Aneurysmal Bone Cyst: A Review of 150 Patients
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《临床肿瘤学》
the Orthopedic Oncology Service, Massachusetts General Hospital and Children's Hospital, Harvard Medical School, Boston, MA
ABSTRACT
PURPOSE: We have reviewed a series of 150 aneurysmal bone cysts treated over the last 20 years.
PATIENTS AND METHODS: The lesions were principally located in the tibia, femur, pelvis, humerus, and spine and, in most cases, presented the imaging appearance originally described by Jaffe and Lichtenstein as a blowout with thin cortices.
RESULTS: Only one of the patients was believed to have an osteoblastoma of the spine with secondary development of an aneurysmal bone cyst, and none of the patients developed additional lesions. The patients were treated primarily with curettage and implantation of allograft chips or polymethylmethacrylate, but some patients were treated with insertion of autografts or allografts. The local recurrence rate was 20%, which is consistent with that reported by other centers.
CONCLUSION: Aneurysmal bone cysts are enigmatic lesions of unknown cause and presentation and are difficult to distinguish from other lesions. Overall, the treatment is satisfactory, but it is possible that newer approaches, such as improved magnetic resonance imaging studies, may help diagnose the lesions and allow the physicians to plan for more effective treatment protocols.
INTRODUCTION
Despite a descriptive history of more than 60 years, the nature, character, and optimal treatment of aneurysmal bone cysts remain obscure. The lesion was first described by Jaffe and Lichtenstein1 in 1942, was subsequently further defined by both of these authors,2,3 and became known as Jaffe-Lichtenstein disease. Despite attempts on the part of investigators to establish a relationship of the disorder to other entities, the term aneurysmal bone cyst remains purely descriptive. It does not provide any concept of pathogenesis or causation mechanisms, and efforts on the part of a number of investigators to discover a genetic or neoplastic cause have failed.4-18 Examination of the tissue at the time of surgery has, in the past, demonstrated a blood-filled cavity within an expanded region of the bone, and the cells that line the cyst wall show fibrous components, macrophages, giant cells, and islands of bone.1,7-9,19-24 The term aneurysmal seems to relate to the blowout distension, and the word cyst reflects the fact that the tumor often presents as a blood-filled cavity.7,9,25 Occasionally in prior studies, there have been findings suggesting the possibility that the aneurysmal cyst is actually a result of hemorrhagic degradative events occurring in patients with other lesions including giant cell tumor, hemangioma, chondroblastoma, osteoblastoma, nonossifying fibroma, fibrous dysplasia, chondromyxoid fibroma, eosinophilic granuloma, and other tumors.1,7,9,19-24 Of greater concern is the possibility that the lesion is not an aneurysmal cyst but a partially necrotic and extremely vascular telangiectatic osteosarcoma, which has a high rate of metastasis.7,9
Many reports have appeared that describe patients with aneurysmal bone cysts.3,6,8,14,16,22,24,27,28,31-36 The lesions are more common in patients in the first two decades of life rather than in later years7,8,28,31,37 and seem to be slightly more frequent in females than males.7,8,28-30 The major sites of occurrence, according to a number of authors, are the femur, tibia, humerus, spine, and pelvis, and although tumors arising in the small bones of the hands and feet are seen occasionally, there are fewer of such instances in most series.3,7,9,14,16,24,32-36 The tumors are usually metaphyseal or diaphyseal and are most often eccentrically located, which is an important distinguishing radiographic feature from unicameral bone cyst in patients in their second decade.7-9,12,20,24,38,39 The appearance of the lesions support the word blowout and show marked thinning of the cortex over the site, with only minimal bone formation; all of which are sometimes best seen on a computed tomography (CT) or a magnetic resonance imagining (MRI) scan.38,39 Controversy exists regarding optimal treatment, and regardless of techniques reported, there remains a recurrence rate that ranges from 5% to greater than 40%.7,24,28-34 At present, curettage and insertion of bone graft or polymethylmethacrylate are the principal techniques used,7,20,24,29,31,33,34 but in the past, radiation has been used.40 In several trials, sclerosing substances, bone substitutes, and other agents seemed to be less effective than conventional curettage.41-43 Our purpose in presenting this material is to review the data obtained over the last 20 years regarding patients with aneurysmal bone cysts to define the appearance, anatomic site, complications, and results of various forms of treatment.
PATIENTS AND METHODS
The Orthopedic Oncology Service at the Massachusetts General and Children's Hospitals has maintained a computerized database containing information regarding more than 17,000 patients with bone and soft tissue tumors treated over the last 30 years.44 Study of the system provided information regarding 223 patients with aneurysmal bone cyst, but only 150 of these patients who had been observed for as long as 20 years had sufficiently accurate descriptions of treatment protocols, definition of pathology, and recent assessment of outcomes to allow statistical analysis (Table 1). The system used to gather information regarding the patients did not, in any way, violate patient confidentiality and was approved by the hospitals' institutional review boards.
Sixty-nine of the 150 patients were male, and 81 were female. The mean age of the patients was 18 ± 12 years, with a range of 3 to 62 years. The mean follow-up time for the patients was 6 ± 7 years (range, 1 to 20 years). The anatomic locations for the lesions are listed in Table 1, and as noted, the most common sites were the tibia, femur, fibula, pelvis, humerus, clavicle, foot, and lumbar spine. The patients' complaints at the time of the initial visit were almost always concerning pain at the site and sometimes indicated pain and numbness extending down the limb. The patients were often disabled by the pain and almost always presented with tenderness over the site of the lesion. Examples of the imaging studies are shown in Figures 1 and 2, and as noted, the lesions are metaphyseal or diaphyseal in location, are usually eccentric with thin cortices, and, in most cases, present the classic blowout appearance (Fig 3). Gross structure is shown in Figure 4, which displays the thin cortices, the expansion, and the chambers often filled with blood. The histologic patterns are shown in Figures 5 and 6. The patterns demonstrate thin cortices; blood elements in the central portion of the tumor; and an array of benign-appearing macrophages, lymphocytes, fibroblasts, bone-forming cells, and giant cells, which are sometimes atypical in terms of structure and nuclear distribution.
As shown in Table 2, 130 patients were treated with curettage, and of these patients, 101 had lesions that were packed with allograft bone, and 20 had lesions that were packed with polymethylmethacrylate cement. Twenty of the patients had an excision or resection of the lesion, and 11 of these patients received an intercalary allograft transplantation.
Statistical studies used analysis of variance and Mantel-Haenzel and Fisher's exact tests using 2 analysis. The systems were provided by BMDP Statistical Software (Los Angeles, CA). P < .05 was considered statistically significant.
RESULTS
None of the patients died of disease, and there were no amputations. The principal problem that the patients encountered with their treatment of the aneurysmal bone cysts was local recurrence, which occurred in 30 (20%) of the 150 patients at 1.2 ± 0.7 years (range, 0.3 to 3 years) after discovery of the lesion. There was no statistical difference for sex. Patient age did not seem to have a significant effect on outcome, although the rate of local recurrence was slightly increased in younger patients (Table 3). Anatomic site seemed to make some difference in rates of local recurrence. The recurrence rate for the 10 patients with lesions of the clavicle was 50%, and the recurrence rate for the 13 patients with tumors in the distal femur was 46%, whereas other sites showed few or no recurrences (Table 3).
Of considerable interest was the recurrence rate data for the various operative procedures performed by our group over the 20+ years of experience in the treatment of patients with aneurysmal bone cysts. The recurrence rate for the 121 patients who were treated with curettage and packing with either allograft chips or polymethylmethacrylate was 22%, which was considerably greater than the 5% recurrence rate for patients who underwent resection and either an autograft or an allograft implantation (Table 2).
The patients who developed a recurrence required subsequent surgery, which consisted of another curettage and packing or resection of the site and autograft or intercalary allograft implantation. Of the 150 patients, 34 required a second operation and 13 required a third operation for recurrences or structural problems related to failed systems. One of the patients was treated with sclerotherapy, and two patients were treated with local injections of alcohol and other agents, all of which were successful. Three of the patients developed fractures through the weakened bony part, which, although not related to recurrence, required further surgery. The 11 allograft implantations were all rated as good or excellent at 6 ± 6 years (range, 1 to 20 years), and only one of the grafts sustained a fracture, which healed after replacement of the fixation. Only one of the patients in our series was found to have tumor suggestive of an osteoblastoma of L4 at the time of biopsy. The lesion was curetted and packed with allograft chips, and there has been no recurrence reported to date.
Fifty-seven of the 150 patients had the DNA content of the tissue obtained at surgery studied by flow cytometric analysis.45 The mean value for the diploid peak was 92 ± 4.3 (range, 86 to 98), and the mean value for the G2+M was 4.7 ± 3.2 (range, 0. to 14). The average mean DNA index was 1.06 ± 0.04 (range, 1 to 1.2). No aneuploid peaks were encountered. These values can be interpreted as being characteristic of benign tumors.45
DISCUSSION
As stated in the Introduction, despite the long experience of radiologists, pathologists, and orthopedists with aneurysmal bone cysts, there is limited knowledge regarding the cause of the lesion, its natural history, and the results of treatment.1,4,5-7,9-17 The concept that the lesion represents a vascular degenerative process for some benign bone lesions is an attractive one, but the pathologic findings, with rare exception, do not really support this proposal. Few pathologic specimens contain tissues that are highly characteristic or diagnostic of giant cell tumor, chondroblastoma, hemangioma, osteoblastoma, nonossifying fibroma, fibrous dysplasia, chondromyxoid fibroma, and other tumors.6,7,9-11,15-17,19,21,26,28,29 Furthermore, the recurrences after surgical treatment do not show evidence of such lesions, particularly aggressive lesions such as giant cell tumor. Only one of our 150 patients showed a finding suggestive of an osteoblastoma at the site of the aneurysmal bone cyst of L4. At best, it was a difficult decision based on the similarity of the repair process to the histologic pattern for osteoblastoma, and the lesion has not recurred at more than 2 years since the surgery.
Of some importance is the difficulty that can occur in diagnosing these lesions. The imaging studies, even CTs and MRIs, sometimes do not provide clearly diagnostic criteria for the diagnosis of aneurysmal bone cyst, and aneurysmal bone cyst is sometimes added on to a list of diagnoses including eosinophilic granuloma, giant cell tumor, nonossifying fibroma, unicameral bone cyst, fibrous dysplasia, chondroblastoma, chondrosarcoma, chondromyxoid fibroma, Ewing's tumor, and, in older patients, metastatic carcinoma or myeloma.7-9,12,20,24,38,39 The lesions are often eccentric and irregular in structure and sometimes show calcification in the central areas. As a rule, the cortex is thin, but there is rarely a cortical defect or a soft tissue mass. CT and MRI are often helpful in defining the extent of the lesion and establishing the diagnosis. A biopsy is often helpful, and many of our patients underwent a needle biopsy before definitive treatment. Needle biopsies are sometimes a problem because the material obtained may consist of mostly blood elements. Often, an open biopsy and frozen section are necessary to establish the diagnosis.
The recurrence rate in this series was 20%, which should be considered high compared with other series and other benign tumors.7 Part of this problem could conceivably be related to the methods of treatment over the 20 years during which these patients were treated. The recurrence rate for patients treated in the earlier years was higher than for patients who were treated more recently (approximately 26% v 17%, respectively). In the past, we used curettage alone, but our principal current approach was biopsy followed by curettage and then implantation of allograft chips or, more recently, polymethylmethacrylate. Autograft implantations or utilization of intercalary allografts were quite successful but were, for the most part, used for patients with lesions that were large or seemed to threaten the integrity of the bone and were used less frequently for patients who experienced failure of their primary procedure.
Although none of our patients died or required an amputation, a number of them had some relatively minor disability as a result of the tumor and its treatment. Thus, it is our opinion that aneurysmal bone cyst is sometimes an aggressive lesion that is difficult to treat. Lesions that occur in the proximal femur should perhaps be treated more aggressively, partly because of the high rate of local recurrence and the risk of fracture. The most appropriate techniques for some of these tumors are primary resective surgery and allograft implantation. Patients with lesions of the proximal or mid fibula or clavicle or body of the scapula could be treated by resection alone, and lesions of the foot might be best treated by resection and arthrodesis using autograft. According to our series, such treatment would at least reduce the local recurrence rate considerably and probably reduce the degree of even minimal disability reported by some of these young patients.
In this last analysis, aneurysmal bone cyst remains an enigma, not only regarding causation, but also regarding clinical and imaging diagnosis and optimal treatment. There is perhaps some hope for implantation of newer agents, such as the bone substitutes, to aid in healing of the lesions. Although there are now some markers that are alleged to be specific for aneurysmal bone cyst,1,9,12-15,18 there is still no system to establish the diagnosis or to support different methods of treatment and, thus, reduce the problems encountered by the patient and the surgeon.
Authors' Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
NOTES
Authors' disclosures of potential conflicts of interest are found at the end of this article.
REFERENCES
Jaffe HL, Lichtenstein L: Solitary unicameral bone cyst: With emphasis on the roentgen picture, the pathologic appearance and the pathogenesis. Arch Surg 44:1004-1025, 1942
Jaffe HL: Aneurysmal bone cyst. Bull Hosp Joint Dis 11:3-13, 1950
Lichtenstein L: Aneurysmal bone cyst: Observations on 50 cases. J Bone Joint Surg 39A:873-882, 1957
Aho HJ, Aho AJ, Einola S: Aneurysmal bone cyst: A study of ultrastructure and malignant transformation. Virchows Arch A Pathol Anat Histol 395:169-179, 1982
Aho HJ, Aho AJ, Peliniemi LJ, et al: Endothelium in aneurysmal bone cyst. Histopathology 9:381-387, 1985
Bonakdarpour A, Levy WM, Aegerter E: Primary and secondary aneurysmal bone cyst: A radiological study of 75 cases. Radiology 126:75-83, 1976
Campanacci M: Aneurysmal bone cyst, in Campanacci M (ed): Bone and Soft Tissue Tumors (ed 2). New York, NY, Springer Verlag, 1999, pp 812-840
Freiberg AA, Loder RT, Heidelburger KP, et al: Aneurysmal bone cysts in young children. J Pediatr Orthop 14:86-91, 1994
Dorfman HD, Czerniak B: Cystic lesions, in Dorfman HD, Czerniak B (eds): Bone Tumors. St Louis, MO, Mosby, 1998, pp 855-912
DaSilva MV, Raby N, Reid R: Fibromyxoid areas and immature osteoid are associated with recurrence of primary aneurysmal bone cysts. Histopathology 43:180-188, 2003
Hadders HN, Oterdoom HJ: The identification of aneurysmal bone cyst with hemangioma. J Pathol Bacteriol 71:193-200, 1956
Kransdorf MJ, Sweet DE: Aneurysmal bone cyst: Concept, controversy, clinical presentation and imaging. AJR Am J Roentgenol 164:573-580, 1995
Leithner A, Machacek F, Haas OA, et al: Aneurysmal bone cyst: A hereditary disease? J Pediatr Orthop B 13:214-217, 2004
Leithner A, Windhager R, Lang S, et al: Aneurysmal bone cyst: A population-based epidemiologic study and literature review. Clin Orthop Relat Res 363:176-179, 1999
Levy WM, Miller AS, Bonakdarpour A, et al: Aneurysmal bone cyst secondary to other osseous lesions: Report of 57 cases. Am J Clin Pathol 63:1-8, 1975
Martinez V, Sissons HA: Aneurysmal bone cyst: A review of 123 cases including primary lesions and those secondary to other bone pathology. Cancer 61:2291-2304, 1988
Szendroi M, Aratgto G, Ezzati A, et al: Aneurysmal bone cyst: Its pathogenesis based on angiographic, immunohistochemical and electron microscopic studies. Pathol Oncol Res 4:277-281, 1998
Oliviera AM, Perez-Atayde AR, Inwards CY, et al: USP6 and CDH11 oncogenes identify the neoplastic cell in aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol 165:1773-1780, 2004
Besse BE Jr, Dahlin DC, Pugh DG, et al: Aneurysmal bone cyst: Additional considerations. Clin Orthop 7:93-102, 1956
Campanacci M, Capanna R, Picci P: Unicameral and aneurysmal bone cysts. Clin Orthop Relat Res 204:25-36, 1986
Lichtenstein L: Aneurysmal bone cyst: A pathological entity commonly mistaken for giant cell tumor and occasionally for hemangioma and osteogenic sarcoma. Cancer 3:279-289, 1950
Ruiter DJ, van Russel TG, van der Velde EA: Aneurysmal bone cysts: A clinicopathological study of 105 cases. Cancer 39:2231-2239, 1977
Tillman BP, Dahlin DC, Lipscomb PR, et al: Aneurysmal bone cyst: An analysis of ninety-five cases. Mayo Clin Proc 43:478-495, 1968
Vergel De Dios AM, Bond JR, Shives TC, et al: Aneurysmal bone cyst: A clinicopathological study of 238 cases. Cancer 69:2921-2931, 1992
Lindbon A, Soderberg G, Spjut HJ, et al: Angiography of aneurysmal bone cyst. Acta Radiol 55:12-16, 1961
Kyriakos M, Hardy D: Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer 68:1770-1780, 1991
Ly JQ, La Gatta LM, Beall DP: Calcaneal chondroblastoma with secondary aneurysmal bone cyst. AJR Am J Roentgenol 182:130, 2004
Ozaki T, Hillmann A, Lindner N, et al: Aneurysmal bone cysts in children. J Cancer Res Clin Oncol 122:767-769, 1996
Bollini G, Jouve JL, Cottalorda J, et al: Aneurysmal bone cyst in children: Analysis of twenty-seven patients. J Pediatr Orthop B 7:274-285, 1998
Campanacci M, Cervallate C, Donati U, et al: Aneurysmal bone cyst: A study of 127 cases, 72 with long term followup. Ital J Orthop Traumatol 2:341-343, 1976
Dormans JP, Hanna BG, Johnston DR, et al: Surgical treatment and recurrence rate of aneurysmal bone cysts in children. Clin Orthop Relat Res 421:205-211, 2004
Hay MC, Paterson D, Taylor TK: Aneurysmal bone cyst of the spine. J Bone Joint Surg 60B:406-411, 1978
Marcove RC, Sheth DS, Takemoto S, et al: The treatment of aneurysmal bone cyst. Clin Orthop Relat Res 311:157-163, 1995
Papagelopoulos PJ, Choudhury SN, Frassica FJ, et al: Treatment of aneurysmal bone cysts of the pelvis and sacrum. J Bone Joint Surg 83A:1674-1681, 2001
Scheil-Bertram S, Hartwig E, Bruderlein S, et al: Metachronous and multiple aneurysmal bone cysts: A rare variant of primary aneurysmal bone cysts. Virchows Arch 444:293-299, 2004
Schreuder HW, Veth RP, Prszczynski M, et al: Aneurysmal bone cysts treated by curettage, cryotherapy and bone grafting. J Bone Joint Surg 79B:20-25, 1997
Hemmadi SS, Cole WG: Treatment of aneurysmal bone cysts with saucerization and bone marrow injection in children. J Pediatr Orthop 19:540-542, 1999
Mahnken AH, Nolte Ernsting CC, Wildberger JE, et al: Aneurysmal bone cyst: Value of MR imaging and conventional radiography. Eur Radiol 13:118-124, 2003
Sullivan RJ, Meyer JS, Dormans JP, et al: Diagnosing aneurysmal and unicameral bone cysts with magnetic resonance imaging. Clin Orthop Relat Res 366:186-190, 1999
Feigenberg SJ, Marcus RB Jr, Zlotecki RA, et al: Megavoltage radiotherapy for aneurysmal bone cysts. Int J Radiat Oncol Biol Phys 49:1243-1247, 2001
Delloye C, De Nayer P, Malghem J, et al: Induced healing of aneurysmal bone cysts by demineralized bone particles: A report of two cases. Arch Orthop Trauma Surg 115:141-145, 1996
Dubois J, Chigot V, Grimard G, et al: Sclerotherapy in aneurysmal bone cysts in children: A review of 17 cases. Pediatr Radiol 33:365-372, 2003
Topouchian V, Mazda K, Kamze B, et al: Aneurysmal bone cysts in children: Complications of fibrosing agent injections. Radiology 232:522-526, 2004
Mankin HJ: A computerized system for orthopaedic oncology. Clin Orthop Relat Res 399:252-261, 2002
Mankin HJ, Fondren G, Hornicek FJ, et al: The use of flow cytometry in assessing malignancy in bone and soft tissue tumors. Clin Orthop Relat Res 397:96-105, 2002(Henry J. Mankin, Francis )
ABSTRACT
PURPOSE: We have reviewed a series of 150 aneurysmal bone cysts treated over the last 20 years.
PATIENTS AND METHODS: The lesions were principally located in the tibia, femur, pelvis, humerus, and spine and, in most cases, presented the imaging appearance originally described by Jaffe and Lichtenstein as a blowout with thin cortices.
RESULTS: Only one of the patients was believed to have an osteoblastoma of the spine with secondary development of an aneurysmal bone cyst, and none of the patients developed additional lesions. The patients were treated primarily with curettage and implantation of allograft chips or polymethylmethacrylate, but some patients were treated with insertion of autografts or allografts. The local recurrence rate was 20%, which is consistent with that reported by other centers.
CONCLUSION: Aneurysmal bone cysts are enigmatic lesions of unknown cause and presentation and are difficult to distinguish from other lesions. Overall, the treatment is satisfactory, but it is possible that newer approaches, such as improved magnetic resonance imaging studies, may help diagnose the lesions and allow the physicians to plan for more effective treatment protocols.
INTRODUCTION
Despite a descriptive history of more than 60 years, the nature, character, and optimal treatment of aneurysmal bone cysts remain obscure. The lesion was first described by Jaffe and Lichtenstein1 in 1942, was subsequently further defined by both of these authors,2,3 and became known as Jaffe-Lichtenstein disease. Despite attempts on the part of investigators to establish a relationship of the disorder to other entities, the term aneurysmal bone cyst remains purely descriptive. It does not provide any concept of pathogenesis or causation mechanisms, and efforts on the part of a number of investigators to discover a genetic or neoplastic cause have failed.4-18 Examination of the tissue at the time of surgery has, in the past, demonstrated a blood-filled cavity within an expanded region of the bone, and the cells that line the cyst wall show fibrous components, macrophages, giant cells, and islands of bone.1,7-9,19-24 The term aneurysmal seems to relate to the blowout distension, and the word cyst reflects the fact that the tumor often presents as a blood-filled cavity.7,9,25 Occasionally in prior studies, there have been findings suggesting the possibility that the aneurysmal cyst is actually a result of hemorrhagic degradative events occurring in patients with other lesions including giant cell tumor, hemangioma, chondroblastoma, osteoblastoma, nonossifying fibroma, fibrous dysplasia, chondromyxoid fibroma, eosinophilic granuloma, and other tumors.1,7,9,19-24 Of greater concern is the possibility that the lesion is not an aneurysmal cyst but a partially necrotic and extremely vascular telangiectatic osteosarcoma, which has a high rate of metastasis.7,9
Many reports have appeared that describe patients with aneurysmal bone cysts.3,6,8,14,16,22,24,27,28,31-36 The lesions are more common in patients in the first two decades of life rather than in later years7,8,28,31,37 and seem to be slightly more frequent in females than males.7,8,28-30 The major sites of occurrence, according to a number of authors, are the femur, tibia, humerus, spine, and pelvis, and although tumors arising in the small bones of the hands and feet are seen occasionally, there are fewer of such instances in most series.3,7,9,14,16,24,32-36 The tumors are usually metaphyseal or diaphyseal and are most often eccentrically located, which is an important distinguishing radiographic feature from unicameral bone cyst in patients in their second decade.7-9,12,20,24,38,39 The appearance of the lesions support the word blowout and show marked thinning of the cortex over the site, with only minimal bone formation; all of which are sometimes best seen on a computed tomography (CT) or a magnetic resonance imagining (MRI) scan.38,39 Controversy exists regarding optimal treatment, and regardless of techniques reported, there remains a recurrence rate that ranges from 5% to greater than 40%.7,24,28-34 At present, curettage and insertion of bone graft or polymethylmethacrylate are the principal techniques used,7,20,24,29,31,33,34 but in the past, radiation has been used.40 In several trials, sclerosing substances, bone substitutes, and other agents seemed to be less effective than conventional curettage.41-43 Our purpose in presenting this material is to review the data obtained over the last 20 years regarding patients with aneurysmal bone cysts to define the appearance, anatomic site, complications, and results of various forms of treatment.
PATIENTS AND METHODS
The Orthopedic Oncology Service at the Massachusetts General and Children's Hospitals has maintained a computerized database containing information regarding more than 17,000 patients with bone and soft tissue tumors treated over the last 30 years.44 Study of the system provided information regarding 223 patients with aneurysmal bone cyst, but only 150 of these patients who had been observed for as long as 20 years had sufficiently accurate descriptions of treatment protocols, definition of pathology, and recent assessment of outcomes to allow statistical analysis (Table 1). The system used to gather information regarding the patients did not, in any way, violate patient confidentiality and was approved by the hospitals' institutional review boards.
Sixty-nine of the 150 patients were male, and 81 were female. The mean age of the patients was 18 ± 12 years, with a range of 3 to 62 years. The mean follow-up time for the patients was 6 ± 7 years (range, 1 to 20 years). The anatomic locations for the lesions are listed in Table 1, and as noted, the most common sites were the tibia, femur, fibula, pelvis, humerus, clavicle, foot, and lumbar spine. The patients' complaints at the time of the initial visit were almost always concerning pain at the site and sometimes indicated pain and numbness extending down the limb. The patients were often disabled by the pain and almost always presented with tenderness over the site of the lesion. Examples of the imaging studies are shown in Figures 1 and 2, and as noted, the lesions are metaphyseal or diaphyseal in location, are usually eccentric with thin cortices, and, in most cases, present the classic blowout appearance (Fig 3). Gross structure is shown in Figure 4, which displays the thin cortices, the expansion, and the chambers often filled with blood. The histologic patterns are shown in Figures 5 and 6. The patterns demonstrate thin cortices; blood elements in the central portion of the tumor; and an array of benign-appearing macrophages, lymphocytes, fibroblasts, bone-forming cells, and giant cells, which are sometimes atypical in terms of structure and nuclear distribution.
As shown in Table 2, 130 patients were treated with curettage, and of these patients, 101 had lesions that were packed with allograft bone, and 20 had lesions that were packed with polymethylmethacrylate cement. Twenty of the patients had an excision or resection of the lesion, and 11 of these patients received an intercalary allograft transplantation.
Statistical studies used analysis of variance and Mantel-Haenzel and Fisher's exact tests using 2 analysis. The systems were provided by BMDP Statistical Software (Los Angeles, CA). P < .05 was considered statistically significant.
RESULTS
None of the patients died of disease, and there were no amputations. The principal problem that the patients encountered with their treatment of the aneurysmal bone cysts was local recurrence, which occurred in 30 (20%) of the 150 patients at 1.2 ± 0.7 years (range, 0.3 to 3 years) after discovery of the lesion. There was no statistical difference for sex. Patient age did not seem to have a significant effect on outcome, although the rate of local recurrence was slightly increased in younger patients (Table 3). Anatomic site seemed to make some difference in rates of local recurrence. The recurrence rate for the 10 patients with lesions of the clavicle was 50%, and the recurrence rate for the 13 patients with tumors in the distal femur was 46%, whereas other sites showed few or no recurrences (Table 3).
Of considerable interest was the recurrence rate data for the various operative procedures performed by our group over the 20+ years of experience in the treatment of patients with aneurysmal bone cysts. The recurrence rate for the 121 patients who were treated with curettage and packing with either allograft chips or polymethylmethacrylate was 22%, which was considerably greater than the 5% recurrence rate for patients who underwent resection and either an autograft or an allograft implantation (Table 2).
The patients who developed a recurrence required subsequent surgery, which consisted of another curettage and packing or resection of the site and autograft or intercalary allograft implantation. Of the 150 patients, 34 required a second operation and 13 required a third operation for recurrences or structural problems related to failed systems. One of the patients was treated with sclerotherapy, and two patients were treated with local injections of alcohol and other agents, all of which were successful. Three of the patients developed fractures through the weakened bony part, which, although not related to recurrence, required further surgery. The 11 allograft implantations were all rated as good or excellent at 6 ± 6 years (range, 1 to 20 years), and only one of the grafts sustained a fracture, which healed after replacement of the fixation. Only one of the patients in our series was found to have tumor suggestive of an osteoblastoma of L4 at the time of biopsy. The lesion was curetted and packed with allograft chips, and there has been no recurrence reported to date.
Fifty-seven of the 150 patients had the DNA content of the tissue obtained at surgery studied by flow cytometric analysis.45 The mean value for the diploid peak was 92 ± 4.3 (range, 86 to 98), and the mean value for the G2+M was 4.7 ± 3.2 (range, 0. to 14). The average mean DNA index was 1.06 ± 0.04 (range, 1 to 1.2). No aneuploid peaks were encountered. These values can be interpreted as being characteristic of benign tumors.45
DISCUSSION
As stated in the Introduction, despite the long experience of radiologists, pathologists, and orthopedists with aneurysmal bone cysts, there is limited knowledge regarding the cause of the lesion, its natural history, and the results of treatment.1,4,5-7,9-17 The concept that the lesion represents a vascular degenerative process for some benign bone lesions is an attractive one, but the pathologic findings, with rare exception, do not really support this proposal. Few pathologic specimens contain tissues that are highly characteristic or diagnostic of giant cell tumor, chondroblastoma, hemangioma, osteoblastoma, nonossifying fibroma, fibrous dysplasia, chondromyxoid fibroma, and other tumors.6,7,9-11,15-17,19,21,26,28,29 Furthermore, the recurrences after surgical treatment do not show evidence of such lesions, particularly aggressive lesions such as giant cell tumor. Only one of our 150 patients showed a finding suggestive of an osteoblastoma at the site of the aneurysmal bone cyst of L4. At best, it was a difficult decision based on the similarity of the repair process to the histologic pattern for osteoblastoma, and the lesion has not recurred at more than 2 years since the surgery.
Of some importance is the difficulty that can occur in diagnosing these lesions. The imaging studies, even CTs and MRIs, sometimes do not provide clearly diagnostic criteria for the diagnosis of aneurysmal bone cyst, and aneurysmal bone cyst is sometimes added on to a list of diagnoses including eosinophilic granuloma, giant cell tumor, nonossifying fibroma, unicameral bone cyst, fibrous dysplasia, chondroblastoma, chondrosarcoma, chondromyxoid fibroma, Ewing's tumor, and, in older patients, metastatic carcinoma or myeloma.7-9,12,20,24,38,39 The lesions are often eccentric and irregular in structure and sometimes show calcification in the central areas. As a rule, the cortex is thin, but there is rarely a cortical defect or a soft tissue mass. CT and MRI are often helpful in defining the extent of the lesion and establishing the diagnosis. A biopsy is often helpful, and many of our patients underwent a needle biopsy before definitive treatment. Needle biopsies are sometimes a problem because the material obtained may consist of mostly blood elements. Often, an open biopsy and frozen section are necessary to establish the diagnosis.
The recurrence rate in this series was 20%, which should be considered high compared with other series and other benign tumors.7 Part of this problem could conceivably be related to the methods of treatment over the 20 years during which these patients were treated. The recurrence rate for patients treated in the earlier years was higher than for patients who were treated more recently (approximately 26% v 17%, respectively). In the past, we used curettage alone, but our principal current approach was biopsy followed by curettage and then implantation of allograft chips or, more recently, polymethylmethacrylate. Autograft implantations or utilization of intercalary allografts were quite successful but were, for the most part, used for patients with lesions that were large or seemed to threaten the integrity of the bone and were used less frequently for patients who experienced failure of their primary procedure.
Although none of our patients died or required an amputation, a number of them had some relatively minor disability as a result of the tumor and its treatment. Thus, it is our opinion that aneurysmal bone cyst is sometimes an aggressive lesion that is difficult to treat. Lesions that occur in the proximal femur should perhaps be treated more aggressively, partly because of the high rate of local recurrence and the risk of fracture. The most appropriate techniques for some of these tumors are primary resective surgery and allograft implantation. Patients with lesions of the proximal or mid fibula or clavicle or body of the scapula could be treated by resection alone, and lesions of the foot might be best treated by resection and arthrodesis using autograft. According to our series, such treatment would at least reduce the local recurrence rate considerably and probably reduce the degree of even minimal disability reported by some of these young patients.
In this last analysis, aneurysmal bone cyst remains an enigma, not only regarding causation, but also regarding clinical and imaging diagnosis and optimal treatment. There is perhaps some hope for implantation of newer agents, such as the bone substitutes, to aid in healing of the lesions. Although there are now some markers that are alleged to be specific for aneurysmal bone cyst,1,9,12-15,18 there is still no system to establish the diagnosis or to support different methods of treatment and, thus, reduce the problems encountered by the patient and the surgeon.
Authors' Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
NOTES
Authors' disclosures of potential conflicts of interest are found at the end of this article.
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