyroid function, and a comprehensive metabolic profile were unremarkable. A low level of vitamin D 25-OH was detected: 21.7 ng/mL (normal range, 32 to 100 ng/mL).

Distal femur x-rays with posteroanterior, lateral, and oblique views were ordered. The imaging revealed a 3 cm x 3 cm lesion projecting from the “distal, somewhat medial” femur, which was diagnosed as a benign femoral osteochondroma. Significant inflammation to the surrounding soft-tissue structures was observed. A questionable old fracture of the osteochondroma was noted. The remaining bony structures and joints appeared normal.

An ultrasound of the lesion was also ordered to investigate soft-tissue swelling. This revealed a hypoechoic collar around the distal end of the osteochondroma, which could represent a fluid collection, hematoma from trauma, or bursitis. The soft tissues were deemed normal.

Because of the extent of inflammation, the radiologist recommended MRI without contrast to rule out bursitis or trauma to the osteochondroma.

DISCUSSION
Osteochondromas, which may be present in up to 3% of the general population, are the most common benign bone tumors.^1-3 An osteochondroma is a cartilage-capped bony projection that arises on the external surface of the bone; it contains a marrow cavity that is continuous with the underlying bone.^2,4 The majority of osteochondromas are solitary, accounting for perhaps 85% to 90% of all such lesions, and they are typically nonhereditary; the remaining 10% to 15% of osteochondromas are hereditary multiple osteochondromas or exostoses^1,2 (see “Definition of Multiple Exostoses Syndrome”^2,5,6,7).

Most lesions are painless and slow growing, and they usually occur in children and adolescents.² They typically stop growing at skeletal maturity with the closure of the growth plates.^3,8,9 There is no predilection for males or females in single lesions.²

Solitary osteochondromas typically appear in the lower extremities and at long tubular bone metaphyses,^1-3,10 especially on the femur, humerus, tibia, spine, and hip. Any part of the skeleton can be affected, but 30% of lesions occur on the femur and 40% at either the proximal metaphysis of the tibia or the distal metaphysis of the femur.^2,11

Most osteochondromas are asymptomatic and are found incidentally.^1,3 However, some patients present with local pain as a result of irritation to adjacent structures, limitation of joint motion, growth disturbance, or fracture of the pedicle.^3,4,9,11,12 A very small proportion of patients (no more than 1%) with solitary osteochondromas experience malignant transformation.^2,3,6,7 No particular blood work is recommended for patients with solitary osteochondromas.²

Differential Diagnosis
In addition to osteochondromas, several other lesions should be considered in the patient with musculoskeletal lesions (see Table 1^5,6,13-19).

Cartilaginous tumors. Chondrosarcomas are malignant cartilaginous tumors.^20-22 They commonly affect long bones, including the humerus and femur, and some flat bones, such as the pelvic bones.^13,22 They are most commonly seen in adults, and have no predisposition by gender.¹³

Chondrosarcomas can be primary (ie, arising de novo) or secondary (developing on preexisting benign cartilaginous neoplasms, including osteochondromas). The majority of chondrosarcomas are slow growing, and they rarely metastasize. It is difficult to differentiate between a benign lesion (such as an osteochondroma) and a chondrosarcoma by either histology or radiology. However, reliable predictors for malignancy include size exceeding 5 cm and location in the axial skeleton.²⁰

Bone tumors.Osteosarcomas are the most common malignant bone tumors in children and adolescents, with 400 to 560 US patients in this age-group diagnosed each year.^14-16 Osteosarcomas are uncommon in children younger than 10; their incidence peaks during the early teenage years (median peak age, 16), then declines rapidly among older patients. They are more common in males than females.¹⁵

Osteosarcomas commonly develop during periods of rapid bone turnover, such as the adolescent growth spurt. Common sites include the distal femur, proximal humerus, and proximal tibia,^15,16 particularly near the knee.¹³ Usually, osteosarcomas present with nonspecific symptoms, including strain-related pain of several months’ duration, which may disrupt sleep.¹⁶ Laboratory findings in affected patients may include elevations in LDH, alkaline phosphatase, and/or ESR.^15,23

Physical exam reveals a visible or palpable mass in the affected area, along with decreased joint motion; localized warmth or erythema may also be present. Late signs of osteosarcoma include weight loss, general malaise, and fever. First-line imaging for the patient with a suspected osteosarcoma is x-ray, which will show ill-defined borders, osteoblastic and/or osteolytic features, and an associated soft tissue mass. Advanced imaging, such as MRI, is warranted.¹⁶

Ewing sarcoma, the second most common bone tumor in children and adolescents, is an aggressive form of childhood cancer.^14,18 Approximately 25% of all Ewing sarcomas arise in soft tissues rather than bones.¹⁸ They are more common in whites than in other ethnic groups and have a slight male predominance.^13,18 The median age at diagnosis is 15.¹³ The most common presenting symptoms are tumor related, such as pain or a noticeable mass. While x-rays are usually ordered first, MRI is preferred.¹⁸

Soft tissue tumors and masses.Rhabdomyosarcomas are malignancies that account for more than half of the soft tissue sarcomas in children and adolescents. Less than one-fifth of cases occur in the extremities, and most occur in children younger than 10. These lesions have a slight male predominance and are more common in whites than in other patients.^14,17,24

Approximately 6% of childhood soft tissue tumors are adipose tissue tumors, which may be benign (eg, lipomas) or malignant (eg, liposarcomas). Lipomas in children account for nearly 4% of all soft tissue tumors and can be classified as superficial (which are often diagnosed clinically) or deep (frequently requiring imaging).²⁵

Lymphomaaccounts for 7% of cancers in US children and adolescents and more than 25% of newly diagnosed cancers in patients between 15 and 19, making it the most common malignancy in adolescents and the third most common in children.^26,27 Non-Hodgkin lymphoma is the fourth leading type of malignancy in US adolescents.²⁷ Rarely, lymphomas present with primary event soft tissue involvement.²⁸

Myositis ossificans (MO) is a rare benign disorder involving formation of heterotrophic bone in skeletal muscles and soft tissues.²⁹ Though possible in patients of any age, MO is most commonly seen in adolescents and young adults. Often the result of soft tissue injury (in which case it is referred to as myositis ossificans circumscripta or traumatic), MO develops in areas that are exposed to trauma, such as the anterior thighs or arms. Lesions can be diagnosed via plain x-ray or CT, although MRI and ultrasound can also be useful evaluation tools.^17,29,30

Because MO circumscripta typically presents as a painful soft tissue mass, it can be mistaken for a soft tissue sarcoma or an osteosarcoma; radiologic evaluation is required to make the proper diagnosis. Less common forms of MO are myositis ossificans progressiva and myositis ossificans without a history of trauma.²⁹

Ollier diseaseis a rare, nonfamilial disorder characterized by multiple enchondromas (or enchondromatoses), which are distributed asymmetrically with areas of dysplastic cartilage. Enchondromas are benign cartilage tumors that frequently affect long tubular bones along the metaphyses in proximity to the growth plate. The enchondromas result in significant growth abnormalities. About one in 1 million people are diagnosed yearly.^5,19 (Similarly, Maffucci syndrome is represented by multiple enchondromas in association with hemangiomas.⁵)

Ollier disease typically manifests during childhood⁵ with bone swelling, local pain, and palpable bony masses, which are often associated with bone deformities.¹⁹ Patients generally present with an asymmetric shortening of one extremity and the appearance of palpable bony masses on their fingers or toes, which may or may not be associated with pathologic fractures.^5,19 In 20% to 50% of patients with Ollier disease, enchondromas are at risk for malignant transformation into chondrosarcomas.⁵

Vascular malformations. Certain abnormalities of vascular development cause birthmarks and abnormalities of varying degree in underlying tissues.³¹ They are usually present at birth and grow proportionally to the child’s growth.^25,31 However, they can also be seen in later childhood and adolescence.

Radiologic Investigation
Plain radiography of the affected area is the first-line radiologic study to be performed.¹³ While most osteochondromas can be diagnosed by plain x-ray, cross-sectional imaging via CT or MRI is recommended in lesions with certain characteristics, such as a broad stalk or location in the axial skeleton. Because MRI involves no radiation exposure, it is a particularly good diagnostic tool for children.³²

Ultrasound is a good imaging method for evaluating for complications of osteochondromas, including bursa formation or vascular compromise.³²

Treatment and Management
Although usually asymptomatic, osteochondroma can trigger some significant symptoms. Osteochondromas are at risk for fracture and can cause body deformities, mechanical joint problems, weakness of the affected limb, numbness, vascular compression, aneurysm, arterial thrombosis, venous thrombosis, pain, acute ischemia, and nerve compression. Clinical signs of malignant transformation include pain, swelling, and increased lesion size.²

Surgical excision is recommended but should be delayed until after the patient has reached skeletal maturity in order to decrease the risk for recurrence.³³

Patient Education and Follow-up
In addition to explaining appropriate pain management (eg, NSAIDs), it is especially important for the pediatric NP or PA to encourage the patient with a solitary osteochondroma to follow up with the pediatric orthopedic surgeon. Reasons include the need to monitor growth of the lesion (which is likely to continue in a patient who has not yet reached skeletal maturity) and assess for associated functional or joint problems. Patients should also be advised to seek the specialist’s attention if such problems develop or if pain increases.

Generally, the pediatric clinician should be sufficiently informed to answer questions about this condition from the patient or family. Any follow-up laboratory work recommended by the specialist can also be performed by the pediatric NP or PA.

OUTCOME FOR THE CASE PATIENT
MRI without contrast, as recommended by the radiologist to rule out a bursa or trauma to the osteochondroma, was considered an important part of the follow-up plan. As the patient had not yet reached skeletal maturity, she was referred to a pediatric orthopedic surgeon for possible excision of the lesion, due to its size and the pain associated with running or other exertion.

CONCLUSION
Solitary osteochondromas are the most common benign bone tumors. Although they are generally asymptomatic, pain and other symptoms can arise as a result of irritation to the adjacent structures. In this case, the patient’s chief complaint was an irritating “bump” that she had had on her right leg for at least six months.

Generally, follow-up monitoring of the osteochondroma and orthopedic follow-up care are warranted, at least until the patient reaches skeletal maturity. At that point, surgical excision of the lesion is recommended.            

REFERENCES
1. Florez B, Mönckeberg J, Castillo G, Beguiristain J. Solitary osteochondroma long-term follow-up. J Pediatr Orthop B. 2008;17:91-94.

2. Kitsoulis P, Galani V, Stefanaki K, et al. Osteochondromas: review of the clinical, radiological and pathological features. In Vivo. 2008;22:633-646.

3. Ramos-Pascua LR, Sánchez-Herráez S, Alonso-Barrio JA, Alonso-León A. Solitary proximal end of femur osteochondroma: an indication and result of the en bloc resection without hip luxation [in Spanish]. Rev Esp Cir Ortop Traumatol. 2012;56:24-31.

4. Payne WT, Merrell G. Benign bony and soft tissue tumors of the hand. J Hand Surg. 2010;35:1901-1910.

5. Pannier S, Legeai-Mallet L. Hereditary multiple exostoses and enchondromatosis. Best Pract Res Clin Rheumatol. 2008;22:45-54.

6. Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008;3(3).

7. Staals EL, Bacchini P, Mercuri M, Bertoni F. Dedifferentiated chondrosarcomas arising in preexisting osteochondromas. J Bone Joint Surg Am. 2007;89:987-993.

8. Singh R, Jain M, Siwach R, et al. Large para-articular osteochondroma of the knee joint: a case report. Acta Orthop Traumatol Turc. 2012;46:139-143.

9. Lee JY, Lee S, Joo KB, et al. Intraarticular osteochondroma of shoulder: a case report. Clin Imaging. 2013;37:379-381.

10. Kim Y-C, Ahn JH, Lee JW. Osteochondroma of the distal tibia complicated by a tibialis posterior tendon tear. J Foot Ankle Surg. 2012;51: 660-663.

11. Allagui M, Amara K, Aloui I, et al. Historical giant near-circumferential osteochondroma of the proximal humerus. J Shoulder Elbow Surg. 2010;19:e12-e15.

12.
Li M, Luettringhaus T, Walker KR, Cole PA. Operative treatment of femoral neck osteochondroma through a digastric approach in a pediatric patient: a case report and review of the literature. J Pediatr Orthop B. 2012;21:230-234.

13. Hogendoorn PC, Athanasou N, Bielack S, et al; ESMO/EUROBONET Working Group. Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 suppl 5:v204-v213.

14. Arndt CAS, Rose PS, Folpe AL, Laack NN. Common musculoskeletal tumors of childhood and adolescence. Mayo Clin Proc. 2012;87:475-487.

15. Ta HT, Dass CR, Choong PF, Dunstan DE. Osteosarcoma treatment: state of the art. Cancer Metastasis Rev. 2009;28:247-263.

16. Messerschmitt PJ, Garcia RM, Abdul-Karim FW, et al. Osteosarcoma. J Am Acad Orthop Surg. 2009;17:515-527.

17. Laffan EE, Ngan B-Y, Navarro OM. Pediatric soft-tissue tumors and pseudotumors: MR imaging features with pathologic correlation: Part 2. Tumors of fibroblastic/myofibroblastic, so-called fibrohistiocytic, muscular, lymphomatous, neurogenic, hair matrix, and uncertain origin. Radiographics. 2009;29:e36.

18. Balamuth NJ, Womer RB. Ewing’s sarcoma. Lancet Oncol. 2010;11(2):184.

19. D’Angelo L, Massimi L, Narducci A, Di Rocco C. Ollier disease. Childs Nerv Syst. 2009;25:647-653.

20. Gelderblom H, Hogendoorn PC, Dijkstra SD, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13:320-329.

21. Nosratzehi T, Pakfetrat A. Chondrosarcoma. Zahedan J Res Med Sci. 2013;15:64-64.

22. Prado FO, Nishimoto IN, Perez DE, et al. Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral Maxillofacial Surg. 2009;47:555-557.

23. Kim HJ, Chalmers PN, Morris CD. Pediatric osteogenic sarcoma. Curr Opin Pediatr. 2010;22:61-66.

24. Sultan I, Qaddoumi I, Yaser S, et al. Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol. 2009;27:3391-3397.

25. Navarro OM, Laffan EE, Ngan B-Y. Pediatric soft-tissue tumors and pseudo-tumors: MR imaging features with pathologic correlation: Part 1. Imaging approach, pseudotumors, vascular lesions, and adipocytic tumors. Radiographics. 2009;29:887-906.

26. Gross TG, Termuhlen AM. Pediatric non-Hodgkin lymphoma. Curr Hematol Malig Rep. 2008;3:167-173.

27. Hochberg J, Waxman IM, Kelly KM, et al. Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma: state of the science. Br J Haematol. 2009;144:24-40.

28. Derenzini E, Casadei B, Pellegrini C, et al. Non-Hodgkin lymphomas presenting as soft tissue masses: A single center experience and meta-analysis of the published series. Clin Lymphoma Myeloma Leuk. 2012 Dec 12. [Epub ahead of print]

29. Micheli A, Trapani S, Brizzi I, et al. Myositis ossificans circumscripta: a paediatric case and review of the literature. Eur J Pediatr. 2009;168:523-529.

30. McKenzie G, Raby N, Ritchie D. Non-neoplastic soft-tissue masses. Br J Radiol. 2009;82:775-785.

31. Buckmiller LM, Richter GT, Suen JY. Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Dis. 2010;16:405-418.

32. Khanna G, Bennett DL. Pediatric bone lesions: beyond the plain radiographic evaluation. Semin Roentgenol. 2012;47:90-99.

33.
Rijal L, Nepal P, Baral S, et al. Solitary diaphyseal exostosis of femur, how common is it? Eur J Orthop Surg Traumatol. 2011;21:363-365.