What is the significance and management of teardrop cells in peripheral blood smear?

Significance and Management of Teardrop Cells in Peripheral Blood Smear

Teardrop cells (dacryocytes) in peripheral blood smear are a significant morphologic finding that primarily indicates bone marrow architectural distortion, most commonly seen in myelofibrosis, but can also appear in other hematologic conditions requiring further investigation.

Diagnostic Significance

Primary Associations

• Myelofibrosis and Myelodysplastic Syndromes (MDS)
  • Teardrop cells are classically associated with primary or secondary myelofibrosis 1
  • Listed as a specific sign of red cell dysplasia in MDS according to ESMO guidelines 1
  • Often accompanied by other peripheral blood findings including:
    • Leukoerythroblastic blood picture
    • Anisocytosis and poikilocytosis
    • Nucleated red blood cells
    • Immature myeloid cells

Other Important Associations

• Autoimmune Hemolytic Anemia (AIHA)

  • Teardrop cells are found in 89% of AIHA cases 2
  • May be related to splenic involvement and extramedullary hematopoiesis 3

• Microangiopathic Hemolytic Anemia (MAHA)

  • Present in 91% of MAHA cases 2
  • Significantly higher dacryocyte counts compared to controls (p<0.0001) 2

• Infiltrative Bone Marrow Disorders

  • Malignant infiltration of bone marrow
  • Metastatic carcinoma
  • Hematologic malignancies with bone marrow involvement

Pathophysiologic Mechanisms

Spleen-Related Mechanisms

• Splenic Influence
  • Splenectomy results in a fourfold decrease in teardrop cells in agnogenic myeloid metaplasia 4
  • Splenomegaly and extramedullary hematopoiesis contribute to teardrop formation 3
  • Resolution of splenomegaly correlates with disappearance of teardrop cells 3

Bone Marrow-Related Mechanisms

• Marrow Architecture Distortion
  • Fibrosis disrupts normal RBC maturation and egress from bone marrow
  • Abnormal passage through distorted marrow sinusoids
  • Chemotherapy that reduces marrow fibrosis can decrease teardrop poikilocytes 5

Diagnostic Approach

Initial Evaluation

• Complete Blood Count with Differential

  • Quantify teardrop cells and other abnormal RBC morphologies
  • Assess for cytopenias, particularly anemia and thrombocytopenia
  • Look for leukoerythroblastic picture (immature WBCs and nucleated RBCs)

• Peripheral Blood Smear Examination

  • Carefully evaluate for other signs of dysplasia in granulocytes, red cells, and platelets 1
  • Document percentage of teardrop cells
  • Look for other RBC abnormalities: anisocytosis, poikilocytosis, dimorphic erythrocytes, polychromasia, hypochromasia, megalocytes, basophilic stippling 1

Further Workup

• Bone Marrow Aspiration and Biopsy

  • Mandatory for evaluation of cellularity, dysplasia, blast percentage, and fibrosis 1
  • Assess for ring sideroblasts and other dysplastic features
  • Reticulin staining to evaluate for fibrosis
  • In case of dry tap, bone marrow biopsy becomes especially important

• Cytogenetic Analysis

  • Essential for detecting clonal chromosome abnormalities 1
  • Prognostic value in MDS and myeloproliferative neoplasms
  • Standard karyotype has highest prognostic value of all IPSS-R parameters in MDS 1

• Molecular Testing

  • Evaluate for mutations associated with myeloid disorders (DNMT3A, ASXL1, TET2, JAK2, TP53) 1
  • Helps distinguish between CHIP, CCUS, ICUS, and IDUS 1

Management Approach

Based on Underlying Condition

1. If Myelofibrosis or MDS:

   • Risk stratification using IPSS-R score
   • Treatment based on risk category and patient factors
   • Consider JAK inhibitors for myelofibrosis
   • Hypomethylating agents for higher-risk MDS

2. If Autoimmune Hemolytic Anemia:

   • Immunosuppressive therapy
   • Monitor for resolution of teardrop cells with treatment of underlying condition 3

3. If Microangiopathic Hemolytic Anemia:

   • Treat underlying cause (TTP, DIC, etc.)
   • Plasma exchange if appropriate

4. If Infiltrative Malignancy:

   • Directed therapy toward primary malignancy
   • Chemotherapy can reduce teardrop poikilocytes 5

Monitoring

• Serial peripheral blood smears to assess response to therapy
• Decreasing teardrop cells may indicate treatment effectiveness 5
• Persistent or increasing teardrop cells may suggest disease progression

Pitfalls and Caveats

• Teardrop cells alone are not pathognomonic for any single condition
• The presence of teardrop cells in peripheral blood should always prompt consideration of bone marrow examination
• Splenomegaly without bone marrow fibrosis can produce teardrop cells 3
• In patients with splenomegaly, teardrop cells may decrease after splenectomy even when the underlying condition persists 4
• Teardrop cells may be present in various hemolytic anemias and should not automatically trigger a diagnosis of myelofibrosis 2