From the Guidelines
Smudge cells are primarily associated with chronic lymphocytic leukemia (CLL), while rouleaux formation is caused by conditions that increase plasma proteins, such as multiple myeloma and Waldenström macroglobulinemia. Smudge cells are characterized by the fragile leukemic cells easily rupturing during blood smear preparation, creating smudged or smeared appearances on the slide, as noted in the guidelines for the diagnosis and treatment of CLL 1. Other lymphoproliferative disorders may occasionally cause smudge cells, but CLL is the most common cause.
Key Causes of Smudge Cells and Rouleaux Formation
- Smudge cells: + Chronic lymphocytic leukemia (CLL) 1 + Other lymphoproliferative disorders
- Rouleaux formation: + Multiple myeloma + Waldenström macroglobulinemia + Inflammatory conditions + Some infections Rouleaux formation, on the other hand, is caused by excessive production of immunoglobulins, which causes red blood cells to stack together like coins, forming rouleaux, as discussed in the consensus recommendations for standard investigative workup for plasma cell disorders 2. Understanding these phenomena is crucial for accurate diagnosis, and further investigation, including flow cytometry, genetic testing, serum protein electrophoresis, and immunofixation studies, should be guided by the presence of smudge cells or rouleaux formation. While these findings are not definitive diagnoses on their own, they serve as important clues in the diagnostic process.
Diagnostic Approach
- Smudge cells: + Flow cytometry + Genetic testing
- Rouleaux formation: + Serum protein electrophoresis + Immunofixation studies In clinical practice, it is essential to consider these findings in the context of the patient's overall clinical presentation and to pursue further testing as needed to establish a definitive diagnosis.
From the Research
Causes of Smudge Cells and Rouleaux Formation
- Smudge cells are often associated with chronic lymphocytic leukemia (CLL) and can be present in other lymphoproliferative disorders 3
- The presence of smudge cells on a peripheral blood smear is not pathognomonic for CLL and requires additional diagnostic examination to establish an accurate diagnosis 3
- Smudge cells are ruptured lymphocytes that can be found on routine blood smears of CLL patients 4, 5
- The percentage of smudge cells on a blood smear has been found to have prognostic significance in CLL patients, with higher percentages associated with better outcomes 4, 5
- Rouleaux formation, which is the stacking of red blood cells, can be caused by various factors, but there is no direct evidence in the provided studies to suggest a specific cause related to smudge cells or CLL
- However, it is worth noting that CLL patients often have abnormal blood cell counts and morphology, which could potentially contribute to Rouleaux formation 6, 7
- Automated morphological analysis of peripheral blood leukocytes has been shown to be a powerful tool for the quantitative morphological stratification of CLL, and may help identify distinct phenotypes and chromosomal aberrations 7