J Oral Maxillofac Surg 66:161-167, 2008
Synovial Sarcoma in the Oral and Maxillofacial Region: Report of 4 Cases
and Review of the Literature
Hu Wang, MD,* Jing Zhang, PhD,† Xing He, PhD,‡ and Yuming Niu§
Synovial sarcoma (SS) is a well-defined tumor that accounts for up to 10% of all soft tissue sarcomas. It arises primarily in the extremities,
1with a predilec- tion for sites in proximity to large joints such as the knee.
2The oral and maxillofacial region is an un- usual site for this tumor. Here we report 4 cases of SS in the oral and maxillofacial region and also present a review of the literature.
Report of Cases
CASE 1
A 32-year-old man had a 9-month history of a progres- sively growing tumor on the left side of his face. Physical examination revealed a 5 cm⫻ 4 cm, firm, slightly ten- der, nonmobile tumor in the left preauricular region.
Facial asymmetry and left facial swelling were observed.
The maximum possible amount of mouth opening was 20 mm. The regional lymph nodes were not enlarged. A computed tomography (CT) scan revealed destruction of the normal structure of left condylar process (Fig 1). The patient underwent surgery under general anesthesia. In- teroperative frozen results were consistent with a diag- nosis of malignant tumor originating from mesenchymal tissue. The tumor was excised with wide margins. His- topathologic examination showed that tumor had infil- trated the condylar process (Fig 2A) and was composed of epithelial cells and spindle-shaped cells (Fig 2B). Im- munohistochemical examination revealed diffuse tumor cell positivity for vimentine (Fig 2C) and CD99 (Fig 2D),
with no reactivity for cytokeratines, smooth muscle actin (SMA), desmin, or CD34. A diagnosis of primary biphasic SS was made on the basis of the histopathologic and immunohistochemical findings.
CASE 2
A 31-year-old woman was referred to our institution due to aggravating left temporal region pain of 6 months’
duration. Four weeks earlier, the patient had presented with mouth-opening limitation and left lower lip numb- ness. The patient’s medical history, family history, trau- matic history, and review of systems were noncontribu- tory.
Physical examination revealed slight swelling and ten- derness in the left temporal region. The maximum pos- sible amount of mouth opening was 15 mm. The occlusal relationship was normal. No appreciable lymphadenopa- thy was detected. Magnetic resonance imaging (MRI) demonstrated a 5 cm⫻ 4.9 cm ⫻ 2.4 cm mass occupying
Received from the Department of Oral Radiology, West China College of Stomatology, Sichuan University, Chengdu, China.
ⴱProfessor and Director.
†Resident.
‡Resident.
§Postgraduate and Resident.
Address correspondence and reprint requests to Dr Zhang: De- partment of Oral Radiology, West China School of Stomatology, Sichuan University, No 14, Section 3, Renmin South Road, Chengdu, Sichuan, China; e-mail: jingz77@163.com
©2008 American Association of Oral and Maxillofacial Surgeons 0278-2391/08/6601-0028$34.00/0
doi:10.1016/j.joms.2007.05.007
FIGURE 1. Case 1. Axial CT showing a nonhomogeneous area in the left condylar process (arrow). The normal structure of the left condylar process was destroyed, obscuring the border of the mass.
Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
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the left infratemporal fossa space (Fig 3). The patient underwent surgery with a marginal excision.
Light microscopic examination revealed that the tumor cells were composed of spindle cells (Fig 4A). Immuno- histochemistry was positive for epithelial membrane an- tigen (EMA) (Fig 4B), vimentin (Fig 4C), CD99, and Pan-CK (cytokeratin) but negative for SMA. Based on the histopathological and immunohistochemical findings, a diagnosis of monophasic (spindle cell) SS was made.
CASE 3
A 34-year-old man was referred with suspected recur- rence of right cheek SS to our hospital in November 2005. The symptoms had been present for approximately 2 months. The patient reported noticing a swelling of the right cheek 6 years earlier, but that he had not paid much attention to it. In 2003, he began to experience local pain, and sought care at the local hospital. The final diagnostic result was not available. One year later, the tumor recurred and was re-excised at the local hospital.
The specimen was sent to the Department of Pathology, West China Hospital for consultation. Light microscopy
showed that the tumor comprised 2 alternating compo- nents, spindle cells and epithelial cells (Figs 5A,B). Im- munohistochemically, the spindle cell components were positive for vimentin and the epithelial cell components were positive for EMA (Fig 5C), whereas tumor cells were negative for SMA, desmin, and S-100. Based on these features, the tumor was classified as a biphasic SS.
At 10 months after the patient’s second surgery, an- other cheek mass reported as SS was removed in another institution. The tumor had recurred again 2 months ear- lier. Physical examination revealed a 5 cm⫻ 2.5 cm firm, nonmobile mass in the right cheek. Mouth opening was limited, a maximum of 10 mm. Submandibular and preau- ricular operative scarring were evident. Chest radio- graphs did not reveal any metastatic change. The regional lymph nodes were not enlarged. Enhanced CT revealed a tumor in the right masseteric space (Fig 6). The diagnosis of recurrence was considered, and the patient underwent surgery with wide tumorectomy, including the overlying cheek soft tissues, zygomatic bone, and the zygomatic arch, along with segmental resection of the right man- dibular ramus and local flap reconstruction.
FIGURE 2. Case 1. Microphotograph of SS in the condylar process. (A) A solid cellular mass infiltrating the condylar process. (Hematoxylin and eosin; original magnification⫻60.) (B) Histological view showing a mixture of epithelial cells (arrow) and spindle-shaped cells. (Hematoxylin and eosin; original magnification⫻50.) (C and D) Immunohistochemical staining showing vimentin-positive (C) and CD99-positive (D) immunoreaction.
(Original magnification⫻100.)
Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
CASE 4
On November 3, 2005, a 30-year-old woman com- plained of swelling of 2 months’ duration in the left parotid region. Physical examination revealed a firm, ten- der, 1.5 cm ⫻ 1.5 cm tumor in the left parotid gland region. Facial nerve function was normal. CT showed a mass in the left parotid gland region involving the tem- poromandibular joint and infratemporal fossa. The lesion was excised and a specimen sent for histological exami- nation. Histologically, tumor cells were found infiltrating the parotid gland and nerve tissue (Figs 7A,B). Biphasic features including nesting-like epithelial cells and spindle cell components were observed (Fig 7C). Immunohisto- chemical examination revealed tumor cell positivity for Pan-CK (cytokeratin) but no reactivity for S-100, CD31, CD34, and desmin. Considering the morphological and immunohistochemical features, a diagnosis of primary left parotid gland SS was made.
Discussion
SS is a highly invasive tumor, but only 3% of all cases occur in the head and neck region. In the last few years, an increasing number of primary SSs have been detected in oral and maxillofacial sites, including the buccal mucosa,
3maxillary sinus,
4mandible,
5,6tongue,
7and floor of the mouth.
8The typical clinical presentation of these lesions is a
slow-growing, deep-seated, palable mass associated with pain in about 50% of cases.
In the 4 cases presented here, 2 occurred in males and the other 2 in females. The patients ranged in age from 30 to 34 years. The 4 lesions were located in the left condylar process, left infra- temporal fossa, right cheek, and left parotid gland.
The clinical presentation of all 4 cases was that of a gradually growing tumor. Case 3 had 3 recurrences.
The biphasic type of SS is more common than the monophasic type; of the 4 cases presented here, 3 were biphasic and 1 was monophasic. To date, 6 cases of cheek SS and 2 cases of parotid SS have been reported in the English literature (Table 1).
9-12Occurrence in the infratemporal fossa or condylar process as illustrated in the current cases appears to be extremely rare.
SS is not restricted to periarticular sites; it some- times appears in locations unrelated to the syno- vium, such as the tongue and soft palate. Thus, the histogenesis of SS remains controversial. Intercellu- lar junctions, microvilli, external lamina, and epi- thelial differentiation are rarely observed in normal synovium but can be seen in tumors.
13According to Leader et al,
14SSs can be more appropriately classified as carcinosarcomas. It is now generally accepted that SSs originate from undifferentiated or pluripotent mesenchymal cells with a dual differen- tiation capacity, both epithelial and mesenchy- mal.
14,15Variants of SS are subclassified into 4 types: (1) biphasic type with distinct epithelial and spindle cell components present in various propor- tions and patterns, (2) monophasic spindle cell type with little or no evidence of epithelial differ- entiation, (3) monophasic epithelial type, and (4) poorly differentiated type.
Immunohistochemically, the spindle cells of SS strongly and uniformly express mesenchymal marker (vimentin) with occasional evidence of cy- tokeratin markers, particularly in biphasic tumors.
In contrast, the epithelial cells usually demonstrate strong expression of epithelial markers (ie, CK7, CK19, EMA). At least 1 of these 2 epithelial markers is expressed in 90% of SSs. CD99 is expressed in most Ewing’s sarcomas and peripheral neuron-ec- todermal tumors; however, CD99 immunoreactivity also can be detected in the cytoplasm of cells in many SSs.
A biphasic SS is easily identified by its histological features. A monophasic spindle cell neoplasm, the most common variant of SS, is usually more prob- lematic. Immunohistochemistry is a very useful tool in classifying these lesions. The tumor cells in SS are generally positive for epithelial markers (ie, cytokeratins and EMA) that are mostly absent in other soft tissue sarcomas, such as fibrosarcomas.
FIGURE 3. Case 2. MRI showing the mass occupying the left infra- temporal fossa space (arrow), without complete inner encapsulation of the lesion.
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FIGURE 4. Case 2. Monophasic SS. (A) Abundant blood vessels can be seen, with the tumor cells composed of spindle cells. (He- matoxylin and eosin; original magnification⫻50.) (B and C) Immu- nohistochemical staining showing EMA-positive (B) and vimentin- positive (C) immunoreactions. (Original magnification: B,⫻145; C,
⫻159.)
Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
FIGURE 5. Case 3. Photomicrographs revealing solid proliferation of spindle cells (A) and the epithelial components forming gland-like structures (arrow), separated by bundles of spindle cells (B). (Hema- toxylin and eosin; original magnification ⫻63.) (C) Immunohisto- chemical staining showing an EMA-positive reaction in tumor cells.
(Original magnification⫻100.)
Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
Muscle-associated markers (eg, desmin, SMA) can be detected in leiomyosarcoma but are rarely seen in SS. S-100 protein is expressed in most malignant peripheral nerve sheath tumors. Considerable prog- nostic information can be provided by immunohis- tochemical analysis of tumor proliferation. A Ki- 67(MIB-1) index greater than 10% may be significantly correlated with the development of metastatic disease.
16Cytogenetically, SS is characterized by the spe- cific t(X;18) (p11.2;q11.2) chromosomal transloca- tion, found in more than 95% of the tumors. At the molecular level, this translocation results in rear- rangements of the SYT gene in 18q11 and 1 of the
SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT-SSX1, SYT-SSX2, or SYT-SSX4 chimeric gene.17The SYT-SSX2 fusion is usually associated with the monophasic type, and the SYT-SSX1 fusion is present in tumors of biphasic or monophasic type.
This relationship is not absolute, however; biphasic tumors with SYT-SSX2 fusion have been report- ed.
17-19The SYT-SSX fusion transcript is a defining diagnostic marker of SS and thus is of high diagnos- tic value.
20-22However, molecular testing is not required if the diagnosis of SS is certain or probable based on clinical, histological, and/or immunohis-
FIGURE 6. Case 3. Enhanced CT scan showing the tumor located in the right masseteric space (arrow), with the surrounding bone intact.
Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
FIGURE 7. Case 4. Biphasic SS. A, Low-power photomicrograph showing the tumor infiltrating the parotid gland, with a prominent hemorrhage in the tumor. (Hematoxylin and eosin; original magni- fication⫻10). B, Higher magnification of the same lesion showing tumor cells infiltrating nerve tissue. (Hematoxylin and eosin; original magnification⫻53). C, A mixture of epithelial cells and spindle- shaped cells, with epithelial cells forming a “nesting” pattern (ar- row). (Hematoxylin and eosin; original magnification⫻98.) Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
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tochemical evaluation.
21Genetic trials were not carried out for the 4 cases reported here. The fusion type presented by SS is a major prognostic indicator. The SYT-SSX1 fusion gene is associated with more aggressive tumor growth and poor out- come. Patients with SYT-SSX1 fusion genes have been reported to have shorter metastasis-free sur- vival compared with patients with SYT-SSX2 fusion genes.
17,18,23,24Owing to the paucity of cases of SS in the oral and maxillofacial area, the information regarding appropri- ate therapy for this tumor is limited. At present, ade- quate surgical excision appears to the most appropriate procedure to prevent local recurrence. In the head and neck, radical excision generally cannot be done without sacrificing vital structures. For this reason, the therapeu- tic strategy frequently avoids radical and mutilating sur- gery but includes postoperative radiation and adjuvant chemotherapy after conservative excision of the tumor.
Post-treatment recurrence rate for SS arising from all body sites is about 50%. Most cases recur in the first 2 years after treatment. Five-year survival rate is about 36% to 51%. Prognosis is affected by tumor size, location, patient age, histological subtype, extent, mi- totic activity, and margin of resection.
1,17,25Tumor size is the most important prognostic factor. Patients with tumors of maximum diameter greater than 5 cm have a poorer prognosis than those with tumors less than 5 cm in diameter.
26Despite advances in the treatment of local disease, distant metastasis remains the predominant cause of death. Recently, some in- vestigations revealed that epidermal growth factor receptor (EGFR) and human epithelial growth factor receptor 2 (HER-2/neu) may play roles in the tumor- igenesis of SS. Thus, antigrowth factor antibody ther- apies may provide a previously unrecognized thera- peutic approach to these tumors.
27,28In summary, this report has presented 4 cases of SS in different oral and maxillofacial regions. All 4 pa- tients underwent surgical resection with negative margins. The final diagnoses were confirmed
by histological and immunohistochemical findings.
Data on post-treatment recurrence and survival rate were not obtained, because all 4 patients were lost to follow-up.
References
1. Bergh P, Meis-Kindblom JM, Gherlinzoni F, et al: Synovial sarcoma: Identification of low- and high-risk groups. Cancer 85:2596, 1999
2. Miloro M, Quinn PD, Stewart JC: Monophasic spindle cell synovial sarcoma of the head and neck: Report of two cases and review of the literature. J Oral Maxillofac Surg 52:309, 1994
3. Goebel WM, High CJ, Kiviat J, et al: Anterior buccal mucosal mass. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:
667, 2004
4. Sun JJ, Rasgon BM, Wild TW, et al: Synovial cell sarcoma of the maxillary sinus: A first reported case. Otolaryngol Head Neck Surg 129:587, 2003
5. Koga C, Harada H, Kusukawa J, et al: Synovial sarcoma arising in the mandibular bone. Oral Oncol EXTRA 41:45, 2005
6. Tilakaratne WM: Synovial sarcoma of the mandible. J Oral Pathol Med 35:61, 2006
7. Carrillo R, EL-Naggar AK, Rodriguez-Peralto JL, et al: Synovial sarcoma of the tongue: Case report and review of the literature.
J Oral Maxillofac Surg 50:904, 1992
8. Meer S, Coleman H, Altini M: Oral synovial sarcoma: A report of 2 cases and a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 96:306, 2003
9. Lee SM, Hajdu SI, Exelby PR: Synovial sarcoma in children. Surg Gynecol Obstet 138:701, 1974
10. Lockey MW: Rare tumors of the ear, nose and throat: Synovial sarcoma of the head and neck. South Med J 69:316, 1976 11. Nunez-Alonso C, Gashti EN, Christ ML: Maxillofacial synovial
sarcoma: Light- and electron-microscopic study of two cases.
Am J Surg Pathol 3:23, 1979
12. Shmookler BM, Enzinger FM, Brannon RB: Orofacial synovial sarcoma: A clinicopathologic study of 11 new cases and review of the literature. Cancer 50:269, 1982
13. Fisher C: Synovial sarcoma: Ultrastructural and immunohisto- chemical features of epithelial differentiation in monophasic and biphasic tumors. Hum Pathol 17:996, 1986
14. Leader M, Patel J, Collins M, et al: Synovial sarcomas: True carcinosarcomas? Cancer 59:2096, 1987
15. Yakushiji T, Yonemura K, Tsuruta J, et al: Capacity for epithe- lial differentiation in synovial sarcoma: Analysis of a new hu- man cell line. J Clin Pathol 53:525, 2000
16. Skytting BT, Bauer HC, Perfekt R, et al: Ki-67 is strongly prog- nostic in synovial sarcoma: Analysis based on 86 patients from the Scandinavian Sarcoma Group register. Br J Cancer 80:1809, 1999
Table 1. SUMMARY OF CLINICAL FEATURES OF 8 PREVIOUSLY REPORTED CASES OF RELATED REGIONS OF SS
Reference Age Gender Location Management Histological type Follow-Up
Lee et al9 15 F Cheek SX INA A&W/15 years
Lockey10 11 F Cheek L SX, RTX, CTX B Dead/0.7 years
Nunez-Alonso et al11 48 M Cheek R SX, RTX B A&W/1.8 years
Shmookler et al12 27 F Cheek L SX B A&W/1.3 years
Shmookler et al12 36 M Cheek R SX, RTX, CTX B Dead/2.1 years
Shmookler et al12 26 M Cheek-pterygomaxillary fossa, R RTX, SX, CTX B Dead/2.6 years
Shmookler et al12 19 M Parotid region, L RTX, CTX, SX B Dead/2.9 years
Shmookler et al12 49 M Parotid region, R SX, RTX B A&W/2.3 years
Abbreviations: SX, surgical excision; RTX, irradiation therapy; CTX, chemotherapy; A&W, alive and well; B, biphasic type; INA, information not available.
Wang et al. Synovial Sarcoma in the Oral and Maxillofacial Region. J Oral Maxillofac Surg 2008.
17. Mezzelani A, Mariani L, Tamborini E, et al: SYT-SSX fusion genes and prognosis in synovial sarcoma. Br J Cancer 85:1535, 2001
18. Inagaki H, Nagasaka T, Otsuka T, et al: Association of SYT-SSX fusion types with proliferative activity and prognosis in syno- vial sarcoma. Mod Pathol 13:482, 2000
19. Kokovic I, Bracko M, Golouh R, et al: Are there geographical differences in the frequency of SYT-SSX1 and SYT-SSX2 chi- meric transcripts in synovial sarcoma? Cancer Detect Prev 28:294, 2004
20. dos Santos NR, de Bruijn DR, van Kessel AG: Molecular mech- anisms underlying human synovial sarcoma development.
Genes Chromosomes Cancer 30:1, 2001
21. Coindre JM, Pelmus M, Hostein I, et al: Should molecular testing be required for diagnosing synovial sarcoma? Cancer 98:2700, 2003
22. Fernebro J, Francis P, Eden P, et al: Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma. Int J Cancer 118:1165, 2006
23. Nilsson G, Skytting B, Xie Y, et al: The SYT-SSX1 variant of synovial sarcomas is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res 59:3180, 1999
24. Ioannis P, Fredrik M, Margareth I, et al: Clinical impact of molecular and cytogenetic findings in synovial sarcoma. Genes Chromosomes Cancer 31:362, 2001
25. Trassard M, Doussal VL, Hacèene K, et al: Prognostic factors in localized primary synovial sarcoma: A multicenter study of 128 adult patients. J Clin Oncol 19:525, 2001
26. Thompson RC Jr, Garg A, Goswitz J, et al: Synovial sar- coma: Large size predicts poor outcome. Clin Orthop 373:
18, 2000
27. Thomas DG, Giordano TJ, Sanders D, et al: Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma. Cancer 103:830, 2005 28. Olsen RJ, Lydiatt WM, Koepsell SA, et al: C-erb-B2 (HER2/neu)
expression in synovial sarcoma of the head and neck. Head Neck 27:883, 2005
J Oral Maxillofac Surg 66:167-169, 2008
Malposed Teeth in the Pterygomandibular Space: Report of 2 Cases
Steven B. Kupferman, DMD, MD,* and Harry C. Schwartz, DMD, MD†
Malposed teeth are well-documented in the litera- ture.
1Normal canines and third molars are most fre- quently found in an abnormal position. Supernumer- ary teeth can also be found in unusual locations, as can teeth that have been displaced by the growth of odontogenic cysts or tumors. We report 2 cases of mandibular third molars that were located in the pterygomandibular space. Although both apparently had some connection with the oral cavity, neither seems to have been displaced by a cyst or a tumor.
Report of Cases
CASE 1
A 49-year-old woman presented to her general dentist with acute right mandibular pain, trismus, and a foul taste in
her mouth. Periapical films showed periodontal bone loss distal to the mandibular right second molar. When a peri- odontal pocket was noted in this location, she was treated with scaling, root planing, and oral clindamycin. Symptoms resolved temporarily but returned 2 weeks later, and the patient was referred to an oral and maxillofacial surgeon. A panoramic radiograph revealed a third molar high in the ascending ramus of the right mandible (Fig 1A). The prac- titioner believed that this represented a cyst, which he could not manage in his office. He referred the patient to our department for care.
A malposed tooth was obvious on x-ray, but a cystic lesion could not be discerned. We obtained a computed tomographic (CT) scan of the mandible (Fig 1B), which showed the third molar crown to be outside of the bone, in the pterygomandibular space. The tooth was inverted, with its root apices attached to bone just below the sigmoid notch. No associated cyst or tumor was noted. Sclerosis in the adjacent mandible was consistent with chronic infec- tion. At surgery, the tooth was easily removed from the area between the lingula and the sigmoid notch. Attachment to bone was observed at the root apices. The crown was blackened and occlusal caries was present, indicating a connection with the periodontal pocket distal to the man- dibular right second molar. The patient was treated with a cephalosporin and made a rapid recovery, with resolution of all symptoms.
CASE 2
A 55-year-old woman was referred to our department by her dentist after 3 days of rapidly increasing left facial swelling, pain, fever, and trismus. No evidence of a dental cause was noted, and the patient reported no previous dental symptoms. An urgent CT scan was obtained, which Received from the Section of Oral and Maxillofacial Surgery, Uni-
versity of California, Los Angeles, CA.
*Resident.
†Professor.
Address correspondence and reprint requests to Dr Kupferman:
Section of Oral and Maxillofacial Surgery, Center for Health Sci- ences, AO-156, 10833 LeConte Avenue, Los Angeles, CA 90095;
e-mail: stevenkupferman@post.harvard.edu
©2008 American Association of Oral and Maxillofacial Surgeons 0278-2391/08/6601-0029$34.00/0
doi:10.1016/j.joms.2006.09.005
KUPFERMAN AND SCHWARTZ
