Hemophilic Pseudotumor Diagnosis, Treatment, and Complications Pamela S. Jensen, MD, Charles E. Putman, MD
Patients with hemophilia are living longer result of improved therapeutic measures. Associated with this longevity is the increased occurrence of complications affecting the osseous system. One of the more serious bone complications is the hemophilic pseudotumor or hemophilic cyst. We studied its diagnosis, treatment, and complications, and report a case of an early hemophilic cyst occurring in a new location, the proximal part of the left clavicle. The increased incidence of this complication should alert the clinician to the possibility of these lesions appearing in previously unreported sites and as a
demonstrating atypical roentgenographic features. Early recognition and treatment is essential if optimal therapeutic results are to be obtained.
joint changes secondary to hemophilia were first de¬ scribed in 1892 by König.1 In 1918, Starker reported a complication of
Bone
and
the disease in which extensive os¬ seous destruction of the femur oc¬ curred in association with a massive hematoma.2 This extra-articular in¬ volvement of bone associated with a soft tissue mass has been called a hé¬
mophilie pseudotumor or hémophilie cyst of bone. To date, the cases of 61 patients with this complication have been reported in the literature, 43 of which have been reported in the past recent in¬ in these pseudotumors proba¬ bly represents in part a true increase in the incidence of this complication due to the greater longevity of hé¬
15
years.311 The apparent
crease
mophilie patients as a result of more effective therapeutic measures. The increase is not as great as would ap¬ pear, however, since it is also a reflec¬ tion of an increase in the frequency Received for publication May 16, 1974; ac3. From the departments of radiology (Drs. Jensen and Putman) and internal medicine (Dr. Putman), Yale University School of Medicine, New Haven, Conn. Reprint requests to Department of Radiology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510 (Dr. Jensen).
cepted Sept
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of reporting the treatment for this le¬ sion. Fifteen cases treated surgically were reported between 1959 and 1966 when operation first became feasible due to the ability of factor VIII transfusions. The lesions had been present prior to therapy for an aver¬ age of nine years with a range of two months to 26 years. We wish to report a hémophilie pseudotumor occurring in a new loca¬ tion, the proximal part of the left clavicle, in which the distinctive roentgenographic features usually as¬ sociated with these pseudotumors are absent. REPORT OF A CASE A 21-year-old man was admitted to the hospital for treatment of acute hemor¬ rhage into his left knee and right hip. His condition was diagnosed as factor VIIIdeficient hemophilia when he was 3 months old. Since that time, he has had approxi¬ mately 100 hospital admissions, mainly for the treatment of hemarthroses although he had had several episodes of gastrointesti¬ nal bleeding and one episode of hematuria. The longest period of time between hospi¬ tal admissions has been five months. Phys¬ ical examination showed no abnormalities except for tenderness of his left knee and right hip, bony deformity of both elbows and knees, and limited range of motion of both shoulders, elbows, hips, and knees. Pertinent laboratory data included the fol¬ lowing: hematocrit reading, 38%; hemoglo¬ bin level, 12.3 gm/100 ml; white blood cell count, 8,400/cu mm, with a normal differ¬ ential count; prothrombin time, 11.8 sec¬ onds (control, 11.4 seconds); partial thromboplastin time, 61.3 seconds (control, 30.8 seconds); and platelet count, 240,000/ cu mm. The patient's antihemophilic factor had previously been measured at less than 1% of normal. A chest roentgenogram ob¬ tained at the time of this current admis¬ sion disclosed an expansile, destructive le¬ sion in the proximal part of the left clavicle (Figure). Mild asymmetry of the clavicular heads, with the left being more prominent than the right, was noted on reexam¬ ination of the patient. This bony promi-
View of sternoclavicular joints. Expansile lesion involving proximal part of left clavicle (large arrows) is readily apparent when compared with patient's normal right clavicle proximally (small arrows).
nontender and there was no as¬ sociated erythema or soft tissue mass. The patient recalled that he had been hit in the chest three months prior to admission by a football thrown by one of his three broth¬ ers, all of whom have classic hemophilia. The patient did not experience any major pain or tenderness in the region of the left clavicle, and had not noted the asymmetry of his clavicular heads until questioned about it. Because of the bleeding diathesis, it was elected to follow up this asympto¬ matic clavicular lesion. Examination of the patient two years after the initial demon¬ stration of the lesion has shown no clinical nence was
or
roentgenographic changes. COMMENT
The cause of the hémophilie pseu¬ dotumor is not fully understood. A re¬ view of the reported cases indicates that lesions occur most commonly in the femur (32 of 71 cases). Lesions also occurred in the pelvis (16 cases), with the ilium most often affected;
tibia (seven), small bones of the hands (five), feet (two), calcaneus (six), humérus (one), olecranon (one), and the radius (one). Seven patients had involvement of more than one bone. Confirmed trauma is a factor in some patients. A number of pseudotu¬ mors have developed following frac¬ ture of the femur. If all of the lesions were due to trauma alone, however, greater involvement of the digits and the upper extremities might be ex¬ pected. Hemorrhage into the muscles as well as joints is a frequent occur¬ rence in hemophiliacs. Large hema¬ tomas with progressive enlargement can secondarily affect the bones by pressure necrosis. This view is sup¬ ported by the observation that the fe¬ mur is the most common site of in¬ volvement. There are wide fibrous insertions attaching the muscles of the thigh to the femur, and hemor-
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rhage into these muscles can dissect along the muscle bundles to the fem¬ oral attachments resulting in subse¬ quent bone destruction. Hemorrhage into the iliacus muscle in
some cases
may account for the progressive de¬ struction of the ilium, the next most
commonly involved site. Subperiosteal hemorrhage causing stripping of the periosteum from the bony cortex and resulting in a soft tissue
that may in turn cause necrosis and further bone pressure destruction has undoubtedly also played a role in the formation of pseudotumors, particularly in cases preceded by fracture. In addition, the presence of intraosseous hemorrhage may also be a factor in the develop¬ ment of the hémophilie cyst. With continued or repeated hemorrhage, the cyst may then increase in size, causing expansion of the bone and thinning of the bony cortex. mass
Establishing the diagnosis of hé¬ mophilie pseudotumor by conven¬ tional methods may further compli¬ cate the patient's disease. Needle or aspiration biopsies may result in chronic fistulous tracks and surgical
that fail to heal, in addition to increasing the possibility of second¬ ary infection." Characteristic roent¬ genographic features of a soft tissue scars
containing coarse calcifications, periosteal elevation, new bone forma¬ tion in the configuration of bony "struts," and varying degrees of bone destruction are usually sufficiently distinctive to indicate the diagnosis. Early in the formation of the pseu¬ dotumor, however, these features are usually absent. The soft tissue mass may contain no roentgenographically mass
demonstrable calcification. Periosteal elevation may be minimal or absent and bone destruction alone may be the key feature. In addition, if the pseudotumor results from intraosse¬ ous hemorrhage, as it may have in our patient, an expansile lesion of bone without an associated soft tissue mass may result. It is this early lesion that is dif¬ ficult to diagnose. Early periosteal elevation resembles that of osteo¬ myelitis, Ewing sarcoma, and metastatic neuroblastoma. The osteolytic bone destruction resembles the le¬ sions of primary bone sarcomas, tuberculosis, coccidioidomycosis, echinococcosis (hydatid disease), aneurysmal bone cyst, giant cell tumor, plasmacytoma (myeloma), and metastatic neoplasms. Hémophilie pseudotumors have been treated surgically, conservative¬ ly, and with radiation therapy. Prior to the availability of factor VIII trans¬
fusions, surgical
treatment
was usu¬
ability to control the patient's bleeding diathesis, sur¬ gical excision and amputation have been reported successful in 16 of 22 patients. The majority of these pa¬ tients had longstanding lesions, many being of incredible proportions, and had been unsuccessfully treated conservatively for many years prior ally
fatal. With the
to the
feasibility of operation. The six reported deaths were due to over¬ whelming septicemia and uncon¬ trollable hemorrhage due to the in¬ ability to maintain sufficient factor VIII levels and in some patients be¬ cause of the development of factor VIII antibodies. Operation appears to
be the treatment of choice when the lesions have been present for many years and nonsurgical management is unsuccessful. Conservative therapy consisting of immobilization and the adminis¬ tration of factor VIII transfusions or factor IX concentrates has been re¬ ported successful in six patients.610 Steel et al10 have been successful in treating two pseudotumors of bone and three simple cysts of muscle (without bony involvement) with the use of prolonged immobilization in
plaster plus replacement therapy
to
control the hemorrhage. Progressive decrease in the soft tissue mass was noted, as well as bony reconstruction and remodeling of a tibial and calcaneal lesion. It must be stressed that this therapy is most effective in le¬ sions of recent onset since it appears to be less effective in patients with chronic lesions. The soft tissue hema¬ toma, if not quickly treated, can re¬ sult in ischemia and ulcération of the overlying skin, with subsequent septi¬ cemia and possible cyst rupture, a sit¬ uation often fatal. Irradiation has been attempted as a primary means of treating four le¬ sions11 and in conjunction with blood transfusions in two additional le¬ sions.7 Brant and Jordan11 believe that doses of 1,000 to 2,000 rads result in an endarteritis in an acutely bleed¬ ing hematoma. They have noticed re¬ gression of the soft tissue mass in acute lesions. Radiation was ineffec¬ tive in treatment of pseudotumors with longstanding bone changes that have been present for years. The de¬ gree of concomitant immobilization of these patients was not indicated, although one patient who demon¬ strated no substantial response to ra¬ diation therapy was treated with a
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brace and when reexamined six months later demonstrated resolution of the soft tissue mass and substan¬ tial bone repair. The use of radiation therapy in the treatment of pseudotu¬ mors is difficult to assess at this time. Conclusion
With increased clinical awareness of the occurrence and nature of the hémophilie pseudotumor, the diag¬ nosis can be made early in the course of the disease and effective control of the lesion can be instituted. This would eliminate, in most cases, major
surgical procedures including
ampu¬
tation and the disability associated with this procedure. References 1. K\l=o"\nigF: Die Gelenkerkrankungen bei Blutern mit besonderer Ber\l=u"\cksichtigung der Diagnose. Samml Klin Vortr Chir 36:233-242, 1892. 2. Starker L: Knochenusur durch ein h\l=a"\mophilessubperiostales H\l=a"\matom.Mitt Grenzgeb Med Chir 31:381-415, 1918-1919. 3. Stiris G: Bone and joint changes in haemophiliacs. Acta Radiol 49:269-275, 1958. 4. Fraenkel GJ, Taylor KB, Richards WCD: Haemophilic blood cysts. Br J Surg 46:383-392, 1959. 5. Abell JM Jr, Bailey RW: Hemophilic in sibpseudotumor: Two cases occurring lings. Arch Surg 81:569-581, 1960. 6. van Creveld S, Kingma MJ: Subperiosteal haemorrhage in haemophilia A and B. Acta Paediatr 50:291-296, 1961. 7. Chen YF: Bilateral hemophilic pseudotumors of calcaneus and cuboid treated by irradiation: Case report. J Bone Joint
Surg 47-A:517-521, 1965. 8. Jones DM: Haemophilic blood cyst: Report of a case. J Bone Joint Surg 47\x=req-\ B:266-267, 1965.
9. de Valderrama JAF, Matthews JM: The haemophilic pseudotumor or haemophilic subperiosteal haematoma. J Bone Joint Surg 47-B:256-265, 1965. 10. Steel WM, Duthie RB, O'Connor BT: Haemophilic cysts: Report of five cases. J Bone Joint Surg 51-B:614-626, 1969. 11. Brant EE, Jordan HH: Radiologic aspects of hemophilic pseudotumors in bone. Am J Roentgenol Radium Ther Nucl Med 115:525-539, 1972. 12. Witzel L, Becker F, Fuchs HF, et al: Pseudotumoren der Knochen bei H\l=a"\mophilie. Dtsch Med Wochenschr 98:206-209, 1973. 13. Forbes CD, Moule B, Grant M, et al: Bilateral pseudotumors of the pelvis in a patient with Christmas disease: With notes on localization by radioactive scanning and ultrasonography. Am J Roentgenol Radium Ther Nucl Med 121:173-176, 1974.
Patients with hemophilia are living longer result of improved therapeutic measures. Associated with this longevity is the increased occurrence of complications affecting the osseous system. One of the more serious bone complications is the hemophilic pseudotumor or hemophilic cyst. We studied its diagnosis, treatment, and complications, and report a case of an early hemophilic cyst occurring in a new location, the proximal part of the left clavicle. The increased incidence of this complication should alert the clinician to the possibility of these lesions appearing in previously unreported sites and as a
demonstrating atypical roentgenographic features. Early recognition and treatment is essential if optimal therapeutic results are to be obtained.
joint changes secondary to hemophilia were first de¬ scribed in 1892 by König.1 In 1918, Starker reported a complication of
Bone
and
the disease in which extensive os¬ seous destruction of the femur oc¬ curred in association with a massive hematoma.2 This extra-articular in¬ volvement of bone associated with a soft tissue mass has been called a hé¬
mophilie pseudotumor or hémophilie cyst of bone. To date, the cases of 61 patients with this complication have been reported in the literature, 43 of which have been reported in the past recent in¬ in these pseudotumors proba¬ bly represents in part a true increase in the incidence of this complication due to the greater longevity of hé¬
15
years.311 The apparent
crease
mophilie patients as a result of more effective therapeutic measures. The increase is not as great as would ap¬ pear, however, since it is also a reflec¬ tion of an increase in the frequency Received for publication May 16, 1974; ac3. From the departments of radiology (Drs. Jensen and Putman) and internal medicine (Dr. Putman), Yale University School of Medicine, New Haven, Conn. Reprint requests to Department of Radiology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510 (Dr. Jensen).
cepted Sept
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/20/2015
of reporting the treatment for this le¬ sion. Fifteen cases treated surgically were reported between 1959 and 1966 when operation first became feasible due to the ability of factor VIII transfusions. The lesions had been present prior to therapy for an aver¬ age of nine years with a range of two months to 26 years. We wish to report a hémophilie pseudotumor occurring in a new loca¬ tion, the proximal part of the left clavicle, in which the distinctive roentgenographic features usually as¬ sociated with these pseudotumors are absent. REPORT OF A CASE A 21-year-old man was admitted to the hospital for treatment of acute hemor¬ rhage into his left knee and right hip. His condition was diagnosed as factor VIIIdeficient hemophilia when he was 3 months old. Since that time, he has had approxi¬ mately 100 hospital admissions, mainly for the treatment of hemarthroses although he had had several episodes of gastrointesti¬ nal bleeding and one episode of hematuria. The longest period of time between hospi¬ tal admissions has been five months. Phys¬ ical examination showed no abnormalities except for tenderness of his left knee and right hip, bony deformity of both elbows and knees, and limited range of motion of both shoulders, elbows, hips, and knees. Pertinent laboratory data included the fol¬ lowing: hematocrit reading, 38%; hemoglo¬ bin level, 12.3 gm/100 ml; white blood cell count, 8,400/cu mm, with a normal differ¬ ential count; prothrombin time, 11.8 sec¬ onds (control, 11.4 seconds); partial thromboplastin time, 61.3 seconds (control, 30.8 seconds); and platelet count, 240,000/ cu mm. The patient's antihemophilic factor had previously been measured at less than 1% of normal. A chest roentgenogram ob¬ tained at the time of this current admis¬ sion disclosed an expansile, destructive le¬ sion in the proximal part of the left clavicle (Figure). Mild asymmetry of the clavicular heads, with the left being more prominent than the right, was noted on reexam¬ ination of the patient. This bony promi-
View of sternoclavicular joints. Expansile lesion involving proximal part of left clavicle (large arrows) is readily apparent when compared with patient's normal right clavicle proximally (small arrows).
nontender and there was no as¬ sociated erythema or soft tissue mass. The patient recalled that he had been hit in the chest three months prior to admission by a football thrown by one of his three broth¬ ers, all of whom have classic hemophilia. The patient did not experience any major pain or tenderness in the region of the left clavicle, and had not noted the asymmetry of his clavicular heads until questioned about it. Because of the bleeding diathesis, it was elected to follow up this asympto¬ matic clavicular lesion. Examination of the patient two years after the initial demon¬ stration of the lesion has shown no clinical nence was
or
roentgenographic changes. COMMENT
The cause of the hémophilie pseu¬ dotumor is not fully understood. A re¬ view of the reported cases indicates that lesions occur most commonly in the femur (32 of 71 cases). Lesions also occurred in the pelvis (16 cases), with the ilium most often affected;
tibia (seven), small bones of the hands (five), feet (two), calcaneus (six), humérus (one), olecranon (one), and the radius (one). Seven patients had involvement of more than one bone. Confirmed trauma is a factor in some patients. A number of pseudotu¬ mors have developed following frac¬ ture of the femur. If all of the lesions were due to trauma alone, however, greater involvement of the digits and the upper extremities might be ex¬ pected. Hemorrhage into the muscles as well as joints is a frequent occur¬ rence in hemophiliacs. Large hema¬ tomas with progressive enlargement can secondarily affect the bones by pressure necrosis. This view is sup¬ ported by the observation that the fe¬ mur is the most common site of in¬ volvement. There are wide fibrous insertions attaching the muscles of the thigh to the femur, and hemor-
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/20/2015
rhage into these muscles can dissect along the muscle bundles to the fem¬ oral attachments resulting in subse¬ quent bone destruction. Hemorrhage into the iliacus muscle in
some cases
may account for the progressive de¬ struction of the ilium, the next most
commonly involved site. Subperiosteal hemorrhage causing stripping of the periosteum from the bony cortex and resulting in a soft tissue
that may in turn cause necrosis and further bone pressure destruction has undoubtedly also played a role in the formation of pseudotumors, particularly in cases preceded by fracture. In addition, the presence of intraosseous hemorrhage may also be a factor in the develop¬ ment of the hémophilie cyst. With continued or repeated hemorrhage, the cyst may then increase in size, causing expansion of the bone and thinning of the bony cortex. mass
Establishing the diagnosis of hé¬ mophilie pseudotumor by conven¬ tional methods may further compli¬ cate the patient's disease. Needle or aspiration biopsies may result in chronic fistulous tracks and surgical
that fail to heal, in addition to increasing the possibility of second¬ ary infection." Characteristic roent¬ genographic features of a soft tissue scars
containing coarse calcifications, periosteal elevation, new bone forma¬ tion in the configuration of bony "struts," and varying degrees of bone destruction are usually sufficiently distinctive to indicate the diagnosis. Early in the formation of the pseu¬ dotumor, however, these features are usually absent. The soft tissue mass may contain no roentgenographically mass
demonstrable calcification. Periosteal elevation may be minimal or absent and bone destruction alone may be the key feature. In addition, if the pseudotumor results from intraosse¬ ous hemorrhage, as it may have in our patient, an expansile lesion of bone without an associated soft tissue mass may result. It is this early lesion that is dif¬ ficult to diagnose. Early periosteal elevation resembles that of osteo¬ myelitis, Ewing sarcoma, and metastatic neuroblastoma. The osteolytic bone destruction resembles the le¬ sions of primary bone sarcomas, tuberculosis, coccidioidomycosis, echinococcosis (hydatid disease), aneurysmal bone cyst, giant cell tumor, plasmacytoma (myeloma), and metastatic neoplasms. Hémophilie pseudotumors have been treated surgically, conservative¬ ly, and with radiation therapy. Prior to the availability of factor VIII trans¬
fusions, surgical
treatment
was usu¬
ability to control the patient's bleeding diathesis, sur¬ gical excision and amputation have been reported successful in 16 of 22 patients. The majority of these pa¬ tients had longstanding lesions, many being of incredible proportions, and had been unsuccessfully treated conservatively for many years prior ally
fatal. With the
to the
feasibility of operation. The six reported deaths were due to over¬ whelming septicemia and uncon¬ trollable hemorrhage due to the in¬ ability to maintain sufficient factor VIII levels and in some patients be¬ cause of the development of factor VIII antibodies. Operation appears to
be the treatment of choice when the lesions have been present for many years and nonsurgical management is unsuccessful. Conservative therapy consisting of immobilization and the adminis¬ tration of factor VIII transfusions or factor IX concentrates has been re¬ ported successful in six patients.610 Steel et al10 have been successful in treating two pseudotumors of bone and three simple cysts of muscle (without bony involvement) with the use of prolonged immobilization in
plaster plus replacement therapy
to
control the hemorrhage. Progressive decrease in the soft tissue mass was noted, as well as bony reconstruction and remodeling of a tibial and calcaneal lesion. It must be stressed that this therapy is most effective in le¬ sions of recent onset since it appears to be less effective in patients with chronic lesions. The soft tissue hema¬ toma, if not quickly treated, can re¬ sult in ischemia and ulcération of the overlying skin, with subsequent septi¬ cemia and possible cyst rupture, a sit¬ uation often fatal. Irradiation has been attempted as a primary means of treating four le¬ sions11 and in conjunction with blood transfusions in two additional le¬ sions.7 Brant and Jordan11 believe that doses of 1,000 to 2,000 rads result in an endarteritis in an acutely bleed¬ ing hematoma. They have noticed re¬ gression of the soft tissue mass in acute lesions. Radiation was ineffec¬ tive in treatment of pseudotumors with longstanding bone changes that have been present for years. The de¬ gree of concomitant immobilization of these patients was not indicated, although one patient who demon¬ strated no substantial response to ra¬ diation therapy was treated with a
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/20/2015
brace and when reexamined six months later demonstrated resolution of the soft tissue mass and substan¬ tial bone repair. The use of radiation therapy in the treatment of pseudotu¬ mors is difficult to assess at this time. Conclusion
With increased clinical awareness of the occurrence and nature of the hémophilie pseudotumor, the diag¬ nosis can be made early in the course of the disease and effective control of the lesion can be instituted. This would eliminate, in most cases, major
surgical procedures including
ampu¬
tation and the disability associated with this procedure. References 1. K\l=o"\nigF: Die Gelenkerkrankungen bei Blutern mit besonderer Ber\l=u"\cksichtigung der Diagnose. Samml Klin Vortr Chir 36:233-242, 1892. 2. Starker L: Knochenusur durch ein h\l=a"\mophilessubperiostales H\l=a"\matom.Mitt Grenzgeb Med Chir 31:381-415, 1918-1919. 3. Stiris G: Bone and joint changes in haemophiliacs. Acta Radiol 49:269-275, 1958. 4. Fraenkel GJ, Taylor KB, Richards WCD: Haemophilic blood cysts. Br J Surg 46:383-392, 1959. 5. Abell JM Jr, Bailey RW: Hemophilic in sibpseudotumor: Two cases occurring lings. Arch Surg 81:569-581, 1960. 6. van Creveld S, Kingma MJ: Subperiosteal haemorrhage in haemophilia A and B. Acta Paediatr 50:291-296, 1961. 7. Chen YF: Bilateral hemophilic pseudotumors of calcaneus and cuboid treated by irradiation: Case report. J Bone Joint
Surg 47-A:517-521, 1965. 8. Jones DM: Haemophilic blood cyst: Report of a case. J Bone Joint Surg 47\x=req-\ B:266-267, 1965.
9. de Valderrama JAF, Matthews JM: The haemophilic pseudotumor or haemophilic subperiosteal haematoma. J Bone Joint Surg 47-B:256-265, 1965. 10. Steel WM, Duthie RB, O'Connor BT: Haemophilic cysts: Report of five cases. J Bone Joint Surg 51-B:614-626, 1969. 11. Brant EE, Jordan HH: Radiologic aspects of hemophilic pseudotumors in bone. Am J Roentgenol Radium Ther Nucl Med 115:525-539, 1972. 12. Witzel L, Becker F, Fuchs HF, et al: Pseudotumoren der Knochen bei H\l=a"\mophilie. Dtsch Med Wochenschr 98:206-209, 1973. 13. Forbes CD, Moule B, Grant M, et al: Bilateral pseudotumors of the pelvis in a patient with Christmas disease: With notes on localization by radioactive scanning and ultrasonography. Am J Roentgenol Radium Ther Nucl Med 121:173-176, 1974.
