Combined use of galectin-3 and thyroid peroxidase improves the differential diagnosis of thyroid tumors.

The differential diagnosis of well-differentiated tumors of follicular cell origin remains the most problematic task in thyroid pathology. Specific morphologic criteria (capsular and/or vascular invasion, nuclear characteristics) are crucial in the diagnosis of these neoplasms. However, the assessment of malignant features is inconclusive in some cases. Moreover, oncocytic thyroid tumors remain controversial in a respect to their pathobiology, behavior and management. Therefore, the useful diagnostic/prognostic thyroid markers are awaited. The aim of our study was to evaluate the expression of galectin-3 and thyroid peroxidase (TPO) in benign and malignant thyroid tumors of follicular cell origin. A total of 186 archival thyroid samples including 38 non-oncocytic follicular adenomas, 53 oncocytic (Hürthle cell) adenomas, 6 non-oncocytic follicular carcinomas, 23 oncocytic (Hürthle cell) carcinomas, 43 non-oncocytic papillary carcinomas, and 23 oncocytic papillary carcinomas were analyzed for galectin-3 and TPO expression by immunohistochemistry. Both types of papillary carcinomas showed significant upregulation of galectin-3 in comparison with the other tumor types, likewise, significant differences in galectin-3 expression were discovered between non-oncocytic and oncocytic variants of studied tumors excluding follicular carcinoma. Significant lowering of TPO was revealed in oncocytic adenomas and papillary carcinomas. In conclusion, the combined use of galectin-3 and TPO markers could help to improve the differential diagnosis of thyroid tumors. Differences in the galectin-3 and TPO expression between some oncocytic and non-oncocytic tumors support their separation in the latest WHO classification of thyroid tumors.

Thyroid FNA diagnostics in a real-life setting: Experiences of the implementation of the Bethesda system in Finland.

INTRODUCTION: The Bethesda system is widely accepted for thyroid FNA diagnostics, but has scarcely been analysed in relation to clinical background data. Our aim was to analyse the thyroid FNA diagnostic process in view of clinical data, and to assess the validity of the Bethesda system during the first year of implementation. METHODS: There were 415 thyroid FNAs taken from 363 patients during October 2011-September 2012 in the Pirkanmaa Hospital District, Finland. The median age of the patients was 59 years, and the female-to-male ratio 4:1. Clinical data were collected from patient registries, and thyroid FNA and histopathological data from the pathology registry. RESULTS: The Bethesda categories were represented as follows: 94 non-diagnostic cases (26%); 177 benign (49%); 32 atypia of undetermined significance/follicular lesion of undetermined significance (9%); 31 follicular neoplasm (9%); 20 suspicious for malignancy (5%); and nine malignant cases (2%). Only 23 (24%) of the non-diagnostic samples and 18 (56%) of the atypia of undetermined significance/follicular lesion of undetermined significance led to repeat FNA. Thyroid cancer was histopathologically diagnosed in 28 cases (8%). When the categories requiring surgical treatment were considered true positive findings, the sensitivity of the Bethesda system was 90%, and specificity was 70%. Interobserver accuracy was 86%. CONCLUSIONS: Already during the first year of implementation, the Bethesda system proved reliable in evaluating the risk of thyroid malignancy. Nevertheless, the clinical judgement of the indication of ultrasound/FNA and management according to the FNA findings need improvement. The relatively high proportion of non-diagnostic FNAs could be diminished by obtaining the samples by radiologists experienced in ultrasound-guided FNA techniques.

Synergistic Expression of Histone Deacetylase 9 and Matrix Metalloproteinase 12 in M4 Macrophages in Advanced Carotid Plaques.

OBJECTIVE/BACKGROUND: Expression patterns and association with cell specific gene expression signatures of the epigenetic regulator histone deacetylase 9 (HDAC9) and matrix metalloproteinase 12 (MMP12) in human plaque are not known. METHODS: This was a prospective cohort study. Genome wide expression analysis was performed in carotid, femoral, aortic plaques (n = 68) and left internal thoracic (LITA) controls (n = 28) and plaque histological severity assessed. Correlation and hierarchical cluster analysis was utilised. RESULTS: HDAC9 was associated with MMP12 expression in carotid plaques (r = .46, p = .012) and controls (r = -.44, p = .034). HDAC9 and MMP12 clustered with inflammatory macrophage markers but not with smooth muscle cell (SMC) rich markers. In plaques from all arterial sites, MMP12 but not HDAC9 showed positive correlation (p < .05) with M2 and M4 polarized macrophage markers, and negative correlation with SMC rich signatures. In the carotid plaques, all M4 macrophage markers associated with MMP12 and HDAC9. The negative association of MMP12 with SMC rich signatures was pronounced in the carotid plaques. Neither HDAC9 nor MMP12 associated consistently with plaque stabilisation or thrombosis related genes. Immunohistochemistry further supported the association between HDAC9 and MMP12 in atherosclerotic plaques. CONCLUSION: M4 macrophages are a possible source for HDAC9 and MMP12 expression in advanced human plaques.

[Molecular Aspects of Thyroid Tumors with Emphasis on MicroRNA and Their Clinical Implications]. / Molekulární aspekty nádoru stítné zlázy se zamerením na mikroRNA a jejich klinické souvislosti.

BACKGROUND: Central to neoplastic transformation and tumor progression is alteration of the signaling pathways that control cell proliferation and apoptosis. The key mechanisms for this neoplastic process are genetic changes (mutations of cancer-related genes) and recently identified epigenetic changes that involve DNA methylation, chromatin remodeling (which has a profound effect on the control of gene expression), and noncoding, regulatory RNA (notably, microRNA - miRNA). MiRNAs control expression of their target gene post-transcriptionally. These molecular factors have potential as diagnostic, prognostic, and predictive molecular markers. Epithelial tumors of the thyroid gland are a histogenetically, morphologically, and pathobiologically heterogeneous group of neoplasms and require new, molecular approaches in clinical practice. AIM: This review aims to present contemporary scientific knowledge of this molecular (genetic and epigenetic) field of sporadic thyroid tumors of follicular cell origin and their potential clinical implications. The fundamental mutations (BRAFV600E, RET/PTC, RAS, and PAX8-PPARG) in selected tumor types are described comprehensively. Special attention is paid to miRNAs, including their biogenesis, function, and expression profiles in the most common thyroid tumors - follicular adenoma, follicular carcinoma, and papillary carcinoma. CONCLUSION: Thyroid cancer medicine has recently entered a new, molecular era. Comprehensive knowledge of all molecular aspects may improve diagnostics and management of thyroid neoplasms through the introduction of novel, progressive treatment strategies for this cancer. Further research on signaling pathway-related targets, standardization of methods, and evaluation of results are required.Key words: thyroid tumors - cancerogenesis - genetics - epigenetics - microRNA The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 19. 10. 2016Accepted: 2. 11. 2016.

[Lymphatic system: morphology and pathology update]. / Lymfatický systém: novinky v morfologii a patologii.

The lymphatic system is crucial for the maintenance of tissue fluid balance, immune surveillance, and fatty acids absorption in the intestine. The lymphatic vessels are also involved in the pathogenesis of tumor metastasis, lymphedema, and various inflammatory processes. Recently, several markers specific for lymphatic endothelium were found. Progress in the field of lymphatic growth factors and their receptors, and molecular lymphatic biology has helped to understand better the lymphatic vasculature. This review summarizes the updates on lymphatic system research and possible applications in routine pathological diagnostics.

Amyloid in the cardiovascular system: a review.

The cardiovascular system is a common target of amyloidosis. This review presents the current clinical and diagnostic approach to amyloidosis, with the emphasis on cardiovascular involvement. It summarises recent nomenclature, classification, and pathogenesis of amyloidosis. In addition, non-invasive possibilities are discussed, together with endomyocardial biopsies in the diagnosis of cardiac amyloidosis. Finally, recent advances in treatment and prognostic implications are presented.

TPS, thymidine kinase, VEGF and endostatin in cytosol of thyroid tissue samples.

The aim of the study was to determine whether VEGF, TPS, TK or Endostatin determination in tissue cytosol may have some additional value in distinguishing among different types of thyroid lesions. These markers were chosen as representatives of the 2 main pathways (angiogenesis and proliferation) involved in thyroid diseases. VEGF is the most potent angiogenic promoter and Endostatin plays an opposing role. Thymidine kinase (TK) is a marker of DNA synthesis and TPS, cytokeratin 18 fragments, is a marker of the rate of proliferation. We determined qualitatively all four markers in tissue extracts: cytosol from 157 tissue specimens (93 goitre, 12 Hashimoto's thyroiditis, 39 adenomas and 13 carcinomas). In 6 cases we were able to compare both normal and pathological tissue samples from a single patient. Statistically significant differences were found in the measured markers, but outliers were present in all groups. This fact does not permit their use in differential diagnosis. The highest levels of all markers were reached in adenomas, being higher than in carcinomas, probably explained by the higher overall metabolic rate in adenomas.

[Pulmonary veins and atrial fibrillation: a pathological study of 100 hearts]. / Plicní zíly a fibrilace síní - studie 100 srdcí.

Pathogenesis of atrial fibrillation (AF), the most common sustained heart arrhythmia, is not yet fully elucidated. Recent electrophysiological studies have shown that in most patients with AF the arrhythmia is triggered by ectopic beats originating from extensions of left atrial myocardium over the pulmonary veins (PVs), so called myocardial sleeves (MSPV). A total of 100 hearts (393 PVs) obtained at autopsy were prospectively studied - 50 from patients with chronic AF (average age 76.9 +/- 7.3 yrs.) and a control group of 50 with a sinus rhythm (aver. age 71.7 +/- 9.5 yrs.). This is a largest study published on this topic so far. It appeared that MSPV frequently harbour pathological lesions, particularly senile atrial amyloid, and scarring. These two pathological changes were evaluated semiquantitatively on a grade 0-3 basis in individual PVs, comparing the results in the AF vs. the control group. Amyloidosis of MSPV was found in 68 % of all hearts and in 55 % of all sleeves. The deposits were most marked in the right superior PV. Amyloidosis was more frequent and more severe in MSPV of patients with AF (58.5 %; average grade 0.89) than of those without AF (51.7 %; aver. grade 0.76); the differences, however, lack statistical significance. Scarring of MSPV was present in all 349 sleeves, more markedly in the left inferior, left superior, and right superior PVs. It was significantly more severe in patients with AF compared to those without the arrhythmia. By an injection metod, we have shown that MSPV are supplied by coronary arteries. However, the degree of scarring of the sleeves did not correlate with the degree of coronary atherosclerosis. We suggest that genesis of the scarring is not postnecrotic but degenerative, due to diffuse hypoxia of the sleeve myocardium. To conclude, amyloidosis and particularly scarring of MSPV appear generally in the elderly population as an arrhythmogenic substrate for AF.

Diagnostic role of markers dipeptidyl peptidase IV and thyroid peroxidase in thyroid tumors.

BACKGROUND: In seeking to improve the differential diagnosis between malignant and benign thyroid tumors of follicular cell origin, we assessed the expression of dipeptidyl peptidase IV (DPP IV) and thyroid peroxidase (TPO). DPP IV is a membrane peptidase expressed in many human tissues, excluding the normal thyroid gland. However, aberrant expression has been described in thyroid carcinomas. TPO is an essential enzyme in the biosynthesis of thyroid hormones with various types of expression in pathological thyroid lesions. MATERIALS AND METHODS: A total of 151 thyroid glands were examined: 24 malignant tumors, 29 benign tumors, 98 benign lesions and 5 normal glands. DPP IV expression was analyzed by a histochemical technique in both frozen sections and imprint/aspirate smears. TPO was assessed immunohistochemically in paraffin-embedded specimens. RESULTS: DPP IV sensitivity in frozen section was 56% and its specificity was 99%, in both cases with a 50% threshold. In cytology, the sensitivity was 68% and the specificity was 98% using the 50% threshold. TPO sensitivity and specificity was 64% and 99%, respectively. The sensitivity and specificity of both markers was 92% and 94%, respectively. CONCLUSION: We recommend adding DPP IV and TPO to the list of diagnostic tumor markers for malignant thyroid tumors of follicular cell origin.

Composite tumor consisting of dermatofibrosarcoma protuberans and giant cell fibroblastoma associated with intratumoral endometriosis. Report of a case.

We present a unique case of composite skin tumor of the vulva consisting of dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) with an intratumoral focus of endometriosis. A 31-year-old female with a 10-year-history of a recurring subcutaneous tumor in the vulvar area underwent excision of the seventh recurrence of the tumor. Microscopic examination revealed a composite fibrohistiocytic tumor consisting of DFSP and GCF. Additionally, a focus of endometriosis within the tumor tissue was found. Malignant transformation of extragonadal endometriosis has already been described; we present, however, the occurrence of a focus of endometriosis within the tissue of a hormonally independent soft tissue tumor. There is a possible link to the occurrence of cutaneous endometriosis at previous surgery sites and in the scars. The presence of endometriosis within the soft tissue tumor represents, to the best of our knowledge, a previously undescribed collision phenomenon.