What is the recommended workup for a patient suspected of having Myelodysplastic Syndromes (MDS)?

MDS Workup

The workup for suspected MDS requires mandatory peripheral blood smear, bone marrow aspirate and biopsy, and cytogenetic analysis, preceded by comprehensive laboratory testing to exclude reversible causes of cytopenias. 1

Initial Clinical Assessment

Before proceeding with invasive testing, obtain a detailed history focusing on:

• Prior exposures: chemotherapy, radiation therapy, radioimmunotherapy, radioiodine, benzene or other occupational/hobby exposures 1
• Medications: current and recent drugs that may cause cytopenias 1
• Lifestyle factors: alcohol intake, smoking history 1
• Symptoms: bleeding/bruising tendencies, infection history 1
• Family history: especially in younger patients, focus on inherited bone marrow failure syndromes (Fanconi anemia, telomere disorders) 1
• Physical examination: assess spleen size 1

Mandatory Laboratory Testing

Hematologic Studies

• Complete blood count with differential: WBC count, RBC count, hemoglobin, platelet count, RBC indices (MCV), reticulocyte count 1
• Peripheral blood morphology: evaluate for dysplastic features including pseudo-Pelger-Huët cells, hypogranulation/degranulation of granulocytes, giant platelets, anisocytosis, poikilocytosis, basophilic stippling 1, 2

Biochemical Studies to Exclude Reversible Causes

• Nutritional deficiencies: RBC-folate/serum folic acid, cobalamin (vitamin B12) 1
• Iron studies: serum iron, total iron binding capacity, ferritin 1
• Hemolysis markers: lactate dehydrogenase, bilirubin, haptoglobin 1
• Renal function: creatinine 1
• Erythropoietin level: useful for treatment planning with erythropoiesis-stimulating agents 1

Viral Studies

• Anti-HIV 1
• Anti-parvovirus B19: particularly in hypoplastic MDS 1
• Cytomegalovirus testing 1
• Hepatitis B antigen and anti-hepatitis C virus: especially in transfusion-dependent patients 1

Additional Testing

• Paroxysmal nocturnal hemoglobinuria (PNH) clone: flow cytometry for PNH if clinical suspicion exists 1
• Specific genetic analyses: if inherited bone marrow failure disorder suspected 1

Mandatory Bone Marrow Examination

Core Components (All Required)

Peripheral Blood Smear 1

• Evaluate dysplasia in one or more cell lines
• Enumerate blasts
• Review at least 200 cells 1, 2

Bone Marrow Aspirate 1

• Evaluate dysplasia in erythroid, granulocytic, and megakaryocytic lineages (≥10% of cells in affected lineage must show dysplasia) 1, 2
• Enumerate blasts (crucial for prognosis; include agranular blasts, myeloblasts, and promonocytes but NOT promyelocytes) 1
• Enumerate ring sideroblasts using Prussian blue (Perls) stain—mandatory in lower-risk MDS 1
• Review up to 500 cells 1
• Assess cellularity, CD34+ cells, and fibrosis 1

Bone Marrow Biopsy 1

• Assess marrow cellularity, fibrosis, and topography 1
• Evaluate histologic architecture 1

Cytogenetic Analysis (Conventional Karyotyping) 1

• Detect acquired clonal chromosomal abnormalities
• Essential for diagnosis and prognostic assessment 1
• Identifies recurrent cytogenetic abnormalities that can establish diagnosis even without robust morphologic markers 1

Recommended Additional Studies

FISH (Fluorescence In Situ Hybridization) 1

• Use when standard G-banding repeatedly fails 1
• Detects targeted chromosomal abnormalities in interphase nuclei 1

Flow Cytometry Immunophenotyping 1

• Detect abnormalities in erythroid, immature myeloid, maturing granulocytes, monocytes, and lymphoid compartments 1
• Recommended but not mandatory 1

SNP Array 1

• Detects chromosomal defects at high resolution when combined with metaphase cytogenetics 1
• Suggested but not mandatory 1

Mutation Analysis 1

• Screen for somatic mutations (particularly TP53, SF3B1, DNMT3A, ASXL1, TET2, JAK2) 1, 2
• Allows conclusive diagnosis and prognostic evaluation 1
• Suggested but not mandatory 1

Critical Diagnostic Pitfalls

When Diagnosis is Uncertain 1

• If only unilineage dysplasia is present, no increase in blasts, ring sideroblasts <15%, and normal karyotype: observe for 6 months with repeat bone marrow examination before confirming MDS diagnosis 1
• These patients typically have mild cytopenia only and unlikely rapid progression 1
• Repeated bone marrow examinations weeks, months, or even years apart may be required to establish diagnosis 1

Differential Diagnoses to Consider 1

• ICUS (Idiopathic Cytopenias of Uncertain Significance): mild cytopenia ≥4 months, <10% dysplasia, <5% blasts, no clonal markers 1
• IDUS (Idiopathic Dysplasia of Unknown Significance): no significant cytopenia, >10% dysplasia, <5% blasts, no clonal markers 1
• CCUS (Clonal Cytopenias of Uncertain Significance): cytopenia ≥4 months, <10% dysplasia, <5% blasts, but MDS-related mutations present with VAF 2-30% 1

Referral and Expertise

All newly diagnosed patients should be evaluated at a center with specific hematologic competence to ensure comprehensive diagnostic approach and optimal treatment planning. 1, 3