Remarks on Desmoid Tumors
'Tying it all together'
Obligatory - This is not medical advice
Muller, in 1838, was the first to call these growths desmoid, based on the Greek word desmos, which means to bond or tie.
What are desmoid tumors?
These are benign fibroblastic lesions that grow in an uncontrolled way as a result of activation of distinct pathways (to be discussed later). They can become very large, quickly. We think of these as being related to, or instigated in the wound healing process, and many of our patients may have an antecedent trauma history. They can happen anywhere in the body.
Even though they are benign, they have the potential to cause significant symptoms and possibly even organ dysfunction—it all depends on where they are, and how they behave. As one could imagine, there’s a tremendous difference between a tumor on the leg, or one near the airway.
How common are they, and who gets them?
The quoted annual incidence is 1-2 per million per year. While I have no reason to doubt that number, most oncologists who see primarily sarcoma will likely tell you that while they’re deemed uncommon, they likely represent a significant proportion of their practice. Anecdotally, I would say that approximately 20% of my weekly visits are devoted to patients with desmoid tumors.1
As far as average age, they happen in individuals between the ages of 15 and 60, with a slight female predominance. They are associated Familial Adenomatous Polyposis syndrome (or germline mutations in APC), and we can review why that is later. For patients who are younger, and are diagnosed with desmoid fibromatosis, it is reasonable to refer to genetic counseling—although whether to do this reflexively continues to be a matter of debate.
There is also classically thought of to be an association between desmoid fibromatosis and high estrogen states, such as pregnancy. I would say that the simple association here has waned in recent years, and we have longitudinal data to guide us in pregnancy. It is more likely that what compels the growth of desmoid tumors is not so simple and study is ongoing.
What makes them grow, anyways?
I am not a molecular biologist. That said, I’ve talked to enough pathologists and attended enough meetings to have a casual familiarity with the Wnt pathway. In essence it is a means of regulating cell proliferation, differentiation, etc.
As you can see in this image (reference included to open access paper), in the absence of Wnt signaling, normal destruction of the beta-catenin protein is mediated by GSK3, AXIN, APC, etc. Variances in the capacity of any of these proteins can lead to elevated levels of beta-catenin, which promotes gene expression, ultimately leading to dysregulated fibroblast growth in desmoids. The majority of desmoid tumors have a mutation in beta-catenin. While various analyses have been performed to look at the significance of the mutated genes in desmoid tumors, we do not yet have data that is conclusive enough to guide our management.23
Some of the medications that we prescribe attempt to act on this pathway. Others might have more indirect effects. How we go about choosing individual medications will be addressed later in separate posts along with more detailed analysis of the trials or data that has led to their incorporation into practice.
How do we get the diagnosis?
Diagnosis is typically made by biopsy, or after resection of a tumor. It relies on both morphological features as well as immunohistochemical staining. Most tumors have bland, ‘spindle’ cells that stain positive for Beta catenin and vimentin. See picture below from pathology outlines.
What is the general treatment approach?
For most patients with desmoid tumors (those without symptoms), a watch and wait approach is recommended. There are certainly exceptions, such as for those with symptoms, or threatened organ function. That stated, given that many desmoid tumors can resolve without treatment, it really is the best option for most patients. Imaging is usually performed every 3-6 months in line with our guidelines, although alterations can be made based on shared decision making with patients.
We’ll talk more about specific therapies in future posts. The last few years have been teeming with new data and medications which can help our patients with desmoids.
https://www.ejcancer.com/article/S0959-8049(20)31389-7/fulltext