DOI: 10.1148/rg.234025154
(Radiographics. 2003;23:852-856.)
© RSNA, 2003
Hemophilic Pseudotumor: Radiologic-Pathologic Correlation1
James M. Stafford, MD,
Tina T. James, MD,
Anton M. Allen, MD and
Lisa R. Dixon, MD
1 From the Departments of Radiology (T.T.J., J.M.S., A.M.A.) and Pathology (L.R.D.), University of Tennessee Medical Center, Knoxville, 1924 Alcoa Hwy, Knoxville, TN 37920. Received October 16, 2002; revision requested November 25 and received January 10, 2003; accepted January 13. Address correspondence to J.M.S. (e-mail: jstaffor@mc.utmck.edu).
Index Terms: Extremities, 45.6563 • Extremities, amputation, 45.452 • Extremities, angiography, 45.124 • Hemophilia, 45.6563
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History
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A 24-year-old Egyptian man with a history of hemophilia A presented with enlargement of the left thigh and lower leg by multiple masses (Fig 1). The patient had a 2-year history of progressive pain and swelling despite treatment with cryoprecipitate and bed rest. Leg weakness prevented him from bearing weight for any extended period of time, and ultimately the leg became nearly functionless. The patient traveled from Egypt to the United States for treatment. Physical examination confirmed severe enlargement and deformity of the middle to distal thigh, knee, and proximal calf secondary to numerous pliable masses. There was bluish discoloration of the skin. Laboratory findings were as follows: hemoglobin, 9.2 mg/dL; hematocrit, 29.6%; prothrombin time, 13.3 seconds; partial thromboplastin time, 84.7 seconds; and factor VIII assay, less than 2%.
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Imaging Findings
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Magnetic resonance (MR) imaging of the left lower extremity revealed a 37 x 22 x 25-cm complex mass in the midthigh that had destroyed the adjacent femur (Fig 2). The mass was circumscribed by a well-defined capsule with low signal intensity. The tumor demonstrated heterogeneous signal intensity internally with both T1- and T2-weighted sequences, a finding that is compatible with blood in various stages of evolution (Fig 3). Fluid-fluid levels were also present. Several other complex masses with similar signal intensity characteristics were present in the distal thigh, knee, and proximal lower leg. Osseous and soft-tissue structures of the knee had been replaced. The neurovascular bundle was seen to be obliterated on multiple sections, and muscles that had not been replaced by the masses were atrophic (Fig 4).
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Figure 2. Axial T1-weighted MR image of the midthigh shows a large, heterogeneous soft-tissue mass occupying most of the central and anterior thigh. Only a small shell of the femur remains. Note the severe displacement and compression of the gracilis (thin arrow) and flexor compartment (arrowheads) muscles. The superficial femoral neurovascular bundle is displaced medially (thick arrow).
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Figure 3a. Coronal T1-weighted (a) and T2-weighted (b) MR images of the thigh show a heterogeneous mass with a low-signal-intensity capsule. In general, the interior of the mass demonstrates high signal intensity on the T1-weighted image and low signal intensity on the T2-weighted image (white arrow), findings that are compatible with intracellular methemoglobin. Smaller areas of high signal intensity compatible with extracellular methemoglobin are seen on both images (arrowhead). Note also the areas of low signal intensity in a and high signal intensity in b representing serous fluid (black arrow).
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Figure 3b. Coronal T1-weighted (a) and T2-weighted (b) MR images of the thigh show a heterogeneous mass with a low-signal-intensity capsule. In general, the interior of the mass demonstrates high signal intensity on the T1-weighted image and low signal intensity on the T2-weighted image (white arrow), findings that are compatible with intracellular methemoglobin. Smaller areas of high signal intensity compatible with extracellular methemoglobin are seen on both images (arrowhead). Note also the areas of low signal intensity in a and high signal intensity in b representing serous fluid (black arrow).
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Figure 4. Axial fat-saturated fast spin-echo MR image of the knee region shows multiple heterogeneous soft-tissue masses that have completely destroyed all the bones about the knee and knee joint. The adjacent soft-tissue structures have been replaced or are severely compressed. Note also the small gastrocnemius muscles posteriorly (arrows).
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Radiography of the femur, knee, and tibia-fibula helped confirm lytic destruction of the middle to distal femur and bones about the knee, including the patella and proximal tibia and fibula (Fig 5). There was a curvilinear, incomplete shell of bone at the end of the femur that suggested the existence of an expansile phase earlier in the evolution of the lesion. Large soft-tissue masses of the thigh and proximal leg showed no internal calcification or ossification. The remaining bones proximally and distally were severely demineralized.
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Figure 5a. Anteroposterior radiographs of the thigh (a) and tibia-fibula (b) show a large soft-tissue mass with lytic destruction of the distal femur and proximal fibula. Severe disuse osteopenia is also present.
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Figure 5b. Anteroposterior radiographs of the thigh (a) and tibia-fibula (b) show a large soft-tissue mass with lytic destruction of the distal femur and proximal fibula. Severe disuse osteopenia is also present.
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Angiography was performed with contrast material injected into the left common femoral artery. This procedure demonstrated the soft-tissue masses to be avascular. Upper thigh vessels were splayed around the masses (Fig 6). The superficial femoral artery was occluded at the level of the proximal thigh. Vessels around the inferior aspect of the masses reconstituted the peroneal artery.
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Figure 6. Arterial phase digital subtraction angiogram of the proximal thigh shows splaying of the vessels around the upper aspect of the dominant pseudotumor. The soft-tissue pseudotumors appeared avascular on all images.
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Pathologic Evaluation
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The patient was taken to the operating room and underwent amputation of the left leg. At gross pathologic examination, the leg weighed over 45 pounds. The leg was distorted by multiple large, fluctuant masses (Fig 7). Dissection revealed a large (37.5-cm) cavity superior to the knee filled with clotted blood. The distal femur was almost completely obliterated, with only a small remnant of bone attached to skeletal muscle superiorly. Three additional smaller cavities ranging in size from 13.3 to 16.5 cm were located medial, lateral, and anterior to the knee. The patella, knee joint, and proximal fibula were destroyed. The cavities were walled off by compressed muscle and fascia. Hemosiderin deposition was grossly evident along the length of the tibia and residual fibula. Neither the popliteal artery nor the anterior or posterior tibial arteries could be identified.
The results of histologic examination confirmed that the masses represented a coagulum of blood products. The walls of the masses consisted of fibrous tissue with hemosiderin-laden macrophages.
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Discussion
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Hemophilic pseudotumors were first described in 1918 by Starker (1). Pseudotumors are an uncommon complication of hemophilia, occurring in 1%–2% of persons with severe forms of the disease (2,3). Because both hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency, or Christmas disease) are X-linked recessive genetic disorders, pseudotumors are found almost exclusively in men between 20 and 70 years of age (4). A hemophilic pseudotumor is an encapsulated, chronic, slowly expanding hematoma seen in patients with a severe coagulation disorder. Many patients recall sustaining an injury prior to development of the pseudotumor (5,6). These lesions usually occur in soft tissues (often intramuscular) but occasionally occur de novo in bone or in a subperiosteal location. Pseudotumors that occur in muscles with broad tendon insertions readily progress to cause severe pressure erosion of adjacent bone (6). The bones most commonly involved by pseudotumors are the femur, pelvis, tibia, and bones of the hand (5).
A pseudotumor consists of blood products in various stages of evolution and has a fibrous capsule that contains hemosiderin-laden macrophages (4,7). Progressive enlargement of a pseudotumor exerts increasing amounts of pressure on adjacent structures. Bones may be completely destroyed, and muscles and skin are often compressed and may undergo necrosis. Compartment syndromes and joint contractures may also occur (6). Pseudotumors are usually painless, but compression of nerves may produce pain or neurologic deficits (4,8). Pathologic fractures may also cause pain (5). Superimposed infection or fistula formation to skin or bowel frequently complicates disease management (2,8). With soft-tissue progression of a pseudotumor, there may be profound loss of function of the involved extremity. In rare instances, exsanguination has resulted from pseudotumor rupture (6,9). Patients with pseudotumors are often asymptomatic or stable for long periods of time, only to suddenly and unpredictably develop one or more of the complications described earlier (2,8,10).
Osseous pseudotumors have a variable radiographic appearance but demonstrate some common features. Osseous pseudotumors are lytic in nature and usually have a well-defined margin; however, they may become quite extensive and completely replace segments of bone, as in this case. Lesions may be intramedullary or eccentric in location and are often expansile. Osseous trabeculae frequently traverse the lesions. Occasionally, calcific or ossific foci are present in the internal matrix; these foci are presumably dystrophic or sequestral in nature (7,11). There is often reactive sclerosis around bone pseudotumors.
Soft-tissue pseudotumors manifest as nonspecific masses at radiography. They may demonstrate internal calcifications or ossifications. There may be no bone involvement or, at the other end of the spectrum, severe replacement of bone. Subperiosteal bone formation may be present focally and may be the only early radiographic sign of a developing soft-tissue pseudotumor (11). Subperiosteal hemorrhage may cause marked elevation of the periosteum. A chronic pseudotumor on the bone surface may lead to a characteristic curvilinear ossification or calcific "strut" that projects into soft tissues (11).
Computed tomography (CT) and MR imaging are useful for determining the extent of the pseudotumor in bone and soft tissues and for defining the anatomic relationship between the pseudotumor and neurovascular structures and joints (12). CT is particularly helpful in the evaluation of bone, whereas MR imaging is superior for displaying the soft tissues and intramedullary spaces. Ultrasonography may also help identify the extent of soft-tissue pseudotumors (13).
The MR imaging appearance of pseudotumors is nonspecific but consistent. Invariably, there are heterogeneous low- and high-signal-intensity areas internally on both T1- and T2-weighted images, findings that represent blood products in various stages of evolution (6). Soft-tissue pseudotumors are circumscribed by a hypointense fibrous capsule (12). Jaovisidha et al (6) found mural nodules to be a common MR imaging finding in soft-tissue pseudotumors. Rarely, MR imaging findings may alter decisions regarding factor replacement by allowing diagnosis of acute rehemorrhage within a pseudotumor (6,12). Acute hemorrhage with intracellular deoxyhemoglobin appears isointense on T1-weighted MR images and hypointense on T2-weighted images (6,12).
Angiography has been used on rare occasions for presurgical planning but can now probably be supplanted by CT or MR angiography. Angiographic findings confirm pseudotumors to be avascular.
The radiologic differential diagnosis for osseous pseudotumor is largely academic because a diagnosis of pseudotumor can be made confidently when characteristic imaging findings are seen in a patient with a severe coagulation disorder (4,5). Nevertheless, there are many malignant bone tumors that may resemble a pseudotumor, including fibrosarcoma, plasmacytoma, malignant fibrous histiocytoma, telangiectatic osteosarcoma, and metastatic disease from primary tumors in the kidney, thyroid gland, or lung. Benign bone tumors such as aneurysmal bone cysts, solitary bone cysts, brown tumors, and desmoplastic fibroma are considerations, as well as unusual infectious processes such as echinococcosis. The hemorrhagic nature of osseous and soft-tissue pseudotumors is not helpful in making the diagnosis; many benign and malignant tumors of the bone and soft tissue with internal hemorrhage have been reported.
Percutaneous drainage or biopsy of a pseudotumor is contraindicated due to the high prevalence of complications, including life-threatening bleeding, fistula formation, and infection (2,8). Therefore, it is vital that the radiologist make the diagnosis of pseudotumor based on patient history and imaging findings.
Therapy for hemophilic pseudotumor is aimed at preserving function; however, no standard therapy exists. Gaary et al (14) suggest that conservative therapy with immobilization and clotting factor replacement works best for pseudotumors resulting from recent hemorrhage, whereas surgical management yields the best results for pseudotumors that have been present for years or for those in which conservative measures have been ineffective (2,14). Other investigators recommend that surgery be performed in most patients (8). Radiation therapy with doses of 10–20 Gy has been used only in patients who do not respond to conservative treatment and in whom surgery is contraindicated (14–16).
In summary, therapy for hemophilic pseudotumor should be selected on a case-by-case basis (2,8). In this case, the patient received a factor VIII infusion. He then underwent above-the-knee amputation followed by further clotting factor replacement. He was ultimately discharged in good condition with plans for physical rehabilitation.
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- Resnick D. Diagnosis of bone and joint disorders 3rd ed. Philadelphia, Pa: Saunders, 1995; 2295-2321.
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