Multidisciplinary collaboration and the advent of targeted therapies for patients with perivascular epithelioid cell tumor (PEComa) offer promise for patients with this disease, although diagnostic challenges and therapeutic barriers signal the continued need for specialized patient attention and research, according to Richard F. Riedel, MD.
“We’re fortunate because we’ve had some recent advancements in the management of the disease,” Riedel said in an interview with OncLive® ahead of Malignant PEComa Awareness Day, which is observed annually on July 12, coinciding with Sarcoma Awareness Month.
In the interview, Riedel discussed how the rarity of PEComa contributes to challenges associated with diagnosing and managing this disease; the gynecological specialist’s role in diagnosing many PEComa cases; the crucial contributions from pathologists during diagnostic workup; and the significance of staging by a sarcoma specialist to determine the extent of disease and eligibility for systemic therapy.
He also explained the increased importance of leveraging specialized expert insights when seeking PEComa management strategies following the November 2021 FDA approval of nab-sirolimus (Fyarro) for the treatment of adult patients with locally advanced unresectable or metastatic malignant PEComa.1 This agent was approved based on data from the phase 2 AMPECT trial (NCT02494570), in which patients who received nab-sirolimus (n = 31) achieved an overall response rate of 39% (95% CI, 22%-58%).
Riedel is a professor of medicine in the Department of Medicine at the Duke University School of Medicine, as well as a member of the Duke Cancer Institute in Durham, North Carolina.
OncLive: What is the prevalence of PEComa, and what are some of the challenges associated with diagnosing this malignancy?
Riedel: PEComa is an extremely rare subtype of sarcoma. We consider it an ultra-rare sarcoma, which means there’s probably less than 1 case per 1 million people here in the United States; we have approximately 350 million people, which means there’s probably less than 350 cases of PEComa [reported per] year. It’s challenging in that regard. It is an entity that is seen by sarcoma specialists.
How is PEComa typically diagnosed? Which specialists are often involved in this process?
[PEComas are] diagnosed based in part on the presenting symptoms, and many PEComas can occur in the uterus, which is why our gynecologic colleagues are oftentimes involved. There [may be] a uterine mass that [is] initially thought to be a fibroid or another uterine malignancy. A hysterectomy is performed, which then leads to a diagnosis of PEComa. However, PEComas are not limited to the uterus. They can occur in the abdominal cavity, [and] they can occur in the chest cavity. They can occur anywhere.
What hallmarks of PEComa do you look for when trying to confirm a diagnosis?
From a histochemical standpoint, [PEComas] will oftentimes have melanocytic markers, such as HMB-45, for example, [which are] markers that can be seen in melanoma. [PEComa is] clearly not a melanoma. We rely on pathologists with soft tissue sarcoma expertise to make this diagnosis. Molecularly, we’ve learned that there can be mutations in the mTOR pathway, specifically in TSC1 and TSC2, which can also aid in the diagnosis if there’s uncertainty.
What are the next steps following an initial PEComa diagnosis?
Once a diagnosis is made, then referral to an individual with expertise is appropriate, and that typically is an individual in a center with sarcoma expertise. As a sarcoma medical oncologist, my questions center around the extent of the disease. We will perform staging studies of the primary site, [as well as of] the most common sites of distant metastatic spread, which could be the lungs. From there, if there is evidence of distant metastatic disease, there’s a conversation regarding the potential role of systemic therapy.
What is the clinical relevance of disease-staging surgery for patients with PEComa?
For patients with localized disease—meaning [disease that is] in one spot and one spot only—surgery is performed with the intent for cure. That’s in contrast to a patient with metastatic disease that may be identified on the staging studies. In [the metastatic] situation, we’re less likely to deal with cure [and are] more likely dealing with an attempt to control the cancer and allow [the patient] to live with the cancer. Staging studies are important because they help with prognostication regarding how the patient’s going to do overall.
What disease factors and patient characteristics inform treatment considerations for this population?
There are tumor factors—namely, whether there’s the presence of metastatic disease and the burden of that disease. Are there symptoms associated with the disease? Then there are patient factors. How fit is the patient? What is their performance status? Are there other comorbidities that could make treatment challenging? [PEComa] treatments [are associated with] adverse effects, which can then exacerbate other co-existing medical conditions. A combination of patient- and disease-related factors all go together to determine [patient] appropriateness for treatment.
How does nab-sirolimus fit into the PEComa treatment paradigm?
The only FDA-approved agent [for PEComa] currently is nab-sirolimus, which is nanoparticle album-bound sirolimus. That’s in contrast to conventional sirolimus, which has been around for many years [and has been] used as an immunosuppressant, for example, in patients who undergo solid organ transplantation. Sirolimus and nab-sirolimus are mTOR pathway inhibitors, and they are designed to target the aberrant pathway that’s active in PEComas. TSC1 and TSC2 mutations result in aberrant signaling through mTOR. [Thusly], the use of an mTOR inhibitor has become attractive.
What is the importance of employing a multidisciplinary approach to PEComa management?
A multidisciplinary team is critical for improving outcomes for patients, particularly when you’re dealing with an ultra-rare disease. Leveraging pathologists with sarcoma expertise can [lead to] a timely diagnosis. Leveraging surgeons with expertise can result in oncologically appropriate surgeries with the intent for cure for patients with localized disease. Leveraging medical oncologists with expertise can allow for appropriate treatment.
Many times, our community-based colleagues are not familiar with the agent that’s currently approved in PEComa, or are [not] aware of the potential role for mTOR inhibitors. At various levels, having a knowledge base about the disease state and then putting that in the context of a team is an effort to improve patient outcomes.
What is your main message for both academic and community colleagues regarding the current state of PEComa management, as well as where the field might be headed in the future?
We are making advances, even in ultra-rare diseases like PEComa. This is largely due to the fact that we have a better understanding of the disease process and the disease pathogenesis, and we’ve been able to leverage that knowledge for therapeutic gain. Given the ultra-rare nature of PEComas, it’s critically important that if there is suspicion of this diagnosis, patients are seen in centers with expertise. That’s typically an academic institution with a sarcoma center. We are happy to partner with community-based colleagues and with patients for the betterment of our patients.
Reference
FDA approves sirolimus protein-bound particles for malignant perivascular epithelioid cell tumor. FDA. Updated November 23, 2021. Accessed July 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sirolimus-protein-bound-particles-malignant-perivascular-epithelioid-cell-tumor