We're celebrating
40 years!
Last updated:
March 24, 2022
Years published: 2022
NORD gratefully acknowledges Andrew J. Wagner, MD, PhD, Medical Director, Adult Ambulatory Oncology; Associate Chief Medical Officer, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, for assistance in the preparation of this report.
Summary
Perivascular epithelioid cell neoplasms (PEComas) are rare soft tissue tumors. They often form around small blood vessels (perivascular spaces) in various body parts such as the lungs, GI tract, kidneys, liver and uterus. PEComas are made up of cells with an epithelioid (cuboidal) shape and have some features that are shared with melanocytes and smooth muscle cells. Melanocytes are cells that are normally found in the skin and produce melanin to give skin its color. PEComa can make some of the same proteins that are used to create pigment. PEComa also make some of the same proteins found in smooth muscle cells, which make up muscles that are not under our conscious control, such as the muscles that make up our internal organs and digestive tract.
PEComas are considered to be a group of tumors that share these characteristic features. However, within this group are specific tumors with their own unique features and more likely to form in certain body parts. These specific tumors include angiomyolipomas (AMLs), clear cell sugar tumors, primary extrapulmonary sugar tumor (PEST), lymphangioleiomyomatosis (LAM), clear-cell myomelanocytic tumor (CCMT) of the falciform ligament/ligamentum teres, primary cutaneous PEComa (CCCMT-cutaneous clear cell myomelanocytic tumor) and PEComas not otherwise specified (NOS).
Most PEComas are benign but some can be malignant with the potential to spread to other parts of the body.
PEComas can also be associated with the genetic condition tuberous sclerosis complex (TSC). In this condition, multiple tumors form in the body. Intellectual disabilities and seizures may also be present.
Introduction
The name perivascular epithelioid cell tumor was first proposed in the early 1990s after researchers noticed shared cellular features between the various tumors that are now members of the PEComa grouping. These features are considered unique to these types of tumors, distinguishing them from other tumors.
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.
Angiomyolipoma
Angiomyolipomas (AMLs) are rare but are the most common benign tumor of the kidneys. AMLs are composed of blood vessels (angio), smooth muscle cells (myo) and fatty (adipose/lipomatous) tissues.
Eighty percent of AML cases are sporadic (occur randomly with no known risk factors) and 20% of cases develop in patients with TSC or LAM (hereditary conditions).
In people with TSC, AMLs are especially common, occurring in approximately 75% of these patients. TSC patients are more likely to have AMLs that cause symptoms. AMLs may also develop in patients with LAM. Patients with AMLs who have TSC or LAM are more likely to have multiple, large and more aggressive AMLs.
When AMLs cause signs and symptoms, they may include a mass that can easily be felt, pain on one side of the body between the abdomen and back (flank pain), weight loss, blood in the urine, anemia, urinary tract infections or kidney failure. More serious symptoms include bleeding in the abdomen (retroperitoneal hemorrhage) which can lead to shock. This is estimated to occur in less than 15% of AML cases.
AMLs can also occur in organs outside of the kidney, such as the liver. These are also usually benign but can be malignant. AMLs can vary in the proportion of cell types they’re composed of. AMLs with more epithelioid cells, especially, may become malignant, although this is rare. Larger tumors are also more likely to spread to other parts of the body.
Clear Cell Sugar Tumor of the Lung (CCTL)
Clear cell “sugar” tumors of the lung are usually benign. They’re called clear cell “sugar” tumors because the cells they’re composed of have thin walls and high levels of glycogen, a stored version of the body’s carbohydrates, or sugars.
CCTL is usually around the size of a coin and occurs as a single tumor. It can occur in any lung lobe but tends to affect the lower lungs.
Symptoms of CCTL may include fever, cough, coughing up blood and shortness of breath, but patients typically do not have symptoms. CCTL rarely affects tissues outside of the lung.
Like other PEComas, CCTLs are also associated with TSC, and it can also occur in patients with LAM without TSC.
Primary Extrapulmonary Sugar Tumor (PEST)
Primary extrapulmonary sugar tumors are similar in structure and appearance to clear cell sugar tumors of the lungs but instead occur outside of the lung, such as in the rectum, vulva, uterus, pancreas, breast, trachea or heart. Symptoms vary depending on location but can include fatigue, rectal bleeding, shortness of breath and heart rhythm disturbances.
Most PESTs are thought to be benign but can be malignant.
Lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare progressive multisystem disorder that predominantly impacts women of reproductive age. LAM is characterized by the spread and uncontrolled growth of specialized cells (smooth muscle-like LAM cells) in certain organs of the body, especially the lungs, kidneys and lymphatics.
There are two main types of LAM: sporadic LAM (that occurs spontaneously) and LAM associated with tuberous sclerosis complex (TSC), a genetic condition.
Symptoms of LAM vary depending on the organs affected. The most common symptom associated with LAM is difficulty breathing (dyspnea), especially on exertion. Affected individuals may also experience complications including lung collapse (pneumothorax) or fluid accumulation around the lungs (pleural effusion) and in the abdomen and angiomyolipomas. The disorder is progressive and, in some patients, may result in chronic respiratory failure (For more information, search “lymphangioleiomyomatosis” in the Rare Disease Database).
Clear Cell Myomelanocytic Tumor of the Falciform Ligament (CCMT)
Clear cell myomelanocytic tumors of the falciform ligament form on this ligament usually in the right lobe of the liver. The falciform ligament connects the liver to the front portion of the abdominal wall.
CCMTs were first described in 2000. These tumors are usually benign and can be large. Symptoms usually include abdominal pain, but CCMTs can be asymptomatic.
Primary Cutaneous PEComa/Cutaneous Clear Cell Myomelanocytic Tumor (CCCMT)
Primary cutaneous PEComas are very rare PEComas that arise in the skin. They are more likely to appear on the limbs or the back. These tumors involve the dermis of the skin and the underlying subcutaneous fat. CCCMT may be confused with malignant melanoma.
PEComas – Not Otherwise Specified (NOS)
PEComas-NOS include tumors composed of perivascular epithelioid cells that do not fit into the other PEComa subtypes based on overall composition and location.
PEComas-NOS typically present as a painless mass and usually occur in women.
PEComas-NOS have been reported in almost every body site. The uterus is the most commonly reported site for this type of PEComa. PEComas-NOS of the uterus may present with vaginal bleeding. Other common sites include the genitourinary tract, gastrointestinal tract and the back side of the abdomen (retroperitoneum). PEComas-NOS have also been reported in the oral cavity, the orbit (socket that holds the eye) and the skull base.
These PEComas can be aggressive, spreading to nearby regions or other organs far from the original tumor. They may also recur after surgical removal.
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 PEComas.
PEComas have been found in people of all ages, from children to older adults. Although they often occur in children with TSC, they also occur sporadically in people with no known risk factors.
In general, PEComas are more likely to occur in middle-aged women, with some studies reporting PEComas are 5 to 7 times more likely in females than males.
However, average age of onset varies widely depending on the type of tumor. For instance, PEComas-NOS of the uterus have an average age of onset of 54 years of age while CCMTs of the falciform ligament occur more often in young women around the age of 20 years of age.
Renal AMLs, the most common and well-described PEComas, have an estimated prevalence of 0.44% in the general population. Sporadic AMLs are more common in women. AMLs associated with TSC affect both females and males equally and appear at a younger age.
CCTLs occur most often in middle-aged adults but have been reported in children as young as 8 years old. They are only slightly more common in females than males.
LAM affects mostly women of childbearing age. Sporadic LAM is estimated to affect 1 in 400,000 women. TSC-associated LAM is estimated to affect 30 to 40% of female patients with TSC. Overall, LAM is estimated to affect 3.4-7.8/1,000,000 women worldwide.
Malignant PEComas are estimated to be diagnosed in 0.12 to 0.24 per one million people.
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.
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.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Limaiem F, Baccouch S, Boujelbene N, et al. Puzzling hepatic tumor: epithelioid angiomyolipoma. Clin Case Rep. 2022;10(1):e05327. Published 2022 Jan 28. doi:10.1002/ccr3.5327
Sobiborowicz, A, Switaj T,Teterycz P, Spałek MJ. Szumera-Cie´ckiewicz A, Wagrodzki M, Zdzienicki M, Czarnecka AM, Rutkowski P. Feasibility and long-term efficacy of PEComa treatment—20 years of experience. J.Clin. Med. 2021; 10: 2200. https://doi.org/10.3390/jcm10102200
Wagner AJ, Ravi V Riedel RF, et al. Nab-sirolimus for patients with malignant perivascular epithelioid cell tumors. J Clin Oncol. 2021 Nov 20;39(33):3660-3670. doi: 10.1200/JCO.21.01728.
Jia R, Jiang L, Zhou Y, et al. Clinical features of 18 perivascular epithelioid cell tumor cases. Medicine (Baltimore). 2020;99(34):e21659. doi:10.1097/MD.0000000000021659
Hakim N, Chornenkyy Y, Qasem S. Malignant perivascular epithelioid cell tumor mimicking renal cell carcinoma: a diagnostic pitfall. American Journal of Clinical Pathology. 2019;152 (1): S62. https://doi.org/10.1093/ajcp/aqz113.061
Chang M, Lim D, Genovesi M. Clear cell “sugar” tumor of the lung: a case report and review of the literature. AME Case Rep. 2018;2:40.
Vos N, Oyen R. Renal angiomyolipoma: the good, the bad, and the ugly. J Belg Soc Radiol. 2018;102(1):41.doi:10.5334/jbsr.1536
Stuart LN, Tipton RG, DeWall MR. et al. Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature. J Cutan Pathol. 2017;44(8):713-721. doi:10.1111/cup.12972
Tsilimigras DI, Bakopoulos A, Ntanasis-Stathopoulos I, et al. Clear cell “sugar tumor” of the lung: Diagnostic features of a rare pulmonary tumor. Respir Med Case Rep. 2017;23:52-54. doi:10.1016/j.rmcr.2017.12.001
Chen Z, Han S, Wu J, et al. A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract. Medicine (Baltimore) 2016 Jul;95(28):e3890. doi: 10.1097/MD.0000000000003890.
D’Andrea D, Hanspeter E, D’Elia C, Martini T, Pycha A. Malignant perivascular epithelioid cell neoplasm (PEComa) of the pelvis: a case report. Urol Case Rep. 2016;6:36-38. doi:10.1016/j.eucr.2016.02.004
Bergamo F, Maruzzo, M, Basso, U. et al. Neoadjuvant sirolimus for a large hepatic perivascular epithelioid cell tumor (PEComa). World J Surg Onc. 2014;12:46. https://doi.org/10.1186/1477-7819-12-46
Tan Y, Zhang H, Wang Xc. Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Indian J Pathol Microbiol. 2014 57:453-5. Available from: https://www.ijpmonline.org/text.asp?2014/57/3/453/138766
Gennatas C, Michalaki V, Kairi PV, et al. Successful treatment with the mTOR inhibitor everolimus in a patient with Perivascular epithelioid cell tumor. World J Surg Onc, 2012; 10:181. https://doi.org/10.1186/1477-7819-10-181
Choi CW, Kim TO, Kim KY, Lee SM, Kim GH, Kang DH, Song GA, Kim S, Kim DH. Perivascular epithelioid cell tumor (PEComa) of abdominal cavity from falciform ligament: a case report. J Korean Med Sci. 2009 Apr;24(2):346-349. https://doi.org/10.3346/jkms.2009.24.2.346
Armah HB, Parwan AV. Perivascular epithelioid cell tumor. Arch Pathol Lab Med 1. 2009; April 133 (4): 648–654. doi: https://doi.org/10.5858/133.4.648
Liegl B, Hornick JL, Fletcher CD. Primary cutaneous PEComa: distinctive clear cell lesions of skin. Am J Surg Pathol. 2008;32(4):608-614. doi:10.1097/PAS.0b013e31815604ab
Bosincu L., Rocca P, Martignoni G, et al. Perivascular epithelioid cell (PEC) tumors of the uterus: a clinicopathologic study of two cases with aggressive features. Mod Pathol. 2005;18:1336–1342. https://doi.org/10.1038/modpathol.3800433
Tazelaar H, Batts K & Srigley J. Primary extrapulmonary sugar tumor (PEST): a report of four ases. Mod Pathol. 2001;14:615–622. https://doi.org/10.1038/modpathol.3880360
Turk JL, Narayanan RB. The origin, morphology, and function of epithelioid cells. Immunobiology. 1982;161(3-4):274-282. doi:10.1016/S0171-2985(82)80083-1
INTERNET
LAM also known as lymphangioleiomyomatosis. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/lam#:~:text=LAM%2C%20or%20lymphangioleiomyomatosis%2C%20is%20a,%2C%20lymph%20nodes%2C%20and%20kidneys. Accessed March 15, 2022.
Perivascular epithelioid cell tumor. National Cancer Institute. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/perivascular-epithelioid-cell-tumor. Accessed March 15, 2022.
Perivascular epithelioid cell neoplasm. Orphanet. Available at: https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=29725&Disease_Disease_Search_diseaseGroup=pecoma&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Perivascular-epithelioid-cell-neoplasm&title=Perivascular%20epithelioid%20cell%20neoplasm&search=Disease_Search_Simple. Accessed March 15, 2022.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/