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Cancers
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Diagnosis of Hematologic Malignancies: 2nd Edition
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Diagnosis of Hematologic Malignancies: 2nd Edition

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 1964

Special Issue Editors

Dr. Leonor Arenillas

E-Mail Website
Guest Editor
1. Hematological Cytology Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain
2. Translational Research on Hematological Neoplasms Group, Cancer Research Program, Hospital del Mar Research Institute (HMRI), 08003 Barcelona, Spain
Interests: hematologic malignancies diagnosis; cytomorphology; flow cytometry; myeloid neoplasms; myelodysplastic syndromes; acute myeloid leukemia
Special Issues, Collections and Topics in MDPI journals
Dr. Xavier Calvo

E-Mail Website1 Website2
Guest Editor
1. Hematological Cytology Laboratory, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain
2. Translational Research on Hematological Neoplasms Group, Cancer Research Program, Hospital del Mar Research Institute (HMRI), 08003 Barcelona, Spain
Interests: hematologic malignancies diagnosis; cytomorphology; flow cytometry; myeloid neoplasms; myelodysplastic syndromes; acute myeloid leukemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, “Diagnosis of Hematologic Malignancies”.

In recent years, we have experienced a change in the paradigm of the diagnosis of hematological malignancies, moving from phenotyping to genotyping, and giving increasing importance to multidisciplinary diagnoses. An accurate diagnosis is necessary for a correct prognostic stratification and an adequate choice of therapy. Although morphology continues to represent the indispensable starting point in the diagnostics of hematological neoplasms, new classifications tend to define nosological entities based on the underlying genetic mechanisms of disease. The World Health Organization’s (WHO) classification of tumors of hematopoietic and lymphoid tissues has provided a global reference for the diagnosis of hematological neoplasms since its third edition in 2001. This classification is based on integrating morphologic (cytology and histology), immunophenotypic, molecular, and cytogenetic data. Recently, in addition to the 2022 edition of the WHO classification, the International Consensus Classification (ICC) system for hematological neoplasms has been published. While many definitions proposed by the ICC and WHO 2022 are concordant, some differ in a number of key aspects and could impact the design of clinical trials, drug development, and regulatory approval, in addition to, as a consequence, patient care. With this, the current Special Issue aims to highlight novel diagnostic and prognostic tools that could improve the management and treatment of hematological neoplasms—we look forward to your contributions.

Dr. Leonor Arenillas
Dr. Xavier Calvo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diagnosis of hematologic malignancies
  • myeloid neoplasms
  • lymphoid neoplasms
  • cytomorphology
  • flow cytometry
  • cytogenetic
  • molecular biology

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Published Papers (3 papers)

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Research

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13 pages, 248 KB  
Article
Expanding the Toolbox: Utility of HistioTrak for Minimal Residual Monitoring in Pediatric Patients with Langerhans Cell Histiocytosis Treated with Targeted Therapy
by Rainelle Nevers, Anusha Rajbhandari, Devon Roeming, Aly Anthony, Megan Gibbs and Anish K. Ray
Cancers 2026, 18(8), 1307; https://doi.org/10.3390/cancers18081307 - 20 Apr 2026
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Abstract
Background/Objectives: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the clonal proliferation of Langerhans-like dendritic cells and constitutive activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) signaling pathway. Nearly 80% of ERK pathway activation can be attributed to [...] Read more.
Background/Objectives: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the clonal proliferation of Langerhans-like dendritic cells and constitutive activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) signaling pathway. Nearly 80% of ERK pathway activation can be attributed to B-Raf proto-oncogene, serine/threonine kinase (BRAF V600E), and mitogen-activated protein kinase kinase 1 (MAP2K1) variants, with BRAF V600E specifically detected in approximately 50% of pediatric LCH cases and associated with a higher risk of severe disease and treatment failure. The use of the HistioTrak clinical assay to detect the presence of BRAF V600E mutations in peripheral blood mononuclear cells (PBMCs) has emerged as a useful diagnostic tool and biomarker. Methods: This study is a single-center retrospective study that explores the favorable outcomes of treatment with trametinib on a small number of patients with LCH. We retrospectively analyzed the records of 11 children with LCH treated with trametinib at diagnosis as front-line therapy (n = 6), due to progressive disease (n = 3) or intolerance (n = 1) to chemotherapy, or at relapse (n = 1). Results: HistioTrak identified the presence of BRAF V600E PBMCs in five patients. In this small single-center retrospective cohort, trametinib was associated with favorable short-term outcomes in all patients, and serial HistioTrak testing appeared feasible in selected patients. Conclusions: Prospective studies are needed before routine diagnostic or monitoring use can be recommended. Full article
(This article belongs to the Special Issue Diagnosis of Hematologic Malignancies: 2nd Edition)
15 pages, 996 KB  
Article
Pleuro-Pulmonary Extramedullary Plasmacytomas in Multiple Myeloma: A 15-Year Experience from a Tertiary Center
by Sorina Badelita, Sinziana Barbu, Camelia Dobrea, Cerasela Jardan, Monica Popescu, Codruta Delia Popa, Claudia Toma, Larisa Zidaru, Mihai Emanuel Himcinschi, Horia Mihail Sandu, Didona Vasilache, Adelina Vlad and Daniel Coriu
Cancers 2026, 18(1), 19; https://doi.org/10.3390/cancers18010019 - 20 Dec 2025
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Abstract
Background/Objectives: Extramedullary involvement in multiple myeloma represents an aggressive disease phenotype, associated with reduced survival and an unfavorable prognosis. Thoracic manifestations are rare and remain poorly characterized in the literature. Methods: We conducted a retrospective, single-center study at the Fundeni Clinical [...] Read more.
Background/Objectives: Extramedullary involvement in multiple myeloma represents an aggressive disease phenotype, associated with reduced survival and an unfavorable prognosis. Thoracic manifestations are rare and remain poorly characterized in the literature. Methods: We conducted a retrospective, single-center study at the Fundeni Clinical Institute, including patients diagnosed with multiple myeloma between February 2010 and February 2025. The study cohort consisted of 34 patients with infiltration of the pulmonary parenchyma, pleura, or the presence of myelomatous pleural effusion. Diagnosis was confirmed using a combination of imaging modalities (computed tomography or magnetic resonance imaging), cytological examination, immunophenotyping, and histopathological confirmation whenever feasible. Results: Out of a total of 2012 patients with multiple myeloma, the incidence of pleuro-pulmonary extramedullary involvement was 1.6%. The median age at diagnosis was 58 years. Pleuro-pulmonary disease was present at initial diagnosis in 26.5% of cases, while 73.5% developed it at relapse. The most common presentation involved combined pleural involvement and myelomatous effusion (70.6%). Adverse prognostic markers included elevated β2-microglobulin levels (in over 80% of cases) and increased lactate dehydrogenase (LDH) in approximately 50%. Cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), t(11;14), and 1q gain were identified. The median overall survival (OS) from the diagnosis of pleuro-pulmonary extramedullary disease was 16 months, with a 2-year survival rate of 25%. No patient survived beyond 5 years. The median progression-free survival (PFS) was 9 months. Conclusions: Our findings confirm the aggressive clinical course and poor prognosis of these disease manifestations, mainly when they occur at relapse. In the absence of standardized treatment guidelines, individualizing therapy and accessing novel strategies may be essential for improving patient survival. Full article
(This article belongs to the Special Issue Diagnosis of Hematologic Malignancies: 2nd Edition)
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Review

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31 pages, 1797 KB  
Review
How Laboratory Innovations Are Shaping the Future of Multiple Myeloma Care
by Joana Caetano, Ana Marta Pires, Carlos Costa, Rui Bergantim, Adriana Roque, Patrícia Ferraz, Maria Rosário Cunha, Niccolo Bolli, Noemi Puig and Cristina João
Cancers 2026, 18(8), 1275; https://doi.org/10.3390/cancers18081275 - 17 Apr 2026
Viewed by 658
Abstract
Multiple myeloma is a complex hematologic malignancy characterized by significant biological heterogeneity, a relapsing–remission clinical course, and a continuously evolving therapeutic landscape. Accurate and timely laboratory assessment is central to disease management, supporting diagnosis, risk stratification, evaluation of treatment response, and long-term monitoring. [...] Read more.
Multiple myeloma is a complex hematologic malignancy characterized by significant biological heterogeneity, a relapsing–remission clinical course, and a continuously evolving therapeutic landscape. Accurate and timely laboratory assessment is central to disease management, supporting diagnosis, risk stratification, evaluation of treatment response, and long-term monitoring. Despite major advances in therapy, a critical need remains for laboratory tools that can detect disease with greater sensitivity, capture spatial and clonal tumor heterogeneity, and reflect the true depth of treatment response beyond conventional serological and bone marrow-based criteria. Recent laboratory innovations have the potential to transform myeloma care by enabling earlier detection, more accurate prognostication, and personalized therapeutic strategies. This review focuses specifically on innovative laboratory technologies for the diagnosis of multiple myeloma and the evaluation of treatment response. Within this scope, we examine the current diagnostic approaches and the role of high-throughput technologies for measurable residual disease assessment. We explore the emerging role of liquid biopsy approaches, including circulating tumor cells, cell-free DNA/RNA, and mass spectrometry for ultrasensitive detection of monoclonal proteins. We further discuss novel molecular biomarkers and the integration of artificial intelligence and machine learning tools to enhance data interpretation. The innovations reviewed here represent a shift in the contribution of laboratory medicine to myeloma care, offering a more precise, less invasive, and biologically informative framework for targeted and adaptive clinical decisions. Full article
(This article belongs to the Special Issue Diagnosis of Hematologic Malignancies: 2nd Edition)
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