The Pathologist’s Role in an MDS Diagnosis | Aplastic Anemia and MDS International Foundation

The Pathologist’s Role in an MDS Diagnosis

Can you explain in general terms what pathologists do and what their specific roles are in an MDS diagnosis?

The pathologist is involved at every stage in the diagnosis and subsequent follow up of a patient being treated for MDS. Often, when the patient is detected to have low blood counts on a CBC, by evaluating a peripheral blood smear, the pathologist alerts the clinician that there may be underlying MDS and the patient should be investigated further in this direction. The pathologist is the one who examines the bone marrow specimen, confirms the diagnosis of MDS, and assesses for morphological features that are required to generate the prognostic score of high-risk or low-risk disease necessary for management decisions. Since the bone marrow sample is sent to the laboratory, often the pathologist is there to triage the specimen and see that it is sent to the cytogenetic lab, and for appropriate molecular testing to make sure all the necessary tests are conducted.

What should the two-way interaction be between an MDS patient’s treating physician and the pathologist?

Communication between the pathologist and clinician is very important in the diagnosis of MDS. A report by the pathologist of dyspoietic or abnormal morphological appearance of the blood cells on the peripheral blood smear of a patient with low blood counts may often initiate the further evaluation of MDS by the clinician However,  neither low counts nor dyspoiesis are specific only to MDS, and several other clinical conditions may mimic MDS morphologically.  Dyspoiesis in peripheral blood or bone marrow is not enough to make an MDS diagnosis. Talking to the clinician to find out the details of the patient history, results of other lab tests that may have been ordered, and other medical issues that may be affecting the patient are important for the correct interpretation of dyspoiesis, and to make a diagnosis of MDS. Sometimes the pathologist has to ask the clinician to order additional tests before a diagnosis can be rendered. An ongoing communication is needed to make this happen. There are situations when a definite categorization of MDS may not be possible, or there are co-morbid conditions confounding the interpretation. In these circumstances in particular, a discussion via a phone call or a meeting between the clinician and pathologist is necessary to resolve the concerns. In academic centers like ours, all newly diagnosed patients are discussed in a team setting at an MDS or leukemia meeting, attended by the treating physician, oncologist, hematopathologists, radiologists, and other specialty physicians as necessary,  so it is definitely a team-based approach.

From a pathologist’s perspective, what factors complicate an MDS diagnosis?

One of the complicating issues is simply not having the right tools, which include the appropriate specimen and the necessary clinical information about the patient. It may be that a CBC is not provided, or there is no concurrent peripheral blood smear with the bone marrow, or that the specimen is inadequate­­­­--and this can happen frequently. The technique of obtaining the bone marrow specimen is very important. Common problems are the biopsy being too small or fragmented or it includes cartilage and bone rather than marrow. Or else, the aspirated bone marrow material may be diluted with peripheral blood, or the smears not prepared properly even if the material is adequate resulting in crushing of the cells. Finally, a perfect specimen may be difficult or impossible to interpret if the staining is not optimal. These pre-analytic issues are the most important ones that can create a problem. Fortunately, these are problems that can be resolved by attention to detail and by training.

Of course then there are issues inherent to the disease. MDS is a diverse disease in terms of morphology with many reactive mimics. Although most often the bone marrow is hypercelluar, in about 5-10% of patients, it may be hypocellular when a distinction from aplastic anemia is very difficult. The dysplastic changes can be very subtle, and more often than not, in a hypocellular setting, when a diagnosis of MDS is dependent on cytogenetics, an adequate specimen for cytogenetic evaluation cannot be obtained. There are situations where the MDS may be associated with fibrosis, and distinction from myelofibrosis or a myeloproliferative/myelodysplastic overlap disease is very difficult. Similar to a hypocellular marrow, marrow aspirate material can often not be obtained from fibrotic marrows.

There are situations when there is an associated hemolysis, or the bone marrow is obtained after repeated transfusions, which can alter the morphology and confound the interpretation. And I must mention there are inherited bone marrow failure syndromes that may present for the first time at an older age. These bone marrow failure syndromes may not only mimic MDS, but they often predispose to MDS. The distinction is important for management and requires specific tools for diagnosis and involvement of geneticists and other specialty physicians.

How involved are pathologists in the diagnostic process in determining an MDS classification or subtype?

I would say very involved since the diagnosis is made and confirmed by the pathologist. The blast percentage important for prognosis is also determined by the pathologist, so the pathologist is very involved in the diagnosis, classification, and generation of the IPSS or other risk score necessary for outlining the treatment strategy for the particular patient.  The involvement does not end with a diagnosis. The pathologist is involved in the follow up – in assessing response to treatment or evolution of the disease.

Should patients be asking their doctor about what happens ‘behind the scenes’ in the pathology lab?

They should be curious to know what happens to the specimen obtained from their body. I think it is important for them to know the processes involved in arriving at a diagnosis. Patients should know about the procedure, ask what the tests are for; or should the specimen be submitted, if cytogenetics will be performed. They need to understand that many quality control measures are required to ensure the pathologist gets the right materials (we discussed the adequacy of the biopsy and the aspirate smears earlier, and the importance of the clinical history). MDS is often a difficult diagnosis, and many patients move from one institution to another before they find a doctor they are most comfortable with.  In most cases, a bone marrow procedure is performed at each institution. So there are several reports with different wording and interpretations, and since the disease may evolve with time, to get a complete picture, as a hematopathologist, I would like to evaluate all the previous materials. For continuity of care, it is important to have copies of all their reports. Generally, the patient does not directly contact the pathologist for questions regarding the report. The treating physician is the better person to answer their question and they should be the first contact, but the patient should know who the hematopathologist is, and if they can contact them if they wish to.

What is most important for patients to know and remember about the pathologist’s involvement in arriving at an MDS diagnosis?

Most patients do not know there is another physician involved in making the diagnosis, other than the one they see at appointments who reads out the report to them. They should understand that the diagnosis and management of MDS is a team approach. Also, if I were the patient, I would want to know if the physician reading their slides has a specialty certification.

How important is it for patients to have a pathologist who sees a significant number of cases of MDS, knows very specifically what to look for, and knows what to communicate to the treating physician?

It is essential. Hematopathology is a very specialized field. Just as a breast or prostate biopsy is best examined by a person who has special training in these fields, has seen many of these biopsies, and knows what to look for, a bone marrow biopsy is best examined by a pathologist with special training in the field, and preferably with many years of experience. Having worked in academic institutions that receive many consult cases, I have seen instances of both over-diagnosis and under-diagnosis of MDS. 

Zeba Singh, MBBS

Position / Title: 
Assistant Professor of Pathology
University of Maryland Medical Center
Education Topics: