Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey.

There is increasing evidence that therapy-related acute lymphoblastic leukemia (trALL) resulting from chemo- and/or radiotherapy represents a distinct entity. However, apart from rearrangements, which have been repeatedly reported in this subgroup, the relevance of other aberrations remains controversial due to divergent study results and sparse molecular analyses. Within our ALL patient cohort, 15% ( = 19/131) met the criteria for trALL with a high proportion of Ph + and rearrangements.

Intervertebral disc cell chondroptosis elicits neutrophil response in spondylodiscitis.

To understand the pathophysiology of spondylodiscitis due to , an emerging infectious disease of the intervertebral disc (IVD) and vertebral body with a high complication rate, we combined clinical insights and experimental approaches. Clinical data and histological material of nine patients suffering from spondylodiscitis were retrospectively collected at a single center. To mirror the clinical findings experimentally, we developed a novel porcine model mimicking acute spondylodiscitis and assessed the interaction between and IVD cells within their native environment.

Secondary sclerosing cholangitis as cause of persistent jaundice in patients with severe COVID-19.

Background & Aims: Little is known about cholestasis, including its most severe variant secondary sclerosing cholangitis (SSC), in critically ill patients with coronavirus disease 19 (COVID-19). In this study, we analysed the occurrence of cholestatic liver injury and SSC, including clinical, serological, radiological and histopathological findings.

Methods: We conducted a retrospective single-centre analysis of all consecutive patients admitted to the intensive care unit (ICU) as a result of severe COVID-19 at the University Hospital Zurich to describe cholestatic injury in these patients.

Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed.

Aggressive primary olfactory neuroblastoma of the sphenoclival region: a case report and literature review.

Olfactory neuroblastoma (ONB) is an uncommon malignant tumor of neural crest origin, which commonly arises in the superior nasal cavity. Ectopic origin of an ONB is exceedingly rare. We describe a rare case of an ectopic sphenoclival ONB with extensive involvement of the central skull base and with development of systemic metastases.

HBME-1 expression in hyalinizing trabecular tumours of the thyroid gland.

Aims: Hyalinizing trabecular tumour (HTT) is a rare thyroid neoplasm with a trabecular growth pattern, marked intratrabecular hyalinization and nuclear features of papillary thyroid carcinoma (PTC). Immunohistochemical HBME-1 expression was reported recently in PTC, but not in HTT. To clarify further the value of HBME-1 expression as a tool in differential diagnosis, we investigated the immunophenotype of HTT.

Rare occurrence of biallelic CYLD gene mutations in classical Hodgkin lymphoma.

Survival of the malignant Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is dependent on constitutive activation of the nuclear factor kappaB (NF-kappaB) transcription factor. The deubiquitinating enzyme CYLD is a negative regulator of NF-kappaB and known to function as a tumor suppressor. To determine whether CYLD mutations play a role in cHL pathogenesis, we sequenced the gene in cHL cell lines and microdissected HRS cells obtained from lymph-node biopsies.

Congenital peribronchial myofibroblastic tumor: a case report.

We describe a rare occurrence of congenital peribronchial myofibroblastic tumor of the lung presenting in early fetal life. A female patient in the 24th week of gestation who presented with polyhydramnios was admitted for examination. Ultrasound examination revealed a mass compromising the lungs.

Absence of measles virus genome and transcripts in Hodgkin-Reed/Sternberg cells of a cohort of Hodgkin lymphoma patients.

In the search for viruses in Hodgkin lymphoma (HL), it was reported that the measles virus (MV) can be detected in the Hodgkin-Reed/Sternberg (HRS) cells of a large fraction of cases from Israel by immunohistochemistry or in situ hybridisation, suggesting a potential role of this virus in HL. To extend and validate this report, we studied HL-derived cell lines and HRS cells microdissected from German and Israeli HL cases for the presence of MV RNA genome and transcripts, analysing three MV genes (nucleoprotein, matrix, haemaglutinin). A cell line infected with MV was used as a positive control for MV RNA detection.

Neuroblastoma in southern Brazil: an 11-year study.

The authors report on the incidence and clinical characteristics of neuroblastoma in southern Brazil. The aims of the study were to evaluate the age at diagnosis, tumor stage, MYCN status, and tumor histopathology, and to relate these factors to survival. All patients with neuroblastoma, 15 years old or younger (n = 125), admitted to the three major pediatric oncology hospitals in the state of Parana over a period of 11 years (between January 1990 and December 2000), were included in the analysis.

Development of lymphoma in Autoimmune Lymphoproliferative Syndrome (ALPS) and its relationship to Fas gene mutations.

Autoimmune Lymphoproliferative Syndrome (ALPS) is generally the result of a mutation in genes associated with apoptosis, like Fas, Fas ligand, Casp 8 and Casp 10. As a result, the normal homeostasis of T- and B-lymphocytes is disturbed and a proliferation of polyclonal T lymphocytes occurs. This leads to hepatosplenomegaly and lymphadenopathy and in most patients also to autoimmune phenomena like anemia and thrombocytopenia.

High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma.

In a search for genes specifically expressed in Reed-Sternberg (RS) cells of Hodgkin lymphoma (HL), we applied the serial analysis of gene expression (SAGE) technique on the HL-derived cell line DEV. Genes highly expressed in DEV were subjected to an RT-PCR analysis to confirm the SAGE results. For one of the genes, a high expression was observed in DEV and other HL-derived cell lines but not in non-Hodgkin lymphoma (NHL)-derived cell lines and normal controls, suggesting an HL-specific expression.

FAS gene mutation in a case of autoimmune lymphoproliferative syndrome type IA with accumulation of gammadelta+ T cells.

A 6-month-old girl presented to the hospital with cervical lymphadenopathy and hepatosplenomegaly. She was known to have an enlarged spleen, anemia, and thrombocytopenia since the age of 1 month. A lymph node biopsy showed a diffuse proliferation of blasts with few remnants of follicles.

Low frequency of FAS mutations in Reed-Sternberg cells of Hodgkin's lymphoma.

Reed-Sternberg (RS) cells, the neoplastic elements of Hodgkin's lymphoma (HL), usually lack B-cell receptor expression. Normal germinal center B cells, with lack of or low-affinity B-cell receptor expression, are eliminated via FAS-induced apoptosis. RS cells express FAS, but are rescued from apoptosis by a transforming event.

Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma.

Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). In some cases the transformed cells are Epstein-Barr virus (EBV)-positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells.

Common and differential chemokine expression patterns in rs cells of NLP, EBV positive and negative classical Hodgkin lymphomas.

Hodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Reed-Sternberg (RS) cells and a vast majority of reactive cells. RS cells produce chemokines that can attract subsets of peripheral blood cells into HL tissues. To gain insight in the chemokines involved in HL, 16 chemokines were selected based on their ability to recruit different subsets of cells.

Germline FAS gene mutation in a case of ALPS and NLP Hodgkin lymphoma.

FAS germline mutations have been associated with the development of autoimmune lymphoproliferative syndrome (ALPS). Occurrence of Hodgkin lymphoma (HL) has been reported in 2 families with ALPS. In both families an uncle of the index patient developed HL.