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

• Clear Cell Myomelanocytic Tumor
• Perivascular Epithelioid-Cell Differentiation Tumour
• PEComa-NOS

What is PEComa? (Definition/Background Information)

• PEComa is a group of soft tissue tumors that show perivascular epithelioid-cell (PEC) differentiation. PEComa tumors may be benign, malignant, or they may be of uncertain malignant potential
• The PEComa family of tumors include:
  • Angiomyolipoma (AML)
  • Lymphangioleiomyomatosis (LAM) type of tumors
  • Clear cell ‘sugar’ tumor (CCST) of lung
  • Primary extrapulmonary sugar tumor: Clear cell ‘sugar’ tumor of pancreas, uterus, urinary bladder, breast, heart, prostate, vulva, etc.
  • Clear-cell myomelanocytic tumor of ligamentum teres/falciform ligament
  • Abdominopelvic sarcoma of perivascular epithelioid cells
  • And, several other tumors originating from PEC, showing the same histological features
• The most common type of PEComas are AML and LAM type of tumors. Other forms of PEComas are generally rare. These tumors are seen among a wide age range of individuals, usually adults
• PEComa tumors can be associated with a syndrome (tuberous sclerosis) in some cases. In a majority of cases, it may not be associated with a syndrome or genetic disorder. The cause of tumor formation is due to genetic defects or mutations
• It can occur at various locations in the body, such as the abdominal cavity, pelvic region (uterus in women), and the gastrointestinal tract. Small-sized tumors may not present any significant signs and symptoms, while large PEComa tumors may compress the surrounding organs and structures causing pain and mass effect
• Typically, a surgical excision of the PEComa with its entire removal may be undertaken. The treatment options for malignant tumors may additionally include chemotherapy and radiation therapy, considered on a case-by-case basis
• The prognosis depends upon whether the tumor is benign or malignant. In many cases, the prognosis of PEComa is generally excellent with its complete removal, since it is a benign tumor. In case of a malignancy, the prognosis depends upon a set of factors that includes the severity of the signs and symptoms, age and overall health of the individual, response to treatment, among other factors

Who gets PEComa? (Age and Sex Distribution)

• PEComa tumors may be seen in a wide age range of individuals (3-97 years). The average age of presentation is 45 years
• Tumors that are associated with genetic disorders or syndromes are seen to appear earlier
• Both male and female genders are affected; though a female predominance is noted (6-7:1 female-male ratio)
• No ethnic or racial preference is seen

What are the Risk Factors for PEComa? (Predisposing Factors)

The tumors can be sporadic in nature (called non-syndromic PEComa) or associated with genetic syndromes (called syndromic PEComa). Currently, no risk factors have been noted for the formation of sporadic PEComa tumors. The sporadic cases are greater in number than cases associated with genetic disorders.

In general, the risk factors for PEComa may include the following:

• Tuberous sclerosis complex: It is an inherited genetic disorder that can cause the formation of other tumor types, such as astrocytomas, rhabdomyomas, phakomas, oncocytomas, and angiofibromas, at various body locations
• Some PEComa tumors are associated with other genetic disorders such as the following:
  • von Recklinghausen disease (neurofibromatosis type I)
  • von Hippel-Lindau disease
  • Sturge-Weber syndrome
  • Autosomal dominant polycystic kidney disease

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 PEComa? (Etiology)

The cause of PEComa tumor formation is due to genetic factors. Research has shown that the tumors arise from cells called perivascular epithelioid cells (PEC), which surrounds the blood vessels.

• Currently, studies indicate defects in the following genes: TSC2 and TFE3
• Additionally, the following chromosomal aberration is noted: Mutations in chromosome 16 due to loss of 16p (short arm)
• A gene fusion (involving the SFPQ and TFE3 genes) was noted in one case of PEComa tumor

What are the Signs and Symptoms of PEComa?

The signs and symptoms of PEComa depend upon whether it is benign (in most of the cases) or malignant. It may vary from one individual to another. The presentations are also based on the location and subtype of the tumor; PEComas may occur in different parts of the body.

The signs and symptoms of PEComa may include:

• Most tumors are small-sized and may not exhibit any significant signs and symptoms
• The size ranges from 5 mm to 30 cm (average size of about 7 cm)
• Large tumors can affect the functioning of the organ that is involved, such as the kidney or liver. Soft tissue tumors can compress surrounding structures or organs (mass effect)
• The common sites of PEComa involvement include the following:
  • Retroperitoneum: Sclerosing PEComas are mostly seen in the abdominal cavities (retroperitoneum)
  • Abdominal and pelvic region
  • Uterus: In women, the uterine corpus is the most common site of involvement
  • Gastrointestinal tract
• In sporadic cases (when not associated with tuberous sclerosis), the tumors are usually single. Often with sporadic tumors, they tend to be larger and so pain may be observed
• With tuberous sclerosis (TS), multiple tumors may be seen around the body or in the same organ. Tumors present with TS are generally known to be more asymptomatic and often discovered incidentally
• Malignant tumors that metastasize may show a variety of signs and symptoms depending on the site of metastasis

How is PEComa Diagnosed?

A diagnosis of PEComa may involve the following tests and procedures:

• Complete physical exam with evaluation of medical history: If PEComa is associated with tuberous sclerosis; then, the signs and symptoms of tuberous sclerosis may be noted. This can also help the healthcare provider to suspect the condition
• Radiological imaging studies, such as ultrasound, CT, MRI scans, of the affected region
• Vascular angiographic studies 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
• Core biopsy of the tumor
• 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
• The tumors may have varying proportions of blood vessels, smooth muscle, and fat cells, when examined by a pathologist under a microscope
• 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, to eliminate the following tumor types is considered, before arriving at a definite diagnosis:

• Adipocytic tumor
• Clear cell sarcoma
• Gastrointestinal stromal tumor (GIST)
• Melanoma
• Smooth muscle tumor

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 PEComa?

The complications are dependent on the site, size, and subtype of the tumor. Many tumors are known to be benign and these do not infiltrate the surrounding structures or organs. However, malignant tumors may infiltrate and affect the function of the organs; they may also metastasize.

The complications of PEComa may include:

• Malignant tumors may undergo metastasis to the liver, lymph nodes, lung, central nervous system, or bones
• Rare cases of metastasis to the heart, pancreas, and urinary bladder have been reported
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication
• Recurrence of the tumor following an incomplete excision; the risk of recurrence increases with advancing age. Malignant tumors have a much higher recurrence rate than benign tumors
• PEComa of skin show a lower risk of recurrence
• Complications due to underlying tuberous sclerosis genetic disorder

How is PEComa Treated?

The treatment options vary from one individual to another and are currently not well-strategized. Even though, the treatment depends upon the location of the tumor.

The treatment measures for PEComa depend on whether it is benign or malignant. Most of the benign tumors, depending on its location, can be completely removed through surgery. Malignant tumors may require a combination of surgery, chemotherapy, and radiation therapy.

• Surgical intervention with complete excision can result in a complete cure. It can also help reduce the chances of tumor recurrence
• In some cases, chemotherapy and/or radiation therapy may be administered to shrink the tumor size, prior to surgery (neoadjuvant therapy)
• Tumor embolization (performed on a case-by-case basis) is a possible treatment option. Here the blood supply to the tumor is blocked resulting in its shrinkage or death
• Targeted therapies have been attempted in some PEComa cases
• Treatment of the underlying or associated conditions, if any present
• Post-operative care is important: A minimum activity level is ensured, until the surgical wound heals
• Follow-up care with regular screening may be recommended by the healthcare provider

How can PEComa be Prevented?

Current medical research has not established a method of preventing both syndromic and non-syndromic forms of PEComa. However, in case it is associated with genetic disorders, such as tuberous sclerosis, then the following may be considered:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as tuberous sclerosis
• Regular medical screening at periodic intervals (long-term) with tests and physical examinations are strongly recommended

What is the Prognosis of PEComa? (Outcomes/Resolutions)

• The prognosis of PEComa depends upon the severity of the signs and symptoms. It also depends upon whether the tumor is benign or malignant, the overall health of the individual, association with tuberous sclerosis, and response to therapy
• Typically, individuals with small-sized tumors have a better prognosis than those with larger-sized tumors. Also, those with non-syndromic (sporadic) tumors have a comparatively better prognosis than individuals with tumors that are seen in association with a genetic disorder (syndromic PEComas)
• In most cases, the prognosis of small-sized, solitary, and benign tumors is excellent with surgical intervention or appropriate treatment. However, some tumors are known to recur after many years following treatment (5 years or more)
• Malignant PEComa tumors have a much higher recurrence rate following surgery (about 70%); while after treatment with non-surgical measures, the recurrence is about 45%. The recurrence of benign tumors after surgery is around 2% and the recurrence rate for tumors of uncertain malignant potential is about 14% (after surgery)
• In case of malignant PEComas, the prognosis may be dependent 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 respectability 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
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment

Additional and Relevant Useful Information for PEComa:

• An angiomyolipoma (AML) is a benign tumor that is a mixture of blood vessels (angio-), smooth muscles (myo-), and fat (or lipoma). The tumor is seen among a wide age range of adults and can occur at various locations in the body. But, the most common location is the kidney

The following link will help you understand angiomyolipoma:

http://www.dovemed.com/diseases-conditions/angiomyolipoma-kidney/