Grading in Soft Tissue Sarcomas
Why knowing the grade is important for patients
Obligatory—this is not medical advice
There are so many questions for the patients with a new diagnosis of sarcoma. A key part of discussion is the stage. Part of what distinguishes soft tissue sarcoma from other types of cancer is that the individual patterns of behavior vary so much by subtype. Most do not spread to lymph nodes, aside from a rare few (eg synovial, epithelioid, angiosarcoma, etc). Most, if they spread, will go to the lungs, while others have different tropisms (myxoid liposarcoma, alveolar soft part sarcoma, etc). While it’s vital to determine the subtype of sarcoma, sometimes that information can take a while to obtain. When this information is all collected, it’s also important to keep in mind that an individual prognosis is unknown, and oncologists reference trends of data measured on other patients from the past. That all said, let’s review a little about how grading factors into staging and prognosis for patients with sarcomas.
What is grade?
In short, grade is a somewhat formalized means of predicting the biologic behavior of a sarcoma based on what’s seen under the microscope. Grades range from low to high. There are multiple systems by which a pathologist could ascertain the grade. The most widely used, and therefore validated, is the FNCLCC (Federation Nationale des Centres de Lutte Contre le Cancer) system.1
3 points are given depending upon differentiation (see table below).
3 points are contingent upon the number of mitoses viewed per 10 high powered fields.
A high powered field is that which is visible at 400x in a field of view.
2 points are given contingent upon the percentage of the specimen that has necrosis.
Therefore, the maximum number of points attributable to a specimen is 8, and the minimum number of points is 2. Low grade is 2-3 points, intermediate grade is 4-5 points, and high grade is 6-8 points (see table below).
Grade and Prognosis
We’ve established how the grade is determined. How has this actually been shown to be a valid means of predicting the risk of recurrence of death from soft tissue sarcoma? Below, you’ll see a figure that shows that the likelihood of metastasis, that is spread, of the cancer is much less common the lower the grade of the sarcoma. As a result of this, it is one of the single most important factors in determining a stage for sarcomas.
Below I have included the staging system for the extremities or trunk. Having a higher grade, even if the tumor is smaller, elevates from a stage I to stage II or III.2
The implications of this jump in stage are significant and are reflected in the following graph which was published in JNCCN. Here we can see that, for instance, if a patient were to have a 9 centimeter tumor of the limb that was grade 1 (stage IB), sarcoma-specific survival would be approximately 95% at 10 years. If the grade were increased to 2 or 3, this becomes a stage IIIA diagnosis with a sarcoma specific survival expected to be around 70% at 10 years, a 25% change. Patients at higher risks may benefit from different types of therapy, which has been explored elsewhere in this substack.
Weaknesses
It is important to understand that this system is far from perfect. As explored above, grading can incorporate a large amount of information that may not be present at the time of initial diagnosis. Grading also has some nuances, as it cannot be performed on specimens from patients who have undergone neoadjuvant treatment. Likewise, there are some diagnoses, that, even if they are higher grade, nonetheless, have better prognoses than others. Other tools, such as nomograms (the sarculator is commonly used), can be helpful in drilling into these numbers further. All of this should be explored with an experienced, sarcoma oncologist so that patients can have the most accurate reflection of their situation. This all needs to be measured in context.
Conclusions
Grading is a system used by pathologists to attempt to define the biologic characteristics of a sarcoma. It is a measurement that can be subjective, and dependent upon where a tumor is sampled. Nonetheless, it can provide useful information to patients and providers that could be employed in order to determine the role of various types of therapy as well as prognosis.
https://pubmed.ncbi.nlm.nih.gov/17090186/
https://jnccn.org/view/journals/jnccn/16/2/article-p144.xml