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Cancers
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Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics
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Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics

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

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 9597

Special Issue Editor

Dr. Sergio Piña-Oviedo

E-Mail Website
Guest Editor
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
Interests: hematolymphoid tumors; thoracic/lung pathology; mediastinal lymphomas; the correlation between morphology and molecular alterations of tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The fields of hematology/oncology and hematopathology are moving at a tremendous speed. Although the diagnosis of most hematolymphoid disorders is still performed by the correlation of clinical, morphological, immunohistochemical, and/or flow cytometry findings, the current standard of care of many of these disorders requires the proper use and interpretation of cytogenetic, fluorescense in situ hybridization, and/or molecular studies. The latter are not only helpful to determine prognostic/predictive parameters and/or dictate the use of targeted therapies, but in some instances have also become part of the definition of specific diseases. This Special Issue focuses on the application of novel technologies for the accurate and improved diagnosis of certain lymphomas, leukemias, and plasma cell neoplasms, which has important repercussions in their management and treatment.

Dr. Sergio Piña-Oviedo
Guest Editor

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 short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • flow cytometry
  • immunohistochemistry
  • cytogenetics
  • next-generation sequencing
  • targeted therapy
  • mutation
  • lymphoma
  • leukemia
  • plasma cell neoplasm

Published Papers (5 papers)

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Research

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18 pages, 3194 KiB  
Article
Single-Step IGHV Next-Generation Sequencing Detects Clonality and Somatic Hypermutation in Lymphoid Malignancies: A Phase III Diagnostic Accuracy Study
by Anna Gazzola, Mohsen Navari, Claudia Mannu, Riccardo Donelli, Maryam Etebari and Pier Paolo Piccaluga
Cancers 2023, 15(18), 4624; https://doi.org/10.3390/cancers15184624 - 19 Sep 2023
Viewed by 890
Abstract
Background: Multiplex PCR based on consensus primers followed by capillary electrophoresis and Sanger sequencing are considered as the gold standard method for the evaluation of clonality and somatic hypermutation in lymphoid malignancies. As an alternative, the next-generation sequencing (NGS) of immune receptor genes [...] Read more.
Background: Multiplex PCR based on consensus primers followed by capillary electrophoresis and Sanger sequencing are considered as the gold standard method for the evaluation of clonality and somatic hypermutation in lymphoid malignancies. As an alternative, the next-generation sequencing (NGS) of immune receptor genes has recently been proposed as a solution, due to being highly effective and sensitive. Here, we designed a phase III diagnostic accuracy study intended to compare the current gold standard methods versus the first commercially available NGS approaches for testing immunoglobulin heavy chain gene rearrangements. Methods: We assessed IGH rearrangements in 68 samples by means of both the NGS approach (LymphoTrack® IGH assay, and LymphoTrack® IGH somatic hypermutation assay, run on Illumina MiSeq) and capillary electrophoresis/Sanger sequencing to assess clonality and somatic hypermutations (SHM). Results: In comparison to the routine capillary-based analysis, the NGS clonality assay had an overall diagnostic accuracy of 96% (63/66 cases). Other studied criteria included sensitivity (95%), specificity (100%), positive predictive value (100%) and negative predictive value (75%). In discrepant cases, the NGS results were confirmed by a different set of primers that provided coverage of the IGH leader sequence. Furthermore, there was excellent agreement of the SHM determination with both the LymphoTrack® FR1 and leader assays when compared to the Sanger sequencing analysis (84%), with NGS able to assess the SHM rate even in cases where the conventional approach failed. Conclusion: Overall, conventional Sanger sequencing and next-generation-sequencing-based clonality and somatic hypermutation analyses gave comparable results. For future use in a routine diagnostic workflow, NGS-based approaches should be evaluated prospectively and an analysis of cost-effectiveness should be performed. Full article
(This article belongs to the Special Issue Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics)
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15 pages, 11732 KiB  
Article
Deep Immune Profiling of Multiple Myeloma at Diagnosis and under Lenalidomide Maintenance Therapy
by Sini Luoma, Philipp Sergeev, Komal Kumar Javarappa, Tiina J. Öhman, Markku Varjosalo, Marjaana Säily, Pekka Anttila, Marja Sankelo, Anu Partanen, Anne Nihtinen, Caroline A. Heckman and Raija Silvennoinen
Cancers 2023, 15(9), 2604; https://doi.org/10.3390/cancers15092604 - 04 May 2023
Viewed by 1877
Abstract
The bone marrow microenvironment interacts with malignant cells and regulates cancer survival and immune evasion in multiple myeloma (MM). We investigated the immune profiles of longitudinal bone marrow samples from patients with newly diagnosed MM (n = 18) using cytometry by time-of-flight. [...] Read more.
The bone marrow microenvironment interacts with malignant cells and regulates cancer survival and immune evasion in multiple myeloma (MM). We investigated the immune profiles of longitudinal bone marrow samples from patients with newly diagnosed MM (n = 18) using cytometry by time-of-flight. The results before and during treatment were compared between patients with good (GR, n = 11) and bad (BR, n = 7) responses to lenalidomide/bortezomib/dexamethasone-based treatment. Before treatment, the GR group had a lower tumor cell burden and a higher number of T cells with a phenotype shifted toward CD8+ T cells expressing markers attributed to cytotoxicity (CD45RA and CD57), a higher abundance of CD8+ terminal effector cells, and a lower abundance of CD8+ naïve T cells. On natural killer (NK) cells, increased expression of CD56 (NCAM), CD57, and CD16 was seen at baseline in the GR group, indicating their maturation and cytotoxic potential. During lenalidomide-based treatment, the GR patients showed an increase in effector memory CD4+ and CD8+ T-cell subsets. These findings support distinct immune patterns in different clinical contexts, suggesting that deep immune profiling could be used for treatment guidance and warrants further exploration. Full article
(This article belongs to the Special Issue Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics)
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Review

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14 pages, 5025 KiB  
Review
Primary Cutaneous Anaplastic Large Cell Lymphoma—A Review of Clinical, Morphological, Immunohistochemical, and Molecular Features
by Carlos Ortiz-Hidalgo and Sergio Pina-Oviedo
Cancers 2023, 15(16), 4098; https://doi.org/10.3390/cancers15164098 - 14 Aug 2023
Cited by 3 | Viewed by 1714
Abstract
Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or [...] Read more.
Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a DUSP22 (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells. Full article
(This article belongs to the Special Issue Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics)
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23 pages, 15082 KiB  
Review
Skin Involvement by Hematological Neoplasms with Blastic Morphology: Lymphoblastic Lymphoma, Blastoid Variant of Mantle Cell Lymphoma and Differential Diagnoses
by Magda Zanelli, Francesca Sanguedolce, Maurizio Zizzo, Valentina Fragliasso, Giuseppe Broggi, Andrea Palicelli, Giuseppe Gaetano Loscocco, Camilla Cresta, Cecilia Caprera, Matteo Corsi, Giovanni Martino, Alessandra Bisagni, Marialisa Marchetti, Nektarios Koufopoulos, Paola Parente, Rosario Caltabiano and Stefano Ascani
Cancers 2023, 15(15), 3928; https://doi.org/10.3390/cancers15153928 - 02 Aug 2023
Cited by 1 | Viewed by 2228
Abstract
Hematological neoplasms sharing a blastic morphology may involve the skin. The skin may be either the primary site of occurrence of hematological malignancies with blastic features or cutaneous lesions are the first manifestation of an underlying systemic malignancy. The assessment of skin biopsies [...] Read more.
Hematological neoplasms sharing a blastic morphology may involve the skin. The skin may be either the primary site of occurrence of hematological malignancies with blastic features or cutaneous lesions are the first manifestation of an underlying systemic malignancy. The assessment of skin biopsies of hematological neoplasms with blastic features poses diagnostic problems and requires expert hematopathologists considering a wide range of differential diagnoses. The precise diagnosis of diseases sharing blastic features but with different outcomes and requiring distinct therapies is essential for patient management. The present paper mainly focuses on cutaneous involvement of the blastoid variant of mantle cell lymphoma and lymphoblastic lymphoma of B-cell or T-cell origin. The relevant literature has been reviewed and the clinical aspects, pathological features, prognosis, and therapy of both blastoid mantle cell lymphoma and lymphoblastic lymphoma involving the skin are discussed. A focus on other hematological entities with blastic features, which may involve the skin, to be taken into consideration in differential diagnosis is also given. Full article
(This article belongs to the Special Issue Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics)
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17 pages, 15935 KiB  
Review
Mast Cell Leukemia: An Update with a Practical Review
by Magda Zanelli, Martina Quintini, Salvatore Magnasco, Lara Aprile, Andrea Palicelli, Maurizio Zizzo, Francesca Sanguedolce, Stefano Ricci, Saverio Pancetti, Valeria Zuccalà, Veronica Martino, Giuseppe Broggi, Rosario Caltabiano, Alberto Cavazza, Paola Parente, Cristina Mecucci, Giovanni Martino and Stefano Ascani
Cancers 2023, 15(6), 1664; https://doi.org/10.3390/cancers15061664 - 08 Mar 2023
Cited by 3 | Viewed by 2269
Abstract
Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous [...] Read more.
Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included. Full article
(This article belongs to the Special Issue Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics)
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