Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma.

Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL.

MicroRNA expression signature as a biomarker in the diagnosis of nodal T-cell lymphomas.

Background: The diagnosis of T-cell lymphomas is typically established through a multiparameter approach that combines clinical, morphologic, immunophenotypic, and genetic features, utilizing a variety of histopathologic and molecular techniques. However, accurate diagnosis of such lymphomas and distinguishing them from reactive lymph nodes remains challenging due to their low prevalence and heterogeneous features, hence limiting the confidence of pathologists. We investigated the use of microRNA (miRNA) expression signatures as an adjunctive tool in the diagnosis and classification of T-cell lymphomas that involve lymph nodes.

Dynamic altruistic cooperation within breast tumors.

Background: Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance.

MicroRNA Landscape in Endometrial Carcinomas in an Asian population: Unraveling Subtype-Specific Signatures.

MicroRNAs (MiRNAs) are small, non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We analyzed the differential expression of miRNAs in 119 endometrial carcinomas, measuring their expression in histological subtypes, molecular subtypes, and tumors with mutations. Tumors were subdivided into histological and molecular subtypes as defined by The Cancer Genome Atlas.

Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma.

Unlabelled: Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets.

Tissue-Specific microRNA Expression Profiling to Derive Novel Biomarkers for the Diagnosis and Subtyping of Small B-Cell Lymphomas.

Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow.

MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics.

Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests.

Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders.

The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56 NK-cells that serve a regulatory function and more mature, circulating CD56 NK-cells with effector cytolytic properties. CD56 NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation.

Primary extraskeletal osteosarcoma of small bowel mesentery presenting with acute bowel obstruction.

Extraskeletal osteosarcoma of the small bowel mesentery is an exceedingly rare condition. It is an aggressive malignant neoplasm of mesenchymal origin characterized by osteoid formation. Final diagnosis is often made by histopathological analysis.

Kikuchi-Fujimoto Disease Post COVID-19 Vaccination: Case Report and Review of Literature.

With the rapid development of various coronavirus disease 2019 (COVID-19) vaccines in a bid to counter and contain the COVID-19 pandemic, unusual and uncommon side effects of COVID-19 vaccination have been increasingly reported in the literature. Ipsilateral lymphadenopathy is a fairly common side effect of vaccination of any kind, with its etiology most commonly related to reactive lymphadenopathy. However, Kikuchi-Fujimoto Disease (KFD) or necrotizing histiocytic lymphadenitis is rarely observed post-vaccination, with only one other case of KFD post COVID-19 vaccination reported to date.

Diagnostic approach to T- and NK-cell lymphoproliferative disorders in the gastrointestinal tract.

Most gastrointestinal NK and T cell lymphomas are aggressive in behavior, although in recent years a subset of indolent lymphoproliferative disorders have been described, which must be distinguished from their more malignant mimics. Intestinal T-cell lymphomas may arise from intra-epithelial lymphocytes and display epitheliotropism, such as enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. They are both aggressive in behavior but differ in their clinic-pathological features.

YJ5 as an immunohistochemical marker of osteogenic lineage.

Overexpression of WLS, an upstream protein in the Wnt pathway, has been implicated in several non-osteogenic tumours. This study represents the first attempt at evaluating WLS expression in various bone and soft tissue tumours using YJ5, a monoclonal antibody specific to WLS, with the aim of elucidating its utility in discerning tumours with aberrant Wnt signalling and as a marker of osteogenic lineage in challenging cases. Tumour tissue sections of 144 bone mass lesions and 63 soft tissue mass lesions were immunostained with the YJ5 antibody following standardised protocols.

PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis.

PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure.

Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach.

Epstein-Barr virus (EBV)-positive T-cell and natural killer (NK)-cell lymphoproliferative diseases (EBV-TNKLPD) are a group of uncommon disorders characterised by EBV infection of T- and NK-cells. As a group, EBV-TNKLPD are more commonly encountered in Asians and Native Americans from Central and South America compared to Western populations. They encompass a spectrum of entities that range from non-neoplastic lesions such as EBV-associated haemophagocytic lymphohistiocytosis (EBV-HLH) to more chronic conditions with variable outcomes such as chronic active EBV infections (CAEBV) of T- and NK-cell type (cutaneous and systemic forms) and malignant diseases such as systemic EBV-positive T-cell lymphoma of childhood, aggressive NK-cell leukaemia, extranodal NK/T-cell lymphoma, nasal-type, and primary EBV-positive nodal T/NK-cell lymphoma.

Clinical impact of the cell-of-origin classification based on immunohistochemistry criteria and Lymph2Cx of diffuse large B-Cell lymphoma patients in a South-east Asian population: a single center experience and review of the literature.

: Previous studies in Western populations, using immunohistochemistry (IHC) methods to subtype diffuse large B-cell lymphoma (DLBCL), suggest that germinal center B-cell lymphomas (GCBs) have improved outcomes. However, data in Asians have been limited and conflicting. This study aims to evaluate the prognostic impact of cell-of-origin (COO) subtyping by IHC and Lymph2Cx in South-East Asian (SEA) DLBCL patients, and to summarize the existing literature.

The contribution of MYC and PLK1 expression to proliferative capacity in diffuse large B-cell lymphoma.

Polo-like kinase-1 (PLK1) regulates the MYC-dependent kinome in aggressive B-cell lymphoma. However, the role of PLK1 and MYC toward proliferation in diffuse large B-cell lymphoma (DLBCL) is unknown. We use multiplexed fluorescent immunohistochemistry (fIHC) to evaluate the co-localization of MYC, PLK1 and Ki67 to study their association with proliferation in DLBCL.

Molecular pathogenic pathways in extranodal NK/T cell lymphoma.

Extranodal NK/T cell lymphoma, nasal type (ENKTL) is an aggressive malignancy with a dismal prognosis. Although L-asparaginase-based chemotherapy has resulted in improved response rates, relapse occurs in up to 50% of patients with disseminated disease. There is hence an urgent need for effective targeted therapy, especially for patients with relapsed or refractory disease.

Histopathological analysis of infiltrating T cell subsets in acute T cell-mediated rejection in the kidney transplant.

Aim: To compare the differential immune T cell subset composition in patients with acute T cell-mediated rejection in the kidney transplant with subset composition in the absence of rejection, and to explore the association of their respective immune profiles with kidney transplant outcomes.

Methods: A pilot cross-sectional histopathological analysis of the immune infiltrate was performed using immunohistochemistry in a cohort of 14 patients with acute T cell-mediated rejection in the kidney transplant and 7 kidney transplant patients with no rejection subjected to biopsy to investigate acute kidney transplant dysfunction. All patients were recruited consecutively from 2012 to 2014 at the Singapore General Hospital.

Analysis of T Cell Subsets in Adult Primary/Idiopathic Minimal Change Disease: A Pilot Study.

Aim: To characterise infiltrating T cells in kidneys and circulating lymphocyte subsets of adult patients with primary/idiopathic minimal change disease.

Methods: In a cohort of 9 adult patients with primary/idiopathic minimal change recruited consecutively at disease onset, we characterized (1) infiltrating immune cells in the kidneys using immunohistochemistry and (2) circulating lymphocyte subsets using flow cytometry. As an exploratory analysis, association of the numbers and percentages of both kidney-infiltrating immune cells and the circulating lymphocyte subsets with kidney outcomes including deterioration of kidney function and proteinuria, as well as time to complete clinical remission up to 48 months of follow-up, was investigated.

Primary Bone Anaplastic Large Cell Lymphoma Masquerading as Ewing Sarcoma: Diagnosis by Anchored Multiplex PCR.

A 3-year-old boy presented with pathologic fracture of the left proximal femur. Magnetic resonance imaging revealed an aggressive expansile bony mass associated with cortical destruction and surrounding myositis. Computed tomography-guided biopsy revealed a monomorphic small round blue cell tumor by histology.

Higher densities of Foxp3 regulatory T cells are associated with better prognosis in triple-negative breast cancer.

Purpose: The role of Forkhead Box Protein 3 (Foxp3) expressing regulatory T cells (Tregs) in breast cancer remains unclear. We examined the abundance and localisation of total T cells, B cells and Tregs within samples from triple-negative breast cancers (TNBCs) and asked whether these parameters were associated with clinicopathological features of the cancer or clinical outcomes.

Methods: Samples from TNBCs diagnosed between 2003 and 2010 in Singapore were divided into "high" and "low" intra-tumoural or stromal groups, based on whether they had higher or lower than median densities of specific tumour-infiltrating lymphocyte populations (CD3 total T cells, Foxp3CD3 Tregs, or CD20 B cells) in the intra-tumoural space or stroma.

Plasmacytoma of the pancreas: an unusual manifestation of multiple myeloma.

Extramedullary plasmacytoma of the pancreas is a rare entity. Although this condition is uncommon, it should be considered in the differential diagnosis of solid mass in the pancreas, especially in patients with underlying multiple myeloma. We report a case of pancreatic plasmacytoma in a 56-year-old woman with newly diagnosed multiple myeloma.