Distribution of lymphomas in Poland according to World Health Organization classification: analysis of 11718 cases from National Histopathological Lymphoma Register project - the Polish Lymphoma Research Group study

Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.     

Carcinoma, a fibrolamellar variant--immunohistochemical analysis of 4 cases

BACKGROUND/AIMS: To analyze, by means of immunocytochemistry, the cases of fibrolamellar variant of hepatocellular carcinoma (FLC), diagnosed in our Department. METHODOLOGY: The material comprised 4 FLC cases of tumors resected surgically. Besides the routine morphological assessment, we used a panel of immunohistochemical stainings including: hepatocellular cytokeratin, CK7, CK19, Ki67, PCNA, chromogranin A, synaptophysin, NSE, insulin, calcitonin, parathormon, CD34, EBV (LMP), Bcl2, cyclin D1. RESULTS: In 3 out of 4 cases, we observed co-expression of CK7 with hepatocellular CK. In addition, there was positive staining with some endocrine markers in the majority of patients. In one case, we found strong cyclin D1 immunoreactivity which correlated with EBV (LMP) immunoreactivity, in the same patient. The score of PCNA positivity varied between 15 and 90%. In all cases Ki67 was negative. CONCLUSIONS: The incidence of FLC, among all hepatocellular carcinomas diagnosed in our Department was 5.1%. In accordance with other reports, all our FLC cases were young patients without underlying liver disease. We were unable to find a correlation between FLC cellular immunophenotype, and histological and clinical markers of malignancy. In addition, it appears that PCNA is a better marker of cell-proliferation in FLC than Ki67. The significance of EBV infection in FLC requires further study.     

Polymorphisms in TS,MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients

Purpose

We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy.

Methods

The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5′-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3′-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations’ results were correlated with disease control rate, progression-free survival (PFS) and overall survival.

Results

Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality.

Conclusion

The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.     

Eosinophilic gastroenteritis and graft‐versus‐host disease induced by transmission of Norovirus with fecal microbiota transplant

Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic‐resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft‐versus‐host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus‐free FMT from another donor.     

Transfusions of blood and blood products and virus infections

Transfusions of blood and blood products are commonly used in medicine, but being biological materials they carry a risk of transmitting infections--viral, bacterial, parasitic, as well as prions. Laboratory tests used for screening of donated blood for viral infections at present cannot detect all infectious units. Criteria for selection of blood donors therefore must be very strict, while methods of inactivation of viruses and laboratory assays for detection of their presence must be improved. Indications for blood transfusion should be restricted.     

Threshold values of maternal blood glucose in early diabetic pregnancy--prediction of fetal malformations

BACKGROUND: The prevention of congenital malformations in the newborns of diabetic mothers still constitutes one of the main problems in this group of patients. AIM: The aim of this study was to analyze the prevalence of fetal malformations in diabetic pregnancies, as well as detection of the cut-off points for the first-trimester glycemia levels, relating to diabetes-induced fetal malformations. METHODS: The data for analysis were collected retrospectively from the case histories of diabetic pregnant women and their newborns, treated in our departments. For the evaluation of maternal diabetes control, the whole-day glycemia profiles as well as glycated hemoglobin (HbA1C) levels were registered. To establish the glucose cut-off values for malformations, we have used receiver operating characteristic (ROC) curves for fasting, 1-hr, and 2-hr postprandial glucose levels. To determine how metabolic control influences the risk of giving birth to a malformed infant, we followed 198 newborns of diabetic mothers and 4700 infants born of healthy mothers (control group). RESULTS: We detected malformations in the infants of 8.6% (n = 17) of diabetic mothers and 3.8% of the control (odds ratio: 2.35, 95% CI = 1.40-3.96). We compared this group of diabetic patients to another diabetic pregnancy group, analyzed over a period of 1988-93 (n = 209), in which 13 newborns (6.2%) manifested congenital malformations (odds ratio: 1.41, 95% CI = 0.67-2.99) (the difference was statistically insignificant). HbA1C level during organogenesis was not significantly higher in women whose infants were malformed. We proved, however, that the risk of malformations was higher, when HbA1C value exceeded 9.3%. The malformation rate in diabetes classes D-H (according to White) was higher than in classes B and C, but the difference was not significant. A wide spectrum of anomalies has been observed in the newborns of diabetic mothers. CONCLUSIONS: Our results confirm the view that diabetic pregnancy, despite the improved metabolic control, is still a strong risk factor for alterations in fetal development, particularly in patients with a tendency to brittle glycemia during first trimester of pregnancy. It seems that keeping fasting glucose levels in first trimester below 5.8 mmol/l and postprandial glucose levels below 9.1 mmol/l can contribute to decreasing number of fetal malformations in pregestational diabetes mellitus (PGDM) pregnancy. The ROC curves appear to be useful and adequate tool for the analysis of factors influencing fetal development in diabetic pregnancy.     

Macular corneal dystrophy including histologic and ultrastructural changes

PURPOSE: The study reports the results of a histological and ultrastructural examination of the corneal button, obtained during penetrating keratoplasty from patient with clinically recognized macular corneal dystrophy. MATERIAL AND METHODS: 34-year-old male patient suffering from macular corneal dystrophy (MCD) has been treated on corneal epithelium defect and photophobia since his early childhood. Visual acuity was decreased on the Snellen test chart to 0.02. Slit-lamp examination, and ultrasonographical measurement of the cornea's thickness were performed. Removed during penetrating keratoplasty corneal button was divided into two pieces. One of them was prepared in standard procedure for histological examination in the light microscopy after having been stained with hematoxylin and eosin, alcian blue and paS-method. From the other part, slides for ultrastructural examination in the transmission electron microscopy were prepared with the use of standard method. The family history from the patient was also taken, and available relatives have undergone examination in search of typical MCD symptoms. RESULTS: Slit-lamp examination findings revealed diffuse, from limbus to limbus, stromal opacification. In measurement by pachymeter cornea's thickness was reduced. In the light microscopy, in typical stained slides, delaminations within stroma and deficit of endothelial cells were observed. After being stained with alcian blue, dark blue deposits in the places of delamination became visible. By transmission electron microscopic examination, intracellular and extracellular deposits were detected in the stroma, Descemet membrane and endothelium. Distended keratocytes with enormous vacuoles containing abnormal material were found. Pedigree was typical for autosomal recessive inherited disease. CONCLUSIONS: Histological and ultrastructural diagnosis is a basis of recognition of macular corneal dystrophy. Analysis of the pedigree as well as ultrasonographical measurement of the cornea's thickness is very helpful to establish the right diagnosis.     

The prognostic significance of shape of demarcation line and ridge in clinical course of active phase of retinopathy of prematurity

PURPOSE: We planed out a comparison of clinic significance between eyes with acute ROP with "bays" and ROP without "bays". Retinopathy of prematurity (ROP) is a main reason of blindness in premature babies. There are no studies about shape of demarcation line and ridge in acute retinopathy of prematurity and its influence for clinical significance of ROP. In 11.42% of eyes with acute ROP we observed irregularities of demarcation line and ridge, which we called "bays". MATERIAL AND METHODS: We observed 140 premature babies (280 eyes) with acute ROP. In 32 eyes (11.42%) we stated "bays". We compared progression to stage ROP3c between group I (eyes with acute ROP and "bays") and group II (eyes with ROP without "bays). RESULTS: In 87.5% eyes with "bays" we observed progression to stage 3 c retinopathy of prematurity. In group without "bays" progression to stage 3c was observed only in 33.47%. CONCLUSIONS: We suppose, that presence of "bays" of demarcation line and ridge brings about worse prognosis at the course of acute retinopathy of prematurity.