Classification of MDS
By Konstantina Bilali Panagiotidou - April 28, 2021
As mentioned above, myelodysplastic syndromes is a term referring to a group of malignant tumors. This means that all the “crew members” this group is made from, have some common characteristics and some differences. Let’s take for instance one person who changes his clothing style every week. He remains the same person but with a different appearance, however his main features like his genetic trait and face features remain the same. Likewise, this cancer can appear in different forms. The first scientific classification of these different forms was called FAB classification. Later, question marks and doubts about the heterogeneity and various distinctions between the subcategories concerning their association with other syndromes started emerging. For this reason, another distinction eventually prevailed, the WHO assortment. In this article, I will refer to all the different ways a myelodysplastic syndrome can appear.
Refractory anemia (RA)
Starting off with RA,
this subtype has many different cell disorders. In the blood we can see
bigger erythrocytes than normal, co-occurence of the condition where the erythrocytes appear in different sizes and
different forms (small and large, schistocytes) {condition which we often see
in severe anemias}. In addition, punctate basophilia can appear, which
is a deviation in the color of the red cells and is a sign of cellular
immaturity (a strong association with myelodysplastic syndromes where proper
hematopoiesis is not performed). The difference in the color is a result of gray
granules observed either scattered throughout the erythrocyte or larger and
thinner. These granules are formed from iron residues of mitochondria,
ribosomes or RNA. At the same time, the bone marrow is over filled with
cells, there is dysplasia only
in the RBCs row and the blasts do not exceed 5%. Ringed sideroblasts can be
seen in the marrow but less than 15%.
In the peripheral
blood and the bone marrow, we can observe the same findings as with the RA
subtype, with only difference laying in the bone marrow where the ringed
sideroblasts go beyond the 15%.
Ringed sideroblasts appear
around the nucleus. They are a result of the disrupted iron intake. This disturbance
leads to the existence of increased iron in the cell and in the mitochondria.
The mitochondria filled with the extra iron, move around the nucleus and create
a ring-shaped format. 
Refractory anemia with excess blasts-1
(RAEB-1)
Refractory anemia with excess blasts-2
(RAEB-2)
Type 2 differs from
type 1, in the number of blasts in the blood and in the bone marrow. In
particular, the blasts vary between 5-19% and 10-19% respectively. Another
difference is the presence of Auer rods both in the peripheral and in the
marrow.
Auer rods are found in myeloblasts and are considered pathological findings. Myeloblasts are the “ancestor” cells of the granule cell layer. Coming across the auer rods, we can see them as elongated sticks or lines with a reddish/blue color. Basically, they are comprised of melted lysosomal granules that contain peroxidase, lysosomal enzymes, and large crystalline inclusions.
Normal myeloblastsource :science-hemopoietic
https://www.slideshare.net/csbrprasad/acute-leukemias-amlcsbrpMyeloblast with Auer rods
Refractory cytopenia with multilineage dysplasia (RCMD)
In this category, there is a decrease in the number of two or more cell types in the mature blood cells while they also suffer from dysplastic lesions. The blasts are not many to be seen since in the peripheral blood they will appear less than 1%. On the other hand, the cells in the bone marrow suffer from dysplasia in two or more cell rows, the blasts emerge less than 5%. Apart from those, the marrow contains ringed sideroblasts even though they are less than 15%.
Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)
The only difference from the RCMD , is the presence of ringed sideroblasts in the marrow that exceeds 15%.
Question(e): Why this category does not match with RARS, which also has ringed sideroblasts in the marrow in the same number? The only differences between them are the dysplasia and the cytopenia which are limited only in the erythrocyte row in the RARS while it affects more cell rows in the RCMD. But could they fit into one category only with those added variations?
Unclassified Myelodysplastic syndrome types (MSD-U)
In the blood, cytopenia is observed without the appearance of blasts or Auer rods. The marrow is often seen to produce fewer cells (in comparison to other types whom their marrow in over filled) or can even be found to have normal production in the number of cells. However, there still is a dysplasia in one cell row and the number of blasts remains below 5%.
Minus 5q
This subtype shows a raise in the size of red cells while the number remains normal or a little increased. The blasts are still passing through the blood flow but they are again less than 5%. However, the marrow is over filled, with a notable reduction of the red cells, megakaryocytes seem smaller than normal with their nucleus lacking lobes. Same as before, the blasts continue to be less than 5%. This is the only classification with a genetic abnormality based on the deletion of chromosome 5q. In other words, people with minus 5q MDS, miss a part of the long arm in the chromosome 5. This “abnormality” is not inherited but happens as a mutation throughout life.
Connection between AML and MDS
It has been concluded that Myelodysplastic syndromes stand a chance in turning into another type of cancer: Acute myeloid leukemia. Each type of MDS has a different percentage of the possibility to become AML.
RA and AML
6%
RARS AND AML
1%
RAEB-1 and AML
25%
RAEB-2 and AML
33%
RCMD/RSMD -RS and AML
11%
Unclassified MDS and AML
*66,67%
10%
The scientific evidence suggests that RAEB-2 holds the biggest possibility to progress into AML. This category of MDS appears to have the most blasts in the blood and in the bone marrow. Additionally, the syndrome appears to have dysplasia in more than one cells rows. It can be indicated that as the dysplasia in the cell row and the blast in the blood increase, there are bigger chances to turn into AML. However, I believe that the progression can be affected by some unknown factors.
Survival rate among the types of MDS
The survival prognosis differs among the MDS categories.
5,5 years
RARS
6 years
RAEB-1
1,5 year
RAEB-2
10 months
RCMD/ RSMD -RS
2,5 years
Unclassified MDS
unsure
MDS 5q and AML
Good prognosis
According to the results, RARS has the best prognosis of the disease while RAEB-2 hold the worse. RAEB-2 has as well the biggest possibility to progress into AML which indicates that it is the worst form of this cancer type. This could be a result of the dysplasia appearing in most of the cell rows in combination with the high number of blasts.
Answer to Question(e): One of the reasons why RCMD-RS falls into a different classification than RARS could be the dissimilarity on their progression to both AML and their prognosis. Out of both, RARS gives chances for the person to survivor more with less fear that it will turn into leukemia.
In conclusion, we can see that MDS is a name given to many subtypes of cancer which share some common expressions of cell and hematopoiesis disorder. Many of them have small deviations, like different number of blasts, mainly variables in the heaviness of the disease. Further investigate should be made to be established if a person with any type of MDS have chances of full recovery.
Sources :
- My own notes
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655460/
- https://www.cancer.org/cancer/myelodysplastic-syndrome/about/mds-types.html
- https://medlineplus.gov/genetics/condition/5q-minus-syndrome/
- http://atlasgeneticsoncology.org/Anomalies/del5qID1092.html
- https://pubmed.ncbi.nlm.nih.gov/28927162/
- https://www.medicalnewstoday.com/articles/319346
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