The clinical value of high fluorescent lymphocytes and smudge cells in the diagnosis of infectious mononucleosis.

BACKGROUND: The diagnostic value of high fluorescent lymphocytes (HFLC) and smudge cells in diseases like sepsis has been confirmed. In this study, we explore the diagnostic value of HFLC and smudge cells for infectious mononucleosis (IM). METHODS: Sixty-two IM patients, 67 healthy controls, 84 patients with upper respiratory tract virus infection, and 35 patients with malignant lymphoid diseases were enrolled. The complete blood counts and leukocyte differential counts are tested, and the smudge cells were manually counted. RESULTS: The value of HFLC% and smudge cells of the IM group were significantly higher than those of healthy controls and disease controls (p < 0.05), and the HFLC% value of IM patients was positively correlated with the number of reactive lymphocytes (r = 0.265). When the cutoff value of HFLC% was 0.4%, and the diagnostic value of IM was high (AUC = 0.995). When the smudge cells >2/100 nucleated cells, it can show better (AUC = 1.000). When the cutoff value of the HFLC% was 1.2%, it can effectively distinguish IM patients from upper respiratory tract virus infection patients (AUC = 0.934); when smudge cells >16/100 nucleated cells, it also has high differential diagnosis value (AUC = 0.913). In addition, the AUC of the combination HFLC% and smudge cells for the differential diagnosis can be increased to 0.968. The performance value of single HFLC% (AUC = 0.942) for distinguishing IM from malignant lymphoid diseases was better than smudge cells and combine index with the cutoff value of 0.4%. CONCLUSION: HFLC% and smudge cells can be used as effective indicators in the early diagnosis and differential diagnosis of IM.

An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio.

Background: Neutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge. Objective: We employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19. Methods: Peripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators. Results: Morphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels. Conclusion: Observing blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia.

OBJECTIVE: We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. METHODS: In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. RESULTS: The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p = 0.0009), CD38 expression (p = 0.039), unmutated IGVH status (p = 0.0009) and presence of cytogenetic abnormalities (for del 13q, p = 0.0012, while for other cytogenetic aberrations, p = 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r = -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p = 0.41) or gender (median, 19% for males vs. 20% for females; p = 0.76). CONCLUSION: When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Lymphocytosis with Smudge Cells Is Not Equivalent to Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) often presents with lymphocytosis and smudge cells (SCs) on routine peripheral blood (PB) tests. In some cases, these findings are assumed to be sufficient to diagnose CLL. We present a 54-year-old male who was referred for further management of progressing CLL. At the initial presentation, he looked unwell and had diffuse lymphadenopathy and splenomegaly. Blood work showed normocytic anemia (hemoglobin 72 g/L), thrombocytopenia (platelet count 74 × 109/L), leukocytosis (white blood cell count 135.5 × 109/L) including lymphocytosis (130.1 × 109/L), and the presence of SCs on a PB smear. Additional workup including flow cytometry (FC), bone marrow biopsy, and lymph node biopsy led to a diagnosis of leukemic stage of advanced-stage mantle cell lymphoma. Although lymphocytosis with SCs is more frequently and in higher quantities seen in CLL they are not pathognomonic and can be present in a variety of lymphoproliferative disorders. Additional diagnostic examination of cell morphology and FC to assess clonality and determine the immunotype of lymphocytes are required to establish an accurate diagnosis and determine appropriate further management of the specific disease type.

Smudge Cells in Chronic Lymphocytic Leukemia: Pathophysiology, Laboratory Considerations, and Clinical Significance.

Chronic lymphocytic leukemia (CLL) is the most commonly encountered leukemia in the clinical laboratory. Cytoskeletal defects in CLL lymphocytes can result in the formation of up to 75% smudge cells (SCs) during blood film preparation. Failure to account for these damaged lymphocytes in the white blood cell (WBC) differential diminishes the accuracy and reproducibility of the results. Lacking clear practice standards on handling SCs in CLL, different laboratories may employ different methods to mitigate SC-induced errors. This review explores the pathophysiology of SCs, their effect on WBC differentials in CLL, and how these results can impact clinical decisions. The pros and cons of various SC corrective methods are described to assist laboratories in developing an optimized protocol to reduce errors and inconsistencies in WBC differentials. Finally, the potential utility of SC enumeration as an indicator of CLL prognosis is discussed in terms of laboratories with differing access to technology.

A Needle in the Haystack: A Rare Case of Spontaneous Tumor Lysis in Newly Diagnosed Chronic Lymphocytic Leukemia Unmasked by Acute Renal Failure.

Tumor lysis syndrome (TLS) is the phenomenon of metabolic derangements that typically follows the initiation of cytotoxic chemotherapy. Metabolic disturbances include hyperphosphatemia, hyperkalemia, hyperuricemia and hypocalcemia. Hematological malignancies are associated with spontaneous TLS (STLS), which is cell lysis in the absence of chemotherapy. STLS is extremely rare in chronic lymphocytic leukemia (CLL). This has been documented only once in the medical literature, making this an extraordinarily uncommon case. We present here a 68-year-old male with a history of benign prostatic hyperplasia (BPH) who is admitted for a two-week history of abdominal pain and three days of anuria, despite adequate fluid intake. Laboratory values yielded a greatly elevated leukocyte count with a lymphocytic predominance and smudge cells. Potassium, phosphorus, and uric acid were also significantly increased. EKG revealed peaked T-waves. Flow cytometry confirmed the presence of an abnormal B-cell population consistent with B-cell chronic lymphocytic leukemia, with the following markers: CD19+, CD20+, CD23+, CD5+, CD10-. He was diagnosed with CLL and treated with aggressive fluid resuscitation, allopurinol and rasburicase. The patient had another similar episode within one month. His CLL fluorescence in-situ hybridization (FISH) showed complex cytogenetics with unmutated IgVH and he was subsequently started on ibrutinib.

Smudge cell percentage as a surrogate marker for ZAP-70 expression in patients with chronic lymphocytic leukemia.

BACKGROUND: This study aimed to evaluate the prognostic value of smudge cell percentage as a surrogate marker for zeta-chain-associated protein kinase 70 (ZAP-70) expression in chronic lymphocytic leukemia (CLL) patients. METHODS: Sixty three newly diagnosed CLL patients were investigated at the Hematology Department of the Medical Research Institute of Alexandria University with complete blood count, lactate dehydrogenase, ß2 microglobulin levels, ZAP-70 expression, and estimation of the percentage of smudge cells. RESULTS: The percentage of smudge cells ranged from 2 to 58% with a mean of 24.03±13.98%. Higher percentages of smudge cells (>30%) were statistically significantly associated with markers of better prognosis (negative ZAP-70, early-stage disease according to the Binet and Rai staging systems, as well as low and intermediate risk CLL prognostic index). The percentage of smudge cells showed significantly negative correlation with the ZAP-70 expression and higher area under the curve for prediction of ZAP-70 positivity with better survival for 36 months in patients with >30% smudge cells. CONCLUSION: The percentage of smudge cells at presentation of newly diagnosed CLL patients could be used as a surrogate marker for ZAP-70 expression and an additional prognostic marker for disease progression.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia

Abstract Objective We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. Methods In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. Results The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p= 0.0009), CD38 expression (p= 0.039), unmutated IGVH status (p= 0.0009) and presence of cytogenetic abnormalities (for del 13q, p= 0.0012, while for other cytogenetic aberrations, p= 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r= -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p= 0.41) or gender (median, 19% for males vs. 20% for females; p= 0.76). Conclusion When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Feasibility of Counting Smudge Cells as Lymphocytes in Differential Leukocyte Counts Performed on Blood Smears of Patients With Established or Suspected Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

BACKGROUND: Lymphocytosis and smudge cells are commonly observed on the blood smears of patients with an established or suspected diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma. Excluding smudge cells from the manual differential count (MDIFF), a common laboratory practice, yields unreliable results and consequently necessitates performing the MDIFF testing on an albuminized blood smear. OBJECTIVE: To assess the reliability of counting smudge cells as lymphocytes in the MDIFFs on nonalbuminized smears and automated differentials (ADIFFs) as a substitute for MDIFFs. METHODS: We compared corresponding results of MDIFFs on nonalbuminized smears vs MDIFFs on albuminized smears (group A, n = 82), ADIFFs vs MDIFFs on nonalbuminized smears (group B, n = 68), and ADIFF vs MDIFFs on albuminized smears (group C, n = 50). Smudge cells on the nonalbuminized smears were counted as lymphocytes. We focused on 2 white blood cell types: neutrophils and lymphocytes. RESULTS: Respective means for % lymphocytes and % neutrophils were 83.2 vs 83.2 and 14.0 vs 13.6 for Group A, 75.0 vs 77.0 and 20.2 vs 19.8 for Group B, and 76.1 vs 79.3 and 18.7 vs 17.4 for Group C. Respective correlation coefficients for % lymphocytes and % neutrophils were 0.92 and 0.94 for group A, 0.94 and 0.97 for group B, and 0.88 and 0.92 for group C. CONCLUSION: Counting smudge cells as lymphocytes on nonalbuminized blood smears yielded reliable MDIFF results. Reportable ADIFF results were generated by the analyzer on 73% of the specimens, of which 93% were reliable.

POEMS syndrome - A case report revealing a complex evolving diagnosis.

Description of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) goes back to 1938 when a patient with sensorimotor peripheral neuropathy, hyperpigmemntation, solitary plasmacytoma, and elevated cerebral spinal fluid protein was reported. Since then, numerous other cases of this condition have been described by various authors including one that followed the first case 18 years later about two patients. Even though this rare condition still remains an oddity in diagnosis calling for clinicians to have a high index of suspicion due to its manifestation with varied clinical features. We present a case of POEMS syndrome that started as an episode of transient ischemic attack (TIA) and elevated levels of digestive enzymes not previously reported.

Automated quantification of apoptosis in B-cell chronic lymphoproliferative disorders: a prognostic variable obtained with the Cell-Dyn Sapphire (Abbott) automated hematology analyzer.

INTRODUCTION: B-chronic lymphocytic leukemia CLL, a neoplastic clonal disorder with monomorphous small B lymphocytes with scanty cytoplasm and clumped chromatin, can be morphologically differentiated in typical and atypical forms with different prognosis: Smudge cells (Gumprecht's shadows) are one of the well-known features of the typical CLL and are much less inconsistent in other different types CLPD. Abbott Cell-Dyn Sapphire uses the fluorescence after staining with the DNA fluorochrome propidium iodide for the measurement of nucleated red blood cells (NRBCs) and nonviable cells (FL3+ cell fraction): We have studied the possible correlation between presence and number of morphologically identifiable smudge cells on smears and the percentage of nonviable cells produced by Cell-Dyn Sapphire. METHODS: 305 blood samples from 224 patients with B-cell lymphoproliferative disorders and 40 healthy blood donors were analyzed by CBC performed by Cell-Dyn Sapphire, peripheral blood smear, and immunophenotype characterization. RESULT: FL3+ fraction in CLPD directly correlated with the percentage of smudge cells and is significantly increased in patients with typical B-CLL. This phenomenon is much less evident in patients with atypical/mixed B-CLL and B-NHL. CONCLUSION: In small laboratories without FCM and cytogenetic, smudge cells%, can be utilized as a preliminary diagnostic and prognostic tool in differential diagnosis of CLPD.

Smudge cell percentage as a surrogate marker for ZAP-70 expression in patients with chronic lymphocytic leukemia

BACKGROUND: This study aimed to evaluate the prognostic value of smudge cell percentage as a surrogate marker for zeta-chain-associated protein kinase 70 (ZAP-70) expression in chronic lymphocytic leukemia (CLL) patients. METHODS: Sixty three newly diagnosed CLL patients were investigated at the Hematology Department of the Medical Research Institute of Alexandria University with complete blood count, lactate dehydrogenase, β2 microglobulin levels, ZAP-70 expression, and estimation of the percentage of smudge cells. RESULTS: The percentage of smudge cells ranged from 2 to 58% with a mean of 24.03±13.98%. Higher percentages of smudge cells (>30%) were statistically significantly associated with markers of better prognosis (negative ZAP-70, early-stage disease according to the Binet and Rai staging systems, as well as low and intermediate risk CLL prognostic index). The percentage of smudge cells showed significantly negative correlation with the ZAP-70 expression and higher area under the curve for prediction of ZAP-70 positivity with better survival for 36 months in patients with >30% smudge cells. CONCLUSION: The percentage of smudge cells at presentation of newly diagnosed CLL patients could be used as a surrogate marker for ZAP-70 expression and an additional prognostic marker for disease progression.

Smudge cells in peripheral blood smears did not differentiate chronic lymphocytic leukemia from other B-cell chronic lymphoprolipherative diseases / Sombras nucleares no esfregaço do sangue periférico não diferenciam a leucemia linfocítica crônica das outras doenças linfoproliferativas B crônicas

Smudge cells has been classically associated with chronic lymphocytic leukemia (CLL), but they are found in peripheral blood tests for other chronic B-cell lymphoproliferative diseases (CLD). We investigated whether the percentage of smudge cells in peripheral blood smears can be used in the clinical practice to differentiate CLL from other B-cell CLD. The peripheral blood smears of 63 patients with the diagnosis of CLL and 62 with other B-cell CLD were analyzed. Three hundred cells (both lymphoid cells and smudge cells) were counted for each peripheral blood smear. A comparison of the percentage of smudge cells between the two groups was performed and, subsequently, 5 cut-off values were fixed (10 percent, 20 percent, 30 percent, 40 percent and 50 percent of smudge cells) with the aim of defining cases as "positive" or "negative" for smudge cells and verifying whether there are any differences between CLL and the other B-cell CLD. The percentage of smudge cells in patients with CLL (median 26 percent, 4 percent-86 percent) was higher than in patients with B-cell CLD (median 14 percent, 1 percent-64 percent). However, none of the cut-off values tested presented suitable values of sensitivity, specificity and positive predictive value to separate the two groups. As it is necessary to have a single cut-off value with high sensitivity, specificity and positive predictive value to infer the diagnosis of CLL in the clinical practice, we concluded that smudge cells are not fitting to differentiate CLL from other B-cell CLD.

As sombras nucleares têm sido classicamente associadasà leucemia linfocítica crônica (LLC), embora possam ser encontradas nos esfregaços do sangue periférico de outras doenças linfoproliferativas B crônicas (DLBC). Nesse estudo, nós investigamos se a porcentagem de sombras nucleares nos esfregaços do sangue periférico pode ser utilizada na prática clínica da hematologia para diferenciar a LLC das outras DLBC. Foram analisados os esfregaços do sangue periférico de 63 pacientes com o diagnóstico de LLC e 62 com outras DLPC. Trezentas células, entre células linfoides e sombras nucleares, foram contadas em cada esfregaço. A comparação da porcentagem de sombras nucleares entre os dois grupos foi realizada e, subsequentemente, foram fixados 5 cut-offs de mais de 10 por cento, 20 por cento, 30 por cento, 40 por cento e 50 por cento de sombras nucleares com o propósito de definir um caso como "positivo para sombras nucleares" e verificar se havia diferenças entre a LLC e as outras DLBC. A porcentagem das sombras nucleares em pacientes com LLC (mediana 26 por cento, 4 por cento-86 por cento) foi maior do que em pacientes com DLBC (mediana 14 por cento, 1 por cento-64 por cento). Entretanto, nenhum dos cut-offs testados apresentou valores apropriados de sensibilidade, especificidade e valor preditivo positivo para distinguir os dois grupos. Desde queé necessário se dispor de um único valor de cut-off com alta sensibilidade, especificidade e valor preditivo positivo para inferir o diagnóstico de CLL na prática clínica, conclui-se que as sombras nucleares não são úteis para diferenciar a LLC das outras DLBC.