Unicameral (simple) bone cysts.
Key Words: simple bone cysts, unicameral bone cysts, fallen leaf sign, fluid-fluid levels
Bone cysts have been studied repeatedly since Virchow's descriptions in 1876. (1) Most accurately described as multiloculated bone cysts, (2-6) these defects are not true neoplasms (Fig. 1). They are expansile, usually serous fluid-containing defects of the tubular and flat bones, discovered in patients between 2 and 72 years old. Peak age ranges are between 3 and 14 (80% of cysts) with an average age of 9 (7) at the time of discovery. While the absolute incidence is not known, the reported rate is 3% of all bone lesions. The male to female ratio is 2:1. (2,5,7) These cysts affect only one bone in most patients, but there are reports of two or three cysts being found in the same patient. (8)
The natural history of these defects is that they are most active in children younger than age ten and later become inactive. Rarely does a cyst progress after closure of the growth plates.
Attempts have been made to classify these lesions into active and inactive types. (8) Active cysts have been defined as those in direct contact with the adjacent growth plate in the skeletally immature patient, and inactive ones are those found at a distance from the growth plate. The so-called "active" cysts reportedly have a higher recurrence rate than the inactive or latent ones (Fig. 2a). Others have suggested that intracystic fluid pressure above 30 mm Hg is predictable of cystic activity. None of these classifications have proven to be reliable with our multivariant analysis.
Recent literature suggests that activity of these cysts is more a function of age. Cysts that occur in patients below age 10 are active and those seen over age 10 tend to be inactive (Fig. 2b and c). Cysts in children older than 10 at the time of initial presentation are usually further away from the growth plate. Limited long-term studies of the cysts, using serial x-rays, have documented that the growth plate moves away from the cyst as the child grows. These observations are also supported by data showing that two thirds of these cysts are not in contact with the growth plate when initially discovered (9) in children age 10 or older.
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Many theories for the development of these cysts have been proposed, from Moncheberg's in 1904, (10) Phemister and Gordon in 1926, (10) Jaffe and Lichtenstein in 1942, (6) Cohen in 1960, (11) and Neer in 1973, (9) in an effort to explain the development of these defects. Presently, the most popular theory is that of venous outflow obstruction in bone, as proposed by Cohen, (12) which results in an elevated intraosseous pressure. This increased pressure phenomenon apparently leads to osteoclastic activation for resorption of bone, presumably from the elevated cytokines (prostaglandins, (13) interleukin 1[beta], and gelatinase (14)) released by the endothelial cells lining the cyst wall. (14)
Many cysts are found serendipitously when films of an involved bone are taken for other reasons. For example, films of the humerus taken of a young patient who has experienced some type of trauma--auto, playground, or sports accidents (Fig. 3).
Pathologic fracture of the cystic defect from relatively minor trauma is also a relatively common presentation, creating an unstable, painful bone (Fig. 4). Otherwise, these cysts are asymptomatic.
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Anatomic and Physiologic Considerations
Ninety-four percent (3) of these cysts occur in the proximal humerus and proximal femur, with the proximal humerus being affected two to three times more frequently than the proximal femur (Fig. 5a and b).
The remaining 6% occur in other bones, including the calcaneus (2%), ilium (2%), talus, tibia, (15-19) (Fig. 6a-d) metatarsals, fibula, ischium, pubic rami, sacrum, vertebral bodies, forearm, and craniofacial bones. (20-24) The cysts that occur in the flat bones (pelvis) are usually found in these locations in patients between the ages of 12 to 72, with an average age of 32. (7) The "late" findings are due to their deep location and lack of symptoms.
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Diagnosis and Recognition
The typical radiographic appearance is that of a lesion concentrically located in the medullary cavity (3,4) of the metaphysis of a long bone (Fig. 1-3) with expansion in all directions, creating an expanded and thinned but unpenetrated cortex. Cysts located in flat bones such as the pelvis are centered between the inner and outer tables of the ilium (Fig. 7), and midportion of the superior pubic ramus. While the cortical rim of the involved bone may be very thin, it remains distinct. The long axis of the lesion in the bone almost always exceeds its width, giving the appearance of a truncated cone. (3) The distal extent of the long axis of the cyst, especially in the humerus, is frequently hard to see on plain films (Fig. 5b) and appears to blend into the metadiaphyseal bone outline. If periosteal reaction is present along the thinned cortex of the cyst wall, one should search carefully for a pathologic fracture in the area. Multilaminated periosteal reactions, Codman triangles, and cortical penetration do not occur.
* The "fallen leaf" sign on plain films is virtually pathognomonic of a multiloculated bone cyst (25) (Fig. 8a and b). This results when a pathologic fracture in the thinned cortical wall of the bone dislodges a fragment of the cortex. The fragment "drops" into the fluid-containing (but often not filled) cavity of the cyst. This fragment can also shift in the fluid, depending on positioning of the patient's involved bone during serial imaging. The cyst is infrequently distributed from one end of the bone to its opposite end. This appearance is almost always found in the skeletally mature or close to skeletally mature patient.
* Fluid: Fluid-fluid levels seen on x-rays of cysts have been reported to be reliable evidence of blood in an aneurysmal bone cyst (ABC). Fluid-fluid levels are also seen on CT scan, but are often vertical because the patient is supine and the images are printed at 90 degrees. More recent literature confirms that this is a nondiagnostic and nonspecific finding, as it has also been confirmed in giant cell tumors and even telangiectatic osteosarcomas. (26) The radiographic presentation of simple cysts and aneurysmal bone cysts are very hard to differentiate on plain films in children under age 8, as both lesions can have identical radiographic and histologic appearances (Fig. 9 and Fig. 1). As will be mentioned further in the text, simple cysts and ABCs are also very difficult to distinguish by aspiration/injection techniques and are difficult to differentiate histologically in children below age 10. (5,27)
* Role and appearance of:
a) Bone scan -- typically, the Tc (99) bone scan shows a photopenic center with a surrounding rim of mild uptake around the cyst. The only confusing bone scan finding is when a pathologic fracture has occurred and areas of healing bone are present throughout the body of the cyst. Such areas will show varying degrees of uptake, depending on the age of the fracture (Fig. 10a and b).
b) CT -- CT scanning is most helpful in evaluating the extent of pelvic cysts but can be used for evaluation of cysts in any location. The plain film alone provides adequate diagnostic information in most long bones (Fig. 1, 2a-c). When the cyst is found in the midshaft of a bone or in an unusual location (Fig. 11), CT may be useful in determining the extent of the defect. If the CT scan is utilized to evaluate these cysts, Houndsfield units should always be included on the films to confirm the existence of fluid, since lipomas of bone also occur, especially in the os calcis, vertebral bodies, and the proximal femur (the second most common location for cysts) and have a similar plain film and CT scan appearance. Fluid within cystic defects is typically less than 20 Houndsfield units (2-18 U). Fat is less than 0 Houndsfield unit (0 to -200), and is helpful for differentiation.
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c) MRI -- the typical bone cyst will show a low [T.sub.1] and high [T.sub.2] signal on MRI (Fig. 12a and b). However, these findings do not clearly differentiate the aneurysmal bone cyst from the simple cyst in the child under age 8.
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d) "Bone-o-gram"/cineradiography -- some authors have recommended injecting a radio-opaque dye into the cystic defect as an additional diagnostic aid, stating that if this material fills the cavity, the diagnosis of a cyst can be safely made. A cyst that does not fill with dye implies a solid tumor. Our experience with over 200 bone cysts shows that the "bone-o-gram" has limited usefulness for diagnostic purposes. Injections of radio-opaque dye into an active cyst rarely fills it, as the dye rapidly traverses the cavity without filling it, and drains into the surrounding venous system, creating a venogram almost instantly (Fig. 13). This observation raises the question of efficacy of any material that is so rapidly cleared. Limited recent reports also show that injection of fluid into the closed medullary cavity of the bone increases the intraluminal pressure fourfold. There has been one report of a fatal embolism during injection techniques into the humeral canal for the treatment of a cyst. Inactive cysts occasionally have well-formed septations that prevent complete filling of the defect (especially if a fracture has previously occurred), thereby giving rise to a confusing picture when the preoperative workup reliably reflects a simple bone cyst (Fig. 14). Probably the most reliable use of the "bone-o-gram" is aspiration of benign-appearing straw-colored fluid from the defect before injection of dye.
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* Aspiration of both unicameral and aneurysmal bone cysts (UBC and ABC) in children below age 10 will frequently produce blood, even with gentle aspiration pressure on the syringe. Therefore, aspiration of bloody fluid from these cysts is also an unreliable indicator for diagnosis. Rarely, simple bone cysts have been noted to cross the physis in very young patients, frequently less than 5 years old, (Fig. 15a and b) but this finding has also been observed in older patients (Fig. 1lb), as documented by MRI and injection techniques.
* The gross appearance of the interior of these cysts is that of a multiloculated fluid-filled chamber, in which many of the chambers are incompletely formed, leaving prominent ridges of bone arranged throughout the cavity of the cyst. (28)
* Material from these ridges were at one time thought to be cementum, but further investigation has shown it to be made of normal bone. (29) The cyst usually contains a yellow-tinged serous fluid with low viscosity, similar to serous effusions of other body cavities. This fluid has been analyzed and found to contain prostaglandins (13) ([E.sub.2] especially), interleukin 1[beta] and metalloproteinases (14) such as gelatinase and collagenase.
* Histologically, a thin, several cell thick lining with deeper layers of fibrous tissue, giant cells containing hemosiderin, and cholesterol clefts are present. The cyst lining is composed of flattened cuboid-like cells. It is appropriate to emphasize that the wall lining of these cysts sometimes "runs out" in the medullary cavity of the affected bone, with no marginal definition (Fig. 2b). Histiocytes and scattered inflammatory cells are often found in this lining, as are dilated blood vessels (Fig. 16a and b). Fibrin deposits in the wall of the cyst can become mineralized enough to produce concentric lamellar structures that resemble cementum, and these calcified deposits can undergo ossification. (24,30-32) This was reported in the older literature as a cementoma, which is incorrect. As noted in the radiology section of these tumors, in children under age 8 to 10, multicameral cysts can have features indistinguishable from aneurysmal bone cysts clinically, radiographically, and histologically.
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The cornerstone of earlier treatment strategies was open curettage of the cyst lining followed by packing of the cavity with a void filling material. This material has ranged form Plaster of Paris (33) to bone grafts (both autogenic and allogenic) and bone graft substitutes. Combinations of these materials have also been used with varying rates of success.
A short history of different methods include:
1. Peltier and Jones used curettage and packing of the cyst cavity with sterilized Plaster of Paris pellets obtaining a 90% success (cure) rate. (33)
2. Subtotal resections of these cysts have been reported, with and without intercalary grafting. (34,35) These procedures had a 9% recurrence rate.
3. Drilling alone of these cysts has also been reported as well as trepanation with drainage of the cyst fluid and saline lavage of the cavity.
4. The results of direct bone grafting of these defects have been varied. Recurrence rates as high as 4% using autograft and 45% using allograft are reported. This success rate is reportedly improved with "complete" packing of the cysts. (36) This technique is not universally successful and is not presently popular.
1. In 1979, Scaglietti et al (37) reported 90% "favorable" results using intracystic injections of methylprednisolone acetate, with no growth inhibition or secondary deformity of the involved bone. When these results were carefully reviewed, a number of treated cysts designated as successes never completely healed radiographically, but were clinically stable and thus were reported as a "favorable" result.
2. Campanacci et al produced similar results in another series of patients but had "incomplete" healing in 30% of the reported "cures". (3)
3. Oppenheim and Galleno (38) compared the use of steroid injections versus surgical curettage and found a recurrence rate of 5% in those patients treated with steroids. Fifty percent of those patients successfully treated with steroids required more than one steroid injection for "cure." In our experience, steroid injections in patients less than 10 years of age have similar rates of recurrence as any other reported treatments. However, this method became the most popular procedure for management of cysts in the humerus during the 1970s to the 1990s.
4. Reports of steroid injections into calcaneal cysts are mixed, (39,40) probably due to the low numbers of reported series. The most concerning results were those of Goel and Kriger (39) who reported no response in two out of three cysts treated with steroid injections. Most series show dismal failure rates after steroid injections in calcaneal cysts. In contrast, curettage and bone grafting of calcaneal cysts (41) has been shown to be successful in six out of six patients, one of whom received three steroid injections before the grafting procedure.
Dissatisfaction with steroid injections in some patients, especially those under 10 years of age, has regenerated interest in other methods of treatment, such as the use of bone graft substitutes. (42) Such substitutes include bioactive ceramics (tricalcium phosphate) Demineralized Bone Matrix (DBM) in a carrier of hyaluronic acid (Musculoskeletal Transplant Foundation, Edison, NJ). demineralized bone matrix in a carrier of glycerol Grafton (Osteotech Inc., Eatontown, NJ), Dynagraft (Dynagraft General Science Regeneration Sciences, mc, Irwine, CA), Osteofil (Regeneration Technologies Inc., Alachua, FL), Calcium sulfate salts; Osteoset pellets (Wright Medical Technologies Inc., Arlington, TN) and Allomatrix (Wright Medical Technology Inc., Arlington, TN). Various mixtures of these substances for the treatment of cysts have also been reported. As previously stated, at least one fatality has been reported with this method from embolization to the lungs during injection of such material into the cyst of a young child.
High porosity calcium hydroxyapatite cubes alone have been used (43) but the major drawbacks of this material appear to be time related, with reports showing it takes as long as five months for new bone to develop around the hydroxyapatite. "Intermingling" of this material into the surrounding cancellous bone may require up to a year. Complete incorporation of this substance into bone has not been reported to our knowledge.
Tricalcium phosphate has also been used (44) to graft defects of the humerus, femur and calcaneus, following curettage. Of the 18 patients treated in one study, 16 demonstrated incorporation of this material with no adverse reactions.
Our experience with trepanation of these cysts, followed by placement of Osteoset pellets (with an applicator tube through the trepanation hole) until the cavity is relatively filled then adding demineralized bone matrix (DBM) putty into the voids between the pellets through the same tube has resulted in healing of 85% (13/16) of cysts in children under 10 years old. It appears that any DBM product (Grafton or DBX) may be used as the "filler," as the materials appear to create similar results.
It would appear that Norian SRS and ETEX[alpha] BSM may produce similarly good results, but the use of these two products in multiloculated bone cysts has not been widely reported.
As previously noted, the only reliable predictor of treatment success, using multivariant analysis studies, is the age of the patient; those older than 10 heal their cysts at a higher rate (90%) than those less than 10 years old (60%), no matter what treatment regimen is utilized. Even in reports showing healing rates of 88% (36) with "complete" packing, patients younger than 10 had a higher recurrence rate following treatment.
Most of these cysts tend to heal to a position of stability after skeletal maturity. They may never remodel to a radio-graphically normal-appearing bone, treated or untreated. The goal of management is the formation of a bone that can withstand the stresses of use by the patient without evidence of continued bone destruction as determined by serial radiographic follow-up. Campanacci (3) advised that 90% of unicameral bone cysts can be treated nonoperatively as a result of these reports. The goal is not a normal-appearing x-ray, but a functionally stable bone.
Conversely, if the patient is at risk for a pathologic fracture of the cyst in a critical weight-bearing area such as the femoral neck or os calcis, and/or if evaluation of the x-rays (initial or serial comparisons) can be used to reasonably predict an impending pathologic fracture, surgical treatment is appropriate. Increased diligence is appropriate with cysts of the femoral neck and the subfacet area of the body of the os calcis, where normal stresses on the anatomic configuration of these bones increase the risk of fracture and complications. The sensitivity of treatment indicators for intervention at these sites needs to be narrowed so that early treatment can help prevent pathologic fractures that may interfere with the blood supply and/or anatomic stability of the areas involved.
Difficulties in the decision-making process usually occur when an unusually active individual or athlete is found to have an asymptomatic cyst discovered on routine radiographic examination of a bone for another reason. Treatment indications can be adjusted to fit the needs of these patients.
It is important to emphasize that once a pathologic fracture occurs in these cysts, it is prudent to allow the cyst to heal before instituting any surgical or injection therapy management. The only exception to this admonition is the displaced fracture of the femoral neck or posterior facet of the os calcis where open reduction and anatomic fixation is preferred to reduce the long-term complications on function caused by interference with critical blood supply or nonanatomic alignment of bone in these areas.
Authors' Preferred Treatment
If a patient presents with a serendipitously discovered asymptomatic cyst, and the plain films demonstrate a stable thick cortical wall, biopsy, injection or surgical treatment is not indicated, regardless of patient age. The authors' preferred current management of choice for unfractured cysts which require treatment is trepanation and injection of bone-stimulating materials into the defect, through a trepanation site large enough to prevent increased intraluminal pressure while the injection is occurring. Management of pathologic fractures is intended to stabilize the fracture until healing occurs before instituting any treatment of the cyst. While injection of steroids into these cysts has a scientific basis due to their role as suppressants of bone resorptive factors (prostaglandins, interleukin 1[beta] and gelatinase), there is no convincing evidence that this actually occurs.
Open reduction, grafting and anatomic fixation of pathologic fractures caused by these cysts is indicated for a displaced femoral neck or posterior facet of the os calcis fractures.
Recent advances in treatment of recalcitrant cysts, especially in children below age 10, using calcium sulfate pellets and demineralized bone matrix, or combinations of these substances, show promising results. (42)
Simple bone cysts may create major structural defects of the humerus, femur, and os calcis when they occur in these bones. While the majority of such cysts occur in the proximal humerus and proximal femur (94%), they also develop in other bones, including the os calcis, ilium, talus, tibia, and small bones of the hands and feet. While the precise age range of development of these cysts is not known, they most probably begin in childhood, around 3 to 7 years of age (Fig. 9), but are not discovered until later, as most do not cause a clinical problem until adolescence. Symptoms and functional limitations are usually due to pathologic fracture. Many are found serendipitously following x-rays of a bone for other reasons. Most cysts tend to heal to a position of stability at skeletal maturity, but the area of bony involvement may never remodel completely.
The x-rays and histologic differentiation between simple bone cysts and aneurysmal bone cysts in children under age 10 can be extremely difficult, as both can have bloody aspirations, hemosiderin and blood in the fibrous tissue linings, as well as similar appearances on radiographic examination.
The only reliable prognostic indicator for successful treatment of these cysts is age related, as patients over age 10 have better results (90%) from any instituted treatment than patients under age ten (60%). Some investigators have suggested that appropriate treatment of these defects in children under the age of 10 should be observation alone, because of the limited response to treatment.
An important principle to remember in the treatment of these defects is that the primary goal of management is a healed bone that can withstand predictable, functional stresses of activity by the patient, no matter what the radiographic appearance of the "healed" bone reflects.
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Truth persuades by teaching, but does not teach by persuading. --Quintus Septimius Tertuillianus
Rafath Baig, MD, and John L. Eady, MD
From the Department of Orthopaedics, University of South Carolina, Columbia, SC.
Reprint requests to Rafath Baig, MD, University of South Carolina. Department of Orthopaedics, Suite 404, 2 Medical Park, Columbia, SC 29203. Email: firstname.lastname@example.org
Accepted April 21, 2006.
RELATED ARTICLE: Key Points
* Ninety-four percent of unicameral bone cysts occur in the proximal humerus and proximal femur, with the proximal humerus being affected two to three times more frequently than the proximal femur.
* The remaining 6% occur in other bones including the calcaneus (2%), ilium (2%), talus, tibia, metatarsals, fibula, ischium, pubic rami, sacrum, vertebral bodies, forearm, and craniofacial bones.
* The typical radiographic appearance is that of a lesion concentrically located in the medullary cavity of the metaphysis of a long bone with expansion in all directions, creating an expanded and thinned but unpenetrated cortex.
* The "fallen leaf" sign on plain films is virtually pathognomonic of a multiloculated bone cyst.
* Aspiration of both unicameral and aneurysmal bone cysts in children below age 10 will frequently produce blood, even with gentle aspiration pressure on the syringe.
* Rarely, simple bone cysts have been noted to cross the physis in very young patients, but this finding has been observed in older patients, as documented by MRI and injection techniques.
* The only reliable predictor of treatment success is the age of the patient; those older than 10 heal at a higher rate (90%) than those under 10 years of age (60%), no matter what treatment regimen is utilized.
* The primary goal of management is a healed bone that can withstand predictable functional stresses of activity by the patient.
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|Title Annotation:||Review Article|
|Author:||Eady, John L.|
|Publication:||Southern Medical Journal|
|Date:||Sep 1, 2006|
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