Aberrant immunophenotype

Emerging evidence implicates the epithelial-mesenchymal transition (EMT) transcription factor Zeb1 as a critical regulator of hematopoietic stem cell (HSC) differentiation. Whether Zeb1 regulates long-term maintenance of HSC function remains an open question. Through use of an inducible Mx-1 Cre mouse model that deletes conditional Zeb1 alleles in the adult hematopoietic system, we found that mice engineered to be deficient in Zeb1 for 32 weeks displayed expanded immunophenotypically defined adult HSCs and multi-potent progenitors associated with increased abundance of lineage-biased/balanced HSC subsets and augmented cell survival characteristics...

Acute myeloid leukemia (AML) is a malignant hematological disorder in which aberrant cytokine signaling and inflammation play a role in disease initiation and progression. Interleukin-40 (IL-40) is a novel cytokine encoded by the chromosome 17 open reading frame 99 (C17orf99) gene. This cytokine is involved in mediating inflammation but its biological significance in the pathogenesis of AML has not been investigated. In this case-control and observational study, mRNA expression and DNA methylation of the C17orf99 gene were evaluated in the peripheral blood of AML patients...

Plasma cell leukemia (PCL) is a rare aggressive variant of multiple myeloma. PCL is diagnosed when clonal plasma cells constitute more than 20 % of the total circulating leukocytes or when the absolute plasma cell count exceeds 2 × 109  /L. Extramedullary involvement including cavity effusion is frequently seen at the time of diagnosis. However, soft tissue involvement is rarely encountered with only one published case in the English literature. We report a 74-year-old man, who presented with progressive shortness of breath over a few months...

Flow cytometric identification of circulating neoplastic cells (Sezary cells) in patients with mycosis fungoides (MF) and Sezary syndrome (SS) is essential for diagnosis, staging and prognosis. While recent advances have improved the performance of this laboratory assay, the complex immunophenotype of Sezary cells and overlap with reactive T cells demand a high level of analytic expertise. We utilized machine learning to simplify this analysis using only 2 pre-defined Sezary cell-gating plots. We studied 114 samples from 59 patients with SS/MF, and 66 samples from unique patients with inflammatory dermatoses...

Somatic-type malignancy (STM) can occur infrequently within a primary or metastatic testicular germ cell tumor (TGCT) and is associated with dismal prognosis and survival. STM with chondrosarcomatous features is exceedingly rare and head and neck involvement has not been previously documented. A 39-year-old white man presented with nasal obstruction and epistaxis. Imaging disclosed a 6.9-cm expansile tumor involving the nasal cavity and skull base with intraorbital and intracranial extension. The histopathologic properties of the tumor were compatible with chondrosarcoma, grade II-III...

Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC translocations) chromosomal events. These are important to detect as they influence prognosis, therapeutic response and disease survival. Currently, cytogenetic testing is most commonly performed by interphase fluorescence in situ hybridisation (FISH) on aspirated bone marrow samples. A number of variations to FISH methodology are available, including prior plasma cell enrichment and incorporation of immunophenotypic plasma cell identification...

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) account for 3-10% of pediatric sarcomas, 50% of which occur in neurofibromatosis type 1 (NF1). Sporadic MPNSTs diagnosis may be challenging due to the absence of specific markers, apart from immunohistochemical H3K27me3 loss. DNA methylation (DNAm) profiling is a useful tool for brain and mesenchymal neoplasms categorization, and MPNSTs exhibit a specific DNAm signature. An MPNST-like group has recently been recognized, including pediatric tumors with retained H3K27me3 mark and clinical/histological features not yet well explored...

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, also called APS-1) is an inborn error of immunity with clear signs of B cell autoimmunity such as neutralising anti-IFN antibodies. In APECED, mutations in the AIRE gene impair thymic negative selection of T cells. The resulting T cell alterations may then cause dysregulation of B cells responses. However, no analysis of interactions of T and B cells in the germinal centres in patients' secondary lymphatic tissues has been reported...

For the routine diagnosis of haematological neoplasms an integrative approach is used considering the morphology, and the immunophenotypic, and molecular features of the tumor sample, along with clinical information. The identification and characterization of recurrent chromosomal aberrations mainly detected by conventional and molecular cytogenetics in the tumor cells has a major impact on the classification of lymphoid neoplasms. Some of the B-cell non-Hodgkin lymphomas are characterized by particular chromosomal aberrations, highlighting the relevance of conventional and molecular cytogenetic studies in their diagnosis and prognosis...

BACKGROUND: A marked increase in PD1-positive TFH cells in nodal MZL cases (NMZL) was reported previously and could prompt suspicion for a diagnosis of peripheral T-cell lymphoma (PTCL), especially angioimmunoblastic T-cell lymphoma (AITL). CASE PRESENTATION: To demonstrate that the pitfall might exist not only in NMZL but also in transformed splenic MZL (tSMZL), two NMZL cases (70 y/o female with enlarged left cervical lymph node and 75 y/o male with generalized lymphadenopathy) and one case of tSMZL (47 y/o male with nodal and extranodal involvement) with obvious PD1-positive T-cell hyperplasia were described here...

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke...

Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials...

BACKGROUND: Multiparametric flow cytometry (MFC) is an essential diagnostic tool in B acute lymphoblastic leukemia (B ALL) to determine the B-lineage affiliation of the blast population and to define their complete immunophenotypic profile. Most MFC strategies used in routine laboratories include leukemia-associated phenotype (LAP) markers, whose expression profiles can be difficult to interpret. The aim of our study was to reach a better understanding of 7 LAP markers' landscape in B ALL: CD9, CD21, CD66c, CD58, CD81, CD123, and NG2...

Multiparameter flow cytometry (MFC) has emerged as a standard method for quantifying measurable residual disease (MRD) in acute myeloid leukemia (AML). However, the limited number of available channels on conventional flow cytometers requires the division of a diagnostic sample into several tubes, restricting the number of cells and the complexity of immunophenotypes that can be analyzed. Full spectrum flow cytometers overcome this limitation by enabling the simultaneous use of up to 40 fluorescent markers...

BACKGROUND: Few data are available on flow cytometry (FC) for monitoring intraepithelial lymphocytes (IELs) in refractory celiac disease (RCD), non-responsive celiac disease (NRCD), and non-celiac enteropathies (NCEs). AIMS: 1) To investigate the significance of monitoring IELs immunophenotype with FC in patients with NRCD, RCD and NCEs; 2) to evaluate FC concordance with immunohistochemistry (IHC) and γ-TCR clonality analysis. METHODS: Patients investigated between January-2012 and February-2023 were divided into two groups: 1)confirmed RCD or NRCD being investigated for persistent symptoms and suspected complications of celiac disease (CD); 2)NCEs lacking clinical/histological response...

Background Observations play a pivotal role in the progress of science, including in pathology. The cause of a disease such as cancer is analyzed by breaking it down into smaller organs, tissues, cells, and molecules. The current standard cancer diagnostic procedure, microscopic observation, relies on preserved morphological characteristics. In contrast, molecular analyses explore oncogenic pathway activation that leads to genetic mutations and aberrant protein expression. Such molecular analyses could potentially identify therapeutic targets and has gained considerable attention in clinical oncology...

INTRODUCTION: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. METHODS: We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP-ALL aged 1-9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples...

CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, bi-allelic CDH1 alterations may be found in non-lobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 bi-allelic genetic alterations. Analysis of 5,842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multi-gene panel was conducted to identify BCs with bi-allelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features...

INTRODUCTION: Aberrant lymphoma phenotypes are frequently found in dogs, but the clinical implications are sparse. METHODS: Twenty-seven dogs with aberrant lymphoma diagnosed using flow cytometry between 2017 and 2023 were analyzed. Major paraneoplastic syndromes, prognostic factors, and clinical features of lymphoma were compared to their immunophenotypes. RESULTS: Twenty-seven dogs had aberrant immunophenotypes, with MHCII- (48%) and CD3+/CD21+ (44%) being the most commonly identified aberrancies...

Mature B-cell acute lymphoblastic leukemia (ALL) is defined by the expression of light chain-restricted surface immunoglobulin (sIg) and usually has features of the leukemic phase of Burkitt lymphoma including FAB-L3 morphology and MYC rearrangement. Recently, another distinct entity in childhood mature B-cell ALL has been characterized as non-L3 morphology and KMT2A rearrangement. Here we report an unusual case of mature B-cell ALL that presented with RUNX1 rearrangement. A 65-year-old male was admitted to our department for thorough examination of leukocytosis and thrombocytopenia...