Perivascular epithelioid cell tumor
Synonyms
PEComa , PEC tumor, Malignant Perivascular Epithelioid Cell Neoplasm, Perivascular Epithelioid Cell Neoplasm,Overview
Perivascular epithelioid cell tumour, also known as PEComa or PEC tumour, is a family of mesenchymal tumours consisting of perivascular epithelioid cells (PECs).These are rare tumours that can occur in any part of the human body.
The cell type from which these tumours originate remains unknown. Normally, no perivascular epitheloid cells exist; the name refers to the characteristics of the tumour when examined under the microscope.
Establishing the malignant potential of these tumours remains challenging although criteria have been suggested; some PEComas display malignant features whereas others can cautiously be labeled as having ‘uncertain malignant potential’. The most common tumours in the PEComa family are renal angiomyolipoma and pulmonary lymphangioleiomyomatosis, both of which are more common in patients with tuberous sclerosis complex. The genes responsible for this multi-system genetic disease have also been implicated in other PEComas.
Many PEComa types shows a female predominance in the sex ratio.
Symptoms
Signs and symptoms of PEComas vary quite a bit between patients and depend on tumor location. Some PEComas cause no symptoms and are found when patients undergo imaging for other reasons.
For patients with symptoms, PEComas may form a visible painful or painless mass. For women with PEComas in the reproductive tract, these tumors may present with vaginal bleeding. PEComas in the GI tract may present with abdominal pain, bloody stools, constipation/bowel obstruction, weight loss and anemia.
Each type of PEComa has unique physical features and potential signs and symptoms associated with it.
Causes
The cause of sporadic cases of PEComas is not known. PEComas may be associated with the genetic condition tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder.
Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
TSC is caused by changes (mutations) in the TSC1 or TSC2 genes. These genes encode the proteins hamartin and tuberin, respectively. Normally, these proteins suppress tumor formation by inhibiting the rapamycin (mTOR) pathway. Mutations in the TSC1 or TSC2 genes lead to overactivation of the mTOR pathway, which in turn causes increased cell growth, blood vessel formation and protein synthesis. This is why multiple tumors form in the body of patients with TSC. TSC is more strongly associated with AML, LAM and CCTL.
An overactive mTOR pathway is also thought to be involved in sporadic cases of AML and other PEComa
Diagnosis
PEComas may be detected by imaging with X-ray, CT scan or MRI. Once a tumor is detected, biopsy is needed to examine the cellular make-up and distinguish it from other types of tumors.
Tissue samples from biopsies will have a characteristic appearance under the microscope to identify tumors as PEComas and differentiate them from other potential tumors.
PEComas typically have mostly epithelioid cells around blood vessels. They also contain protein markers similar to melanocytes (melanin-producing cells) and smooth muscle cells.
Malignant PEComas can be detected from biopsy as well. Malignancy is more likely in PEComas that are larger in size, begin to grow into surrounding tissues and have a higher percentage of cells that are actively growing.
Genetic testing is available to identify patients with TSC who are at an increased risk of developing PEComas.
For patients with LAM, a blood test for detecting increased levels of vascular endothelial growth factor D (VEGF-D) may aid in diagnosing this PEComa subtype. VEGF-D stimulates growth of new blood vessels and high levels may be involved in tumor spread.
Treatment
Surgery to remove a localized PEComa that has not spread is currently the recommended form of treatment. Surgery may be curative for patients with benign PEComas, although tumor regrowth can occur. If regrowth occurs, surgery is again recommended to remove the regrowth. Surgery is not usually recommended to remove tumors that have spread (metastasized) to other parts of the body. Instead, medical treatment is usually recommended.
Regular monitoring of tumors with imaging exams may be recommended in some patients where surgery is not possible or where tumors have a potential for malignancy.
For patients with LAM, bronchodilators that help relax and open the airways may be prescribed. Oxygen therapy may also be needed at some point. For more advanced LAM, lung transplants may be recommended.
Some PEComas are caused by TSC1 or TSC2 gene mutations. In these cases, patients may benefit from everolimus, an mTOR inhibitor that blocks this overactive pathway thought to lead to tumor formation when these genetic mutations are present.
Everolimus is a medication taken by mouth and approved by the U.S. Food and Drug Administration (FDA) to treat AMLs that occur in patients with TSC.
Sirolimus is another mTOR inhibitor taken by mouth and developed as an immunosuppressive drug for transplant patients to prevent organ rejection. Sirolimus has been approved by the FDA to treat LAM.
Sirolimus protein-bound (previously nab-sirolimus) is a different formulation of sirolimus given intravenously and approved by the FDA to treat malignant PEComa that has spread or cannot be removed surgically.