De Novo CD5-positive diffuse large B-cell lymphoma: A genomic profiling study and prognostic analysis of 46 patients.

We reported 46 cases of Diffuse Large B-cell lymphoma which abnormally expressed CD5 protein (De Novo CD5-positive DLBCL), which had attracted researcher's attention for a period of time for its poor prognosis. However, there were few studies on its molecular change. In the present article, we summarized the genetic alterations using a lymphopanel detection method by Next Generation Sequencing(NGS). The most frequently mutated genes were MYD88L265P (20/46, 43.5%), followed by PIMI (19/46, 41.3%), IGLL5 (13/46, 28.3%)and CD79B (11/46, 23.9%). We further investigated the relationship between gene alterations and prognosis using OS(Overall survival) and PFS(Progression-free survival). MYD88, CREBBP, and ACTB mutation were significantly associated with inferior OS (P = 0.032, 0.000, 0.001), PIMI, CREBBP, ACTB and CXCR4 mutation were significantly associated with inferior PFS (P = 0.016, 0.001, 0.045, 0.024). Meanwhile, we found that De Novo CD5-positive DLBCL had BCL-6(9/46,19.6%), C-MYC (4/46, 8.7%) and IRF4 (2/19, 10.5%) rearrangement, but without BCL-2 rearrangement, there were no significantly associations with prognosis. In summary, our research explored the gene alterations of De Novo CD5-positive DLBCL in a relatively large scale for the first time, the most common gene mutation was MYD88L265P which was also a potential prognostic factor, providing a potential therapeutic target for the patients of De Novo CD5-positive DLBCL.

B cell lymphoma with IRF4 rearrangement: A clinicopathological study of 13 cases.

Interferon regulatory factor 4 (IRF4) rearrangement is commonly detected in patients with a range of lymphoproliferative malignancies, including myelomas, large B cell lymphomas and low-grade B cell neoplasms. However, IRF4 rearrangement is generally a relatively rare finding in these latter two cancer types. In the present article, we describe and summarize the clinicopathological and genetic features of 13 cases of B cell lymphoma with IRF4 rearrangement, including 12 cases of large B cell lymphoma and one case of low-grade lymphoma exhibiting such rearrangement. These cases were detected in six females and seven males between 14 and 71 years of age. From a morphological perspective, large B cell lymphoma tumors included in this analysis exhibited large neoplastic cells in diffuse or follicular patterns, while the case of low-grade lymphoma mainly composed of small lymphocytes. All analyzed cases exhibited a split in the IRF4 gene consistent with IRF4 translocation. Three of six analyzed large B cell lymphoma cases harbored IGLL5 mutations. Mutations in SAMHD1 were detected in the low-grade lymphoma with IRF4 rearrangement case. In summary, our results offer further insight into the morphological and molecular heterogeneity of cases of B cell lymphoma exhibiting IRF4 rearrangements.

Non-neoplastic B-cell predominant lymphoid proliferations at the organs exposed to external environment mimicking lymphoma: A potential diagnostic pitfall.

Background: Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified into one category, particularly in mucosal areas that are in contact with the external environment.Aims: To explore the morphology, immunophenotype, and molecular changes of Non-neoplastic B-cell predominant lymphoid proliferations (NBPLP) in pathological areas that are exposed to external surroundings which mimicked lymphoma.Methods and Results: 18 cases of Atypical lymphoid hyperplasia (AtLP)  were retrieved in this study. The biopsy samples were mucosal samples obtained from areas exposed to external surroundings, including intestines, urethra, cervix, tonsils, and tongue. Microscopically, there is a different level of B cell hyperplasia accompanied by morphological atypia. We categorized the morphology into 4 groups: type A (7/18), type B (3/18), type C (3/18), type D (5/18). Part of the AtLP was found positive for BCR gene rearrangement (6/15), and TCR gene rearrangement (1/4). The follow-up period ranged from 14.2 to 70 months. No evidence of lymphoma was found. Therefore, we diagnosed all of the presented cases as NBPLP. We illustrated the key differential points and provided valuable diagnostic experience on each subtype.Conclusions: Areas exposed to the external environment are commonly exposed to antigen and easily present with AtLP of NBPLP, accompanying with positive IGH rearrangement. Therefore, a comprehensive evaluation of macroscopic, morphology, immunophenotype, and molecular diagnostics is required to prevent the overdiagnosis of lymphoma.