Central adenoid cystic carcinoma of the mandible: Case report and literature review of 16 cases Jehad Al-Sukhun, PhD, MSc, BDSa, Christian Lindqvist, PhD, MD, DDSb, Jarkko Hietanen, PhD, MSc, MD, DDSc, Ilmo Leivo, PhD, MDd, and Heikki Penttilä, MDe Helsinki, Finland HELSINKI UNIVERSITY HOSPITAL, HUSLAB, UNIVERSITY OF HELSINKI
Central intraosseous adenoid cystic carcinoma (ACC) of the mandible, formerly known as cylindroma, is a rare neoplasm with only 16 cases reported in the literature. We describe the diagnosis, etiology, and treatment of a central ACC located in the mandibular premolar region. We also review the literature. This case illustrates 2 key facts regarding the diagnosis and etiology of ACC. First, central salivary gland tumors should be considered in the differential diagnosis of cystic lytic lesions in the mandible. Second, even though the origin of this type of tumor is still unknown, the presence of ectopic tissue anterior to the submandibular gland in the submandibular area indicates that this tumor might be made up of ectopic embryogenic inclusions. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:304-308)
Adenoid cystic carcinoma (ACC), arising centrally within the mandible is extremely rare, with about 16 reported cases (Table I).1-16 It most commonly affects adults, with a peak incidence in the fourth to sixth decades.17 Adenoid cystic carcinoma, formerly known as cylindroma, forms only 2% of parotid gland tumors but is the commonest tumor affecting the minor salivary glands.17,18 It occurs most frequently in the palate, cheek, and floor of the mouth.15-17 The typical appearance is of a smooth lump. The lesion is painless initially but at a later stage pain may result from invasion of adjacent nerves.17,18 Locally, adenoid cystic carcinomas grow slowly and widely due to the propensity of the tumour for perineural invasion. Lymph nodes metastases are often late events. By contrast, systemic metastases are common.17-19 With the propensity for adenoid cystic carcinoma to spread widely along perineural spaces, resection must be wide, and in the parotid gland sacrifice of the facial nerve is unavoida
Senior registrar and clinical research associate, Department of Oral and Maxillofacial Surgery, Helsinki University Hospital, Helsinki, Finland. b Professor and Chair, Department of Oral and Maxillofacial Surgery, Helsinki University Hospital, Helsinki, Finland. c Professor, HUSLAB, Department of Oral Pathology, Institute of Dentistry, University of Helsinki, Helsinki, Finland. d Consultant, Department of Pathology, Helsinki University Hospital, Helsinki, Finland. e Consultant, Plastic surgery, Department of Oral and Maxillofacial Surgery, Helsinki University Hospital, Helsinki, Finland. 1079-2104/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.tripleo.2005.06.029
able.17-19 We report an unusual case of intraosseal ACC, primarily affecting the mandibular bone, that was initially diagnosed as a periapical/cystic lesion during dental treatment. CASE REPORT An 80-year-old female was referred by a general dental practitioner for the management of persisting pain in the left premolar region of the mandible following root canal treatment of the lower left first premolar. A panoramic radiograph (Fig. 1) and intraoral periapical radiographss showed an irregular “ginger bread–shaped” lytic lesion related to the premolar region. The lesion was ⬃3 cm in maximum diameter. The lesion was confined within the mandibular bone, without erosion of the cortical bone. All the teeth including the lower left second premolar were vital. The lesion was clinically diagnosed by her dentist as a periapical cystic lesion, and root canal treatment on the first premolar was performed. The endodontic treatment resulted in increased pain, and a slowgrowing swelling of the vestibular mucosa overlying the premolars was detected. The pain was resistant to medical treatment, and the patient was referred to the Department of Oral and Maxillofacial Surgery at the Helsinki University Central Hospital. Histology of the lesion showed 3 patterns of growth of an adenocystic carcinoma tumor: cribriform, tubular, and solid. However, islands of epithelial cells containing numerous spherical spaces giving a “Swiss cheese” appearance were predominant. The spaces were pseudocysts and consisted of proteoglycans and reduplicated basement membrane material. The histologic features were consistent with a cribriform variant of ACC of possible salivary gland origin (Fig. 2). Subsequent examination, including MRI and CT scan of the salivary glands and cervical region, did not disclose additional neoplastic deposits in the head and neck; no other lesions of the major or minor salivary glands were present. The only additional finding detected on the CT scan and the
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Al-Sukhun et al. 305
Table 1. Published data on 16 patients with central adenoid cystic carcinoma of the mandible. Age (Y)
Hämori et al3 Shin et al4
Dahwan et al5
Slavin et al6 Burkes EJ7
Yoshimura Y et al8
Osteomyelitis Fibro-osseous lesion Malignant tumour Ameloblastoma Odontogenic infection Cystic lesion
Trismus, pain, swelling Otalgia Trismus, pain
Mushimoto et al9 Kaneda et al10
Amelobalstoma Cystic lesion
Gingell et al11
Hirota J & Osaki12
Brookstone et al13
Clark et al14
Angle, Body Body
Favia et al15
Chen et al16
Denture irritation Malignant tumour Malignant tumour Peri-apical lesion Peri-apical lesion Peri-apical lesion
Surgery, radiotherapy Surgery
Pulmonary metastasis -
Paraesthesia, tooth mobility Swelling Swelling, tooth mobility Pain
Surgery, radiotherapy Surgery, radiotherapy Surgery
Lost to follow-up Pulmonary metastasis
7-years follow-up, lost to follow-up Died of pneumonia 4.5-years follow-up, free of tumour 14-year follow-up, free of tumour -
Fig. 1. Preoperative OPG radiograph showing an irregular low-grade lytic lesion related to the premolar region in the left mandible (black arrows). Inset: Periapical radiograph displays endodontic treatment performed on the first premolar, where the lesion was misdiagnosed as a periapical/cystic lesion.
306 Al-Sukhun et al.
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Fig. 2. Microscopic view of the adenoid cystic carcinoma. The tumor grows in clusters which widely infiltrate the surrounding bone. Pseudocystic spaces, containing eosinophilic material, are evident and identify the typical cribriform pattern of this neoplasm (H&E, ⫻60).
Fig. 3. Preoperative CT scan showing ectopic tissue of similar appearance to the salivary gland, anterior to the submandibular gland (white arrow).
MRI was the presence of ectopic tissue of similar appearance to salivary gland, anterior to the submandibular gland (Fig. 3). Also, the whole-body CT scan and bone scan excluded distant metastases (lung and bone). The patient underwent wide
DISCUSSION Adenoid cystic carcinoma was first described by Theodor Bilroth in 1856. He studied its histologic features and described the long amorphous compartments as cylinders. Thus the term “cylindroma” was coined. It is only recently that the tumor has been renamed as adenoid cystic carcinoma.1-16 Among the first to use the latter term was Spies in 1930.14 Until the 1940s, the tumor was thought to be a benign variant of the mixed salivary gland tumor. In 1943, Dockerty and Mayo emphasized the malignant nature of this tumor.14 Primary ACC of the mandible is a rare tumor. In the 16 cases previously reported, swelling (14%) and pain (57%) were the most common clinical findings. The age of the patients ranged from 24 to 82 years, with no gender predilection. This is similar to that reported in patients with ACC arising in the major or minor salivary glands.17-19 The most common site was the posterior body or angle of the mandible. CT and MR imaging are useful in surgical planning, especially with regard to the submucosal extent and perineural spread, which can be difficult to assess clinically. The lesions are generally poorly defined and have infiltrative margins. The center of the lesion, as was the case with our patient, is usually low density on the CT scan and radiograph, a characteristic that can help differentiate it from a primary squamous cell carcinoma.20 Erroneous diagnoses, based on preliminary clinical and radiologic findings, include focal sclerosing osteitis, cementoblastoma, cementifying and ossifying fibroma, periapical cemental dysplasia, complex odontoma, and calcifying epithelial odontogenic tumor. Owing to the exceedingly rare occurrence of primary intraosseous ACC, the diagnosis of such neoplasms is troublesome and, regardless of the histology, should rely on the application of strict diagnostic criteria,13 including: 1) radiographic evidence of osteolysis; 2) presence of intact cortical plates; 3) absence of any primary tumor within the major or minor salivary glands; and 4) histologic confirmation of the typical architectural and morphologic features of ACC. All these diagnostic criteria were satisfied in the case reported here. The pathogenesis of central salivary gland neoplasms is unknown, but several theories have been proposed. Some theories propose that the pathogenesis most likely involves a neoplastic transformation of the mucus-secreting cells commonly found in the epithelial linings of dentigerous cysts.13, 21
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Ectopic salivary gland tissue has been observed in several head and neck locations, including the cervical skin, middle ear, mastoid, maxilla, and mandible. Although rare, salivary gland malignancies can arise in such ectopic salivary gland tissue. Brookstone et al.13 reviewed the relevant literature and found 137 such cases arising in the maxilla and mandible. ACC was the second most common histologic subtype (23 cases), following mucoepidermoid carcinoma (81 cases). It is thought that ectopic entrapment of retromolar mucous glands or developmentally included embryonic remnants of submandibular glands within recesses or lacunae of the mandible could explain the intraosseous origin of a tumor.22,23 The presence of ectopic tissue that mimics the appearance of salivary glands in the case reported here corroborates this hypothesis. It was not possible to identify the tissue histologically because it was left in place and not included in the surgical resection. Histologically, 3 patterns of growth have been described.17,19 The typical ACC has a cribrifrom pattern: Nests and columns of cells of rather bland appearance are arranged concentrically around gland-like spaces which are filled with hyaline periodic acid-Schiff–positive material. Some have a predominantly tubular pattern and a few others have a solid pattern. The prevalence of cribriform or tubular growth patterns is associated with a better prognosis, in contrast to the presence of ⬎50% solid areas, which indicates an aggressive clinical course.13,17,24 Although it was thought that such histologic grading offers valuable prognostic information, contradictory reports suggest that clinical staging is more reliable for assessing prognosis.20 The clinical stage seems to have a major impact on prognosis, with tumours ⬎4 cm being associated with an unfavorable outcome.22 In addition, the primary site of the tumor also influences the prognosis, with tumors of the minor salivary glands showing a more aggressive behavior.17,18 The occurrence of 4 or more symptoms at presentation, perineural invasion, and lymph node metastasis also are predictors of poor prognosis.24 Patients with conventional ACC of the salivary glands show a good 5-year survival rate, despite poor clinical outcome after prolonged observation (10-20 years).20,24 Overall, the long-term survival of these patients is poor, owing to the occurrence of late recurrences or metastases, even for low-grade tumors.20,24 About 40%-60% of patients develop distant metastases (lungs, bone, and soft tissues), despite local control of the tumor.19 The occurrence of bone metastases usually corresponds to rapid tumor dissemination and death of the patient, whereas lung metastases demonstrates a less aggressive clinical course, susceptible of remission after surgical resection.19,22
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The treatment of adenoid cystic carcinoma involves surgical resection with wide margins.1-17 ACC is considered to be radiosensitive but not radiocurable. The surgeon must pay particular attention to obtaining clear margins around regional nerves.14 The surgical ablation must be individualized because radically mutilating surgery does not appear to improve the prognosis in highly aggressive tumors. Neck dissection should be performed in those patients who have clinical or radiologic evidence of cervical lymphatic metastasis. Prophylactic neck dissection is generally not recommended.1-17 Postoperative radiation therapy enhances local and regional control in ACC. Radical surgery followed by postoperative radiation therapy results in 5- and 10-year survival rates of 77% and 57%, respectively.25 Adenoid cystic carcinoma in our patient was a primary intraosseous lesion. The patient underwent wide surgical excision of the tumor, with an en-bloc partial resection of the mandible. Perineural infiltration was not evident, and the surgical margins were tumor free. The morphologic features of the tumor were consistent with the diagnosis of ACC of possible salivary gland origin. The defect was reconstructed using a free bone graft and the teeth were replaced with a dental prosthesis supported by implants, which provided an excellent functional and cosmetic result. No postoperative radiation therapy was administered to the primary site. The patient is alive and well, with no evidence of recurrence or distant metastases 3 years from the original diagnosis. However, long-term follow-up is essential regardless of the site because of the tumor’s propensity for late recurrence and metastasis. This case illustrates 2 key facts regarding the diagnosis and etiology of adenoid cystic carcinoma. First, central salivary gland tumors should be considered in the differential diagnosis of cystic lytic lesions in the mandible. Second, even though the origin of this type of tumor is still unknown, the presenc of ectopic salivary tissue anterior to the submandibular gland indicates that this tumor might be made up of ectopic embryogenic inclusions. We would like to thank Dr Anni Suomalainen, consultant radiologist and Mr Jarmo Nummenpää, medical illustrator, for their technical expertise in providing the relevant radiographs and images. REFERENCES 1. Bumstead WD. Cylindroma of the mandible. Oral Surg 1955;8:546. 2. Bradley JC. A case of cylindroma of the mandible. Br J Oral Surg 1968;5:186-93. 3. Hämori J, Krasznai G. A mandibula cylindromaja [Hungarian]. Orv Hetil 1969;5:186. 4. Shin MS, Kim HP, Kim ZS, Yuh I, Chang HR, Chung KK. Adenoid cystic carcinoma of the mandible. Taehan Chikkwa Uisa Hyophoe Chi 1972;10:241.
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308 Al-Sukhun et al. 5. Dhawan IK, Bhargava S, Nayak NC, Gupta RK. Central salivary gland tumours of jaws. Cancer 1970;26:211-7. 6. Slavin G, Mitchel RM. Adenoid cystic carcinoma of the mandible. Br J Surg 1971;58:546. 7. Burkes EJ. Adenoid cystic carcinoma of the mandible masquerading as periapical inflammation. J Endod 1978;1:76. 8. Yoshimura Y, Hasega K, Wada T, Fujita K, Kawakatsu K. Metastasis of adenoid cystic carcinoma of the mandible to the Gasserian ganglion. J Am Dent Assoc 1978;94:469. 9. Mushimoto K, Hashimoto Y, Tabuchi M. Central adenoid cystic carcinoma of the mandible: report of a case. Jpn J Oral Surg 1978;24:973. 10. Kaneda T, Mizuno N, Takeuchi M, Yamashita T. Primary central adenoid cystic carcinoma of the mandible. J Oral Maxillofac Surg 1982;40:741. 11. Gingell JC, Siegel MA. Adenoid cystic carcinoma of the mandible. J Am Dent Assoc 1983;107:600. 12. Hirota J, Osaki T. Primary adenoid cystic carcinoma of the mandible. J Oral Maxillofac Surg 1989;47:176. 13. Brookstone MS, Huvos AG, Spiro RH. Central adenoid cystic carcinoma of the mandible. J Oral Maxillofac Surg 1990; 48:1329-33. 14. Clark JM, Triana RJ, Meredith SD. Uncontrolled central adenoid cystic carcinoma: case report. Ear Nose Throat J 2000;79:784. 15. Favia G, Maiorano E, Orsini G, Piattelli A. Central (intraosseous) adenoid cystic carcinoma of the mandible: report of a case with periapical involvement. J Endod 2000;12:760-3. 16. Chen YK, Chen CH, Lin CC, Hsue SS, Lin YR, Lin LM. Central adenoid cystic carcinoma of the mandible manifesting as an endodontic lesion. Int Endod J 2004;10:711-6.
17. Langdon JD, Henk. JM. Malignant tumours of the mouth, jaws and salivary glands. London: Edward Arnold; 1995. 18. Foote FW, Frazell EL. Tumours of the major salivary glands. Cancer 1953;6:1065-133. 19. Ellis GL, Auclair PL. Tumors of the salivary glands. Atlas of tumor pathology. 3rd series. Bethesda (MD): Armed Forces Institute of Pathology; 1996. p. 203–16. 20. de Kerviler E, Bely N, Laccourreye O, Clement O, Halimi P, Frija G. The aryepiglottic fold as a rare location of adenoid cystic carcinoma. AJNR Am J Neuroradiol 1995;16:1375-7. 21. Schafer WG, Hine MK, Levy BM. Textbook of oral pathology. Philadelphia: Saunders; 1974. 22. Jafek BW, Strife JL. Accessory lobe of the submandibular gland. Diagn Radiol 1973;75-7. 23. Cohen JI: Submandibular accessory salivary gland causing Warthin’s duct obstruction. Head Neck 2000;717-21. 24. Fordice J, Kershaw C, El-Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck. Predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg 1999;125:149-52. 25. Black KM, Fitzpatrick PJ, Palmer JA. Adenoid cystic carcinoma of the salivary glands. Can J Surg 1980;23:32-5.
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The Journal wishes to extend its sincere appreciation to Jay Chitwood and Dennis Dunsmore of Kodak Dental Systems, PracticeWorks, Inc. for their generous underwriting of oral-maxillofacial surgery resident subscriptions to our monthly publication. This clearly represents Kodak Dental Systems, PracticeWorks, Inc.’s dedication to health professional education and is particularly important at this time of mounting economic pressures on residency programs, and their faculty and trainees. Residents will regularly benefit from the peer-reviewed, up-to-date articles in TripleO in disciplines of importance to them as they prepare to become surgeons and get ready for their in-service and board certification examinations. James R. Hupp Editor-in-Chief