case report multicentric giant cell tumor of bone...

Hindawi Publishing CorporationCase Reports in OrthopedicsVolume 2013, Article ID 756723, 5 pageshttp://dx.doi.org/10.1155/2013/756723

Case ReportMulticentric Giant Cell Tumor of Bone: Synchronous andMetachronous Presentation

Reiner Wirbel,1 Frank Blümler,1 Dirk Lommel,2 Guido Syré,3 and Veit Krenn4

1 Department of Trauma, Hand and Reconstructive Surgery, Verbundkrankenhaus Bernkastel-Wittlich, Koblenzer Street 91,54516 Wittlich, Germany

2 Institute of Diagnostic Radiology, Verbundkrankenhaus Bernkastel-Wittlich, Koblenzer Street 91, 54516 Wittlich, Germany3 Strahlentherapie Trier, August Antz Street 21, 54293 Trier, Germany4Medical Center of Histology and Molecular Diagnostics, Max-Planck-Street 18, 54296 Trier, Germany

Correspondence should be addressed to Reiner Wirbel; [email protected]

Received 5 July 2013; Accepted 12 August 2013

Academic Editors: A. Ramasamy and A. Saw

Copyright © 2013 Reiner Wirbel et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A 27-year-oldman treated 2.5 years ago for synchronousmulticentric giant cell tumor of bone located at the right proximal humerusand the right 5th finger presented now with complaints of pain in his right hip and wrist of two-month duration. Radiology andmagnetic resonance revealed multicentric giant cell tumor lesions of the right proximal femur, the left ileum, the right distal radius,and the left distal tibia. The patient has an eighteen-year history of a healed osteosarcoma of the right tibia that was treated withchemotherapy, resection, and allograft reconstruction. A literature review establishes this as the first reported case of a patient withsynchronous and metachronous multicentric giant cell tumor who also has a history of osteosarcoma.

1. Introduction

Giant cell tumors (GCT) of bone account for 4% to 5%of all primary bone tumors [1–3]. Multicentricity of GCTof bone is an extreme rarity accounting for less than 1%of these tumors. The biological behaviour and the clinicalpresentation (e.g., localization, age, and gender distribution)seem to be different from solitary lesions [1–3]. We like topresent an additional case of a patient with multicentric giantcell tumor of bone. The typical features of multicentricityshould be pointed out.

2. Case Presentation

A 27-year-old man presented in March 2012 with pain in hisright hip and right wrist of two-month duration. Physicalexamination revealed no restriction in range of motion toeither joint, but localized tenderness was present in the rightmedial thigh and the dorsoradial region of the right wrist.

Eighteen years prior, the patient was treated for osteosar-coma of the proximal tibia with chemotherapy and with

resection and reconstruction using allograft. The followupincluded regular clinical and radiographic examination.Treatment was considered successful after ten years withoutrecurrence.

Three years prior, the patient has a lytic lesion of theright proximal humerus (Figure 1(a)) and open biopsy, it wasdetermined to be a giant cell tumor. The lesion was curettedand the cavity was filled with bone graft (Figure 1(b)). Twomonths later, a biopsy of a swelling of the distal phalanx ofthe right 5th finger was diagnosed as a giant cell tumor byour Histology Department. Amputation of the distal phalanxwas performed. The patient fell two months later after thephalanx amputation resulting in a pathologic fracture of theright proximal humerus (Figure 1(c)). Treatment includedcurettage of the right proximal humerus and filling the cavitywith bone cement (Figure 1(d)). Histological examinationconfirmed the diagnosis of synchronous multicentric giantcell tumor of bone. Whole-body technetium bone scanshowed no further lesions. Follow-up, semiannual, clinical,and radiographic examinations revealed no signs of localrecurrence.

2 Case Reports in Orthopedics

(a) (b) (c) (d)

Figure 1: Conventional radiography, AP view of the proximal right humerus: (a) lytic lesion of the proximal humerus, (b) after curettageand filling the defect with cancellous bone graft, (c) presenting with pathological fracture (arrow) four months later, and (d) the lesion wascuretted and the cavity was filled with bone cement.

∗

Figure 2: Conventional radiography, AP view of the pelvis: lyticlesions of the right proximal femur (asterisk) and of the left ileum(arrow) became obvious.

Radiographic examination of the patient revealed lesionsin both painful areas. Plain radiograph of the pelvis (Figure 2)revealed a typical 3 cm lytic lesion involving the right proxi-mal medial femur and a 4 cm lytic lesion involving the leftileum. MRI of the pelvis (Figure 3) showed the extension ofthe lesions with soft tissue involvement of the right thigh andof the left gluteal region.

Plain radiograph and CT of the right wrist (Figure 4)revealed a 4 cm lytic lesion involving the epiphyseal subchon-dral region of the distal radius but without cortical breach.

Further radiographic examinations were performed torule out the presence of other lesions or metastasis. Thewhole-body technetium bone scan revealed an additional

increased uptake in the left distal tibia. The plain radiograph(Figure 5(a)) and the CT (Figures 5(b) and 5(c)) of theleft ankle joint showed a further 2 cm lytic lesion of thesubchondral region of the distal dorsolateral tibia. CT of thethorax and abdomen confirmed the absence of metastasis.

To rule out hyperparathyroidism acid and alkaline phos-phatase and serum calciumwere within normal range. Serumparathyroid hormone level was also normal.

All lesions were removed using powered burrs and werechemically cauterized with phenol solution. The resultingbone cavities were filledwith bone cement. Prophylactic bonestabilization was performed in all areas where lesions wereremoved. A dynamic hip screw was used to stabilize theright hip; a plate was used to fix both the left posterior iliaccrest (Figure 6) and the right distal radius; a single screw wasadequate to fix the left distal tibia. The postoperative coursewas uneventful with full weight bearing was possible withintwo weeks.

Histological examination of all lesions revealed the typ-ical findings of a giant cell tumor of a bone (Figure 7).The tissue was composed of large osteoclasts and uniformmononuclear cellswith ovoid nuclei.Thegiant cells contained50 to 100 nuclei. The nuclei of the stromal cells were similarto the nuclei of the osteoclasts having a so-called openchromatin pattern with indistinct nucleoli. The cytoplasmswere ill-defined with very few intercellular collagen, broadsinus, and retraction artefacts. Mitotic figures were very rare.

Radiation therapy was recommended for the two pelviclesions, by ourmultidisciplinary tumor board, because of softtissue involvement.

Informed consent was taken from the patient prior tooperation for the procedures as well as using his clinical datain this case report.

Case Reports in Orthopedics 3

(a) (b)

Figure 3: Magnetic resonance imaging: (a) coronal image of the right proximal femur shows the soft tissue involvement (arrow) of the lessertrochanteric region, and (b) axial image of the pelvis demonstrates the soft tissue involvement of the right gluteal region (arrow) nearby theiliac wing and the sacroiliac joint.

Figure 4: Computed tomography of the right wrist (coronalsection): the extension of the lytic lesion in the subchondral regionof the distal radius is well recognized.

3. Discussion

A literature review was undertaken to determine the preva-lence of synchronous and metachronous, multicentric giantcell tumor of bone. Giant cell tumor (GCT) of bone is abenign primary neoplasm accounting for 4% to 5% of allprimary bone tumors [1–4]. GCT of bone typically presentsas a solitary lytic lesion of the metaphyseal-epiphyseal regionof a long bone of adults [1] and in nearly 50% of the cases theyoccur adjacent to the knee joint [3–6].

Multicentric GCT of bone is extremely rare and accountsfor less than 1% of GCTs [1–3]. Approximately 100 cases havebeen reported worldwide, mostly single case descriptions orstudies of small series [3–5, 7–15].

Multicentric lesions are considered to occur more oftenthan solitary lesions in younger patients [1–3, 7–9, 11–13]

with an average age of twenty years at presentation and 59%of patient younger than twenty [3]. It occurs more often infemales (twice as often as in males) and skeletal immaturepatients [1–4, 9, 11, 13].

Patients usually present with two to three lesions, butone patient with ten tumors has been described [14]. Whencompared with solitary lesions, multicentric GCT is reportedmore frequently in the short bones of the hands and feet[3, 4, 8, 9, 13, 15].

Multicentric lesions are considered to be more frequentlyrestricted to the metaphyseal or diaphyseal-metaphysealregion of the long bones than solitary lesions, which predom-inantly involve the metaphysis and the epiphysis [1–4, 6].

Lesions of multicentric GCT of bone are classified asmetachronous or synchronous. When multiple tumors arediscovered at the initial presentation or when a second lesionis diagnosed within six months, the lesions are classified assynchronous [1–3].

Synchronous tumors occur less frequently thanmetachronous tumors [1–3, 5]. If a second tumor developsmore than six months after the first lesion, the lesions areclassified as metachronous.

In most cases of metachronous GCTs additional tumorsare developed within two years after the discovery of theprimary lesion; however, they may develop twenty or moreyears later [10]. This is apparently the first reported case ofmulticentric giant cell tumor of bone with synchronous andmetachronous presentation, since no other caseswere presentin the literature where both synchronous and metachronouslesions occurred in the same patient.

The pathogenesis of the multicentricity in GCT is stillunclear but various mechanisms have been suggested includ-ing contiguous spread, iatrogenic seeding of tumor cells,benign metastasis, malignant transformation, and de novomultifocal formation [4, 10, 15].

In most cases of multicentric GCTs diagnosis can beguided by clinical, serological, and radiographic findings.They should be distinguished from other multifocal lesions;

4 Case Reports in Orthopedics

(a) (b) (c)

Figure 5: Conventional radiography and computed tomography of the left distal tibia: (a) plain film (AP view) presents the lytic lesion (arrow)of the left lateral distal tibia, and (b) coronal and (c) sagittal CT sections can recognize the exact extension of the subchondral distal regionof the dorsolateral left tibia.

Figure 6: Conventional radiography of the pelvis (AP view): aftercurettage of the lesions at the right proximal femur and of the leftiliac wing, the defects were filled with bone cement; prophylacticstabilizations using a dynamic hip screw at the right side and a plateat the left posterior iliac crest were performed.

such as brown tumors of hyperparathyroidism, multifo-cal giant-cell reparative granuloma, Paget’s disease, fibrousdysplasia, fibrosarcoma, metastasis, osteosarcoma, multiplemyeloma, and multifocal osteomyelitis [1, 3, 8, 16].

Radiographic examination using plain film usuallydemonstrates an ecpansile, excentric radiolucent lesion at theepiphyseal, subchondral region with well-defined geograph-ical margins. In the affected area there is a lack of sclerosisand of internal mineralization and the cortices of the boneare expanded or destroyed. MRI is currently the best imagingmodality allowing accurate tumor delineation, extraosseousextent, and articular surface involvement. The tumor mass isisointense in T1 imaging and slightly hyperintense in the T2imaging with contrast media enhancement. Necrotic areas ofthe tumor appear hypointense in the T1 but hyperintense inthe T2-weighted image [1, 3, 6]. CT is a reasonable alternative

Figure 7: Microscopic pathology: H-E stain at 200x at the lesion ofthe right femur: the specimen demonstrated large osteoclasts anduniform mononuclear cells with ovoid nuclei, giant cells containingabout 50 to 100 nuclei, and ill-defined cytoplasm with very fewintercellular collagen.

especially to define the intra-osseous extension of the tumor[3, 6].

Scintigraphic bone scan usually demonstrates a diffuseincreased radionuclide uptake or a peripherally increaseduptake and photopenia centrally (“donut” sign) [3].

The histogenetic origin of the GCT of bone is unknown.The histological appearance of the tumor is very variableand consists mainly of giant cells containing multiple nucleias well as single nucleus stroma cells. Multicentric GCT ofbone is histologically indistinguishable from solitary lesion;however, fibroblastic and fibrohistiocytic areas are consideredto be a major component of these tumors [1, 3].

Although there are clinical and radiographic similaritiesbetween solitary and multicentric lesions, the risk of pul-monary metastases is reported at 5–10% in patients withmulticentric GCTs but only at 1-2% in patients with solitaryGCTs [1, 3].

Case Reports in Orthopedics 5

Theprimary goal of treatment of this tumor is to eradicatethe lesions and to preserve the function of the affected bonesand joints. The preferred treatment method is intralesionalcuretting and filling the cavity with bone cement [1, 3, 5, 6, 8].Since the detection of recurrent lesions is enhanced by theuse of bone cement it is considered more appropriate thanthe use of primary bone graft. Thermal cauterization of thebone cement, by its exothermic reaction in combination withlocal chemical cauterization using phenol may help destroymicroscopic tumor cells and reduce the chance of recurrence[1, 5].

Recurrence after intralesional curettage is reported to be25% whereas wide excision is associated with a rate of 5%[1, 3, 8], but wide excisions usually require endoprostheticreplacement or arthrodesis because of the tumors frequentjuxta-articular localization.

Exclusive radiation therapy is generally ineffective incontrolling these tumors, but it is reserved for lesions thatare not amenable to surgical removal. Radiation therapy isrecommended in patients with soft tissue involvement (aftertreatment with curettage and bone cement) because theymayhave an increased risk of local recurrence [1–3, 6, 8].

Malignant transformation of GCT of bone can be definedas a sarcoma, usually a fibrosarcoma or osteosarcoma. Noexact data were found in the literature about malignanttransformation ofmulticentric lesions but up to 5%of solitarylesions undergo malignant changes [1, 3].

Prior to this case report, the development of multicentricGCT after an osteosarcoma has not been described in theliterature.

This occurrence of multicentric lesions developing afteran osteosarcoma and the well-documented tendency ofmulticentric tumors to affect younger patients [3, 5, 9, 11, 13]suggest that there may be a germ-line genetic abnormalitythat predisposes these patients to the development ofmultipletumors, but familial forms of multicentric GCTs of bone havenot been reported [3].

Bones scan screening at unusual sites (i.e., diaphysealregion, small bones) is recommended for patients withsolitary lesions on a semiannual basis for five years sincemostcases of multicentricity occur within this period [3].

In patients with GCT of bone multicentricity has to betaken in consideration when the patients are of younger ageor when the lesion is located at unusual sites (i.e., diaphysealregion, small bones of the hands or feet). MRI is consideredto be the best imaging modality allowing accurate tumordelineation, as well as the soft tissue and articular surfaceinvolvement.

Conflict of Interests

The authors declare that there are no conflict of interests.

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[10] A. Haskell, O. Wodowoz, and J. O. Johnston, “Metachronousmulticentric giant cell tumor: a case report and literaturereview,” Clinical Orthopaedics and Related Research, no. 412, pp.162–168, 2003.

[11] K. F. Taylor, W. Yingsakmongkol, K. A. Conard, and R. P.Stanton, “Multicentric giant cell tumor of bone: a case reportand review of the literature,” Clinical Orthopaedics and RelatedResearch, no. 410, pp. 267–273, 2003.

[12] V. Sanghvi, M. Lala, S. Desai, P. Chaturvedi, and G. Rodrigues,“Synchronousmulticentric giant cell tumour: a case report withreview of literature,” European Journal of Surgical Oncology, vol.25, no. 6, pp. 636–637, 1999.

[13] M. Zahid, N. Asif, A. Bin Sabir, Y. S. Siddiqui, and M. Julfiqar,“Metachronous multicentric giant cell tumour of the upperextremity in a skeletally immature girl: a rare presentation,”ActaOrthopaedica Belgica, vol. 76, no. 5, pp. 694–698, 2010.

[14] I.-H. Park and I.-H. Jeon, “Multicentric giant cell tumor of bone:ten lesions at presentation,” Skeletal Radiology, vol. 32, no. 9, pp.526–529, 2003.

[15] C. I. Leichtle, U. G. Leichtle, V. Gartner, H. Schimmel, J. T.Hartmann, andM. Rudert, “Multiple skeletal metastases from agiant cell tumour of the distal fibula with fatal outcome,” Journalof Bone and Joint Surgery, vol. 88, no. 3, pp. 396–399, 2006.

[16] B. G. H. Vardhan, K. Saraswathy, andD. Koteeswaran, “Primaryhyperparathyroidism presenting as multiple giant cell lesions,”Quintessence International, vol. 38, no. 6, pp. e342–e347, 2007.

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