CHICAGO – William J. Gradishar, MD, outlines key research on breast cancer treatment presented at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, discusses the take-home messages on pertuzumab for HER2+ breast cancer, PARP inhibitors for BRCA-mutated breast cancer, and CDK4/6 inhibitors for ER+ breast cancers.

In another video interview, Katherine O’Brien of the Metastatic Breast Cancer Network provides the patient advocate view on this years’ meeting.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – William J. Gradishar, MD, outlines key research on breast cancer treatment presented at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, discusses the take-home messages on pertuzumab for HER2+ breast cancer, PARP inhibitors for BRCA-mutated breast cancer, and CDK4/6 inhibitors for ER+ breast cancers.

In another video interview, Katherine O’Brien of the Metastatic Breast Cancer Network provides the patient advocate view on this years’ meeting.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – William J. Gradishar, MD, outlines key research on breast cancer treatment presented at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, discusses the take-home messages on pertuzumab for HER2+ breast cancer, PARP inhibitors for BRCA-mutated breast cancer, and CDK4/6 inhibitors for ER+ breast cancers.

In another video interview, Katherine O’Brien of the Metastatic Breast Cancer Network provides the patient advocate view on this years’ meeting.

[email protected]

On Twitter @NikolaidesLaura

Clinicians who are counseling vaccine-hesitant parents about vaccination may want to consider adding immunization requirements of universities to their armamentarium, recommended Allison Noesekabel, a medical student at Wayne State University, Detroit, and Ada M. Fenick, MD, a pediatrician at Yale University, New Haven, Conn.

After identifying the 200 top-ranked U.S. universities in the US News and World Report 2014 National University rankings and sending a survey on university prematriculation immunization requirements (PIRs), the responding 124 universities spanned 44 states and the District of Columbia. Of those who responded, 94% had at least one PIR, 84% had at least two, 63% had at least three, and 16% required all the vaccines as required by any jurisdictional law for attendance at universities (hepatitis B, meningococcus, MMR, TdaP, and varicella). Only 6% of the universities had no immunization requirements.

Of the 121 universities with PIRs, 2% did not allow medical exemptions, 2% did not allow religious exemptions, and 46% did not allow philosophical belief exemptions. Medical exemptions were hardest to obtain for 24% of the 121 universities with PIRs, religious exemptions were the most difficult to obtain at 40%, and philosophical belief exemptions were hardest to obtain at 60% of the universities with PIRs. The most common administrative responses to lack of immunization were “the placement of a hold on registration of classes (89% of universities), additional registration fees (13%), and a hold on student housing (11%),” Ms. Noesekabel and Dr. Frenik reported.

Ms. Noesekabel and Dr. Frenik said they chose highly ranked universities for their study because these were likely to be desirable to vaccine-hesitant families, who tend to be highly educated and affluent. Therefore, the findings of this study may not be representative of all 4-year U.S. colleges, they said.

Read more at Vaccine (2017. doi: 10.1016/j.vaccine.2017.05.038).

[email protected]

Clinicians who are counseling vaccine-hesitant parents about vaccination may want to consider adding immunization requirements of universities to their armamentarium, recommended Allison Noesekabel, a medical student at Wayne State University, Detroit, and Ada M. Fenick, MD, a pediatrician at Yale University, New Haven, Conn.

After identifying the 200 top-ranked U.S. universities in the US News and World Report 2014 National University rankings and sending a survey on university prematriculation immunization requirements (PIRs), the responding 124 universities spanned 44 states and the District of Columbia. Of those who responded, 94% had at least one PIR, 84% had at least two, 63% had at least three, and 16% required all the vaccines as required by any jurisdictional law for attendance at universities (hepatitis B, meningococcus, MMR, TdaP, and varicella). Only 6% of the universities had no immunization requirements.

Of the 121 universities with PIRs, 2% did not allow medical exemptions, 2% did not allow religious exemptions, and 46% did not allow philosophical belief exemptions. Medical exemptions were hardest to obtain for 24% of the 121 universities with PIRs, religious exemptions were the most difficult to obtain at 40%, and philosophical belief exemptions were hardest to obtain at 60% of the universities with PIRs. The most common administrative responses to lack of immunization were “the placement of a hold on registration of classes (89% of universities), additional registration fees (13%), and a hold on student housing (11%),” Ms. Noesekabel and Dr. Frenik reported.

Ms. Noesekabel and Dr. Frenik said they chose highly ranked universities for their study because these were likely to be desirable to vaccine-hesitant families, who tend to be highly educated and affluent. Therefore, the findings of this study may not be representative of all 4-year U.S. colleges, they said.

Read more at Vaccine (2017. doi: 10.1016/j.vaccine.2017.05.038).

[email protected]

Clinicians who are counseling vaccine-hesitant parents about vaccination may want to consider adding immunization requirements of universities to their armamentarium, recommended Allison Noesekabel, a medical student at Wayne State University, Detroit, and Ada M. Fenick, MD, a pediatrician at Yale University, New Haven, Conn.

After identifying the 200 top-ranked U.S. universities in the US News and World Report 2014 National University rankings and sending a survey on university prematriculation immunization requirements (PIRs), the responding 124 universities spanned 44 states and the District of Columbia. Of those who responded, 94% had at least one PIR, 84% had at least two, 63% had at least three, and 16% required all the vaccines as required by any jurisdictional law for attendance at universities (hepatitis B, meningococcus, MMR, TdaP, and varicella). Only 6% of the universities had no immunization requirements.

Of the 121 universities with PIRs, 2% did not allow medical exemptions, 2% did not allow religious exemptions, and 46% did not allow philosophical belief exemptions. Medical exemptions were hardest to obtain for 24% of the 121 universities with PIRs, religious exemptions were the most difficult to obtain at 40%, and philosophical belief exemptions were hardest to obtain at 60% of the universities with PIRs. The most common administrative responses to lack of immunization were “the placement of a hold on registration of classes (89% of universities), additional registration fees (13%), and a hold on student housing (11%),” Ms. Noesekabel and Dr. Frenik reported.

Ms. Noesekabel and Dr. Frenik said they chose highly ranked universities for their study because these were likely to be desirable to vaccine-hesitant families, who tend to be highly educated and affluent. Therefore, the findings of this study may not be representative of all 4-year U.S. colleges, they said.

Read more at Vaccine (2017. doi: 10.1016/j.vaccine.2017.05.038).

[email protected]

LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.

Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.

[email protected]

LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.

Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.

[email protected]

LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.

Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.

[email protected]

[polldaddy:9772731]

[polldaddy:9772731]

[polldaddy:9772731]

Paris – One-year outcomes were significantly worse in patients with acute coronary syndrome whose revascularization was deferred based upon the results of fractional flow reserve than with instantaneous wave-free ratio, in the largest-ever study of patients whose revascularization decision was guided by physiologic measurements obtained via a pressure guidewire.

“The hypothesis that some authors have put forth – that in an ACS the hyperemic response of the myocardium is blunted by the ACS, and that this will affect the FFR hyperemic index – is now strengthened,” Javier Escaned, MD, said in presenting the study results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The study was a pooled, patient-level meta-analysis of the 4,529 participants with angiographically determined intermediate-risk stenoses in the previously reported randomized DEFINE FLAIR (N Engl J Med. 2017 May 11;376[19]:1824-34) and iFR SWEDEHEART (N Engl J Med. 2017 May 11;376[19]:1813-23) studies. The primary endpoint was the composite of death, nonfatal MI, or unplanned coronary revascularization within 12 months. And while the analysis brought unwelcome news for proponents of FFR with regard to the subset of patients with ACS, such patients comprised only 17% of the total study population.

Bruce Jancin/Frontline Medical News

•  More patients were deferred from PCI when iFR was used for decision-making: 50%, compared with 45% in the FFR arm. Yet 1-year outcomes were as good in the deferred iFR group as in the FFR group overall, and better than with FFR in the deferred ACS patients.

•  Event rates were significantly higher in deferred ACS patients overall than in deferred patients with stable coronary disease: 5.9% versus 3.6%. But the deferral tool made a difference: When iFR was utilized, the 1-year event rate was 5.4% in deferred ACS patients, not significantly different from the 3.8% rate in deferred patients with stable coronary disease. In contrast, the event rate in ACS patients with FFR-based deferral was 6.4%, significantly higher than the 3.4% rate in FFR-deferred patients with stable coronary disease.

Dr. Escaned noted that this finding is consistent with the cautionary results of several recent studies, including one, albeit tenfold smaller, in which ACS patients in whom revascularization was deferred based on FFR had a 25% rate of major adverse cardiovascular events at 3.4 years, compared with a 12% rate in patients with stable coronary disease (J Am Coll Cardiol. 2016 Sep 13;68[11]:1181-91).

Discussant Peter Jüni, MD, professor of medicine at the University of Toronto, said “the main results of your study show in a completely waterproof fashion that there is no signal of harm with the experimental strategy” of deferred revascularization based on physiologic measurements, at least in patients with stable ischemic coronary disease.

The results, however, also raise the question of whether physiology-based revascularization decision-making in ACS patients is the best strategy.

“Considering that the event rate in the deferred ACS group was nearly twice as high compared with stable patients, my question to you is: Should we ignore any functional testing in ACS patients and just say, ‘Let’s move forward with revascularization because this clinical presentation is a very good clinical characteristic for risk stratification?’ ”

Dr. Escaned rejected that option. He noted that both the European and U.S. guidelines now state that it’s inappropriate to base a revascularization decision solely on a coronary vessel’s angiographic appearance, because that has been shown to result in unnecessary treatment, which causes harm. Adoption of pressure guidewires to assist in revascularization decision making, whether by FFR or iFR, is still limited in interventional cardiology. The priority in the field now should be to encourage more widespread use of this technology, regardless of which method is selected, he argued.

“The biggest room in the world is the room for improvement,” the cardiologist mused.

“I think one of the real problems that’s impeding adoption of physiologic testing is that many physicians are still afraid of leaving a stenosis without treatment,” he continued. “It’s strange: If you perform angioplasty and it wasn’t indicated and there is a complication, physicians seem to have some type of peace of mind that they did their best and they were trying to help the patient. That’s why it’s so important to establish that deferring revascularization – not treating when it is not needed – is safe.”

The DEFINE FLAIR and iFR SWEDEHEART studies were funded by unrestricted grants from Philips Volcano. Dr. Escaned reported serving as a consultant to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, and Philips Healthcare.

[email protected]

Paris – One-year outcomes were significantly worse in patients with acute coronary syndrome whose revascularization was deferred based upon the results of fractional flow reserve than with instantaneous wave-free ratio, in the largest-ever study of patients whose revascularization decision was guided by physiologic measurements obtained via a pressure guidewire.

“The hypothesis that some authors have put forth – that in an ACS the hyperemic response of the myocardium is blunted by the ACS, and that this will affect the FFR hyperemic index – is now strengthened,” Javier Escaned, MD, said in presenting the study results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The study was a pooled, patient-level meta-analysis of the 4,529 participants with angiographically determined intermediate-risk stenoses in the previously reported randomized DEFINE FLAIR (N Engl J Med. 2017 May 11;376[19]:1824-34) and iFR SWEDEHEART (N Engl J Med. 2017 May 11;376[19]:1813-23) studies. The primary endpoint was the composite of death, nonfatal MI, or unplanned coronary revascularization within 12 months. And while the analysis brought unwelcome news for proponents of FFR with regard to the subset of patients with ACS, such patients comprised only 17% of the total study population.

Bruce Jancin/Frontline Medical News

•  More patients were deferred from PCI when iFR was used for decision-making: 50%, compared with 45% in the FFR arm. Yet 1-year outcomes were as good in the deferred iFR group as in the FFR group overall, and better than with FFR in the deferred ACS patients.

•  Event rates were significantly higher in deferred ACS patients overall than in deferred patients with stable coronary disease: 5.9% versus 3.6%. But the deferral tool made a difference: When iFR was utilized, the 1-year event rate was 5.4% in deferred ACS patients, not significantly different from the 3.8% rate in deferred patients with stable coronary disease. In contrast, the event rate in ACS patients with FFR-based deferral was 6.4%, significantly higher than the 3.4% rate in FFR-deferred patients with stable coronary disease.

Dr. Escaned noted that this finding is consistent with the cautionary results of several recent studies, including one, albeit tenfold smaller, in which ACS patients in whom revascularization was deferred based on FFR had a 25% rate of major adverse cardiovascular events at 3.4 years, compared with a 12% rate in patients with stable coronary disease (J Am Coll Cardiol. 2016 Sep 13;68[11]:1181-91).

Discussant Peter Jüni, MD, professor of medicine at the University of Toronto, said “the main results of your study show in a completely waterproof fashion that there is no signal of harm with the experimental strategy” of deferred revascularization based on physiologic measurements, at least in patients with stable ischemic coronary disease.

The results, however, also raise the question of whether physiology-based revascularization decision-making in ACS patients is the best strategy.

“Considering that the event rate in the deferred ACS group was nearly twice as high compared with stable patients, my question to you is: Should we ignore any functional testing in ACS patients and just say, ‘Let’s move forward with revascularization because this clinical presentation is a very good clinical characteristic for risk stratification?’ ”

Dr. Escaned rejected that option. He noted that both the European and U.S. guidelines now state that it’s inappropriate to base a revascularization decision solely on a coronary vessel’s angiographic appearance, because that has been shown to result in unnecessary treatment, which causes harm. Adoption of pressure guidewires to assist in revascularization decision making, whether by FFR or iFR, is still limited in interventional cardiology. The priority in the field now should be to encourage more widespread use of this technology, regardless of which method is selected, he argued.

“The biggest room in the world is the room for improvement,” the cardiologist mused.

“I think one of the real problems that’s impeding adoption of physiologic testing is that many physicians are still afraid of leaving a stenosis without treatment,” he continued. “It’s strange: If you perform angioplasty and it wasn’t indicated and there is a complication, physicians seem to have some type of peace of mind that they did their best and they were trying to help the patient. That’s why it’s so important to establish that deferring revascularization – not treating when it is not needed – is safe.”

The DEFINE FLAIR and iFR SWEDEHEART studies were funded by unrestricted grants from Philips Volcano. Dr. Escaned reported serving as a consultant to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, and Philips Healthcare.

[email protected]

Paris – One-year outcomes were significantly worse in patients with acute coronary syndrome whose revascularization was deferred based upon the results of fractional flow reserve than with instantaneous wave-free ratio, in the largest-ever study of patients whose revascularization decision was guided by physiologic measurements obtained via a pressure guidewire.

“The hypothesis that some authors have put forth – that in an ACS the hyperemic response of the myocardium is blunted by the ACS, and that this will affect the FFR hyperemic index – is now strengthened,” Javier Escaned, MD, said in presenting the study results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The study was a pooled, patient-level meta-analysis of the 4,529 participants with angiographically determined intermediate-risk stenoses in the previously reported randomized DEFINE FLAIR (N Engl J Med. 2017 May 11;376[19]:1824-34) and iFR SWEDEHEART (N Engl J Med. 2017 May 11;376[19]:1813-23) studies. The primary endpoint was the composite of death, nonfatal MI, or unplanned coronary revascularization within 12 months. And while the analysis brought unwelcome news for proponents of FFR with regard to the subset of patients with ACS, such patients comprised only 17% of the total study population.

Bruce Jancin/Frontline Medical News

•  More patients were deferred from PCI when iFR was used for decision-making: 50%, compared with 45% in the FFR arm. Yet 1-year outcomes were as good in the deferred iFR group as in the FFR group overall, and better than with FFR in the deferred ACS patients.

•  Event rates were significantly higher in deferred ACS patients overall than in deferred patients with stable coronary disease: 5.9% versus 3.6%. But the deferral tool made a difference: When iFR was utilized, the 1-year event rate was 5.4% in deferred ACS patients, not significantly different from the 3.8% rate in deferred patients with stable coronary disease. In contrast, the event rate in ACS patients with FFR-based deferral was 6.4%, significantly higher than the 3.4% rate in FFR-deferred patients with stable coronary disease.

Dr. Escaned noted that this finding is consistent with the cautionary results of several recent studies, including one, albeit tenfold smaller, in which ACS patients in whom revascularization was deferred based on FFR had a 25% rate of major adverse cardiovascular events at 3.4 years, compared with a 12% rate in patients with stable coronary disease (J Am Coll Cardiol. 2016 Sep 13;68[11]:1181-91).

Discussant Peter Jüni, MD, professor of medicine at the University of Toronto, said “the main results of your study show in a completely waterproof fashion that there is no signal of harm with the experimental strategy” of deferred revascularization based on physiologic measurements, at least in patients with stable ischemic coronary disease.

The results, however, also raise the question of whether physiology-based revascularization decision-making in ACS patients is the best strategy.

“Considering that the event rate in the deferred ACS group was nearly twice as high compared with stable patients, my question to you is: Should we ignore any functional testing in ACS patients and just say, ‘Let’s move forward with revascularization because this clinical presentation is a very good clinical characteristic for risk stratification?’ ”

Dr. Escaned rejected that option. He noted that both the European and U.S. guidelines now state that it’s inappropriate to base a revascularization decision solely on a coronary vessel’s angiographic appearance, because that has been shown to result in unnecessary treatment, which causes harm. Adoption of pressure guidewires to assist in revascularization decision making, whether by FFR or iFR, is still limited in interventional cardiology. The priority in the field now should be to encourage more widespread use of this technology, regardless of which method is selected, he argued.

“The biggest room in the world is the room for improvement,” the cardiologist mused.

“I think one of the real problems that’s impeding adoption of physiologic testing is that many physicians are still afraid of leaving a stenosis without treatment,” he continued. “It’s strange: If you perform angioplasty and it wasn’t indicated and there is a complication, physicians seem to have some type of peace of mind that they did their best and they were trying to help the patient. That’s why it’s so important to establish that deferring revascularization – not treating when it is not needed – is safe.”

The DEFINE FLAIR and iFR SWEDEHEART studies were funded by unrestricted grants from Philips Volcano. Dr. Escaned reported serving as a consultant to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, and Philips Healthcare.

[email protected]

Take-Home Points

• Stability of the foot is dependent on both the medial and lateral longitudinal columns; injuries to a single column alone are extremely rare.
• Midfoot fractures that are recognized and treated early have generally favorable outcomes compared to those identified in a delayed fashion.
• The most frequent complication of navicular dislocation is AVN, which is said to occur in as many as 25% of cases.
• Many specialists agree that navicular dislocations are best treated with open reduction.
• Ultimately, the goals of surgical intervention are to minimize pain and to establish stability of the plantigrade foot.

Traumatic dislocation of the tarsal navicular (especially without a navicular body fracture) is uncommon.¹ The regional anatomy and ligamentous architecture confer stability to the midfoot.^2-6 Navicular dislocation is part of a complex disruption involving structures in the adjacent column.⁶

Navicular dislocation has been associated with several bony and soft-tissue injury patterns, including comminuted intra-articular fracture of the calcaneus and associated calcaneocuboid joint subluxation; fracture and subluxation of the calcaneocuboid joint; fracture-dislocation of the calcaneocuboid joint with fractures of the third and fourth metatarsals; and a combination of fractures of the intermediate cuneiform, the second through fourth metatarsals, and the cuboid.^4–11 In this article, we report a case of open complete navicular dislocation with talar head fracture and associated subtalar and calcaneocuboid subluxations in a 45-year-old man. The injury was managed with open reduction and stabilization with Kirschner wires (K-wires), which later required naviculocuneiform and intercuneiform fusion for posttraumatic avascular necrosis (AVN). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 45-year-old man sustained blunt trauma to the right foot in a high-speed head-on collision. He was hemodynamically stable with isolated complaints of pain in the foot. Physical examination revealed a grossly open 10-cm wound extending from the heel pad medially to the dorsal surface of the navicular. The navicular was clearly visible through the wound.

Plain radiographs of the foot showed complete medial dislocation of the navicular with complete disruption of all 3 naviculocuneiform joints (Figures 1A-1C).

Discussion

The naviculocuneiform joints are important for the dissipation of loading stresses on the midfoot but provide little motion. The plantar and dorsal ligaments are thick structures that stabilize these joints, predisposing the navicular to fracture rather than isolated dislocation. The stability of the foot is dependent on both the medial and lateral longitudinal columns, and it is thought impossible to injure one column without disrupting the other.⁶ Several patterns of associated lateral column disruptions have been documented, including 3 cases similar to our patient’s, involving navicular dislocation with associated calcaneocuboid joint injuries.^5,6,10

Authors have proposed several mechanisms accounting for navicular dislocations. In the setting of acute trauma, the navicular displaces dorsally as the result of forefoot plantar flexion and axial loading.⁴ A severe abduction/pronation injury leading to a midtarsal dislocation followed by a spontaneous reduction can force the navicular to dislocate medially.⁶ This disruption of the naviculocuneiform joint and concurrent “nutcracker” injury to the lateral column can produce an associated disruption of the calcaneocuboid joint.⁶ Depending on the direction of the deforming force, the forefoot can dislocate superolaterally if the force is plantar or inferolaterally if the force is dorsal. The remaining soft-tissue attachments help determine the position of the navicular. A third postulated mechanism involves a complex wringing injury to the forefoot.¹⁰Most specialists agree that navicular dislocations are best treated with open reduction.^4,6 The goal of surgical intervention is to establish a stable plantigrade foot and to minimize pain. The current literature supports using either wires or screws to maintain reduction of midfoot injuries. Wires can be used for both talonavicular and naviculocuneiform fixation. Screws can be placed across the naviculocuneiform joints, as there is little normal physiologic motion through these joints.⁴ The talonavicular joint and the cuboid-metatarsal joints provide most of the motion in the midfoot and should not be readily fused.⁵ Stabilization of both columns is considered necessary to avoid complications such as subluxation and midfoot deformity.Given the postreduction stability of the lateral column in the present case, bicolumnar stabilization was not considered necessary. It is possible that subsequent collapse of the midfoot may have been attenuated in the presence of lateral fixation, but this would not necessarily have prevented complications of AVN.

Midfoot fractures that are recognized and treated early have generally favorable outcomes,^5-11 though chronic pain and subsequent deformity are not uncommon. Perhaps the most frequently reported complication of navicular dislocation is AVN, which is thought to occur in approximately 25% of cases.¹² AVN is a well-recognized complication of hindfoot and midfoot trauma. In the tarsal navicular, blood supply to the central-third watershed region is marginal. Small branches of the posterior tibial and dorsalis pedis arteries that supply the medial and lateral areas are readily injured. Not surprisingly, the risk for AVN is high when the dislocated bone is severely displaced.⁶ In some circumstances, the shared blood supply of the posterior tibialis may be the only remaining osseous supply. The tendon and its soft-tissue attachments should therefore be carefully monitored during dissection and reduction.⁶ In most cases, AVN of the foot manifests clinically within the first 10 months after injury, as was the case with our patient.¹³ AVN can result in the Charcot-like collapse of the medial column, leading to progressive midfoot plantar deformities.⁴ Variations of midfoot fusion are often required.^4,6AVN may be difficult to differentiate from posttraumatic arthritis. These conditions can have similar clinical presentations and appearances on plain radiographs. In such situations, magnetic resonance imaging or bone scintigraphy may determine the diagnosis. Damage to the articular surface at time of injury and residual articular displacement, instability, and joint subluxation after injury are considered risk factors for the development of posttraumatic arthritis in the foot and ankle.¹⁴ Reports suggest that the severity of the damage to the articular surface is directly proportional to the degree of arthritis.¹⁴ Such damage may not be initially visible, especially in axial impaction injuries, but latent deterioration of the articular surface can occur.¹⁵ For patients with significant dislocations of the naviculocuneiform joints, some authors advocate primary and early fusion¹⁵ instead of the more conservative approach used here. Primary fusions are argued to have minimal deleterious effects on function, secondary to the absence of normal physiologic motion through the affected joints.¹⁵ However, there is relatively little published evidence on long-term outcomes in primary versus secondary naviculocuneiform fusions.

Successful treatment of midfoot fractures and dislocations requires intimate knowledge of foot and ankle anatomy and mechanics. Surgeons must be able to anticipate, identify, and counsel patients about acute and delayed complications in these already challenging injuries.

Am J Orthop. 2017;46(3):E186-E189. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Stability of the foot is dependent on both the medial and lateral longitudinal columns; injuries to a single column alone are extremely rare.
• Midfoot fractures that are recognized and treated early have generally favorable outcomes compared to those identified in a delayed fashion.
• The most frequent complication of navicular dislocation is AVN, which is said to occur in as many as 25% of cases.
• Many specialists agree that navicular dislocations are best treated with open reduction.
• Ultimately, the goals of surgical intervention are to minimize pain and to establish stability of the plantigrade foot.

Traumatic dislocation of the tarsal navicular (especially without a navicular body fracture) is uncommon.¹ The regional anatomy and ligamentous architecture confer stability to the midfoot.^2-6 Navicular dislocation is part of a complex disruption involving structures in the adjacent column.⁶

Navicular dislocation has been associated with several bony and soft-tissue injury patterns, including comminuted intra-articular fracture of the calcaneus and associated calcaneocuboid joint subluxation; fracture and subluxation of the calcaneocuboid joint; fracture-dislocation of the calcaneocuboid joint with fractures of the third and fourth metatarsals; and a combination of fractures of the intermediate cuneiform, the second through fourth metatarsals, and the cuboid.^4–11 In this article, we report a case of open complete navicular dislocation with talar head fracture and associated subtalar and calcaneocuboid subluxations in a 45-year-old man. The injury was managed with open reduction and stabilization with Kirschner wires (K-wires), which later required naviculocuneiform and intercuneiform fusion for posttraumatic avascular necrosis (AVN). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 45-year-old man sustained blunt trauma to the right foot in a high-speed head-on collision. He was hemodynamically stable with isolated complaints of pain in the foot. Physical examination revealed a grossly open 10-cm wound extending from the heel pad medially to the dorsal surface of the navicular. The navicular was clearly visible through the wound.

Plain radiographs of the foot showed complete medial dislocation of the navicular with complete disruption of all 3 naviculocuneiform joints (Figures 1A-1C).

Discussion

The naviculocuneiform joints are important for the dissipation of loading stresses on the midfoot but provide little motion. The plantar and dorsal ligaments are thick structures that stabilize these joints, predisposing the navicular to fracture rather than isolated dislocation. The stability of the foot is dependent on both the medial and lateral longitudinal columns, and it is thought impossible to injure one column without disrupting the other.⁶ Several patterns of associated lateral column disruptions have been documented, including 3 cases similar to our patient’s, involving navicular dislocation with associated calcaneocuboid joint injuries.^5,6,10

Authors have proposed several mechanisms accounting for navicular dislocations. In the setting of acute trauma, the navicular displaces dorsally as the result of forefoot plantar flexion and axial loading.⁴ A severe abduction/pronation injury leading to a midtarsal dislocation followed by a spontaneous reduction can force the navicular to dislocate medially.⁶ This disruption of the naviculocuneiform joint and concurrent “nutcracker” injury to the lateral column can produce an associated disruption of the calcaneocuboid joint.⁶ Depending on the direction of the deforming force, the forefoot can dislocate superolaterally if the force is plantar or inferolaterally if the force is dorsal. The remaining soft-tissue attachments help determine the position of the navicular. A third postulated mechanism involves a complex wringing injury to the forefoot.¹⁰Most specialists agree that navicular dislocations are best treated with open reduction.^4,6 The goal of surgical intervention is to establish a stable plantigrade foot and to minimize pain. The current literature supports using either wires or screws to maintain reduction of midfoot injuries. Wires can be used for both talonavicular and naviculocuneiform fixation. Screws can be placed across the naviculocuneiform joints, as there is little normal physiologic motion through these joints.⁴ The talonavicular joint and the cuboid-metatarsal joints provide most of the motion in the midfoot and should not be readily fused.⁵ Stabilization of both columns is considered necessary to avoid complications such as subluxation and midfoot deformity.Given the postreduction stability of the lateral column in the present case, bicolumnar stabilization was not considered necessary. It is possible that subsequent collapse of the midfoot may have been attenuated in the presence of lateral fixation, but this would not necessarily have prevented complications of AVN.

Midfoot fractures that are recognized and treated early have generally favorable outcomes,^5-11 though chronic pain and subsequent deformity are not uncommon. Perhaps the most frequently reported complication of navicular dislocation is AVN, which is thought to occur in approximately 25% of cases.¹² AVN is a well-recognized complication of hindfoot and midfoot trauma. In the tarsal navicular, blood supply to the central-third watershed region is marginal. Small branches of the posterior tibial and dorsalis pedis arteries that supply the medial and lateral areas are readily injured. Not surprisingly, the risk for AVN is high when the dislocated bone is severely displaced.⁶ In some circumstances, the shared blood supply of the posterior tibialis may be the only remaining osseous supply. The tendon and its soft-tissue attachments should therefore be carefully monitored during dissection and reduction.⁶ In most cases, AVN of the foot manifests clinically within the first 10 months after injury, as was the case with our patient.¹³ AVN can result in the Charcot-like collapse of the medial column, leading to progressive midfoot plantar deformities.⁴ Variations of midfoot fusion are often required.^4,6AVN may be difficult to differentiate from posttraumatic arthritis. These conditions can have similar clinical presentations and appearances on plain radiographs. In such situations, magnetic resonance imaging or bone scintigraphy may determine the diagnosis. Damage to the articular surface at time of injury and residual articular displacement, instability, and joint subluxation after injury are considered risk factors for the development of posttraumatic arthritis in the foot and ankle.¹⁴ Reports suggest that the severity of the damage to the articular surface is directly proportional to the degree of arthritis.¹⁴ Such damage may not be initially visible, especially in axial impaction injuries, but latent deterioration of the articular surface can occur.¹⁵ For patients with significant dislocations of the naviculocuneiform joints, some authors advocate primary and early fusion¹⁵ instead of the more conservative approach used here. Primary fusions are argued to have minimal deleterious effects on function, secondary to the absence of normal physiologic motion through the affected joints.¹⁵ However, there is relatively little published evidence on long-term outcomes in primary versus secondary naviculocuneiform fusions.

Successful treatment of midfoot fractures and dislocations requires intimate knowledge of foot and ankle anatomy and mechanics. Surgeons must be able to anticipate, identify, and counsel patients about acute and delayed complications in these already challenging injuries.

Am J Orthop. 2017;46(3):E186-E189. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Stability of the foot is dependent on both the medial and lateral longitudinal columns; injuries to a single column alone are extremely rare.
• Midfoot fractures that are recognized and treated early have generally favorable outcomes compared to those identified in a delayed fashion.
• The most frequent complication of navicular dislocation is AVN, which is said to occur in as many as 25% of cases.
• Many specialists agree that navicular dislocations are best treated with open reduction.
• Ultimately, the goals of surgical intervention are to minimize pain and to establish stability of the plantigrade foot.

Traumatic dislocation of the tarsal navicular (especially without a navicular body fracture) is uncommon.¹ The regional anatomy and ligamentous architecture confer stability to the midfoot.^2-6 Navicular dislocation is part of a complex disruption involving structures in the adjacent column.⁶

Navicular dislocation has been associated with several bony and soft-tissue injury patterns, including comminuted intra-articular fracture of the calcaneus and associated calcaneocuboid joint subluxation; fracture and subluxation of the calcaneocuboid joint; fracture-dislocation of the calcaneocuboid joint with fractures of the third and fourth metatarsals; and a combination of fractures of the intermediate cuneiform, the second through fourth metatarsals, and the cuboid.^4–11 In this article, we report a case of open complete navicular dislocation with talar head fracture and associated subtalar and calcaneocuboid subluxations in a 45-year-old man. The injury was managed with open reduction and stabilization with Kirschner wires (K-wires), which later required naviculocuneiform and intercuneiform fusion for posttraumatic avascular necrosis (AVN). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 45-year-old man sustained blunt trauma to the right foot in a high-speed head-on collision. He was hemodynamically stable with isolated complaints of pain in the foot. Physical examination revealed a grossly open 10-cm wound extending from the heel pad medially to the dorsal surface of the navicular. The navicular was clearly visible through the wound.

Plain radiographs of the foot showed complete medial dislocation of the navicular with complete disruption of all 3 naviculocuneiform joints (Figures 1A-1C).

Discussion

The naviculocuneiform joints are important for the dissipation of loading stresses on the midfoot but provide little motion. The plantar and dorsal ligaments are thick structures that stabilize these joints, predisposing the navicular to fracture rather than isolated dislocation. The stability of the foot is dependent on both the medial and lateral longitudinal columns, and it is thought impossible to injure one column without disrupting the other.⁶ Several patterns of associated lateral column disruptions have been documented, including 3 cases similar to our patient’s, involving navicular dislocation with associated calcaneocuboid joint injuries.^5,6,10

Authors have proposed several mechanisms accounting for navicular dislocations. In the setting of acute trauma, the navicular displaces dorsally as the result of forefoot plantar flexion and axial loading.⁴ A severe abduction/pronation injury leading to a midtarsal dislocation followed by a spontaneous reduction can force the navicular to dislocate medially.⁶ This disruption of the naviculocuneiform joint and concurrent “nutcracker” injury to the lateral column can produce an associated disruption of the calcaneocuboid joint.⁶ Depending on the direction of the deforming force, the forefoot can dislocate superolaterally if the force is plantar or inferolaterally if the force is dorsal. The remaining soft-tissue attachments help determine the position of the navicular. A third postulated mechanism involves a complex wringing injury to the forefoot.¹⁰Most specialists agree that navicular dislocations are best treated with open reduction.^4,6 The goal of surgical intervention is to establish a stable plantigrade foot and to minimize pain. The current literature supports using either wires or screws to maintain reduction of midfoot injuries. Wires can be used for both talonavicular and naviculocuneiform fixation. Screws can be placed across the naviculocuneiform joints, as there is little normal physiologic motion through these joints.⁴ The talonavicular joint and the cuboid-metatarsal joints provide most of the motion in the midfoot and should not be readily fused.⁵ Stabilization of both columns is considered necessary to avoid complications such as subluxation and midfoot deformity.Given the postreduction stability of the lateral column in the present case, bicolumnar stabilization was not considered necessary. It is possible that subsequent collapse of the midfoot may have been attenuated in the presence of lateral fixation, but this would not necessarily have prevented complications of AVN.

Midfoot fractures that are recognized and treated early have generally favorable outcomes,^5-11 though chronic pain and subsequent deformity are not uncommon. Perhaps the most frequently reported complication of navicular dislocation is AVN, which is thought to occur in approximately 25% of cases.¹² AVN is a well-recognized complication of hindfoot and midfoot trauma. In the tarsal navicular, blood supply to the central-third watershed region is marginal. Small branches of the posterior tibial and dorsalis pedis arteries that supply the medial and lateral areas are readily injured. Not surprisingly, the risk for AVN is high when the dislocated bone is severely displaced.⁶ In some circumstances, the shared blood supply of the posterior tibialis may be the only remaining osseous supply. The tendon and its soft-tissue attachments should therefore be carefully monitored during dissection and reduction.⁶ In most cases, AVN of the foot manifests clinically within the first 10 months after injury, as was the case with our patient.¹³ AVN can result in the Charcot-like collapse of the medial column, leading to progressive midfoot plantar deformities.⁴ Variations of midfoot fusion are often required.^4,6AVN may be difficult to differentiate from posttraumatic arthritis. These conditions can have similar clinical presentations and appearances on plain radiographs. In such situations, magnetic resonance imaging or bone scintigraphy may determine the diagnosis. Damage to the articular surface at time of injury and residual articular displacement, instability, and joint subluxation after injury are considered risk factors for the development of posttraumatic arthritis in the foot and ankle.¹⁴ Reports suggest that the severity of the damage to the articular surface is directly proportional to the degree of arthritis.¹⁴ Such damage may not be initially visible, especially in axial impaction injuries, but latent deterioration of the articular surface can occur.¹⁵ For patients with significant dislocations of the naviculocuneiform joints, some authors advocate primary and early fusion¹⁵ instead of the more conservative approach used here. Primary fusions are argued to have minimal deleterious effects on function, secondary to the absence of normal physiologic motion through the affected joints.¹⁵ However, there is relatively little published evidence on long-term outcomes in primary versus secondary naviculocuneiform fusions.

Successful treatment of midfoot fractures and dislocations requires intimate knowledge of foot and ankle anatomy and mechanics. Surgeons must be able to anticipate, identify, and counsel patients about acute and delayed complications in these already challenging injuries.

Am J Orthop. 2017;46(3):E186-E189. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Yes, functional TR is worth repairing (David H. Adams, MD)

Functional tricuspid regurgitation is a common finding in patients undergoing degenerative mitral valve repair. Severe tricuspid regurgitation is unusual, and clearly there is little debate on the merits of concomitant tricuspid repair for these patients. Moderate tricuspid regurgitation is identified preoperatively in around 15% of patients undergoing degenerative mitral repair (J Thorac Cardiovasc Surg. 2011;142:608-13), and concomitant tricuspid repair in these patients is certainly supported by both the American and European guidelines (J Am Coll Cardiol. 2017. doi: 10.1016/j.jacc.2017.03.011; Eur Heart J. 2012;33:2451-96).

What experience and evidence has led us to a more aggressive approach? One of the most important influences on our early adoption of tricuspid repair at the time of mitral surgery was linked to observations that tricuspid regurgitation (TR) sometimes progressed after isolated mitral valve repair (MVR), with some patients developing moderate or worse insufficiency. Certainly, the impact of significant tricuspid regurgitation on the quality and length of patients’ lives and the challenges of reoperation for isolated tricuspid regurgitation are well known to all surgeons.

Dr. Adams is cardiac surgeon-in-chief, Mount Sinai Health System, and Marie-Josée and Henry R. Kravis Professor and Chairman, department of cardiovascular surgery, Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital, and president-elect of the American Association for Thoracic Surgery. He disclosed he is the national co-principal investigator for the Medtronic NeoChord trial, and receives royalties from Medtronic and Edwards Lifesciences. The Icahn School of Medicine at Mount Sinai receives royalty payments from Edwards Lifesciences and Medtronic for intellectual property related to Dr. Adams’ involvement in the development of 2 mitral valve repair rings and 1 tricuspid valve repair ring.​

No, a patient with FTR does not necessarily need repair (Tirone David, MD)

In our clinic, a patient who undergoes MVR and has FTR generally goes home without an annuloplasty. We now have 12 years or more of follow-up in these patients, and they do not develop TR if their MVR is competent. We have reported that preoperative TR in patients who had MVR is associated with mitral valve disease and often improves after the operation (J Thorac Cardiovasc Surg. 2017;154:110-22). New postoperative TR is uncommon.

Ninety percent of my mitral valve repair patients today have no symptoms. Of those patients, a small proportion have moderate TR.

Dr. David is a professor of surgery at Toronto General Hospital. He reported no financial relationships.

Yes, but repair of FTR requires caution (Gilles Dreyfus, MD)

The controversy surrounding the legitimacy of concomitant tricuspid annuloplasty for functional TR during MVR begs for a clinical trial, but before we can conduct a clinical trial, we must define the primary and secondary endpoints. We’ve seen recent prospective, randomized trials that have reported faulty conclusions because the primary endpoints were wrong.

We need a strong debate to agree on those endpoints. Mortality as an endpoint will probably take a very long time to arrive at.

We’re mixing up many different factors. We’re mixing up TR grading, and we know that grading is unreliable. We have all seen patients with full-fledged TR, and after we put them on Lasix (furosemide, Sanofi), 3 days later they have mild TR. So the same patient with no treatment becomes let’s say a “Dreyfus indication,” and then suddenly in 3 days the patient doesn’t need surgery. At any further stage of his life this patient can experience severe TR again; tricuspid annuloplasty will prevent that from happening.

Dr. Dreyfus is director of the medical and surgical team at the Cardiothoracic Centre of Monaco in Monte Carlo and professor of cardiothoracic surgery at Paris V University and the Imperial College of London. He disclosed receiving speaker fees from Edwards Lifesciences, LivaNova, and Medtronic.

No, few FTR patients at risk after MVR (Hartzell Schaff, MD)

Echocardiography can provide a great deal of information about when concomitant repair for TR is indicated during MVR. We’ve found that if the patient has no right-sided signs, has normal right atrial pressure, and has mild or mild/moderate TR at the time of repair to the journey mitral valve, the chance of him returning for a tricuspid valve procedure is near zero.

A few patients do return after MVR. They develop atrial fibrillation and may need a pacemaker, but we see very few patients return for tricuspid surgery.

Dr. Schaff is a cardiothoracic surgeon at Mayo Clinic Foundation, Rochester, Minn. He reported no financial relationships.
 

Yes, functional TR is worth repairing (David H. Adams, MD)

Functional tricuspid regurgitation is a common finding in patients undergoing degenerative mitral valve repair. Severe tricuspid regurgitation is unusual, and clearly there is little debate on the merits of concomitant tricuspid repair for these patients. Moderate tricuspid regurgitation is identified preoperatively in around 15% of patients undergoing degenerative mitral repair (J Thorac Cardiovasc Surg. 2011;142:608-13), and concomitant tricuspid repair in these patients is certainly supported by both the American and European guidelines (J Am Coll Cardiol. 2017. doi: 10.1016/j.jacc.2017.03.011; Eur Heart J. 2012;33:2451-96).

What experience and evidence has led us to a more aggressive approach? One of the most important influences on our early adoption of tricuspid repair at the time of mitral surgery was linked to observations that tricuspid regurgitation (TR) sometimes progressed after isolated mitral valve repair (MVR), with some patients developing moderate or worse insufficiency. Certainly, the impact of significant tricuspid regurgitation on the quality and length of patients’ lives and the challenges of reoperation for isolated tricuspid regurgitation are well known to all surgeons.

Dr. Adams is cardiac surgeon-in-chief, Mount Sinai Health System, and Marie-Josée and Henry R. Kravis Professor and Chairman, department of cardiovascular surgery, Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital, and president-elect of the American Association for Thoracic Surgery. He disclosed he is the national co-principal investigator for the Medtronic NeoChord trial, and receives royalties from Medtronic and Edwards Lifesciences. The Icahn School of Medicine at Mount Sinai receives royalty payments from Edwards Lifesciences and Medtronic for intellectual property related to Dr. Adams’ involvement in the development of 2 mitral valve repair rings and 1 tricuspid valve repair ring.​

No, a patient with FTR does not necessarily need repair (Tirone David, MD)

In our clinic, a patient who undergoes MVR and has FTR generally goes home without an annuloplasty. We now have 12 years or more of follow-up in these patients, and they do not develop TR if their MVR is competent. We have reported that preoperative TR in patients who had MVR is associated with mitral valve disease and often improves after the operation (J Thorac Cardiovasc Surg. 2017;154:110-22). New postoperative TR is uncommon.

Ninety percent of my mitral valve repair patients today have no symptoms. Of those patients, a small proportion have moderate TR.

Dr. David is a professor of surgery at Toronto General Hospital. He reported no financial relationships.

Yes, but repair of FTR requires caution (Gilles Dreyfus, MD)

The controversy surrounding the legitimacy of concomitant tricuspid annuloplasty for functional TR during MVR begs for a clinical trial, but before we can conduct a clinical trial, we must define the primary and secondary endpoints. We’ve seen recent prospective, randomized trials that have reported faulty conclusions because the primary endpoints were wrong.

We need a strong debate to agree on those endpoints. Mortality as an endpoint will probably take a very long time to arrive at.

We’re mixing up many different factors. We’re mixing up TR grading, and we know that grading is unreliable. We have all seen patients with full-fledged TR, and after we put them on Lasix (furosemide, Sanofi), 3 days later they have mild TR. So the same patient with no treatment becomes let’s say a “Dreyfus indication,” and then suddenly in 3 days the patient doesn’t need surgery. At any further stage of his life this patient can experience severe TR again; tricuspid annuloplasty will prevent that from happening.

Dr. Dreyfus is director of the medical and surgical team at the Cardiothoracic Centre of Monaco in Monte Carlo and professor of cardiothoracic surgery at Paris V University and the Imperial College of London. He disclosed receiving speaker fees from Edwards Lifesciences, LivaNova, and Medtronic.

No, few FTR patients at risk after MVR (Hartzell Schaff, MD)

Echocardiography can provide a great deal of information about when concomitant repair for TR is indicated during MVR. We’ve found that if the patient has no right-sided signs, has normal right atrial pressure, and has mild or mild/moderate TR at the time of repair to the journey mitral valve, the chance of him returning for a tricuspid valve procedure is near zero.

A few patients do return after MVR. They develop atrial fibrillation and may need a pacemaker, but we see very few patients return for tricuspid surgery.

Dr. Schaff is a cardiothoracic surgeon at Mayo Clinic Foundation, Rochester, Minn. He reported no financial relationships.
 

Yes, functional TR is worth repairing (David H. Adams, MD)

Functional tricuspid regurgitation is a common finding in patients undergoing degenerative mitral valve repair. Severe tricuspid regurgitation is unusual, and clearly there is little debate on the merits of concomitant tricuspid repair for these patients. Moderate tricuspid regurgitation is identified preoperatively in around 15% of patients undergoing degenerative mitral repair (J Thorac Cardiovasc Surg. 2011;142:608-13), and concomitant tricuspid repair in these patients is certainly supported by both the American and European guidelines (J Am Coll Cardiol. 2017. doi: 10.1016/j.jacc.2017.03.011; Eur Heart J. 2012;33:2451-96).

What experience and evidence has led us to a more aggressive approach? One of the most important influences on our early adoption of tricuspid repair at the time of mitral surgery was linked to observations that tricuspid regurgitation (TR) sometimes progressed after isolated mitral valve repair (MVR), with some patients developing moderate or worse insufficiency. Certainly, the impact of significant tricuspid regurgitation on the quality and length of patients’ lives and the challenges of reoperation for isolated tricuspid regurgitation are well known to all surgeons.

Dr. Adams is cardiac surgeon-in-chief, Mount Sinai Health System, and Marie-Josée and Henry R. Kravis Professor and Chairman, department of cardiovascular surgery, Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital, and president-elect of the American Association for Thoracic Surgery. He disclosed he is the national co-principal investigator for the Medtronic NeoChord trial, and receives royalties from Medtronic and Edwards Lifesciences. The Icahn School of Medicine at Mount Sinai receives royalty payments from Edwards Lifesciences and Medtronic for intellectual property related to Dr. Adams’ involvement in the development of 2 mitral valve repair rings and 1 tricuspid valve repair ring.​

No, a patient with FTR does not necessarily need repair (Tirone David, MD)

In our clinic, a patient who undergoes MVR and has FTR generally goes home without an annuloplasty. We now have 12 years or more of follow-up in these patients, and they do not develop TR if their MVR is competent. We have reported that preoperative TR in patients who had MVR is associated with mitral valve disease and often improves after the operation (J Thorac Cardiovasc Surg. 2017;154:110-22). New postoperative TR is uncommon.

Ninety percent of my mitral valve repair patients today have no symptoms. Of those patients, a small proportion have moderate TR.

Dr. David is a professor of surgery at Toronto General Hospital. He reported no financial relationships.

Yes, but repair of FTR requires caution (Gilles Dreyfus, MD)

The controversy surrounding the legitimacy of concomitant tricuspid annuloplasty for functional TR during MVR begs for a clinical trial, but before we can conduct a clinical trial, we must define the primary and secondary endpoints. We’ve seen recent prospective, randomized trials that have reported faulty conclusions because the primary endpoints were wrong.

We need a strong debate to agree on those endpoints. Mortality as an endpoint will probably take a very long time to arrive at.

We’re mixing up many different factors. We’re mixing up TR grading, and we know that grading is unreliable. We have all seen patients with full-fledged TR, and after we put them on Lasix (furosemide, Sanofi), 3 days later they have mild TR. So the same patient with no treatment becomes let’s say a “Dreyfus indication,” and then suddenly in 3 days the patient doesn’t need surgery. At any further stage of his life this patient can experience severe TR again; tricuspid annuloplasty will prevent that from happening.

Dr. Dreyfus is director of the medical and surgical team at the Cardiothoracic Centre of Monaco in Monte Carlo and professor of cardiothoracic surgery at Paris V University and the Imperial College of London. He disclosed receiving speaker fees from Edwards Lifesciences, LivaNova, and Medtronic.

No, few FTR patients at risk after MVR (Hartzell Schaff, MD)

Echocardiography can provide a great deal of information about when concomitant repair for TR is indicated during MVR. We’ve found that if the patient has no right-sided signs, has normal right atrial pressure, and has mild or mild/moderate TR at the time of repair to the journey mitral valve, the chance of him returning for a tricuspid valve procedure is near zero.

A few patients do return after MVR. They develop atrial fibrillation and may need a pacemaker, but we see very few patients return for tricuspid surgery.

Dr. Schaff is a cardiothoracic surgeon at Mayo Clinic Foundation, Rochester, Minn. He reported no financial relationships.
 

BOSTON – The most rigorous study of its kind suggests that apomorphine subcutaneous infusion (APO) via pump can substantially reduce ‘off’ time when conventional therapy fails to control dyskinesias in patients with Parkinson’s disease.

“When a patient´s off periods start to become refractory to adjustments to their oral medication, consider continuous dopaminergic drug delivery such as subcutaneous apomorphine infusion, which has proven efficacy and is generally well tolerated in this group of patients,” lead author Regina Katzenschlager, MD, head of the department of neurology and the Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders at Danube Hospital in Vienna, said in an interview.

tupungato/Thinkstock

BOSTON – The most rigorous study of its kind suggests that apomorphine subcutaneous infusion (APO) via pump can substantially reduce ‘off’ time when conventional therapy fails to control dyskinesias in patients with Parkinson’s disease.

“When a patient´s off periods start to become refractory to adjustments to their oral medication, consider continuous dopaminergic drug delivery such as subcutaneous apomorphine infusion, which has proven efficacy and is generally well tolerated in this group of patients,” lead author Regina Katzenschlager, MD, head of the department of neurology and the Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders at Danube Hospital in Vienna, said in an interview.

tupungato/Thinkstock

BOSTON – The most rigorous study of its kind suggests that apomorphine subcutaneous infusion (APO) via pump can substantially reduce ‘off’ time when conventional therapy fails to control dyskinesias in patients with Parkinson’s disease.

“When a patient´s off periods start to become refractory to adjustments to their oral medication, consider continuous dopaminergic drug delivery such as subcutaneous apomorphine infusion, which has proven efficacy and is generally well tolerated in this group of patients,” lead author Regina Katzenschlager, MD, head of the department of neurology and the Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders at Danube Hospital in Vienna, said in an interview.

tupungato/Thinkstock

LUGANO, SWITZERLAND – A combination of ibrutinib and umbralisib, an investigational inhibitor of phosphatidylinostiol 3-kinase (PI3K), induced high response rates in patients with relapsed/refractory B-cell malignancies, with no dose-limiting toxicities, based on updated early efficacy results from a phase I/IB dose-escalation study.

One-year progression-free survival (PFS) was 88% for patients with chronic lymphocytic leukemia (CLL), and 1-year overall survival (OS) was 94%, reported Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

LUGANO, SWITZERLAND – A combination of ibrutinib and umbralisib, an investigational inhibitor of phosphatidylinostiol 3-kinase (PI3K), induced high response rates in patients with relapsed/refractory B-cell malignancies, with no dose-limiting toxicities, based on updated early efficacy results from a phase I/IB dose-escalation study.

One-year progression-free survival (PFS) was 88% for patients with chronic lymphocytic leukemia (CLL), and 1-year overall survival (OS) was 94%, reported Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

LUGANO, SWITZERLAND – A combination of ibrutinib and umbralisib, an investigational inhibitor of phosphatidylinostiol 3-kinase (PI3K), induced high response rates in patients with relapsed/refractory B-cell malignancies, with no dose-limiting toxicities, based on updated early efficacy results from a phase I/IB dose-escalation study.

One-year progression-free survival (PFS) was 88% for patients with chronic lymphocytic leukemia (CLL), and 1-year overall survival (OS) was 94%, reported Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Take-Home Points

• Rare and histologically indistinguishable from osteosarcoma of bone.
• Most common presentation is an enlarging mass in the thigh or buttock.
• Secondary extraosseous osteosarcoma usually arises in the field of prior external beam radiation or brachytherapy.
• Radiographic pattern of mineralization is central amorphous or cloudlike.
• On cross sectional imaging, the soft-tissue mass is separate from the underlying bone and periosteum.

Aside from multiple myeloma, osteosarcoma is the most common primary malignancy of bone, but extraosseous osteosarcoma is rare and accounts for only 1% of soft-tissue sarcomas and only 4% of all osteosarcomas.^1-3 Benign mesenchymal tumors, such as lipomas, are common, and they are estimated to outnumber their malignant counterparts by more than a factor of 100. However, the true ratio is unknown, as many clinically benign lipomas are not biopsied.⁴ Conventional lipoma is the most common lipoma and is biologically indolent. Conventional lipoma generally does not transform biologically into a more aggressive type of neoplasm—unlike atypical lipomatous tumors, which may demonstrate this type of evolution with multiple local recurrences.

This article is the first report of a case of radiation-associated extraosseous osteosarcoma that developed within a benign conventional lipoma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

In March 2013, a 72-year-old woman presented to a general surgeon with a right thigh mass of several weeks’ duration. The patient, who had a remote history of thyroid carcinoma, underwent thyroidectomy in 1991, excision of melanoma of the chest in 1998, and resection and adjuvant external beam radiotherapy (30 fractions) for Merkel cell carcinoma of the right proximal lateral leg (malignancy images unavailable) at an outside institution in 2003. Regional lymph node dissection at the time was negative. The patient remained disease-free the next 10 years. On presentation, magnetic resonance imaging (MRI) showed a 2.2-cm mass encircled by a tumor of lipomatous tissue within the vastus intermedius muscle, adjacent to but separate from the right distal femur (Figures 1A-1C).

Physical examination revealed marked ecchymosis of the left groin at the access site for embolization as well as massive ecchymosis and swelling along the right distal thigh, medial knee, and medial lower leg. The neurovascular structures were intact with full motor function and sensation distally, as well as normal distal pulses. No inguinal adenopathy was identified. The proximal portion of the prior radiation tattoo was at the inferior extent of the lesion on MRI.

The patient was treated with doxorubicin and ifosfamide (2 cycles) while waiting for the hematoma to shrink. Contrast-enhanced MRI showed a 2.2-cm enhancing mass with isointense T1 signal and heterogeneously hyperintense STIR (short tau inversion recovery) signal surrounded by a circumscribed nonenhancing lipomatous tumor within the vastus intermedius muscle, adjacent to the distal femoral cortex. There was no invasion of the bone, and a fat plane between the enhancing mass and the femoral cortex was identified (Figures 2A-2E).

Discussion

Extraosseous osteosarcoma, typically a high-grade malignant neoplasm of the soft tissues that produces osteoid or cartilaginous matrix, is histologically indistinguishable from osteosarcoma of bone.

Conventional lipoma, the most common subtype of lipoma, is a benign mesenchymal tumor. Other subtypes are hibernoma, fibrolipoma, angiolipoma, myelolipoma, spindle-cell lipoma, pleomorphic lipoma, and atypical lipomatous tumor.⁷ Atypical lipomatous tumor and well-differentiated liposarcoma are distinguished from each other by location: The World Health Organization recommends the term atypical lipomatous tumor for tumors that arise in the extremities and trunk lesions and well-differentiated liposarcoma for neoplasms that develop in the retroperitoneum, peritoneum, mediastinum, spermatic cord, and thoracic cavity.⁸ On PET, hypermetabolic activity is nonspecific and can be seen in malignant tumors and some benign reactive processes, such as evolving heterotopic ossification. However, simple lipomas, including those with mature ossification or dystrophic calcification, do not manifest increased FDG avidity.⁹

We are not aware of any published cases of extraosseous osteosarcoma arising within a conventional lipoma. A limited number of cases of coexisting conventional lipoma and spindle-cell lipoma or liposarcoma have been reported.^10-13 Retroperitoneal liposarcoma with areas of dedifferentiation into osteosarcoma has also been described.¹⁴ Development of malignant fibrous histiocytoma and liposarcoma have also been reported within intraosseous lipomas.¹⁵ One theory is based on premalignancy as a biological concept as opposed to a morphologic one. In other words, lesions that may be considered morphologically benign may already have the biological phenotype for malignancy that is not yet reflected morphologically.¹⁶ However, it has been suggested that such findings may instead result from initial sampling error or histologic misdiagnosis.^17,18There is a spectrum of findings on imaging studies of extraosseous osteosarcoma. Plain radiographs show a soft-tissue density with variable degrees of central calcification that reflects mineralization of deposited neoplastic bone. The pattern of calcification is characteristically amorphous or cloudlike, as opposed to the ring-and-arc observed in cartilage matrix. On CT, the soft-tissue mass of extraosseous osteosarcoma is separate from the underlying bone and periosteum—a defining characteristic that distinguishes it from conventional intramedullary and juxtacortical osteosarcoma.⁶ The central pattern of amorphous calcification helps to differentiate extraosseous osteosarcoma from heterotopic ossification, which characteristically demonstrates zonation, with trabecular architecture and mature cortical bone peripherally.¹ Enhancement of extraskeletal osteosarcoma tends to be heterogeneous and depends on the quantity of necrosis. Extraskeletal osteosarcoma tends to be isointense on T1-weighted MRI and mildly hyperintense on T2-weighted MRI.^1,6 Areas of very low signal intensity on both T1- and T2-weighted MRI may reflect mineralization.¹⁹ If intratumoral hemorrhage has occurred, there may be signal intensity of blood products of various ages.^1,3 Tumors with abundant hemorrhage can be mistaken for hematoma. FDG-PET radiotracer accumulation tends to be intense peripherally with variable central activity depending on quantity of necrosis and hemorrhage.¹The radiologic differential diagnosis includes myositis ossificans, chondrosseous lipoma, parosteal lipoma (ossifying variant), liposarcoma with metaplastic bone, dedifferentiated liposarcoma with osteosarcoma or chondrosarcoma component, and malignant mesenchymoma. Other common soft-tissue sarcomas, such as fibrosarcoma, leiomyosarcoma, and pleomorphic undifferentiated sarcoma, are excluded by the presence of fat within the tumor. The radiographic pattern of osteoid matrix produced by the tumor in our patient may be seen in heterotopic ossification, but the absence of mature ossification with zonation was evidence against heterotopic ossification, and microscopically it was neoplastic rather than reactive osteoid. In addition, it is possible that, because of the small size of the soft-tissue component, it was difficult to appreciate the less mature osteoid matrix peripherally. The lack of characteristic rings and arcs helps exclude benign and malignant cartilage containing neoplasms. Malignant mesenchymoma is a diagnosis of exclusion, and such tumors are usually better classified as sarcomas that have undergone heterologous differentiation.

The histologic diagnosis of extraosseous osteosarcoma requires identification of malignant mesenchymal cells that secrete neoplastic osteoid that may or may not mineralize. It is important to exclude the possibility that the malignant bone-forming tumor is part of a different type of sarcoma, the most common being dedifferentiated liposarcoma. Immunohistochemistry can be helpful in this situation, as dedifferentiated liposarcomas demonstrate nuclear expression of MDM2, CDK4, and p16, a constellation of findings rare in conventional and extraosseous osteosarcoma.^20-23 Osteosarcoma has not previously been reported as arising in a lipoma; in our patient’s case, we excluded the possibility that the fatty component represented an underlying atypical lipomatous tumor/well-differentiated or dedifferentiated liposarcoma on the basis of morphology and lack of expression of MDM2, CDK4, and p16.

Although histologically identical to osteosarcoma of bone, extraosseous osteosarcoma is treated differently because of its relatively decreased chemosensitivity and radiosensitivity. Treatment tends to be focused on limb-sparing wide local excision, and local recurrence complicates about 50% of cases.¹ Neoadjuvant or adjuvant treatment with radiation or chemotherapy is often provided.⁶ Platinum and doxorubicin chemotherapeutic agents, which are first-line treatments for osteosarcoma of bone, tend to be less effective in extraosseous osteosarcoma, and ifosfamide is more often used instead.⁵

Primary extraosseous osteosarcoma classically has a poor prognosis, with 2- to 3-year mortality of 50%, and prognosis tends to be worse for secondary radiation-induced sarcomas than for primary sarcomas.^2,6 However, with there being improved treatment protocols involving surgery and chemoradiation, more recent 5-year survival rates without metastatic disease are between 60% and 80%, though there is no definite consensus regarding the optimal systemic therapy regimen.^1,24 In a 2014 review of 53 patients who presented with localized disease, Choi and colleagues²⁵ identified a 3-year cumulative 39% incidence of death caused by disease, and in 2016 Sio and colleagues²⁶ reported that 55% of patients, most of whom had stage 3 disease, were alive at median follow-up of 45 months. Similar to osteosarcoma of bone, metastases may develop up to 10 years after primary treatment and are most commonly to the lung (80%-88%). Because extraosseous osteosarcoma is rare, no definite prognostic factors have been determined, but metastases at presentation and large tumor size (>5 cm) likely portend a worse prognosis.^2,3,27 Fibroblastic and chondroblastic subtypes may have a slightly better prognosis.^6,28

Conclusion

Extraosseous osteosarcoma is a rare malignancy that should be considered in the appropriate clinical and imaging scenario. This article is the first report of a case of a radiation-associated extraosseous osteosarcoma that developed within a lipoma with preoperative and postoperative multimodality imaging.

Am J Orthop. 2017;46(3):E200-E206. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Rare and histologically indistinguishable from osteosarcoma of bone.
• Most common presentation is an enlarging mass in the thigh or buttock.
• Secondary extraosseous osteosarcoma usually arises in the field of prior external beam radiation or brachytherapy.
• Radiographic pattern of mineralization is central amorphous or cloudlike.
• On cross sectional imaging, the soft-tissue mass is separate from the underlying bone and periosteum.

Aside from multiple myeloma, osteosarcoma is the most common primary malignancy of bone, but extraosseous osteosarcoma is rare and accounts for only 1% of soft-tissue sarcomas and only 4% of all osteosarcomas.^1-3 Benign mesenchymal tumors, such as lipomas, are common, and they are estimated to outnumber their malignant counterparts by more than a factor of 100. However, the true ratio is unknown, as many clinically benign lipomas are not biopsied.⁴ Conventional lipoma is the most common lipoma and is biologically indolent. Conventional lipoma generally does not transform biologically into a more aggressive type of neoplasm—unlike atypical lipomatous tumors, which may demonstrate this type of evolution with multiple local recurrences.

This article is the first report of a case of radiation-associated extraosseous osteosarcoma that developed within a benign conventional lipoma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

In March 2013, a 72-year-old woman presented to a general surgeon with a right thigh mass of several weeks’ duration. The patient, who had a remote history of thyroid carcinoma, underwent thyroidectomy in 1991, excision of melanoma of the chest in 1998, and resection and adjuvant external beam radiotherapy (30 fractions) for Merkel cell carcinoma of the right proximal lateral leg (malignancy images unavailable) at an outside institution in 2003. Regional lymph node dissection at the time was negative. The patient remained disease-free the next 10 years. On presentation, magnetic resonance imaging (MRI) showed a 2.2-cm mass encircled by a tumor of lipomatous tissue within the vastus intermedius muscle, adjacent to but separate from the right distal femur (Figures 1A-1C).

Physical examination revealed marked ecchymosis of the left groin at the access site for embolization as well as massive ecchymosis and swelling along the right distal thigh, medial knee, and medial lower leg. The neurovascular structures were intact with full motor function and sensation distally, as well as normal distal pulses. No inguinal adenopathy was identified. The proximal portion of the prior radiation tattoo was at the inferior extent of the lesion on MRI.

The patient was treated with doxorubicin and ifosfamide (2 cycles) while waiting for the hematoma to shrink. Contrast-enhanced MRI showed a 2.2-cm enhancing mass with isointense T1 signal and heterogeneously hyperintense STIR (short tau inversion recovery) signal surrounded by a circumscribed nonenhancing lipomatous tumor within the vastus intermedius muscle, adjacent to the distal femoral cortex. There was no invasion of the bone, and a fat plane between the enhancing mass and the femoral cortex was identified (Figures 2A-2E).

Discussion

Extraosseous osteosarcoma, typically a high-grade malignant neoplasm of the soft tissues that produces osteoid or cartilaginous matrix, is histologically indistinguishable from osteosarcoma of bone.

Conventional lipoma, the most common subtype of lipoma, is a benign mesenchymal tumor. Other subtypes are hibernoma, fibrolipoma, angiolipoma, myelolipoma, spindle-cell lipoma, pleomorphic lipoma, and atypical lipomatous tumor.⁷ Atypical lipomatous tumor and well-differentiated liposarcoma are distinguished from each other by location: The World Health Organization recommends the term atypical lipomatous tumor for tumors that arise in the extremities and trunk lesions and well-differentiated liposarcoma for neoplasms that develop in the retroperitoneum, peritoneum, mediastinum, spermatic cord, and thoracic cavity.⁸ On PET, hypermetabolic activity is nonspecific and can be seen in malignant tumors and some benign reactive processes, such as evolving heterotopic ossification. However, simple lipomas, including those with mature ossification or dystrophic calcification, do not manifest increased FDG avidity.⁹

We are not aware of any published cases of extraosseous osteosarcoma arising within a conventional lipoma. A limited number of cases of coexisting conventional lipoma and spindle-cell lipoma or liposarcoma have been reported.^10-13 Retroperitoneal liposarcoma with areas of dedifferentiation into osteosarcoma has also been described.¹⁴ Development of malignant fibrous histiocytoma and liposarcoma have also been reported within intraosseous lipomas.¹⁵ One theory is based on premalignancy as a biological concept as opposed to a morphologic one. In other words, lesions that may be considered morphologically benign may already have the biological phenotype for malignancy that is not yet reflected morphologically.¹⁶ However, it has been suggested that such findings may instead result from initial sampling error or histologic misdiagnosis.^17,18There is a spectrum of findings on imaging studies of extraosseous osteosarcoma. Plain radiographs show a soft-tissue density with variable degrees of central calcification that reflects mineralization of deposited neoplastic bone. The pattern of calcification is characteristically amorphous or cloudlike, as opposed to the ring-and-arc observed in cartilage matrix. On CT, the soft-tissue mass of extraosseous osteosarcoma is separate from the underlying bone and periosteum—a defining characteristic that distinguishes it from conventional intramedullary and juxtacortical osteosarcoma.⁶ The central pattern of amorphous calcification helps to differentiate extraosseous osteosarcoma from heterotopic ossification, which characteristically demonstrates zonation, with trabecular architecture and mature cortical bone peripherally.¹ Enhancement of extraskeletal osteosarcoma tends to be heterogeneous and depends on the quantity of necrosis. Extraskeletal osteosarcoma tends to be isointense on T1-weighted MRI and mildly hyperintense on T2-weighted MRI.^1,6 Areas of very low signal intensity on both T1- and T2-weighted MRI may reflect mineralization.¹⁹ If intratumoral hemorrhage has occurred, there may be signal intensity of blood products of various ages.^1,3 Tumors with abundant hemorrhage can be mistaken for hematoma. FDG-PET radiotracer accumulation tends to be intense peripherally with variable central activity depending on quantity of necrosis and hemorrhage.¹The radiologic differential diagnosis includes myositis ossificans, chondrosseous lipoma, parosteal lipoma (ossifying variant), liposarcoma with metaplastic bone, dedifferentiated liposarcoma with osteosarcoma or chondrosarcoma component, and malignant mesenchymoma. Other common soft-tissue sarcomas, such as fibrosarcoma, leiomyosarcoma, and pleomorphic undifferentiated sarcoma, are excluded by the presence of fat within the tumor. The radiographic pattern of osteoid matrix produced by the tumor in our patient may be seen in heterotopic ossification, but the absence of mature ossification with zonation was evidence against heterotopic ossification, and microscopically it was neoplastic rather than reactive osteoid. In addition, it is possible that, because of the small size of the soft-tissue component, it was difficult to appreciate the less mature osteoid matrix peripherally. The lack of characteristic rings and arcs helps exclude benign and malignant cartilage containing neoplasms. Malignant mesenchymoma is a diagnosis of exclusion, and such tumors are usually better classified as sarcomas that have undergone heterologous differentiation.

The histologic diagnosis of extraosseous osteosarcoma requires identification of malignant mesenchymal cells that secrete neoplastic osteoid that may or may not mineralize. It is important to exclude the possibility that the malignant bone-forming tumor is part of a different type of sarcoma, the most common being dedifferentiated liposarcoma. Immunohistochemistry can be helpful in this situation, as dedifferentiated liposarcomas demonstrate nuclear expression of MDM2, CDK4, and p16, a constellation of findings rare in conventional and extraosseous osteosarcoma.^20-23 Osteosarcoma has not previously been reported as arising in a lipoma; in our patient’s case, we excluded the possibility that the fatty component represented an underlying atypical lipomatous tumor/well-differentiated or dedifferentiated liposarcoma on the basis of morphology and lack of expression of MDM2, CDK4, and p16.

Although histologically identical to osteosarcoma of bone, extraosseous osteosarcoma is treated differently because of its relatively decreased chemosensitivity and radiosensitivity. Treatment tends to be focused on limb-sparing wide local excision, and local recurrence complicates about 50% of cases.¹ Neoadjuvant or adjuvant treatment with radiation or chemotherapy is often provided.⁶ Platinum and doxorubicin chemotherapeutic agents, which are first-line treatments for osteosarcoma of bone, tend to be less effective in extraosseous osteosarcoma, and ifosfamide is more often used instead.⁵

Primary extraosseous osteosarcoma classically has a poor prognosis, with 2- to 3-year mortality of 50%, and prognosis tends to be worse for secondary radiation-induced sarcomas than for primary sarcomas.^2,6 However, with there being improved treatment protocols involving surgery and chemoradiation, more recent 5-year survival rates without metastatic disease are between 60% and 80%, though there is no definite consensus regarding the optimal systemic therapy regimen.^1,24 In a 2014 review of 53 patients who presented with localized disease, Choi and colleagues²⁵ identified a 3-year cumulative 39% incidence of death caused by disease, and in 2016 Sio and colleagues²⁶ reported that 55% of patients, most of whom had stage 3 disease, were alive at median follow-up of 45 months. Similar to osteosarcoma of bone, metastases may develop up to 10 years after primary treatment and are most commonly to the lung (80%-88%). Because extraosseous osteosarcoma is rare, no definite prognostic factors have been determined, but metastases at presentation and large tumor size (>5 cm) likely portend a worse prognosis.^2,3,27 Fibroblastic and chondroblastic subtypes may have a slightly better prognosis.^6,28

Conclusion

Extraosseous osteosarcoma is a rare malignancy that should be considered in the appropriate clinical and imaging scenario. This article is the first report of a case of a radiation-associated extraosseous osteosarcoma that developed within a lipoma with preoperative and postoperative multimodality imaging.

Am J Orthop. 2017;46(3):E200-E206. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Rare and histologically indistinguishable from osteosarcoma of bone.
• Most common presentation is an enlarging mass in the thigh or buttock.
• Secondary extraosseous osteosarcoma usually arises in the field of prior external beam radiation or brachytherapy.
• Radiographic pattern of mineralization is central amorphous or cloudlike.
• On cross sectional imaging, the soft-tissue mass is separate from the underlying bone and periosteum.

Aside from multiple myeloma, osteosarcoma is the most common primary malignancy of bone, but extraosseous osteosarcoma is rare and accounts for only 1% of soft-tissue sarcomas and only 4% of all osteosarcomas.^1-3 Benign mesenchymal tumors, such as lipomas, are common, and they are estimated to outnumber their malignant counterparts by more than a factor of 100. However, the true ratio is unknown, as many clinically benign lipomas are not biopsied.⁴ Conventional lipoma is the most common lipoma and is biologically indolent. Conventional lipoma generally does not transform biologically into a more aggressive type of neoplasm—unlike atypical lipomatous tumors, which may demonstrate this type of evolution with multiple local recurrences.

This article is the first report of a case of radiation-associated extraosseous osteosarcoma that developed within a benign conventional lipoma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

In March 2013, a 72-year-old woman presented to a general surgeon with a right thigh mass of several weeks’ duration. The patient, who had a remote history of thyroid carcinoma, underwent thyroidectomy in 1991, excision of melanoma of the chest in 1998, and resection and adjuvant external beam radiotherapy (30 fractions) for Merkel cell carcinoma of the right proximal lateral leg (malignancy images unavailable) at an outside institution in 2003. Regional lymph node dissection at the time was negative. The patient remained disease-free the next 10 years. On presentation, magnetic resonance imaging (MRI) showed a 2.2-cm mass encircled by a tumor of lipomatous tissue within the vastus intermedius muscle, adjacent to but separate from the right distal femur (Figures 1A-1C).

Physical examination revealed marked ecchymosis of the left groin at the access site for embolization as well as massive ecchymosis and swelling along the right distal thigh, medial knee, and medial lower leg. The neurovascular structures were intact with full motor function and sensation distally, as well as normal distal pulses. No inguinal adenopathy was identified. The proximal portion of the prior radiation tattoo was at the inferior extent of the lesion on MRI.

The patient was treated with doxorubicin and ifosfamide (2 cycles) while waiting for the hematoma to shrink. Contrast-enhanced MRI showed a 2.2-cm enhancing mass with isointense T1 signal and heterogeneously hyperintense STIR (short tau inversion recovery) signal surrounded by a circumscribed nonenhancing lipomatous tumor within the vastus intermedius muscle, adjacent to the distal femoral cortex. There was no invasion of the bone, and a fat plane between the enhancing mass and the femoral cortex was identified (Figures 2A-2E).

Discussion

Extraosseous osteosarcoma, typically a high-grade malignant neoplasm of the soft tissues that produces osteoid or cartilaginous matrix, is histologically indistinguishable from osteosarcoma of bone.

Conventional lipoma, the most common subtype of lipoma, is a benign mesenchymal tumor. Other subtypes are hibernoma, fibrolipoma, angiolipoma, myelolipoma, spindle-cell lipoma, pleomorphic lipoma, and atypical lipomatous tumor.⁷ Atypical lipomatous tumor and well-differentiated liposarcoma are distinguished from each other by location: The World Health Organization recommends the term atypical lipomatous tumor for tumors that arise in the extremities and trunk lesions and well-differentiated liposarcoma for neoplasms that develop in the retroperitoneum, peritoneum, mediastinum, spermatic cord, and thoracic cavity.⁸ On PET, hypermetabolic activity is nonspecific and can be seen in malignant tumors and some benign reactive processes, such as evolving heterotopic ossification. However, simple lipomas, including those with mature ossification or dystrophic calcification, do not manifest increased FDG avidity.⁹

We are not aware of any published cases of extraosseous osteosarcoma arising within a conventional lipoma. A limited number of cases of coexisting conventional lipoma and spindle-cell lipoma or liposarcoma have been reported.^10-13 Retroperitoneal liposarcoma with areas of dedifferentiation into osteosarcoma has also been described.¹⁴ Development of malignant fibrous histiocytoma and liposarcoma have also been reported within intraosseous lipomas.¹⁵ One theory is based on premalignancy as a biological concept as opposed to a morphologic one. In other words, lesions that may be considered morphologically benign may already have the biological phenotype for malignancy that is not yet reflected morphologically.¹⁶ However, it has been suggested that such findings may instead result from initial sampling error or histologic misdiagnosis.^17,18There is a spectrum of findings on imaging studies of extraosseous osteosarcoma. Plain radiographs show a soft-tissue density with variable degrees of central calcification that reflects mineralization of deposited neoplastic bone. The pattern of calcification is characteristically amorphous or cloudlike, as opposed to the ring-and-arc observed in cartilage matrix. On CT, the soft-tissue mass of extraosseous osteosarcoma is separate from the underlying bone and periosteum—a defining characteristic that distinguishes it from conventional intramedullary and juxtacortical osteosarcoma.⁶ The central pattern of amorphous calcification helps to differentiate extraosseous osteosarcoma from heterotopic ossification, which characteristically demonstrates zonation, with trabecular architecture and mature cortical bone peripherally.¹ Enhancement of extraskeletal osteosarcoma tends to be heterogeneous and depends on the quantity of necrosis. Extraskeletal osteosarcoma tends to be isointense on T1-weighted MRI and mildly hyperintense on T2-weighted MRI.^1,6 Areas of very low signal intensity on both T1- and T2-weighted MRI may reflect mineralization.¹⁹ If intratumoral hemorrhage has occurred, there may be signal intensity of blood products of various ages.^1,3 Tumors with abundant hemorrhage can be mistaken for hematoma. FDG-PET radiotracer accumulation tends to be intense peripherally with variable central activity depending on quantity of necrosis and hemorrhage.¹The radiologic differential diagnosis includes myositis ossificans, chondrosseous lipoma, parosteal lipoma (ossifying variant), liposarcoma with metaplastic bone, dedifferentiated liposarcoma with osteosarcoma or chondrosarcoma component, and malignant mesenchymoma. Other common soft-tissue sarcomas, such as fibrosarcoma, leiomyosarcoma, and pleomorphic undifferentiated sarcoma, are excluded by the presence of fat within the tumor. The radiographic pattern of osteoid matrix produced by the tumor in our patient may be seen in heterotopic ossification, but the absence of mature ossification with zonation was evidence against heterotopic ossification, and microscopically it was neoplastic rather than reactive osteoid. In addition, it is possible that, because of the small size of the soft-tissue component, it was difficult to appreciate the less mature osteoid matrix peripherally. The lack of characteristic rings and arcs helps exclude benign and malignant cartilage containing neoplasms. Malignant mesenchymoma is a diagnosis of exclusion, and such tumors are usually better classified as sarcomas that have undergone heterologous differentiation.

The histologic diagnosis of extraosseous osteosarcoma requires identification of malignant mesenchymal cells that secrete neoplastic osteoid that may or may not mineralize. It is important to exclude the possibility that the malignant bone-forming tumor is part of a different type of sarcoma, the most common being dedifferentiated liposarcoma. Immunohistochemistry can be helpful in this situation, as dedifferentiated liposarcomas demonstrate nuclear expression of MDM2, CDK4, and p16, a constellation of findings rare in conventional and extraosseous osteosarcoma.^20-23 Osteosarcoma has not previously been reported as arising in a lipoma; in our patient’s case, we excluded the possibility that the fatty component represented an underlying atypical lipomatous tumor/well-differentiated or dedifferentiated liposarcoma on the basis of morphology and lack of expression of MDM2, CDK4, and p16.

Although histologically identical to osteosarcoma of bone, extraosseous osteosarcoma is treated differently because of its relatively decreased chemosensitivity and radiosensitivity. Treatment tends to be focused on limb-sparing wide local excision, and local recurrence complicates about 50% of cases.¹ Neoadjuvant or adjuvant treatment with radiation or chemotherapy is often provided.⁶ Platinum and doxorubicin chemotherapeutic agents, which are first-line treatments for osteosarcoma of bone, tend to be less effective in extraosseous osteosarcoma, and ifosfamide is more often used instead.⁵

Primary extraosseous osteosarcoma classically has a poor prognosis, with 2- to 3-year mortality of 50%, and prognosis tends to be worse for secondary radiation-induced sarcomas than for primary sarcomas.^2,6 However, with there being improved treatment protocols involving surgery and chemoradiation, more recent 5-year survival rates without metastatic disease are between 60% and 80%, though there is no definite consensus regarding the optimal systemic therapy regimen.^1,24 In a 2014 review of 53 patients who presented with localized disease, Choi and colleagues²⁵ identified a 3-year cumulative 39% incidence of death caused by disease, and in 2016 Sio and colleagues²⁶ reported that 55% of patients, most of whom had stage 3 disease, were alive at median follow-up of 45 months. Similar to osteosarcoma of bone, metastases may develop up to 10 years after primary treatment and are most commonly to the lung (80%-88%). Because extraosseous osteosarcoma is rare, no definite prognostic factors have been determined, but metastases at presentation and large tumor size (>5 cm) likely portend a worse prognosis.^2,3,27 Fibroblastic and chondroblastic subtypes may have a slightly better prognosis.^6,28

Conclusion

Extraosseous osteosarcoma is a rare malignancy that should be considered in the appropriate clinical and imaging scenario. This article is the first report of a case of a radiation-associated extraosseous osteosarcoma that developed within a lipoma with preoperative and postoperative multimodality imaging.

Am J Orthop. 2017;46(3):E200-E206. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.