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Squamous Cell Carcinoma Arising in a Residual Odontogenic Cyst: Case Report
1231
SWINSON, JERJES, AND THOMAS
J Oral Maxillofac Surg 63:1231-1233, 2005
Squamous Cell Carcinoma Arising in a Residual Odontogenic Cyst: Case Report Brian D. Swinson, AFRSC, FDSRCS(Eng),* Waseem Jerjes, BDS, MSc,† and Gareth J. Thomas, BDS, MScD, FDS, PhD‡ Squamous cell carcinoma arising within the lining of a residual odontogenic cyst is a very rare, although recognized, entity. A review of the literature revealed only 22 previous cases proven by histology, with few diagnosed preoperatively. The literature estimates the incidence of malignant change in cysts to be between 0.13% and 2%. It is twice as common in males and 4 times more common in the mandible than in the maxilla. In general, the prognosis is poor, with a tendency to aggressive local and perineural spread rather than lymph node involvement. Clinical features are usually nonspecific, and diagnosis is made radiographically or by histopathology retrospectively. We present a case in which the diagnosis of malignancy was established preoperatively. Rapid radical surgery was instigated with follow-up radiotherapy, but aggressive local and perineural spread, in keeping with the nature of this lesion, ultimately proved overwhelming.
Report of a Case The patient, a 58-year-old woman, was referred having first noticed a swelling near the left angle of the mandible 3 months previously. She reported that there had been a gradual onset of paraesthesia of the left side of the lower lip. Pain had only recently become a feature and was occasionally referred to her left ear. There were no other symptoms nor relevant medical history. On examination, she presented with a firm swelling at the left angle of the mandible measuring approximately 7 *Specialist Registrar, Department of Oral and Maxillofacial Surgery, University College Hospital, London, England. †Clinical Assistant, Department of Oral and Maxillofacial Surgery, University College Hospital, London, England. ‡Specialist Registrar, Oral and Maxollofacial Surgery Unit, Eastman Dental Institute, University College London, London, England. Address correspondence and reprint requests to Dr Swinson: Specialist Registrar in Maxillofacial Surgery, Maxillofacial Department, St Georges Hospital, London, SW17 0QT England; e-mail: [email protected] © 2005 American Association of Oral and Maxillofacial Surgeons
0278-2391/05/6308-0029$30.00/0 doi:10.1016/j.joms.2005.04.016
cm ⫻ 5 cm, the overlying skin being mobile and of normal color. There was profound paraesthesia of the left side of the lower lip. Intraoral examination revealed a moderate buccal and lingual expansion of the edentulous mandibular ridge in the molar region with normal overlying mucosa. The tongue was freely mobile. No cervical lymphadenopathy was detected. An orthopantomograph (Fig 1) showed a region of radiolucency extending from the region of the left mental foramen to the lingula posteriorly. Its upper part had a well-defined cortical margin, whereas the remainder had an ill-defined motheaten appearance. The inferior alveolar canal appeared to be displaced below its normal position at the anterior part of the radiolucency while it was destroyed posteriorly. A chest radiograph was clear. In view of the history, the normal color of the overlying skin, and the radiographic appearance, a provisional diagnosis of malignancy associated with an odontogenic cyst was established and arrangements were made for an incisional biopsy. Under general anesthesia, an extensive incisional biopsy was undertaken. The cystic lesion containing pale browncolored fluid was easily enucleated except toward the lower border of the jaw, where it was found to have involved the neurovascular bundle and infiltrated extensively through the periosteum into the submandibular region. From the lower part of the cyst, a frozen section confirmed the diagnosis of squamous cell carcinoma. The wound was closed and arrangements were made for radical excision. The patient was subsequently admitted for left hemimandibulectomy and a left selective neck dissection. At operation, the tumor was found to involve the inferior alveolar nerve at the lingula, so dissection was undertaken up to the foramen ovale before dividing the nerve. The condylar head was left in situ in the hope of using it in the future reconstructive surgery. Unfortunately, histopathologic examination revealed tumor at both the symphyseal cut and the condylar neck. The proximal limit of the inferior alveolar nerve was also found to be infiltrated. She underwent a further left condylectomy and mandibular resection as far as the right mental foramen region. She made a reasonable recovery from the surgery, but because of the presence of the tumor at foramen ovale, she was referred for radiotherapy. Over the following month, she received a total of 4,600 rad to the primary site and left neck. The response to this was very poor, and the patient was then considered for chemotherapy. However, after the first injection of 15 mg bleomycin, she developed a severe allergic reaction and treatment had to be discontinued. Her condition rapidly deteriorated, and she died from local growth of the tumor, 5 months after the original incisional biopsy operation.
1232
CARCINOMA ARISING IN A RESIDUAL CYST
tended beyond the cyst wall to involve the neurovascular bundle of the inferior alveolar nerve (Fig 2G). The tumor stroma consisted of loose fibroblastic tissue, and there was no evidence of an immune response.
Discussion FIGURE 1. An orthopantomogram showing a large cystic area with uniform cystic lining superiorly but irregular “moth-eaten” appearance of the lower border. Swinson, Jerjes, and Thomas. Carcinoma Arising in a Residual Cyst. J Oral Maxillofac Surg 2005.
HISTOPATHOLOGY
Macroscopically, the opened cyst measured 4 cm ⫻ 2 cm ⫻ 1.5 cm (Fig 2A). The wall was generally thin and soft, but it was thickened inferiorly. Microscopically, the lining of almost the entire upper part of the cyst was stratified squamous nonkeratinizing epithelium, which was in places very thin (Fig 2B), consistent with a residual odontogenic cyst. The lining of the lower part of the cyst showed progressive changes from normal through atypia and fullthickness dysplasia to invasive well-differentiated keratinizing squamous carcinoma (Figs 2B-D). Surface keratinization was seen only where the epithelium was either dysplastic or neoplastic, and suprabasilar clefting was seen in many places. There was extensive infiltration of the cyst wall by moderately differentiated tumor in which keratin formation was prominent (Figs 2E, F). The tumor ex-
Malignant transformation within an odontogenic cyst is a relatively rare occurrence, and the vast majority of tumors are squamous cell carcinomas. Herman documented the first case in 1889,1 and since then there have been several further accounts in the literature. The majority of these tumors appear to arise from the epithelial cyst lining, although the pathogenesis is unclear. Carcinomas have been described in several types of odontogenic cyst, including dentigerous, calcifying odontogenic, lateral periodontal, odontogenic keratocyst, and residual cysts.2-14 Gardner reviewed this literature in 1969 and 197515,16 and found that a number of cases purported to be malignancy arising in an odontogenic cyst were either surface carcinomas that had invaded bone and involved a cyst, or fusion of a cyst with a primary intraosseous carcinoma. He then established widely accepted criteria for squamous cell carcinoma developing within an odontogenic cyst; namely, that they demonstrate: 1. A microscopic transition area from benign cystic epithelial lining to invasive malignant squamous cell carcinoma
FIGURE 2. A, Macroscopic appearance of specimen. B, Low-power view of cyst. Inferiorly the cyst wall was thickened and infiltrated by squamous cell carcinoma (original magnification ⫻10). C, Superiorly the cyst was lined by typical, nonkeratinized stratified squamous epithelium (original magnification ⫻100). D-F, In places the epithelium was dysplastic and islands of squamous cell carcinoma infiltrated the fibrous cyst wall (original magnification ⫻40, ⫻25, and ⫻100, respectively). G, Islands of tumor infiltrated along the inferior alveolar nerve (arrow; original magnification ⫻25). H, Islands of tumor infiltrated mandibular bone (original magnification ⫻25). Swinson, Jerjes, and Thomas. Carcinoma Arising in a Residual Cyst. J Oral Maxillofac Surg 2005.
1233
SWINSON, JERJES, AND THOMAS
2. No carcinomatous changes in the overlying epithelium 3. No source of carcinoma in adjacent structures Gardner suggested that the first point being the only incontrovertible proof of carcinoma arising in an odontogenic cyst, while evidence of communication between the cyst and the oral cavity precludes the diagnosis. Schwimmer et al carried out a review of the literature17 and found 56 cases that strictly adhered to Gardner’s criteria. They showed the mean age at diagnosis to be 57 years, with a 2:1 male-to-female ratio. The mandible was affected 4 times as frequently as the maxilla. In this series, there were 21 cases of carcinoma arising in a residual cyst, which constituted 55% of the cases documented. A current review of the literature in which we examined malignant change in residual cysts revealed a further case in the English literature,18 2 in the Japanese literature,19 and 1 in the Brazilian literature.20 To our knowledge, this is the 23rd case of malignant change within a residual dental cyst in the English literature. Such tumors more commonly affect the mandible and usually present as a rapid, firm, nontender enlargement of the jaw. Most mandibular cases have not been associated with loss of sensation in the lip, which may account for the very low incidence (3 cases) of malignant change being suspected in the differential diagnosis at the initial visit.21 Most cases are then treated by enucleation. However, infiltration of the inferior alveolar nerve may be seen,2,15,22 and in the present case was responsible for the aggressive course of the disease. A commonly cited feature of these carcinomas is the rarity of metastasis to regional lymph nodes.21 The reported cases where metastases have occurred show very poor survival rates. Waldron and Mustoe14 reviewed 36 cases of malignant transformation in odontogenic cysts and reported a 2-year survival rate of 53% if node positive. This study also demonstrated that node-negative cases had a much better prognosis. In most patients, mortality appears to be due to local extension of the malignancy rather than metastatic disease. At present, the preferred treatment would seem to be wide resection and primary reconstruction with a free vascularized bone graft. The need for routine radical neck dissection seems unsupported due to the low frequency of cervical metastasis.3 These tumors are rare and are usually diagnosed pathologically following cyst enucleation. It was unusual that this case demonstrated several presenting features, which allowed a confident provisional diagnosis of malignant change occurring within a cyst. These features included the radiographic appearance of a transition from smooth cyst lining to an ill-defined “moth-eaten” appearance in the bone, the history of
referred otalgia and paraesthesia of the lower lip, and the normal overlying mucosa. Despite the negative cervical node status, this tumor pursued an aggressive course primarily due to extensive perineural spread. This serves to underline the need for an accurate diagnosis based on a careful examination of the radiographic changes and a review of the histologic specimens.
References 1. Herman M: Beitrag zur Entwicklung der Kieferzysten. Erlangan, Germany, Innag Dies, 1889 2. Maxymiw WG, Wood RE: Carcinoma arising in a dentigerous cyst: A case report and review of the literature. J Oral Maxillofac Surg 49:639, 1991 3. Johnson LM, Sapp JP, McIntre DN: Squamous cell carcinoma arising in a dentigerous cyst. J Oral Maxillofac Surg 52:987, 1994 4. Yasuoka T, Yonemoto K, Kato Y, et al: Squamous cell carcinoma in a dentigerous cyst. J Oral Maxillofac Surg 58:900, 2000 5. Norris LH, Baghaei-Rad M, Maloney PL, et al: Bilateral maxillary odontogenic tumours and the malignant transformation of a mandibular radiolucent lesion. J Oral Maxillofac Surg 42:827, 1984 6. Roofe SB, Boyd EM Jr, Houston GD, et al: Squamous cell carcinoma arising in the epithelial lining of a dentigerous cyst. South Med J 92:611, 1999 7. Foley WL, Terry BC, Jacoway JR: Malignant transformation of an odontogenic keratocyst: Report of a case. J Oral Maxillofac Surg 49:768, 1991 8. Anand VK, Arrowood JP Jr, Krolls SO: Malignant potential of the odontogenic keratocyst. Otolaryngol Head Neck Surg 111: 124, 1994 9. Dabbs DJ, Schweitzer RJ, Schweitzer LE, et al: Squamous cell carcinoma arising in recurrent odontogenic keratocyst: Case report and literature review. Head Neck 16:375, 1994 10. Makowski GJ, McGuff S, Van Sickels JE: Squamous cell carcinoma in a maxillary odontogenic keratocyst. J Oral Maxillofac Surg 59:76, 2001 11. Stoelinga PJW, Bronkhorst FB: The incidence, multiple presentation and reoccurrence of aggressive cysts of the jaws. J Craniomaxillofac Surg 16:184, 1987 12. Eversole LR, Sabes WR, Rovin S: Aggressive growth and neoplastic potential of odontogenic cysts. Cancer 35:270, 1975 13. Fanibundea K, Soames JV: Malignant and premalignant change in odontogenic cysts. J Oral Maxillofac Surg 53:1469, 1995 14. Waldron C, Mustoe T: Primary interosseous carcinoma of the mandible with probable origin in an odontogenic cyst. Oral Surg Oral Med Oral Pathol 67:716, 1989 15. Gardner A: A survey of odontogenic cysts and their relationship to squamous cell carcinoma. J Can Dent Assoc 41:161, 1975 16. Gardner A: The odontogenic cyst as a potential carcinoma: A clinicopathologic appraisal. J Am Dent Assoc 78:746, 1969 17. Schwimmer AM, Aydin F, Morrison N: Squamous cell carcinoma arising in residual odontogenic cyst: Report of a case and review of literature. Oral Surg Oral Med Oral Pathol 72:218, 1991 18. van der Wal KGH, de Visscher JGAM, Eggink HF: Squamous cell carcinoma arising in a residual cyst. Int J Oral Maxillofac Surg 22:350, 1993 19. Saito T, Okada H, Akimoto Y, et al: Primary intraosseous carcinoma arising from an odontogenic cyst: A case report and review of the Japanese cases. J Oral Sci 44:49, 2002 20. Olivera JA, Costa IM, Loyde AM: Squamous odontogenic tumour-like proliferation in residual cyst: A case report. Braz Dent J 6:59, 1995 21. Browne R, Gough N: Malignant change in epithelium lining odontogenic cysts. Cancer 29:1199, 1972 22. Lapin R, Garfinkel AV, Catania AF, et al: Squamous cell carcinoma arising in a dentigerous cyst. J Oral Surg 31:354, 1973
SWINSON, JERJES, AND THOMAS
J Oral Maxillofac Surg 63:1231-1233, 2005
Squamous Cell Carcinoma Arising in a Residual Odontogenic Cyst: Case Report Brian D. Swinson, AFRSC, FDSRCS(Eng),* Waseem Jerjes, BDS, MSc,† and Gareth J. Thomas, BDS, MScD, FDS, PhD‡ Squamous cell carcinoma arising within the lining of a residual odontogenic cyst is a very rare, although recognized, entity. A review of the literature revealed only 22 previous cases proven by histology, with few diagnosed preoperatively. The literature estimates the incidence of malignant change in cysts to be between 0.13% and 2%. It is twice as common in males and 4 times more common in the mandible than in the maxilla. In general, the prognosis is poor, with a tendency to aggressive local and perineural spread rather than lymph node involvement. Clinical features are usually nonspecific, and diagnosis is made radiographically or by histopathology retrospectively. We present a case in which the diagnosis of malignancy was established preoperatively. Rapid radical surgery was instigated with follow-up radiotherapy, but aggressive local and perineural spread, in keeping with the nature of this lesion, ultimately proved overwhelming.
Report of a Case The patient, a 58-year-old woman, was referred having first noticed a swelling near the left angle of the mandible 3 months previously. She reported that there had been a gradual onset of paraesthesia of the left side of the lower lip. Pain had only recently become a feature and was occasionally referred to her left ear. There were no other symptoms nor relevant medical history. On examination, she presented with a firm swelling at the left angle of the mandible measuring approximately 7 *Specialist Registrar, Department of Oral and Maxillofacial Surgery, University College Hospital, London, England. †Clinical Assistant, Department of Oral and Maxillofacial Surgery, University College Hospital, London, England. ‡Specialist Registrar, Oral and Maxollofacial Surgery Unit, Eastman Dental Institute, University College London, London, England. Address correspondence and reprint requests to Dr Swinson: Specialist Registrar in Maxillofacial Surgery, Maxillofacial Department, St Georges Hospital, London, SW17 0QT England; e-mail: [email protected] © 2005 American Association of Oral and Maxillofacial Surgeons
0278-2391/05/6308-0029$30.00/0 doi:10.1016/j.joms.2005.04.016
cm ⫻ 5 cm, the overlying skin being mobile and of normal color. There was profound paraesthesia of the left side of the lower lip. Intraoral examination revealed a moderate buccal and lingual expansion of the edentulous mandibular ridge in the molar region with normal overlying mucosa. The tongue was freely mobile. No cervical lymphadenopathy was detected. An orthopantomograph (Fig 1) showed a region of radiolucency extending from the region of the left mental foramen to the lingula posteriorly. Its upper part had a well-defined cortical margin, whereas the remainder had an ill-defined motheaten appearance. The inferior alveolar canal appeared to be displaced below its normal position at the anterior part of the radiolucency while it was destroyed posteriorly. A chest radiograph was clear. In view of the history, the normal color of the overlying skin, and the radiographic appearance, a provisional diagnosis of malignancy associated with an odontogenic cyst was established and arrangements were made for an incisional biopsy. Under general anesthesia, an extensive incisional biopsy was undertaken. The cystic lesion containing pale browncolored fluid was easily enucleated except toward the lower border of the jaw, where it was found to have involved the neurovascular bundle and infiltrated extensively through the periosteum into the submandibular region. From the lower part of the cyst, a frozen section confirmed the diagnosis of squamous cell carcinoma. The wound was closed and arrangements were made for radical excision. The patient was subsequently admitted for left hemimandibulectomy and a left selective neck dissection. At operation, the tumor was found to involve the inferior alveolar nerve at the lingula, so dissection was undertaken up to the foramen ovale before dividing the nerve. The condylar head was left in situ in the hope of using it in the future reconstructive surgery. Unfortunately, histopathologic examination revealed tumor at both the symphyseal cut and the condylar neck. The proximal limit of the inferior alveolar nerve was also found to be infiltrated. She underwent a further left condylectomy and mandibular resection as far as the right mental foramen region. She made a reasonable recovery from the surgery, but because of the presence of the tumor at foramen ovale, she was referred for radiotherapy. Over the following month, she received a total of 4,600 rad to the primary site and left neck. The response to this was very poor, and the patient was then considered for chemotherapy. However, after the first injection of 15 mg bleomycin, she developed a severe allergic reaction and treatment had to be discontinued. Her condition rapidly deteriorated, and she died from local growth of the tumor, 5 months after the original incisional biopsy operation.
1232
CARCINOMA ARISING IN A RESIDUAL CYST
tended beyond the cyst wall to involve the neurovascular bundle of the inferior alveolar nerve (Fig 2G). The tumor stroma consisted of loose fibroblastic tissue, and there was no evidence of an immune response.
Discussion FIGURE 1. An orthopantomogram showing a large cystic area with uniform cystic lining superiorly but irregular “moth-eaten” appearance of the lower border. Swinson, Jerjes, and Thomas. Carcinoma Arising in a Residual Cyst. J Oral Maxillofac Surg 2005.
HISTOPATHOLOGY
Macroscopically, the opened cyst measured 4 cm ⫻ 2 cm ⫻ 1.5 cm (Fig 2A). The wall was generally thin and soft, but it was thickened inferiorly. Microscopically, the lining of almost the entire upper part of the cyst was stratified squamous nonkeratinizing epithelium, which was in places very thin (Fig 2B), consistent with a residual odontogenic cyst. The lining of the lower part of the cyst showed progressive changes from normal through atypia and fullthickness dysplasia to invasive well-differentiated keratinizing squamous carcinoma (Figs 2B-D). Surface keratinization was seen only where the epithelium was either dysplastic or neoplastic, and suprabasilar clefting was seen in many places. There was extensive infiltration of the cyst wall by moderately differentiated tumor in which keratin formation was prominent (Figs 2E, F). The tumor ex-
Malignant transformation within an odontogenic cyst is a relatively rare occurrence, and the vast majority of tumors are squamous cell carcinomas. Herman documented the first case in 1889,1 and since then there have been several further accounts in the literature. The majority of these tumors appear to arise from the epithelial cyst lining, although the pathogenesis is unclear. Carcinomas have been described in several types of odontogenic cyst, including dentigerous, calcifying odontogenic, lateral periodontal, odontogenic keratocyst, and residual cysts.2-14 Gardner reviewed this literature in 1969 and 197515,16 and found that a number of cases purported to be malignancy arising in an odontogenic cyst were either surface carcinomas that had invaded bone and involved a cyst, or fusion of a cyst with a primary intraosseous carcinoma. He then established widely accepted criteria for squamous cell carcinoma developing within an odontogenic cyst; namely, that they demonstrate: 1. A microscopic transition area from benign cystic epithelial lining to invasive malignant squamous cell carcinoma
FIGURE 2. A, Macroscopic appearance of specimen. B, Low-power view of cyst. Inferiorly the cyst wall was thickened and infiltrated by squamous cell carcinoma (original magnification ⫻10). C, Superiorly the cyst was lined by typical, nonkeratinized stratified squamous epithelium (original magnification ⫻100). D-F, In places the epithelium was dysplastic and islands of squamous cell carcinoma infiltrated the fibrous cyst wall (original magnification ⫻40, ⫻25, and ⫻100, respectively). G, Islands of tumor infiltrated along the inferior alveolar nerve (arrow; original magnification ⫻25). H, Islands of tumor infiltrated mandibular bone (original magnification ⫻25). Swinson, Jerjes, and Thomas. Carcinoma Arising in a Residual Cyst. J Oral Maxillofac Surg 2005.
1233
SWINSON, JERJES, AND THOMAS
2. No carcinomatous changes in the overlying epithelium 3. No source of carcinoma in adjacent structures Gardner suggested that the first point being the only incontrovertible proof of carcinoma arising in an odontogenic cyst, while evidence of communication between the cyst and the oral cavity precludes the diagnosis. Schwimmer et al carried out a review of the literature17 and found 56 cases that strictly adhered to Gardner’s criteria. They showed the mean age at diagnosis to be 57 years, with a 2:1 male-to-female ratio. The mandible was affected 4 times as frequently as the maxilla. In this series, there were 21 cases of carcinoma arising in a residual cyst, which constituted 55% of the cases documented. A current review of the literature in which we examined malignant change in residual cysts revealed a further case in the English literature,18 2 in the Japanese literature,19 and 1 in the Brazilian literature.20 To our knowledge, this is the 23rd case of malignant change within a residual dental cyst in the English literature. Such tumors more commonly affect the mandible and usually present as a rapid, firm, nontender enlargement of the jaw. Most mandibular cases have not been associated with loss of sensation in the lip, which may account for the very low incidence (3 cases) of malignant change being suspected in the differential diagnosis at the initial visit.21 Most cases are then treated by enucleation. However, infiltration of the inferior alveolar nerve may be seen,2,15,22 and in the present case was responsible for the aggressive course of the disease. A commonly cited feature of these carcinomas is the rarity of metastasis to regional lymph nodes.21 The reported cases where metastases have occurred show very poor survival rates. Waldron and Mustoe14 reviewed 36 cases of malignant transformation in odontogenic cysts and reported a 2-year survival rate of 53% if node positive. This study also demonstrated that node-negative cases had a much better prognosis. In most patients, mortality appears to be due to local extension of the malignancy rather than metastatic disease. At present, the preferred treatment would seem to be wide resection and primary reconstruction with a free vascularized bone graft. The need for routine radical neck dissection seems unsupported due to the low frequency of cervical metastasis.3 These tumors are rare and are usually diagnosed pathologically following cyst enucleation. It was unusual that this case demonstrated several presenting features, which allowed a confident provisional diagnosis of malignant change occurring within a cyst. These features included the radiographic appearance of a transition from smooth cyst lining to an ill-defined “moth-eaten” appearance in the bone, the history of
referred otalgia and paraesthesia of the lower lip, and the normal overlying mucosa. Despite the negative cervical node status, this tumor pursued an aggressive course primarily due to extensive perineural spread. This serves to underline the need for an accurate diagnosis based on a careful examination of the radiographic changes and a review of the histologic specimens.
References 1. Herman M: Beitrag zur Entwicklung der Kieferzysten. Erlangan, Germany, Innag Dies, 1889 2. Maxymiw WG, Wood RE: Carcinoma arising in a dentigerous cyst: A case report and review of the literature. J Oral Maxillofac Surg 49:639, 1991 3. Johnson LM, Sapp JP, McIntre DN: Squamous cell carcinoma arising in a dentigerous cyst. J Oral Maxillofac Surg 52:987, 1994 4. Yasuoka T, Yonemoto K, Kato Y, et al: Squamous cell carcinoma in a dentigerous cyst. J Oral Maxillofac Surg 58:900, 2000 5. Norris LH, Baghaei-Rad M, Maloney PL, et al: Bilateral maxillary odontogenic tumours and the malignant transformation of a mandibular radiolucent lesion. J Oral Maxillofac Surg 42:827, 1984 6. Roofe SB, Boyd EM Jr, Houston GD, et al: Squamous cell carcinoma arising in the epithelial lining of a dentigerous cyst. South Med J 92:611, 1999 7. Foley WL, Terry BC, Jacoway JR: Malignant transformation of an odontogenic keratocyst: Report of a case. J Oral Maxillofac Surg 49:768, 1991 8. Anand VK, Arrowood JP Jr, Krolls SO: Malignant potential of the odontogenic keratocyst. Otolaryngol Head Neck Surg 111: 124, 1994 9. Dabbs DJ, Schweitzer RJ, Schweitzer LE, et al: Squamous cell carcinoma arising in recurrent odontogenic keratocyst: Case report and literature review. Head Neck 16:375, 1994 10. Makowski GJ, McGuff S, Van Sickels JE: Squamous cell carcinoma in a maxillary odontogenic keratocyst. J Oral Maxillofac Surg 59:76, 2001 11. Stoelinga PJW, Bronkhorst FB: The incidence, multiple presentation and reoccurrence of aggressive cysts of the jaws. J Craniomaxillofac Surg 16:184, 1987 12. Eversole LR, Sabes WR, Rovin S: Aggressive growth and neoplastic potential of odontogenic cysts. Cancer 35:270, 1975 13. Fanibundea K, Soames JV: Malignant and premalignant change in odontogenic cysts. J Oral Maxillofac Surg 53:1469, 1995 14. Waldron C, Mustoe T: Primary interosseous carcinoma of the mandible with probable origin in an odontogenic cyst. Oral Surg Oral Med Oral Pathol 67:716, 1989 15. Gardner A: A survey of odontogenic cysts and their relationship to squamous cell carcinoma. J Can Dent Assoc 41:161, 1975 16. Gardner A: The odontogenic cyst as a potential carcinoma: A clinicopathologic appraisal. J Am Dent Assoc 78:746, 1969 17. Schwimmer AM, Aydin F, Morrison N: Squamous cell carcinoma arising in residual odontogenic cyst: Report of a case and review of literature. Oral Surg Oral Med Oral Pathol 72:218, 1991 18. van der Wal KGH, de Visscher JGAM, Eggink HF: Squamous cell carcinoma arising in a residual cyst. Int J Oral Maxillofac Surg 22:350, 1993 19. Saito T, Okada H, Akimoto Y, et al: Primary intraosseous carcinoma arising from an odontogenic cyst: A case report and review of the Japanese cases. J Oral Sci 44:49, 2002 20. Olivera JA, Costa IM, Loyde AM: Squamous odontogenic tumour-like proliferation in residual cyst: A case report. Braz Dent J 6:59, 1995 21. Browne R, Gough N: Malignant change in epithelium lining odontogenic cysts. Cancer 29:1199, 1972 22. Lapin R, Garfinkel AV, Catania AF, et al: Squamous cell carcinoma arising in a dentigerous cyst. J Oral Surg 31:354, 1973