Etiology
- Primary (de novo): Most common, cause is unknown. Risk increases with age (>70 years).
- Secondary (t-MDS): Occurs after exposure to chemotherapy (especially alkylating agents, topoisomerase II inhibitors), radiation, or toxins like benzene.
Pathophysiology
- Clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, leading to peripheral blood cytopenias despite a typically hypercellular bone marrow.
- Considered a premalignant condition, with a variable risk of transformation to Acute Myeloid Leukemia (AML).
Classification
French American British (FAB) Classification System
The FAB system divides MDS in to five subtypes based on percentage of blasts in the bone marrow and the peripheral blood. It is now used less frequently than the WHO classification, but is included here as a reference.
| FAB-type | % blasts in blood | % blasts in bone marrow |
|---|---|---|
| RA (Refractory Anemia) | < 1 | < 5 |
| RARS (Refractory Anemia with Ring Sideroblasts | < 1 | < 5 |
| RAEB (Refractory Anemia with Excess Blasts in Transmission) Note: Now called AML (acute myelogenous leukemia) | < 5 | 5 - 20 |
| RAEB-t (Refractory Anemia with Excess Blasts in Transformation) | > 5 | 21 - 30 |
| CMML (chronic myelomonocytic Leukemia) | > 5 | 5 - 20 |
Mnemonic
试着联想记忆： 按照排名分类，人才名单只有＜5%，其次是热爱二本的在5%～20%，最后是热爱二本的体育生在20%～30%，所以有Auer小体。其中热爱二本的人也喜欢穿纯棉面料（5%～20%）。
人才名单—RCMD— ＜5% 热爱二本—RAEB— 5%～20% 热爱二本-体—RAEB-t— 20%～30% 纯棉面料—CMML— 5%～20%
Clinical features
- Often asymptomatic and discovered on routine blood work.
- Symptoms are related to the specific cytopenia(s):
- Anemia (most common): Fatigue, weakness, dyspnea, pallor.
- Neutropenia: Recurrent or severe infections.
- Thrombocytopenia: Petechiae, ecchymoses, epistaxis, or other bleeding.
- Splenomegaly can be seen, particularly in Chronic Myelomonocytic Leukemia (CMML), an MDS/MPN overlap syndrome.
Diagnostics
Tip
MDS is marked by the following:
- ≥1 cytopenias: normal hematopoiesis is impaired due to neoplastic cell replication in the bone marrow; therefore, patients usually present with symptoms of ≥1 cytopenia such as fatigue/dyspnea on exertion (anemia), bleeding/bruising (thrombocytopenia), or infections (leukopenia). Because erythrocyte production is impaired, reticulocyte count will be low despite significant anemia. However, significant extramedullary hematopoiesis does not occur, so hepatosplenomegaly is rare.
- Dysplasia of erythrocytes and neutrophils: peripheral blood smear usually shows normocytic or macrocytic erythrocytes with a variety of abnormalities (eg, oval macrocytes). Neutrophils are typically hypolobulated and hypogranular.
- Normocytic or macrocytic anemia (rarely microcytic) of refractory type (refractory anemia)
- Leukocytopenia and/or thrombocytopenia
- Nucleated RBCs
- Pseudo-Pelger-Huet anomaly
- Neutrophils with hyposegmented nuclei (usually bilobed)
- Seen in peripheral blood smears of patients undergoing chemotherapy
- Neutrophils with hyposegmented nuclei (usually bilobed)
- Bone marrow biopsy: hypercellular, dysplastic bone marrow
- Ringed sideroblasts
- Chromosome analysis: In > 50% of patients, chromosomal aberrations can be detected at the time of diagnosis