Monday 8 March 2004
Mixed tumor, salivary gland type; salivary pleomorphic adenoma; salivary benign mixed tumor
Case 183 (HPC:183) : Pleomorphic adenoma of the parotid gland
Definition: Pleomorphic adenoma is a benign neoplastic tumor of the salivary glands. As the name implies, these epithelial tumors are characterized by great histologie diversity; but despite increased cellularity, they are essentially benign lesions.
Pleomorphic adenoma is the most common type of salivary gland tumor and the most common tumor of the parotid gland. It derives its name from the architectural pleomorphism (variable appearance) seen by light microscopy.
It is also known as "Mixed tumor, salivary gland type", which describes its pleomorphic appearance as opposed to its dual origin from epithelial and myoepithelial elements.
Pleomorphic adenomas typically present as a painless, persistent swelling and can occur at any age.
Pleomorphic adenomas are most common in adults during the third through fifth decades of life but, on rare occasion, may be found during childhood.
Rapid growth of a salivary gland tumor suggests a malignant lesion. A history of slow, minimal growth in a tumor over many years is no assurance that it is benign. Facial nerve involvement is most uncharacteristic for a benign pleomorphic adenoma.
The tumor is usually solitary and presents as a slow growing, painless, firm single nodular mass. Isolated nodules are generally outgrowths of the main nodule rather than a multinodular presentation.
It is usually mobile unless found in the palate and can cause atrophy of the mandibular ramus when located in the parotid gland. When found in the parotid tail, it may present as an eversion of the ear lobe.
Though it is classified as a benign tumor, pleomorphic adenomas have the capacity to grow to large proportions and may undergo malignant transformation, to form carcinoma ex-pleomorphic adenoma, a risk that increases with time.
Although it is "benign", the tumor is aneuploid. It can recur after resection. It invades normal adjacent tissue and distant metastases have been reported after long (+10 years) time intervals.
On gross examination, the lesional tissue is made up of nodules connected by a delicate network of fibrous connective tissue.
True multicentric tumor presentation is practically nonexistent except when the tumor is recurrent following inadequate, previous surgery. This multifocal recurrence is due to a surgical "shelling out" procedure that leaves tiny pseudopod-like transcapsular processes of the tumor in the adjacent salivary gland.
The various histologic patterns seen in these tumors are determined by the interplay of the differentiating epithelial elements and by the amount, as well as the characteristics, of the stroma. It is highly variable in appearance, even within individual tumors.
Classically, it is biphasic and is characterized by an admixture of polygonal epithelial and spindle-shaped myoepithelial elements in a variable background stroma that may be mucoid, myxoid, cartilaginous or hyaline.
Both the epithelial and stromal components are so delicately intertwined that their separation from each other is not feasible.
The epithelial structures may show trabecular, tubular, or cystic features. The ductular proliferation includes both epithelial and myoepithelial components. Epithelial elements may be arranged in duct-like structures, sheets, clumps and/or interlacing strands and consist of polygonal, spindle or stellate-shaped cells (hence pleiomorphism).
Areas of squamous metaplasia and epithelial pearls may be present. The tumor is not enveloped, but it is surrounded by a fibrous pseudocapsule of varying thickness.
The stroma is both myxoid and mucoid, containing considerable amounts of mucopolysaccharide. Chondroid and osseous elements may also be focal stroma! elements.
The tumor extends through normal glandular parenchyma in the form of finger-like pseudopodia, but this is not a sign of malignant transformation.
Occasionally, tubular structures with a double-layered epithelial lining are seen. The outer layer is considered to be a neoplastic likeness of normal myo¬epithelial cells, which are positive for myosin and vimen¬tin but only rarely positive for keratin.
In contrast, the inner tubular lining cells do not stain for myosin but are positive for keratin. The hyaline cells and the spindle cells show a negative reaction for myosin but coexpress both vimentin and keratin.
The varions immunohistochemical studies provide conflicting results for keratin staining of the myoepithelial components of pleomorphic adenomas, which can be explained, at least in part, by the différence in the molecular weights (51-57 kd) of the keratins (KRTs) employed in the study.
Epithelial-predominant pleomorphic adenoma
In rare instances, the epithelial component predominates the histologic picture, with only a minimal number of stromal elements being discernible. In these rare instances a monomorphic adenoma diagnosis is a distinct consideration, if the mucoid myxoid stroma is completely absent.
Pleomorphic adenomas display a wide variety of cell types. These include the inner and squamous cells; myxochondroid cuna formation or without lacunar spaces; hyaline cells; and spindle cells. The boundaries between the epithelial and the mesenchymal components meld imperceptibly.
The tumor often displays characteristic chromosomal translocations between chromosomes 3 and 8. This causes the PLAG1 gene to be juxtaposed to the gene for Beta-catenin. This activates the catenin pathway and leads to inappropriate cell division.