The lesion is well-demarcated and bulges from the surrounding thin rim of normal tissue. It has a solid, tan and lobulated appearance.
Patient with a large PA prior to excision.
Cross section of the (above) excised giant pleomorphic adenoma. Almost complete necrosis of the tumor is evident, with hemorrhage. Despite its size, the mass remains well-circumscribed and encapsulated, consistent with a benign salivary neoplasm.
A classic FNA appearance of pleomorphic adenoma shows myxoid matrix with scattered bland plasmacytoid (myoepithelial) cells intermingled.
Metachromatic fibrillary matrix is a highly useful diagnostic feature on FNA.
Another image of metachromatic matrix containing oval nuclei. This consistency and color of the matrix on air-dried slides are suggestive of the diagnosis.
An intimate blending of epithelial and mesenchymal elements is characteristic of pleomorphic adenoma. A characteristic feature of this tumor are myoepithelial cells which 'melt' into the myxoid stroma. Note the presence of more solid islands of myoepithelial cells.
More cellular islands of epithelium are seen admixed with a richly myxoid, blue tinged stroma. Note again the presence of single spindled myoepithelial cells suspended in the stroma.
Primitive duct formation is evident in this more cellular focus. Although difficult to tell here, the lumen of ducts are lined by epithelial cells, whereas abluminal cells are myoepithelial cells.
Peculiar eosinophilic aggregates are seen in some cases of pleomorphic adenoma.
Higher power shows the aggregates are eosinophilic crystals that form floral arrangements made up of tyrosine. The incidence of these crystalloids widely varies, between 1.5% and 21% of salivary gland tumors (as these crystals are not restricted to pleomorphic adenoma).
This FNA specimen contains the same orange crystals, within the myxochondroid stroma.
Diversity in cellularity and architecture is typical. To to the left are ductal type structures in which a two cell layer can be identified. To the right the basaloid cells lack any particular structure and appear randomly aggregated within the myxoid blue matrix.
Angulated tubular structures are seen nicely in this image.
Spindled cells (left) may also represent part of the cellular diversity of pleomorphic adenoma.
Pleomorphic adenomas may also show epithelial cellularity showing squamoid differentiation. Note the intercellular bridges present (yellow arrowhead) and more abundant eosinophilic cytoplasm.
Cells can be seen encircling small round collagenous balls of eosinophilic material.
Focal areas may show features resembling the cribriform spaces of adenoid cystic carcinoma, but these areas are usually quite limited.
Pleomorphic adenoma (PA) is the most common benign salivary gland neoplasm (60-70% of all tumors in the major salivary glands). The vast majority (75%) arise in the parotid gland; other common sites include the minor salivary glands (especially the palate) and submandibular glands.1,2
Grossly, the tumor is well-circumscribed and variably encapsulated. The cut surface is white-tan and shiny. Microscopically, there is a wide range of histologic patterns as implied by its name. Fortunately, all pleomorphic adenomas are composed of three basic elements: (1) epithelial cells (luminal) forming ductal structures; (2) myoepithelial (abluminal) cells; (3) a mesenchymal stroma.
Of note, molecular studies have now revealed a monoclonal origin of pleomorphic adenoma, whereby both the stromal and epithelial elements derive from a single epithelial precursor, and thus, these tumors are considered pure epithelial tumors. However, it is still helpful to think of pleomorphic adenomas as an amalgamation of the three aforementioned components.1
Although the wide array of patterns of pleomorphic adenoma may be overwhelming, there is (thankfully) a basic organization to this tumor. Tubular structures are lined by eosinophilic epithelial (luminal) cells. Surrounding these ductal structures are abluminal myoepithelial cells which radiate outward and 'melt' into the the background stroma. This melting phenomenon of the myoepithelial cells is quite unique to pleomorphic adenomas and obscures the delineation between the cellular component and background stroma.1
Whereas the epithelial ductal cells are usually cuboidal or flat with eosinophlic cytoplasm, the myoepithelial cells have a very wide range of morphologies including spindled, stellate, cuboidal, clear (hydropic) and plasmacytoid. Plasmacytoid cells are very helpful when identified because they only occur in pleomorphic adenomas and myoepitheliomas. The myoepithelial cells can form sheets, nests, trabeculae or be singly suspended in the stroma. The stroma generally appears myxoid and chondroid. Thus, when chondromyxoid stroma is identified in a salivary gland tumor, you can almost hang your hat on a diagnosis of pleomorphic adenoma.
Occasionally, there is very scanty stroma and the tumor is very cellular -- this variant is called cellular pleomorphic adenoma. Please visit our separate case for this entity to read about it in more detail.
PA is most common during adulthood with a peak incidence at age 4th to 5th decade, however, they can arise in childhood as well. There is a slight female predominance of (F:M of 1.5:1) in tumors that arise in adulthood -- in contrast, there is male predilection in tumors arising in childhood.1,2
Most patients present with a history of a slowly growing mass noted incidentally. Usually, the PAs are in the 2-3 cm range before they are clinically apparent in the parotid region. Occasionally patients may present with advanced disease and large (>6 cm) lesions. Most patients with parotid PAs typically do not present with facial nerve palsy. This slow growing tumor typically involves the superfical parotid or stretches the nerve in the case of a deep lobe tumor. Presence of this symptom should prompt consideration of a different diagnosis or of malignant transformation.
About 3-4% of PAs will undergo malignant transformation to carcinoma-ex pleomorphic adenoma, mostly related to the duration of disease.2
The mainstay of treatment of pleomorphic adenoma is surgical excision. In the case of parotid PAs, this is accomplished with facial nerve preservation, as the tumor does not typically encase nerve branches. Tumors deep to the facial nerve can also be excised with nerve preservation, allbeit with more disection of the nerve required. In some instances, PAs may grow medially into the paraglottic space. In these cases the tumor will typically demonstrate a dumbell appearance as its medial growth is confined by the sphenomandibular ligament.
Because PAs may have a pseudo capsule with tumor cells external to the easiest plane of surgical dissection, it is recommended that PAs be excised with a portion of the normal surrounding salivary gland in conjunction with facial nerve dissection.
Recurrence rate after complete excision is approximately 3.4% and 6.3% after 5 and 10 years respectively. Recurrence is directly related to adequacy of excision. When the tumor recurs, it forms multiple nodules at the site of prior surgical incision. Supposedly, when the surgeon excises the adenoma, microscopic foci of tumor may be innoculated or implanted in the surgical site. Thus, it would make sense that stroma-rich variants of pleomorphic adenoma tend to recur as these tumors are more 'sticky'.1
Malignant transformation (carcinoma ex pleomorphic adenoma) occurs is approximately 2-7% of tumors. Factors that increase this risk include: older age, long-standing tumor, local recurrence, submandibular location, size greater than 2 cm in diameter and moderate mitotic activity.1,2
→Histologically, the tumor is composed of an epithelial and mesenchymal component. A myxochondroid stroma is highly characteristic.
1 Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 244-252.
2 Thomspon LDR. Endocrine Pathology: Foundations in Diagnostic Pathology. Philadelphia, PA: Elsevier; 2006: 295-300.
Other good references:
Laccourreye H, Laccourreye O, Cauchois R, et al. Total conservative parotidectomy for primary benign pleomorphic adenoma of the parotid gland: a 25-year experience with 229 patients. Laryngoscope. 1994;104:1487–1494.
Ohtake S, Cheng J, Ida H, et al. Precancerous foci in pleomorphic adenoma of the salivary gland: recognition of focal carcinoma and atypical tumor cells by P53 immunohistochemistry. J Oral Pathol Med. 2002;31:590–597.
Gilcrease MZ, Nelson FS, Guzman-Paz M. Tyrosine-rich crystals associated with oncocytic salivary gland neoplasms. Arch Pathol Lab Med 1998;122:644–649.