What are the other Names for this Condition? (Also known as/Synonyms)

• Metastasizing Benign Mixed Tumor of Salivary Gland
• Salivary Gland Metastasizing Pleomorphic Adenoma

What is Metastasizing Pleomorphic Adenoma of Salivary Gland? (Definition/Background Information)

• A pleomorphic adenoma is the most common benign overgrowth arising from the salivary tissue. It may be present in individuals of a wide age range (including children and adults) and normally arises in the parotid gland (major salivary gland)
• A Metastasizing Pleomorphic Adenoma of Salivary Gland is an extremely rare form of pleomorphic adenoma that presents metastasis (spread) to other parts of the body. The spread may be to local or distant sites. Currently, the reason behind this behavior is unknown
• However, such metastasizing pleomorphic adenomas have been observed following numerous recurrences. The recurrences take place after a long duration of time, following incomplete surgery (partial tumor removal). This may be the leading factor for causing tumor metastasis through the vascular system
• Most primary tumors (in the salivary glands) and metastatic tumors (at other sites) are well-formed. Tumor spread is seen to involve the bone, lung and lymph nodes. The treatment of the condition is a complete surgical removal of the tumor with adequate margins
• The prognosis of Metastasizing Pleomorphic Adenoma of Salivary Gland is generally unpredictable and may be assessed on a case-by-case basis. The death rate from the tumor is high

Who gets Metastasizing Pleomorphic Adenoma of Salivary Gland? (Age and Sex Distribution)

• Between 60-65% of all salivary gland tumors are pleomorphic adenomas; it is the most frequently observed benign salivary gland tumor
• The incidence of Metastasizing Pleomorphic Adenoma of Salivary Gland is unknown, but is very infrequent. Less than 50 cases have been reported worldwide
• Both males and females and all racial and ethnic groups may be affected

What are the Risk Factors for Metastasizing Pleomorphic Adenoma of Salivary Gland? (Predisposing Factors)

• Metastasizing Pleomorphic Adenoma of Salivary Gland are believed to arise from incompletely excised pleomorphic adenomas (often after multiple recurrence of the benign tumor)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Metastasizing Pleomorphic Adenoma of Salivary Gland? (Etiology)

Currently, the cause of formation of Metastasizing Pleomorphic Adenomas of Salivary Gland is unknown.

• It is researched that these malignancies form over time following multiple attempts to surgically remove them, and after multiple recurrences
• Benign pleomorphic adenomas have shown certain chromosomal rearrangements, translocations, and other genetic abnormalities. However, metastasizing pleomorphic adenomas have not shown any distinctive genetic and chromosomal mutations

What are the Signs and Symptoms of Metastasizing Pleomorphic Adenoma of Salivary Gland?

The signs and symptoms of Metastasizing Pleomorphic Adenoma of Salivary Gland may include:

• Most primary tumors are confined to the major salivary glands; i.e., the parotid glands, in about 80% of the cases. The submandibular glands are affected next (in nearly 10% of the cases)
• Some primary pleomorphic adenomas occur in the minor salivary glands (around 10% of the cases). The locations include the mouth, cheek, around the jaw, soft and hard palate, etc.
• The benign pleomorphic adenomas are smooth, firm, and mobile. They are also well-defined and spherical or oval
• The time interval between the appearance of a metastatic tumor, following a diagnosis and surgical removal of the primary tumor, may vary from 18 months to as high as 55 years
• Prior to the formation of a metastatic tumor, multiple tumor recurrences (at the same site) may be noted
• Metastatic pleomorphic adenoma tumors are not known to be aggressive
• They may be present at the following locations:
  • 50% of the cases involve the bones
  • 30% are observed in the lymph nodes
  • 30% are observed in the lungs
  • Other body parts are rarely affected
• The tumors that have metastasized to various sites appear well-defined
• Signs and symptoms of the body part or organ affected due to tumor metastasis may be observed

How is Metastasizing Pleomorphic Adenoma of Salivary Gland Diagnosed?

The following exams and procedures may be used in the diagnosis of Metastasizing Pleomorphic Adenoma of Salivary Gland:

• Evaluation of the individual’s medical history and a through physical examination
• Plain X-ray of the head and neck region
• Ultrasound scan of the affected salivary gland
• CT or CAT scan with contrast of the head and neck may show a well-defined mass. This radiological procedure creates detailed 3-dimensional images of structures inside the scanned region
• MRI scans of head and neck region: A magnetic field is used to create high-quality pictures of certain parts of the body, such as tissues, muscles, nerves, and bones. These high-quality pictures may reveal the presence of the tumor

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include: 

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy may be recommended.  
• Salivary gland core biopsy of the tumor
• Salivary gland open biopsy of the tumor

Tissue biopsy:

• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note: A differential diagnosis, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Metastasizing Pleomorphic Adenoma of Salivary Gland?

The following complications due to Metastasizing Pleomorphic Adenoma of Salivary Gland may be observed:

• Severe emotional stress and cosmetic concerns (due to facial disfigurement)
• The tumor recurrence rate may range from 3-50%. Also, long-term recurrences have been observed (even after 10 years)
• Tumors that recur are known to appear widespread in the oral cavity; they are usually multifocal (arising simultaneously at many locations). The treatment in such cases can be difficult or complicated
• Occasionally, pleomorphic adenomas are known to transform into malignant tumors. Although, this may take place over 10-15 years
• Surgical complications: Surgery to remove the tumor mass may result in facial nerve palsy and gustatory sweating (Frey syndrome)
• Post-surgical wound infection
• Side effects from chemotherapy (such as toxicity), radiation therapy

How is Metastasizing Pleomorphic Adenoma of Salivary Gland Treated?

• A complete surgical excision with clear or wide margins is the preferred mode of treatment of Metastasizing Pleomorphic Adenoma of Salivary Gland. When tumors involve the parotid gland, a superficial parotidectomy is the treatment of choice
• Removal of the metastatic focus (termed metastasectomy) improves the survival rate
• Tumor recurrence leads to the need for multiple surgeries and more extensive therapies
• Radiation and chemotherapy may be recommended based on the healthcare provider’s assessment
• Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals

Long-term follow-up is required, because recurrence at the site of surgery and tumor metastasis to distant sites, have been reported many years (even decades) after surgery.

How can Metastasizing Pleomorphic Adenoma of Salivary Gland be Prevented?

• Current medical research has not established a method of preventing the formation of Metastasizing Pleomorphic Adenoma of Salivary Gland
• Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations, are mandatory for those who have been diagnosed with the tumor
• Due to its metastasizing potential and chances of recurrence, often several years of active follow-up and vigilance is recommended

What is the Prognosis of Metastasizing Pleomorphic Adenoma of Salivary Gland? (Outcomes/Resolutions)

The prognosis of pleomorphic adenoma of salivary gland is generally excellent with surgical intervention and complete removal, since it is a benign tumor. However, in case of metastasis, the prognosis may depend upon several factors including:

• Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
• Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
• Age of the individual: Older individuals generally have poorer prognosis than younger individuals
• Individuals with bulky disease have a poorer prognosis
• Involvement of vital organs may complicate the condition
• The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
• Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
• Response to treatment of salivary gland cancer: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• Progression of the condition makes the outcome worse

According to studies, based on a small number of cases, the prognosis of Metastasizing Pleomorphic Adenoma of Salivary Glands can only be assessed on a case-by-case basis. About 47% of the individuals were tumor-free, while the death rate is found to be high at 40%.

Additional and Relevant Useful Information for Metastasizing Pleomorphic Adenoma of Salivary Gland:

There are 3 major types of salivary glands and these include the following:

• Parotid glands, found on the sides of the face
• Submandibular glands located at the back of mouth, on both sides of the jaw
• Sublingual glands that are seen under the floor of the mouth

The salivary glands produce saliva that helps in:

• Lubricating the mouth
• Swallowing
• Protects the teeth against bacteria
• Digestion of food