What is the likely diagnosis and treatment for a patient presenting with hypochromia, tear drop cells, and microcytosis, suggestive of a underlying bone marrow disorder such as myelofibrosis?

Diagnostic Approach to Hypochromia with Teardrop Cells and Microcytosis

The combination of hypochromia, teardrop cells (dacryocytes), and microcytosis most strongly suggests myelodysplastic syndrome (MDS), and requires immediate bone marrow examination with cytogenetic analysis to establish the diagnosis and exclude myelofibrosis. 1, 2

Primary Differential Diagnosis

The triad of hypochromia, teardrop cells, and microcytosis points to two main diagnostic considerations:

Myelodysplastic Syndrome (Most Likely)

• Teardrop cells are explicitly listed as a sign of red cell dysplasia in MDS by ESMO guidelines, appearing alongside hypochromasia, anisocytosis, and poikilocytosis 1, 2
• MDS typically presents with persistent cytopenias (hemoglobin <11.0 g/dL, neutrophils <1500/mL, and/or platelets <100,000/mL) lasting at least 4 months 1
• The presence of hypochromia with microcytosis in MDS reflects dysplastic erythropoiesis with impaired hemoglobinization 1
• Additional dysplastic features strengthen the diagnosis: pseudo-Pelger-Huët cells, hypogranulation of granulocytes, giant platelets, basophilic stippling, and nucleated red blood cells 1

Myelofibrosis (Must Exclude)

• While teardrop cells are traditionally considered a hallmark of myelofibrosis, in prefibrotic primary myelofibrosis (PMF), only "few if any" dacryocytes are present 1
• Established myelofibrosis shows prominent leukoerythroblastosis (immature myeloid and erythroid precursors in peripheral blood) alongside teardrop cells 1, 3
• Myelofibrosis features bone marrow hypercellularity with megakaryocytic proliferation and clustering, not typically associated with isolated microcytic hypochromic anemia 1

Diagnostic Algorithm

Step 1: Assess Complete Blood Count Pattern

• Document all cytopenias present: Isolated anemia versus bicytopenia versus pancytopenia 1
• Quantify reticulocyte count: Low reticulocytes suggest inadequate marrow response (MDS, myelofibrosis); elevated reticulocytes indicate hemolysis or blood loss 2, 4
• Evaluate mean corpuscular volume (MCV): Microcytosis with hypochromia in MDS reflects dysplastic erythropoiesis, distinct from iron deficiency 1

Step 2: Perform Comprehensive Peripheral Blood Smear Review

• Quantify teardrop cells: Even occasional teardrops warrant investigation if accompanied by cytopenias or other dysplastic features 2
• Identify additional dysplastic features 1:
  • Granulocytes: Pseudo-Pelger-Huët cells, hypogranulation, abnormal chromatin clumping
  • Platelets: Giant platelets, anisometry
  • Red cells: Basophilic stippling, nucleated erythroid precursors, dimorphic population
• Assess for leukoerythroblastosis: Presence of immature myeloid and erythroid precursors strongly suggests myelofibrosis over MDS 1, 2

Step 3: Obtain Targeted Laboratory Studies

• Iron studies (serum iron, total iron binding capacity, ferritin): To exclude iron deficiency as cause of microcytic hypochromic anemia 1
• Vitamin B12 and folate levels: To exclude nutritional deficiencies causing dysplastic changes 1
• Lactate dehydrogenase, bilirubin, haptoglobin: To assess for hemolysis 1, 4
• Erythropoietin level: Typically elevated in MDS with anemia 1

Step 4: Proceed to Bone Marrow Examination (Mandatory)

Bone marrow examination is mandatory when MDS is suspected, particularly in elderly patients with unexplained cytopenias and dysplastic peripheral blood features 1, 2

Required Components:

• Bone marrow aspirate 1:

  • Evaluate dysplasia in erythroid, myeloid, and megakaryocytic lineages
  • Enumerate blasts (must be <5% for MDS without excess blasts)
  • Perform Prussian blue (Perls) stain to identify ring sideroblasts
  • Assess cellularity

• Bone marrow trephine biopsy (strongly recommended in addition to aspirate) 1:

  • Assess for reticulin and collagen fibrosis using reticulin stain
  • Evaluate megakaryocyte morphology and distribution
  • Exclude hypoplastic MDS or fibrotic MDS
  • In case of dry tap, biopsy allows definitive diagnosis

• Cytogenetic analysis (mandatory) 1:

  • Standard karyotype from at least two different cell cultures (24h and 48h)
  • Analysis of at least 20 metaphases if normal karyotype
  • Clonal chromosomal abnormalities occur in >80% of MDS patients
  • Specific abnormalities (del(5q), -7/del(7q), complex karyotype) provide presumptive evidence of MDS even with minimal dysplasia 1

• Flow cytometry immunophenotyping (recommended) 1, 4:

  • Detect abnormalities in erythroid, immature myeloid, and maturing granulocyte compartments
  • Helps distinguish clonal from reactive processes

Critical Clinical Pitfalls

Do Not Assume Myelofibrosis Exclusively

While traditionally associated with myelofibrosis, teardrop cells are now recognized as a common dysplastic feature in MDS 1, 2. The presence of hypochromia and microcytosis without prominent leukoerythroblastosis favors MDS over myelofibrosis 1, 2.

Do Not Delay Bone Marrow Examination

If only unilineage dysplasia is present without increased blasts, ring sideroblasts <15%, and no recurrent cytogenetic abnormalities, an observation period of 6 months with repeat bone marrow may be appropriate 1. However, in elderly patients with persistent cytopenias and multiple dysplastic features including teardrop cells, proceed directly to bone marrow examination 1, 2.

Do Not Overlook Iron Deficiency

Iron deficiency can cause reactive thrombocytosis and must be excluded before diagnosing essential thrombocythemia or other myeloproliferative neoplasms 1. However, iron deficiency does not typically produce teardrop cells in combination with other dysplastic features 1.

Recognize MDS with Fibrosis

MDS can present with bone marrow fibrosis (fibrotic MDS), which requires bone marrow biopsy for diagnosis, especially in cases of dry tap 1. This entity must be distinguished from primary myelofibrosis based on megakaryocyte morphology and degree of leukoerythroblastosis 1.

Treatment Considerations

Once MDS is diagnosed, treatment depends on risk stratification using the International Prognostic Scoring System-Revised (IPSS-R), which incorporates cytogenetics as the highest prognostic value parameter 1. Lower-risk MDS may be managed with supportive care, erythropoiesis-stimulating agents, or lenalidomide (for del(5q) MDS), while higher-risk MDS requires hypomethylating agents or consideration for allogeneic stem cell transplantation 1.

If myelofibrosis is diagnosed instead, JAK inhibitors (ruxolitinib, fedratinib, pacritinib) are standard treatment for symptomatic disease, though allogeneic stem cell transplantation remains the only curative option 5, 6, 7.