Translocation t(1;9) is a recurrent cytogenetic abnormality associated with progression of essential thrombocythemia patients displaying the JAK2 V617F mutation

A cohort of 338 patients diagnosed with myeloproliferative neoplasms was investigated by conventional cytogenetics and evaluated for the presence of the JAK2 V617F mutation. A t(1;9)(p10;q10) in addition to two extra der(1;9)(q10;p10) chromosomes was observed in two patients of essential thrombocythemia that transformed to acute myelogenous leukemia or to myelofibrosis. These findings suggest that the presence of extra derivative chromosomes der(1q;9p) in combination with the JAK2 V617F mutation may play a role in the progression of myeloproliferative neoplasms and supports the use of cytogenetics in the follow-up of the disease.     

The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

BACKGROUND:

Percutaneous fine‐needle aspiration (FNA) cytology is an important diagnostic test for the evaluation and management of selected renal masses. Cytogenetic analysis of cytology specimens can serve as an adjunct for precise classification because certain tumors are associated with specific chromosomal aberrations. This study summarizes our experience with the application of conventional cytogenetics and fluorescence in situ hybridization (FISH) to renal FNA specimens.

METHODS:

All percutaneous renal FNAs performed during 2005 through 2008 were identified from the electronic pathology database. Results of cytogenetic and FISH analyses were correlated with the final diagnoses of the renal FNAs.

RESULTS:

A total of 303 renal FNAs were performed. During an onsite assessment, a portion of the cytology specimen was allocated for cytogenetic analysis in 74 cases. Karyotypic analysis or FISH was successful in 44 (59%) of these. Characteristic chromosomal abnormalities were observed in 27 cases. In 17 cases, a karyotype revealed a combination of trisomies/tetrasomies and in another 5 cases, FISH revealed trisomy 7 and 17, both of which are consistent with papillary renal cell carcinoma (RCC). Two cases showed 3p deletions consistent with clear cell RCC. Trisomy 3 was observed in 1 case of clear cell RCC. Monosomy 1 and 17 was observed in a case of papillary RCC comprised oncocytic cells. In 1 case of primary renal synovial sarcoma, FISH revealed a rearrangement at the SYT locus (18q11.2).

CONCLUSIONS:

Renal FNA specimens are amenable to analysis by cytogenetics and FISH in the diagnosis and subclassification of renal neoplasms. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

FISHing in the dark: How the combination of FISH and conventional karyotyping improves the diagnostic yield in CpG‐stimulated chronic lymphocytic leukemia

Despite significant advances in molecular genetic approaches, fluorescence in situ hybridization (FISH) remains the gold standard for the diagnostic evaluation of genomic aberrations in patients with chronic lymphocytic leukemia (CLL). Efforts to improve the diagnostic utility of molecular cytogenetic testing have led to the expansion of the traditional 4‐probe CLL FISH panel. Not only do these efforts increase the cost of testing, they remain hindered by the inherent limitations of FISH studies ‐ namely the inability to evaluate genomic changes outside of the targeted loci. While array‐based profiling and next generation sequencing (NGS) have critically expanded our understanding of the molecular pathogenesis of CLL, these methodologies are not routinely used by diagnostic laboratories to evaluate copy number changes or the mutational profile of this disease. Mitogenic stimulation of CLL specimens with CpG‐oligonucleotide (CpG‐ODN) has been identified as a reliable and reproducible means of obtaining a karyotype, facilitating a low‐resolution genome‐wide analysis. Across a cohort of 1255 CpG‐ODN‐stimulated CLL specimens, we describe the clinical utility associated with the combinatorial use of FISH and karyotyping. Our testing algorithm achieves a higher diagnostic yield (～10%) through the detection of complex karyotypes, well‐characterized chromosomal aberrations not covered by the traditional CLL FISH panel and through the detection of concurrent secondary malignancies. Moreover, the single cell nature of this approach permits the evaluation of emerging new clinical concepts including clonal dynamics and clonal evolution. This approach can be broadly applied by diagnostic laboratories to improve the utility of traditional and molecular cytogenetic studies of CLL. Am. J. Hematol. 91:978–983, 2016. © 2016 Wiley Periodicals, Inc.     

Evaluation of Erythropoiesis by Serum Transferrin Receptor and Ferritin in Infants Aged 0–6 Months

The aim of this study was to evaluate erythropoiesis in 198 healthy babies aged 0–6 months by determination of their blood count, serum transferrin receptor (STfR), and ferritin levels. Anemia and microcytosis were present in 9% and 13% of the sample, respectively. Microcytosis rate was as high as 45% in 6-month-old babies. In infants with normal blood counts, the values of sTfR/ferritin and sTfR-F index were increasing with the increase of sTfR and decrease of ferritin beginning from 2 months of age. In the 5- to 6-month-old group, sTfR concentrations, sTfR/ferritin ratio, and sTfR-F index were higher in infants with anemia and microcytosis. This research showed a high frequency of iron deficiency detected in otherwise healthy babies. Only problems with early weaning practices were found to be significantly more common in babies with iron deficiency.     

Evaluation of malnutrition status and related risk factors in geriatric outpatient clinic

BACKGROUND/OBJECTIVESMalnutrition risk and malnutrition among the elderly is a public health concern. In combating this health-related problem, it is critically important to evaluate the risk factors in a multidimensional way and to apply appropriate nutrition intervention based on the results.SUBJECTS/METHODSA cross-sectional study was conducted on 215 elderly patients (32.6% male, 67.4% female) in a geriatric outpatient clinic of a hospital in Turkey. Nutritional questionnaires that incorporated the 24-h recall method were applied to determine general characteristics of patients, their health status, nutritional habits, and daily energy and nutrient intakes. Mini Nutritional Assessment was used to determine nutritional status. Relevant anthropometric measurements were obtained.RESULTSThe subjects'' mean age was 76.1 ± 7.0 years, and the prevalence of malnutrition (n = 7) and risk of malnutrition (n = 53) among the 215 subjects was 3.2% and 24.7%, respectively. Patients with malnutrition or risk of malnutrition were found to be single, have a depression diagnosis, in an older age group, have less appetite, more tooth loss, have more frequent swallowing/chewing difficulty, and have more frequent meal skipping. In addition, mean daily energy, carbohydrate, fat, fiber, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin C, folates, potassium, magnesium, phosphorus, iron intake, and water consumption were found to be statistically significantly low in subjects with malnutrition or risk of malnutrition. After performing regression analysis to determine confounding factors, malnutrition risk was significantly associated with marital status, loss of teeth, appetite status, and depression.CONCLUSIONSRoutine nutritional screening and assessment of the elderly should be performed. If nutritional deficiencies cannot be diagnosed early and treated, self-sufficiency in the elderly may deteriorate, resulting in increased institutionalization.     

Prevalence and progression of internal carotid artery stenosis in patients with peripheral arterial occlusive disease

OBJECTIVE: The purpose of this study was to determine the prevalence of significant carotid stenosis, to identify risk factors increasing this prevalence, and to determine the risk of progression of stenosis, in patients with peripheral arterial occlusive disease who are neurologically asymptomatic. STUDY DESIGN: Consecutive patients who underwent evaluation in a vascular laboratory for peripheral arterial occlusive disease, who had no recent neurologic symptoms, were investigated. RESULTS: From July 1999 to December 2000, 620 patients underwent duplex scanning on one occasion, and 417 on two occasions. The average age was 72 +/- 10 years, and 61% were men. An occluded internal carotid artery was found in 4.8% of patients. The prevalence of a carotid stenosis >50% was 33% on the initial evaluation. Age of more than 70 years (P =.007), diabetes mellitus (P =.042), history of stroke (P =.011), and ankle/brachial index of less than 0.8 (P =.0006), were independently associated with carotid stenosis >50%. The odds ratio associated with each of these risk factors was similar. The prevalence of carotid stenosis >50% was 16%, 21%, 38%, 47%, and 44% for patients with no, one, two, three, and four risk factors, respectively. The highest prevalence of carotid stenosis >50% was identified in patients with ankle/brachial indices of less than 0.4 (59%). During the follow-up period, no patient had a cerebrovascular event. In 15% of carotid arteries, progression from one class of stenosis to a more severe class was observed, and 6.5% of patients progressed from a lower degree to 50% to 99% stenosis. No differences in progression of disease were identified when the variables of age, diabetes, previous stroke, and ankle/brachial index of less than 0.8 were studied or when patients with zero to two of these putative risk factors were compared with patients with three or four. CONCLUSION: Screening for carotid stenosis in asymptomatic patients with peripheral vascular disease is justifiable, but not mandatory, when two or more risk factors are present or when the ankle/brachial index is less than 0.4. Rates of progression to clinically significant stenosis are low and do not justify reevaluation every 6 months. Further research to identify the optimal interval for reevaluation is needed.     

BRD4 Bromodomain Gene Rearrangement in Aggressive Carcinoma with Translocation t(15;19)

Translocation t(15;19)(q13;p13.1) defines a lethal midline carcinoma arising adjacent to respiratory tract in young people. To characterize molecular alterations responsible for the distinctly aggressive biological behavior of this cancer, we mapped the chromosome 15 and 19 translocation breakpoints by fluorescence in situ hybridization (FISH) and Southern blotting. To evaluate preliminarily the frequency, anatomical distribution, and histological features of t(15;19) cancer, we developed a FISH assay for paraffin sections. Our findings reveal a novel oncogenic mechanism in which the chromosome 19 translocation breakpoint interrupts the coding sequence of a bromodomain gene, BRD4. These studies implicate BRD4 as a potential partner in a t(15;19)-associated fusion oncogene. In addition, we localized the chromosome 15 breakpoint to a 9-kb region in each of two cases, thereby identifying several candidate oncogenes which might represent the BRD4 fusion partner. FISH evaluation of 13 pediatric carcinomas revealed t(15;19) in one of four sinonasal carcinomas, whereas this translocation was not detected in thymic (n = 3), mucoepidermoid (n = 3), laryngeal (n = 2), or nasopharyngeal (n = 1) carcinomas. Our studies shed light on the oncogenic mechanism underlying t(15;19) and provide further evidence that this highly lethal cancer arises from respiratory mucosa.