VEXAS syndrome is a new entity, described as the first one of a new class of hemato-inflammatory diseases. Through this article and based on the first case highlighted at the CHU of Liege, we offer you a review of the literature as well as an overview of different laboratory techniques used for the diagnosis of this syndrome.

Malaria is a potentially severe disease, particularly in Africa. In Europe, the majority of malaria cases come from travelers returning from endemic areas. The non-specific symptomatology may not alert the clinician if this notion of travel is not addressed. However, diagnosis and rapid initiation of treatment prevent the evolution of severe forms of the disease, especially in the case of Plasmodium falciparum infection, which can be life-threatening within 24 hours. Thin and thick blood smears microscopy is the main tools for diagnosis, but some automated hematology analyzers have demonstrated their ability to participate in early diagnosis. We describe two cases illustrating the contribution of the Sysmex XN-9100 automated system for the diagnosis of malaria. The first clinical case described a young man infected with numerous Plasmodium falciparum gametocytes. WNR (white blood cell count) and WDF (white blood cell differenciation) scattergrams showed an additional population, corresponding to gametocytes. The second case focused on a man with neuromalaria and high Plasmodium falciparum parasitaemia. Parasitized red blood cells form an inconspicuous double population on the reticulocyte scattergram, located at the discrimination limit between mature red blood cells and reticulocytes. Scattergram abnormalities, which can be visualized in a few minutes, offer an anticipation of the diagnosis of malaria in comparison to thin and thick smears microscopy, that requiring considerable time and expertise.

Although acute myeloid leukemias (AML) are well known and are not rarely reported, in time of coronavirus disease 2019 (COVID-19) pandemic, diagnosis, follow-up, and care of patients with AML can become a huge challenge for clinicians and clinical laboratory specialists, due to a lack of experience and the presence of divergences in both clinical examination and laboratory results. A 61-year-old patient in complete remission for 6 years for an AML with maturation diagnosed with trisomy 8 and treated by allogeneic stem cell transplantation (SCT), was admitted in the emergency department for a flu syndrome with productive cough, headaches, anosmia, and ageusia. At the admission, physical examination showed only a mild hypoventilation. Chest computed-tomography (CT) scan revealed no abnormalities suggestive of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nasopharyngeal swab was realized for SARS-CoV-2 polymerase chain reaction (PCR) detection and bone marrow (BM) aspirate was performed due to the patient's AML history. Laboratory tests indicated an inflammatory syndrome (C-reactive protein 30.5 mg/L), a pancytopenia (hemoglobin 10.9 g/dL, white blood cells count 1.13 × 109 cells/L, and platelets count 66 × 109 cells/L), and the presence of multiple plasma cells (5.5%) and activated lymphocytes (4.5%) in the peripheral blood smear (Figure 1). The BM aspirate smear revealed a fibrous marrow with a mild lymphocytosis (23%) characterized by the presence of few activated lymphocytes and some plasma cells (approximately 5%), both were also previously noticed in the peripheral blood sample. Otherwise, a large blast population (approximately 24%) was visualized in the BM but was not found in peripheral blood smear (Figure 2). Flow cytometry immunophenotypic analysis identified the presence of 5% myeloblasts, with weak CD45, HLA-DR, CD34, CD117, strong CD33, weak CD11c, weak CD15, and CD13 expression confirming the increased blast population seen in BM aspirate smear and the probable relapse of AML. SARS-CoV-2 PCR detected the presence of the virus in the nasopharyngeal swab of the patient and confirmed the COVID-19 disease, despite negative chest CT scan and absence of severe respiratory symptoms. Morphological anomalies of circulating blood cells in COVID-19 patients were already reported and could be caused by cytokine storm and inflammatory syndrome, two pathogenic factors of the SARS-CoV-2 infection.1-3 In this case, presence of plasma cells and activated lymphocytes in both peripheral blood and BM smear samples highlighted the reactive state caused by the SARS-CoV-2 infection while the homogeneous blast population only found in the BM sample showed the probable relapse of AML. AML relapse of the patient was confirmed by the cytogenetic analysis. Indeed, the majority of mitoses analyzed in the BM sample presented with trisomy 8, identical to the tumor clone present at the time of diagnosis, 6 years earlier. Concurrent diagnosis of COVID-19 and AML relapse involved an unconventional care by treating two potentially life-threatening diseases at the same time. Recommendations suggested a delayed therapy for the AML in order to provide appropriate care of the SARS-CoV-2 infection and the healing of the disease.4 If possible, negative SARS-CoV-2 PCR was required prior to start the induction treatment of AML.5-8 However, the management of COVID-19 leukemia patients must be done case-by-case by the hematologists in collaboration with pneumologists and intensivists. In this case, the patient was treated by Remdesivir for five days as recommended by the National Institute Health (NIH) USA guidelines and AML therapy was delayed until a negative SARS-CoV-2 PCR. Four weeks later, BM aspirate smear revealed a fibrous and hypocellular marrow with elevated lymphocytosis (40.3%), few plasma cells (2.3%) and an increased blastosis (27%). Flow cytometry immunophenotypic analysis identified 6.5% myeloblasts with weak CD45, HLA-DR, CD34, CD117, strong CD33, and weak CD11c. Peripheral blood smear showed 3% blasts proving the evolution of AML and its blood infiltration. Finally, the patient was treated by a second allogeneic SCT two months after the diagnosis of the AML relapse. In conclusion, simultaneous diagnosis of COVID-19 and hematological malignancies represent an important and a critical challenge for clinicians and clinical laboratory specialists to provide to the patient a right diagnosis, an appropriate care, and an adequate treatment. None. The authors have no competing interests. Data openly available in a public repository that issues datasets with DOIs.

Background: Leishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many other infectious or malignant diseases. The disease can present in three ways: cutaneous, mucocutaneous, or visceral leishmaniasis, which rarely occur together or consecutively.Case presentation: The patient was a 52 years old immunosuppressed Belgian woman with a long history of severe rheumatoid arthritis. She underwent bone marrow biopsy to explore thrombocytopenia. Diagnosis of visceral leishmaniasis was made by identification of Leishman Donovan (LD) bodies in macrophages. Treatment with liposomal amphotericin B was successful. She later developed cutaneous leishmaniasis treated with amphotericin B lipid complex. She next presented with relapsing cutaneous lesions followed by rapidly progressing lymphadenopathies. Biopsy confirmed the diagnosis of leishmaniasis. Treatments by miltefosine, amphotericin B, N-methyl-glucamine antimoniate were subsequently initiated. She later presented a recurrent bone marrow involvement treated with intramuscular paromomycin and miltefosine. She died two years later from leukemia. At the time of death, she presented with a mucosal destruction of the nose. A Leishmania specific PCR (Polymerase Chain Reaction) identified L. infantum as etiological agent.Conclusions: Clinicians should be aware of the potential concomitant or sequential involvement of multiple anatomic localizations of Leishmania in immunosuppressed patients.

Monoclonal B-cell lymphocytosis (MBL) is defined as an asymptomatic condition characterized by the presence of less than 5,000 monoclonal B-cells per microliter and the absence of clinical signs or symptoms of a B-cell lymphoproliferative disorder. Most MBL cases involve B cells presenting an identical phenotype to CLL (CLL-like MBL) with a Catovsky-Matutes score of 3 to 5 and share the same chromosomal abnormalities than CLL. Depending on the absolute B cell count, one may distinguish low-count CLL-like MBL (<500 B cells/μL) which have no evidence of progression, no reduction in overall survival, no increase in infection risk and do not require any specific follow-up. Patients with clinical CLL-like MBL (>500 B cells/μL) have a 1% to 2% per year risk of progression to CLL requiring therapy, a higher risk of infectious complications and mortality implicating an annual follow-up by hematologist. MBL may also express other less common phenotypes and are named atypical MBL in case of CD5 antigen expression (Catovsky-Matutes score: 1-2) and non-CLL-like MBL for CD5 negative cases (Catovsky-Matutes score: 0-2). Their poorer prognosis implicates imaging studies, bone marrow biopsy and cytogenetic analysis in addition to physical examination in order to rule out non-hodgkinien lymphoma, and require a more frequent follow-up. This review focuses on key concepts in the classification, diagnosis, monitoring and biology of MBL in laboratory practice.

La leucemie lymphoide chronique (LLC) est la leucemie la plus frequente chez les adultes dans les pays occidentaux, puisqu’elle represente 30 % des leucemies et 10 % des hemopathies malignes.Les criteres de diagnostic ont evolue au fil des annees, notamment grâce aux progres technologiques en cytometrie de flux. En effet, dans les annees 1990, le score immunophenotypique de Catovsky-Matutes [1], etabli sur 5 points et attribuant 0 ou 1 point aux antigenes CD5, CD23, CD22, FMC7, [...]

International Journal of Laboratory HematologyVolume 37, Issue 4 p. e85-e86 Letter to the Editor Atypical plasma cells with coexpression of myeloid markers and bundles of Auer rod-like inclusions A. Keutgens, A. Keutgens [email protected] Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this authorJ. Foguenne, J. Foguenne Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this authorA. Gothot, A. Gothot Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this authorFr. Tassin, Fr. Tassin Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this author A. Keutgens, A. Keutgens [email protected] Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this authorJ. Foguenne, J. Foguenne Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this authorA. Gothot, A. Gothot Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this authorFr. Tassin, Fr. Tassin Department of Laboratory Hematology, CHU Liège, Liege, BelgiumSearch for more papers by this author First published: 30 December 2014 https://doi.org/10.1111/ijlh.12322Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Gupta R, Hussain N, Rahman K, Nityanand S. Plasma cell myeloma with unusual morphology – a series of 6 cases. Eur J Haematol 2014; 93: 165–70. 10.1111/ejh.12310 PubMedWeb of Science®Google Scholar 2Auer J. Some hitherto undescribed structures found in the large lymphocytes of a case of acute leukemia. Am J Med Sci 1906; 131: 1002–15. 10.1097/00000441-190606000-00008 Web of Science®Google Scholar 3Steinmann B. Uber azurophile stäbchenförmige Einschlüsse in den Zellen eines multiplen Myeloms. Dt Arch Klin Med 1940; 185: 49–61. Google Scholar 4Casciaro S, Clavio M, Boccaccio P. Unusual intracellular and extracellular crystal inclusions in light chain multiple myeloma. Haematologica 1999; 84: 1046–7. CASPubMedWeb of Science®Google Scholar 5Tsuchikawa K, Yokomichi H, Satoh I, Suzuki C, Watanabe Y, Tajima G. A study of intracytoplasmic inclusions in myeloma cells from two patients with multiple myeloma. Tohoku J Exp Med 1987; 153: 11–20. 10.1620/tjem.153.11 CASPubMedWeb of Science®Google Scholar 6Metzgeroth G, Back W, Maywald O, Schatz M, Willer A, Hehlmann R, Hastka J. Auer rod-like inclusions in multiple myeloma. Ann Hematol 2003; 82: 57–60. 10.1007/s00277-002-0574-0 CASPubMedWeb of Science®Google Scholar 7Raman SB, Van Slyck EJ. Nature of intracytoplasmic crystalline inclusions in myeloma cells (morphologic, cytochemical, ultrastructural, and immunofluorescent studies). Am J Clin Pathol 1983; 80: 224–8. 10.1093/ajcp/80.2.224 CASPubMedWeb of Science®Google Scholar 8Castoldi G, Piva N, Tomasi P. Multiple myeloma with Auer-rod-like inclusions. Haematologica 1999; 84: 859–60. CASPubMedWeb of Science®Google Scholar 9Hütter G, Nowak D, Blau IW, Thiel E. Auer rod-like intracytoplasmic inclusions in multiple myeloma. A case report and review of the literature. Int J Lab Hematol 2009; 31: 236–40. 10.1111/j.1751-553X.2007.01023.x CASPubMedWeb of Science®Google Scholar 10Ruiz-Argüelles GJ, San Miguel JF. Cell surface markers in multiple myeloma. Mayo Clin Proc 1994; 69: 684–90. 10.1016/S0025-6196(12)61350-0 CASPubMedWeb of Science®Google Scholar Volume37, Issue4August 2015Pages e85-e86 ReferencesRelatedInformation

European Journal of HaematologyVolume 92, Issue 2 p. 179-180 Letter to the Editor Haematological and molecular responses in refractory anaemia with ring sideroblasts and thrombocytosis treated with lenalidomide Jo Caers, Corresponding Author Jo Caers Department of Hematology, CHU of Liège, Liège, BelgiumCorrespondence Dr Jo Caers, MD, PhD, Department of Clinical Hematology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, Bâtiment B 35, B-4000 Liège, Belgium. Tel: +32 4 366 77 04; Fax: +32 4 366 88 55; e-mail: [email protected]Search for more papers by this authorKaoutar Hafraoui, Kaoutar Hafraoui Department of Hematology, CHU of Liège, Liège, BelgiumSearch for more papers by this authorAurore Keutgens, Aurore Keutgens Department of Laboratory Hematology, CHU Sart Tilman, Liège, BelgiumSearch for more papers by this authorJean-Hubert Caberg, Jean-Hubert Caberg Department of Genetics, CHU of Liège, Liège, BelgiumSearch for more papers by this authorFrederic Lambert, Frederic Lambert Department of Genetics, CHU of Liège, Liège, BelgiumSearch for more papers by this authorFrancoise Tassin, Francoise Tassin Department of Laboratory Hematology, CHU Sart Tilman, Liège, BelgiumSearch for more papers by this author Yves Beguin, Yves Beguin Department of Hematology, CHU of Liège, Liège, BelgiumSearch for more papers by this author Jo Caers, Corresponding Author Jo Caers Department of Hematology, CHU of Liège, Liège, BelgiumCorrespondence Dr Jo Caers, MD, PhD, Department of Clinical Hematology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, Bâtiment B 35, B-4000 Liège, Belgium. Tel: +32 4 366 77 04; Fax: +32 4 366 88 55; e-mail: [email protected]Search for more papers by this authorKaoutar Hafraoui, Kaoutar Hafraoui Department of Hematology, CHU of Liège, Liège, BelgiumSearch for more papers by this authorAurore Keutgens, Aurore Keutgens Department of Laboratory Hematology, CHU Sart Tilman, Liège, BelgiumSearch for more papers by this authorJean-Hubert Caberg, Jean-Hubert Caberg Department of Genetics, CHU of Liège, Liège, BelgiumSearch for more papers by this authorFrederic Lambert, Frederic Lambert Department of Genetics, CHU of Liège, Liège, BelgiumSearch for more papers by this authorFrancoise Tassin, Francoise Tassin Department of Laboratory Hematology, CHU Sart Tilman, Liège, BelgiumSearch for more papers by this author Yves Beguin, Yves Beguin Department of Hematology, CHU of Liège, Liège, BelgiumSearch for more papers by this author First published: 08 November 2013 https://doi.org/10.1111/ejh.12233Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume92, Issue2February 2014Pages 179-180 RelatedInformation

The body fluid mode on the Sysmex XE-5000 automated hematology analyzer was evaluated on 99 body fluids and 60 cerebrospinal fluids. Erythrocyte and leukocyte numeration was compared to microscopic counts on Fuchs-Rosenthal chambers. Differentiation of mononuclear (MN) and polymorphonuclear (PMN) cells on the XE-5000 was compared to manual differential on cytospin slides. A good agreement was found between the XE-5000 and the manual method with correlation coefficients more than 0.8 for erythrocyte counts, leukocyte counts and leukocyte differentiation in most types of body fluids. The functional sensitivity limit (i.e., within run precision more than 20%) was reached for red blood cell counts more than 400/mu L and white blood cell counts more than 30/mu L. Carry over was negligible and linearity was adequate for as low as 400 erythrocytes/mu L and 30 leucocytes/mu L. Our results demonstrate that the automated body fluid analysis on the XE-5000 is an acceptable alternative to the microscopic reference method for erythrocyte and leukocyte numeration as well as MN and PMN differential for most body fluids including cerebrospinal fluids. (C) 2011 Elsevier Masson SAS. All rights reserved.

Bhalla, S., Balasubramanian, S., David, K., Sirisawad, M., Buggy, J., Mauro, L., Prachand, S., Miller, R., Gordon, L.I. & Evens, A.M. (2009) PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clinical Cancer Research, 15, 3354–3365. Buglio, D., Georgakis, G.V., Hanabuchi, S., Arima, K., Khaskhely, N.M., Liu, Y.J. & Younes, A. (2008) Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines. Blood, 112, 1424–1433. Feuerborn, A., Moritz, C., Von Bonin, F., Dobbelstein, M., Trumper, L., Sturzenhofecker, B. & Kube, D. (2006) Dysfunctional p53 deletion mutants in cell lines derived from Hodgkin’s lymphoma. Leukemia and Lymphoma, 47, 1932– 1940. Garcia, J.F., Camacho, F.I., Morente, M., Fraga, M., Montalban, C., Alvaro, T., Bellas, C., Castano, A., Diez, A., Flores, T., Martin, C., Martinez, M.A., Mazorra, F., Menarguez, J., Mestre, M.J., Mollejo, M., Saez, A.I., Sanchez, L. & Piris, M.A. (2003) Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood, 101, 681–689. Gillenwater, A.M., Zhong, M. & Lotan, R. (2007) Histone deacetylase inhibitor suberoylanilide hydroxamic acid induces apoptosis through both mitochondrial and Fas (Cd95) signaling in head and neck squamous carcinoma cells. Molecular Cancer Therapeutics, 6, 2967–2975. Gloghini, A., Buglio, D., Khaskhely, N.M., Georgakis, G., Orlowski, R.Z., Neelapu, S.S., Carbone, A. & Younes, A. (2009) Expression of histone deacetylases in lymphoma: implication for the development of selective inhibitors. British Journal of Haematology, 147, 515– 525. Hartlapp, I., Pallasch, C., Weibert, G., Kemkers, A., Hummel, M. & Re, D. (2009) Depsipeptide induces cell death in Hodgkin lymphoma-derived cell lines. Leukemia Research, 33, 929–936. Küppers, R. (2009) The biology of Hodgkin’s lymphoma. Nature Reviews Cancer, 9, 15–27. Mathas, S., Lietz, A., Anagnostopoulos, I., Hummel, F., Wiesner, B., Janz, M., Jundt, F., Hirsch, B., Johrens-Leder, K., Vornlocher, H.P., Bommert, K., Stein, H. & Dorken, B. (2004) c-FLIP mediates resistance of Hodgkin/Reed-Sternberg cells to death receptor-induced apoptosis. The Journal of Experimental Medicine, 199, 1041–1052. Sanchez-Aguilera, A., Montalban, C., de la Cueva, P., Sanchez-Verde, L., Morente, M.M., GarciaCosio, M., Garcia-Larana, J., Bellas, C., Provencio, M., Romagosa, V., de Sevilla, A.F., Menarguez, J., Sabin, P., Mestre, M.J., Mendez, M., Fresno, M.F., Nicolas, C., Piris, M.A. & Garcia, J.F. (2006) Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma. Blood, 108, 662–668.

Inositide-specific phospholipase c β 1 gene deletion is a rare event in myelodysplastic syndromes

In their letter,1 commenting to our paper,2 Lo Vasco et al. precise the prognostic data of the MDS patients included in their original paper3 on cryptic deletions of the inositide-specific phospholipase c 1 gene (PI-PLC 1). All the patients with MDS and a normal karyotype at diagnosis were at high risk as evaluated by clinical meanings (French-American-British classification (FAB), International Prognostic Scoring System (IPSS)). In our series,2 selection of the patients was done according to the unique criteria given by Lo Vasco et al. in their original paper,3 that is, the evidence of a normal karyotype at diagnosis. The IPSS score in our cases was low (12 patients), intermediate (10) or high (1). The discrepancies between the results of both studies probably can be explained by differences in the selection of the MDS populations. The data of Lo Vasco,1, 3 strictly related to high-risk IPSS categories, show that, respectively, 4/9 and 4/13 cases bear the PI-PLC 1 deletion. On the contrary, in our series where only one patient was at high risk, none of the 23 patients showed a cryptic deletion of band 20p12.3.2 Similar observations were recently done by Verburgh et al.4 who failed to detect a deletion of the PI-PLC 1 gene in a series of 33 MDS patients with normal karyotype, of which two belonged to the high-risk group as defined by the IPSS. In the same way, no deletion was observed in the 10 low-risk MDS patients reported in the comment of Lo Vasco et al.1 All these data indicate that the deletion of the PI-PLC 1 gene probably will not be detected in MDS patients with normal karyotype and low or intermediate IPSS risks. Conversely, in the high-risk group, the deletion could be frequent (about one-third of the reported cases till now) and associated with alterations of the signalling pathways and short survivals.