Assessment of Peripheral Blood Lymphocytosis in Adults: Determination of Thresholds for Differential Diagnosis between Clonal and Reactive Lymphocytosis

Background and objectives: Differential diagnosis between clonal lymphocytosis (CL) and reactive lymphocytosis (RL) is often established through blood smear examination but with some limitations. We aimed to evaluate ability of clinical data and extended-cells blood count (CBC) parameters to discriminate CL from RL and to establish a decision-making algorithm for moderate lymphocytosis in adults. Methods: A total of 85 samples were collected from adults with absolute lymphocytescount of >5G/l. The samples were divided into RL group (n=34) and newly diagnosed CL group (n=51).Demographic data, CBC parameters including high fluorescence lymphocytes cells percentage (HFLC%) and abnormal lymphocytes or blasts (’AbnLym/BL’’) morphological flag were evaluated for each study group. New threshold for discriminating parameters were determined using receiver operating characteristic (ROC) curves and used in an algorithm for moderate lymphocytosis. Results: Age, high lymphocytes count and the presence of the ’AbnLym/BL’’ flag and low HFLC% were predictor of malignant lymphocytosis. Age threshold of 62.5 years and absolute lymphocytes count of > 10.47 G/l were highly effective in CL detection with area under the ROC curve of 0.9 and 0.99, respectively. In addition, HFLC% showed an area under the ROC curve of 0.71. Considering ALC threshold of 10.47 G/l alone, a sensitivity of 96.7% and a specificity of 100 % were achieved. For moderate lymphocytosis ranging between 5 and 10.47G/l, no false positive or negative result was detected when we considered both the proposed ALC and age cut-offs. Conclusion: A combination threshold for ALC and age appears to be helpful for screening CL, especially in moderate lymphocytosis for both laboratory and clinical routine practice.