ELN iMDS flow working group validation of the monocyte assay for chronic myelomonocytic leukemia diagnosis by flow cytometry.

BACKGROUND: It was proposed that peripheral blood (PB) monocyte profiles evaluated by flow cytometry, called "monocyte assay," could rapidly and efficiently distinguish chronic myelomonocytic leukemia (CMML) from other causes of monocytosis by highlighting an increase in the classical monocyte (cMo) fraction above 94%. However, the robustness of this assay requires a large multicenter validation and the assessment of its feasibility on bone marrow (BM) samples, as some centers may not have access to PB. METHODS: PB and/or BM samples from patients displaying monocytosis were assessed with the "monocyte assay" by 10 ELN iMDS Flow working group centers with harmonized protocols. The corresponding files were reanalyzed in a blind fashion and the cMo percentages obtained by both analyses were compared. Confirmed diagnoses were collected when available. RESULTS: The comparison between cMo percentages from 267 PB files showed a good global significant correlation (r = 0.88) with no bias. Confirmed diagnoses, available for 212 patients, achieved a 94% sensitivity and an 84% specificity. Hence, 95/101 CMML patients displayed cMo ≥94% while cMo <94% was observed in 83/99 patients with reactive monocytosis and in 10/12 patients with myeloproliferative neoplasms (MPN) with monocytosis. The established Receiver Operator Curve again provided a 94% cut-off value of cMo. The 117 BM files reanalysis led to an 87% sensitivity and an 80% specificity, with excellent correlation between the 43 paired samples to PB. CONCLUSIONS: This ELN multicenter study demonstrates the robustness of the monocyte assay with only limited variability of cMo percentages, validates the 94% cutoff value, confirms its high sensitivity and specificity in PB and finally, also confirms the possibility of its use in BM samples.

Radar plots facilitate differential diagnosis of acute promyelocytic leukemia and NPM1+ acute myeloid leukemia by flow cytometry.

BACKGROUND: Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological emergencies and requires a prompt correct diagnosis by cytomorphology and flow cytometry (FCM) with later confirmation by cytogenetics/molecular genetics. However, nucleophosmin 1 muted acute myeloid leukemia (NPM1+ AML) can mimic APL, especially the hypogranular variant of APL. Our study aimed to develop a novel, Radar plot-based FCM strategy to distinguish APLs and NPM1+ AMLs quickly and accurately. METHOD: Diagnostic samples from 52 APL and 32 NPM1+ AMLs patients were analyzed by a 3-tube panel of 10-color FCM. Radar plots combining all markers were constructed for each tube. Percentages of positive leukemic cells and mean fluorescence intensity were calculated for all the markers. RESULTS: APL showed significantly higher expression of CD64, CD2, and CD13, whereas more leukemic cells were positive for CD11b, CD11c, CD15, CD36, and HLA-DR in NPM1+ AMLs. Radar plots featured CD2 expression, a lack of a monocytic component, lack of expression of HLA-DR and CD15, and a lack of a prominent CD11c+ population as recurring characteristics of APL. The presence of blasts with low SSC, presence of at least some monocytes, some expression of HLA-DR and/or CD15, and a prominent CD11c population were recurrent characteristics of NPM1+ AMLs. Radar plot analysis could confidently separate all hypergranular APL cases from any NPM1+ AML and in 90% of cases between variant APL and blastic NPM1+ AML. CONCLUSION: Radar plots can potentially add to differential diagnostics as they exhibit characteristic patterns distinguishing APL and different types of NPM1+ AMLs.

Retrospective statistical analysis on the diagnostic value of ductography based on lesion pathology in patients presenting with nipple discharge.

PURPOSE: To compare sensitivities and specificities of ductography to noninvasive imaging studies in determining the cause of nipple discharge and assess the value of ductography on the basis of pathologic results. METHODS: In this retrospective review of women with nipple discharge who underwent ductography between January 1, 2005 and October 30, 2015, at our institution, we compared ductography with noninvasive imaging results (mammography, ultrasound, MRI) to determine its relative diagnostic sensitivity, specificity, and relative accuracy. Diagnosis was defined from pathology results, clinical notes, and minimum of 1-year follow-up monitoring. The primary endpoints include accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The analyses were carried out in different configurations to compare results by the following pathologic categories: cancer, high-risk lesion, intraductal papilloma (IP) without atypia, and benign pathology and/or normal imaging results. RESULTS: In patients with breast cancer, ductography and noninvasive breast imaging had similar sensitivities. In patients with a high-risk lesion, ductography was significantly more sensitive than noninvasive imaging modalities. In patients with intraductal papilloma without atypia, ductography was more sensitive than noninvasive imaging, but the difference was of only borderline significance. For women with benign pathology and/or normal imaging, noninvasive imaging showed a significantly higher specificity than ductography. CONCLUSION: In the absence of standard diagnostic algorithm for patients presenting with nipple discharge, the clinician has numerous options to choose a diagnostic approach that will yield the most accurate information with the least disruption to the patient. Our results indicate the value of ductography compared to value of noninvasive imaging modalities when cancer is suspected and when high risk lesion is suspected. While we show the sensitivity of ductography is similar to noninvasive imaging modalities in the setting of cancer, the sensitivity of ductography is statistically valuable for diagnosing high-risk lesions. Our hope is that this study will emphasize more research and more understanding in clinical utility and management of high-risk lesions, leading to patient-focused algorithm for diagnosing the etiology of abnormal nipple discharge.

Plasma cell leukaemia: a management conundrum.

Primary plasma cell leukaemia in a young transplant eligible patient brings forth a number of perplexing questions and many remain unanswered. There are good data to suggest the superiority of novel agents over conventional chemotherapy regimens, however choosing between autologous and allogeneic haematopoietic stem cell transplant in first remission remains a therapeutic conundrum. We report a case of primary plasma cell leukaemia in a young patient and the dilemmas in its management.

Isolated injury of the cuboid bone.

The purpose of this study was to describe isolated injury of the cuboid bone as a potentially radiographically occult cause of foot pain. The imaging studies of 17 patients, 13 women and 4 men aged 17-79 years (average 45 years), who presented with pain over the lateral aspect of the midfoot were retrospectively reviewed. Frontal, lateral, and inversion-oblique radiographs were available for all patients. In addition, MR imaging was performed in eight patients, CT in two, conventional tomography in two, and bone scan in one. Conventional radiographs revealed cuboid fracture in seven patients. Of the remaining ten, eight underwent MR imaging which demonstrated four fractures, three bone bruises, and one stress reaction, and two had tomography, CT, and/or bone scan, all of which documented an isolated cuboid fracture. Isolated fracture of the cuboid may be radiographically occult. Other imaging modalities, particularly MR imaging, can document this injury as the source of pain.