Low-burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation.

TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS-based mutation analysis in a 'real-world' cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high-burden mutations, while 52% were low-burden TP53 mutations. Low-burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low-burden TP53 mutation. Patients harbouring low-burden TP53 mutations had significantly lower time to first treatment compared to patients with wild-type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low-burden TP53 mutations. By demonstrating that patients with sole low-burden TP53 variants represent more than one-third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting.

[Whipple's disease. Do we think of it enough?]. / Whipple-kór. Vajon gondolunk-e mindig rá?

UNLABELLED: Whipple's disease is a chronic, systemic, relapsing bacterial illness, which is always fatal without treatment, and means a diagnostic challenge for both clinicians and pathologists. It occurs in Caucasian, white, middle-aged men in 80 % of the cases. CASE REPORT: The authors present three cases, and review the etiology, clinical features, presumed pathomechanism and the possibilities of treatment. CONCLUSION: Several immune-mechanisms have been discussed in the background of Whipple's disease, but their primary or secondary role is yet undetermined. First of all, this is a gastrointestinal disease; however, extraintestinal symptoms may be present many years before the final diagnosis. The histological hallmark for the diagnosis is the presence of numerous macrophages in the duodenal mucosa showing periodic acid-Schiff (PAS)-positive inclusions, and the polymerase chain reaction. The choice of antibiotics and the length of the treatment is empiric, but in most cases there is an immediate response to therapy. Relapses are common, especially the involvements of central nervous system.

[Clodronat therapy of hypercalcaemia associated with male breast cancer] / Férfi emlôtumorhoz társuló hypercalcaemia kezelése clodronattal.

OBJECTIVES: The aim of this study is to survey the treatment of bone metastases and hypercalcaemia. MATERIALS AND METHODS: A case of male breast cancer is presented here by the authors. The applied clodronat therapy was beneficial. RESULTS: The diagnostic difficulties of such rare, unusually localised, metastasizing male breast cancer are discussed with the survey of Hungarian and world literature. CONCLUSION: The bisphosphonates - beside treating the hypercalcaemia caused by bone metastasis - provide a better quality of life.