How To Diagnose Benign Bone Tumors In The Lower Extremity

Author(s): 
By Bradley W. Bakotic, DPM, DO

While some researchers have suggested that bone tumors affect the feet in a disproportionately small number of cases, one must keep in mind that most major studies on the subject have been assembled at major centers for the treatment of cancer.1,2 Therefore, lesions that have clearly benign clinical or radiologic features are largely omitted. Also be aware that most tumors of the bones of the distal extremities may be readily biopsied or excised, histopathologically evaluated and treated in a community hospital setting. These lesions would similarly never find their way into the files of large cancer centers or consultation services. In order to identify bone tumors of the feet accurately, one must understand the relative frequency with which various tumors of bone occur in that location. Occasional tumors of bone such as Dupuytren’s (subungual) exostosis occur in the feet in the vast majority of cases. In contrast, osteochondroma, the most common benign bone tumor, is rare in the small bones of the feet. Though many large bone tumor series have grouped lesions of the hands with those of the feet, even these sites are affected at different rates. In 1997, Ostrowski and Spjut published a series of 240 “lesions” of the bones of the hands and feet.3 They noted a relatively large number of reactive or reparative lesions of bone within their series. They identified conditions such as florid reactive periostitis, bizarre parosteal osteochondromatous proliferation (Nora’s lesion) and giant cell reparative granuloma at a much higher rate than has been described outside of the hands and feet.3 Alternate investigators have recorded similar findings and added Dupuytren’s (subungual) exostosis to their list of reactive lesions.4 A curious finding in the series by Ostrowski and Spjut was the paucity of Dupuytren’s (subungual) exostosis among their reported cases as it only accounted for one of the 240 cases in their series.3 The authors did not elaborate on this finding or why osteochondromas outnumbered Dupuytren’s exostosis six to one among their cases, although these findings seem to contrast sharply with other reports on the subject.1,4-6 It is reasonable to assume that at least some Dupuytren’s exostoses in their series were misdiagnosed as osteochondromas. In keeping with the high number of reactive or reparative bone lesions that have been reported in the bones of the hands and feet, there is an overwhelming predominance of benign lesions, as compared to malignant lesions, in these locations. The ratio of benign to malignant in various series has ranged from 5:1 to 21:1.3,4 This ratio differed somewhat from the 1.2:1 benign to malignant ratio reported in a series of pedal bone tumors assembled at the Memorial Sloan-Kettering Cancer Center.5 The authors of this latter series attributed the relatively few benign lesions in their study to the fact that their cases were assembled in a center that specializes in the treatment of cancer. This source certainly led to a bias toward malignant tumors by largely eliminated lesions that were radiologically, and/or histopathologically, benign from their series. For the purpose of discussion, we’ll divide bone lesions of the small bones of the feet into three categories: reactive/reparative lesions, benign neoplasms and malignant neoplasms. The prevailing thinking is that reactive/reparative lesions of bone are non-neoplastic proliferations or hyperplasias that are incited by trauma or stress in most cases. In contrast, neoplasms are autologous new growths that are clonal in nature in that they emanate from a single genetically identical “mother cell.” In most cases, neoplasms do not form in response to trauma or involute upon removal of a stimulus. What You Should Know About Reactive/Reparative Lesions We will begin by summarizing the non-neoplastic lesions most commonly seen in the bones of the feet. The combination of giant cell reparative granuloma, florid reactive periostitis, Dupuytren’s exostosis and bizarre parosteal osteochondromatous proliferation accounted for 50 of the 151 benign lesions in the series published by Ostrowski and Spjut (excluding those lesions that were classified as a reaction to injury, fracture or osteomyelitis).3 Being aware of these lesions, which share atypical histopathologic and clinical features, can help prevent erroneous clinical diagnoses and facilitate referrals for outside pathology consultations when indicated. Giant cell reparative granulomata (GCRG) accounted for 24 of 203 benign “lesions” reported by Ostrowski and Spjut.3 In 1953, Jaffe described these tumors as intraosseous tumors comprised of a mixture of giant cells and fibrous stroma. They are believed to arise in response to hemorrhage.7 Some investigators have viewed giant cell reparative granuloma (GCRG) as a solid variant of aneurysmal bone cyst.8 Most cases will present as solitary painful and swollen lesions among teenagers or people who are in their twenties.8,9 These lesions more commonly affect the hands than the feet and a history of trauma is an exceptional finding.8,9 Radiologically, GCRG appear as radiolucent lesions measuring from 2 to 2.5 cm in greatest diameter. You will see bone expansion and cortical thinning but you usually won’t see evidence of destruction.8 There is no surrounding sclerosis nor intralesional calcifications and the epiphyseal ends of long bones are spared in most cases.8 Ostrowski and Spjut identified florid reactive periostitis (FRP) 16 times among the 203 benign “lesions” in their study.3 Spjut and Dorfman described this lesion in 1981 as a reactive process leading to metaplastic bone and cartilage formation.10 As they pointed out, it’s imperative to be aware of this lesion given its radiologic and histopathologic similarities with parosteal osteogenic sarcoma and osteochondroma. FRP most commonly causes pain and swelling of a finger or, less commonly, a toe of an adult in his or her 20s. However, it may affect people of all ages.10,11 There is a slight female predominance and a history of trauma is noted in roughly 40 percent of the cases.11 In most cases, FRP appears radiologically as a fusiform soft tissue mass enveloping the proximal phalanx, but be aware that it can affect any of the tubular bones of the hands and feet.10 A laminated periosteal reaction is evident in about a third of cases. Although you won’t see overt destructive radiological features indicative of malignancy, keep in mind that some cases may superficially resemble parosteal osteogenic sarcoma as each lesion may envelop metatarsals in a similar fashion. Pertinent Pointers On Recognizing Dupuytren’s Exostosis Dupuytren’s (subungual) exostosis (DE) represented 13 percent of the benign tumors of the bones of the feet described in the Memorial Sloan-Kettering Cancer Center series.6 Unlike osteochondromas, which are neoplastic proliferations of epiphyseal cartilage, such exostoses are metaplastic osteochondral proliferations that result from persistent microtrauma.6 This reactive and metaplastic origin for DE has been accepted by the vast majority of authors who have studied the subject.12-15 First described by Dupuytren in 1847, this tumor most commonly arises within the soft tissue deep to the medial nail bed of the hallux and thus was originally designated as a “subungual exostosis.”16 Over time, one will see progressive mineralization and bone formation. As the lesion progresses, one will see eventual fusion of the lesion with the underlying phalanx. Unlike an osteochondroma, a neoplastic tumor of bone, DE does not show a tendency toward malignant transformation and is not associated with familial osteochondromatosis.6,12,13 Dupuytren’s exostosis is usually seen in patients who are in their teenage years or their 20s. However, these tumors can occur in patients of any age.12,13 While it is exceedingly uncommon to see this tumor among preadolescent children, I have seen this occur in my podiatric pathology practice. Approximately 75 to 80 percent of DE cases involve the hallux with the remaining cases involving the lesser digits and fingers.6,12,13 Lesions often manifest clinically as a chronic paronychia, a persistent discrete ulcer medial to the nail bed, or a subungual, pyogenic granuloma-like mass. Complete excision of the cartilage cap is curative. However, be aware that incomplete excision of actively growing lesions may result in recurrence and accelerated growth.13 The radiologic appearance of DE varies depending on its stage of development. Early in its natural history, DE appears as soft tissue densities clearly detached from the underlying phalanx. As lesions evolve, one will note progressive mineralization and bone formation, resulting in a radiodense mass. At this stage, one may or may not see a cartilage cap radiologically. As these lesions develop, one will see progressive bone formation culminating with its fusion with the underlying distal phalanx by a broad or narrow base.12,13,15 The underlying phalanx is uniformly free of cortical destruction or a significant periosteal reaction. Finding Nora’s Lesion Bizarre parosteal osteochondromatous proliferation (Nora’s lesion) accounted for nine of the 203 benign tumors in the Baylor study and three of 82 benign lesions in the series from Memorial Sloan-Kettering.3,6 First characterized in 1983 by Nora and colleagues of the Mayo Clinic, this unusual lesion typically arises around the proximal phalanges, metacarpals or metatarsals, and presents as a painless and rapidly growing mass.17 When patients do report symptoms, they are most often related to tumefaction.17,18 In a minority of cases, patients may have a history of trauma.17-19 The hands are involved at a significantly higher rate of frequency than are the feet.17,18 Like many of the reactive/reparative lesions described herein, having an awareness of bizarre parosteal osteochondromatous proliferation (BPOP) is particularly important due to the lesion’s tendency for local recurrence and its atypical histopathologic features. If this diagnosis is a clinical possibility, be aware that it can be mistaken for sarcoma by inexperienced pathologists so you should consider requesting an outside expert opinion. Radiologically, one will see BPOPs as well-delineated partially mineralized masses emanating from the cortical surface of the involved bone. Larger lesions are lobulated and exhibit a haphazard pattern of mineralization. There is no medullary continuity between the underlying bone and the periosteal mass, and, in most cases, the underlying bone remains free of alteration with the exception of slight cortical thickening at the point of attachment.18 Some investigators believe BPOP is related to DE. This is partly due to the fact that in early developing BPOP (and similar to DE), there may be a lack of mineralization and there may be no clear point of attachment to the underlying bone.18 A Closer Look At Benign Neoplasms Just as the bones of the feet (and hands) are unique with regard to the frequency with which they are affected by reactive/reparative lesions, they are similarly affected by many benign neoplasms at frequencies that contrast sharply with the skeletal system at large. As an example, osteochondromas, the most common benign neoplasm in the skeletal system, account for between 40 to 50 percent of all benign neoplasms of bone. However, such tumors represent only 3 to 8 percent of such neoplasms in the feet.1,3,5,6 Aneurysmal bone cysts (ABC) were initially described in 1942 by Jaffe and Lichtenstein as reactive (non-neoplastic) processes of bone.20 In recent years, characteristic genetic translocations have been described in many cases of ABC.21,22 This creates a strong argument for clonality among a subset of the cysts and thus suggests that some are actually neoplastic. Since many aneurysmal bone cysts appear to exhibit genetic mosaicism (two populations of cells; one with a mutation and the other without it) for the aforementioned mutation, it is possible these cysts begin as a reactive process in which a population of neoplastic cells emerges. Similar to giant cell reparative granulomas, these cysts have been theorized to emerge secondary to vascular compromise, whether it is due to an inborn vascular malformation, trauma or an associated neoplasm. Aneurysmal bone cysts have traditionally been classified as either primary or secondary. In the Memorial Sloan-Kettering series, the combination of primary and secondary cysts accounted for 16 of the 82 benign lesions in the series.6 Researchers believe primary ABCs emerge in the absence of an alternate neoplasm while secondary ABCs are engrafted upon another tumor.6 Authors believe that approximately 50 to 71 percent of ABC cases are primary in nature.6,23 In the feet, associated neoplasms include chondroblastoma, giant cell tumor, non-ossifying fibroma, osteoblastoma and osteosarcoma.6 People with these cysts most often present with localized pain and swelling. In a small number of cases, one may see pathologic fractures.24 In the long bones, the mean age at presentation is 13.9 years, significantly younger than those with ABC in the feet (21 years).6,24 Radiologic features of ABC include preferential involvement of the metaphysic of short tubular bones. In the feet, there is often concurrent involvement of the diaphysis and/or epiphysis.24 The diaphysis is solely affected in only 8 percent of patients.24 Unlike most other tumors of bone, ABC will cross open growth plates in 23 percent of cases.24 Expansion of the involved bone with cortical thinning is a characteristic feature of ABC and is found in up to 93 percent of cases.23,24 This percentage is likely higher when considering ABC of the small bones of the feet in isolation.6 In roughly half of the cases, the radiographic margin is distinct but not sclerotic. However, keep in mind that sclerosis is present in about a third of cases.24 About 14 percent of ABC cases lack distinct margination, making them appear frankly malignant in some instances.24,25 Since the cysts are lytic processes and at least focal cortical destruction is seen up to 54 percent of the time, these lesions cannot be radiologically distinguished from malignancies in 42 percent of cases.24 A Key Guide To Enchondromas Enchondromas are benign neoplasms of bone that exhibit hyaline cartilage differentiation. It has been theorized that these neoplasms arise from cartilaginous rests displaced during development. Roughly half of all cases arise in the bones of the hands and feet, where they accounted for 29 of 203 benign “lesions” in the series published by Ostrowski and Spjut.1,3 In most cases, enchondromas have a characteristic radiologic appearance and are often wholly asymptomatic so it is likely that they are underrepresented in many of the large series, as most were assembled in academic centers or centers that specialize in the treatment of cancer. Enchondromas may affect patients of all ages. However, most people present with a palpable swelling between their teenage years and their 30s.1 Lesions in the bones of the hands and feet are more commonly symptomatic than those arising elsewhere in the skeletal system. In most cases, enchondromas are solitary lesions although multiple bones may be involved, especially in the setting of Maffucci syndrome or Ollier disease (enchondromatosis). In the small bones of the feet, one will typically see bone expansion and cortical thinning with these tumors. Also keep in mind that a pathologic fracture is not an uncommon finding. These neoplasms are characteristically radiolucent and well-delineated. However, there may be a varying degree of mineralization.26 When these tumors are mineralized, there is often a characteristically stippled pattern. In the short tubular bones, enchondromas are frequently expansile and may be eccentric or central. Larger lesions often appear central as they occupy the entire marrow space.26 In contrast to lesions arising in the small tubular bones, cortical expansion and endosteal erosion in large long bones warrant a suspicion of malignancy. How To Detect Chondroblastomas Chondroblastoma is a benign but locally aggressive neoplasm. In 1942, Jaffe and Lichtenstein named the tumor due to the chondroblast-like cytologic appearance of lesional cells.27 Roughly 23 percent of all chondroblastomas arise in the bones of the hands and feet.28 Of the chondroblastomas affecting the hands and feet, 79 percent arise in the talus and calcaneus.28 The mean age at which chondroblastoma is diagnosed in the feet is between 26 to 33 years, significantly older than the average of 17.3 years for people who have such tumors affecting the long bones.6,29,30 In the series put forth by Kurt, et. al., 90 percent of the chondroblastomas that arose in the feet were located in the rearfoot tarsal bones.28 As with many tumors of bone, there is a marked male predominance among people with chondroblastomas. This predominance is yet more significant when the bones of the feet are involved. When these tumors affect the feet, 83 percent of the patients are male.29 When chondroblastomas arise in the feet, the most common presenting complaint is pain without a corresponding history of trauma.29,30 In a minority of cases, one may see accompanying edema. Chondroblastomas are often longstanding, leading a protracted clinical course before the diagnosis is made.29 “Benign” chondroblastoma may, in rare instances, exhibit pulmonary spread. In such cases, the pulmonary deposits maintain the same benign histopathologic appearance that one would see in the primary lesion and surgical excision is curative.29 Radiologically, most pedal chondroblastomas present themselves as moderately well circumscribed lesions in the posterior subchondral regions of the talus or calcaneus.29 Occasionally, these tumors affect the calcaneal apophysis. Involvement of the talar articular facets may lead to nondisplaced subchondral fractures.29 Lesions are consistently radiolucent with geographic zones of bone destruction.30 There is little or no matrix production.29 Researchers saw scalloping or expansion of the cortex in 69 percent of tumors involving the bones of the feet in one series.29 In up to one of three cases, there is an associated secondary aneurysmal bone cyst.28 What You Should Know About Giant Cell Tumors The giant cell tumor of bone (GCT) is a benign but locally aggressive tumor characterized by a dense infiltrate of reactive osteoclast-like giant cells scattered among a neoplastic population of small epithelioid or slightly spindled mononuclear cells. Giant cell tumors account for approximately 20 percent of all benign tumors of the skeletal system.1 Their incidence within the small bones of the feet has been estimated to be about 1.8 percent.5 In the feet, the rearfoot tarsal bones are most commonly affected.1,5 This is one of the few tumors of bone where there is a significant female predominance.1,3 Researchers have described a similar female predominance when summarizing such neoplasms in the feet.31 These patients most commonly present with either localized pain and swelling, or with pain in the absence of swelling.31 The giant cell tumor is a neoplasm of the mature skeletal system and most often affects people in their third decade of life. Less than 2 percent of cases arise in association with an immature physis.32 Some investigators have related a more aggressive behavior in the presence of genetic abnormalities.33 Like chondroblastomas, benign GCTs may also exhibit pulmonary spread. In the bones of the feet, GCTs average almost 3 cm in greatest dimension.31 When these tumors arise within long bones, they invariably involve the physis. These tumors are largely lytic, but they may disclose trabeculation that can vary from fine to moderately coarse.31 This trabeculation leads to the characteristic “soap-bubble” appearance. Most lesions are well demarcated. Perilesional sclerosis is not a typical finding. If you do see this, the finding argues against this diagnosis. With these tumors, one would rarely see periosteal reactions typical of osteosarcoma (Codman’s triangle, sunburst) and Ewing’s sarcoma (onion skinning).34 Many GCTs in the small bones of the feet produce cortical erosion and expansion.31 In the vast majority of cases in which there appears to be soft tissue expansion, the lesion is covered by a thin layer of periosteal new bone that is not apparent radiologically. In 1983, Enneking described a staging system for GCT based on its margination.35 Enneking considered Stage I tumors to be latent lesions without radiological features indicative of local aggressiveness. Stage II tumors showed more significant bone alteration in the form of radiolucency and cortical expansion. Stage III GCT were felt to be aggressive in nature, exhibiting cortical destruction and soft tissue extension.35 Reviewing The Characteristics Of Osteoblastomas Osteoblastoma was described simultaneously by Jaffe and Lichtenstein in 1956 as a benign bone forming tumor with features reminiscent of osteoid osteoma but with a tendency for progressive growth.36,37 While osteoblastomas are relatively uncommon neoplasms of bone, they have a disproportionately high frequency in the bones of the feet. Researchers have noted that approximately 12 percent of osteoblastomas arise in this location.38 Most patients present in their second or third decade of life and there is a marked male predominance.38 Nearly all patients (97 percent) complain of low grade aching pain and about one in four experience concurrent swelling.38 Clinicians should be aware that aggressive variants may show a propensity for widely destructive behavior and local recurrence following excision.39 Radiologically, osteoblastomas are round or oval, well circumscribed, and range from 2 to 10 cm in size. Most form radiolucent expansile masses that lack the sclerotic margin seen in association with osteoid osteoma. Centrally, the majority of osteoblastomas are entirely lytic, though some have a focally granular or stippled character.40 When these lesions present in the small bones of the feet, you may note large expansile lesions that only have a thin shell-like covering of perosteal bone. The talus is the most commonly affected bone of the foot.38 Diagnosing Osteoid Osteomas Osteoid osteomas are uncommon in the feet as Huvos only found one out of 77 lesions.5 Of the 151 benign lesions that were not classified as either a reaction to injury, a fracture, or osteomyelitis, Ostrowski and Spjut found only nine osteoid osteomas in their series.3 There were only three cases among the 150 tumors of bone described in the Memorial Sloan-Kettering series.6 The striking paucity of such tumors in many of these series is probably due to the tumor’s characteristically benign radiological appearance. Just as with osteoblastomas, people with osteoid osteomas typically present with pain, a feature noted in all but two of 200 cases summarized at the Mayo clinic.1 The discomfort may range from dull to intense and usually shows nocturnal exacerbation. Greater than 80 percent of patients experience relief of the associated pain following treatment with NSAIDs.41 Investigators have demonstrated unmyelinated nerve fibers and excessive prostaglandin E2 production in the nidus of osteoid osteoma.42 Osteoid osteomas arising near joints may precipitate swelling, effusions and loss of function.43 Be aware that children and adolescents are most commonly affected by osteoid osteoma and these lesions may be initially misdiagnosed as “growing pains.” Osteoid osteomas have a characteristic radiological appearance. There is a dense, often fusiform, ring of sclerosis surrounding a radiolucent nidus. The degree to which the nidus is evident in plain films varies depending on the amount of peripheral sclerosis. Ossification of the nidus may occur, leading to a targetoid radiologic appearance.44 In instances when the nidus is not evident in plain films, one may see it with a technetium 99 bone scan. Dr. Bakotic is the Director of the Divisions of Podiatric and Dermatopathology at ProPath Services in Dallas, Texas. He is also a Diplomate of the American Board of Pathology. Editor’s Note: In the forthcoming August 2004 issue of Podiatry Today, Dr. Bakotic will discuss malignant bone tumors in the lower extremity. CE Exam #119 Choose the single best response to each question listed below. 1. Most of the large studies evaluating tumors of the skeletal system have overestimated the frequency with which such lesions affect the small bones of the feet. a) true b) false 2. In contrast with the skeletal system at large, the small bones of the feet are affected by 5 to 20 times more benign lesions than those that are malignant. a) true b) false 3. Which of the following statements is false? Giant cell reparative granulomata … a) are reactive processes that may arise in response to intraosseous hemorrhage. b) are associated with overt bony destruction. c) are rare benign neoplasms. d) more commonly affect bones of the hands than those of the feet. 4. Which of the following statements is false? Florid reactive periostitis … a) is associated with a history of trauma in a significant number of cases. b) like most reactive/reparative lesions affecting the bones of the feet, most often manifests in people in their second or third decade. c) appears radiologically as a fusiform soft tissue mass that may closely resemble parosteal osteogenic sarcoma. d) cause frank cortical destruction in the majority of cases. 5. Which of the following statements is false? Dupuytren’s (subungual) exostoses … a) most commonly arise at the medial aspect of the distal hallux. b) represent a form of osteochondroma. c) begin as metaplastic cartilage that arises in the setting of chronic inflammation. d) in their final stages of evolution form an attachment with the underlying distal phalanx by either a narrow or broad base. 6. Which of the following statements is false? Bizarre parosteal osteochondromatous proliferation (Nora’s lesion) … a) are benign neoplasms that show a high rate of malignant conversion. b) are so named because of their malignant-like histopathologic appearance. c) are rapidly growing tumors whose symptomatology is secondary to tumefaction. d) do not exhibit medullary continuity with the underlying affected bone. 7. Which of the following statements is false? Aneurysmal bone cysts … a) are now uniformly accepted to be reactive (non-neoplastic) in nature. b) have a frankly malignant appearance in plain films in a large number of cases. c) may be related to giant cell reparative granuloma. d) may be primary or may be engrafted upon an alternate neoplasm. 8. Which of the following statements is false? Enchondromas … a) involve the hands and/or feet in roughly half of all cases. b) are likely underrepresented in most large series summarizing tumors of bone. c) have a characteristic and benign radiologic appearance. d) are less commonly symptomatic when they arise in the bones of the feet. 9. Which of the following statements is false? Chondroblastomas … a) are benign neoplasms that may show pulmonary spread. b) most often arise in the posterior subchondral region of the talus. c) involve the bones of the feet in approximately 4 percent of cases. d) arise in the feet in an older patient population than that affected by such lesions in the axial skeleton. Instructions for Submitting Exams Fill out the postage-paid card that appears on the following page or log on to www.podiatrytoday.com and respond electronically. Within 60 days, you will be advised that you have passed or failed the exam. A score of 70 percent or above will comprise a passing grade. A certificate will be awarded to participants who successfully complete the exam. Responses will be accepted up to 12 months from the publication date.
 

 

References:

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Br J Radiol 39:451-455, 1966. 16. Dupuytren G. On the Injuries and Diseases of Bones, F. LeGros Clark, trans. ed. London: Publications of the Sydenham Society, 1847:408-411. 17. Nora FE, Dahlin DC, Beabout JW. Bizarre Parosteal Osteochondromatous Proliferations of the hands and feet. Am J Surg Pathol 7(3):245-250, 1983. 18. Meneses MF, Unni KK, Swee RG. Bizarre Parosteal Osteochondromatous Proliferation of Bone (Nora’s lesion). Am J Surg Pathol 17(7):691-697, 1993. 19. Bandiera S, Bacchini P, Bertoni F. Bizarre Parosteal Osteochondromatous Proliferation of Bone. Skeletal Radiol 27:154-156, 1998. 20. Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst: With emphasis on the roentgen picture, the pathologic appearance, and the pathogenesis. Arch Surg 44:1004-10025, 1942. 21. Panoutsakopoulos G, Pandis N, Kyriazoglou I, Gustafson P, Mertens F, Mandahl N. Recurrent t(16;17)(q22;p13) in Aneurysmal Bone Cysts. Genes Chromosomes Cancer 26:265-266, 1999. 22. 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Fink BR, Temple T, Chiricosta FM, Mizel MS, Murphey MD. Chondroblastoma of the Foot. Foot Ankle Int 18(4):236-242, 1997. 30. Bloem JL, Mulder JD. Chondroblastoma: A clinical and radiological study of 104 cases. Skeletal Radiol 14:1-9, 1985. 31. Biscaglia R, Bacchini P, Bertoni F. Giant cell tumor of the bones of the hand and foot. Cancer 88:2022-2032, 2000. 32. Picci P, Manfrini M, Zucchi V. et al. Giant cell tumor in skeletally immature patients. J Bone Joint Surg [Am] 65:486-490, 1983. 33. Bridge JA, Neff JR, Bhatia PS, Sanger WG, Murphey MD. Cytogenetic findings and biologic behavior of giant cell tumors of bone. Cancer 65:2697-2703, 1990. 34. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant cell tumor of bone. J Bone Joint Surg [Am] 69:106-114, 1987. 35. Enneking WF. Musculoskeletal tumor surgery. New York: Churchill Livingstone, 1983:87-88. 36. Jaffe HL, Benign osteoblastoma. Bull Hosp Jt Dis Orthop Inst 17:141-151, 1956. 37. Lichtenstein L, Sawyer WR. 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