Carcinoma Ex Pleomorphic Adenoma of Salivary Gland

Carcinoma Ex Pleomorphic Adenoma of Salivary Gland

Article
Dental Health
Diseases & Conditions
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Contributed byKrish Tangella MD, MBANov 18, 2019

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

  • Ca ex PA of Salivary Gland
  • Carcinoma of Salivary Gland arising in a Benign Mixed Tumor
  • Carcinoma of Salivary Gland arising in a Pleomorphic Adenoma

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

  • Carcinoma Ex Pleomorphic Adenoma (Ca-ex-PA) of Salivary Gland is a malignancy of the major salivary glands (mostly) that arises from a pleomorphic adenoma
  • It is generally observed in elderly adults. The cause of formation of this salivary gland malignancy is believed to be due to genetic factors
  • Ca-ex-PA of Salivary Gland is classified into the following 3 types based on examination of a tumor specimen by the pathologist under a microscope:
    • Non-Invasive Carcinoma Ex Pleomorphic Adenoma of Salivary Gland
    • Minimally-Invasive Carcinoma Ex Pleomorphic Adenoma of Salivary Gland: 1.5 mm or less penetration of the malignancy into adjacent soft tissue is noted. These tumors do not penetrate the capsule and are confined within it
    • Invasive Carcinoma Ex Pleomorphic Adenoma of Salivary Gland: Over 1.5 mm penetration of the malignant component of the tumor into adjacent soft tissue is seen. These penetrate the tumor capsule and are also termed as being ‘widely-invasive’
  • The presenting signs and symptoms of Carcinoma Ex Pleomorphic Adenoma of Salivary Gland may include a sudden growth of existing pleomorphic adenoma, associated with pain in some cases, facial paralysis, and eating/chewing difficulties
  • The treatment for Carcinoma Ex Pleomorphic Adenoma of Salivary Gland may involve a combination of surgery, chemotherapy, and radiation therapy, but it also depends upon the classification of the tumor
  • The prognosis of the Ca-ex-PA tumor depends on several factors, but most importantly on the histopathological classification of the tumor. In most cases, the prognosis of invasive tumor type is poor, while the lesser invasive ones have better prognosis

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

  • Carcinoma Ex Pleomorphic Adenoma of Salivary Gland has been recorded in adults (peak age range 50-70 years)
  • The average age at diagnosis of Ca-ex-PA is typically 10 years more than the diagnostic period of individuals with pleomorphic adenoma
  • Both male and female genders are affected
  • No ethnic or racial preference has been observed
  • The tumor represents 2.8% to 42.4% of all malignant salivary gland tumors (average 12%); and, between 0.9% to 14% of all benign and malignant salivary gland tumors (average 3.6%)

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

Carcinoma Ex Pleomorphic Adenoma of Salivary Gland is associated with the following factor:

  • Individuals with a history of pleomorphic adenoma (a benign tumor of the salivary gland)
  • It is reported that between 1.9% to 23.3% (average 6.2%) of pleomorphic adenomas may develop into Ca-ex-PA tumors

The following risk factors are generally noted for salivary gland cancers:

  • Exposure to ionizing radiation (which may be from natural or artificial sources)
  • Occupations involving woodwork, plumbing, and mining (asbestos)
  • Working in manufacturing industry related to certain materials, such as rubber products

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 Carcinoma Ex Pleomorphic Adenoma of Salivary Gland? (Etiology)

Carcinoma Ex Pleomorphic Adenoma of Salivary Gland develops from a pre-existing pleomorphic adenoma that is present for a long duration (typically over 3 years). It is researched that several genetic factors play a role in their formation.

  • The following genetic abnormalities have been observed:
    • Loss of genetic material involving chromosome 5 and 6
    • Presence of chromosomal translocation t(10;12)(p15;q14-15)
    • Involvement (amplification or deletion of material) of the following genes - HMGIC and MDM2. Both genes may be responsible for the transformation of a benign pleomorphic adenoma to a malignancy
    • Chromosome 8 rearrangement is often seen (involving the region 8q12)
    • Loss of heterozygosity (LOH) involving chromosome 8 and 17 (at 8q and 17p respectively)
    • Microsatellite instability (MSI) has been observed in both benign and malignant tumors (adenoma and carcinoma respectively)
  • In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
  • The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
  • These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

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

Carcinoma Ex Pleomorphic Adenoma of Salivary Gland signs and symptoms may include the following:

  • The presence of a rapidly-growing pleomorphic adenoma that remained stable in size for many years
  • The sudden growth may be observed over a few months
  • Ca-ex-PAs may grow to be double in size of the existing benign adenoma. It may range in size from 1.5 to 25 cm
  • The existing adenoma may have been present for over 3 years, in most of the cases; while, some are known to develop into a carcinoma much earlier than 3 years
  • The tumor mass usually presents no pain; pain is present in some cases
  • Malignant tumors may cause neurological signs and symptoms, such as facial muscle weakness, paralysis, and pain, due to facial nerve involvement
  • Most carcinomas are highly-infiltrative and known to destroy the adjoining tissue structures
  • Pain while eating/chewing
  • Most tumors are firm and poorly-defined (few are well-defined though)
  • Presence of visible swelling, typically on the side of the face, or sometimes inside the mouth
  • Initially, the overlying skin may not appear inflamed or present changes in texture or color
  • As the tumor progress and becomes larger in size, changes in the overlying skin including ulceration may be noted
  • Persistent facial pain at the site of swelling of the tumor; this requires an immediate checkup by a healthcare provider

Location of the malignant tumor:

  • Major salivary glands: Involvement of the parotid gland is observed in many cases; some are known to involve the submandibular glands
  • Minor salivary glands: Some cases are noted in the minor salivary glands. The hard/soft palate is the most common location within the minor glands. Very few cases are noted at other locations including the nasopharynx

How is Carcinoma Ex Pleomorphic Adenoma of Salivary Gland Diagnosed?

A diagnosis of Carcinoma Ex Pleomorphic Adenoma of Salivary Gland is made using the following tools:

  • Complete evaluation of family (medical) history, along with a thorough physical examination
  • Plain X-ray of the head and neck
  • Ultrasound scan of the affected salivary gland
  • CT or CAT scan with contrast of the head and neck may show a tumor mass. This radiological procedure creates detailed 3-dimensional images of structures inside the body
  • MRI scans of head and neck: Magnetic resonance imaging (MRI) uses a magnetic field 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 is preferred
  • Salivary gland core biopsy of the tumor
  • Salivary gland open biopsy of the tumor

Tissue biopsy of the tumor:

  • A tissue biopsy of the nodule 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

A differential diagnosis may be necessary to eliminate the following tumors presenting similar signs and symptoms and for a definitive diagnosis:

  • Carcinomas arising in a background of monomorphic adenoma (carcinoma ex monomorphic adenoma): Such tumors have generally better prognoses than Carcinoma Ex Pleomorphic Adenomas of Salivary Gland

Note: When examined by a pathologist under the microscope, the salivary gland tumor may consist of elements that are both benign and malignant.

  • The malignant elements are usually a salivary duct type adenocarcinoma (poorly-differentiated), an adenocarcinoma NOS, or an undifferentiated carcinoma. Nevertheless, any other malignancy type could be observed
  • Salivary Gland Ca-ex-PAs are grouped into the following subtypes based on their potential for invasion and destruction of the surrounding tissues:
    • Non-invasive type (the tumors do not invade through the capsule)
    • Minimally-invasive type
    • Invasive type (the tumors invade through the capsule)

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 Carcinoma Ex Pleomorphic Adenoma of Salivary Gland?

Complications of Carcinoma Ex Pleomorphic Adenoma of Salivary Gland may include:

  • Cosmetic concerns (facial disfigurement) and severe emotional stress
  • Ulceration and bleeding from the tumor
  • Large-sized tumors may compress adjoining tissues and structures resulting in additional complications
  • Breathing or swallowing difficulties (if tumor mass obstructs the food-pipe or wind-pipe)
  • Recurrence of the tumor locally, after surgery, is noted to be generally high for invasive tumors than for minimally-invasive or non-invasive tumors. Non- and minimally- invasive tumor recurrences may take place after 1 to 4 years (average period 2.5 years)
  • Tumor metastasis to local and distant sites including to the lung (most often affected), bones, central nervous system (including the spine), and abdomen, may be noted. Metastasis is generally not observed in the case of both minimally-invasive and non-invasive Ca-ex-PA tumors. The rate of metastasis for invasive tumor type may be as high as 70%
  • 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 Carcinoma Ex Pleomorphic Adenoma of Salivary Gland Treated?

Surgery with lymph node dissection is the preferred treatment for non-invasive, minimally-invasive, and invasive tumors. This may be followed by adjuvant radiation therapy and chemotherapy, if necessary, when the malignant components are of high-grade. Low-grade tumors that are not invasive or are minimally-invasive may not be treated using radiation, if the tumors are completely excised.

The treatment measures for Carcinoma Ex Pleomorphic Adenoma of Salivary Gland may involve:

  • Wide surgical excision with removal of the entire lesion is the standard treatment mode. This is usually followed by dissection of the lymph nodes
  • High-dose radiation therapy may be used after surgery, to destroy the remaining tumor cells
  • When the tumor is at an inaccessible location, or is unsafe for surgical intervention, non-invasive procedures, such as chemotherapy and radiation therapy (using fast neutron-beam), may be considered
  • Recurrent salivary gland tumors are also known to respond better to fast neutron-beam radiation therapy than other treatment modes
  • Embolization is used to provide temporary relief from the symptoms, and reduce blood loss during a surgical procedure
  • Clinical trial therapies (especially for stage IV disease) including therapeutic drugs, radiation, stem cell transplantation, and monoclonal antibodies, either singly or in combination of various therapies
  • Post-operative care is important: A minimum activity level is to be ensured until the surgical wound heals
  • Follow-up care with regular screening and check-ups are important, to watch for recurrence and any metastatic behavior

How can Carcinoma Ex Pleomorphic Adenoma of Salivary Gland be Prevented?

  • Current medical research has not established a method of preventing the formation of Carcinoma Ex 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 high metastasizing potential and chances of recurrence, often several years of active follow-up and vigilance is recommended

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

  • The prognosis of Carcinoma Ex Pleomorphic Adenoma of Salivary Gland is generally dependent upon the sub-classification of the tumor:
    • Individuals with minimally-invasive or non-invasive tumors have an excellent prognosis; the risk of metastasis and tumor recurrence is extremely low. The prognosis may be similar to that of a benign pleomorphic adenoma
    • Generally, individuals with invasive tumors have a poor prognosis, since these are highly-aggressive carcinomas; the risk of metastasis is very high and the rate of tumor recurrence is substantial
  • Invasive carcinoma ex pleomorphic adenoma tumors:
    • It is a tumor that penetrates the tumor capsule to over 1.5 mm length/distance. The rates of survival are between 25-65% for 5 years, between 18-50% for 10 years, between 10-35% for 15 years, and between 0-38% for 20 years
    • The rate of tumor recurrence varies from 23% to 50%; in some cases, multiple recurrences are observed
    • The rate of cancer spread can be as high as 70% and vital organs/structures, such as the lungs and central nervous system, may be sites of metastasis
    • According to some studies, the death rate is nearly 100% when tumors penetrate/extend more than 8 mm from their capsules
    • Grade of the tumor and tumor size are also key prognostic indicators with higher-grade and larger tumor sizes portending poorer prognoses
  • The type and percentage of malignant component in the Ca-ex-PA tumor also affect the outcomes:
    • The death rate, when high-grade carcinoma component is present in the tumor, is nearly 37%; while, deaths are not observed from the presence of low-grade carcinomatous components
    • The survival rate from the presence of terminal duct carcinoma element is 96%
    • The survival rate from the presence of ductal carcinoma element is 62%
    • The survival rate from the presence of myoepithelial carcinoma element is 50%
    • The survival rate from the presence of undifferentiated carcinoma element is 30%
  • The prognosis of salivary gland cancer, in general, depends upon a set of several factors that include:
    • 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 the lymph node can adversely affect the 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

Additional and Relevant Useful Information for Carcinoma Ex 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 following article link will help you understand other cancers and benign tumors:

http://www.dovemed.com/diseases-conditions/cancer/

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Krish Tangella MD, MBA picture
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Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team

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