The 2016 published revision of the World Health Organization’s (WHO) classification of tumors and hematopoietic and lymphoid tissues provided pathologists with refinements to diagnosis, prognosis, and therapeutic approaches for myeloid neoplasms, but there is still much to discern, according to Nichon L. Grupka, MD.
“Now, there are prognostic implications for therapy and potentially classification. Though a lot of the criteria are the same, all of the myelodysplastic syndrome (MDS) categories have been altered to streamline the process,” said Grupka. “That includes more specific wording and the incorporation of new technology.”
Pathologists are now working to define what role these technologies, such as next-generation sequencing, will have in the classification and identification of disease states. She adds that pathologists are still working to understand the relationship between a number of mutations and malignancies.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Grupka, a pathologist at Novant Health Thomasville Medical Center, discussed advances in hematopathology, specifically mutations as prognostic indicators, disease-associated versus disease-causing mutations, and advice for physicians who are working to navigate the field.
OncLive: What advances have there been in hematopathology?
: The biggest advancement is the release of the 2016 WHO classification; that incorporates a whole area of somatic mutations. We’d like to use next-generation sequencing to determine if a patient who has an abnormality in their genome has MDS. We’re still figuring out if we can use this technology to define that criteria.
Subsequently, what do we do with that information? That can be confusing for a lot of people because older people who do not have MDS, or any hematologic malignancy, can also possess these mutations. Some of those patients may even be cytopenic. The challenge is taking all of this technology and information and incorporating it into a body of knowledge that is constantly changing. We know the basic entities and, because of the WHO, a few additional criteria have been recognized. It's difficult if you've been practicing for a long period of time.
Everyone is busy seeing patients, so finding the time to sit down and read the revised guidelines can be difficult. That's where I see my role as a pathologist coming in. If a patient has a molecular mutation, we can use these new technologies to classify the patient. Sometimes, I can outright call it MDS, and sometimes I can't. Oftentimes, it’s a phone call to relay the information and describe what's missing from the criteria that's required for MDS.
A lot of these mutations in MDS are not necessarily specific to a particular disease entity. For instance, if someone has a t(9;22), a Philadelphia chromosome, they are likely to have chronic myeloid leukemia. However, if they have an SF3B1
mutation, the patient could have chronic lymphocytic leukemia (CLL) or MDS. The same is true with the BRAF
mutation. We can see that in nonhematologic malignancies and hairy cell leukemia.
As I said, some mutations are not specific to a malignancy, and the presence of one may not mean anything for your patient at that time. It might mean that they have a predisposition to a malignancy downstream, or it might mean they have a predisposition to something nonhematopoietic, like a propensity for arteriosclerosis. It’s a vast field, and it's changing rapidly. Plasma cells will likely play a role in the field, as well.
What are some mutations that have prognostic features?
Patients with an SF3B1
mutation typically are associated with a very specific morphologic pattern. Patients with MDS who are associated with a ring sideroblast, oftentimes have a [different] disease course. It really depends on the context of that particular disease as opposed to it showing up in a patient with CLL. Some people have a TET2
mutation, and a lot of these patients have a neutral prognosis. Is that actually a mutation that allows for other mutations to accumulate? Does its presence predispose to other conditions, or does it potentiate other conditions? That's the difficulty because most of them are not necessarily very specific.
Are there reasons why these mutations may carry these abnormalities?
Our genes have uniqueness, and we can have what's called polymorphisms. There’s the standard sequence of base pairs and DNA. Some people can have diversions, but it’s not necessarily disease-causing mutations. Usually you can sample bone marrow so you can determine whether or not it’s constitutional. You can take a buccal swab and sequence the DNA to see if they possess that polymorphism in an area of the body that isn’t suspected to have disease. Then you can determine whether or not it’s just a part of their makeup.