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Juxtacortical chondrosarcoma of the mandible: report of a unique case and review of the literature
Int. J. Oral Maxillofac. Surg. 2005; 34: 94–98 doi:10.1016/j.ijom.2004.02.011, available online at http://www.sciencedirect.com
Case Report Pathology
Juxtacortical chondrosarcoma of the mandible: report of a unique case and review of the literature
Ph. A. Van Damme1, P. C. M. de Wilde2, R. A. C. Koot3, I. Bruaset1, P. J. Slootweg4, D. J. Ruiter2 1 Department of Oral and CranioMaxillofacial Surgery, Nijmegen, The Netherlands; 2 Department of Pathology, University Medical Centre Nijmegen, Nijmegen, The Netherlands; 3Department of Pathology, Rijnstate Hospital Arnhem, Arnhem, The Netherlands; 4Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
Ph. A. Van Damme, P. C. M. de Wilde, R. A. C. Koot, I. Bruaset, P. J. Slootweg, D. J. Ruiter: Juxtacortical chondrosarcoma of the mandible: report of a unique case and review of the literature. Int. J. Oral Maxillofac. Surg. 2005; 34: 94–98. # 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The clinical, radiographic, and pathological features of a juxtacortical chondrosarcoma of the mandible in a 25-year-old Caucasian woman are presented and the differential diagnostic aspects are discussed. To the best of our knowledge, this rare tumor has not previously been reported in the maxillofacial skeleton. Ten years after surgery there is no evidence of local recurrence or metastatic disease. As the prognosis of juxtacortical chondrosarcoma of the long bones seems to be relatively favorable compared with the usual central chondrosarcoma of similar grade of malignancy, this might also be expected for a similar tumor presentation in the maxillofacial skeleton.
Chondrosarcomas comprise 1012% of all malignant bone tumors. They most commonly occur in the femur, humerus, pelvis, and sacrum. Chondrosarcomas of the maxillofacial region are rare locally aggressive tumors, accounting for approximately 1% of chondrosarcomas of the entire body3,13,23. In general, chondrosarcomas are reported to have a poor prognosis3, however, mesenchymal chondrosarcoma of the jaw bones appears to have a more indolent course than mesenchymal chondrosarcoma of other anatomic sites27,31. The mandible is a rather infrequent site of occurrence and the clinicopathological features are predominantly based on case reports and reviews of the literature2,3,8,10–13,19–21,23,27,29–31. The embryology of the mandible, originating from Meckel’s cartilage, might play a role in 0901-5027/010094 + 05 $30.00/0
chondrosarcoma pathogenesis6, however, the mandibular symphyseal region is the most reported with at least 12 cases13,20. Juxtacortical chondrosarcoma, a distinct malignant cartilage forming tumor arising from the external surface of a bone, accounts for less than 2% of all chondrosarcomas. In almost all reported cases this tumor involved the shaft of a long bone, most often the femur5,9,16– 18,25,26,32 . Dedifferentiation to an osteosarcoma has been described16. To the best of our knowledge juxtacortical chondrosarcoma involving the maxillofacial skeleton has never been reported. The clinicopathological features, enzyme and immunohistochemical findings of a case of juxtacortical chondrosarcoma of the mandible in a 25-yearold Caucasian woman are presented and the differential diagnosis is discussed.
Key words: juxtacortical; chondrosarcoma; periosteal; parosteal; mandible; maxillofacial; jaw. Accepted for publication 10 February 2004 Available online 6 May 2004
Case report
A 25-year-old Caucasian woman presented with a swelling of 3.0 cm diameter at the left molar region of the mandible. The swelling was noticed four weeks earlier because of hindrance. There were no complaints of pain, trismus or paresthesia. Clinical examination showed a smooth bulging swelling adherent to the mandible in the submandibular region, which was firm on palpation. Radiographic examination by an orthopantomograph showed a diffuse radiopacity in the caudal area of the mandibular angle with projection outside the cortical contour (Fig. 1). The outer cortex was not clearly continuous. The MRI showed a tumorous process on the medial side of the mandible with an expanding character and minor invasion of the neighboring
# 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Juxtacortical chondrosarcoma of the mandible
Fig. 1. Orthopantomogram. Detail of the initial orthopantomogram with a diffuse representation of the tumor mass at the left mandibular angle (arrows).
structures. Some minor destruction of the mandibular angle was seen. There were no indications for bone marrow invasion (Fig. 2). Total body Technetium scintigraphy showed no other lesions. Pathologic findings on biopsy specimens: Fine-needle aspiration biopsy of the tumor revealed some strongly atypical mesenchymal cells, requiring an open incisional biopsy to obtain more adequate histological evaluation. The incisional biopsy specimen had a firm, grey-blue aspect, typical for cartilaginous tissue. Microscopic examination of the biopsy material showed a rather poorly cellular tumor with a predominantly myxoid growth pattern. Focally cartilaginous differentiation was evident with hypercellularity and a more abundant hyaline matrix. The nuclei moderately varied in size with stellate, spindle-shaped and rounded cells, showing plumpness of nuclei with coarse hyperchromatism. Large nuclei and some double nuclei were found. Mitotic figures were not observed. There were no connective tissue septa present within the matrix, neither were tumor osteoid nor calcifications found in the biopsy specimen.
These histological features were consistent with a low grade chondrosarcoma with a predominant myxoid pattern. Pathologic findings on resection specimen: Two months after the initial presentation a segmental en bloc resection of the left mandible was performed. The surgical specimen (15:5 cm 7:0 cm 5:0 cm) showed a solid, eccentric tumor mass located on the medialcaudal side of the angle of the mandible (Fig. 3a). The periphery of the tumor seemed to be well demarcated and was covered by a markedly mobile apparent capsule of soft tissue. On cut surface the tumor presented as a lobulated, clearly extraosseous and juxtacortical mass, measuring 3.5 cm in diameter with a grey-blue color and reddish hemorrhagic spots. The surface was well defined and covered by a thick fibrous layer of lifted periosteum, which was in continuation with the periosteum of the adjacent mandibular bone (Fig. 3b). Thus, the tumor was localized subperiosteally. At the surface the tumor had a soft consistency, but the deeper regions of the tumor were firm elastic. The underlying cortex seemed slightly eroded and irregularly thickened adjacent
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to the tumor mass. There was no involvement of the medullary cavity. Microscopic findings: Multiple sections were taken from the surgical specimen. The tumor was multilobulated, and the lobules showed variations in size and shape. The lobules were separated by small bands of fibrous tissue. In the tumor, myxoid and cartilaginous areas were present. The periphery of the tumor showed a predominant myxoid pattern, while towards the center a cartilaginous differentiation with a more abundant hyaline matrix containing some scattered matrix calcifications was observed (Fig. 4a–d). In the myxoid area, the tumor cells were stellate or spindle shaped. The nuclei were plump and hyperchromatic, and exhibited moderate nuclear atypia. Binucleated tumor cells were also present. In the areas with cartilaginous differentiation the tumor cells were localized in lacunae. The nuclear pattern was the same as in the biopsy specimens and the frequency of mitoses was low (1 mitotic figure/10 HPF; 400). Tumor necrosis was not present. Although multiple sections were taken, no tumor osteoid, neither areas of enchondral ossification were found. The mandibular bone was eroded and infiltrated by the tumor. The diagnosis of low grade juxtacortical chondrosarcoma was made and the surgical resection margins were found to be free of tumor. Enzyme and immunohistochemical findings: The alkaline phosphatase staining technique according to the diazo procedure was performed on cryostat sections from fresh unfixed tumor tissue24. The enzyme histochemical demonstration of alkaline phosphatase may be very helpful in discriminating between osteogenic and chondrogenic sarcomas24. In the present case, no alkaline phosphatase was expressed by the tumor cells; this observation gives further support to the histological diagnosis of a chondrosarcoma. Tumor cells were negative for smooth muscle actine (a sm-1) and glial fibrillary acid protein (GFAP), thereby excluding the presence of myoepithelial cells. S-100 staining (both positive in cartilage forming tumors and mixed salivary gland tumors) was positive. The cell proliferation rate was investigated by immunohistochemical assessment of cell proliferation-associated nuclear antigen expression (Ki-67 antigen) with the monoclonal MIB-1 antibody (dilution 1:50; Immunotech SA, Marseille, France) on microwave paraffin-processed sections28. Bound MIB-1
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Fig. 2. MRI. Magnetic resonance images of the head in two perpendicular planes, axial and coronal. A tumorous process is present on the medial left side of the mandible with minor invasion of the adjacent structures and without bone marrow invasion.
antibody was visualized using the avidinbiotin-peroxidase complex (ABC kit, Vector Laboratories, Burlingame, CA, USA). The percent proportion of MIB-1 positive nuclei was 4.8% (defined by 1000-cell counts in representative areas of the tumor) confirming a low cell proliferation rate and consecutive low malignancy grade28. Follow-up: Initially after the segmental en bloc resection of the left mandible, an AO-reconstruction plate was inserted and fixed with four screws anteriorly and three posteriorly. Sixteen months later, because of fracture of the plate, a free vascularized osteomyocutaneous anterior iliac crest graft was transplanted with an end-to-side anastomosis of the arteria iliaca circumflexa profunda to the arteria carotis communis and an end-to-side anastomosis of the vena iliaca circumflexa profunda and the vena jugularis. A new AO-plate was used to fix the transplant with five screws. Again after 18 months, the AO-plate was removed and two Bra˚ nemark implants were inserted, for supporting a denture.
Ten years after initial surgery, the patient is still free of disease, without signs of local recurrence and distant metastases, and functioning adequately. Discussion
The term juxtacortical chondrosarcoma was introduced by JAFFE in 195814, and is also referred to as parosteal or periosteal chondrosarcoma. Later on, it was accepted in the WHO classification as a distinct entity. The descriptive term emphasizes the close relationship of the tumor to the adjacent bony cortex. In most reported cases the lesion involved the shaft of long bones, especially the femur and less frequently the humerus, pelvis, sacrum and rarely the rib or foot5,9,16–18,25,26,32. A recent cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes showed normal chromosome numbers in two juxtacortical chondrosarcomas, and the authors stated that juxtacortical and peripheral chondrosarcomas are two clinicopathologically different entities with a different genetic
background4. To the best of our knowledge (PubMed-search) the juxtacortical chondrosarcoma has not yet been described in the maxillofacial skeleton. The juxtacortical chondroma, juxtacortical chondroblastic osteosarcoma, juxtacortical osteogenic sarcoma, periosteal osteosarcoma, chondromyxoid fibroma, and mixed salivary gland tumor must be considered in the differential diagnosis7,15,22,23. The tumor presented here showed obvious destruction of the outer cortex and spotty matrix calcifications, which is uncommon in juxtacortical chondromas. In addition, there were several cytomorphologic features of malignancy, i.e. hypercellularity, variation of nuclear size, plumpness of nuclei with coarse hyperchromatism, and presence of mitotic figures which justified a diagnosis of low grade malignancy. Osteosarcomas of the jaw frequently have chondroblastic differentiation, causing confusion with chondrosarcomas22,23. The absence of neoplastic osteoid, neoplastic bone or alkaline phosphatase expressing tumor cells
Juxtacortical chondrosarcoma of the mandible
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Fig. 3. Surgical specimen. (a) Lateral and medial view. (b) Cut surface, and separate detail. A solid extraosseous and juxtacortical tumor mass, is well delimited and covered by a fibrous capsule.
Fig. 4. Histological features of the tumor. (a) A microscopic detail of the surgical specimen shows that the fibrous capsule is the lifted periosteum which is continuous with the periosteum of the adjacent, non-involved mandible (Hematoxylin and Eosin, 12). (b) and (c) The periphery of the tumor shows a lobulated predominantly myxoid pattern with absence of vascularized connective tissue septa or multinucleated giant cells (Hematoxylin and Eosin, 200). (d) The center of the tumor exhibits cartilaginous differentiation with the cytomorphologic features of a chondroid tumor of low grade of malignancy (Alcian-Blue, 200).
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excluded the probability of a chondroblastic osteosarcoma. The latter tumor, in contrast to the presented case, often contains chondroblastic areas with highly pleiomorphic chrondrocytes9. Malignant transformation in the cartilage cap of an osteochondroma seems to be unlikely due to the absence of a pedicle of cancellous bone continuous with the spongiosa beneath the medullary cavity. Other objections against this possibility are that malignant transformation in osteochondroma is most frequently observed in the autosomal dominant hereditary osteochondromatosis and that solitary osteochondromas of the mandible are almost exclusively limited to the condylar and coronoid processes1,27. Although the present case exhibited gross features compatible with a diagnosis of chondromyxoid fibroma, this diagnosis could be ruled out as microscopical features typical for that tumor, such as lobules separated by fibrous septa and multinucleated giant cells were not observed11. Although multiple sections were taken, epithelial structures in the tumor mass could not be found. Furthermore, immunohistochemical stainings for a sm-1 and GFAP were negative, making a diagnosis of mixed salivary gland tumor unlikely. In conclusion, histopathologic appearance, subperiosteal tumor localization, and lack of features compatible with a diagnosis of juxtacortical chondroma, chondroblastic osteosarcoma, chondromyxoid fibroma, or mixed salivary gland tumor prompt us to conclude that the presented case is the first one of a juxtacortical chondrosarcoma of the mandible. As the prognosis of the juxtacortical chondrosarcoma of long bones seems to be much better than the central chondrosarcoma of similar histologic grade of malignancy26, the prognosis for the mandibular variant is probably alike, witness the 10-year tumor-free follow-up. The segmental en bloc resection advised for long bone tumors seems also to be the treatment of choice for this tumor localized in the mandible. References 1. BARNES L. Surgical Pathology of the Head and Neck. New York: Marcel Dekker Inc. 1985: 944. 2. Batsakis JG. Osteogenic and chondrogenic sarcomas of the jaws. Ann Otol Rhinol Laryngol 1987: 96: 474–475. 3. Benateau H, Rigau V, Martin JP, Labbe D, Compere JF. Difficultes diagnostiques du chondrosarcome des maxillaires. A propos d’un cas et revue de la
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litterature [Diagnostic difficulties of chondrosarcoma of the jaw. Apropos of a case and review of the literature]. Rev Stomatol Chir Maxillofac 2000: 101: 80–85. Bovee JV, Sciot R, Cin PD, DebiecRychter M, van Zelderen-Bhola SL, Cornelisse CJ, Hogendoorn PC. Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes. Diagn Mol Pathol 2001: 10: 228–235. Cooper RR. Juxtacortical chondrosarcoma. A case report. J Bone Joint Surg 1965: 47: 524–528. da Rosa Santos OL, Moreira AM, Lopes Cardoso IC, Rodrigues Terra BA, Bellizzi A, Ramos-e-Silva M. Sarcoma of Meckel’s cartilage. Int J Dermatol 1996: 35: 353–354. Devisme L, de Roquancourt A, Engelmann A, Chanterelle A, Brocheriou C. Osteosarcome perioste des maxillaires. A propos de deux observations [Periosteal osteosarcoma of the jaw. Apropos of 2 cases]. Arch Anat Cytol Pathol 1994: 42: 96–102. Ebata K, Usami T, Tohnai I, Kaneda T. Chondrosarcoma and osteosarcoma arising in polyostotic fibrous dysplasia. J Oral Maxillofac Surg 1992: 50: 761–764. FECHNER RE, MILLS SE. Tumors of the Bones and Joints. 3rd series. Washington DC: Armed Forces Institute of Pathology 1993: l21. Gadwal SR, Fanburg-Smith JC, Gannon FH, Thompson LD. Primary chondrosarcoma of the head and neck in pediatric patients: a clinicopathologic study of 14 cases with a review of the literature. Cancer 2000: 88: 2181–2188. Gallia L, Tideman H, Bronkhorst F. Chondrosarcoma of the mandible misdiagnosed as chondromyxoid fibroma. Int J Oral Surg 1980: 9: 221–224. Hebbar GK, Hazarika P, Murty PS, Ashok MP. Chondrosarcoma of the mandible. Ear Nose Throat J 1990: 69: 652–654. Izadi K, Lazow SK, Solomon MP, Berger JR. Chondrosarcoma of the anterior mandible. A case report. NY State Dent J 2000: 66: 32–34. JAFFE HL. Tumors and Tumorous Conditions of the Bones and Joints. Philadelphia: Lea & Febiger 1958: 30. Kawasaki T, Ono N, Watanabe K, Hoshi K. Chondroblastic osteosarcoma of the mandible: report of a case. J Oral Maxillofac Surg 1996: 54: 1123–1127. Kumta SM, Griffith JF, Chow LT, Leung PC. Primary juxtacortical chondrosarcoma dedifferentiating after 20 years. Skelet Radiol 1998: 27: 569–573. Mena JC, Kaakaji Y, Chalpin DB, Nietzschman HR. Case 1: juxtacortical chondrosarcoma. Am J Roentgenol 1998: 171: 861. Mitchell A, Rudan JR, Fenton PV. Juxtacortical dedifferentiated chondrosarcoma from a primary periosteal chondrosarcoma. Mol Pathol 1996: 9: 279–283.
19. Murayama S, Suzuki I, Nagase M, Shingaki S, Kawasaki T, Nakajima T, Fukushima M, Ishiki T. Chondrosarcoma of the mandible. Report of a case and a survey of 23 cases in the Japanese literature. J Craniomaxillofac Surg 1988: 16: 287–292. 20. Ormiston IW, Piette E, Tideman H, Wu PC. Chondrosarcoma of the mandible presenting as periodontal lesions: report of 2 cases. J Craniomaxillofac Surg 1994: 22: 231–235. 21. Ozkul H, Kayhan FT, Kiyak E, Cevansir B, Sarikahya I. Pathologic quiz case 1. Chondrosarcoma of the mandible. Arch Otolaryngol Head Neck Surg 1995: 121: 694–696. 22. Piattelli A, Favia GF. Periosteal osteosarcoma of the jaws: report of 2 cases. J Periodontol 2000: 71: 325–329. 23. Saito K, Unni KK, Wollan PC, Lund BA. Chondrosarcoma of the jaw and facial bones. Cancer 1995: 76: 1550–1558. 24. Sanerkin NG. Definitions of osteosarcoma. Cancer 1980: 46: 178–185. 25. Schajowicz F. Juxtacortical chondrosarcoma.J BoneJointSurg1977:59: 473–480. 26. SCHAJOWICZ F. Tumors and Tumor Like Lesions of Bone. 2nd edn. Berlin: Springer Verlag 1994: 230. 27. Vencio EF, Reeve CM, Unni KK, Nascimento AG. Mesenchymal chondrosarcoma of the jaw bones: clinicopathologic study of 19 cases. Cancer 1998: 82: 2350– 2355. 28. Vollmer E, Roessner A, Gerdes J, Mellin W, Stein H, Chong-Schachel S, Grundmann E. Improved grading of bone tumors with the monoclonal antibody Ki-67. J Cancer Res Clin Oncol 1986: 112: 281–282. 29. Weiss WW, Bennett JA. Chondrosarcoma: a rare tumor of the jaws. J Oral Maxillofac Surg 1986: 44: 73–79. 30. Zachariades N, Vairaktaris E, Mezitis M, Triantafyllou D, Papavassiliou D. Chondrosarcoma of the orofacial region. Review of the literature and report of two cases. Rev Stomatol Chir Maxillofac 1987: 88: 382–387. 31. Zakkak TB, Flynn TR, Boguslaw B, Adamo AK. Mesenchymal chondrosarcoma of the mandible: case report and review of the literature. J Oral Maxillofac Surg 1998: 56: 84–91. 32. Zenmyo M, Komiya S, Nakashima M, Irie K, Kakizoe M, Inoue A. Giant juxtacortical chondrosarcoma of the humerus. Orthopedics 2000: 23: 497–498. Address: Philip. A. Van Damme Department of Oral and CranioMaxillofacial Surgery (421) University Medical Centre Nijmegen P.O. Box 9101 6500 HB Nijmegen The Netherlands. Tel: þ31 24 3614561; Fax: þ31 24 3541165 E-mail : [email protected]
Case Report Pathology
Juxtacortical chondrosarcoma of the mandible: report of a unique case and review of the literature
Ph. A. Van Damme1, P. C. M. de Wilde2, R. A. C. Koot3, I. Bruaset1, P. J. Slootweg4, D. J. Ruiter2 1 Department of Oral and CranioMaxillofacial Surgery, Nijmegen, The Netherlands; 2 Department of Pathology, University Medical Centre Nijmegen, Nijmegen, The Netherlands; 3Department of Pathology, Rijnstate Hospital Arnhem, Arnhem, The Netherlands; 4Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
Ph. A. Van Damme, P. C. M. de Wilde, R. A. C. Koot, I. Bruaset, P. J. Slootweg, D. J. Ruiter: Juxtacortical chondrosarcoma of the mandible: report of a unique case and review of the literature. Int. J. Oral Maxillofac. Surg. 2005; 34: 94–98. # 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The clinical, radiographic, and pathological features of a juxtacortical chondrosarcoma of the mandible in a 25-year-old Caucasian woman are presented and the differential diagnostic aspects are discussed. To the best of our knowledge, this rare tumor has not previously been reported in the maxillofacial skeleton. Ten years after surgery there is no evidence of local recurrence or metastatic disease. As the prognosis of juxtacortical chondrosarcoma of the long bones seems to be relatively favorable compared with the usual central chondrosarcoma of similar grade of malignancy, this might also be expected for a similar tumor presentation in the maxillofacial skeleton.
Chondrosarcomas comprise 1012% of all malignant bone tumors. They most commonly occur in the femur, humerus, pelvis, and sacrum. Chondrosarcomas of the maxillofacial region are rare locally aggressive tumors, accounting for approximately 1% of chondrosarcomas of the entire body3,13,23. In general, chondrosarcomas are reported to have a poor prognosis3, however, mesenchymal chondrosarcoma of the jaw bones appears to have a more indolent course than mesenchymal chondrosarcoma of other anatomic sites27,31. The mandible is a rather infrequent site of occurrence and the clinicopathological features are predominantly based on case reports and reviews of the literature2,3,8,10–13,19–21,23,27,29–31. The embryology of the mandible, originating from Meckel’s cartilage, might play a role in 0901-5027/010094 + 05 $30.00/0
chondrosarcoma pathogenesis6, however, the mandibular symphyseal region is the most reported with at least 12 cases13,20. Juxtacortical chondrosarcoma, a distinct malignant cartilage forming tumor arising from the external surface of a bone, accounts for less than 2% of all chondrosarcomas. In almost all reported cases this tumor involved the shaft of a long bone, most often the femur5,9,16– 18,25,26,32 . Dedifferentiation to an osteosarcoma has been described16. To the best of our knowledge juxtacortical chondrosarcoma involving the maxillofacial skeleton has never been reported. The clinicopathological features, enzyme and immunohistochemical findings of a case of juxtacortical chondrosarcoma of the mandible in a 25-yearold Caucasian woman are presented and the differential diagnosis is discussed.
Key words: juxtacortical; chondrosarcoma; periosteal; parosteal; mandible; maxillofacial; jaw. Accepted for publication 10 February 2004 Available online 6 May 2004
Case report
A 25-year-old Caucasian woman presented with a swelling of 3.0 cm diameter at the left molar region of the mandible. The swelling was noticed four weeks earlier because of hindrance. There were no complaints of pain, trismus or paresthesia. Clinical examination showed a smooth bulging swelling adherent to the mandible in the submandibular region, which was firm on palpation. Radiographic examination by an orthopantomograph showed a diffuse radiopacity in the caudal area of the mandibular angle with projection outside the cortical contour (Fig. 1). The outer cortex was not clearly continuous. The MRI showed a tumorous process on the medial side of the mandible with an expanding character and minor invasion of the neighboring
# 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Juxtacortical chondrosarcoma of the mandible
Fig. 1. Orthopantomogram. Detail of the initial orthopantomogram with a diffuse representation of the tumor mass at the left mandibular angle (arrows).
structures. Some minor destruction of the mandibular angle was seen. There were no indications for bone marrow invasion (Fig. 2). Total body Technetium scintigraphy showed no other lesions. Pathologic findings on biopsy specimens: Fine-needle aspiration biopsy of the tumor revealed some strongly atypical mesenchymal cells, requiring an open incisional biopsy to obtain more adequate histological evaluation. The incisional biopsy specimen had a firm, grey-blue aspect, typical for cartilaginous tissue. Microscopic examination of the biopsy material showed a rather poorly cellular tumor with a predominantly myxoid growth pattern. Focally cartilaginous differentiation was evident with hypercellularity and a more abundant hyaline matrix. The nuclei moderately varied in size with stellate, spindle-shaped and rounded cells, showing plumpness of nuclei with coarse hyperchromatism. Large nuclei and some double nuclei were found. Mitotic figures were not observed. There were no connective tissue septa present within the matrix, neither were tumor osteoid nor calcifications found in the biopsy specimen.
These histological features were consistent with a low grade chondrosarcoma with a predominant myxoid pattern. Pathologic findings on resection specimen: Two months after the initial presentation a segmental en bloc resection of the left mandible was performed. The surgical specimen (15:5 cm 7:0 cm 5:0 cm) showed a solid, eccentric tumor mass located on the medialcaudal side of the angle of the mandible (Fig. 3a). The periphery of the tumor seemed to be well demarcated and was covered by a markedly mobile apparent capsule of soft tissue. On cut surface the tumor presented as a lobulated, clearly extraosseous and juxtacortical mass, measuring 3.5 cm in diameter with a grey-blue color and reddish hemorrhagic spots. The surface was well defined and covered by a thick fibrous layer of lifted periosteum, which was in continuation with the periosteum of the adjacent mandibular bone (Fig. 3b). Thus, the tumor was localized subperiosteally. At the surface the tumor had a soft consistency, but the deeper regions of the tumor were firm elastic. The underlying cortex seemed slightly eroded and irregularly thickened adjacent
95
to the tumor mass. There was no involvement of the medullary cavity. Microscopic findings: Multiple sections were taken from the surgical specimen. The tumor was multilobulated, and the lobules showed variations in size and shape. The lobules were separated by small bands of fibrous tissue. In the tumor, myxoid and cartilaginous areas were present. The periphery of the tumor showed a predominant myxoid pattern, while towards the center a cartilaginous differentiation with a more abundant hyaline matrix containing some scattered matrix calcifications was observed (Fig. 4a–d). In the myxoid area, the tumor cells were stellate or spindle shaped. The nuclei were plump and hyperchromatic, and exhibited moderate nuclear atypia. Binucleated tumor cells were also present. In the areas with cartilaginous differentiation the tumor cells were localized in lacunae. The nuclear pattern was the same as in the biopsy specimens and the frequency of mitoses was low (1 mitotic figure/10 HPF; 400). Tumor necrosis was not present. Although multiple sections were taken, no tumor osteoid, neither areas of enchondral ossification were found. The mandibular bone was eroded and infiltrated by the tumor. The diagnosis of low grade juxtacortical chondrosarcoma was made and the surgical resection margins were found to be free of tumor. Enzyme and immunohistochemical findings: The alkaline phosphatase staining technique according to the diazo procedure was performed on cryostat sections from fresh unfixed tumor tissue24. The enzyme histochemical demonstration of alkaline phosphatase may be very helpful in discriminating between osteogenic and chondrogenic sarcomas24. In the present case, no alkaline phosphatase was expressed by the tumor cells; this observation gives further support to the histological diagnosis of a chondrosarcoma. Tumor cells were negative for smooth muscle actine (a sm-1) and glial fibrillary acid protein (GFAP), thereby excluding the presence of myoepithelial cells. S-100 staining (both positive in cartilage forming tumors and mixed salivary gland tumors) was positive. The cell proliferation rate was investigated by immunohistochemical assessment of cell proliferation-associated nuclear antigen expression (Ki-67 antigen) with the monoclonal MIB-1 antibody (dilution 1:50; Immunotech SA, Marseille, France) on microwave paraffin-processed sections28. Bound MIB-1
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Fig. 2. MRI. Magnetic resonance images of the head in two perpendicular planes, axial and coronal. A tumorous process is present on the medial left side of the mandible with minor invasion of the adjacent structures and without bone marrow invasion.
antibody was visualized using the avidinbiotin-peroxidase complex (ABC kit, Vector Laboratories, Burlingame, CA, USA). The percent proportion of MIB-1 positive nuclei was 4.8% (defined by 1000-cell counts in representative areas of the tumor) confirming a low cell proliferation rate and consecutive low malignancy grade28. Follow-up: Initially after the segmental en bloc resection of the left mandible, an AO-reconstruction plate was inserted and fixed with four screws anteriorly and three posteriorly. Sixteen months later, because of fracture of the plate, a free vascularized osteomyocutaneous anterior iliac crest graft was transplanted with an end-to-side anastomosis of the arteria iliaca circumflexa profunda to the arteria carotis communis and an end-to-side anastomosis of the vena iliaca circumflexa profunda and the vena jugularis. A new AO-plate was used to fix the transplant with five screws. Again after 18 months, the AO-plate was removed and two Bra˚ nemark implants were inserted, for supporting a denture.
Ten years after initial surgery, the patient is still free of disease, without signs of local recurrence and distant metastases, and functioning adequately. Discussion
The term juxtacortical chondrosarcoma was introduced by JAFFE in 195814, and is also referred to as parosteal or periosteal chondrosarcoma. Later on, it was accepted in the WHO classification as a distinct entity. The descriptive term emphasizes the close relationship of the tumor to the adjacent bony cortex. In most reported cases the lesion involved the shaft of long bones, especially the femur and less frequently the humerus, pelvis, sacrum and rarely the rib or foot5,9,16–18,25,26,32. A recent cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes showed normal chromosome numbers in two juxtacortical chondrosarcomas, and the authors stated that juxtacortical and peripheral chondrosarcomas are two clinicopathologically different entities with a different genetic
background4. To the best of our knowledge (PubMed-search) the juxtacortical chondrosarcoma has not yet been described in the maxillofacial skeleton. The juxtacortical chondroma, juxtacortical chondroblastic osteosarcoma, juxtacortical osteogenic sarcoma, periosteal osteosarcoma, chondromyxoid fibroma, and mixed salivary gland tumor must be considered in the differential diagnosis7,15,22,23. The tumor presented here showed obvious destruction of the outer cortex and spotty matrix calcifications, which is uncommon in juxtacortical chondromas. In addition, there were several cytomorphologic features of malignancy, i.e. hypercellularity, variation of nuclear size, plumpness of nuclei with coarse hyperchromatism, and presence of mitotic figures which justified a diagnosis of low grade malignancy. Osteosarcomas of the jaw frequently have chondroblastic differentiation, causing confusion with chondrosarcomas22,23. The absence of neoplastic osteoid, neoplastic bone or alkaline phosphatase expressing tumor cells
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Fig. 3. Surgical specimen. (a) Lateral and medial view. (b) Cut surface, and separate detail. A solid extraosseous and juxtacortical tumor mass, is well delimited and covered by a fibrous capsule.
Fig. 4. Histological features of the tumor. (a) A microscopic detail of the surgical specimen shows that the fibrous capsule is the lifted periosteum which is continuous with the periosteum of the adjacent, non-involved mandible (Hematoxylin and Eosin, 12). (b) and (c) The periphery of the tumor shows a lobulated predominantly myxoid pattern with absence of vascularized connective tissue septa or multinucleated giant cells (Hematoxylin and Eosin, 200). (d) The center of the tumor exhibits cartilaginous differentiation with the cytomorphologic features of a chondroid tumor of low grade of malignancy (Alcian-Blue, 200).
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excluded the probability of a chondroblastic osteosarcoma. The latter tumor, in contrast to the presented case, often contains chondroblastic areas with highly pleiomorphic chrondrocytes9. Malignant transformation in the cartilage cap of an osteochondroma seems to be unlikely due to the absence of a pedicle of cancellous bone continuous with the spongiosa beneath the medullary cavity. Other objections against this possibility are that malignant transformation in osteochondroma is most frequently observed in the autosomal dominant hereditary osteochondromatosis and that solitary osteochondromas of the mandible are almost exclusively limited to the condylar and coronoid processes1,27. Although the present case exhibited gross features compatible with a diagnosis of chondromyxoid fibroma, this diagnosis could be ruled out as microscopical features typical for that tumor, such as lobules separated by fibrous septa and multinucleated giant cells were not observed11. Although multiple sections were taken, epithelial structures in the tumor mass could not be found. Furthermore, immunohistochemical stainings for a sm-1 and GFAP were negative, making a diagnosis of mixed salivary gland tumor unlikely. In conclusion, histopathologic appearance, subperiosteal tumor localization, and lack of features compatible with a diagnosis of juxtacortical chondroma, chondroblastic osteosarcoma, chondromyxoid fibroma, or mixed salivary gland tumor prompt us to conclude that the presented case is the first one of a juxtacortical chondrosarcoma of the mandible. As the prognosis of the juxtacortical chondrosarcoma of long bones seems to be much better than the central chondrosarcoma of similar histologic grade of malignancy26, the prognosis for the mandibular variant is probably alike, witness the 10-year tumor-free follow-up. The segmental en bloc resection advised for long bone tumors seems also to be the treatment of choice for this tumor localized in the mandible. References 1. BARNES L. Surgical Pathology of the Head and Neck. New York: Marcel Dekker Inc. 1985: 944. 2. Batsakis JG. Osteogenic and chondrogenic sarcomas of the jaws. Ann Otol Rhinol Laryngol 1987: 96: 474–475. 3. Benateau H, Rigau V, Martin JP, Labbe D, Compere JF. Difficultes diagnostiques du chondrosarcome des maxillaires. A propos d’un cas et revue de la
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