Pleomorphic adenoma is a common benign salivary gland neoplasm characterised by neoplastic proliferation of epithelial (ductal) cells along with myoepithelial components, having a malignant potentiality. It is the most common type of
salivary gland tumor
Salivary gland tumours, also known as mucous gland adenomas or neoplasms, are tumours that form in the tissues of salivary glands. The salivary glands are classified as major or minor. The major salivary glands consist of the parotid, submandibu ...
and the most common tumor of the
parotid gland
The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the man ...
. It derives its name from the architectural
Pleomorphism
Pleomorphism may refer to:
* Pleomorphism (cytology), variability in the size and shape of cells and/or their nuclei
* Pleomorphism (microbiology), the ability of some bacteria to alter their shape or size in response to environmental conditions
* ...
(variable appearance) seen by light microscopy. It is also known as "Mixed tumor,
salivary gland
The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands (parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary gla ...
type", which refers to its dual origin from epithelial and myoepithelial elements as opposed to its pleomorphic appearance.
Clinical presentation
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
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
of the
mandibular ramus
In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower teeth in place. The mandible sits beneath the maxilla. It is the only movable bone ...
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
A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...
, pleomorphic
adenoma
An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...
s have the capacity to grow to large proportions and may undergo malignant transformation, to form
carcinoma ex-pleomorphic adenoma
Carcinoma ex pleomorphic adenoma (ca ex PA) is a type of cancer typically found in the parotid gland. It arises from the benign tumour pleomorphic adenoma.
Its prognosis depends on the stage. Early tumours have essentially a benign behaviour.
Sig ...
, a risk that increases with time (9.5% chance to convert into malignancy in 15 years). Although it is "benign", the tumor is
aneuploid
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...
, it can recur after resection, it invades normal adjacent tissue, and distant metastases have been reported after long (+10 years) time intervals. This tumour most often presents in the lower pole of the superficial lobe of the gland, about 10% of the tumours arise in the deeper portions of the gland. It occurs more frequently in females than in males, the ratio approximating 6:4. The majority of the lesion are found in patients in the fourth to sixth decades with an average age of occurrences of about 43 years, but these are relatively common in young adults and have been known to occur in children.
Histology
![Pleomorphic adenoma (1) parotid gland](https://upload.wikimedia.org/wikipedia/commons/f/f8/Pleomorphic_adenoma_%281%29_parotid_gland.jpg)
Morphological diversity is the most characteristic feature of this neoplasm. Histologically, it is highly variable in appearance, even within individual tumors. Classically it is biphasic and is characterized by an admixture of polygonal
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
and spindle-shaped
myoepithelial
Myoepithelial cells (sometimes referred to as myoepithelium) are cells usually found in glandular epithelium as a thin layer above the basement membrane but generally beneath the luminal cells. These may be positive for alpha smooth muscle actin a ...
elements in a variable background
stroma that may be mucoid, myxoid, cartilaginous or hyaline. 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 tumor extends through normal glandular parenchyma in the form of finger-like pseudopodia, but this is not a sign of malignant transformation.
The tumor often displays characteristic chromosomal translocations between chromosomes #3 and #8. This causes the
PLAG gene to be juxtaposed to the gene for
beta catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcriptio ...
. This activates the catenin pathway and leads to inappropriate cell division.
Diagnosis
![Pleomorphicadenoma](https://upload.wikimedia.org/wikipedia/commons/2/29/Pleomorphicadenoma.jpg)
The diagnosis of salivary gland tumors utilize both tissue sampling and radiographic studies. Tissue sampling procedures include
fine needle aspiration
Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, aft ...
(FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include
ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
,
computer tomography
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
(CT) and
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI).
Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with
sensitivity around 90%. FNA can also distinguish primary salivary tumor from metastatic disease.
Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic
accuracy
Accuracy and precision are two measures of ''observational error''.
''Accuracy'' is how close a given set of measurements (observations or readings) are to their ''true value'', while ''precision'' is how close the measurements are to each other ...
greater than 97%. Furthermore, core needle biopsy allows more accurate histological typing of the tumor.
In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound. Ultrasound is also frequently used to guide FNA or core needle biopsy.
CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as
perineural invasion
In pathology, perineural invasion, abbreviated PNI, refers to the invasion of cancer to the space surrounding a nerve. It is common in head and neck cancer, prostate cancer and colorectal cancer.
Unlike perineurial spread (PNS), which is defined ...
when compared to CT only.
Treatment
![Relative incidence of parotid tumors](https://upload.wikimedia.org/wikipedia/commons/b/b1/Relative_incidence_of_parotid_tumors.png)
Overall, the mainstay of the treatment for salivary gland tumor is surgical resection.
Needle biopsy is highly recommended prior to surgery to confirm the diagnosis. More detailed surgical technique and the support for additional
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to:
* Adjuvant therapy in cancer management
* Analgesic ...
radiotherapy depends on whether the tumor is malignant or benign.
Surgical treatment of parotid gland tumors is sometimes difficult, partly because of the anatomical relationship of the facial nerve and the parotid lodge, but also through the increased potential for postoperative relapse.
Thus, detection of early stages of a tumor of the parotid gland is extremely important in terms of prognosis after surgery.
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There have been several approaches for surgery of parotid pleomorphic adenoma in the course of time. Enucleation of the tumor (i.e. intracapsular dissection), a procedure that was common in the early 20th century, is nowadays obsolete due to very high incidence of recurrence.
After the time of enucleations, pleomorphic adenomas of parotid gland were recommended to be routinely treated with superficial or total parotidectomy. These procedures combine complete tumor removal and identification of the main trunk of facial nerve during surgery to avoid any lesions to the nerve. However, extensive surgery may cause significant morbidity, such as Frey´s syndrome (excessive sweat while eating) and salivary fistula. Also, aesthetic outcome may be compromised. Therefore, less invasive procedures have been preferred in selected cases during the recent years, and introduction of perioperative neuromonitoring enabled the evolution of several different surgical techniques some twenty years ago.
Currently, the choice of surgical approach for parotid pleomorphic adenoma is mainly based on the size, location, and mobility of the tumor. The recommended main techniques include extracapsular dissection, partial superficial parotidectomy, and lateral or total parotidectomy. Nevertheless, the experience of surgeon plays a key role in the results of these distinct procedures.
An important point of view is that recurrent pleomorphic adenomas may occur after a very long time from primary surgery, on average over 7–10 years but up to 24 years afterwards.
Thus, it is of utmost importance to evaluate the ultimate results of these different surgical techniques in the future.
The benign tumors of the
submandibular gland
The paired submandibular glands (historically known as submaxillary glands) are major salivary glands located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimula ...
is treated by simple excision with preservation of mandibular branch of the
facial nerve
The facial nerve, also known as the seventh cranial nerve, cranial nerve VII, or simply CN VII, is a cranial nerve that emerges from the pons of the brainstem, controls the muscles of facial expression, and functions in the conveyance of tas ...
, the
hypoglossal nerve
The hypoglossal nerve, also known as the twelfth cranial nerve, cranial nerve XII, or simply CN XII, is a cranial nerve that innervates all the extrinsic and intrinsic muscles of the tongue except for the palatoglossus, which is innervated by ...
, and the
lingual nerve
The lingual nerve carries sensory innervation from the anterior two-thirds of the tongue. It contains fibres from both the mandibular division of the trigeminal nerve (CN V3
) and from the facial nerve (CN VII). The fibres from the trigeminal nerve ...
. Other benign tumors of minor salivary glands are treated similarly.
Malignant salivary tumors usually require wide local resection of the primary tumor. However, if complete resection cannot be achieved, adjuvant radiotherapy should be added to improve local control.
This surgical treatment has many sequelae such as cranial nerve damage,
Frey's syndrome
Frey's syndrome (also known as Baillarger's syndrome, Dupuy's syndrome, auriculotemporal syndrome, or Frey-Baillarger syndrome) is a rare neurological disorder resulting from damage to or near the parotid glands responsible for making saliva, an ...
, cosmetic problems, etc.
Usually about 44% of the patients have a complete histologic removal of the tumor and this refers to the most significant survival rate.
See also
*
Warthin's tumor
Warthin's tumor, also known as papillary cystadenoma lymphomatosum, is a benign cystic tumor of the salivary glands containing abundant lymphocytes and germinal centers (lymph node-like stroma). It is named for pathologist Aldred Scott Warthin, wh ...
- monomorphic adenoma
*
Carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
*
Sialadenitis
Sialadenitis (sialoadenitis) is inflammation of salivary glands, usually the major ones, the most common being the parotid gland, followed by submandibular and sublingual glands. It should not be confused with sialadenosis (sialosis) which is a non ...
References
External links
{{DEFAULTSORT:Pleomorphic Adenoma
Benign neoplasms
Salivary gland neoplasia