Central Adenoid Cystic Carcinoma the Mandible MITCHELL
S. BROOKSTONE, DDS,* ANDREW G. HUVOS, MD,t AND RONALD H. SPIRO, MD*
Adenoid cystic carcinoma is a malignant epithelial neoplasm of salivary gland origin that was originally recognized in 1853 by Robin and Laboulbene.’ The term “cylindroma” was coined by Billroth because of its characteristic top-hat, honeycomb, Swiss-cheese, or cribriform appearance.‘T2 Other synonyms for adenoid cystic carcinoma include basaloma, adenomyoepithelioma, and adenoid cystic epithelioma. It is worth noting that tumors resembling adenoid cystic carcinoma may arise in other anatomic sites, including the lacrimal glands, paranasal sinuses, pharynx, trachea, digestive tract, skin, and breast.3,4 Malignant salivary gland tumors are relatively uncommon (less than 7% of all head and neck cancers), and only 10% prove to be adenoid cystic carcinomas. Although adenoid cystic carcinoma is the most common malignant tumor arising in the submandibular and minor salivary glands, parotid origin predominates in most reports (more than 70%).5,6 Adenoid cystic carcinoma of salivary gland origin occurs most commonly during the fifth and sixth decade of life. Patients often present with the symptoms associated with malignant salivary gland tumors: pain, swelling, ulceration, and facial nerve paralysis.’ Adenoid cystic carcinoma arising centrally within the mandible is extremely rare, with only 12 cases previously reported. *-I9 The proper diagnosis of an intramandibular salivary gland tumor may be confused with osteolytic odontogenic cysts. This study
Received from the Memorial Sloan-Kettering Cancer Center, New York. * Fellow, Dental Service, Department of Surgery. t Attending Pathologist, Department of Pathology. $ Attending Surgeon, Head and Neck Service, Department of Surgery. Address correspondence and reprint requests to Dr Huvos: Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. D 1990 American Association of Oral and Maxillofacial geons
describes an additional case of adenoid cystic carcinoma arising within the mandible. Report of a Case A 33-year-old woman was referred to the Head and Neck Service of Memorial Sloan-Kettering Cancer Center (MSKCC) on November 20, 1989, complaining of slight soreness of her right mandible that she had noticed some 3 weeks previously. At that time, the patient went to her private dentist for what she thought was an endodontic problem involving the mandibular right second molar. A throbbing pain of l-day’s duration, slight trismus, and no indication of swelling or purulence was reported. Following radiographic examination, the patient was referred to an oral and maxillofacial surgeon. A panoramic radiograph taken showed a radiolucent lesion of the right angle and body of the mandible. extending posteriorly towards the coronoid process and anteriorly involving the mesial root of the second molar (Fig 1). After further radiographic studies of the mandible were completed, the oral surgeon obtained some clear fluid by needle aspiration, and an incisional biopsy was performed. A histologic diagnosis of adenoid cystic carcinoma was established and the patient was subsequently referred to MSKCC. Clinical examination showed a well-developed, heaithy, young, white woman, with a very slight fullness overlying the body of the right mandible, just anterior to the angle. There was no other facial asymmetry and no significant pathologic alterations. Results of the neck examination were entirely negative. The patient was able to open her mouth widely without pain to show a peculiar mucosal thickening involving the retromolar gingiva. Laterally, there was slight fullness and tenderness. There was no evidence of paresthesia, and the patient reported that her third molars were extracted at the age of 17 years without incident. No other significant previous medical history was noted. A second panoramic radiograph confirmed the previous findings, although, at this time, the mandibular radiolucency seemed to extend further anteriorly towards the region of the second premolar (Fig 2). Computed tomography (CT) scan demonstrated a well-defined osteolytic lesion involving the posterior body and ascending ramus of the right mandible in intimate relationship to the roots of the second molar tooth. Marked expansion of both lingual and buccal cortices was noticed, without evidence of extraosseous extension (Fig 3). Review of the initial biopsy confirmed the malignant diagnosis; however, paraffin blocks were requested for a more specific characterization. Histologic and radio-
CENTRAL ADENOID CYSTIC CARCINOMA OF MANDIBLE
FIGURE 1. Panoramic radiographic showing a radiolucency of the right mandibular angle and ascending ramus, extending anteriorly towards the mesial root of the second molar.
graphic findings at that time were most consistent with ameloblastoma. The patient was admitted to MSKCC on November 30, 1989. Admission, hematology, serology, chest radiograph, and other data were all within normal limits. On December 1, 1989, a right hemimandibulectomy with preservation of the condyloid process, right supraomohyoid neck dissection (levels 1 to 3), tracheostomy, and mandibular reconstruction using a microvascular fibula free flap were performed (Fig 4). The patient’s postoperative course was uneventful, and on December 15, 1989, she was discharged. MACROSCOPIC
On gross examination, the fleshy, focally hemorrhagic tumor measured 3.5 x 2 x 1.5 cm. Almost all of the grossly visible lesional tissue was located within the medulla of the mandible, with only a small area of tumor present outside the cortex in adjacent soft tissue. Microscopically, the lesional tissue was composed of groups of small cells with darkly stained, uniform nuclei, showing scant cytoplasm and ill-defined cell borders. The tumor cells were arranged in glandular or cylindromatous growth patterns separated by a poorly cellular, fibrous, and hyaline connective tissue stroma typical of a grade 1, cribriform, adenoid cystic carcinoma (Fig 5).
Primary central adenoid mandible is an uncommon
cystic carcinoma of the lesion. In the 12 cases
previously reported, swelling and pain were the most common clinical findings (Table 1). The age of the patients ranged from 24 to 82 years, without gender predilection. This is similar to that reported in patients with adenoid cystic carcinomas arising in the major and minor salivary glands.20 The angle or posterior body of the mandible was involved in each instance. Erroneous diagnoses, based on preliminary clinical and radiographic findings, included osteolytic odontogenic cystic lesions and ameloblastoma. Our search of the English language literature yielded 85 documented salivary gland tumors arising within the mandible. Table 2 summarizes the histologic diagnosis in these patients.8-19,21-26 The most frequently reported histologic variant was mucoepidermoid carcinoma (60 patients). Other subtypes, in addition to adenoid cystic carcinoma, included be-
FIGURE 2. Panoramic radiograph showing extension of the radiolucency anteriorly to include the right second premolar.
FIGURE 3. Computed tomography scan showing a lowdensity lesion of the right mandible, with expansion of the intact buccal and lingual cortices.
nign and malignant mixed tumors, adenocarcinomas, and acinic cell carcinoma. Although the pathogenesis of central salivary gland neoplasms is unknown, several theories have been proposed. 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 intraosseous origin. Most believe, however, that the pathogenesis most likely involves a neoplastic transformation of the mucous-secreting
FIGURE 4. Postoperative panoramic radiograph showing the microvascular fibula free flap in place following hemimandibulectomy.
1331 cells commonly found in the epithelial linings of dentigerous cysts.7 In considering the origin of aberrant salivary gland inclusions in the mandible, Browne showed that 42% of dentigerous cysts have mucous secreting cells in the surface layer of their epithelial lining. 27 In the central mandibular adenoid cystic carcinoma reported by Gingell, the lesion had invaded the periodontal ligament space of a retained root tip, suggesting origin from odontogenic rests or cystic epithelium.” The lesion reported in this case was intimately involved with the roots of the mandibular second molar, giving credence to the theory of neoplastic transformation of cystic or odontogenie epithelium. Regardless of histogenetic origin, definitive criteria establishing origin within the mandible should include 1) radiographic evidence of osteolysis; 2) intact cortical plates; 3) absence of any primary lesion within the salivary glands or other tissues that resemble the architecture of salivary lesions; and 4) histologic confirmation of adenoid cystic carcinoma. 28 Our case seems to fulfill these criteria. It has been shown that adenoid cystic carcinoma has a slow, yet insidiously malignant clinical course, characterized by microscopic foci of tumor which infiltrate nerves, perineural spaces, and tissue planes, explaining the high incidence of recurrence.3*4’6 Yoshimura reported a case of adenoid cystic carcinoma arising in the mandible that had spread along the inferior alveolar nerve eventually invading the Gasserian ganglion.” Lymph node metastases are unusual, but hematogenous tumor spread, usually to the lungs, is quite characteristic.29 Of six patients with central mandibular lesions who had adequate follow up, pulmonary metastasis occurred in four. Histologically, at least three major subtypes of
CENTRAL ADENOID CYSTIC CARCINOMA OF MANDIBLE
FIGURE 5. Photomicrograph showing characteristic cylindromatous glandular structure in the intramandibular adenoid cystic carcinoma. The spaces are lined by a double-cell layer (hematoxylineosin, original magnification X200).
Published Cases of Central Adenoid Cystic Carcinoma of the Mandible 4%
Surgery, radiotherapy Surgery
Trismus, pain Swelling
Pulmonary metastasis Lost to follow-up Pulmonary metastasis*
Loosening of tooth, parathesia of V, Swelling
Loosening of tooth, swelling Pain
Radiotherapy, chemotherapy Surgery, reconstruction, radiotherapy
Mucoepidermoid carcinoma Osteomyelitis
Trismus, pain, swelling Otalgia
Dhawan et al” Slavin13
Ascending ramus Angle
Fibro-osseous lesion Malignant tumor Ameloblastoma
Odontogenic pupal inflammation Cystic lesion
Mushimoto et all6 Kaneda”
Hirota et all9
Brookstone et al
Malignant tumor Malignant tumor
* Data from Burkes Jr (personal communication, February 1990). t Data from Gingell (personal communication, February 1990).
7 Years free of disease, lost to follow-up? Died of
Table 2. Central Salivary Gland Tumors of the Mandible No. of Reported Cases
Histologic Type Mucoepidermoid carcinoma2’,22 Adenoid cystic carcinoma8-‘9 Benign mixed tumo? Malignant mixed tumor’2.23 Adenocarcinoma”~“~ZS Acinic cell carcinoma’(’ Total
60 12 6 3 3
% Total 70 14 7 4 4
adenoid cystic carcinoma can be distinguished. The most common is the cribriform type which displays epithelial cell nests forming a honeycomblike pattern. The tubular type is characterized by epithelial cordlike structures accompanied by a hyaline stroma. The least frequently occurring type, which exhibits slender cuboidal tumor cells with a basophilic cytoplasm and dark-staining nuclei, is the basaloid or solid variant.4*6S29 While it has been thought that such histologic grading offers valuable prognostic information, contradictory reports suggest that clinical staging is more reliable for assessing prognosis .*O Surgery is the treatment of choice, because adenoid cystic carcinoma is considered to be a radiosensitive, but not a radiocurable, tumor. Even when complete resection is possible, the relentless infiltrative capacity of these tumors has suggested that radiotherapy may enhance local control. In this patient, postoperative irradiation was initiated 6 weeks following resection and primary microvascular free flap reconstruction. Summary
A patient with adenoid cystic carcinoma arising centrally within the mandible, a rare location for this malignant salivary gland tumor, is described. Current concepts regarding the etiology, diagnosis, histology, and treatment of central intramandibular salivary gland tumors are discussed and the literature is reviewed.
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