Pleomorphic Adenoma

Etiology

The etiology of pleomorphic adenoma is unknown, but the incidence of this tumor has been increasing in the last 15-20 years in relation to the exposure of radiation. One study suggests that oncogenic simian virus (SV40) may play a role in the onset or progression of pleomorphic adenoma.  Prior head and neck irradiation is also a risk factor for the development of these tumors. [4]

Epidemiology

Pleomorphic adenoma is the most common benign salivary gland neoplasm. In most studies, it represents 45-75% of all salivary gland tumors; the annual incidence is approximately two to three and a half cases per 100,000 population. Pleomorphic adenoma occurs in individuals of all ages; however, it is most common in the third to sixth decades. Pleomorphic adenoma incidence is slightly more in females than in males (2:1 ratio). Pleomorphic adenomas account for 70-80% of benign salivary gland tumors and are especially common in the parotid gland. [5]Pleomorphic adenoma predominantly affects superficial lobe of the parotid gland. Distribution among the various salivary glands is as follows: 

• Parotid gland: 84% 
• Submandibular gland: 8%
• Minor salivary glands: 6.5% 

Pathophysiology

Microscopically pleomorphic adenoma has a highly variable appearance, hence the name pleomorphic. It is characterized by mixed proliferation of polygonal epithelial and spindle-shaped myoepithelial cells in a variable stroma matrix of mucoid, myxoid, cartilaginous or hyaline origin. Epithelial elements are usually of polygonal, spindle or stellate-shaped cells which may be arranged to form duct-like structures, sheets, clumps,  or interlacing strands. The ducts and tubules are seen usually exhibiting an outer lining in addition to an inner cuboidal epithelial cell layer. This is outer myoepithelial cell layer (or layers) which merges into the surrounding stroma which also contains dispersed or clumped myoepithelial element cells. Areas of squamous metaplasia and epithelial pearls can be found. The tumor lacks the true capsule and is surrounded by a fibrous pseudo capsule of variable thickness. The tumor extends through normal glandular parenchyma in the form of finger-like pseudopodia. These microscopic extensions account for the high risk of recurrence in cases treated with simple enucleation or surgical resections performed with inadequate surgical margins.

Histopathology

Histology will reveal proliferation of myoepithelial and epithelial cells of the ducts. There is also a marked increase in stromal components. The tumor is usually not well encapsulated.

History and Physical

Pleomorphic adenoma mostly presents as a  solitary mobile slow-growing, painless mass, which may be present for many years. Symptoms and signs mainly depend on size, location, and potential to undergo malignant transformation. In the parotid gland, signs of facial nerve weakness occur when the tumor is large or if it undergoes malignant change. Pleomorphic adenoma in the deep lobe of the parotid gland may present as an oral retro tonsillar or para-pharyngeal mass which is visible or usually palpable. Rapid enlargement of a tumor nodule should raise a concern of malignant change. Minor salivary gland tumors may present with a variety of symptoms, including dysphagia, hoarseness,  dyspnea, difficulty in chewing, and epistaxis dependent on the site of the tumor.

Evaluation

The diagnosis is made both on tissue sampling and radiographic studies. Tissue sampling procedures including fine needle aspiration (FNA) and core needle biopsy which can be done in an outpatient setting. These procedures are associated with very low tumor seeding rates.[6][7]

FNA can determine whether the tumor is malignant in nature with an approximate sensitivity of 90%. Core needle biopsy is more invasive but provides more accurate histological typing of the tumor with a diagnostic accuracy of around 97%. Immunohistochemistry may prove to be supportive in delineating the different cell components.

CT examination a pleomorphic adenoma usually appears as smoothly marginated or lobulated homogeneous soft tissue density globular mass. Necrosis can be seen in larger masses. Few foci of calcification are common. Smaller tumors show early homogenous prominent enhancement while in the case of larger tumors enhancement is less marked and delayed.

MRI is similar to CT; smaller masses appear well-circumscribed and homogeneous whereas larger tumors appear heterogeneous.

• T1: usually of low intensity.
• T2: usually of very high intensity (especially myxoid type) 6 often have a rim of decreased signal intensity on T2-weighted images representing the surrounding fibrous capsule.
• T1 C+ (Gd): usually demonstrates homogeneous enhancement. 
• The presence of either T2 hypointensity or ill-defined margins after contrast administration can be a simple MR imaging malignancy test for parotid tumors, with a sensitivity and specificity of 0.70 and 0.73, respectively.
• Post contrast STIR images help the delineate the perineural spread of tumor in case of malignant change.

Ultrasound pleomorphic adenomas characteristically appear hypoechoic in texture.  They usually show a lobulated distinct border with or without posterior acoustic enhancement. Ultrasound guided biopsy or FNA are minimally invasive and cost effective procedures. 

Angiography (DSA) can also be considered.

Treatment / Management

Previously carried out enucleation procedure has been abandoned because of high associated rates of recurrence. Presently pleomorphic adenoma of the parotid gland is treated either with superficial (Patey's operation) or total parotidectomy with the latter being the more frequently performed procedure due to lower incidence of recurrence. Meticulous technique is required to preserve the facial nerve. The tumors of the submandibular glands are treated with simple excision procedure with preservation of adjacent nerve including the mandibular branch of the trigeminal nerve, the hypoglossal nerve, and the lingual nerve.[8]

When in the minor salivary glands, a five mm margin should be obtained. These tumors do not invade into periosteum. Thus, the bone need not be resected. When tumor bed recurrences occur, they show significant resistance to treatment, with management options including monitoring only, surgery, and radiotherapy.

Pleomorphic adenomas harbor a small risk of malignant transformation. The malignant potential is proportional to the time the lesion is in situ (1.5% in the first five years, 9.5% after 15 years). Therefore, excision is warranted in almost all cases. Other risk factors for malignancy include advanced age, radiation therapy, large size, and recurrent tumors.

Differential Diagnosis

Differentials for pleomorphic adenoma include Warthin tumor, parotid nodal metastasis, facial nerve schwannomas, myoepitheliomas, mucoepidermoid and adenoid cystic carcinoma, and a large variety of other neoplasms nonspecific to salivary glands. Histopathology remains the gold standard in differentiating them all.