J. Cranio-Max.-Fac.Surg. 19 (1991) J. Cranio-Max.-Fac. Surg. 19 (1991) 267-271 © Georg Thieme Verlag Stuttgart • New York
Ameloblastic Carcinoma Report of an Aggressive Case and Review of the Literature Robert A. Bruce ~, Ian T. Jackson 2 i Dept. of Oral and Maxillofacial Surgery (Head: Prof. S. Fineberg, D. D. S., Ph. D.), The University of Michigan, Ann Arbor, 2 Institute for Craniofacial and Reconstructive Surgery (Director: I. T. Jackson, M. D., F. R. C. S., F. A. C. S., F. R. A. C. S. (Hon.)), Southfield, Michigan, USA Submitted 3.3. 1991; accepted 15.4. 1991
Introduction Ameloblasfic carcinoma is an extremely rare, malignant neoplasm of the jaws, presenting a significant challenge in diagnosis, treatment, and prediction of prognosis. It is one of the rare odontogenic carcinomas classified in the World Health Organization's International Histological Classification (Pindborg et al., 1982) as follows: A. Malignant ameloblastoma B. Primary intraosseous carcinoma C. Other carcinomas arising from the odontogenic epithelium including those arising from odontogenic cysts. Cases of odontogenic carcinoma in the literature have been reviewed and additional cases presented so the classification as modified and expanded by Elzay (1982), Slootweg and Miiller (1984), and McClatchey et al. (1989) is currently:
Odontogenic Carcinoma: Type 1. Primary intraosseous carcinoma ex odontogenic cyst Type 2. A. Malignant ameloblastoma B. Ameloblastic carcinoma 1. De novo a. Central b. Peripheral 2. Ex ameloblastoma 3. Ex odontogenic cyst Type 3. Primary intraosseous carcinoma arising de novo A. Nonkeratinizing B. Keratinizing Primary intraosseous carcinoma is a squamous cell carcinoma arising from remnants of epithelial odontogenic rests derived embryologically from the tooth forming dental lamina (nests of Malassez) (McClatchey et al., 1987). The neoplasm can also arise from enclaved epithelium at sites of fusion of the embryonic facial processes. The diagnosis of this neoplasm is dependent upon the exclusion of: A. bony extension from a surface or sinus mucosal carcinoma, B. malignant transformation of an odontogenic cyst,
267
Summary Odontogenic carcinomas of the jaws are classified as malignant ameloblastoma, ameloblastic carcinoma or primary intraosseous carcinoma. Because these lesions are extremely rare, microscopic diagnosis is difficult. An aggressive case of ameloblastic carcinoma of the mandible is presented. In spite of radical surgery and radiotherapy, the patient expired eight months following initial diagnosis. - A review of the literature seems to indicate that so called simple ameloblastomas rarely can dedifferentiate and metastasize following multiple inadequate surgical procedures. Although radical surgery is not necessary, local excision should be thorough. - Ameloblastic carcinoma and primary intraosseous carcinomas may be histogenetically similar. They are highly malignant turnouts which should be treated aggressively. Metastasis is common and prognosis is poor.
Key words Ameloblastic - Odontogenic - Primary Intraosseous - Malignant - Carcinoma
C. distant metastasis of a visceral neoplasm, D. ameloblastic carcinoma, or E. a central mucoepidermoid carcinoma. In 1982 Elzay, after an extensive and critical review of the literature, found 12 cases which could be acceptably classified as primary intraosseous carcinoma. Two cases were added by Ruskin et al. in 1988. The features of Elzay's (1982) cases were: male to female ratio of 3 : 1, ages 4 - 7 5 years with a mean of 45. Of the 12 cases, 11 occurred in the mandible (most in the posterior area). Histologically, seven were nonkeratinizing, five had an alveolar pattern and five exhibited a plexiform pattern. Six of ten patients died within the first two years after initial surgery. Cervical lymph node involvement was common. Malignant ameloblastoma is a neoplasm which metastasizes but histologically demonstrates features of a typical ameloblastorna in both primary and secondary lesions. Efforts to predict metastatic potential from histological characteristics (i. e. clear or granular cell types) have been unsuccessful (Tsukada et al., 1965, Hartman, 1974; Waldron et al., 1985). Typically, metastasis occurs following multiple surgical procedures and recurrences over a long period of time (Kunze et al., 1985; Ueda et al., 1989). Laughlin (1989) reported a case of malignant ameloblastoma and reviewed 42 previously published cases in 1989. Features of the cases were: male to female ratio of 1 : 5.1, ages 5 - 6 0 years with a mean of 30.5, mandible to maxilla ratio of 8 : 1. The site of metastases was lung in 75 % of the cases, with cervical nodes and spine accounting for 15 % of the cases. Median disease free interval after initial treatment was nine years. Nineteen patients died of the disease. The median survival time after treatment of the metastases was only two years. The histological features revealed a "benign" or typical histology in both the primary and metastatic lesions.
268
J. Cranio-Max.-Fac.Surg. 19 (1991)
Fig. 1 Soft tissue enhanced coronal CT scan showing medial and lateral expansion of the ameloblastic carcinoma through the ramus of the mandible.
tLA. Bruce, I. T. Jackson the authors did not present the clinical course. Histological features generally resembled those of conventional ameloblastoma, but the epithelium displayed various cytological features of malignant disease. Slootweg and Miiller, in 1984, reported two cases of ameloblastic carcinoma and reviewed cases in the literature reported as malignant ameloblastoma. They found two cases in which the metastasis exhibited a less-differentiated pattern than the primary tumour. In nine cases the primary and metastatic growth exhibited dedifferentiation. In 14 cases the primary ameloblastoma had undergone anaplastic transformation but metastatic disease was not present or, if present, was not histologically proven. Cases, which under the present classification would be categorized as ameloblastic carcinoma (malignant features in the primary tumour), were generally found in the mandible (mandible to maxilla ratio of 19:4). There were 13 males and 10 females, ages 4 - 7 5 years with a mean of 33.5. Metastasis occurred most commonly to the lung. From the limited information presented, it appeared in most cases that there was a significant time span between initial treatment and the occurrence of metastasis. However, when the disease had spread, death occurred within a year or so. Subsequent cases of ameloblastic carcinoma have been reported by Andersen and Bang (maxilla) (1986), Dorner et al. (mandible with pulmonary metastasis) (1988) and McClatchey et al. (peripheral ameloblastic carcinoma) (1989). Odontogenic carcinomas can be similar in histological appearance, and diagnosis can be very difficult. Whether malignant ameloblastoma, ameloblastic carcinoma and primary intraosseous carcinoma are separate entities or simply progressive stages of the same process is unclear. The clinical significance can ultimately be determined only by additional well documented cases.
Case Report Ameloblastic carcinoma is a neoplasm demonstrating histological evidence of malignant transformation of the ameloblastoma-like epithelial component in the primary tumour whether or not it has metastasized (Shafer et al., 1974). Metastatic lesions often do not resemble the primary tumour but, rather, a less well differentiated squamous cell carcinoma. It may arise de novo from remnants of the dental lamina or from odontogenic cysts and may be located centrally in the jaws or peripherally in the surrounding mucosa (McClatchey et al., 1989). Since Elzay's 1982 review and classification of primary intraosseous carcinoma (odontogenic carcinoma), others have reported cases of ameloblastic carcinoma as a separate entity. In 1987 Corio et al. reviewed eight cases from the files of the Armed Forces Institute of Pathology (AFIP). Four cases appeared to arise from a cyst lining. Patient ages ranged from 1 5 - 8 4 with a mean of 30.1 years. Seven cases involved the mandible, one involved the maxilla. One case presented with cervical metastases. The most common sign was swelling (six cases), followed by pain and/or rapid growth. In most cases an ill-defined destructive radiolucency with focal radiopacities was noted. Root resorption and perforation of buccal and lingual plates occurred. The lesions were aggressive, extending beyond bone into adjacent soft tissue. The five year survival rate was not available, as
In July 1989, a 57-year-old white male was referred by his dentist for treatment of a large painful mass located in the right posterior mandible extending into the cheek and mucobuccal fold. The patient felt the swelling had been present a few weeks and was enlarging rapidly. He also noticed progressive numbness of his right lower lip. Past medical history included treatment for traumatic fracture of his right humerus, repair of hiatus hernia and occasional treatment for duodenal ulcer. The patient had smoked one and a half packs of cigarettes a day for over 40 years and admitted to social drinking. A panoramic radiograph demonstrated a 2.5 x i cm, poorly defined radiolucent area extending from the mandibular foramen to the distal body of the right mandible. A C T scan of the mandible showed a 4 × 4 cm mass in the right ramus extending through both cortices, displacing the masseter and medial pterygoid muscles (Fig. 1). The head of the condyle and the pterygoid processes of the sphenoid or maxilla were not involved radiographically. A biopsy showed a tumour composed of two processes (Fig. 1). In some areas follicles of well differentiated columnar epithelial cells containing nuclei polarized from the basement membrane were located in fibrous connective tissue (Fig. 2). The central area of the islands of epithelial nests consisted of cyst-like spaces and loosely arranged cells
Ameloblastic Carcinoma
J. Cranio-Max.-Fac. Surg. 19 (1991)
269
Fig.3
Fig.2 Photomicrograph of the ameloblastic carcinoma showing typical ameloblastoma pattern as well as invading plexiform cords of tumour (HE x 20).
Photomicrograph showing a follicular pattern of the ameloblastic carcinoma. The epithelial cells demonstrate reversed nuclear polarity and surround stetlate reticutum (HE x 50),
Fig,4 Photomicrograph of the ameloblastic carcinoma in which the cells are in a plexiform pattern. (HE x 20)
Fig.5 Photomicrograph of the ameloblastic carcinoma metastatic to the lung (HE x 50).
resembling stellate reticulum. In other areas, infiltrating plexiform strands or poorly differentiated cells invaded bone and muscle (Fig. 3). These cells showed marked nuclear pleomorphism along with increased, atypical mitotic activity (Fig. 4). A mucincarmine stain was faintly positive. Several consultant pathologists reported the turnout as ameloblastic carcinoma, with an admonition to rule out metastasis to the mandible from a distant site. Accordingly, CT scans with contrast were done of the brain, thorax, and abdomen; they were negative for evidence of turnout. Clinical physical examination showed the patient to be in apparent good health except for the mandibular tumour. Surgery in early August, 1989, consisted of modified radical neck dissection and resection of the right mandible from the bicuspid region to the condylar neck, leaving the head of the condyle. The masseter, pterygoid muscles and contents of the pterygoid space were resected. A total parotidectomy with preservation of the facial nerve was completed. The mandible was reconstructed with a metal prosthesis which was enveloped buccally and lingually with ster-
nocleidomastoid muscle. The resulting lateral facial contour defect was reconstructed with a temporalis muscle flap. Frozen sections done at the time of surgery showed margins to be clear. However, the final report of the fixed specimen showed neoplasm to extend to the medial and inferior edges. The patient was referred for postoperative radiotherapy, given over an eight-week period, consisting of 6,800 rads to the area of the right mandible and pterygoid fossa and 5,000 fads to the right cervical and supra clavicular nodes. At completion of radiotherapy the patient developed a cervical mass in the midneck which was biopsied and diagnosed as metastasis from the original mmour. The patient developed a left pneumothorax four months following surgery and a mass was noted in the left lung. Sputum cytology and open biopsy demonstrated mmour metastasis with features of the original ameloblastic carcinoma (Fig. 5). The patient was started on a regimen of 5-FU with Cis-Platinum infusions, but he was unable to tolerate
270
J. Cranio-Max.-Fac. Surg. 19 (1991)
the effects of chemotherapy and expired shortly thereafter, eight months after the original diagnosis of the tumour. Discussion and Conclusions This case is similar to cases of ameloblastic carcinomas reported in the literature. Swelling, pain, rapid growth and erosion through bone to involve adjacent soft tissue were apparent clinically. Radiographically this tumour presented as an ill defined radiolucency. Although Corio et al. (1987) noted occasional radiopacities in the cases they reviewed, this was not seen in our case. The histological features were similar to those described in the literature, generally resembling a conventional ameloblastoma but with cytological features of epithelial malignant disease. The lung metastasis demonstrated a less differentiated pattern, but the ameloblastic-like pattern was apparent in some sections. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Local recurrence and metastasis to the neck and lungs is common. The clinical course of this case was even more aggressive than cases described in the literature. The patient survived only eight months from the time of initial diagnosis to death, despite aggressive treatment by surgery, radiotherapy and limited chemotherapy. This case can be compared to the 12 cases of primary intraosseous carcinoma evaluated by Elzay (1982). In 66 % of these cases, the tumour recurred after excision and 60 % died within two years. The remaining four patients who survived more than two years had either clinical and/or histological evidence of metastasis to cervical nodes at the time of initial therapy. Similiarly, four of six patients who succumbed to their disease within two years had clinical and/or histological manifestations of metastasis to cervical lymph nodes. Three of seven cases of ameloblastic carcinoma presented by Corio et al. (1987) had recurrences within one year. Patients with ameloblastic carcinoma evaluated by Slootweg and Mi~ller in 1984, (in which both the primary and metastatic growth exhibited dedifferentiation), died within two years after metastasis. More recently, the case of ameloblastic carcinoma reported by Anderson and Bang (1986) showed aggressive recurrence and early metastasis. It should be noted that the tumour presented in this case was radioresistant. Generally this is consistent with the previously reported cases, but a few authors have reported radiosensitive tumours (Appel and Verbin, 1985). It is difficult to note major histological differences between primary intraosseous carcinoma and ameloblastic carcinoma as described in the literature. Corio et al. (1987) state: "Although the primary intra-alveolar carcinoma and the ameloblastic carcinoma exhibit some clinical differences, their histological features are similar enough to suggest a histogenetic relationship. It is possible then that the primary intra-alveolar carcinoma may represent simply a less differentiated, usually nonkeratinizing form of ameloblastic carcinoma both lesions being derived basically from odontogenic epithelial remnants." From a surgeon's perspective, it is difficult to discern if the histological "lumping or splitting" of the classification of odontogenic carcinomas is warranted. However, clinically it is apparent that ameloblastic carcinoma, as exemplified by this case, is an extremely aggressive neoplasm and should be treated accordingly. From our experience with
R.A. Bruce, L T. Jackson
this case and a review of the literature we do not totally concur with McClatchey et al. (1989) who state: "... both malignant ameloblastoma and ameloblastic carcinoma act like well-differentiated squamous cell carcinoma - locally aggressive neoplasms that metastasize late to regional lymph nodes and/or lungs. Wide local exision on the primary site is generally curative." There is ample evidence in the literature that so-called benign ameloblastomas can dedifferentiate with time, and multiple inadequate surgical procedures are associated with metastasis. Although it may take years for the tumour to dedifferentiate, morbidity increases significantly after metastasis. The rational approach to these turnouts is adequate surgery initially to prevent recurrence and certainly, if the lesion recurs, aggressive definitive surgery is indicated. It is apparent from the case in this report that ameloblastic carcinomas do not consistantly behave as "well differentiated squamous cell carcinomas". We feel that when odontogenic carcinomas have histological characteristics of malignancy, whether they are called primary intraosseous carcinoma or ameloblastic carcinoma, they should be treated aggressively with wide local excision. Although radical neck surgery should be considered, there are too few reported cases to make a definitive recommendation. Finally, radiotherapy seems to be of limited value for ameloblastic carcinomas and chemotherapy is as yet unproven. References Andersen, E., G. Bang: Ameloblastic carcinoma of the maxilla. J. Max-Fac. Surg. 14 (1986) 338-340 Appel, B. N., tL S. Verbin: Odontogenic Tumors. Chapter 21 in: Surgical Pathology of the Head and Neck. Barnes L. (Ed.). Dekker, NewYork 1985, p. 1355 Corio, 1L L., L. L GoIdblatt, P.A. Edwards, K.S. Hartman: Ameloblastic carcinoma: a clinicopathologic study and assessment of eight cases. Oral Surg. 64 (1987) 570-576 Dorner, L., A.J. Sear, G. T. Smith: A case of ameloblastic carcinoma with pulmonary metastases. Br. J. Oral MaxillofacSurg. 26 (1988) 503-510 Elzay, tL P.: Primaryintraosseous carcinoma of the jaws. Reviewand update of odontogenic carcinomas. Oral. Surg. 54 (1982) 299 -303 Hartman, K.S.: Granular cell ameloblastoma. Oral Surg. 28 (1974) 241 Kunze, E., K. Donath, H. G. Luhr, W. Englehardt, IL DeVivie: Biology of metastasizing ameloblastoma path. Path. Res. Pract. 180 (1985) 526-535. Laughlin, E.H.: Metastasizing ameloblastoma. Cancer 64 (1989) 776-780 McCIatchey, K.D.: Tumors of the dental lamina: a selectivereview. Seminars in Diagnostic Pathology 4 (1987) 200-204 McClatchey, K.D., M.J. Sullivan, D.R. Paugh: Peripheral ameloblastic carcinoma: a case report of a rare neoplasm. J. Otolaryng. 18 (1989) 109-111 Pindborg, J.J., I.R.H. Kramer, H. Torloni: Histologic typing of odontogenic tumours, jaw cysts and allied lesions. World Health Organization, Geneva, 1982 Ruskin, J.D., D.M. Cohen, L.F. Davis: Primary intraosseous carcinoma: report of two cases. J. Oral Maxillofac. Surg. 46 (1988) 425-432 ~hafer, W. G., M. K. Hine, B.M. Levy: A Textbook of Oral Pathology. Saunders, Philadelphia 1974, pp. 251-258 Slootweg, P. J., H. Mf~ller: Malignant ameloblastoma or ameloblastic carcinoma. Oral Surg. 57 (1984) 168-176 Tsukada, Y., S. de la Pava, J. W. Pickren: Granular cell ameloblastoma with metastasis to the lungs. Report of a case and review of the literature. Cancer 18 (1965) 916
Ameloblastic Carcinoma Ueda, M, T. Kaneda, M. Imaizumi, 7". Ave: Mandibular ameloblastoma with metastasis to the lungs and lymph nodes: a case report and review of the literature. J. Oral Maxillofac. Surg. 47 (1989) 623-628 Waldron, C.A., I.A. Small, H. Silverman: Clear cell ameloblastoma an odontogenic carcinoma. J. Oral Maxilofac. Surg. 43 (1985) 707-717 -
J. Cranio-Max.-Fac. Surg. 19 (1991) Dr. R. A. Bruce Departement of Oral & Maxillofacial Surgery 2010 School of Dentistry The University of Michigan Ann Arbor, M148109-1078 USA
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Ameloblastic Carcinoma Report of an Aggressive Case and Review of the Literature Robert A. Bruce ~, Ian T. Jackson 2 i Dept. of Oral and Maxillofacial Surgery (Head: Prof. S. Fineberg, D. D. S., Ph. D.), The University of Michigan, Ann Arbor, 2 Institute for Craniofacial and Reconstructive Surgery (Director: I. T. Jackson, M. D., F. R. C. S., F. A. C. S., F. R. A. C. S. (Hon.)), Southfield, Michigan, USA Submitted 3.3. 1991; accepted 15.4. 1991
Introduction Ameloblasfic carcinoma is an extremely rare, malignant neoplasm of the jaws, presenting a significant challenge in diagnosis, treatment, and prediction of prognosis. It is one of the rare odontogenic carcinomas classified in the World Health Organization's International Histological Classification (Pindborg et al., 1982) as follows: A. Malignant ameloblastoma B. Primary intraosseous carcinoma C. Other carcinomas arising from the odontogenic epithelium including those arising from odontogenic cysts. Cases of odontogenic carcinoma in the literature have been reviewed and additional cases presented so the classification as modified and expanded by Elzay (1982), Slootweg and Miiller (1984), and McClatchey et al. (1989) is currently:
Odontogenic Carcinoma: Type 1. Primary intraosseous carcinoma ex odontogenic cyst Type 2. A. Malignant ameloblastoma B. Ameloblastic carcinoma 1. De novo a. Central b. Peripheral 2. Ex ameloblastoma 3. Ex odontogenic cyst Type 3. Primary intraosseous carcinoma arising de novo A. Nonkeratinizing B. Keratinizing Primary intraosseous carcinoma is a squamous cell carcinoma arising from remnants of epithelial odontogenic rests derived embryologically from the tooth forming dental lamina (nests of Malassez) (McClatchey et al., 1987). The neoplasm can also arise from enclaved epithelium at sites of fusion of the embryonic facial processes. The diagnosis of this neoplasm is dependent upon the exclusion of: A. bony extension from a surface or sinus mucosal carcinoma, B. malignant transformation of an odontogenic cyst,
267
Summary Odontogenic carcinomas of the jaws are classified as malignant ameloblastoma, ameloblastic carcinoma or primary intraosseous carcinoma. Because these lesions are extremely rare, microscopic diagnosis is difficult. An aggressive case of ameloblastic carcinoma of the mandible is presented. In spite of radical surgery and radiotherapy, the patient expired eight months following initial diagnosis. - A review of the literature seems to indicate that so called simple ameloblastomas rarely can dedifferentiate and metastasize following multiple inadequate surgical procedures. Although radical surgery is not necessary, local excision should be thorough. - Ameloblastic carcinoma and primary intraosseous carcinomas may be histogenetically similar. They are highly malignant turnouts which should be treated aggressively. Metastasis is common and prognosis is poor.
Key words Ameloblastic - Odontogenic - Primary Intraosseous - Malignant - Carcinoma
C. distant metastasis of a visceral neoplasm, D. ameloblastic carcinoma, or E. a central mucoepidermoid carcinoma. In 1982 Elzay, after an extensive and critical review of the literature, found 12 cases which could be acceptably classified as primary intraosseous carcinoma. Two cases were added by Ruskin et al. in 1988. The features of Elzay's (1982) cases were: male to female ratio of 3 : 1, ages 4 - 7 5 years with a mean of 45. Of the 12 cases, 11 occurred in the mandible (most in the posterior area). Histologically, seven were nonkeratinizing, five had an alveolar pattern and five exhibited a plexiform pattern. Six of ten patients died within the first two years after initial surgery. Cervical lymph node involvement was common. Malignant ameloblastoma is a neoplasm which metastasizes but histologically demonstrates features of a typical ameloblastorna in both primary and secondary lesions. Efforts to predict metastatic potential from histological characteristics (i. e. clear or granular cell types) have been unsuccessful (Tsukada et al., 1965, Hartman, 1974; Waldron et al., 1985). Typically, metastasis occurs following multiple surgical procedures and recurrences over a long period of time (Kunze et al., 1985; Ueda et al., 1989). Laughlin (1989) reported a case of malignant ameloblastoma and reviewed 42 previously published cases in 1989. Features of the cases were: male to female ratio of 1 : 5.1, ages 5 - 6 0 years with a mean of 30.5, mandible to maxilla ratio of 8 : 1. The site of metastases was lung in 75 % of the cases, with cervical nodes and spine accounting for 15 % of the cases. Median disease free interval after initial treatment was nine years. Nineteen patients died of the disease. The median survival time after treatment of the metastases was only two years. The histological features revealed a "benign" or typical histology in both the primary and metastatic lesions.
268
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Fig. 1 Soft tissue enhanced coronal CT scan showing medial and lateral expansion of the ameloblastic carcinoma through the ramus of the mandible.
tLA. Bruce, I. T. Jackson the authors did not present the clinical course. Histological features generally resembled those of conventional ameloblastoma, but the epithelium displayed various cytological features of malignant disease. Slootweg and Miiller, in 1984, reported two cases of ameloblastic carcinoma and reviewed cases in the literature reported as malignant ameloblastoma. They found two cases in which the metastasis exhibited a less-differentiated pattern than the primary tumour. In nine cases the primary and metastatic growth exhibited dedifferentiation. In 14 cases the primary ameloblastoma had undergone anaplastic transformation but metastatic disease was not present or, if present, was not histologically proven. Cases, which under the present classification would be categorized as ameloblastic carcinoma (malignant features in the primary tumour), were generally found in the mandible (mandible to maxilla ratio of 19:4). There were 13 males and 10 females, ages 4 - 7 5 years with a mean of 33.5. Metastasis occurred most commonly to the lung. From the limited information presented, it appeared in most cases that there was a significant time span between initial treatment and the occurrence of metastasis. However, when the disease had spread, death occurred within a year or so. Subsequent cases of ameloblastic carcinoma have been reported by Andersen and Bang (maxilla) (1986), Dorner et al. (mandible with pulmonary metastasis) (1988) and McClatchey et al. (peripheral ameloblastic carcinoma) (1989). Odontogenic carcinomas can be similar in histological appearance, and diagnosis can be very difficult. Whether malignant ameloblastoma, ameloblastic carcinoma and primary intraosseous carcinoma are separate entities or simply progressive stages of the same process is unclear. The clinical significance can ultimately be determined only by additional well documented cases.
Case Report Ameloblastic carcinoma is a neoplasm demonstrating histological evidence of malignant transformation of the ameloblastoma-like epithelial component in the primary tumour whether or not it has metastasized (Shafer et al., 1974). Metastatic lesions often do not resemble the primary tumour but, rather, a less well differentiated squamous cell carcinoma. It may arise de novo from remnants of the dental lamina or from odontogenic cysts and may be located centrally in the jaws or peripherally in the surrounding mucosa (McClatchey et al., 1989). Since Elzay's 1982 review and classification of primary intraosseous carcinoma (odontogenic carcinoma), others have reported cases of ameloblastic carcinoma as a separate entity. In 1987 Corio et al. reviewed eight cases from the files of the Armed Forces Institute of Pathology (AFIP). Four cases appeared to arise from a cyst lining. Patient ages ranged from 1 5 - 8 4 with a mean of 30.1 years. Seven cases involved the mandible, one involved the maxilla. One case presented with cervical metastases. The most common sign was swelling (six cases), followed by pain and/or rapid growth. In most cases an ill-defined destructive radiolucency with focal radiopacities was noted. Root resorption and perforation of buccal and lingual plates occurred. The lesions were aggressive, extending beyond bone into adjacent soft tissue. The five year survival rate was not available, as
In July 1989, a 57-year-old white male was referred by his dentist for treatment of a large painful mass located in the right posterior mandible extending into the cheek and mucobuccal fold. The patient felt the swelling had been present a few weeks and was enlarging rapidly. He also noticed progressive numbness of his right lower lip. Past medical history included treatment for traumatic fracture of his right humerus, repair of hiatus hernia and occasional treatment for duodenal ulcer. The patient had smoked one and a half packs of cigarettes a day for over 40 years and admitted to social drinking. A panoramic radiograph demonstrated a 2.5 x i cm, poorly defined radiolucent area extending from the mandibular foramen to the distal body of the right mandible. A C T scan of the mandible showed a 4 × 4 cm mass in the right ramus extending through both cortices, displacing the masseter and medial pterygoid muscles (Fig. 1). The head of the condyle and the pterygoid processes of the sphenoid or maxilla were not involved radiographically. A biopsy showed a tumour composed of two processes (Fig. 1). In some areas follicles of well differentiated columnar epithelial cells containing nuclei polarized from the basement membrane were located in fibrous connective tissue (Fig. 2). The central area of the islands of epithelial nests consisted of cyst-like spaces and loosely arranged cells
Ameloblastic Carcinoma
J. Cranio-Max.-Fac. Surg. 19 (1991)
269
Fig.3
Fig.2 Photomicrograph of the ameloblastic carcinoma showing typical ameloblastoma pattern as well as invading plexiform cords of tumour (HE x 20).
Photomicrograph showing a follicular pattern of the ameloblastic carcinoma. The epithelial cells demonstrate reversed nuclear polarity and surround stetlate reticutum (HE x 50),
Fig,4 Photomicrograph of the ameloblastic carcinoma in which the cells are in a plexiform pattern. (HE x 20)
Fig.5 Photomicrograph of the ameloblastic carcinoma metastatic to the lung (HE x 50).
resembling stellate reticulum. In other areas, infiltrating plexiform strands or poorly differentiated cells invaded bone and muscle (Fig. 3). These cells showed marked nuclear pleomorphism along with increased, atypical mitotic activity (Fig. 4). A mucincarmine stain was faintly positive. Several consultant pathologists reported the turnout as ameloblastic carcinoma, with an admonition to rule out metastasis to the mandible from a distant site. Accordingly, CT scans with contrast were done of the brain, thorax, and abdomen; they were negative for evidence of turnout. Clinical physical examination showed the patient to be in apparent good health except for the mandibular tumour. Surgery in early August, 1989, consisted of modified radical neck dissection and resection of the right mandible from the bicuspid region to the condylar neck, leaving the head of the condyle. The masseter, pterygoid muscles and contents of the pterygoid space were resected. A total parotidectomy with preservation of the facial nerve was completed. The mandible was reconstructed with a metal prosthesis which was enveloped buccally and lingually with ster-
nocleidomastoid muscle. The resulting lateral facial contour defect was reconstructed with a temporalis muscle flap. Frozen sections done at the time of surgery showed margins to be clear. However, the final report of the fixed specimen showed neoplasm to extend to the medial and inferior edges. The patient was referred for postoperative radiotherapy, given over an eight-week period, consisting of 6,800 rads to the area of the right mandible and pterygoid fossa and 5,000 fads to the right cervical and supra clavicular nodes. At completion of radiotherapy the patient developed a cervical mass in the midneck which was biopsied and diagnosed as metastasis from the original mmour. The patient developed a left pneumothorax four months following surgery and a mass was noted in the left lung. Sputum cytology and open biopsy demonstrated mmour metastasis with features of the original ameloblastic carcinoma (Fig. 5). The patient was started on a regimen of 5-FU with Cis-Platinum infusions, but he was unable to tolerate
270
J. Cranio-Max.-Fac. Surg. 19 (1991)
the effects of chemotherapy and expired shortly thereafter, eight months after the original diagnosis of the tumour. Discussion and Conclusions This case is similar to cases of ameloblastic carcinomas reported in the literature. Swelling, pain, rapid growth and erosion through bone to involve adjacent soft tissue were apparent clinically. Radiographically this tumour presented as an ill defined radiolucency. Although Corio et al. (1987) noted occasional radiopacities in the cases they reviewed, this was not seen in our case. The histological features were similar to those described in the literature, generally resembling a conventional ameloblastoma but with cytological features of epithelial malignant disease. The lung metastasis demonstrated a less differentiated pattern, but the ameloblastic-like pattern was apparent in some sections. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Local recurrence and metastasis to the neck and lungs is common. The clinical course of this case was even more aggressive than cases described in the literature. The patient survived only eight months from the time of initial diagnosis to death, despite aggressive treatment by surgery, radiotherapy and limited chemotherapy. This case can be compared to the 12 cases of primary intraosseous carcinoma evaluated by Elzay (1982). In 66 % of these cases, the tumour recurred after excision and 60 % died within two years. The remaining four patients who survived more than two years had either clinical and/or histological evidence of metastasis to cervical nodes at the time of initial therapy. Similiarly, four of six patients who succumbed to their disease within two years had clinical and/or histological manifestations of metastasis to cervical lymph nodes. Three of seven cases of ameloblastic carcinoma presented by Corio et al. (1987) had recurrences within one year. Patients with ameloblastic carcinoma evaluated by Slootweg and Mi~ller in 1984, (in which both the primary and metastatic growth exhibited dedifferentiation), died within two years after metastasis. More recently, the case of ameloblastic carcinoma reported by Anderson and Bang (1986) showed aggressive recurrence and early metastasis. It should be noted that the tumour presented in this case was radioresistant. Generally this is consistent with the previously reported cases, but a few authors have reported radiosensitive tumours (Appel and Verbin, 1985). It is difficult to note major histological differences between primary intraosseous carcinoma and ameloblastic carcinoma as described in the literature. Corio et al. (1987) state: "Although the primary intra-alveolar carcinoma and the ameloblastic carcinoma exhibit some clinical differences, their histological features are similar enough to suggest a histogenetic relationship. It is possible then that the primary intra-alveolar carcinoma may represent simply a less differentiated, usually nonkeratinizing form of ameloblastic carcinoma both lesions being derived basically from odontogenic epithelial remnants." From a surgeon's perspective, it is difficult to discern if the histological "lumping or splitting" of the classification of odontogenic carcinomas is warranted. However, clinically it is apparent that ameloblastic carcinoma, as exemplified by this case, is an extremely aggressive neoplasm and should be treated accordingly. From our experience with
R.A. Bruce, L T. Jackson
this case and a review of the literature we do not totally concur with McClatchey et al. (1989) who state: "... both malignant ameloblastoma and ameloblastic carcinoma act like well-differentiated squamous cell carcinoma - locally aggressive neoplasms that metastasize late to regional lymph nodes and/or lungs. Wide local exision on the primary site is generally curative." There is ample evidence in the literature that so-called benign ameloblastomas can dedifferentiate with time, and multiple inadequate surgical procedures are associated with metastasis. Although it may take years for the tumour to dedifferentiate, morbidity increases significantly after metastasis. The rational approach to these turnouts is adequate surgery initially to prevent recurrence and certainly, if the lesion recurs, aggressive definitive surgery is indicated. It is apparent from the case in this report that ameloblastic carcinomas do not consistantly behave as "well differentiated squamous cell carcinomas". We feel that when odontogenic carcinomas have histological characteristics of malignancy, whether they are called primary intraosseous carcinoma or ameloblastic carcinoma, they should be treated aggressively with wide local excision. Although radical neck surgery should be considered, there are too few reported cases to make a definitive recommendation. Finally, radiotherapy seems to be of limited value for ameloblastic carcinomas and chemotherapy is as yet unproven. References Andersen, E., G. Bang: Ameloblastic carcinoma of the maxilla. J. Max-Fac. Surg. 14 (1986) 338-340 Appel, B. N., tL S. Verbin: Odontogenic Tumors. Chapter 21 in: Surgical Pathology of the Head and Neck. Barnes L. (Ed.). Dekker, NewYork 1985, p. 1355 Corio, 1L L., L. L GoIdblatt, P.A. Edwards, K.S. Hartman: Ameloblastic carcinoma: a clinicopathologic study and assessment of eight cases. Oral Surg. 64 (1987) 570-576 Dorner, L., A.J. Sear, G. T. Smith: A case of ameloblastic carcinoma with pulmonary metastases. Br. J. Oral MaxillofacSurg. 26 (1988) 503-510 Elzay, tL P.: Primaryintraosseous carcinoma of the jaws. Reviewand update of odontogenic carcinomas. Oral. Surg. 54 (1982) 299 -303 Hartman, K.S.: Granular cell ameloblastoma. Oral Surg. 28 (1974) 241 Kunze, E., K. Donath, H. G. Luhr, W. Englehardt, IL DeVivie: Biology of metastasizing ameloblastoma path. Path. Res. Pract. 180 (1985) 526-535. Laughlin, E.H.: Metastasizing ameloblastoma. Cancer 64 (1989) 776-780 McCIatchey, K.D.: Tumors of the dental lamina: a selectivereview. Seminars in Diagnostic Pathology 4 (1987) 200-204 McClatchey, K.D., M.J. Sullivan, D.R. Paugh: Peripheral ameloblastic carcinoma: a case report of a rare neoplasm. J. Otolaryng. 18 (1989) 109-111 Pindborg, J.J., I.R.H. Kramer, H. Torloni: Histologic typing of odontogenic tumours, jaw cysts and allied lesions. World Health Organization, Geneva, 1982 Ruskin, J.D., D.M. Cohen, L.F. Davis: Primary intraosseous carcinoma: report of two cases. J. Oral Maxillofac. Surg. 46 (1988) 425-432 ~hafer, W. G., M. K. Hine, B.M. Levy: A Textbook of Oral Pathology. Saunders, Philadelphia 1974, pp. 251-258 Slootweg, P. J., H. Mf~ller: Malignant ameloblastoma or ameloblastic carcinoma. Oral Surg. 57 (1984) 168-176 Tsukada, Y., S. de la Pava, J. W. Pickren: Granular cell ameloblastoma with metastasis to the lungs. Report of a case and review of the literature. Cancer 18 (1965) 916
Ameloblastic Carcinoma Ueda, M, T. Kaneda, M. Imaizumi, 7". Ave: Mandibular ameloblastoma with metastasis to the lungs and lymph nodes: a case report and review of the literature. J. Oral Maxillofac. Surg. 47 (1989) 623-628 Waldron, C.A., I.A. Small, H. Silverman: Clear cell ameloblastoma an odontogenic carcinoma. J. Oral Maxilofac. Surg. 43 (1985) 707-717 -
J. Cranio-Max.-Fac. Surg. 19 (1991) Dr. R. A. Bruce Departement of Oral & Maxillofacial Surgery 2010 School of Dentistry The University of Michigan Ann Arbor, M148109-1078 USA
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