Histological Features of MDS-MLD
In MDS-MLD, bone marrow biopsy and aspirate specimens are essential for diagnosis. The histological examination often reveals hypercellularity with
dysplastic changes in multiple cell lineages:
Erythroid Dysplasia: This includes megaloblastic changes, nuclear irregularities, and multinucleation. Ring sideroblasts may be present.
Granulocytic Dysplasia: Features include hypogranulation, nuclear hyposegmentation (pseudo-Pelger-Huët anomaly), and abnormal chromatin clumping.
Megakaryocytic Dysplasia: Seen as micromegakaryocytes, abnormal nuclear lobulation, and small mononuclear forms.
Pathophysiology of MDS-MLD
At the cellular level, MDS-MLD is characterized by
genetic mutations and epigenetic alterations that disrupt normal hematopoiesis. Commonly mutated genes include
SF3B1,
SRSF2, and
TET2. These mutations result in impaired differentiation and increased apoptosis of hematopoietic progenitor cells.
Diagnosis and Classification
The diagnosis of MDS-MLD requires a comprehensive clinical workup including a complete blood count (CBC), peripheral blood smear, and bone marrow examination. The World Health Organization (WHO) classification system is used to define this subtype of MDS based on the presence of dysplasia in multiple lineages and
cytogenetic abnormalities.
Clinical Manifestations
Patients with MDS-MLD often present with symptoms related to cytopenias such as anemia, neutropenia, and thrombocytopenia. Fatigue, recurrent infections, and easy bruising or bleeding are common complaints. The severity of symptoms correlates with the degree of dysplasia and cytopenia.Prognosis and Risk Stratification
The prognosis of MDS-MLD is variable and depends on factors such as the degree of cytopenias, cytogenetic abnormalities, and patient age. The
Revised International Prognostic Scoring System (IPSS-R) is commonly used for risk stratification, which helps in guiding treatment decisions.
Treatment Options
Treatment strategies for MDS-MLD include supportive care, such as transfusions and growth factors, and disease-modifying therapies like hypomethylating agents (
azacitidine,
decitabine) and immunomodulatory drugs. In selected cases, allogeneic hematopoietic stem cell transplantation may be considered.
Future Directions
Research is ongoing to better understand the molecular underpinnings of MDS-MLD and to develop targeted therapies. Advances in
genomic profiling and the identification of novel biomarkers hold promise for more personalized treatment approaches and improved outcomes for patients with this complex disorder.
