Case report

A 64-year-old female was referred to the authors’ hospital in 2009 with a complaint of a painful swelling in the right mandible. The lesion had been present for 10 months and had gradually increased in size. Initially, the patient consulted the department of oral and maxillofacial surgery at a local hospital where radiographic examination suggested two possible diagnoses, odontogenic cyst or odontogenic tumour. The patient was then referred to the authors’ department. On initial assessment, no systemic symptoms were evident. Extraoral examination was unremarkable. Regional lymph nodes were not palpable. Intraoral examination revealed a diffuse swelling extending from the distal second premolar area to the retromolar area of the right mandible. The overlying mucosa was intact and no ulceration was noted. Panoramic radiography showed a multilocular radiolucent lesion in the right mandible ( Fig. 1 A) .

(A) Panoramic radiograph showing multilocular radiolucent cystic lesion in the right mandible. (B) CT scan showing a well-demarcated multilocular osteolytic lesion in the right mandible.

Computed tomography (CT) showed a well-defined multilocular osteolytic lesion in the body of the right mandible ( Fig. 1 B), and an ill-defined soft tissue mass with destruction of cortical bone was visible in the right retromolar area in soft tissue mode. On CT examination of the abdominal and thoracic regions, no other specific findings were observed. Biopsy findings suggested salivary gland adenocarcinoma. The patient underwent partial resection of the right mandible with supraomohyoid neck dissection. Macroscopically, the tumour measured 35 mm × 25 mm and consisted of cysts and solid areas within the right mandible ( Fig. 2 ).

Macroscopic view of gross specimen.

Microscopically, the tumour was well circumscribed but not encapsulated completely. The tumour contained numerous cystic lumina of various sizes with papillary structures ( Fig. 3 A) . The cyst walls were composed primarily of small cuboidal cells with a few low columnar cells ( Fig. 3 B). Mucus was also observed in the cystic lumina. Nuclear atypia was slight and mitotic figures were rare. Mucous and clear cells were infrequent in the tumour cells. Mucicarmine or Alcian blue stains confirmed no mucin production in the tumour cells of the cyst walls. Zymogen-secreting cells were not detected on PAS or dPAS staining in the tumour cells.

(A) Low-power view of a histopathological section showing cystic lumina of various sizes with papillary projections and intraluminal proteinaceous secretions confirmed as mucin. There was no evidence of intracytoplasmic mucin in the tumour cells (haematoxylin–eosin (H–E) stain; magnification: 20×). (B) High-power view showing cystic lumina lined predominantly with small cuboidal cells (H–E stain; magnification: 100×).

Immunohistochemical investigations revealed positive staining for CK7 and CK34βE12, but negative staining for S100, vimentin, and carcinoembryonic antigen. These histopathological features led to the diagnosis of papillary cystadenocarcinoma. Follow-up for 26 months after surgery indicated no recurrence or metastasis.

Discussion

PCAC of the salivary gland is a rare malignant tumour defined as a low-grade malignancy. In a large study of 57 cases of this lesion by Foss et al., local recurrence and the occurrence of regional lymph node metastasis were 7.7% and 10%, respectively, while no distal metastasis was observed. Most patients presented with a painless, slow-growing mass. According to this study, PCAC was classified into 3 differential histological subtypes based on cell distribution. The most frequent type was composed predominantly of small cuboidal cells with minimal cytological atypia (61%). The second was composed predominantly of either large cuboidal cells (16%) or tall columnar cells (12%). The third type was composed of an admixture of these 3 cell types (11%). The type containing predominantly columnar cells appeared to be more aggressive and metastasised, and this type was therefore considered to be a high-grade variant of PCAC. In the present case, the lesion was composed of cystic lumina of varying sizes, and the cyst walls were predominantly covered with small cuboidal cells. Nuclear atypia and mitotic figures were also rare. Thus, the lesion was regarded as a low-grade malignancy.

The occurrence of salivary gland PCAC accounts for 2% of salivary gland malignant neoplasia. The parotid gland or minor salivary glands of the lip and palate are usually affected. Salivary gland PCAC has also been reported to arise in unusual sites, including the tongue, retromolar area, and submandibular gland. Salivary gland PCAC presenting in the mandible is exceedingly rare, with only 2 cases having been described. In the case reported by Johnston et al. the tumour presented in the mandible and resembled a cystic lesion on radiography. The second case was documented by Li et al. in a retrospective analysis of 22 central malignant salivary gland tumour cases in Southwest China from 1986 to 2006. This was a case of cystadenocarcinoma that also presented in the mandible with local recurrence within 8 months of initial treatment. Central malignant salivary gland tumours are relatively rare. In 1987, Waldron et al. reported only 6 cases (1.4%) of central salivary gland carcinoma in a large study of 426 minor salivary gland tumours from 11 institutions.

Brookstone and Huvos reported 11 cases of central salivary gland tumour of the mandible registered at the Memorial Sloan–Kettering Cancer Center in New York from 1950 to 1990. Martinez-Madrigal et al. reported 16 cases of central salivary gland carcinoma arising in the mandible treated at the University of Texas M.D. Anderson Cancer Center and the Institute Gustave Roussy from 1950 to 1990. Li et al. have recently reported 22 cases of central salivary gland tumour treated at West China Stomatology Hospital of Sichuan University from 1986 to 2006, and also retrospectively reviewed a large series of 197 cases of central malignant salivary gland tumour from the literature. According to this review, the most frequent histological type of tumour was mucoepidermoid carcinoma (68.5%), followed by adenoid cystic carcinoma (16.2%), adenocarcinoma not organ specific, (5%), acinic cell carcinoma (4.6%), carcinoma ex pleomorphic adenoma (4.1%), and epithelial–myoepithelial carcinoma (1.5%).

Available data and prognostic information are limited because of the rarity of PCAC. Criteria for diagnosis, pathogenic origin of the lesion, and consensus for clinical management remains controversial. Some authors proposed similar diagnostic criteria for salivary gland tumours of central origin. Li et al. summarized these and suggested that diagnosis be based on the following criteria: clinical manifestation of osteolysis; radiographic evidence of primary central bone destruction; absence of any primary tumour within the major or minor salivary glands; and histological confirmation of the typical architectural and morphological features of malignant salivary gland tumours.

Various theories have been suggested for the origin of central salivary gland tumours. Ectopic salivary gland tissue is presumed to be one source and has been identified at multiple sites, including the hypophysis, mandible, skin of the neck, cervical lymph nodes, larynx, thyroid gland, mediastinum, stomach, and rectum. In a large study of intraosseous salivary tissue, 13 (0.3%) of 5034 maxillofacial bone samples were shown to contain heterotopic salivary tissue. Odontogenic cyst or impacted tooth has also been suggested to be associated with the origin of central salivary gland tumours. Salivary gland tumour presenting within the mandible has been thought to arise initially from the retromolar mucous gland. This theory is controversial, however, because it is unreasonable to postulate that a lesion arising from the retromolar mucous gland would extend deep into the underlying bone without extraosseous expansion. Neoplastic transformation of heterotopic salivary gland tissue or the epithelial lining of an odontogenic cyst are thought to be likely sources of central salivary gland tumours, although direct evidence for such pathogeneses is lacking.

Treatment for PCAC is similar to that for other low-grade salivary adenocarcinomas. In general, for central salivary gland malignant tumours, wide local excision has been suggested.

Although the effectiveness of radiotherapy or chemotherapy has not been elucidated, observation of perineural invasion during final pathological examination may lead to consideration of postoperative radiation. Brookstone and Huvos established a clinical staging system for salivary gland tumours within the mandible, which is helpful in formulating a treatment plan. This staging system is based on the degree of mandibular destruction: stage I, intact cortical plates with no evidence of bony expansion; stage II, intact cortical plates but some degree of intraosseous expansion; and stage III, cortical perforation, disintegration of the overlying periosteum, or nodal metastasis.

The case presented here was considered as a low-grade type of cystadenocarcinoma. Cervical lymph node metastasis has been reported in a case diagnosed histologically as low-grade cystadenocarcinoma. Taking these factors into consideration, patients diagnosed with PCAC require careful follow-up over the long term.