Polymorphous low-grade adenocarcinoma of the parotid gland.

Abstract

Polymorphous low-grade adenocarcinoma (PLGA) of the parotid gland is rare. We describe a new case in which the patient underwent parotidectomy only to experience an extensive recurrence 2 years later The recurrence was treated with radical surgical excision and radiation therapy, and the patient remained disease-free at 5 years of follow-up. We also review the literature on primary parotid PLGA.

Introduction

Polymorphous low-grade adenocarcinoma (PLGA) is an uncommon salivary gland tumor that usually arises from a minor salivary gland. Origin in the parotid gland is rare; to the best of our knowledge, only 28 cases have been previously reported in the literature. Although PLGA is considered to be a low-grade tumor, it does occasionally exhibit two characteristics of malignancy--extensive local infiltration and perineural spread--and therefore it has a propensity for local recurrence. In this article, we describe a new case of primary parotid PLGA, and we review the literature.

Case report

A 45-year-old man presented with an 18-month history of a gradually enlarging left cheek mass. Two years earlier, he had undergone parotidectomy for the treatment of a benign lesion at another institution. The new mass had begun as a painless swelling that progressed to intraoral fullness in the left cheek and soft palate. The mass was not associated with any dysphagia, odynophagia, dysphonia, pain, or bleeding. An oral surgeon performed a transoral biopsy, the results of which were reported as consistent with a pleomorphic adenoma.

The physical examination was significant for the presence of an extensive parotid lesion (figure 1, A). The mass measured 20 x 11 cm, and it was firm, nontender, and noncompressible. It occupied the area of the left parotid gland and extended medially to involve the entire left buccal mucosa. The intraoral component extended into the maxilla and soft palate, displacing the tonsil medially and filling the left side of the oral cavity and oropharynx (figure 1, B). Weakness of the left marginal mandibular branch of the facial nerve was present. A well-healed Blair incision from the previous parotidectomy was noted.

[FIGURE 1 OMITTED]

Computed tomography (CT) of the facial bones revealed that a large, heterogenous parotid mass had filled the left masticator space and eroded the body and angle of the mandible and the left maxilla, with effacement of the oropharynx (figure 2). No lymphadenopathy was seen, and a metastatic workup was negative.

[FIGURE 2 OMITTED]

The patient was taken to surgery, where he underwent a left total parotidectomy with facial nerve sacrifice and mandibular resection in continuity with wide local excision of the soft palate and buccal mucosa, a partial maxillectomy, and an ipsilateral modified radical neck dissection. Histologic examination revealed that the mass was a PLGA; it was made up of clusters of cells with predominantly round to oval nuclei, small nucleoli, and scant cytoplasm arranged in islands surrounded by a mucohyaline stroma (figure 3). In other areas of the mass, central tumor necrosis and increased mitotic activity were noted. The tumor had focally infiltrated the mandible, but bone and soft-tissue resection margins were negative for tumor involvement. Many areas of lymphovascular and perineural invasion were seen. No metastasis to cervical lymph nodes was identified.

[FIGURE 3 OMITTED]

The patient underwent postoperative radiation therapy to 5,000 cGy. At 5 years of follow-up, he exhibited no evidence of recurrence.

Discussion

PLGAs account for 10% of all tumors of the minor salivary glands and 25% of all malignancies of the minor salivary glands. (1) The origin of this tumor in a major salivary gland is rare. The first cases of a PLGA arising from the parotid were published almost simultaneously in 1991 by George et al (2) and Miliauskas. (3) To the best of our knowledge, only 27 other cases of primary parotid PLGA have been reported in the literature since then, including ours. There are no reports of PLGA arising from the submandibular gland. (4,5)

Before its characterization as a separate diagnostic entity in 1983, PLGA was classified as a variant of pleomorphic adenoma, a variant of monomorphic adenoma, an adenoid cystic carcinoma, a malignant mixed tumor, and an adenocarcinoma not otherwise specified. (6,7)

Primary parotid PLGA presents as a slowly growing, asymptomatic tumor that most often involves the superficial lobe. (4,7,8) Demographic characteristics of patients with major and minor salivary gland PLGAs are similar, with the possible exception of some sex differences; Kemp et al reported that the female-to-male ratio was 7:1 for major salivary gland tumors and 2:1 for minor gland tumors. (8) Most patients present in the fifth decade of life. (6-8)

The recurrence rate of parotid PLGA has been reported to be 33.3%; recurrences have been diagnosed as long as 8 to 10 years after the initial presentation and treatment. (2,8,9) Although PLGA is considered to be a low-grade tumor, Kemp et al reported that 6.6% of primary parotid PLGAs metastasized to regional lymph nodes. (8) In a few rare instances, distant metastases have been reported in patients with PLGA of a minor salivary gland, but no case of distant metastasis has been reported in a case of PLGA of parotid origin. (7,8)

Diagnosis. Fine-needle aspiration biopsy is a useful aid to diagnosis. Transoral open biopsy is not recommended prior to definitive treatment because of the risk of seeding the oral mucosa, as occurred in our patient.

On gross examination, PLGA appears as a well-circumscribed, nonencapsulated, firm, homogeneous, tan mass. (l,7) Infiltration of the surface epithelium may give the tumor an ulcerated appearance, but central necrosis is rare. (5,7)

Histologically, PLGAs are partially circumscribed with peripheral infiltration that is characterized by clusters of duct-like structures or individual cells in single file. PLGAs typically exhibit a variety of patterns: solid, trabecular, glandular, cystic, ductal, spindled, fascicular, cribriform, and papillary. (1,5,10) Compared with minor salivary gland tumors, parotid PLGAs tend to (1) have a more uniform histologic structure, (2) contain papillary structures more often, and (3) exhibit less perineural invasion. (8,9) PLGA cytology is characterized by the presence of cuboidal cells with abundant cytoplasm, round to oval nuclei, and inconspicuous nucleoli. (1,5,10) Mitotic figures are rarely seen. (1,5)

Immunohistochemical staining can assist in making a diagnosis of PLGA, as 90% of cells stain positively with S-100 protein and epithelial membrane antigen (EMA). (10) The results of staining with high-molecular-weight keratin are somewhat more variable, as 75 to 95% of the cells stain positively. Muscle-specific actin and carcinoembryonic antigen are poor markers of PLGA because of their high variability in staining. (10) PLGAmay stain with glial fibrillary acidic protein (GFAP), but this is usually less consistent than is GFAP staining of pleomorphic adenomas. Most PLGAs stain poorly with proliferation markers p53 and Ki-67, which supports the clinical observation that PLGAs are slowly growing tumors. (7)

Differential diagnosis. Because PLGAs share many of the histologic characteristics of pleomorphic adenomas, monomorphic adenomas, adenoid cystic carcinomas, and low-grade papillary adenocarcinomas, these other tumors should be considered in the differential diagnosis of PLGA. (5)

Pleomorphic adenomas. PLGAs and pleomorphic adenomas are best distinguished by the presence of PLGA characteristics, such as poor circumscription, peripheral infiltration, and the tendency for perineural invasion. (1,5,10)

Monomorphic adenomas. PLGAs are best differentiated from monomorphic adenomas on the basis of a PLGA's infiltrative borders. (5)

Adenoid cystic carcinomas. PLGAs and adenoid cystic carcinomas may both display cribriform patterns, local infiltration, and perineural invasion, but they can be distinguished from one another by cytology; adenoid cystic carcinomas exhibit basaloid cells with scant cytoplasm. (1,6,7) In addition, PLGAs show spindling, and adenoid cystic carcinomas do not. (5,10) Finally, while PLGAs stain widely with S-100 protein and EMA, adenoid cystic carcinomas stain much less diffusely. (10)

Low-grade papillary adenocarcinomas. A distinction should be made between PLGAs and low-grade papillary adenocarcinomas because the latter display a more aggressive behavior; their rates of both local recurrence and regional lymph node metastasis are higher. (1,6,7) Most authors agree that if the histologic features are predominately papillary, the tumor should be identified as a low-grade papillary adenocarcinoma. (1,6,7,10)

Treatment. The treatment of choice for PLGA is wide local excision with clear margins. The facial nerve should be preserved unless tumor infiltration precludes complete removal without nerve sacrifice. Postoperative radiation therapy is reserved for cases of positive or close surgical margins, but it has not been shown to alter outcome in patients without lymph node metastasis. (7) The presence of cervical metastasis is considered an indication for adjuvant radiation therapy. For the treatment of recurrences, radical excision is warranted. (1)

Follow-up. No patient has died as a direct result of a primary PLGA of the parotid, although a few deaths have been attributed to local extension of a minor salivary gland PLGA into vital structures. (7) Local recurrence can occur many years after the initial presentation, so lifelong follow-up is warranted. (2,6-8)

References

(1.) Peel RL. Disease of the salivary glands. In: Barnes L, ed. Surgical Pathology of the Head and Neck. 2nd ed. New York: Marcel Dekker; 2001:714-17.

(2.) George MK, Mansour P, Pahor AL. Terminal parotid duct carcinoma. J Laryngol Otol 1991;105:780-1.

(3.) Miliauskas JR. Polymorphous low-grade (terminal duct) adenocarcinoma of the parotid gland. Histopathology 1991;19:555-7.

(4.) Puxeddu R, Puxeddu P, Parodo G, Faa G. Polymorphous low-grade adenocarcinoma of the parotid gland. Eur J Morphol 1998;36(suppl):262-6.

(5.) Gibbons D, Saboorian MH, Vuitch F, et al. Fine-needle aspiration findings in patients with polymorphous low grade adenocarcinoma of the salivary glands. Cancer 1999;87:31-6.

(6.) Vincent SD, Hammond HL, Finkelstein MW. Clinical and therapeutic features of polymorphous low-grade adenocarcinoma. Oral Surg Oral Med Oral Pathol 1994;77:41-7.

(7.) Castle JT, Thompson LD, Frommelt RA, et al. Polymorphous low grade adenocarcinoma: A clinicopathologic study of 164 cases. Cancer 1999;86:207-19.

(8.) Kemp BL, Batsakis JG, el-Naggar AK, et al. Terminal duct adenocarcinomas of the parotid gland. J Laryngol Otol 1995;109:466-8.

(9.) Merchant WJ, Cook MG, Eveson JW. Polymorphous low-grade adenocarcinoma of parotid gland. Br J Oral Maxillofac Surg 1996;34: 328-30.

(10.) Gnepp DR, Chen JC, Warren C. Polymorphous low-grade adenocarcinoma of minor salivary gland. An immunohistochemical and clinicopathologic study. Am J Surg Pathol 1988;12:461-8.

Ashli K. O'Rourke, MD; Christine G. Gourin, MD; Zane K. Wade, MD; Richard B. Hessler, MD

From the Department of Otolaryngology-Head and Neck Surgery (Dr. O'Rourke and Dr. Gourin) and the Department of Pathology (Dr. Wade and Dr. Hessler), Medical College of Georgia, Augusta.

Reprint requests: Christine G. Gourin, MD, Associate Professor, Department of Otolaryngology-Head and Neck Surgery, Medical College of Georgia, 1120 15th St., BP 4109, Augusta, GA 30912. Phone: [phone]; fax: [phone]; e-mail: [e-mail]