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