Proof-of-concept study evaluating humoral primary immunodeficiencies via CJ:KREC ratio and serum BAFF level.

Humoral primary immunodeficiencies are the most prevalent form of primary immunodeficiency (PID). Currently, there is no convenient method to quantify newly formed B cells. The aim of this proof-of-concept study was to quantitate the ratio of coding joints (CJs) to Kappa-deleting recombination excision circles (KRECs) and serum B cell activating factor (BAFF) in patients with humoral primary immunodeficiency and assess if they correlate with disease severity. This IRB-approved study was conducted at one academic children's hospital. Patients with humoral PIDs and healthy controls were included. CJ and KREC levels were measured via qPCR. Serum BAFF levels were measured using Mesoscale. 16 patients with humoral PID and 5 healthy controls were included. The mean CJ:KREC ratio in the CVID, antibody deficiency syndromes, and controls groups, respectively were 13.04 ± 9.5, 5.25 ± 4.1, and 4.38 ± 2.5 (p = 0.059). The mean serum BAFF levels in CVID, antibody deficiency syndromes and controls were 216.3 ± 290 pg/mL, 107.9 ± 94 pg/mL and 50.9 ± 12 pg/mL, respectively (p = 0.271). When the CVID patients were subdivided into CVID with or without lymphoproliferative features, the BAFF level was substantially higher in the CVID with lymphoproliferation cohort (mean 372.4 ± 361 pg/mL, p = 0.031). Elevated CJ:KREC ratio was observed in CVID, although statistical significance was not achieved, likely due to the small sample size. Serum BAFF levels were significantly higher in CVID patients with lymphoproliferative features. We speculate that the CJ:KREC ratio and serum BAFF levels can be utilized in patients with humoral PID, once more extensive studies confirm this exploratory investigation.

Losing CD45 and various B-cell markers in a case of MYC-driven pediatric high-grade B-cell lymphoma, not otherwise specified that transformed from Burkitt's lymphoma during rituximab-containing treatments: a case report.

In this study, we reported a seldom case of pediatric high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS) with loss of B-cell markers (CD19, CD20, CD22, CD79a, CD38, Pax5, OCT2, and BOB1) and CD45, which bring great challenges to exclude a non-lymphomatous neoplasm. However, no evidence was found to support the diagnosis of sarcoma and carcinoma. Thus, due to the patient's prior history of Burkitt's lymphoma treated by rituximab-containing therapies, we carefully searched for any indication of B-cell differentiation. Eventually, NGS results revealed the monoclonal rearrangement of IGH (IGHD2-8-IGHJ6 and IGHV4-30-2-IGHJ4) in both pre-treatment and present tumors, confirming the same B-cell lineage. Moreover, both tumors exhibited the same IGHA1-MYC translocation and somatic mutations of c-MYC, TP53, ID3, and CCND3. Therefore, in addition to strong expression of BCL2 in the present tumor, we finally arrived at a diagnosis of pediatric HGBL, NOS with loss of B-cell lineage markers and CD45.

B-cell Receptor Recombinations in Lung Adenocarcinoma Exome Files Correlate With a Higher Overall Survival Rate.

BACKGROUND/AIM: While there has been a rapid development in genomic data mining approaches for T-cell receptor recombinations (TcR), less emphasis has been placed on B-cell receptor (BcR) recombinations. MATERIALS AND METHODS: We obtained lung cancer exome files from the cancer genome atlas (TCGA) and mined the files for TcR and BcR recombination reads. RESULTS: There was a robust detection of BcR light chain recombination reads in lung adenocarcinoma (TCGA-LUAD) samples, and there was a correlation between the detection of light chain recombination reads and a more favorable outcome. This result was supported by analyses of the expression of B-cell markers as indicated by LUAD RNASeq files. CONCLUSION: BcR and TcR recombination reads recovered from LUAD WXS files, either alone or in combination with the human leukocyte antigen (HLA) type, are likely to have prognostic value.

Primary Central Nervous System T-Cell Lymphoma With Aberrant Expression of CD20 and CD79a: A Diagnostic Pitfall.

Primary central nervous system T-cell lymphoma (PCNSTCL) is rare, accounting for 2% of CNS lymphomas. We report the first case of PCNSTCL with aberrant expression of CD20 and CD79a in an 81-year-old man with a left periventricular brain mass. A biopsy revealed dense lymphoid infiltrate consisting of medium-sized cells in a background of gliosis and many histiocytes. The lymphoid cells were positive for CD2, CD3, CD7, CD8, T-cell intracellular antigen-1, granzyme B, CD20, and CD79a and negative for CD4, CD5, PAX-5, OCT-2, BOB-1, human herpes virus-8, and Epstein-Barr virus-encoded small RNAs. Molecular studies revealed clonal TCR-ß and TCR-γ gene rearrangements and negative immunoglobulin gene rearrangements. The patient was treated with chemotherapy (vincristine and methotrexate) and rituximab, but he died 1 month after the diagnosis. This is a unique case that emphasizes the use of a multimodal approach, including a broad immunohistochemical panel and molecular studies in lineage determination for lymphomas with ambiguous phenotype.

Identification of an Atypical Enzootic Bovine Leukosis in Japan by Using a Novel Classification of Bovine Leukemia Based on Immunophenotypic Analysis.

Bovine leukemia is classified into two types: enzootic bovine leukosis (EBL) and sporadic bovine leukosis (SBL). EBL is caused by infection with bovine leukemia virus (BLV), which induces persistent lymphocytosis and B-cell lymphoma in cattle after a long latent period. Although it has been demonstrated that BLV-associated lymphoma occurs predominantly in adult cattle of >3 to 5 years, suspicious cases of EBL onset in juvenile cattle were recently reported in Japan. To investigate the current status of bovine leukemia in Japan, we performed immunophenotypic analysis of samples from 50 cattle that were clinically diagnosed as having bovine leukemia. We classified the samples into five groups on the basis of the analysis and found two different types of EBL: classic EBL (cEBL), which has the familiar phenotype commonly known as EBL, and polyclonal EBL (pEBL), which exhibited neoplastic proliferation of polyclonal B cells. Moreover, there were several atypical EBL cases even in cEBL, including an early onset of EBL in juvenile cattle. A comparison of the cell marker expressions among cEBL, pEBL, and B-cell-type SBL (B-SBL) revealed characteristic patterns in B-cell leukemia, and these patterns could be clearly differentiated from those of healthy phenotypes, whereas it was difficult to discriminate between cEBL, pEBL, and B-SBL only by the expression patterns of cell markers. This study identified novel characteristics of bovine leukemia that should contribute to a better understanding of the mechanism underlying tumor development in BLV infection.

Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers.

AIMS: Rare cases of B cell lymphomas do not express conventional B cell markers (CD20, CD79a and PAX5), and these types of lymphomas include anaplastic lymphoma kinase (ALK)-positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma and the solid variant of primary effusion lymphoma, extracavitary human herpesvirus 8 (HHV8)-positive large B cell lymphoma. Establishing accurate diagnoses of these B cell lymphomas can be challenging, and often requires a large panel of immunohistochemical stains, molecular assays and cytogenetic studies. B cell-specific transcription factors, Oct2 and Bob1, have been shown to be expressed consistently in most, if not all, B cell lymphomas, and therefore we investigated the utility of Oct2 and Bob1 immunohistochemistry in lineage determination of the aforementioned B cell lymphomas. METHODS AND RESULTS: We selected 34 cases of previously diagnosed B cell lymphomas with no or weak expression of CD20, CD79a and PAX5. Oct2 and Bob1 were positive in 74% (25 of 34) and 85% (29 of 34) of the cases, respectively. When we combined the results of these two immunostains, 94% (32 of 34) cases expressed at least one of these two markers. We also included 51 control cases of non-B cell neoplasms, and none of them expressed either Oct2 or Bob1. CONCLUSIONS: Oct2 and Bob1 are very reliable in determining B cell lineage in the absence of expression of other pan-B cell markers, and it should provide great diagnostic benefit to include them both in a panel of immunohistochemistry to assess undifferentiated malignant neoplasms.