Unclassifiable Myelodysplastic Syndromes

(MDS-U)

When receiving your MDS diagnosis, you might encounter a rare subtype of MDS, unclassifiable MDS (MDS-U). Before the pathologist (the doctor who evaluates tissue samples and cells) can designate a case as MDS-U, all other classifications have to be ruled out. This means the diagnostic workup must be complete, and studies should be performed optimally to be sure it is unclassifiable. 

So, MDS-U is a myeloid neoplasm characterized by ineffective blood cell production in the bone marrow, and it does not meet the criteria for any other MDS subtype. 

Scenarios that could indicate you have an undetermined case of MDS: 

• Cases of MDS with less than 5% bone marrow blasts that have 1% blasts in the peripheral blood, reported on at least two separate occasions
• Cases of MDS with abnormal cell growth limited to one type of cells or family of cells (MDS with single lineage dysplasia], MDS with ring sideroblasts, and single lineage dysplasia that have low blood cell count (hemoglobin < 10 g/dL, absolute neutrophil count < 1.8 x 109/L and platelet count < 100 x 109/L)
• Persistent, unexplained low blood cell counts lacking the diagnostic appearance of MDS cells that have specific cytogenetic abnormalities.  

Clinical Features

The way MDS-U presents varies depending on the specific type. Patients usually present with symptoms related to low blood cell counts in one or more lines of cell types.

Morphologic Features

Morphologic dysplasia in at least one lineage characterizes most types of MDS-U. Cases with morphologic dysplasia are placed into the MDS-U category if they have discordant cytopenias (pancytopenia with dysplasia limited to one lineage) or peripheral blood blast count (1% blasts in the peripheral blood with no increase in blasts in the bone marrow)

Cytogenetic abnormalities 

There is no specific immunophenotype of MDS-U. When excess blasts are lacking or there are enough abnormalities in the cell production of any line (lymphoid or myeloid) your physician may determine that it could be a case of  MDS-U if any one of the following cytogenetic abnormalities is detected in the karyotype analysis of the bone marrow cells sample; deletion of chromosomes 7q, 5q, 17q, 17p, 13q, 11q, 12p, 9q, and translocations t(11;16)(q23;p13.3), t(3;21)(q26;q22.1), t(1;3)(p36.3;q21.2), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34).

However, many of these abnormalities are not specific to MDS-U. Other classifications have to be ruled out before coming up with a diagnosis of unclassifiable MDS. These genetic abnormalities can also be present in myeloproliferative neoplasm types. 

If you receive a diagnosis of MDS-U, your case should be followed carefully and further reclassified as one of the defined subtypes of MDS if it is found to meet the criteria after evaluation. This opens the window to study MDS-U further to understand its clinical behavior.  Further study could help is predict or treat MDS-U in a more specific and targeted manner. 

REFERENCE: 

Pathology of Unclassified Myelodysplastic Syndromes - Medscape