J Oral Maxillofac 50:66-71,
Surg
1992
Squamous Cell Carcinoma of the Oral Cavity After irradiation for Nonmalignant Lesions: Report of Four Cases HITOSHI
SHIBUYA,
MD,* MINORU TAKAGI, DDS,t MASANOBU AND SHIGEAKI SHIOIRI, DDS§
Radiation therapy in childhood is well known to be associated with the development of a secondary benign or malignant tumors, as well as the inhibition of normal developmental body growth. The incidence of development of a second tumor after radiotherapy for malignant disease in childhood is reported to be as high as 12% by the age of 20 years, an incidence 20 times that of the normal population.’ With the increased awareness of radiation-induced cancer, irradiation treatment for benign diseases of childhood is now avoided and increased protection against radiation is now standard in clinical practice. A marked decrease in incidence, therefore, is expected.* However, radiation-induced cancers are still seen in patients previously irradiated during their childhood or adolescence. Postirradiation sarcoma and skin, hypopharynx, and thyroid cancers have been reported; however, there are few reports of oral squamous cell carcinoma occurring after irradiation for benign head and neck lesions.3-5 We report four cases of squamous cell carcinoma of the mouth that developed 24 to 52 years after irradiation for benign lesions. Three of these four patients had been treated by combined orthovoltage x-ray irradiation and brachytherapy.
KITAGAWA,
MD,*
mycosis was diagnosed and intermittent orthovoltage x-ray (200 kV) irradiation was given from February 1952 to June 1953, with a total dose of approximately 14,700 R in 52 fractions over a period of 1 year and 4 months. In March 1956, partial mandibulectomy and skin graft was performed for osteoradionecrosis (Fig 1). In January 1976, the patient noticed a tumorous swelling in the right retromolar region (T2NOMO). Biopsy showed keratinizing squamous cell carcinoma and tumor resection was performed. In April 1976, the tumor recurred and was treated by external irradiation with 12 MeV betatron (20 Gy/ 10 fractions/ 14 d) and simultaneous intramuscular bleo-
Report of Cases Case I This male patient first noticed swelling, induration, pain of the right buccal region, and stiffness of the right mandibular joint in February 1951, when he was 22 years old. Actino-
Received from Tokyo Medical and Dental University. * Assistant Professor, Department of Radiology. t Professor, Department of Pathology. $ Assistant, Department of Pathology. 5 Lecturer, Department of Maxillofacial Surgery. Address correspondence and reprint requests to Dr Shibuya: Department of Radiology, Tokyo Medical and Dental University, S45, Yushima I-chome, Bunkyo-ku, Tokyo 113, Japan. 0 1992 American
Association
of Oral and Maxillofacial
Surgeons
FIGURE 1. CaseI. Large ulcer with exposure of necrotic bone 4 years after x-ray irradiation.
0278-2391/92/5001-0015$3.00/O
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SHIBUYA
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ET AL
FIGURE 2. Case 2. Multiple 222Rn seeds remaining in the buccal region.
mycin 50 mg in 10 fractions. The tumor was well controlled; however. the patient died in January I980 from local necrosis and pulmonary infection.
Case ,7 This male patient was born in 1937 with bilateral hemangioma of the upper and lower jaws and neck that was treated by intermittent external radium y-ray irradiation from 1938 to 1943. Intermittent orthovoltage x-ray (200 kV) therapy was performed from 1949 to 1950. The cumulative dosage of external irradiation was not accurately known, but was estimated to be greater than 8,000 R. Radon Rn 222 seed implantation (40 mCi) was performed in several fractions (approximately 50 Gy for the buccal region) from 1959 to 1960 (Fig 2). In 1962, osteoradionecrosis developed and a sequestrum in the left mandible was excised. In March 1987, the patient noted a tumor of the right lateral border of the tongue, which was diagnosed by biopsy as squamous cell carcinoma T3NOMO (Fig 3). The tumor was treated with intra-arterial perfusion of CDDP 390 mg and methotrexate 250 mg in July, and external cobalt irradiation 54 Gy in 27 fractions from July to August 1987. In January 1988, the right external carotid artery was ligated because of continuing intraoral bleeding. In April 1988, pulmonary metastases were detected, and the patient died of multiple metastases in February 1989. At the time of autopsy, a tumor of more than 20 cm showing contiguous invasion of the tongue, gingiva, mandible, floor of the mouth, palate, upper lip, pharynx, larynx, cervical soft tissue, and trachea was found. Microscopic examination showed that most of the bulky tumor in the mouth and neck consisted of spindle cell carcinoma, and keratinizing squamous cell carcinoma was observed only in the portion of tumor invading the trachea (Figs 4. 5). Multiple, large, metastatic foci in the lung and pleura consisted of both spindle cell carcinoma and squamous cell carcinoma, with a predominance of the spindle cell pattern. In the thyroid, a 2-
cm-sized tumor was incidentally found at autopsy. which microscopically showed papillary adenocarcinoma, and metastases to the cervical lymph nodes were identified (Fig 6). Venous hemangioma was seen in the submucosa, dermis. and subcutaneous tissue of the upper lip. face, and neck.
FIGURE 3. Cuss 2. Keratinizing squamous cell tongue (hematoxylin-eosin
carcinoma
stain. original magnification
X4?).
of the
68
RADIATION-INDUCED
CANCER OF THE ORAL CAVITY
FIGURE 4. Case 2. Spindle cell carcinoma seen in the recurrent tumor at autopsy (hematoxylin-eosin stain, original magnification x 170).
FIGURE 6. Case 2. Papillary adenocarcinoma metastasis in a cervical lymph node (hematoxylin-eosin stain, original magnification X42).
Case 3
Case 4
This male patient presented for treatment of a hemangioma of the left buccal area measuring 20 X 15 cm (Fig 7) in 196 1,
This female patient was born in 1937 with hemangioma of the right cheek and maxilla. In 1938, she was treated with radium cone irradiation at another hospital. Radiotherapy was commenced at our hospital in May 1954. Modality and doses were as follows: cobalt 60 mould therapy 1,500 R in 1954, cobalt 60 mould therapy 1,500 R in 1955, 170 kV xray 1,500 R in 1960, cobalt 60 mould therapy 1,500 R in
when he was 17 years old. ***Rn seed inplantation (53 mCi) was performed in six fractions from November 1959 to August 1961 (approximately 40 to 50 Gy for buccal hemangioma) (Fig 8). External orthovoltage x-ray therapy (200 kV) with a total dose of 2,150 R was performed in 196 1. Partial resection of the hemangioma was performed at another hospital. In January 1987, a 5 X 3.5-cm ulcerating lesion developed in the buccal mucosa (T3NOMO) and a diagnosis of squamous cell carcinoma, coexisting with the remaining hemangioma, was made. The patient was treated with combined external radiotherapy and intra-arterial infusion of 5-fluorouracil(5FU). A total dose of 48 Gy of telecobalt and 6,000 mg of 5FU was given over 71 days. In January 1988, pulmonary metastases developed and he died of generalized bone and pulmonary metastases in March 1988.
FIGURE 5. &se 2. Transition zone between spindle cell carcinoma and squamous cell carcinoma (hematoxylin-eosin stain, original magnification X 170).
FIGURE 7.
Case 3. Large hemangioma in the left buccal region.
SHIBUYA ET AL
69
FIGURE 8. Case 3. Multiple ***Rn seeds remaining in the left buccal region.
196 1, 200 kV x-ray 4,000 R in 196 I,60 kV x-ray tube 5,950 R in 1966, intra-arterial infusion of 5-FU 2,718 mg over 16 days in 1974. In May 1990, a tumor developed in the irradiated portion of the right buccal mucosa (T 1NOMO). It was diagnosed microscopically as squamous cell carcinoma. The carcinoma was treated with Au 198 grain with a dose of 76 Gy. It healed without any complications and the patient now is under observation. Microscopically, the squamous cell carcinoma was moderately differentiated, and epithelial dysplasia was observed in the oral mucosa adjacent to the carcinoma (Fig 9).
Discussion Radiation-induced solid tumors usually have a latent period of at least 10 years and often longer, and their
FIGURE 9. Case 4. Atypical epithelium adjacent to cancer tissue (hematoxylin-eosin stain, original magnification X67).
incidence directly increases with the dose of radiation and the time since treatment.2,6‘9 The latent period is longer after larger doses of irradiation, and inversely related to the radiation dose. lo The radiation-related cancer rate in exposed tissues has been estimated to be 1.8 cases per million personyears per rad. ” In another report, the dose-effect relationship between epithelial cancers and radiation for the exposed skin was shown to be 40 carcinomas/ lo4 persons/ Gy for a median follow-up period of 4 1 years2 The patient’s age at the time of irradiation also may affect the latent period; the older the age at irradiation, the shorter the latent period.” There has been conjecture as to whether radiationinduced cancer is more common following orthovoltage than megavoltage irradiation.‘3.‘4 Megavoltage radiotherapy with improved dose characteristics has been discussed with respect to its diminished frequency of development of new neoplasms in irradiated tissues. ’ Most radiation-induced skin cancers are basal cell carcinoma, with a small percentage of squamous cell carcinoma.2 A striking increase in the risk of developing brain, parotid, and thyroid tumors has been reported after scalp irradiation.3 Among the cancers of the head and neck that developed in atomic bomb survivors, a suggestive relationship to radiation dose was found for accessory sinus cancers, but the increase in incidence could not be definitively concluded to be the result of atomic bomb radiation.15 Bergstroem et al found that in more than 1,500 patients who were irradiated for cervical adenitis during childhood, 32 patients developed malignant tumors,
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RADIATION-INDUCED
including 12 skin tumors, 5 oral cavity tumors, and one patient with both thyroid carcinoma and basal cell carcinoma.16 In five patients, development of squamous cell carcinoma in the areas irradiated for laryngeal carcinoma was reported 7 to 12 years after successful therapeutic irradiation.” The predominant histologic types of radiation-induced sarcoma are fibrosarcoma, osteosarcoma, and malignant fibrous histiocytoma.4*‘0.‘8~19Development of bone sarcoma as a second malignant neoplasm in children was found to be influenced by radiation and genetic predisposition. *’ The potential risk of development of thyroid cancer after radiation exposure is a major factor in radiation-induced cancer.21-23The child and adult population exposed to radiation at Hiroshima and Nagasaki have a high incidence of thyroid carcinoma.24,25 Hempelman et al reported that in 2,900 persons who received x-ray therapy during infancy, 19 developed thyroid cancer and 22 developed thyroid adenomas.’ Cerletty et al found 34 cases of thyroid carcinoma in 1,825 subjects with a history of head and neck irradiation, including 17 papillary, 10 mixed papillary-follicular, 6 follicular, and 1 medullary mixed carcinoma.26 Diagnosis of our four cases of radiation-induced cancer was made according to the criteria used for the diagnosis of radiation-induced osteosarcoma.” These four patients received radiation treatment for hemangioma or actinomycosis of the oral cavity during early childhood or adolescence. All cases were proven squamous cell carcinoma with histologic features quite different from the original benign lesion. The minimum latent period was 24 years (mean, 38 years), an extremely long latency compared to other reported cases. The lowest cumulative radiation dose was 60 Gy in one patient treated by combined orthovoltage x-ray therapy and brachytherapy. However, in this case, the doses administered close to the small source were of course greater than 100 Gy. Long-term low-dose irradiation whose accumulated sum is equal to a larger dose may also be related to carcinogenesis in these cases. A higher risk of development of malignant tumors has been reported following combined radiation therapy and chemotherapy, especially in the treatment of Hodgkin’s disease. 28 In our cases, only one patient had a history of intra-arterial infusion of 5-F’U. Two had a history of radiation osteonecrosis and excision of a sequestrum. Continuous chronic inflammation due to radiation ulcer and osteonecrosis was evident in these two cases. Management of radiation-induced cancer includes surgery and radiotherapy, depending on the site and extent of tumor involvement. Two cases were controlled by radiation, although one later died of radiotherapy complications. One of the four patients is still alive and well with no complications. In view of late
radiation effects, x-ray irradiation of benign skin lesions is contraindicated, especially in view of the evidence that treatment with low doses of radiation given over a long period has a high risk of carcinogenesis.’ There is, of course, a small possibility that these cases represent spontaneously occurring cancers rather than radiation-induced cancers. However, the incidence of spontaneously occurring cancer is extremely low; the incidence of oral cancer is approximately one in 33,000 persons per year in Japan. 29No obvious histologic differences are known to exist between spontaneous and radiation-induced carcinoma; however, one case showed transformation to a spindle cell carcinoma after radiation treatment. The occurrence of squamous cell carcinoma in patients treated with radiotherapy for benign lesions may suggest that radiation-induced cancers should be included in the “recurrent cancer” category because they develop long after the radiation treatment for squamous cell carcinoma of the oral cavity.
CANCER OF THE ORAL C‘AVITY
References I. Li FP: Second malignant tumors after cancer in childhood. Cancer 40:1899, 1977 2. van Vloten WA, Hermans J, van Daal WAJ: Radiation-induced skin cancer and radiodermatitis of the head and neck. Cancer 59:41 I, 1987 3. Modan B, Baidatz D, Mart H, et al: Radiation induced head and neck tumors. Lancet 1:277, 1974 4. Coia LR. Fazekas JT. Kramer S: Postirradiation sarcoma of the head and neck: A report of three late sarcomas following therapeutic irradiation for primary malignancies of the paranasal sinus, nasal cavity, and larynx. Cancer 46: 1982, 1980 5. Ward CM, Buchanan R: Hemangiosarcoma following irradiation of a hemangioma of the face. J Maxillofac Surg 5: 164, 1977 6. Martin H, Strong E, Spiro RH: Radiation-induced skin cancer of the head and neck. Cancer 2561, 1970 7. Hempelmann LH, Hall WJ, Phillips M, et al: Neoplasms in persons treated with X-rays in infancy: Fourth survey in 20 years. JNCI 55:5 19, 1975 8. Hutchison GB: Late neoplastic changes following medical irradiation. Cancer 37:1102, 1976 9. Shore RE, Albert RE, Pastemack BS: Follow-up study of patients treated by x-ray epilation for tinea capitis. Arch Environ Health 31:17. 1976 10. Kim JH. Chu FC. Woodard HQ, et al: Radiation-induced soft tissue and bone sarcoma. Radiology 129501, 1978 11. Li FP, Cassady JR, Jaffe N: Risk of second tumors in survivors of childhood cancer. Cancer 35:1230, 1975 12. Nishimura Y. Sakai K. Kitamura T. et al: Radiation-induced cancers following radiotherapy for benign diseases: The second mail survey in Japan. Jpn J Cancer Chemother 13:1492, 1986 13. Hatfield PM, Shulz MD: Post-irradiation sarcoma. Radiology 96:593, 1970 14. Steeves RA, Bataini J-P: Neoplasms induced by megavoltage radiation in the head and neck region. Cancerb7: 1770, 1981 15. Pinkston JA. Wakabavashi T. Yamamoto T. et al: Cancer of the head and neck in atomic bomb survivors:‘Hiroshima and Nagasaki, 1957-1976. Cancer 48:2172, 1981 16. Bergstroem B, Fogh A, Ranudd NE: Late complications after irradiation treatment for cervical adenitis in childhood. Acta Dtolaryngol (Stockh) lOO:lSl, 1985 17. Schindel J, Castoriano IM: Late-appearing (radiation-induced) carcinoma. Arch Otolaryngol 95205, 1972 18. Arlen M, Higinbotham NL, Huvos AG, et al: Radiation-induced sarcoma of bone. Cancer 28: 1087, 197 1
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19. Souba WW, McKenna RJ, Meis J, et al: Radiation-induced sarcomas of the chest wall. Cancer 57:610, 1986 20. Sagerman RH, Cassady JR, Tretter P, et al: Radiation-induced neoplasia following external beam therapy in children with retinoblastoma. Am J Roentgenol 105529, 1969 2 I. Favus MJ, Schneider AB, Strachura ME, et al: Thyroid cancer occuring as a late consequence of head and neck irradiation: Evaluation of 1056 patients. New Engl J Med 294:1019,1976 22. Janower ML, Miettinen OS: Neoplasms after childhood irradiation of the thymus gland. JAMA 2 15:753, 197 1 23. Scanlon EF, Sener SF: Head and neck neoplasia following irradiation for benign conditions. Head Neck Surg 4: 139, 198 1 24. Sampson RJ, Key CR, Buncher CR, et al: Thyroid carcinoma in Hiroshima and Nagasaki. I Prevalence of thyroid carcinoma at autopsy. JAMA 209:65, 1969
J Oral Maxillofac 50:71-75,
25. Parker LN, Belsky JL, Yamamoto T, et al: Thyroid carcinoma after exposure to atomic radiation. A continuing survey of a fixed population, Hiroshima and Nagasaki, 1958- 197 1. Ann Intern Med 80:600, 1974 26. Cerletty JM, Guansing AR, Engbring NH, et al: Radiation-related thyroid carcinoma. Arch Surg 113:1072. I978 27. Cahan WG, Woodward HG, Higinbotham NL, et al: Sarcoma arising in irradiated bone: Report of eleven cases. Cancer I: 3, 1948 28. Cannelos GP, Arsenau JC, Devita VT, et al: Second malignancies complicating Hodgkin’s disease in remission. Lancet 1:947, 1975 29. Fujimoto I: The report of the research group for population based cancer registration in Japan. Osaka Adult Disease Center, 1988
Surg
1992
Hydroxylapatite Block Closure of Oroantral Fistulas: Report of Cases MICHAEL
F. ZIDE, DDS,* AND NESTOR
An oroantral communication may challenge the surgeon who wishes to obtain a permanent closure and prevent sinus disease. Long-term successful closure of the oroantral fistula depends on the acuteness of the problem, absence of sinus disease, size and location of the defect, and the amount and condition of the adjacent tissue. The literature has shown that openings greater than 5 mm in diameter have a substantially decreased chance of spontaneous primary closure.‘32 Treatment includes the use of local or distant tissue flaps and interpositional autogenous grafts or alloplastic implants. Local flaps use tissue from either the buccal vestibule or palate. When buccal tissue is advanced over the fistula, which is the commonest closure method, a decrease in vestibular depth may occur with a loss of attached gingiva after healing. Several types of palatal flaps have been described for closure; however, all require secondary granulation of denuded tissue and temporarily limit the patient’s ability to wear * Associate Director. Department of Oral and Maxillofacial Surgery. John Peter Smith Hospital, Fort Worth. TX. t Resident, Department of Oral and Maxillofacial Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Address correspondence and reprint requests to Dr Zide: Department ofOral and Maxillofacial Surgery, John Peter Smith Hospital, 1625 St Louis St, Ft Worth, TX 76104. 8 1992
American
Association
0278-2391/92/5001-0016$3.00/O
of Oral and Maxillofacial
Surgeons
D. KARAS,
DDSt
a prosthesis. In addition, it is difficult for palatal flaps to reach the lateral alveolus. Several double-layer closure flap techniques using buccal and palatal tissues have been suggested, but these procedures produce larger denuded areas and an increased time is required to raise these flaps. Tissue taken from either the tongue or buccal mucosa have also been used, but these procedures usually require a general anesthetic and there is increased donor site morbidity. Obturating of fistulas has involved both autogenous grafts and alloplastic implants. Bone grafts from the iliac crest and cranium have been used in patients with large defects and those previously treated unsuccessfully with soft tissue closure. 3-5 Concern about donor site morbidity and hospitalization suggests use of this method only for large defects. Alloplastic materials that have been used for the closure of oroantral fistulas include gold foil, gold plate, tantalum plate, soft polymethylmethacrylate, and lyophilized collagen. The advantages of alloplastic materials are simplicity of use and prevention of breakdown, which may occur with soft tissue alone. Dense hydroxylapatite (HA) provides the surgeon with an inert material capable of exposure to the oral cavity without deleterious effects. For the past year, we have used HA blocks to close both acute and chronic oroantral fistulas. The technique appears to have some major advantages over current techniques.
Surg
1992
Squamous Cell Carcinoma of the Oral Cavity After irradiation for Nonmalignant Lesions: Report of Four Cases HITOSHI
SHIBUYA,
MD,* MINORU TAKAGI, DDS,t MASANOBU AND SHIGEAKI SHIOIRI, DDS§
Radiation therapy in childhood is well known to be associated with the development of a secondary benign or malignant tumors, as well as the inhibition of normal developmental body growth. The incidence of development of a second tumor after radiotherapy for malignant disease in childhood is reported to be as high as 12% by the age of 20 years, an incidence 20 times that of the normal population.’ With the increased awareness of radiation-induced cancer, irradiation treatment for benign diseases of childhood is now avoided and increased protection against radiation is now standard in clinical practice. A marked decrease in incidence, therefore, is expected.* However, radiation-induced cancers are still seen in patients previously irradiated during their childhood or adolescence. Postirradiation sarcoma and skin, hypopharynx, and thyroid cancers have been reported; however, there are few reports of oral squamous cell carcinoma occurring after irradiation for benign head and neck lesions.3-5 We report four cases of squamous cell carcinoma of the mouth that developed 24 to 52 years after irradiation for benign lesions. Three of these four patients had been treated by combined orthovoltage x-ray irradiation and brachytherapy.
KITAGAWA,
MD,*
mycosis was diagnosed and intermittent orthovoltage x-ray (200 kV) irradiation was given from February 1952 to June 1953, with a total dose of approximately 14,700 R in 52 fractions over a period of 1 year and 4 months. In March 1956, partial mandibulectomy and skin graft was performed for osteoradionecrosis (Fig 1). In January 1976, the patient noticed a tumorous swelling in the right retromolar region (T2NOMO). Biopsy showed keratinizing squamous cell carcinoma and tumor resection was performed. In April 1976, the tumor recurred and was treated by external irradiation with 12 MeV betatron (20 Gy/ 10 fractions/ 14 d) and simultaneous intramuscular bleo-
Report of Cases Case I This male patient first noticed swelling, induration, pain of the right buccal region, and stiffness of the right mandibular joint in February 1951, when he was 22 years old. Actino-
Received from Tokyo Medical and Dental University. * Assistant Professor, Department of Radiology. t Professor, Department of Pathology. $ Assistant, Department of Pathology. 5 Lecturer, Department of Maxillofacial Surgery. Address correspondence and reprint requests to Dr Shibuya: Department of Radiology, Tokyo Medical and Dental University, S45, Yushima I-chome, Bunkyo-ku, Tokyo 113, Japan. 0 1992 American
Association
of Oral and Maxillofacial
Surgeons
FIGURE 1. CaseI. Large ulcer with exposure of necrotic bone 4 years after x-ray irradiation.
0278-2391/92/5001-0015$3.00/O
66
SHIBUYA
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ET AL
FIGURE 2. Case 2. Multiple 222Rn seeds remaining in the buccal region.
mycin 50 mg in 10 fractions. The tumor was well controlled; however. the patient died in January I980 from local necrosis and pulmonary infection.
Case ,7 This male patient was born in 1937 with bilateral hemangioma of the upper and lower jaws and neck that was treated by intermittent external radium y-ray irradiation from 1938 to 1943. Intermittent orthovoltage x-ray (200 kV) therapy was performed from 1949 to 1950. The cumulative dosage of external irradiation was not accurately known, but was estimated to be greater than 8,000 R. Radon Rn 222 seed implantation (40 mCi) was performed in several fractions (approximately 50 Gy for the buccal region) from 1959 to 1960 (Fig 2). In 1962, osteoradionecrosis developed and a sequestrum in the left mandible was excised. In March 1987, the patient noted a tumor of the right lateral border of the tongue, which was diagnosed by biopsy as squamous cell carcinoma T3NOMO (Fig 3). The tumor was treated with intra-arterial perfusion of CDDP 390 mg and methotrexate 250 mg in July, and external cobalt irradiation 54 Gy in 27 fractions from July to August 1987. In January 1988, the right external carotid artery was ligated because of continuing intraoral bleeding. In April 1988, pulmonary metastases were detected, and the patient died of multiple metastases in February 1989. At the time of autopsy, a tumor of more than 20 cm showing contiguous invasion of the tongue, gingiva, mandible, floor of the mouth, palate, upper lip, pharynx, larynx, cervical soft tissue, and trachea was found. Microscopic examination showed that most of the bulky tumor in the mouth and neck consisted of spindle cell carcinoma, and keratinizing squamous cell carcinoma was observed only in the portion of tumor invading the trachea (Figs 4. 5). Multiple, large, metastatic foci in the lung and pleura consisted of both spindle cell carcinoma and squamous cell carcinoma, with a predominance of the spindle cell pattern. In the thyroid, a 2-
cm-sized tumor was incidentally found at autopsy. which microscopically showed papillary adenocarcinoma, and metastases to the cervical lymph nodes were identified (Fig 6). Venous hemangioma was seen in the submucosa, dermis. and subcutaneous tissue of the upper lip. face, and neck.
FIGURE 3. Cuss 2. Keratinizing squamous cell tongue (hematoxylin-eosin
carcinoma
stain. original magnification
X4?).
of the
68
RADIATION-INDUCED
CANCER OF THE ORAL CAVITY
FIGURE 4. Case 2. Spindle cell carcinoma seen in the recurrent tumor at autopsy (hematoxylin-eosin stain, original magnification x 170).
FIGURE 6. Case 2. Papillary adenocarcinoma metastasis in a cervical lymph node (hematoxylin-eosin stain, original magnification X42).
Case 3
Case 4
This male patient presented for treatment of a hemangioma of the left buccal area measuring 20 X 15 cm (Fig 7) in 196 1,
This female patient was born in 1937 with hemangioma of the right cheek and maxilla. In 1938, she was treated with radium cone irradiation at another hospital. Radiotherapy was commenced at our hospital in May 1954. Modality and doses were as follows: cobalt 60 mould therapy 1,500 R in 1954, cobalt 60 mould therapy 1,500 R in 1955, 170 kV xray 1,500 R in 1960, cobalt 60 mould therapy 1,500 R in
when he was 17 years old. ***Rn seed inplantation (53 mCi) was performed in six fractions from November 1959 to August 1961 (approximately 40 to 50 Gy for buccal hemangioma) (Fig 8). External orthovoltage x-ray therapy (200 kV) with a total dose of 2,150 R was performed in 196 1. Partial resection of the hemangioma was performed at another hospital. In January 1987, a 5 X 3.5-cm ulcerating lesion developed in the buccal mucosa (T3NOMO) and a diagnosis of squamous cell carcinoma, coexisting with the remaining hemangioma, was made. The patient was treated with combined external radiotherapy and intra-arterial infusion of 5-fluorouracil(5FU). A total dose of 48 Gy of telecobalt and 6,000 mg of 5FU was given over 71 days. In January 1988, pulmonary metastases developed and he died of generalized bone and pulmonary metastases in March 1988.
FIGURE 5. &se 2. Transition zone between spindle cell carcinoma and squamous cell carcinoma (hematoxylin-eosin stain, original magnification X 170).
FIGURE 7.
Case 3. Large hemangioma in the left buccal region.
SHIBUYA ET AL
69
FIGURE 8. Case 3. Multiple ***Rn seeds remaining in the left buccal region.
196 1, 200 kV x-ray 4,000 R in 196 I,60 kV x-ray tube 5,950 R in 1966, intra-arterial infusion of 5-FU 2,718 mg over 16 days in 1974. In May 1990, a tumor developed in the irradiated portion of the right buccal mucosa (T 1NOMO). It was diagnosed microscopically as squamous cell carcinoma. The carcinoma was treated with Au 198 grain with a dose of 76 Gy. It healed without any complications and the patient now is under observation. Microscopically, the squamous cell carcinoma was moderately differentiated, and epithelial dysplasia was observed in the oral mucosa adjacent to the carcinoma (Fig 9).
Discussion Radiation-induced solid tumors usually have a latent period of at least 10 years and often longer, and their
FIGURE 9. Case 4. Atypical epithelium adjacent to cancer tissue (hematoxylin-eosin stain, original magnification X67).
incidence directly increases with the dose of radiation and the time since treatment.2,6‘9 The latent period is longer after larger doses of irradiation, and inversely related to the radiation dose. lo The radiation-related cancer rate in exposed tissues has been estimated to be 1.8 cases per million personyears per rad. ” In another report, the dose-effect relationship between epithelial cancers and radiation for the exposed skin was shown to be 40 carcinomas/ lo4 persons/ Gy for a median follow-up period of 4 1 years2 The patient’s age at the time of irradiation also may affect the latent period; the older the age at irradiation, the shorter the latent period.” There has been conjecture as to whether radiationinduced cancer is more common following orthovoltage than megavoltage irradiation.‘3.‘4 Megavoltage radiotherapy with improved dose characteristics has been discussed with respect to its diminished frequency of development of new neoplasms in irradiated tissues. ’ Most radiation-induced skin cancers are basal cell carcinoma, with a small percentage of squamous cell carcinoma.2 A striking increase in the risk of developing brain, parotid, and thyroid tumors has been reported after scalp irradiation.3 Among the cancers of the head and neck that developed in atomic bomb survivors, a suggestive relationship to radiation dose was found for accessory sinus cancers, but the increase in incidence could not be definitively concluded to be the result of atomic bomb radiation.15 Bergstroem et al found that in more than 1,500 patients who were irradiated for cervical adenitis during childhood, 32 patients developed malignant tumors,
70
RADIATION-INDUCED
including 12 skin tumors, 5 oral cavity tumors, and one patient with both thyroid carcinoma and basal cell carcinoma.16 In five patients, development of squamous cell carcinoma in the areas irradiated for laryngeal carcinoma was reported 7 to 12 years after successful therapeutic irradiation.” The predominant histologic types of radiation-induced sarcoma are fibrosarcoma, osteosarcoma, and malignant fibrous histiocytoma.4*‘0.‘8~19Development of bone sarcoma as a second malignant neoplasm in children was found to be influenced by radiation and genetic predisposition. *’ The potential risk of development of thyroid cancer after radiation exposure is a major factor in radiation-induced cancer.21-23The child and adult population exposed to radiation at Hiroshima and Nagasaki have a high incidence of thyroid carcinoma.24,25 Hempelman et al reported that in 2,900 persons who received x-ray therapy during infancy, 19 developed thyroid cancer and 22 developed thyroid adenomas.’ Cerletty et al found 34 cases of thyroid carcinoma in 1,825 subjects with a history of head and neck irradiation, including 17 papillary, 10 mixed papillary-follicular, 6 follicular, and 1 medullary mixed carcinoma.26 Diagnosis of our four cases of radiation-induced cancer was made according to the criteria used for the diagnosis of radiation-induced osteosarcoma.” These four patients received radiation treatment for hemangioma or actinomycosis of the oral cavity during early childhood or adolescence. All cases were proven squamous cell carcinoma with histologic features quite different from the original benign lesion. The minimum latent period was 24 years (mean, 38 years), an extremely long latency compared to other reported cases. The lowest cumulative radiation dose was 60 Gy in one patient treated by combined orthovoltage x-ray therapy and brachytherapy. However, in this case, the doses administered close to the small source were of course greater than 100 Gy. Long-term low-dose irradiation whose accumulated sum is equal to a larger dose may also be related to carcinogenesis in these cases. A higher risk of development of malignant tumors has been reported following combined radiation therapy and chemotherapy, especially in the treatment of Hodgkin’s disease. 28 In our cases, only one patient had a history of intra-arterial infusion of 5-F’U. Two had a history of radiation osteonecrosis and excision of a sequestrum. Continuous chronic inflammation due to radiation ulcer and osteonecrosis was evident in these two cases. Management of radiation-induced cancer includes surgery and radiotherapy, depending on the site and extent of tumor involvement. Two cases were controlled by radiation, although one later died of radiotherapy complications. One of the four patients is still alive and well with no complications. In view of late
radiation effects, x-ray irradiation of benign skin lesions is contraindicated, especially in view of the evidence that treatment with low doses of radiation given over a long period has a high risk of carcinogenesis.’ There is, of course, a small possibility that these cases represent spontaneously occurring cancers rather than radiation-induced cancers. However, the incidence of spontaneously occurring cancer is extremely low; the incidence of oral cancer is approximately one in 33,000 persons per year in Japan. 29No obvious histologic differences are known to exist between spontaneous and radiation-induced carcinoma; however, one case showed transformation to a spindle cell carcinoma after radiation treatment. The occurrence of squamous cell carcinoma in patients treated with radiotherapy for benign lesions may suggest that radiation-induced cancers should be included in the “recurrent cancer” category because they develop long after the radiation treatment for squamous cell carcinoma of the oral cavity.
CANCER OF THE ORAL C‘AVITY
References I. Li FP: Second malignant tumors after cancer in childhood. Cancer 40:1899, 1977 2. van Vloten WA, Hermans J, van Daal WAJ: Radiation-induced skin cancer and radiodermatitis of the head and neck. Cancer 59:41 I, 1987 3. Modan B, Baidatz D, Mart H, et al: Radiation induced head and neck tumors. Lancet 1:277, 1974 4. Coia LR. Fazekas JT. Kramer S: Postirradiation sarcoma of the head and neck: A report of three late sarcomas following therapeutic irradiation for primary malignancies of the paranasal sinus, nasal cavity, and larynx. Cancer 46: 1982, 1980 5. Ward CM, Buchanan R: Hemangiosarcoma following irradiation of a hemangioma of the face. J Maxillofac Surg 5: 164, 1977 6. Martin H, Strong E, Spiro RH: Radiation-induced skin cancer of the head and neck. Cancer 2561, 1970 7. Hempelmann LH, Hall WJ, Phillips M, et al: Neoplasms in persons treated with X-rays in infancy: Fourth survey in 20 years. JNCI 55:5 19, 1975 8. Hutchison GB: Late neoplastic changes following medical irradiation. Cancer 37:1102, 1976 9. Shore RE, Albert RE, Pastemack BS: Follow-up study of patients treated by x-ray epilation for tinea capitis. Arch Environ Health 31:17. 1976 10. Kim JH. Chu FC. Woodard HQ, et al: Radiation-induced soft tissue and bone sarcoma. Radiology 129501, 1978 11. Li FP, Cassady JR, Jaffe N: Risk of second tumors in survivors of childhood cancer. Cancer 35:1230, 1975 12. Nishimura Y. Sakai K. Kitamura T. et al: Radiation-induced cancers following radiotherapy for benign diseases: The second mail survey in Japan. Jpn J Cancer Chemother 13:1492, 1986 13. Hatfield PM, Shulz MD: Post-irradiation sarcoma. Radiology 96:593, 1970 14. Steeves RA, Bataini J-P: Neoplasms induced by megavoltage radiation in the head and neck region. Cancerb7: 1770, 1981 15. Pinkston JA. Wakabavashi T. Yamamoto T. et al: Cancer of the head and neck in atomic bomb survivors:‘Hiroshima and Nagasaki, 1957-1976. Cancer 48:2172, 1981 16. Bergstroem B, Fogh A, Ranudd NE: Late complications after irradiation treatment for cervical adenitis in childhood. Acta Dtolaryngol (Stockh) lOO:lSl, 1985 17. Schindel J, Castoriano IM: Late-appearing (radiation-induced) carcinoma. Arch Otolaryngol 95205, 1972 18. Arlen M, Higinbotham NL, Huvos AG, et al: Radiation-induced sarcoma of bone. Cancer 28: 1087, 197 1
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19. Souba WW, McKenna RJ, Meis J, et al: Radiation-induced sarcomas of the chest wall. Cancer 57:610, 1986 20. Sagerman RH, Cassady JR, Tretter P, et al: Radiation-induced neoplasia following external beam therapy in children with retinoblastoma. Am J Roentgenol 105529, 1969 2 I. Favus MJ, Schneider AB, Strachura ME, et al: Thyroid cancer occuring as a late consequence of head and neck irradiation: Evaluation of 1056 patients. New Engl J Med 294:1019,1976 22. Janower ML, Miettinen OS: Neoplasms after childhood irradiation of the thymus gland. JAMA 2 15:753, 197 1 23. Scanlon EF, Sener SF: Head and neck neoplasia following irradiation for benign conditions. Head Neck Surg 4: 139, 198 1 24. Sampson RJ, Key CR, Buncher CR, et al: Thyroid carcinoma in Hiroshima and Nagasaki. I Prevalence of thyroid carcinoma at autopsy. JAMA 209:65, 1969
J Oral Maxillofac 50:71-75,
25. Parker LN, Belsky JL, Yamamoto T, et al: Thyroid carcinoma after exposure to atomic radiation. A continuing survey of a fixed population, Hiroshima and Nagasaki, 1958- 197 1. Ann Intern Med 80:600, 1974 26. Cerletty JM, Guansing AR, Engbring NH, et al: Radiation-related thyroid carcinoma. Arch Surg 113:1072. I978 27. Cahan WG, Woodward HG, Higinbotham NL, et al: Sarcoma arising in irradiated bone: Report of eleven cases. Cancer I: 3, 1948 28. Cannelos GP, Arsenau JC, Devita VT, et al: Second malignancies complicating Hodgkin’s disease in remission. Lancet 1:947, 1975 29. Fujimoto I: The report of the research group for population based cancer registration in Japan. Osaka Adult Disease Center, 1988
Surg
1992
Hydroxylapatite Block Closure of Oroantral Fistulas: Report of Cases MICHAEL
F. ZIDE, DDS,* AND NESTOR
An oroantral communication may challenge the surgeon who wishes to obtain a permanent closure and prevent sinus disease. Long-term successful closure of the oroantral fistula depends on the acuteness of the problem, absence of sinus disease, size and location of the defect, and the amount and condition of the adjacent tissue. The literature has shown that openings greater than 5 mm in diameter have a substantially decreased chance of spontaneous primary closure.‘32 Treatment includes the use of local or distant tissue flaps and interpositional autogenous grafts or alloplastic implants. Local flaps use tissue from either the buccal vestibule or palate. When buccal tissue is advanced over the fistula, which is the commonest closure method, a decrease in vestibular depth may occur with a loss of attached gingiva after healing. Several types of palatal flaps have been described for closure; however, all require secondary granulation of denuded tissue and temporarily limit the patient’s ability to wear * Associate Director. Department of Oral and Maxillofacial Surgery. John Peter Smith Hospital, Fort Worth. TX. t Resident, Department of Oral and Maxillofacial Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Address correspondence and reprint requests to Dr Zide: Department ofOral and Maxillofacial Surgery, John Peter Smith Hospital, 1625 St Louis St, Ft Worth, TX 76104. 8 1992
American
Association
0278-2391/92/5001-0016$3.00/O
of Oral and Maxillofacial
Surgeons
D. KARAS,
DDSt
a prosthesis. In addition, it is difficult for palatal flaps to reach the lateral alveolus. Several double-layer closure flap techniques using buccal and palatal tissues have been suggested, but these procedures produce larger denuded areas and an increased time is required to raise these flaps. Tissue taken from either the tongue or buccal mucosa have also been used, but these procedures usually require a general anesthetic and there is increased donor site morbidity. Obturating of fistulas has involved both autogenous grafts and alloplastic implants. Bone grafts from the iliac crest and cranium have been used in patients with large defects and those previously treated unsuccessfully with soft tissue closure. 3-5 Concern about donor site morbidity and hospitalization suggests use of this method only for large defects. Alloplastic materials that have been used for the closure of oroantral fistulas include gold foil, gold plate, tantalum plate, soft polymethylmethacrylate, and lyophilized collagen. The advantages of alloplastic materials are simplicity of use and prevention of breakdown, which may occur with soft tissue alone. Dense hydroxylapatite (HA) provides the surgeon with an inert material capable of exposure to the oral cavity without deleterious effects. For the past year, we have used HA blocks to close both acute and chronic oroantral fistulas. The technique appears to have some major advantages over current techniques.
