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Hairy cell leukemia (HCL) is an uncommon mature B-cell malignancy characterized by a typical morphology, immunophenotype, and clinical profile. The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy. However, several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements. These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene. Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms. Identification, functional characterization, and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required. [ABSTRACT FROM AUTHOR]

Background: Hairy cell leukemia (HCL) is rare leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. Although the association of venous thromboembolism (VTE) with cancer is well established, there is no systematic study describing VTE in HCL. Aim: To analyze prevalence and risk factors associated with VTE in HCL patients. Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023. Results: The median age at diagnosis was 59 years (range, 37–94), and 49 patients (87%) were male. With a median follow-up of 122 months (1–291), we identified 11 episodes of VTE in 8 (14%) HCL patients: pulmonary embolism (PE) (5 cases) with or without concurrent deep venous thrombosis (DVT), and DVT alone (6 cases). All thrombotic episodes occurred after the diagnosis of HCL, or at the same time of it, as presenting clinical manifestation of the HCL. Risk factors for VTE other than cancer were identified in only 3 patients. Conclusion: Our study found a high incidence of VTE in patients with HCL, mostly in the absence of other provoking factors, suggesting that this hematologic malignancy is associated with an underlying thrombophilic state. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 51-year-old man who initially presented with dysphnea, cough, and fatigue, later developing a rash after antibiotic treatment, raising concerns of Stevens-Johnson syndrome. Topics discussed include the differential diagnosis of pneumonia and exanthematous drug eruptions, the role of laboratory findings in diagnosis, and the challenges in distinguishing between infectious and drug-related rashes.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumour target currently used for the development of novel therapeutic modalities, such as antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and others. Success of these new drugs depends on the selection of relevant indications based on ROR1 tumour prevalence, staining heterogeneity, and subcellular localization, among other parameters. We investigated ROR1 immunophenotype using validated antibody clones for immunohistochemistry (IHC) and flow cytometry (FC), analyzing 292 tumour specimens from 7 haematological malignancies and triple negative breast cancer (TNBC) as a reference solid tumour indication. ROR1 prevalence varied significantly across distinct tumour types, showing 100% of ROR1 positivity in all chronic lymphocytic leukaemia (n = 48) and hairy cell leukaemia (n = 14) specimens analyzed via FC with ranges between 1.1–99.8% and 0.8–62.1%, respectively. Samples analysed via IHC showed ROR1 membrane/cytoplasmic positivity in 44% of mantle cell lymphoma tumour samples (n = 27; H-score range: 10–285 in positive cases); 30% in TNBC (n = 46; H-score range: 1–200); 15% in diffuse large B-cell lymphoma (n = 45; H-score: 40–250); and 11% in follicular lymphoma (n = 34; H-score: 2–300). Finally, all acute myeloid leukaemia (n = 52) and most T-cell non-Hodgkin lymphoma (n = 31/32) tested samples were negative for ROR1 via IHC. In conclusion, ROR1 shows a heterogeneous tumour cell expression profile across multiple leukaemias and lymphomas, making it a tumour target that would require different patient selection strategies to develop novel therapeutic modalities. [ABSTRACT FROM AUTHOR]

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The mature splenic B‐cell lymphomas are an enigmatic group of lymphoid neoplasms that have long caused significant difficulty for the practicing pathologist due to overlapping diagnostic features among entities and the decreasing availability of splenic tissue for assessment. While some entities have highly characteristic and specific clinicopathological features (e.g. hairy cell leukaemia), others are substantially more difficult to recognise (e.g. splenic diffuse red pulp lymphoma). At the same time, classification systems have been evolving, resulting in multiple changes to the boundaries among these entities and even the existence of some entities in their own right. Moreover, unbiased multi‐omic interrogation (whole genome/transcriptome sequencing, methylome) of the splenic B‐cell lymphomas over the past decade has given us significant insights into the underling biology of these neoplasms. We present a clinicopathological perspective on the historical, current and future state of the diagnosis and classification of splenic B‐cell lymphomas integrating multi‐omic data and highlighting areas of focus for the field in order to continue to strive to improve patient outcomes through accurate diagnosis. [ABSTRACT FROM AUTHOR]

The New England Journal of Medicine article delves into Hairy-Cell Leukemia (HCL), a rare cancer affecting mature B cells, primarily in males. HCL is characterized by specific symptoms like cytopenias and splenomegaly, with a genetic cause linked to the BRAFV600E mutation. Treatment options include purine analogues, rituximab, and BRAF inhibitors, with newer therapies like ibrutinib showing promise. The text emphasizes the importance of genetic testing, challenges in managing infections and leukopenia, and explores potential treatments like allogeneic stem cell transplantation and immunotherapy for HCL. [Extracted from the article]

Hairy cell leukemia (HCL) is a rare B-cell leukemia. This study aimed to investigate the clinical and demographic features and treatment responses of HCL patients diagnosed and treated at our center. Thirteen patients were diagnosed between March 2019 and February 2024. Morphology, immunohistochemistry, and flow cytometry were used for diagnosis. All patients received cladribine as first -line treatment. Patients with partial response or less and those who relapsed received salvage therapy. The median age of the patients was 53. Seven patients (53.8%) had pancytopenia. BRAF V600E mutation was positive in 9 patients (69%). Splenomegaly was present in 10 patients (76.9%) at diagnosi s. Cladribine treatment achieved complete response in 11 patients (84%), partial response in 1 patient (7%). One patient did not respond to treatment. Two patients relapsed and achieved complete remission with pentostatin or rituximab treatment. The 5 -year overall survival (OS) rate was 92.3% and progression-free survival (PFS) rate was 84.6%. The demographic and laboratory features and treatment outcomes of HCL patients followed at our center are consistent with the literature. Cladribine is highly effective as a first-line treatment in HCL and provides high response rates. Pentostatin and rituximab monotherapy were found to be effective in relapsed patients. [ABSTRACT FROM AUTHOR]

The article in the British Journal of Haematology discusses the treatment of refractory severe idiopathic immune thrombocytopenia (ITP) with daratumumab, an anti-CD38 antibody. The study reports on a case series of seven patients who received daratumumab treatment, with four patients achieving sustained complete remission. The findings suggest that daratumumab may be a valid treatment option for refractory ITP patients, leading to durable responses in some cases. Additional data from prospective clinical trials are needed to further evaluate the efficacy of daratumumab in treating ITP. [Extracted from the article]

Abstract Hairy cell leukemia is an uncommon B‐cell malignancy with excellent response to purine analogs and to targeted therapies such as ibrutinib and vemurafenib. However, purine analogs are known to be highly immunosuppressive and the infection burden in this patient population with current therapies is unknown. We therefore conducted a retrospective cohort study following 149 patients. Median follow‐up time was 6.9 years. Thirty‐six percent developed an opportunistic or serious infection requiring hospitalization. Most cases were bacterial and most coincided with neutropenia and/or CD4 T‐lymphopenia. No single treatment agent was significantly associated with increased or decreased incidence of infection. Reassuringly, the cumulative incidence of infections plateaued 2 months after initial treatment suggesting clinically significant immune recovery. Only one patient in our cohort passed away due to infection. Estimated 10‐year overall survival was 99% suggesting that infections may not cause as much mortality as was seen prior to current therapies.

Aim: Sarcopenia may develop in patients with hairy cell leukemia (HCL). There is no study in the literature showing the prognostic importance of sarcopenia in patients with HCL. In this study, the effect of pretreatment sarcopenia on clinical outcomes in patients with HCL was investigated. Methods: This study included 34 patients with pre-treatment abdominal computed tomography (CT) images who received cladribine (purine nucleoside analog) treatment between April 2006 and April 2022 at Ondokuz Mayıs University Hospital. To ensure measurement standardization, measurements were performed using abdominal CT sections showing the L3 vertebra. The optimal cut-off value for the skeletal mass index to be used for the prediction of sarcopenia was determined by receiver operating characteristic analysis. Patients were divided into two groups according to whether they were sarcopenic or not, and their clinical results were compared. Results: Overall survival (OS) tended to be shorter in the sarcopenic group than in the non-sarcopenic group (p=0.046). Progression-free survival was significantly better in the non-sarcopenic group than in the sarcopenic group (p=0.009). In the multivariate analysis, sarcopenia (hazard ratio=0.154, p=0.043) was an effective variable for OS. Conclusion: Sarcopenia is a prognostic factor for prognosis and treatment parameters in patients with HCL.

This letter to the editor discusses a study that identified a new genetic variant in the TNFRSF13B gene in a family with lymphoid neoplasms. The TNFRSF13B gene is linked to immunodeficiency and an increased risk of certain cancers. The study provides clinical details of two patients with lymphoid malignancies and identifies other genetic variants related to hematologic malignancies. The findings suggest a possible genetic predisposition to tumors in this family. The authors recommend genetic screening for patients with a family history of tumors to aid in treatment planning and counseling. [Extracted from the article]

Aim: Sarcopenia may develop in patients with hairy cell leukemia (HCL). There is no study in the literature showing the prognostic importance of sarcopenia in patients with HCL. In this study, the effect of pretreatment sarcopenia on clinical outcomes in patients with HCL was investigated. Methods: This study included 34 patients with pre-treatment abdominal computed tomography (CT) images who received cladribine (purine nucleoside analog) treatment between April 2006 and April 2022 at Ondokuz Mayis University Hospital. To ensure measurement standardization, measurements were performed using abdominal CT sections showing the L3 vertebra. The optimal cut-off value for the skeletal mass index to be used for the prediction of sarcopenia was determined by receiver operating characteristic analysis. Patients were divided into two groups according to whether they were sarcopenic or not, and their clinical results were compared. Results: Overall survival (OS) tended to be shorter in the sarcopenic group than in the non-sarcopenic group (p=0.046). Progressionfree survival was significantly better in the non-sarcopenic group than in the sarcopenic group (p=0.009). In the multivariate analysis, sarcopenia (hazard ratio=0.154, p=0.043) was an effective variable for OS. Conclusion: Sarcopenia is a prognostic factor for prognosis and treatment parameters in patients with HCL. [ABSTRACT FROM AUTHOR]

Simple Summary: Diagnosis of hairy cell leukemia is based on the presence of hairy cells in bone marrow and peripheral blood as well as the characteristic immunophenotype. Moreover, in classic HCL, most patients present with a BRAF V600E mutation. The typical symptoms of classic hairy cell leukemia include pancytopenia, massive splenomegaly and increased risk of infection. However, rarer manifestations of HCL are occasionally reported, including cutaneous symptoms, bone infiltration, arthritis and central nervous system symptoms, as well as gastrointestinal tracts, heart, lungs, ocular involvement and other symptoms. Background: Hairy cell leukemia (HCL) is a rare indolent B-cell lymphoid malignancy. The majority of patients are asymptomatic and HCL is usually diagnosed incidentally during a routine blood cell count. In symptomatic patients, typical symptoms are related to pancytopenia and splenomegaly. In this review, we present rare clinical symptoms in patients with HCL. Methods: A literature search was conducted of PubMed, Web of Science and Google Scholar for articles concerning hairy cell leukemia, leukemia cutis, bone lesions, neurological manifestations, pulmonary symptoms, ocular manifestations, cardiac manifestation and rare symptoms. Publications from January 1980 to August 2024 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles. Results: Extramedullary and extranodal manifestations of classic HCL are rare. However, leukemic involvement in the skin, bone, central nervous system, gastrointestinal tract, heart, kidney, liver, lung, ocular system and other organs have been reported. [ABSTRACT FROM AUTHOR]

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%–60% of human melanomas, 30%–50% of human thyroid carcinomas and 10%–20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety‐six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology. [ABSTRACT FROM AUTHOR]

We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40–18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings. [ABSTRACT FROM AUTHOR]

The presence of BRAF mutation in hematological malignancies, excluding Hairy cell leukemia, and its significance as a driver mutation in myeloid neoplasms (MNs) remains largely understudied. This research aims to evaluate patient characteristics and outcomes of BRAF-mutated MNs. Among a cohort of 6667 patients, 48 (0.7%) had BRAF-mutated MNs. Notably, three patients exhibited sole BRAF mutation, providing evidence supporting the hypothesis of BRAF's role as a driver mutation in MNs. In acute myeloid leukemia, the majority of patients had secondary acute myeloid leukemia, accompanied by poor-risk cytogenic and RAS pathway mutations. Although the acquisition of BRAF mutation during disease progression did not correlate with unfavorable outcomes, its clearance through chemotherapy or stem cell transplant exhibited favorable outcomes (median overall survival of 34.8 months versus 10.4 months, p = 0.047). Furthermore, G469A was the most frequently observed BRAF mutation, differing from solid tumors and hairy cell leukemia, where V600E mutations were predominant. [ABSTRACT FROM AUTHOR]

Background/Aim: Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients. Case Report: We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells. Conclusion: Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis. [ABSTRACT FROM AUTHOR]

The article discusses Poland's first case of Erdheim-Chester Disease (ECD) with cerebellar manifestations, a rare inflammatory disorder with only about 1,500 documented cases worldwide. The case study highlights the diagnostic and therapeutic challenges faced by neurological specialists in treating ECD. The patient, a 39-year-old male, presented with speech difficulties, gait problems, weight loss, and other neurological symptoms, leading to the diagnosis of ECD confirmed through genetic testing. Treatment with vemurafenib was initiated, and the patient remained stable for two years under continuous medical follow-up. [Extracted from the article]

The article highlights the transformative impact of antibiotics introduced in the mid-20th century. Topics include the exploration of secondary metabolites from microorganisms as potential new antimicrobial drugs, the three approaches to antibiotic production—fermentation, semi-synthetic modification, and chemical synthesis—and a study on the metabolic potential of Arctic fungi, which revealed novel secondary metabolites and biosynthetic gene clusters.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare type of lymphoma that affects the spleen, bone marrow, and peripheral blood. It was initially thought to be a variant of splenic marginal zone lymphoma (SMZL) but is now recognized as a separate entity. SDRPL is difficult to diagnose based on peripheral blood and bone marrow samples alone, and a splenectomy is often necessary for an accurate diagnosis. The pathogenesis of SDRPL is not well understood, but it is associated with specific genetic changes, including mutations in BCOR, CCND3, NOTCH pathway genes, and MAP2K1. The prognosis and treatment response of SDRPL vary, but TP53 inactivation, through mutation and/or deletion, is associated with an aggressive clinical course. [Extracted from the article]

Introduction: Hairy cell leukemia (HCL) is an indolent B-cell lymphoma characterized by a specific genetic mutation, BRAF V600E, which affects the specific morphology and oncogenesis. For HCL, few reports regarding secondary central nervous system involvement (SCNSI) are available. Herein, we present the case of an 80-year-old woman who had a relapse of HCL with SCNSI. Case Presentation: The diagnosis of HCL was made in June 2015 after identifying BRAF V600E proteins by immunohistochemical analysis, and the disease was then controlled for 6 years by employing chemoimmunotherapy. In February 2021, the patient was admitted with neurological symptoms such as dizziness. Magnetic resonance imaging of the brain showed abnormal enhancement in the cerebrum, and cerebrospinal fluid analysis revealed neoplastic cells without transformation into large cells. Thus, the patient was diagnosed as having SCNSI in HCL. Conclusion: We report a case of a rare clinical presentation of SCNSI in HCL with literature review. [ABSTRACT FROM AUTHOR]

Background: Hairy cell leukemia (HCL) is rare leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. Although the association of venous thromboembolism (VTE) with cancer is well established, there is no systematic study describing VTE in HCL.Aim: To analyze prevalence and risk factors associated with VTE in HCL patients.Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023.Results: The median age at diagnosis was 59 years (range, 37–94), and 49 patients (87%) were male. With a median follow-up of 122 months (1–291), we identified 11 episodes of VTE in 8 (14%) HCL patients: pulmonary embolism (PE) (5 cases) with or without concurrent deep venous thrombosis (DVT), and DVT alone (6 cases). All thrombotic episodes occurred after the diagnosis of HCL, or at the same time of it, as presenting clinical manifestation of the HCL. Risk factors for VTE other than cancer were identified in only 3 patients.Conclusion: Our study found a high incidence of VTE in patients with HCL, mostly in the absence of other provoking factors, suggesting that this hematologic malignancy is associated with an underlying thrombophilic state.

A 62-year-old man diagnosed with acute myeloid leukemia (AML) showed limited responses to two courses of azacitidine (AZA) + Venetoclax (VEN) therapy. Twenty days after being transferred to our hospital, flow cytometry with broad antigen coverage and mutation analysis confirmed the presence of a second malignancy, hairy cell leukemia (HCL). Following haploidentical combined umbilical cord blood transplantation, the patient achieved complete remission (CR) for both AML and HCL. This CR has been maintained for the past 14 months. Patients with dual hematologic malignancies may not respond well to conventional therapy regimens. Early initiation of hematopoietic stem cell transplantation is beneficial for improving prognosis and extending overall survival. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) is a rare type of leukemia that primarily affects men and is characterized by abnormal B cells with cytoplasmic projections. The standard treatment for HCL has been purine analogs, which have shown high response rates but also carry risks of immunosuppression and disease relapse. Recent studies have explored the use of rituximab in combination with purine analogs, showing promising results in relapsed HCL patients. Additionally, a study from the MD Anderson group demonstrated the efficacy and safety of sequential cladribine followed by rituximab as a first-line therapy for HCL. The role of measurable residual disease (MRD) as a predictor of treatment response and remission duration is still being investigated. Furthermore, the use of the BRAF inhibitor vemurafenib in combination with obinutuzumab has shown promising results in previously untreated HCL patients. Overall, these findings suggest that chemo-immunotherapy may be a more effective standard of care for HCL, and future research should focus on refining treatment protocols and exploring other treatment options. [Extracted from the article]

BACKGROUND: Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder. Modern therapy with purine analogs and immunotherapy can provide long-term remission, but the risk of recurrence remains about 40%–50%. The aim of this study was to evaluate the outcome of patients with HCL who received treatment in Nanakali Hospital. PATIENTS AND METHODS: A retrospective cross-sectional study was carried out on 50 patients of HCL diagnosed from 2004 to 2022 in Nanakali Hospital in Erbil City, Kurdistan Region, Iraq. Demographics, clinical presentation, treatment data, complications, response, recurrence, and survival data were collected from medical records. The results were presented with descriptive statistics. Variables were compared by Chi-square analysis. RESULTS: The mean age was 52.64 ± 12.37 years, and 84% were male. The most common presenting symptoms were splenomegaly (18%) and fatigue (14%). The majority (69.6%) received cladribine; the response rate was 73.9%, with a complete remission (67.4%). 47.8% had recurrent disease. The most common adverse effects were febrile neutropenia (58.7%) and Grade III and IV hematologic toxicity (41.3%). The results were significantly associated with ANC pretreatment (P = 0.019), comorbidity (P = 0.001), and treatment response (P = 0.004). Cladribine–rituximab combination resulted in complete remission (100%). Ten-year overall survival was 70%. CONCLUSIONS: The results were broadly consistent with literature reports, demonstrating the efficacy and safety of cladribine with/without rituximab as first-line therapy for HCL but with a 30% mortality of concern. Further studies should identify modifiable factors that affect poor prognosis in subgroups to guide improvements in risk management of HCL.

Simple Summary: The diagnosis of hairy-cell leukemia (HCL) and HCL-like disorders including the variant form of HCL (HCL-V), splenic diffuse red pulp lymphoma (SDRPL) and splenic marginal zone lymphoma (SMZL) is a challenge in clinical practice. We discuss the major points for the diagnosis of HCL and HCL-like disorders and we propose recommendations for the diagnosis of HCL, treatment in first line and in relapsed/refractory patients. Introduction: Hairy-cell leukemia (HCL) is a rare B-cell chronic lymphoproliferative disorder (B-CLPD), whose favorable prognosis has changed with the use of purine nucleoside analogs (PNAs), such as cladribine (CDA) or pentostatin (P). However, some patients eventually relapse and over time HCL becomes resistant to chemotherapy. Many discoveries have been made in the pathophysiology of HCL during the last decade, especially in genomics, with the identification of the BRAFV600E mutation and cellular biology, including the importance of signaling pathways as well as tumor microenvironment. All of these new developments led to targeted treatments, especially BRAF inhibitors (BRAFis), MEK inhibitors (MEKis), Bruton's tyrosine kinase (BTK) inhibitors (BTKis) and recombinant anti-CD22 immunoconjugates. Results: The following major changes or additions were introduced in these updated guidelines: the clinical relevance of the changes in the classification of splenic B-cell lymphomas and leukemias; the increasingly important diagnostic role of BRAFV600E mutation; and the prognostic role of the immunoglobulin (IG) variable (V) heavy chain (H) (IGHV) mutational status and repertory. We also wish to insist on the specific involvement of bones, skin, brain and/or cerebrospinal fluid (CSF) of the disease at diagnosis or during the follow-up, the novel targeted drugs (BRAFi and MEKi) used for HCL treatment, and the increasing role of minimal residual disease (MRD) assessment. Conclusion: Here we present recommendations for the diagnosis of HCL, treatment in first line and in relapsed/refractory patients as well as for HCL-like disorders including HCL variant (HCL-V)/splenic B-cell lymphomas/leukemias with prominent nucleoli (SBLPN) and splenic diffuse red pulp lymphoma (SDRPL). [ABSTRACT FROM AUTHOR]

Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001–Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001–13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001–13. Median follow-up time was 13 years (IQR 13–14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9–86·5) and Hodgkin lymphoma (79·3% [78·6–79·9]) and lowest for plasma cell neoplasms (29·5% [28·9–30·0]). RER increased with age at diagnosis, particularly from 55–64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7–60·0) in the first quartile, 57·6% (55·2–58·7) in the second quartile, 55·4% (54·3–56·5) in the third quartile, and 44·7% (43·6–45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79–0·82) in the first, 0·91 (0·90–0·93) in the second, 0·94 (0·92–0·96) in the third, and 1·45 (1·42–1·48) in the fourth quartiles. Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. Italian Ministry of Health, European Commission, Estonian Research Council. [ABSTRACT FROM AUTHOR]

Background: Rare oncogenic driver events, particularly affecting the expression or splicing of driver genes, are suspected to substantially contribute to the large heterogeneity of hematologic malignancies. However, their identification remains challenging. Methods: To address this issue, we generated the largest dataset to date of matched whole genome sequencing and total RNA sequencing of hematologic malignancies from 3760 patients spanning 24 disease entities. Taking advantage of our dataset size, we focused on discovering rare regulatory aberrations. Therefore, we called expression and splicing outliers using an extension of the workflow DROP (Detection of RNA Outliers Pipeline) and AbSplice, a variant effect predictor that identifies genetic variants causing aberrant splicing. We next trained a machine learning model integrating these results to prioritize new candidate disease-specific driver genes. Results: We found a median of seven expression outlier genes, two splicing outlier genes, and two rare splice-affecting variants per sample. Each category showed significant enrichment for already well-characterized driver genes, with odds ratios exceeding three among genes called in more than five samples. On held-out data, our integrative modeling significantly outperformed modeling based solely on genomic data and revealed promising novel candidate driver genes. Remarkably, we found a truncated form of the low density lipoprotein receptor LRP1B transcript to be aberrantly overexpressed in about half of hairy cell leukemia variant (HCL-V) samples and, to a lesser extent, in closely related B-cell neoplasms. This observation, which was confirmed in an independent cohort, suggests LRP1B as a novel marker for a HCL-V subclass and a yet unreported functional role of LRP1B within these rare entities. Conclusions: Altogether, our census of expression and splicing outliers for 24 hematologic malignancy entities and the companion computational workflow constitute unique resources to deepen our understanding of rare oncogenic events in hematologic cancers. [ABSTRACT FROM AUTHOR]

The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably Mycobacterium kansasii. The exact pathophysiology is not known. We report a case of a 31-year-old male with concomitantly diagnosed HCL and disseminated M kansasii infection who presented with rash, pancytopenia, and bulky axillary lymphadenopathy. The M kansasii was initially diagnosed through use of cell-free DNA detection and confirmed by bone marrow and lymph node cultures. Hairy Cell Leukemia was diagnosed with peripheral flow cytometry and confirmed via the same bone marrow sample. His HCL was put into remission with a single course of cladribine and rituximab chemotherapy; however, his M kansasii infection persisted for 6 months despite aggressive antimicrobial and surgical therapy. It was finally controlled using high-dose rifampin in combination with azithromycin and ethambutol. This case highlights the known link between HCL and M kansasii. Furthermore, it hints at potential causes beyond chemotherapy-induced immunocompromise. Notable possibilities include HCL cells acting as sanctuary sites for M kansasii to evade the immune system, and subclinical M kansasii infections causing NLRP3 inflammasome overactivation to trigger the oncogenic transformation to HCL. More research into the pathophysiologic link between HCL and M kansasii infections would allow for more effective prevention, diagnosis, and treatment of these severe atypical infections which are the major cause of morbidity in the cladribine era of HCL treatment. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of β-rapidly accelerated fibrosarcoma (BRAF) proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and β-2-microglobulin concentration are also important in the patient's assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses the case of a 47-year-old woman with relapsed/refractory hairy cell leukemia (cHCL) who achieved complete remission (CR) following treatment with the bispecific antibody mosunetuzumab. The patient had previously undergone various treatments, including cladribine, pentostatin, rituximab, vemurafenib, and moxetumomab pasudotox, but experienced relapse or insufficient response. Mosunetuzumab therapy resulted in hematologic CR for at least nine months, with negative measurable residual disease (MRD) based on blood tests. The use of bispecific antibodies in the treatment of cHCL shows promise and warrants further investigation. [Extracted from the article]

Hairy cell leukemia (HCL) and HCL‐like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real‐world setting. We analyzed 225 HCL and 26 HCLv patients with median follow‐up of 67.9 months (HCL) and 20.1 months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5 years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, BRAFV600E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front‐line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine‐based regimen (91.2%). Overall response rate (ORR) was higher in cladribine‐treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second‐line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first‐line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10‐year TTNT was estimated at 74.1%. HCLv patients who underwent first‐line treatment had a median TTNT of 56 months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5 years. These data confirm an excellent prognosis for HCL patients treated with cladribine‐based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed. [ABSTRACT FROM AUTHOR]

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Simple Summary: The prevalence of second neoplasms among patients with hairy cell leukemia (HCL) treated with cladribine is not negligible. Immunosuppression, high rate of cure, and aging may have a role in the pathogenesis of second cancers after HCL. We aimed to compare the risk of cancer between patients with HCL treated with cladribine and the general population. Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2–169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4–409.2 months), while the median OS from second cancer was 27.6 months (range: 1–117.8 months). The SIR was 0.86 (95% CI: 0.54–1.30) for males and 1.13 (95% CI: 0.36–2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm. [ABSTRACT FROM AUTHOR]

Summary: First‐line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long‐lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression‐free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine. [ABSTRACT FROM AUTHOR]

A 70-year-old woman presented with itching and skin lesions on her torso, arms, and legs. She had a medical history of hypertension and chronic myelomonocytic leukemia type 1 (CMML-1). Physical examination revealed mixed purpuric and erythematous maculopapular lesions on her trunk and limbs. Laboratory tests showed low platelet and white blood cell counts. A punch biopsy confirmed the presence of myelomonocytic leukemia in the skin. This case highlights the rare occurrence of cutaneous involvement in CMML and the importance of prompt diagnosis and appropriate treatment. [Extracted from the article]

Abstract Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy.

A 32-year-old woman presented to the dermatology clinic with a 3-year history of progressive skin thickening. She had thickened skin on her face and body, with papules and induration. She also experienced tingling and occasional pain in her hands. Tests revealed fibroblast proliferation with collagen and mucin deposition in the skin, as well as monoclonal gammopathy. The diagnosis was scleromyxoedema with smouldering multiple myeloma. Treatment with thalidomide resulted in significant improvement. Scleromyxoedema is a rare condition characterized by skin lesions and is associated with monoclonal gammopathy. It can have diverse internal manifestations and requires a skin biopsy for diagnosis. [Extracted from the article]

Atraumatic splenic rupture is a complex surgical pathology owing to its rarity, non-specificity of symptoms and gravity of possible outcomes. This case outlines the investigation and management of a patient with atraumatic splenic rupture secondary to undiagnosed hairy cell leukaemia. While the patient was initially managed conservatively, they went on to have a splenectomy owing to ongoing transfusion requirements. A review of the literature has also been performed and presented to highlight the potential causes of atraumatic splenic rupture and the various options for confirming diagnosis and definitive management. [ABSTRACT FROM AUTHOR]

Interferon alpha-2b (IFN- α 2b) is an essential cytokine widely used in the treatment of chronic hepatitis C and hairy cell leukemia, and serum albumin is the most abundant plasma protein with numerous physiological functions. Effective single-step aqueous biphasic system (ABS) extraction for the simultaneous purification of IFN- α 2b and BSA (serum albumin protein) was developed in this work. Effects of the ionic liquid (IL)-based ABS functionalization, fluorinated ILs (FILs; [C ​ 2 C ​ 1 Im][C ​ 4 F ​ 9 SO ​ 3 ] and [N ​ 1112 (OH) ][C ​ 4 F ​ 9 SO ​ 3 ]) vs. mere fluoro-containing IL ([C ​ 4 C ​ 1 Im][CF ​ 3 SO ​ 3 ]), in combination with sucrose or [N ​ 1112 (OH) ][H ​ 2 PO ​ 4 ] (well-known globular protein stabilizers), or high-charge-density salt K ​ 3 PO ​ 4 were investigated. The effects of phase pH, phase water content (%wt), phase composition (%wt), and phase volume ratio were investigated. The phase pH was found to have a significant effect on IFN- α 2b and BSA partition. Experimental results show that simultaneous single-step purification was achieved with a high yield (extraction efficiency up to 100%) for both proteins and a purification factor of IFN- α 2b high in the enriched IFN- α 2b phase (up to 23.22) and low in the BSA-enriched phase (down to 0.00). SDS-PAGE analysis confirmed the purity of both recovered proteins. The stability and structure of IFN- α 2b and BSA were preserved or even improved (FIL-rich phase) during the purification step, as evaluated by CD spectroscopy and DSC. Binding studies of IFN- α 2b and BSA with the ABS phase-forming components were assessed by MST, showing the strong interaction between FILs aggregates and both proteins. In view of their biocompatibility, customizable properties, and selectivity, FIL-based ABSs are suggested as an improved purification step that could facilitate the development of biologics. [ABSTRACT FROM AUTHOR]

The fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO‐HAEM5) is the product of an evidence‐based evolution of the revised fourth edition with wide multidisciplinary consultation. Nonetheless, while every classification incorporates scientific advances and aims to improve upon the prior version, medical knowledge remains incomplete and individual neoplasms may not be easily subclassified in a given scheme. Thus, optimal classification requires ongoing study, and there are certain aspects of some entities and subtypes that require further refinements. In this review, we highlight a selection of these challenging areas to prompt more research investigations. These include (1) a 'placeholder term' of splenic B‐cell lymphoma/leukaemia with prominent nucleoli (SBLPN) to accommodate many of the splenic lymphomas previously classified as hairy cell leukaemia variant and B‐prolymphocytic leukaemia, a clear new start to define their pathobiology; (2) how best to classify BCL2 rearrangement negative follicular lymphoma including those with BCL6 rearrangement, integrating the emerging new knowledge on various germinal centre B‐cell subsets; (3) what is the spectrum of non‐IG gene partners of MYC translocation in diffuse large B‐cell lymphoma/high‐grade B‐cell lymphoma and how they impact MYC expression and clinical outcome; how best to investigate this in a routine clinical setting; and (4) how best to define high‐grade B‐cell lymphoma not otherwise specified and high‐grade B‐cell lymphoma with 11q aberrations to distinguish them from their mimics and characterise their molecular pathogenetic mechanism. Addressing these questions would provide more robust evidence to better define these entities/subtypes, improve their diagnosis and/or prognostic stratification, leading to better patient care. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Haemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, excess immune activation syndrome. Diagnosis can be challenging due to its several clinical mimics including sepsis. There are multiple aetiologies of HLH; in adults, it is most commonly triggered by infection, malignancy, drugs and autoimmune processes. Failure to rapidly diagnose and treat this condition can be fatal. The management of HLH includes identifying and removing the trigger, supportive management and immunosuppression. Identifying the trigger is essential to inform the most appropriate type of immunosuppression. Here, we report a case of likely drug-induced HLH in a patient recently treated for hairy cell leukaemia. The culprit drug was thought to be co-trimoxazole and this case report highlights a very rare complication of this commonly used drug. We discuss our management approach with steroid monotherapy and withdrawal of co-trimoxazole. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) is an infrequent and persistent B-cell inert lymphoid leukemia. In this study, we present the case of a 71-year-old female patient with a previous diagnosis of variant HCL who experienced a severe herpes zoster infection leading to an extensive skin eruption. The patient's initial diagnosis of HCL occurred 7 years ago, and she underwent treatment with cladribine, interferon, COP (cyclophosphamide, vincristine, and prednisone), benztropine tablets + clarithromycin dispersible, and ibrutinib. Immune disorders resulting from repeated prior chemotherapy and targeted therapy may potentially precipitate herpes zoster infection. Despite an initial two-week period of unresponsiveness to antivirals and nerve nutrition treatments, the introduction of topical Coptis liquid to the treatment regimen yielded significant efficacy. This case report underscores the potential of Chinese medicine as an adjunct to conventional antiviral therapy in the management of herpes zoster infection in immunocompromised patients. This treatment protocol has the potential to enhance efficacy, enhance quality of life, and serve as a more robust foundation for clinical diagnosis and improved treatments. [ABSTRACT FROM AUTHOR]

The variant form of hairy cell leukaemia (HCL‐V) is a rare disease very different from hairy cell leukaemia (HCL), which is a very well‐defined entity. The 5th WHO edition (Leukemia, 36, 2022 and 1720) classification (WHO‐HAEM5) introduced splenic lymphomas/leukaemias including four different entities: (1) HCL, (2) splenic marginal zone lymphoma (SMZL) with circulating villous cells in the peripheral blood, (3) splenic lymphoma with prominent nucleolus (SLPN), which replaced HCL‐V and CD5 negative B‐prolymphocytic leukaemia (B‐PLL), and (4) splenic diffuse red pulp lymphoma (SDRPL). All these entities have to be distinguished because of a different clinical course and the need for a different treatment. The diagnosis can be challenging because of complex cases and overlap and/or grey zones between all the entities and needs integrating clinical, histologic, immunophenotypic, cytogenetic and molecular data. We review the diagnostic criteria including clinical, immunophenotypic and molecular characteristics of patients with HCL‐V and other HCL‐like disorders including HCL, SDRPL, SMZL, B‐PLL and the Japanese form of HCL. We also discuss the different criteria allowing us to separate these different entities and we will update the recent therapeutic options that have emerged, in particular the advances with chemoimmunotherapy and/or targeted therapies. [ABSTRACT FROM AUTHOR]

Context: Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) aka hairy cell leukemia variant (HCL-v) is a rare B-cell chronic lymphoproliferative disorder. The main diagnostic challenge is to differentiate SBLPN from Classical hairy cell leukemia (HCL-c), as the former faces inferior responses to therapies and a poor prognosis. Aims: The aim is to discuss the clinic-hematological and immunophenotyping findings of three cases of SBLPN. Settings and Design: This is a retrospective observational study. Methods and Material: From the year 2011 to 2021, flow cytometry of all the cases with HCL diagnosis was reviewed, and three cases with negative or dim CD25 and hematological presentation matching with SBLPN were picked up. Statistical Analysis Used: Descriptive statistics is used. Results: All the cases were male. The age ranges from 43 to 64 years. Median hemoglobin concentration, total leucocyte count, and platelet count were 8.6 g/dL, 6.9 × 109/L, and 53 × 109/L, respectively. The atypical cells were medium to large. All three showed prominent nucleoli. Bone marrow biopsies showed an interstitial pattern of infiltration in all the cases. The hairy cells were positive for CD20, CD11c, and CD103. CD25 was dim positive in one case. Annexin A1 was negative in all three cases. BRAF V600E mutation analysis was done in one case and turned out negative for the mutation. Conclusions: SBLPN is a rare entity, usually on-flow cytometry CD25 negative. However, in dim CD25-positive cases, BRAFV600E mutational analysis helps in discerning SBLPN diagnosis and differentiating it from HCL-c. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm that accounts for less than 1% of all primary cutaneous neoplasms. The majority of MCC cases (80%) are caused by Merkel cell polyomavirus (MCPyV) clonal integration into the host genome. In the remaining 20% of cases, UV mutations are responsible, and prolonged UV exposure is a factor. Herein, we present two cases of this rare tumor: a 48-year-old female with a diagnosis of hairy cell leukemia and an elderly male previously healthy. [ABSTRACT FROM AUTHOR]

This article discusses the development of a lentiviral vector-based gene therapy platform for the treatment of liver metastases (LMS). Liver metastases commonly arise from gastrointestinal tumors and are difficult to treat due to the immunosuppressive environment of the liver. The lentiviral vector delivers interferon-alpha (IFNα) to liver macrophages, which activates the immune system and reduces the growth of LMS. The study also found that combining gene-based IFNα delivery with monoclonal antibodies blocking CTLA-4 resulted in a strong therapeutic response. The use of lentiviral vectors in gene therapy has shown promise in various clinical applications and has the potential to be used in the treatment of LMS. [Extracted from the article]

Flow cytometry (FCM) has become a method of choice for immunologic characterization of chronic lymphoproliferative disease (CLPD). To reduce the potential subjectivities of FCM data interpretation, we developed a machine learning random forest algorithm (RF) allowing unsupervised analysis. This assay relies on 16 parameters obtained from our FCM screening panel, routinely used in the exploration of peripheral blood (PB) samples (mean fluorescence intensity values (MFI) of CD19, CD45, CD5, CD20, CD200, CD23, HLA‐DR, CD10 in CD19‐gated B cells, ratio of kappa/Lambda, and different ratios of MFI B‐cells/T‐cells [CD20, CD200, CD23]). The RF algorithm was trained and validated on a large cohort of more than 300 annotated different CLPD cases (chronic B‐cell leukemia, mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, splenic red pulp lymphoma, hairy cell leukemia) and non‐tumoral selected from PB samples. The RF algorithm was able to differentiate tumoral from non‐tumoral B‐cells in all cases and to propose a correct CLPD classification in more than 90% of cases. In conclusion the RF algorithm could be proposed as an interesting help to FCM data interpretation allowing a first B‐cells CLPD diagnostic hypothesis and/or to guide the management of complementary analysis (additional immunologic markers and genetic). [ABSTRACT FROM AUTHOR]