From the Guidelines
Smudge cells are a characteristic morphologic feature of chronic lymphocytic leukemia (CLL) and indicate the presence of this disease or other lymphoproliferative disorders. These cells are damaged lymphocytes that appear on a blood smear as fragile cells with smeared nuclear material and disrupted cell membranes, giving them a "smudged" appearance, as described in the guidelines for the diagnosis and treatment of CLL 1. They form during the preparation of blood smears when malignant lymphocytes rupture due to their fragility. Some key features of smudge cells include:
- They are found as cell debris, also known as Gumprecht nuclear shadows
- They are characteristic of CLL, but can also be seen in other conditions like hairy cell leukemia or lymphomas
- Their presence should prompt further diagnostic evaluation, including flow cytometry, bone marrow biopsy, and cytogenetic testing to confirm the diagnosis, as outlined in the guidelines for CLL diagnosis and treatment 1. The diagnosis of CLL requires the presence of at least 5 × 10^9 B lymphocytes/L (5000/L) in the peripheral blood, and the clonality of the circulating B lymphocytes needs to be confirmed by flow cytometry 1. Some important considerations when evaluating smudge cells include:
- The percentage of prolymphocytes, which may comprise up to 55% of the blood lymphocytes in CLL
- The presence of lymphadenopathy or organomegaly, cytopenias, or disease-related symptoms, which can indicate a more advanced disease state
- The potential for monoclonal B-lymphocytosis to progress to frank CLL at a rate of 1% to 2% per year 1.
From the Research
Smudge Cells Indication
Smudge cells are ruptured lymphocytes present on routine blood smears of chronic lymphocytic leukemia (CLL) patients. The percentage of smudge cells on a blood smear has been evaluated as a prognostic factor in CLL patients.
- The studies 2, 3, 4, 5 suggest that a higher percentage of smudge cells is associated with a better prognosis, including longer progression-free and overall survival.
- A lower percentage of smudge cells (less than 30%) has been correlated with poorer outcomes, such as shorter time to first treatment and overall survival 2, 3, 4, 5.
- The percentage of smudge cells has also been associated with other prognostic factors, including CD38 expression, ZAP-70 status, and cytogenetic abnormalities 3, 4, 5.
Prognostic Significance
The prognostic significance of smudge cells has been evaluated in several studies:
- A study published in 2014 found that patients with ≤ 30% smudge cells had a shorter median progression-free period and lower 5-year survival rate compared to patients with more than 30% smudge cells 2.
- A study published in 2009 found that the percentage of smudge cells was an independent predictor of overall survival in CLL patients 3.
- A study published in 2010 found that the percentage of smudge cells was a novel prognostic factor in CLL, with patients having < 20% smudge cells having a significantly shorter time to first treatment and overall survival 4.
- A study published in 2022 found that a low smudge cell percentage (< 30%) was correlated with poorer outcomes, including Binet stage B/C, CD38 expression, unmutated IGVH status, and presence of cytogenetic abnormalities 5.
Clinical Significance
The clinical significance of smudge cells has been evaluated in various diseases, including hematological malignancies and solid tumors:
- A study published in 2016 found that smudge cells were frequently presented in out-of-hospital cardiac arrest, infections, hematological cancers, and solid cancers, but there was no relationship between the percentage of smudge cells and patient mortality in all diseases 6.
- However, in patients with all cancers, those who had higher percentage of smudge cells were prone to have poor outcomes when compared with the subjects with lower percentage of smudge cells 6.