Eric Nadler, MD

“[Sarcomas] run the gamut, like many things in oncology, from these isolated and easy to diagnose [cases] to very challenging to diagnose problems [that] even spread into the metastatic picture.”

Eric Nadler, MD, MPP, a medical oncologist and medical director of US Oncology Health Informatics and Internet Technology, discussed the inherent complexity of diagnosing sarcomas, underscoring their heterogeneous nature and diverse clinical presentations.

Sarcomas are rare malignancies that may arise in a variety of anatomic locations, often complicating initial recognition. Nadler noted that many cases are first identified in the abdomen or pelvic region, where they may be encountered by gynecologists or gynecologic oncologists. This highlights the importance of interdisciplinary collaboration in both diagnosis and treatment planning. Less commonly, sarcomas may present in the thoracic cavity or other body sites, adding to the diagnostic variability.

One of the central challenges in diagnosing sarcomas lies in their broad biological spectrum. These tumors can range from lesions that are indolent and clinically manageable to highly aggressive malignancies capable of local invasion and widespread metastasis. They may also present as multifocal disease, further complicating the diagnostic and therapeutic approach. This heterogeneity requires careful pathologic review and, frequently, expert consultation at specialized centers to ensure diagnostic accuracy.

Nadler emphasized that the diagnostic process often extends beyond the initial histopathologic assessment. Imaging studies, molecular profiling, and multidisciplinary review are frequently required to differentiate between benign and malignant lesions, as well as to determine the extent of disease. Given the diverse natural history of sarcomas, misclassification can have significant consequences for treatment selection and outcomes.

He also highlighted the importance of contextualizing sarcomas within the broader framework of oncology. Unlike many more common solid tumors, sarcomas defy a uniform treatment paradigm and require highly individualized strategies. This includes not only systemic therapies, but also surgical and radiation-based interventions tailored to the disease site, histologic subtype, and clinical behavior.

Nadler concluded by noting that the complexity of sarcoma diagnosis reinforces the necessity of specialized expertise and multidisciplinary collaboration. Gynecologic oncologists, radiologists, surgeons, and medical oncologists must work closely to establish accurate diagnoses and guide treatment decisions. Recognizing the variability in presentation and biology is essential to improving patient outcomes, particularly as new diagnostic tools and therapeutic options continue to evolve.

Videos

Eric Nadler, MD, MPP, discusses the inherent complexity of diagnosing sarcomas.

Dr Nadler on the Inherent Complexity of Diagnosing Sarcomas

Dr Riedel on the Role of the Multidisciplinary Team in PEComa Management

“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.”

Richard F. Riedel, MD, 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, discussed the importance of multidisciplinary perivascular epithelioid cell tumor (PEComa) management, as well as the importance of facilitating collaboration between community and academic oncologists when diagnosing and treating patients with this disease.

A multidisciplinary approach is essential to optimizing clinical outcomes in patients, particularly in the context of ultra-rare malignancies, such as PEComa, Riedel began. Involving subspecialized pathologists with sarcoma expertise facilitates accurate and timely histopathologic diagnosis, he said. Similarly, surgical management by oncologic surgeons experienced in treating patients with sarcoma ensures that resections are performed with curative intent when feasible, particularly in cases of localized disease, he emphasized. In addition, medical oncologists with specific expertise in rare sarcomas are more likely to implement evidence-based systemic therapies, including agents approved for PEComa and the appropriate application of mTOR inhibitors, he stated.

Often, oncologists in community-based settings are unaware of the availability of nab-sirolimus (Fyarro), the agent approved for the management of PEComa, Riedel noted. Therefore, disease-specific expertise is vital at multiple levels to guide the clinical decision-making process within a collaborative, team-based framework, he reported. These efforts collectively contribute to improved outcomes, even in the management of ultra-rare neoplasms, he continued.

Recent advances in PEComa management are primarily attributable to enhanced understanding of the molecular and pathophysiologic underpinnings of the disease, which have enabled the development and application of rational targeted therapies, according to Riedel. Given the rarity of PEComa, it is imperative that patients with suspected disease are evaluated at specialized centers—typically academic institutions with dedicated sarcoma programs—where multidisciplinary teams can provide comprehensive diagnostic and therapeutic care, he highlighted. Collaboration between academic centers and community practitioners remains fundamental to optimizing patient care, Riedel concluded.

Richard F. Riedel, MD, discusses the importance of multidisciplinary PEComa management and the role of sarcoma specialists in this disease setting.

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 

 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.

 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.

: What is the prevalence of PEComa, and what are some of the challenges associated with diagnosing this malignancy?

: 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 

, 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. 

 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.

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

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