Two‐site evaluation of a new workflow for the detection of malignant cells on the Sysmex XN‐1000 body fluid analyzer

Abstract

Introduction The presence of high fluorescent cells (HF‐BF) on the Sysmex XN‐1000 hematology analyzers has gained interest regarding the prediction of malignant cells in body fluids, but lacks sensitivity. We aimed to increase this sensitivity by combining HF‐BF value, automated results, and clinical information. Methods We evaluated a new workflow for the management of body fluids in the hematology laboratory, including the HF‐BF criterion and clinical information. In two laboratories, 1623 serous fluids were retrospectively analyzed on the XN‐1000 BF mode. All samples were morphologically screened for malignant cells. Optimal HF‐BF cutoffs were determined to predict their presence. Thereafter, the added value of clinical information was evaluated. Other reflex testing rules (eosinophilic count >5% and presence of the WBC Abnormal Scattergram flag) were also used to refine our workflow. Results Optimal HF‐BF cutoffs in the two hematology centers were 108 and 45 cells/µL, yielding a sensitivity/specificity of 66.7/93.6% and 86.8/66.6% for malignant cell detection. When adding clinical information, sensitivity/specificity evolved to 100.0/68.9% and 100.0%/not determined. Of 104 samples containing malignant cells, 97 had positive clinical information; the remainder had a HF‐BF > cutoff. Conclusion Combining clinical information and HF‐BF reached 100% sensitivity for malignant cell detection in body fluid analysis. Lack of robustness of the optimal HF‐BF cutoff deserves the use of local cutoffs. Rapid automated results reporting from the XN‐1000 BF mode are also feasible in clinical practice. Prospective evaluation of the workflow is needed before its implementation in clinical practice.

Clinical application of an algorithm to screen for malignant cells in body fluids using an automated hematology analyzer

“…Manual examination is basically performed for CSF, but refers to the HF‐BF value calculated through automated analysis, comparing it with the cutoff. Suspicious for malignancy or atypical (indeterminate) cell is defined as a cell with a relatively large size, high nuclear to cytoplasmic ratio, and prominent nucleoli and variable features, such as nuclear molding, cannibalism, or presence of tridimensional clusters 5 …”

“…Detecting malignant cells is a major problem in clinical laboratories 2 . Conventionally, cytological examination (microscopic method) has been the gold standard for detecting malignant cells in BFs 3–8 . However, conventional microscopic examination is time‐ and manpower‐consuming, and variability between observers can affect the results 3,4,8,9 …”

“…Sysmex's XN series (Sysmex, Kobe, Japan) can carry out differential calculation of leukocytes using flow cytometry by applying fluorescence intensity as a differential coefficient index along with forward scattering and lateral scattering using a semiconductor laser; the results of such evaluation have been reported 3–5,7,10–12 . As this device has a complete blood count (CBC) and BF mode, it can determine the CBC and BF counts, respectively.…”

El recuento automatizado de células en líquidos biológicos: una revisión

“…Esta alarma es un indicador de la presencia de células con una elevada relación núcleo-citoplasma y un elevado contenido en ácidos nucleicos y su presencia ha sido propuesta como criterio para la revisión mediante microscopía óptica de la celularidad de la muestra por un experto cualificado, dado que su recuento se ha correlacionado de forma significativa con la presencia de células mesoteliales y/o malignas [33]. Sin embargo, son todavía varias las limitaciones para la implantación de las HF-cells, incluyendo la falta de estandarización entre las diferentes metodologías [33] y la falta de consenso respecto a que recuento o porcentaje de las mismas debe ser considerado como criterio para la revisión microscópica manual, probablemente debido a diferencias en los criterios utilizados en los estudios para establecer la positividad de la microscopía óptica y en los objetivos finales de estos estudios, realizados principalmente con analizadores Sysmex [17,[56][57][58][59][60][61][62][63][64][65] (Tabla 3). En el HF-BF, además de células de origen neoplásico, se clasifican otros tipos de células benignas como macrófagos y células mesoteliales, que reducirían la especificidad de esta magnitud para la detección de malignidad [66], con valores que varían entre el 55% y el 87% [61][62][63]; la modificación del algoritmo utilizado por el analizador Sysmex-XN 1000 para la detección de HF-cells en base a las características de la célula maligna puede ser útil para mejorar la especificidad en la detección de dicho tipo de células [67].…”

“…(4) La evaluación de la imprecisión del recuento celular en líquidos biológicos requiere de materiales de control de calidad específicos para este tipo de espécimen [6,19]. (5) Deben diseñarse algoritmos para el análisis de líquidos biológicos que incorporen criterios para la toma de decisiones respecto a la revisión por personal cualificado [2,17,58,65].…”