Differential Diagnosis

Given the heterogeneity of myelodysplastic syndromes (MDS), as well as the clinical and morphologic characteristics, the diagnosis of MDS is complex. MDS share characteristics and symptoms with other disorders, such as pre-MDS disorders and dysplasias associated with other disorders.1

The main characteristics of MDS are clonality, dysplasia, and cytopenias.2 There are several pre-MDS disorders that have many of the characteristics of MDS but do not meet the criteria for MDS.3 When one of these features is absent, it is considered an MDS-related disorder.2 However, these pre-MDS conditions may develop into MDS or other hematopoietic neoplasms over time.3

Distinguishing MDS from MDS-related disorders (pre-MDS)2

Clonality Dysplasia Cytopenias Bone Marrow Blast (%)
“Non-clonal” ICUS
(idiopathic cytopenias of undetermined significance)
+ <5
(clonal hematopoiesis of indeterminate potential)
+ <5
(clonal cytopenias of undetermined significance)
+ + <5
Lower-risk MDS + + + <5
Higher-risk MDS + + + <19

Adapted from Steensma DP et al. Blood. 2015;126(1):9-16.

MDS share symptoms with many other disorders4

Rule out diagnosis through exclusion of the following: Disease states that may present the same clinically:
  • Viruses
  • Alcohol abuse
  • Nutritional deficiencies
  • Medications
  • Autoimmune disorders
  • Hepatic or renal diseases
  • Paroxysmal nocturnal hemoglobinuria
  • Large granular leukemia
  • Aplastic anemia
  • Acute myeloid leukemia
  • Fanconi anemia
  • Myeloproliferative neoplasms

Adapted from Bejar R. Curr Hematol Malig Rep. 2015;10(3):282-291.

Malignant diseases that mimic MDS
Some patients can have overlapping syndromes, including aplastic anemia (AA), paroxysmal nocturnal hematuria (PNH), T-cell large granular lymphocytic leukemia (T-LGL), or myeloproliferative neoplasms (MPNs), and may be misdiagnosed as having MDS.1

Non-malignant diseases that mimic MDS
It’s important to differentiate MDS from other dysplasias associated with:

Viral Infection
  • Viral infections, including HIV infection, can produce morphologic changes in immature blood cells and show clinical signs of cytopenias and hypercellular marrow.5 However, HIV is associated with cellular debris and increased plasma cells/lymphocytes in bone marrow5
Nutritional Deficiencies
  • Vitamin B12 and folate deficiencies are associated with megaloblastic changes and often severe dyserythropoiesis6
  • Copper deficiency can cause anemia, neutropenia, vacuolization of early granulocyte and erythroid precursors, and ringed sideroblasts in the bone marrow, which may be assessed by laboratory testing5,7
  • Malabsorption of nutrients (eg, iron, copper) following gastric bypass procedures8
Drug Use
  • Drugs that interfere with vitamin B12- or folic acid-related processes, or with DNA synthesis, can cause anemia with macrocytosis9

To accurately diagnose MDS, it is important that an experienced hematopathologist assesses the bone marrow findings.

References: 1. DeZern AE, Sekeres MA. The challenging world of cytopenias: distinguishing myelodysplastic syndromes from other disorders of marrow failure. Oncologist. 2014;19(7):735-745. 2. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9-16. 3. Valent P, Orazi A, Steensma DP, et al. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions. Oncotarget. 2017;8(43):73483-73500. 4. Bejar R. Myelodysplastic syndromes diagnosis: what is the role of molecular testing? Curr Hematol Malig Rep. 2015;10(3):282-291. 5. Orazi A, Czader MB. Myelodysplastic syndromes. Am J Clin Pathol. 2009;132(2):290-305. 6. Heaney ML, Golde DW. Myelodysplasia. N Engl J Med. 1999;340(21):1649-1660. 7. Sutton L, Vusirikala M, Chen W. Hematogone hyperplasia in copper deficiency. Am J Clin Pathol. 2009;132(2):191-199. 8. Chen M, Krishnamurthy A, Mohamed AR, Green R. Hematological disorders following gastric bypass surgery: emerging concepts of the interplay between nutritional deficiency and inflammation. BioMed Res Intl. 2013;205467:1-8. 9. Carey PJ. Drug-induced myelosuppression: diagnosis and management. Drug Safety. 2003;26(10):691-706.