Bone marrow contains megakaryocytes, the cells responsible for producing platelets. Platelets are small cell fragments that circulate in the blood and are essential for forming clots to stop bleeding. A normal megakaryocyte is a giant cell, typically 50 to 100 micrometers in diameter, with a large, multi-lobated nucleus. The term “dysplastic” refers to abnormal development or shape. A dysplastic megakaryocyte is a malformed version of this cell, indicating a disruption in the normal process of cell maturation.
Characteristics and Identification
The identification of dysplastic megakaryocytes hinges on recognizing specific abnormalities in their appearance, or morphology. Pathologists look for features that deviate from the normal, large cell with a complex, lobed nucleus. One common feature is the presence of micromegakaryocytes, which are significantly smaller than their healthy counterparts and are an indicator of dysplasia.
Another defining characteristic is an abnormal nucleus. Instead of the typical large, interconnected multi-lobed structure, dysplastic cells may have a single, small, non-lobated nucleus or multiple, separate nuclei. Pathologists may also observe cells with nuclear features that are hyposegmented, meaning they lack the proper number of lobes. These features are often more easily identified in a bone marrow biopsy compared to an aspirate smear.
A bone marrow examination is required to identify these cells. A hematopathologist performs a bone marrow aspirate and biopsy, procedures where a sample of liquid marrow and a core of bone marrow tissue are removed from the hip bone. These samples are then processed and stained for examination under a microscope. To confirm significant dysplasia, at least 10% of the megakaryocytes must display these abnormal features.
Associated Medical Conditions
The presence of dysplastic megakaryocytes is strongly linked to a group of cancers known as Myelodysplastic Syndromes (MDS). MDS are clonal hematopoietic stem cell diseases where the bone marrow fails to produce enough healthy blood cells. In these disorders, immature blood cells, or blasts, do not develop correctly, leading to low counts of one or more types of blood cells, a condition called cytopenia. The diagnosis of MDS often relies on identifying this level of dysplasia in one or more of the major myeloid cell lines.
While prominently associated with MDS, dysplastic megakaryocytes can also be a feature of other myeloid disorders. They are sometimes found in cases of Acute Myeloid Leukemia (AML), a cancer characterized by the rapid growth of abnormal myeloid cells. In some instances, MDS can progress and transform into AML.
Another condition where these abnormal cells may be present is Chronic Myelomonocytic Leukemia (CMML). CMML is an overlap syndrome, sharing features of both myelodysplastic and myeloproliferative neoplasms, the latter being characterized by the overproduction of blood cells. In these conditions, the dysplastic cells are a sign of disordered blood cell formation from a mutated hematopoietic stem cell.
Physiological Consequences
The abnormal structure of dysplastic megakaryocytes impairs their primary function: producing platelets. This leads to a condition called thrombocytopenia, a lower-than-normal number of platelets in the blood. Platelets are required for hemostasis, the process that causes bleeding to stop. When a blood vessel is injured, platelets are among the first responders, sticking to the site of injury to form a temporary plug.
Ineffective platelet production, or dysmegakaryopoiesis, means the body cannot mount an adequate response to even minor injuries. Consequently, patients often experience symptoms related to poor blood clotting. These can include easy bruising, prolonged bleeding from cuts, and the appearance of petechiae—tiny red or purple spots on the skin that result from minor bleeding.
Other common manifestations include frequent or severe nosebleeds and bleeding from the gums. The severity of thrombocytopenia in conditions like MDS often correlates with the risk of bleeding complications. It is not just the low number of platelets but also their function that can be compromised, as they may have defects in their ability to form a stable clot.
Prognostic Significance
The discovery of dysplastic megakaryocytes carries significant weight for a patient’s prognosis. Pathologists and hematologists evaluate the percentage and specific types of these abnormal cells to help classify the subtype of a disease like MDS. For instance, a high percentage of micromegakaryocytes or megakaryocytes with a single nucleus can be independent adverse prognostic factors.
This morphological assessment is a component of scoring systems, such as the Revised International Prognostic Scoring System (IPSS-R). These systems combine multiple factors to predict the likely course of the disease. Factors include the types and severity of cytopenias, the percentage of immature blast cells in the bone marrow, and specific chromosomal abnormalities.
By integrating the findings about megakaryocyte dysplasia with these other data points, clinicians can build a more complete picture of the patient’s condition. This evaluation helps to stratify patients into different risk categories, from very low to very high risk. Such risk stratification is important for guiding treatment decisions, determining whether a patient might benefit from more intensive therapies or a watch-and-wait approach.