Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. Thirteen cases of IVLBCL with a median age of 56 years were analyzed retrospectively. Nonspecific symptoms such as fever and hepatosplenomegaly were the most common manifestations, and the bone marrow was usually involved in 8/13 (61.5%) cases. All tumors expressed CD20, and 12/13 (92.3%) of the tumors exhibited a nongerminal center phenotype by Hans algorithm. CD5 was expressed in 3/12 (25%) of the tumors. MYC was negative in all cases, and BCL2 was positive in 10/12 (83.3%) cases. Cytogenetic analysis revealed 5 cases that did not have rearrangements in either the MYC or the BCL2 gene. No association with Epstein-Barr virus was found. Seven of 11 patients received chemotherapy. The median survival time was 6 months. Patients with hemophagocytic syndrome had poor prognoses. Our study demonstrates that IVLBCL has a poor clinical outcome with a high frequency of bone marrow involvement and that the MYC gene may not play an important role in the poor prognosis of IVLBCL.

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK + ALCL) is most frequent in youth and possesses a broad morphologic spectrum. However, involvement in central nervous system (CNS) is definitely rare. The case we presented was a 12-year-old Chinese male who presented with headache and emesis for a couple of days. The neoplastic component was smaller cells resembling starry-sky growth pattern and immunohistochemical stained positively for CD30, ALK1, and CD56. Monoclonal T-cell receptor (TCRγ) gene rearrangement and gene translocation involving ALK identified by fluorescence in situ hybridization (FISH) using ALK break apart probe supported the diagnosis of ALK + ALCL. This case showed ALK + ALCL occur in a rare site with an abnormal CD56 expression. Awareness of this entity is important to distinguish it from other intracranial lymphoma.

Primary cutaneous anaplastic large‐cell lymphoma (pC‐ALCL) is distinguished from systemic anaplastic large‐cell lymphoma (S‐ALCL) with cutaneous involvement. Although pC‐ALCL is a unique entity with different genetics, clinical characteristics, and prognosis, its causes are unknown. Herein, we report the case of a Chinese woman with a 4‐month history of a gradually enlarged ulcerative mass in her right forearm following an unidentified insect bite. Biopsy revealed an extensive infiltrate with patches of large anaplastic lymphoid cells. These cells were immunohistochemically positive for CD45, CD30, and TIA‐1 and negative for CD2, CD3, CD4, CD5, CD20, CD7, CD8, and ALK‐1. DUSP22‐IRF4 rearrangement was detected; on the other hand, TP63 rearrangement was not observed by fluorescence in situ hybridization (FISH). No Epstein‐Barr virus‐encoded small RNAs (EBERs) were detected by ISH. Rearrangement of monoclonal TCR gene was found using BIOMED‐2 polymerase chain reaction. No abnormality was found on the subsequent positron emission tomography‐computed tomography (PET‐CT) scan. After five cycles of cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP) chemotherapy, the patient achieved complete remission. This is the first report of a unique pC‐ALCL with DUSP22‐IRF4 rearrangement following an insect bite other than S‐ALCL involving the skin.

Background Tumor mutational burden (TMB) is a valuable prognostic biomarker. This study explored the predictive value of TMB and the potential association between TMB and immune infiltration in diffuse large B-cell lymphoma (DLBCL). Methods We downloaded the gene expression profile, somatic mutation, and clinical data of DLBCL patients from The Cancer Genome Atlas (TCGA) database. We classified the samples into high-and low-TMB groups to identify differentially expressed genes (DEGs). Functional enrichment analyses were performed to determine the biological functions of the DEGs. We utilized the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm to estimate the abundance of 22 immune cells, and the significant difference was determined by the Wilcoxon rank-sum test between the high- and low-TMB group. Hub gene had been screened as the prognostic TMB-related immune biomarker by the combination of the Immunology Database and Analysis Portal (ImmPort) database and the univariate Cox analysis from the Gene Expression Omnibus (GEO) database including six DLBCL datasets. Various database applications such as Tumor Immune Estimation Resource (TIMER), CellMiner, konckTF, and Genotype-Tissue Expression (GTEx) verified the functions of the target gene. Wet assay confirmed the target gene expression at RNA and protein levels in DLBCL tissue and cell samples. Results Single nucleotide polymorphism (SNP) occurred more frequently than insertion and deletion, and C > T was the most common single nucleotide variant (SNV) in DLBCL. Survival analysis showed that the high-TMB group conferred poor survival outcomes. A total of 62 DEGs were obtained, and 13 TMB-related immune genes were identified. Univariate Cox analysis results illustrated that CD1c mutation was associated with lower TMB and manifested a satisfactory clinical prognosis by analysis of large samples from the GEO database. In addition, infiltration levels of immune cells in the high-TMB group were lower. Using the TIMER database, we systematically analyzed that the expression of CD1c was positively correlated with B cells, neutrophils, and dendritic cells and negatively correlated with CD8+ T cells, CD4+ T cells, and macrophages. Drug sensitivity showed a significant positive correlation between CD1c expression level and clinical drug sensitivity from the CellMiner database. CREB1, AHR, and TOX were used to comprehensively explore the regulation of CD1c-related transcription factors and signaling pathways by the KnockTF database. We searched the GETx database to compare the mRNA expression levels of CD1c between DLBCL and normal tissues, and the results suggested a significant difference between them. Moreover, wet experiments were conducted to verify the high expression of CD1c in DLBCL at the RNA and protein levels. Conclusions Higher TMB correlated with poor survival outcomes and inhibited the immune infiltrates in DLBCL. Our results suggest that CD1c is a TMB-related prognostic biomarker.

Diffuse large B cell lymphoma (DLBCL) is a group of biologically heterogeneous tumors with different prognoses. The tumor microenvironment plays a vital role in the tumorigenesis and development of DLBCL, and activated memory CD4⁺ T cells are an essential component of immunological cells in the lymphoma microenvironment. So far, there are few reports about activated memory CD4+T cells infiltration and related genes in the DLBCL tumor microenvironment. This study obtained the mRNA expression profile information of the testing GSE87371 dataset and another six validation datasets (GSE53786, GSE181063, GSE10846, GSE32918, GSE32018, GSE9327, GSE3892, TCGA-DLBC) from the GEO and TCGA databases. Weighted Gene Co-expression Network Analysis (WGCNA) screened gene module associated with activated memory CD4⁺ T cells infiltration. CIBERSORT and TIMER (immune cells infiltrating estimation analysis tools) were used to identify the relationship between activated memory CD4⁺ T cells and genes associated with immune infiltrating cells in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) built the risk prediction model and verified it using nomogram and Kaplan-Meier analysis. Further functional characterization includes Gene Ontology, KEGG pathway analysis and Gene Set Enrichment Analysis (GSEA) to investigate the role and underlying mechanisms of these genes. These results suggest that the expression of FCER1G can reflect the invasion of activated memory CD4⁺ T cells in DLBCL, which provides a new idea for studying the tumor microenvironment and may become a potential predictive biomarker for the assessment of DLBCL.

Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive mature T-cell non-Hodgkin lymphoma. Its typical characteristics include positive CD30 and ALK expression detected by immunohistochemistry, and it is often accompanied by ALK gene translocation, among which the chromosomal translocation t (2;5) is the most common. This disease predominantly affects young individuals, with extranodal involvement being relatively common. However, cases involving the digestive tract are relatively rare. We report a rare case of a 14-year-old female with ALK+ALCL presenting with fever and peripheral blood leukocytosis as initial manifestations and complicated by diffuse involvement of the entire gastrointestinal tract. The patient showed significant remission having completed 4 chemotherapy sessions. In further studies, RNA sequencing confirmed the presence of NPM1::ALK gene fusion in this case; whole-exome sequencing (WES) detected somatic mutations in multiple genes of the JAK-STAT pathway (including JAK1, PTPN6, MTOR , and TYK2 ). It is noteworthy that such genetic alterations are more commonly observed in ALK-negative anaplastic large cell lymphoma (ALK-ALCL) but are less commonly reported in ALK+ALCL.