Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome.

OBJECTIVES: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS. METHODS: Thirty six newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene. RESULTS: Mutations were present in 11 out of 36 patients (31%), which were not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (P = 0.039) and lower TIBC (P = 0.018). Ferritin was found to be higher for the untransfused mutated patients (P = 0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (P = 0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival in addition to a poorer leukemia free survival (LFS) (P = 0.004 and P = 0.003, respectively). DISCUSSION: The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anemia. The effect of mutations on survival could be mediated by changes in iron metabolism. CONCLUSION: The HFE genotype may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy.

[The use of peripherally inserted central catheter (PICC) in patients with hematological malignancies--a single center experience]. / Upotreba periferno uvedenoga centralnog venskog katetera (picc) u bolesnika sa zlocudnim hematoloskim bolestima--prikaz vlastitih iskustava.

UNLABELLED: AIM. In this study we presented our experience with peripherally inserted central venous catheter (PICC) in patients with hematological malignancies. METHODS: In the period from 2009 to 2012, a total of 105 PICCs were inserted in 90 patients. Patients with Non-Hodgkin lymphoma treated with DA-EPOCH comprised almost 40% of the cohort. RESULTS: The total PICC in-dwell time was 14781 days with a median of 129 days (range 8-570 days). Malposition of the PICC occurred in 12 patients (11.4%) with a successful reposition or re-insertion. In 39 patients (37%) PICC was removed before the end of treatment due to suspected or proven infection (30 patients, 29%; 2.03 per 1000 PICC days), thrombosis associated with PICC in four patients (3.8%), occlusion of the PICC (two patients), misplaced catheter (two patients), and suspected thromboembolism in a single patient. CONCLUSION: PICC is a safe and convenient long-term venous access in patients with hematological malignancies.

A fatal Mycobacterium chelonae infection in an immunosuppressed patient with systemic lupus erythematosus and concomitant Fahr's syndrome.

We present a case of systemic Mycobacterium chelonae infection in an immunosuppressed patient with systemic lupus erythematosus (SLE), idiopathic hypoparathyroidism, and hypothyroidism. The patient was treated for 3 months for skin infection with clarithromycin monotherapy. Since her condition deteriorated, the antibiotic therapy was switched to intravenously administered clindamycin, cloxacillin, and meropenem. Due to further deterioration and isolation of M. chelonae from the blood culture, antimicrobial therapy was changed to azithromycin and amikacin. Drug-test sensitivity was performed, and the isolate was susceptible to clarithromycin only. The patient's deteriorating status prevented orally administered medication with clarithromycin (parenteral formulation is not registered in Croatia). The same antibiotic regime was continued until the isolation of Pseudomonas aeruginosa and Candida albicans. In addition, extensive calcifications in her brain were found on a computed tomography (CT) scan, which suggested Fahr's syndrome. Despite all measures and supportive care, the patient developed multiorgan failure and eventually died. There has been an increase in the number of infections by rapidly growing mycobacteria, but only a few cases of severe systemic infection with M. chelonae have been described. If the infection is diagnosed early and a patient is treated with appropriate drugs, dissemination can be avoided despite immunosuppression. For serious skin, bone, and soft-tissue disease, a minimum of 4 months of a combined drug therapy is necessary. This is the first report of M. chelonae infection in Croatia and the first-described M. chelonae infection in a patient with concomitant Fahr's syndrome.

Fine needle aspiration cytology of metastatic Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is uncommon cutaneous malignant neuroendocrine tumour of the elderly people with rapidly growing skin nodules found frequently on sun-exposed areas of the body. MCC is often an aggressive tumour with high tendency for local recurrence, lymph node involvement and distant metastases. This paper reports a case of metastatic MCC diagnosed by fine needle aspiration cytology (FNAC), flow cytometric deoxiribonucleated acid (DNA) analysis, pathohistology and electron microscopy. The cytological features in aspirate (stained with Papenheim and Papanicolaou staining) included increased cellularity, discohesive groups of small-to-medium size malignant cells with uniform, round-to-oval nuclei with moulding effect, fine chromatin, multiple micronucleoli and scanty cytoplasm. DNA flow cytometric analysis of the aspirate showed unexpected results for clinically aggressive behaviour of this tumour (the patient died after 21 months), and revealed that tumour contained diploid peak with DNA index of 1.1. The proliferation was high with elevated S-phase fraction (21%). The cytological diagnosis of possible metastatic MCC was confirmed by histological one as well as by electron microscopy presented the pathognomonic features for this tumour: dense-core neurosecretory granules with diameter of 100-250 nm surrounded by whorls of intermediate filaments. MCC provides an enormous challenge for the morphologist because of a wide range of differential diagnosis and for the clinician because this tumour has a highly malignant potential for local recurrence, nodal and distant spread and very often is combined with other tumours. Therefore it is important to perform FNAC of different lesions in the same patient because it can distinguish MCC from the other tumours.

Cytogenetics of multiple myeloma.

Great studies of multiple myeloma (MM) strongly suggested that specific chromosomal changes are of prognostic significance in patients with MM1. We have performed cytogenetic analysis and recently fluorescent in situ hybridization (FISH) on 43 cases of MM. Clonal chromosomal changes were present in 24 (56%) cases. Hyperdiploid karyotype was found in 12 (50%) cases, hypodiploid in 8 (33%) cases, and 4 (17%) cases had a pseudodiploid karyotype. The most common numerical abnormalities were gains of whole chromosomes 15, 11, 3 and 6. Whole chromosome losses were also frequent involving chromosomes X, 13, 14, and 8. Most cases showed also structural rearrangements 71% (n = 17): del(1p), dup(1q), del(5q), del(13q), del(17p) and t(11;14)(q13;q32) (n = 4, 17%). Chromosome -13/13q deletion was found in 42% (n = 10) cases; complete loss of 13 was observed in 67% (n = 7) cases, whereas 33% (n = 3) had interstitial deletions. In the majority of the cases there was a mixture of abnormal and normal metaphases.

[Cholesterol crystal embolism and renal insufficiency: case report and literature review]. / Kolesterolska embolizacija i bubrezna insuficijencija: prikaz bolesnika i pregled literature.

Cholesterol crystal embolism with renal impairment is increasingly recognised as an iatrogenic complication of invasive vascular procedures. We present a 58-year-old patient in whom the presence of a classic triad of precipitating event (coronary angiography), subacute presentation of renal failure and cutaneous lesions (livedo reticularis and Blue Toe syndrome) suggested this entity. The confirmatory diagnosis was made by means of renal biopsy which revealed cholesterol crystals lodged in arteries. In our patient severe renal insufficiency requiering hemodialysis ensued. Glucocorticoid and statin therapy failed to recover the renal function. The patient died from acute myocardial infarction. Invasive cardiac procedures are increasing in number especially in the elderly population so higher incidence of cholesterol crystal embolism coud be expected in the future. Increased awareness of this syndrome is necessary for early recognition, which is crucial for treatment, and defining the high-risk patient in whom other modalities of coronary diagnostics coud be considered.

Bone marrow renin-angiotensin system expression in polycythemia vera and essential thrombocythemia depends on JAK2 mutational status.

Recent observations raise possibility for constitutively active, mutated JAK2 to modulate expression of RAS genes in CMPD. We analyzed the expression of AGT, renin, AT2R1 and ACE genes in normal and bone marrows of PV and ET patients with the respect to the presence of V617F JAK2 mutation. PV and ET had different expression patterns of major RAS components compared to normal BM which was primarily associated with the JAK2V617F mutation and less with PV or ET disease phenotype. However, AT2R1 was exclusively markedly upregulated only in PV, while ET showed moderate expression irrespective of the JAK2 mutational status.