Pathologic Quiz Case: A 67-Year-Old Woman With a Lump in the Right Cheek

A 67-year-old woman presented with a lump in her right cheek of approximately 6 months' duration. Physical examination revealed an ovoid, freely mobile, firm nodule, which was located 3 to 4 cm anterior to the preauricular area. No intraoral or other lesions were identified. Computed tomographic scan of the head and neck showed no evidence of mass lesions in the normally located bilateral parotid glands and no lymphadenopathy. The patient subsequently underwent an excisional biopsy of the lesion.Gross examination revealed a 10 × 6-mm, well-circumscribed, rubbery, gray-tan mass with small cystic areas. Microscopically, the mass was surrounded by serous salivary gland tissue and showed a variety of histologic patterns with solid areas, microcysts, and papillary fronds projecting into larger cystic spaces and lined by “hobnail” cells (Figure 1). The cystic spaces contained eosinophilic material and were reminiscent of thyroid follicles. The cells were predominantly cuboidal and had a moderate amount of amphophilic to eosinophilic cytoplasm. Many vacuolated cells were present (Figure 2). Significant focal cellular atypia was noted (Figure 1). Mitotic rate averaged 4 mitoses per 10 high-power fields; no atypical mitoses were identified.Acinic cell adenocarcinoma is a relatively rare malignant neoplasm of salivary glands. Published large series of salivary gland tumors and experience at the Armed Forces Institute of Pathology have shown that approximately 83% of all acinic cell adenocarcinomas occur in the parotid gland.1 Other sites include minor salivary glands and submandibular gland. Acinic cell carcinoma accounts for only 2.5% to 7% of all parotid epithelial tumors and 12.5% of parotid gland carcinomas.2 The tumor is often bilateral in the parotid glands, ranking third to mixed tumor and Warthin tumor and first among salivary gland carcinomas.1,2 Most series show a female predominance with an age distribution from the second to seventh decades; the peak incidence is in the fourth through sixth decades. However, the tumor also occurs in the elderly and in children. In children aged 12 years or younger, it is the second most common epithelial salivary gland tumor after mucoepidermoid carcinoma.1,3Acinic cell adenocarcinomas arise from pluripotential reserve or stem cells normally found at the acinar-intercalated duct junctions or in the intercalated ducts proper of mature salivary glands.2The typical clinical history describes a slowly enlarging, painless mass in the parotid gland region (78% for primary and 63% for recurrent).4 Most patients report duration of symptoms of less than a year; however, several patients reported the presence of a lump for more than 30 years. The mass tends to be well circumscribed, may appear encapsulated, and commonly involves the superficial lobe of the parotid gland. Clinical symptoms of pain, short duration of symptoms, fixation to skin or muscle, facial nerve paralysis, and a surgeon's impression of gross invasion are often associated with worse prognosis and increased risk of local recurrence or metastases.1,4,5 Involvement of the deep lobe of the parotid gland is also thought to be associated with poorer outcome.Histologically, acinic cell carcinoma may exhibit any and all of the following growth patterns: solid, microcystic with thyroidlike appearance, papillary-cystic, and follicular. The most common patterns are solid and microcystic. An unusual variant of “dedifferentiated” acinic cell carcinoma has also been described in the literature.6Cytologically, the tumor is composed of well-differentiated acinic cells and/or intercalated ductlike cells, which can have a “hobnail” appearance. An additional important diagnostic clue is the presence of vacuolated cells, which are rather unique (although not pathognomonic) for acinic cell carcinoma.No correlation between specific cell type or architectural pattern and prognosis has been found to date. Certain histologic features, however, are often associated with a higher rate of local recurrence, metastasis, or both. These features include increased mitotic rate, significant atypia, invasion of the adjacent tissue, and positive surgical margins. Still, for acinic cell carcinoma, surgical stage remains a better predictor of clinical outcome than histologic grade.The diagnosis of acinic cell carcinoma is relatively simple and is based on clinical data, characteristic architecture, and typical cytology. Occasionally, special stains and ancillary studies may be needed. Useful special stains are periodic acid–Schiff, lysozyme, and amylase. Electron microscopy can identify both acinar and ductal types of cells. The acinar cells show characteristic cytoplasmic, membrane-bound, electron-dense granules that are smaller and more variable in size than the granules of normal serous cells. The intercalated duct-type cells are small, show few or no secretory granules, and may contain lipid inclusions. Differential diagnoses for papillary-cystic and follicular types of acinic cell carcinoma include metastatic papillary and follicular thyroid carcinoma. Immunostaining for thyroglobulin should resolve the problem. The papillary-cystic type of acinic cell carcinoma may be confused with the rare cystadenocarcinoma of the salivary gland. The distinction is more of academic interest, since the treatment is essentially the same. The distinction can be made by identifying vacuolated cells, which are characteristic for acinic cell carcinoma, and by using special stains such as periodic acid–Schiff, amylase, lysozyme, and mucin.Disease progression, which varies widely, has been studied in several series of acinic cell carcinomas. The local recurrence rate has been reported as ranging from 30% to 50%, with metastases (lymph node, distant, or both) occurring in 7% to 29% of patients. Late recurrences are common. In one study by Lewis et al,4 the patient developed the first local recurrence after more than 30 years of disease-free survival. The goal of treatment is to achieve a complete surgical excision of the primary or recurrent tumor. Incomplete resection or enucleation is associated with an increased risk of local recurrence and metastasis. Radiation therapy is not commonly used, but may be beneficial for some patients for whom complete resection of the tumor cannot be accomplished.In summary, this case illustrates a relatively rare malignant neoplasm of the parotid gland, which developed in an unusual location, the accessory right parotid. The tumor demonstrated characteristic histologic and cytologic features and showed strong immunoreactivity with lysozyme.