Managing Desmoid Tumors With Molecular Profiling and Recent Guidelines

Desmoid tumors are rare, non-metastatic soft tissue neoplasms that arise from connective tissue and often require careful diagnosis and management. A virtual Case-Based Roundtable discussion was moderated by Tony Philip, MD, director of Quality and Patient Safety for Medical Oncology at Monter Cancer Center and assistant professor at Hofstra/Northwell. Participants from New Jersey, New York, and Pennsylvania explored the role of molecular profiling, including next-generation sequencing (NGS) to identify mutations like APC or CTNNB1. Philip also reviewed the 2024 Desmoid Tumor Working Group guidelines, highlighting active surveillance for asymptomatic patients and treatment initiation based on tumor progression or quality-of-life impact.

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CASE SUMMARY

• A 41-year-old woman presented to her gynecologist with a 6-month history of a discrete, tender, and enlarging mass in her right abdominal wall.
• No presenting symptoms
• The patient denies prior trauma to the site.

Past Medical and Social History

• Two prior pregnancies, age 38
• Prior cesarean section
• Denies chronic comorbidities and concomitant, prescription medications
• Normal menses
• Report of latest pap smear: negative for intraepithelial lesion or malignancy

Focused Physical Examination

• Abdominopelvic: firm, well-defined, immobile mass tender to palpation in the right upper quadrant

Imaging Studies

• Contrast-enhanced CT: Round, iso-dense mass along right rectus abdominis muscle with well-defined margins with vascular enhancement

Initial Treatment Plan

• Biopsy showed desmoid tumor and her gynecologist decided to observe the patient for enlargement of her abdominal mass and symptoms onset.
• Management consisted of over-the-counter nonsteroidal anti-inflammatory drugs as directed.

Four Months Later

• The patient returned to her gynecologist with complaints of visceral pain and bloating, nausea, and constipation.

Focused Physical Examination

• Abdominopelvic: Right upper quadrant mass now associated with muscular rigidity, localized edema and pain to palpation
• Follow-up T2 weighted MRI: Mass rapidly enlarged (15%), now measuring 4.2 x 5.7 cm with well-defined margins and vascular enhancement

DISCUSSION QUESTIONS

1. Would you obtain a molecular profile on this patient?
   1. If so, what is your preferred assay?
2. What is the importance of immunohistochemical markers for desmoid tumors?

Tony Philip, MD: How many folks would consider getting any kind of molecular profiling in this patient case and what would you consider doing for someone like this?

Mohammed Ali, MD: On these tests, we do NGS for almost everything. I think it's important to do NGS.

Philip: It's a reasonable thing to do. Unless we kind of do more, we're not going to know what else is out there. Also, you could be missing another diagnosis potentially. But if it looks like desmoid, chances are they going to have either APC or CTNNB1.

David Gallinson, DO: I would do NGS. Can we still do a colonoscopy on this patient?

Philip: Let's say she got NGS and had an APC mutation, then I would probably do germline testing. And if she had germline APC, then yes, from a colonoscopy standpoint. But if she had the CTNNB1 [mutation] and didn't have any other family history, let's say if she was 40 years old, probably not right away. Maybe when she gets to 45 years old and then meets general guidelines, I would do it that way. I've had some patients where we do the testing, but they have some bowel issues or some blood in their stool, and we’re not sure [whether we should].

I [treat] gastrointestinal and sarcoma. These young patients who are sometimes blown off or delayed because they had bowel issues, no one's thinking about early onset colon cancer. I think we put people through enough that trying to send them for a colonoscopy is not the biggest of issues.

From a molecular or pathology standpoint, we're not all trying to be pathologists, but in terms of staining this nuclear β-catenin is probably the most important thing in order to call it a desmoid tumor. It is typically vimentin positive. I'm not aware that my pathology, or anyone is doing COX-2, androgen receptor, or estrogen receptor staining, not routinely and I'm not aware that you need that there in order to offer them hormone therapy, if that's something you're considering. But for me, a lot of the hormone stuff has fallen by the wayside in terms of real treatment options for patients.

For negative staining, CD34 or c-KIT is something I would think of if I'm worried about a gastrointestinal stromal tumor, rather than a desmoid tumor. But I think we're typically getting this from our pathologists, and you want to make sure your pathologist is someone who knows sarcomas. If they're unsure, it should be reviewed, just to make sure you're not missing something, and it's not misdiagnosed.

DISCUSSION QUESTION

What is your familiarity with desmoid treatment diagnosis and management?

Philip: As of 2024, in JAMA Oncology, they came out with the Desmoid Tumor Working Group management guidelines.¹ You need a pathologist who is comfortable reading soft tissue tumors. Not everyone necessarily needs to be referred to a sarcoma referral center. But if there's lack of clarity about whether a person needs treatment or if there is a trial, I think it's something worth considering. Most of my colleagues who are at different sarcoma centers are looking just to make sure that patients are on the appropriate treatment. Do we have a trial to offer them? But most of the treatments that are in the desmoid space, whether it's new oral agents or some of the older intravenous chemotherapies, are things they're looking to get treated locally, and not necessarily something that's going to be taken within the center itself.

If the patient is coming in and they're not symptomatic from a quality-of-life standpoint or daily functioning, the frontline approach is to try and actively surveil them with imaging. If they are asymptomatic and quality of life is maintained, you do not necessarily need to start treating them, but if there is persistent growth, if they get more than 2 to 3 scans and we're seeing growth, then I'll start treating them or if there are changes in quality of life.

Gallinson: I think this goes back to the one-third concept. You have to learn the pace of disease, pay attention to the location, and pay attention to the patient. I think you need to be thoughtful with caring for your patients with desmoid tumors.

Philip: That's a great point. For patients to understand that education part of it, that just because it's there doesn't necessarily warrant treatment right away, and if there's a chance that one-third of the time, this may just regress on its own, it's very reasonable to place them on surveillance and hope this gets better on its own.

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DISCLOSURES: Philip previously reported honoraria from SpringWorks Therapeutics and a consulting or advisory role with Foundation Medicine, Daiichi Sankyo/AstraZeneca, and Deciphera.

REFERENCE:

1. Kasper B, Baldini EH, Bonvalot S, et al. Current Management of Desmoid Tumors: A Review. JAMA Oncol. 2024;10(8):1121-1128. doi:10.1001/jamaoncol.2024.1805