Effective Use of microRNA, BRAF and Sonographic Risk Assessment in Bethesda III Thyroid Nodules Requires a Different Approach to Nodules with Features of Nuclear Atypia and Other Types of Atypia.

The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.

Optimization of the Management of Category III Thyroid Nodules Using Repeat FNA and TIRADS.

The aim of the study was to examine the benefits of the joint use of repeat FNA (rFNA) and EU-TIRADS in category III nodules in relation to the kind of atypia: nuclear vs. architectural (denoted by AUS and FLUS respectively). The study included 127 AUS and 1739 FLUS nodules with a known category of EU-TIRADS. Repeat FNA was performed in 82 AUS and 934 FLUS nodules of which 57 and 515 were excised, respectively. AUS nodules had higher malignancy risk than FLUS nodules. EU-TIRADS showed higher accuracy for AUS nodules, the opposite to rFNA, that had higher accuracy for FLUS nodules. The combined criterion for AUS nodules (at least rFNA-V or EU-TIRADS-4) maximized sensitivity (92.3%) with acceptable specificity (70.0%); OR: 28.0. In the case of FLUS nodules, the combined criterion (rFNA-V or EU-TIRADS-5) maximized specificity (95.2%) with 57.7% sensitivity and a low percentage (13.9%) of positive nodules, OR: 27.0. In both types of nodules, the low risk category in EU-TIRADS and benign result of rFNA excluded cancer. Concluding, category III nodules with and without nuclear atypia differ in their risk of malignancy and, consequently, diagnostic criteria adopted for the evaluation of these nodules with rFNA and EU-TIRADS should be specific to AUS and FLUS nodules.

Low reproducibility of equivocal categories of the Bethesda System for Reporting Thyroid Cytology makes the associated risk of malignancy specific to the diagnostic center.

PURPOSE: Equivocal categories (III, IV, V) of the Bethesda System for Reporting Thyroid Cytology (BSRTC) are characterized by high variability of the estimated risk of malignancy. The aim of the study was to analyze the reproducibility of classification of nodules into an equivocal category and the frequency of malignancy (FoM) observed in such categories. METHODS: Five experienced cytopathologists from three centers (A, B, C) independently performed reclassification of smears obtained from 213 thyroid nodules with equivocal routine cytology and known results of the postoperative histopathological examination. RESULTS: The interobserver agreement among all cytopathologists was poor, with a Krippendorff's alpha coefficient equaling 0.34. The intra-center agreement was higher than the inter-center (fair vs poor). Pathologists of the center A classified smears into categories II and III significantly less often and categories IV and V more often than pathologists of centers B and C. The joint FoM of nodules classified into any of categories IV-VI (regarded as an indication for surgery) was different among centers (A: 40.0%, B: 66.7%, C: 80.6%). The FoM of category III nodules with features of nuclear atypia (AUS) in center B and C was two times higher than that of other nodules of category III (FLUS), while in center A the FoM was similar. CONCLUSIONS: The use of published data on the risk of malignancy in nodules of particular BSRTC categories without concern for the uniqueness of the diagnostic center may lead to erroneous conclusions.

Concentrations of cadmium and selected essential elements in malignant large intestine tissue.

INTRODUCTION: Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. AIM: Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. MATERIAL AND METHODS: Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. RESULTS: The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. CONCLUSIONS: The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer.

Mycobacterium tuberculosis as a sarcoid factor? A case report of family sarcoidosis.

PATIENT: Male, 26 FINAL DIAGNOSIS: Sarcoidosis Symptoms: Disseminated lung parenchymal changes Medication: - Clinical Procedure: - Specialty: Pulmonology. OBJECTIVE: Rare disease. BACKGROUND: Sarcoidosis is a granulomatous inflammatory disease that is induced by unknown antigen(s) in a genetically susceptible host. Although the direct link between Mycobacterium tuberculosis (MTB) infection and sarcoidosis can be excluded on the basis of a current knowledge, the non-infectious mechanisms may explain the causative role of mycobacterial antigens. The co-incidence of tuberculosis (TB) and sarcoidosis, and higher incidence of mycobacterial DNA in biological samples of sarcoid patients, have been reported by many authors. CASE REPORT: We present a case in which MTB infection in 1 family member triggered a sarcoid reaction in the infected subject and 2 other non-infected family members. We discuss different aspects of diagnosis and differentiation, as well as up-to-date hypotheses on the possible mechanisms leading to sarcoid inflammation in patients exposed to MTB. CONCLUSIONS: This case series documents the possibility of familial spreading of sarcoidosis, and points to MTB as a potential etiological factor.

RAD51 genotype and triple-negative breast cancer (TNBC) risk in Polish women.

The most lethal damage for the cell among all damage is double-strand breaks (DSB) of DNA. DSB cause development of cancer diseases including the triple-negative molecular subtype of breast cancer. The aim of this work was to evaluate the single nucleotide polymorphism -135G>C (rs1801320) of the RAD51 gene encoding DNA repair proteins by homologous recombination (HR) in triple-negative breast cancer (TNBC). We assessed the RAD51 -135G>C polymorphism in 50 women with triple-negative breast cancer and in 50 women from the control group. RAD51 polymorphism was analysed by the PCR-RFLP (restriction fragment length polymorphism) technique. Our results demonstrated a significant positive association between the RAD51 C/C genotype and TNBC, with an adjusted odds ratio (OR) of 5.95 (p = 0.002). The homozygous C/C genotype was found in 68% of breast cancer cases and 20% of controls. The variant 135C allele of RAD51 increased TNBC risk. This is the first study linking single nucleotide polymorphisms of the RAD51 gene with TNBC incidence in the population of Polish women. In conclusion, RAD51 polymorphisms may be regarded as predictive factors of triple-negative breast cancer in the female population. Large studies are needed to confirm our findings.

ß-catenin as a prognostic factor for prostate cancer (PCa).

INTRODUCTION: The prostate cancer is difficult to predict, and treatment failure is associated with local infiltration, as well as distant metastases. Adhesion and migration abilities to of cancer cells play a major role in formation of metastasis. The participation of ß-catenin in pathogene-sis of many types of cancer and benign processes has been an important discovery of recent years. MATERIAL AND METHODS: The studied material was obtained by transrectal, sextant core biopsy from 102 patients hospitalized in Department of Urology, Regional Hospital in Kalisz (2001-2004). The aim of our study was to determine the predictive value of ß-catenin immunoexpression in prostate cancer, to analyze the prognostic aspect of some histopathological features and finally to assess the relationship between ß-catenin immunoreactivity and the microscopic image of the tumor. Relationships between the investigated variables were analyzed using the Chi(2) test of compatibility. We used the Kaplan-Meier curves to assess survival differences between groups of patients. Finally we established which of the studied factors significantly affect the patient outcome, using the method of Cox proportional hazard regression. RESULTS: In prostate cancer in comparison with the normal epithelium, both the location and the strength of ß-catenin immunoexpression are impaired. CONCLUSIONS: Our results indicate that the presence of disorders in ß-catenin immunoexpression in prostate cancer cells indicates a high risk of death due to tumor progression and makes it imperative for immediate treatment procedures.

[The practical value of breast cancer molecular classification]. / Praktyczna wartosc molekularnej klasyfikacji raków sutka.

Breast cancer is the most common female cancer in the Western World and the leading cause of cancer death among women. It is a clinically heterogeneous clinical entity. Histologically similar tumors may have different prognosis and may respond to therapy differently. It is believed that these divergences in clinical behavior are due to molecular differences between microscopically similarneoplasmas. Breast cancer is a complex disease of genetic background characterized by accumulation of molecular alterations resulting in an important clinical heterogeneity. Current prognostic factors (including lymph node status, tumor size, histological grade, hormone receptor status, ERBB2 expression and patient age) are insufficient to predict accurately the clinical outcome. Microarray expression profiling classifies breast cancer into five (or six) molecular subtypes: luminal A, luminal B, basal-like, HER2 and normal breast-like (sometime luminal C, too). The different molecular classes of breast cancer not only have different prognoses but also show distinct sensitivities to preoperative chemotherapy. They have specific clinical profiles, as well (reproductive factors, age and race). It means that new, modified prevention strategy for breast cancer is necessary.

Langerhans cell histiocytosis in a 3-year-old girl: a case report and literature review.

The report presents a case of Langerhans cell histiocytosis with diagnostic problems and fatal outcome in a 3-year-old girl, as well as a short literature review.

Morphological analysis of vascular density in ependymomas.

Ependymomas generally show slow growth rate and are associated with a long clinical history. In some cases however the biology of these tumours is considered to be unpredictable on the basis of histologic criteria. Density of microvessels was shown to serve in various malignant neoplasms as a prognostic factor that correlates with increased risk of metastasis and overall free survival. Some data suggest that density of blood vessels may be of prognostic value also in patients with neuroepithelial tumours. The aim of this study was to determinate whether that observation can be applied to ependymomas. The materials included 51 ependymomas G2 and G3 according to the WHO classification. Vasculature was visualized immunohistochemically in paraffin-embedded sections of tumour samples with CD31 and FVIII antibody. Density of blood vessels was calculated using a computed image analyzing system. The data were statistically evaluated. The density of blood vessels in anaplastic (WHO G3) ependymomas was shown to be significantly higher than that in WHO G2 type of the tumour, while there was no statistical difference between subtypes of WHO G2 ependymomas. The results suggest a connection between density of vasculature and the degree of histological malignancy in gliomas of ependymal derivation.

Cystic nephroma in adults. A report of two cases and review of the literature.

We present two cases of cystic nephroma in a 55-year old and a 61-year old women. In both patients the results of ultrasound and clinical examinations were not characteristic enough to establish the precise preoperative diagnosis. Due to the age of the patients and the location of the lesions, possibility of clear cell carcinoma with cystic changes was considered. However, microscopic examination of postoperative specimens revealed benign nature of the tumors.