ABSTRACT
Kaposi's sarcoma (KS) is a vascular / mesenchymal tumor with an indefinite degree of malignancy, caused by complex etiopathogenetic factors including Human Herpes Virus-8 infection of immunocompromised patients. For example, KS is more common in adult men with HIV. We describe 2 very rare cases of iatrogenic KS in children after hematopoietic stem cell transplant with isolated organ damage (case 1: lung; case 2: inguinal lymph node). KS is a potential complication of bone marrow transplant in pediatric patients and can occur in different age groups and at atypical sites.
Subject(s)
Hematopoietic Stem Cell Transplantation , Herpesvirus 8, Human , Sarcoma, Kaposi , Child , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Immunocompromised Host , Lung , Lymph Nodes , Sarcoma, Kaposi/etiologyABSTRACT
Non-anaplasticperipheral T-cell lymphomas (PTCL) are rare tumors in children, adolescents, and young adults (CAYA) with poor prognosis and scarce genetic data. We analyzed lymphoma tissue from 36 patients up to 18 years old with PTCL, not otherwise specified (PTCL-NOS), hepatosplenic T-cell lymphoma, Epstein-Barr virus (EBV)-positive T-lymphoproliferative diseases, subcutaneous panniculitis-like T-cell lymphoma, and other PTCL types. Twenty-three patients (64%) had at least one genetic variant detectable, including TET2, KMT2C, PIK3D, and DMNT3A. TP53 and RHOA variants, commonly found in adults, were not identified. Eight of 20 (40%) CAYA PTCL-NOS had no detectable mutations. The genetic findings suggest that CAYA PTCL differ from adult cases.
Subject(s)
Epstein-Barr Virus Infections , Lymphoma, T-Cell, Peripheral , Lymphoma, T-Cell , Adolescent , Child , Herpesvirus 4, Human , Humans , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell, Peripheral/geneticsABSTRACT
INTRODUCTION: The live-attenuated BCG vaccine is known to cause disseminated Mycobacterium bovis infection in patients with severe combined immunodeficiency (SCID). However, BCG-related post-hematopoietic stem cell transplantation (HSCT) immune reconstitution inflammatory syndromes, similar to those described in patients with HIV infections, are less-known complications of SCID. PATIENTS AND METHODS: We reported on 22 BCG-vaccinated SCID patients who had received conditioned allogeneic HSCT with TCRαß+/CD19+ graft depletion. All BCG-vaccinated patients received anti-mycobacterial therapy pre- and post-HSCT. Post-transplant immunosuppression consisted of tacrolimus in 10 patients and of 8 mg/kg tocilizumab (d-1, + 14, + 28) and 10 mg/kg abatacept (d-1, + 5, + 14, + 28) in 11 patients. RESULTS: Twelve patients, five of whom had BCG infection prior to HSCT, developed BCG-related inflammatory syndromes (BCG-IS). Five developed early BCG-IS with the median time of manifestation 11 days after HSCT, corresponding with a dramatic increase of CD3+TCRγδ+ in at least two patients. Early BCG-IS was noted in only one out of 11 patients who received tocilizumab/abatacept and 4 out of 11 patients who did not. Seven patients developed late BCG-IS which corresponded to T cell immune recovery; at the time of manifestation (median 4.2 months after HSCT), the median number of CD3+ cells was 0.42 × 109/ and CD3+CD4+ cells 0.27 × 109/l. In all patients, late BCG-IS was controlled with IL-1 or IL-6 inhibitors. CONCLUSION: BCG-vaccinated SCID patients undergoing allogeneic HSCT with TCRαß+/CD19+ graft depletion are at an increased risk of early and late BCG-IS. Anti-inflammatory therapy with IL-1 and IL-6 blockade is efficient in the prevention of early and treatment of late BCG-IS.
Subject(s)
BCG Vaccine/immunology , Hematopoietic Stem Cell Transplantation , Inflammation/immunology , Severe Combined Immunodeficiency/immunology , Anti-Inflammatory Agents/therapeutic use , Antigens, CD19/metabolism , Female , Humans , Immunosuppressive Agents/therapeutic use , Infant , Infant, Newborn , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Lymphocyte Depletion , Lymphocytes/metabolism , Male , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Risk , Severe Combined Immunodeficiency/therapy , Syndrome , Transplantation, Homologous , Vaccination , Vaccines, AttenuatedABSTRACT
Anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma is characterized by morphological variability. Morphological variants (non-common subtype) are associated with a poor outcome. They display abundant reactive bystander cells admixed with the lymphoma cells. So far, the difficulty in distinguishing lymphoma cells from bystander cells by visual inspection has prevented detailed and reliable immunophenotypic analysis using conventional immunohistochemistry. To overcome these limitations, we analyzed 124 cases of pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma treated within clinical trials using immunofluorescence multi-staining and digital image analysis combining antibodies against anaplastic lymphoma kinase to specifically identify lymphoma cells with antibodies against CD30, CD3, CD5, CD8, Ki67 and phosphorylated STAT3. Non-common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas express CD8 more frequently than common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas (35.4% and 5.6%, respectively; P=0.0002). CD8 expression was associated with a poorer outcome. Importantly, in a multivariate analysis including clinical risk factors, histological subtype and CD8 expression, CD8-positivity proved to be an independent prognostic predictor of worse outcome (hazard ratio for survival 3.38, P=0.042).
Subject(s)
CD8 Antigens/biosynthesis , Gene Expression Regulation, Neoplastic , Lymphoma, Large-Cell, Anaplastic/diagnosis , Lymphoma, Large-Cell, Anaplastic/enzymology , Receptor Protein-Tyrosine Kinases/biosynthesis , Adolescent , Anaplastic Lymphoma Kinase , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Lymphoma, Large-Cell, Anaplastic/therapy , Male , Treatment OutcomeABSTRACT
Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin D1, a mediator of G1-S phase transition. Thus MCL is regarded as a paradigm of lymphoma with a dysregulated cell cycle. The proliferation rate of MCL is in fact a strong predictor of outcome. We analyzed proteins that are expressed at defined cell cycle phases, such as Ki67, survivin and phosphorylated histone H3 as well as cyclin D1, p53 and p27, on the cellular level by immunofluorescence double stainings in MCL biopsy specimens. Unexpectedly, we did not detect a shortening of early phases in MCL in vivo. Despite the control of the immunoglobulin enhancer, cyclin D1 was expressed in a cell cycle-dependent manner. However, the proliferating Ki67-positive tumor cells expressed low amounts of cyclin D1. Therefore, the expression of cyclin D1 appears not to be the driving factor behind the total proliferation rate of MCL.
Subject(s)
Biomarkers, Tumor/metabolism , Cell Cycle/physiology , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Ki-67 Antigen/metabolism , Lymphoma, Mantle-Cell/pathology , Tumor Suppressor Protein p53/metabolism , Biomarkers, Tumor/genetics , Cyclin D1/genetics , Cyclin-Dependent Kinase Inhibitor p27/genetics , Fluorescent Antibody Technique , Humans , Inhibitor of Apoptosis Proteins/genetics , Ki-67 Antigen/genetics , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/metabolism , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survivin , Tumor Suppressor Protein p53/geneticsABSTRACT
Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.