Pleomorphic adenoma is a benign salivary gland tumor. It is almost 85% found in the Parotid gland and the remainder less commonly seen in the submandibular salivary gland (10%) and is seldom encountered in the sublingual gland (1%) and minor salivary glands.
This tumor is also referred to as a benign mixed tumor. It is histologically the most common type of benign salivary gland tumor, which comprises approximately half of all salivary tumors. Other rarer benign salivary gland tumors include Warthin tumor, basal cell adenoma, and canalicular adenoma.
Causes of Pleomorphic Adenoma
Pleomorphic adenomas may occur at any age, but the highest incidence is in the third to sixth decades of life. The average age at presentation is between 43 and 46 years It also represents the most common salivary neoplasm in children. Pleomorphic adenoma is seen more often in females than in males (2:1 ratio). The cause of this tumor is mostly unknown but few associations are seen which includes
- Radiation: the incidence of this tumor has been found to increase 15-20 years after exposure to radiation.
- Viral infection
- Environmental factors and industrial exposure to factors such as rubber manufacturing, hairdressers, beauty shops, and nickel compounds
- Genetic: Rearrangement of chromosome band 8q12 (the target gene is pleomorphic adenoma gene 1 [PLAG1]) and Rearrangement of chromosome band 12q13-15 (high mobility group AT-hook 2 gene, HMGA2) are linked with the tumor
Pathophysiology of Pleomorphic adenoma
The tail of the superficial lobe of the parotid salivary gland is the most common site of occurrence for pleomorphic adenoma (70-80% of cases), although this lesion can occur in any parotid location. The tumor has the following 3 components:
- An epithelial cell component
- A myoepithelial cell component
- A stromal (mesenchymal) component
The epithelial component consists of epithelial and myoepithelial cells. The stromal component is a product of the modified myoepithelial cells and may appear mucoid, myxoid, hyaline, chondroid, myxochondroid, or even osseous Chondroid areas represent true cartilage formation (containing type II collagen and keratin sulphate)
Microscopic satellite tumor nodules, pseudopodia, and capsular penetration may be seen beyond the capsule. This may be the cause of the recurrence of pleomorphic adenomas in cases that were treated with simple enucleation or in cases in which surgical resection was performed with inadequate surgical margins.
Sign and symptoms of Pleomorphic adenoma
It presents as a slow-growing, painless mass, which may be present for many years. In the parotid gland, these neoplasms usually occur in the posterior inferior aspect of the superficial lobe In the submandibular glands they present as well-defined palpable masses. In the parotid gland, the tumors are usually several centimeters in diameter but can reach much larger sizes if left untreated. Rapid enlargement of a tumor nodule should raise a concern about the development of malignant change.
The signs or symptoms indicative of facial nerve involvement (eg, facial nerve paralysis) is generally indicative of a malignant rather than a benign tumor. In minor salivary gland tumors may present with a variety of symptoms, depending on the site of the tumor; such symptoms include dysphagia, dyspnea, hoarseness, difficulty in chewing, and epistaxis. If present in the deep lobe of the parotid gland, it may present as an oral retrotonsillar mass or parapharyngeal space tumor.
How to Diagnose pleomorphic adenoma?
Cancers of the major glands are staged according to the eighth edition (2017) of the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) tumor, node, metastasis (TNM) system
- Computed tomography (CT) scanning
- primary imaging modalities used to assess tumors of the salivary glands.
- It allows the detection of lesions and assessment of their extension and characteristics as well as their relationships to nearby Structures typically smooth, well-marginated tumors, though nodularity along the outer surface.
- Fine Needle aspiration: pleomorphic adenoma is made through straightforward microscopic identification. However, immunohistochemistry (IHC) may be supportive and helpful in delineating the different cell types – Keratin, P-63, Calponin, maspin, S-100 to name a few. Tissue diagnosis is required to make the diagnosis of a salivary gland tumor and to determine whether such a tumor is benign or malignant, ultrasound can facilitate fine needle aspiration (FNA) and core needle biopsy
- Magnetic resonance imaging (MRI): The higher accuracy levels might be obtained through which shows circumscribed, homogeneous masses with low intensity on T1-weighted images, and high intensity on T2-weighted images.
- PET scan: dual-isotope imaging with technetium Tc 99m and thallium Tl 201 single-photon emission.
- CT (SPECT) is accurate in distinguishing various tumors of the salivary glands. Not done routinely,
- Fludeoxyglucose (FDG) positron emission tomography (PET) has good diagnostic accuracy in the assessment of regional lymph nodes and distant metastases in patients with salivary gland malignancies.
- Sialography has been used in the past to diagnose.
For Benign and malignant tumors of the salivary gland, the differential diagnosis of patients includes salivary cysts, cysts of the first branchial cleft, salivary gland stones, sarcoid, Sjögren syndrome, metastases from other tumors, lymphoepithelial cysts (particularly in an immunocompromised host), chronic sclerosing sialadenitis (Küttner tumor), and regional lymphadenopathy from infectious, inflammatory, or malignant diseases.
The malignant parotid tumor must be distinguished from Bell’s palsy. The sarcoid infiltration of the parotid gland (known as Heerfordt syndrome) and intra-parotid facial nerve schwannoma also presents with Facial nerve palsy.
Management of Pleomorphic adenoma
Surgical removal with adequate margins is the principal treatment. For most patients with benign, well-circumscribed tumors, the prognosis is excellent after surgical resection. However, recurrence can be a problem with pleomorphic adenomas.
Because of its microscopic projections, this tumor requires a wide resection to avoid recurrence. A superficial parotidectomy is sufficient for the majority of these lesions. A small tumor in the tail of the parotid gland may be removed with a wide margin of normal tissue sparing the remainder of the superficial lobe. The lesions that occur in the submandibular gland are treated by the removal of the entire gland.
- Recurrence: In spite of the capsule, close excision should not be attempted, as this can lead to recurrence of the tumor.
- Malignant transformation: The signs of Malignant transformation includes rapidly growing tumor and facial nerve involvement. There are three types of malignant transformation, which are metastasizing pleomorphic adenoma (MPA), carcinoma ex pleomorphic adenoma, and true malignant mixed tumor (carcinosarcoma). For a tumor to be malignant, there should be features indicative of malignancy (ie, anaplasia, necrosis, increased mitosis, and an invasive growth pattern). Second, the primary site must be separate from the metastatic site, and both sites must show the features of biphasic benign pleomorphic adenoma.
- Spread: It has been postulated that the tumor may gain access to the vascular or lymphatic system as a result of iatrogenic manipulation during a surgical procedure. The first site of lymphatic spread is the intraparotid lymph nodes, followed by level I and level II cervical nodes. Distant metastases most frequently localize to lung, followed by bone and liver
2. Image from wikipedia: https://en.wikipedia.org/wiki/File:Pleomorphic_adenoma_(1)_parotid_gland.jpg