[Pathology of parathyroid glands: Practical aspects for routine pathological investigations]. / Pathologie der Nebenschilddrüse : Praktisches für den pathologischen Alltag.

The diagnostic histopathology of parathyroid glands comprises mostly benign diseases associated with primary, secondary and rarely tertiary hyperparathyroidism. Parathyroid adenoma and hyperplasia are the most common diagnoses, whereas parathyroid carcinomas and atypical adenomas are exceptional causes of hyperparathyroidism, the latter being purely a diagnosis by exclusion. This article deals with the major histopathological criteria of the various diagnoses with special emphasis on the clinical manifestation.

Expression of the cAMP binding protein EPAC1 in thyroid tumors and growth regulation of thyroid cells and thyroid carcinoma cells by EPAC proteins.

The thyrotropin receptor-cAMP pathway is central in growth regulation of thyroid cells and thyroid tumorigenesis, and it regulates expression of thyroid specific genes. Recently, 2 new protein kinase A-independent cAMP effectors named EPAC1 and 2 were described that activate additional intracellular pathways. The aim of our study was to investigate the role of EPAC proteins in growth regulation of thyroid cells and thyroid carcinomas. EPAC1 expression was investigated immunohistochemically in tissues of various thyroid tumors. Utilizing MTT assay, the effect of EPAC stimulation on proliferation in thyroid carcinoma cells and in non-transformed rat FRTL5 cells was investigated. The activation of intracellular signaling pathways was examined by RAP pull-down assay and Western blots. EPAC1 expression was strong in non-oxyphilic follicular thyroid adenomas and carcinomas and in follicular papillary thyroid carcinomas. It was moderate in oxyphilic follicular tumors and classical and tall cell papillary carcinomas. In contrast, EPAC1 expression was low in poorly differentiated carcinomas and very low in anaplastic carcinomas. Thyroid carcinoma cell lines showed no or very weak EPAC1 expression and exhibited no growth-promoting effect after EPAC stimulation. Non-transformed rat FRTL5 cells were growth-stimulated by an EPAC-specific cAMP-analogue and showed EPAC-dependent activation of RAP, ERK, and p70S6 kinase. EPAC1 expression and cellular response to EPAC activation in rat FRTL5 cells reflect cellular responses to cAMP and TSH stimulation in non-transformed thyroid cells. In undifferentiated thyroid carcinomas, loss of EPAC1 expression may be in accordance with the loss of thyroid-specific functions and the loss of responsiveness of the TSHR-cAMP pathway.

Valproic acid downregulates NF-κB p50 activity and IRAK-1 in a progressive thyroid carcinoma cell line.

Histone deacetylase inhibitor (HDACI) valproic acid (VPA) is a promising drug, currently in clinical phase 2, for the therapy of advanced/poorly differentiated thyroid cancer. The nuclear factor-κB (NF-κB) pathway is constitutively activated in most tumors, including thyroid carcinomas; this often contributes to aggressive tumor growth and therapeutic resistance. We hypothesized that VPA could be useful to decrease NF-κB activity in human thyroid cancer cells. To clarify this, we treated the highly progressive thyroid cancer cell line BHT-101 with VPA (1.0-3.0 mM) for 48 h. Real-time polymerase chain reaction (PCR) and Western blot were used to measure expression of NF-κB-regulatory genes and proteins. NF-κB p50 activity was measured using an ELISA-based colorimetric transcription factor assay kit. We found that VPA significantly and dose-dependently impaired NF-κB activity reducing DNA binding activity of NF-κB p50 subunit by 30% at 1 mM, 40% at 1.5 mM, and 70% at 3 mM. Expression of interleukin-1 receptor-associated kinase-1 (IRAK-1) protein, an upstream mediator of NF-κB activation, was reduced by Ì´30% at 1 and 1.5 mM. Furthermore, 3 mM VPA treatment significantly decreased expressions of IRAK-1, phospho-IκBα and NF-κB p50 subunit protein by Ì´ 50%. This is the first study to demonstrate that VPA decreases NF-κB activity in a progressive thyroid cancer cell line. Intriguingly, 1mM of VPA, a clinically safe dose in the therapeutic range for epilepsy, was sufficient to reduce NF-κB activity. Thus, VPA may be a promising agent to overcome chemoresistance in cancer therapy and to improve therapeutic efficiency.

[MicroRNA profiles in fine needle biopsy of the thyroid]. / MicroRNA-Profile in der Feinnadelbiopsie der Schilddrüse.

MicroRNAs (miRNAs) are small (20-24 nucleotides), non-coding ribonucleid acids, which regulate gene expression on the post-transcriptional level, thus influencing physiological processes including cellular growth, differentiation and apoptosis. Several miRNAs (e. g. miRNAs 146b, 221 and 222) have been shown to be consistently over-expressed in papillary thyroid carcinoma. The present overview describes and discusses the utilization and problems of miRNA analysis in material from thyroid nodules obtained by fine needle biopsy. Particularly the analysis of defined sets of miRNAs should improve the diagnostic value of this procedure and contribute to a better management of patients with cold thyroid nodules.

Success rate of repeated fine needle aspiration biopsy of clinically suspicious thyroid nodules.

UNLABELLED: In this study we evaluated the success rate of double fine needle aspiration biopsy (FNAB) of clinically suspicious thyroid nodules in one session. AIM: The success rate of FNAB in clinical setting is quite low. There were several attempts made to improve the success rate of this method. It is anticipated that a double FNAB in one session would increase the success rate of FNAB. PATIENTS, METHODS: 176 consecutive patients (130 women, 46 men; mean age 56 years ± 11) with at least one clinically suspicious nodule were included in this study. Each individual nodule was biopsied twice (20G- and 21G-needle). In 33 patients, two suspicious nodules were biopsied, accounting for a total of 209 biopsied thyroid nodules. To evaluate the success rate the number of cell formations and the total number of cells in each cell formation were counted. RESULTS: The biopsy with the 20G needle provided in mean 40 cell cluster with a mean of 830 cells whereas the 21G needle provided in mean 41 cell cluster with a mean of 1010 cells. With the 20G needle the success rate was 73%, with the 21G needle 78% and the combination of the both biopsies provided a success rate of 87% (p = 0.01). Based on the number of cell formations and the total number of cells, the difference between the two needle sizes was not significant (p = 0.5 for cell formations and p = 0.9 for the total number of cells, respectively). CONCLUSION: A double FNAB of suspicious thyroid nodules in one session provides a higher success rate, and a 21G needle is sufficient enough.

[Hypofunctional thyroid tumor]. / Hypofunktioneller Schilddrüsenknoten.

Fine needle aspiration biopsy is considered to be the most valuable tool in the preoperative diagnosis of papillary thyroid carcinoma but the diagnostic criteria have to be strictly applied to avoid unnecessary surgery. In cases of cellular and encapsulated thyroid tumor serial sections from the tumor capsule should to be taken to exclude capsular and/or vascular invasion.

[Hyalinizing trabecular tumor of the thyroid. An overcautious designation of a benign thyroid tumour?]. / Der hyalinisierende trabekuläre Tumor der Schilddrüse. Eine übertrieben vorsichtige Bezeichnung für einen gutartigen Tumor?

Hyalinizing trabecular tumours of the thyroid represent a rare entity of follicular cell derived tumours and are characterized by a marked intratrabecular hyalinisation. These tumours share architectural similarities with medullary thyroid carcinomas and exhibit nuclear features such as nuclear pseudoinclusions resembling papillary thyroid carcinoma. However, the clinical behaviour remains unclear. On the basis of their inconspicuous appearance and absence of invasion or recurrence during follow-up, the tumour was initially classified as an adenoma. Subsequently, molecular findings such as the detection of RET / PTC rearrangements in some hyalinizing trabecular tumours favoured the designation as a variant of papillary thyroid carcinoma. However, miRNA profiling of hyalinizing trabecular tumours compared with benign thyroid lesions and papillary thyroid carcinoma failed to demonstrate the characteristic up-regulation found in papillary thyroid carcinoma. This article summarizes conventional diagnostic criteria with supplementary information regarding molecular pathogenesis of hyalinizing trabecular tumours of the thyroid.

[Optimization of the fine needle aspiration biopsy (FNAB) of thyroid nodules- automatic aspirator versus manual technique]. / Optimierung der Schilddrüsen-Feinnadelpunktion. Automatischer Mikroaspirator versus manuelle Technik.

OBJECTIVE: Optimization of a specially developed automatic microaspirator for fine-needle aspiration of suspicious thyroid nodules. PATIENTS, METHOD: In a preliminary test biopsy effectiveness was evaluated in 20 native resected thyroid glands in vitro with both a Cameco® gun and a specially designed microaspirator respectively. In addition in both techniques two different needles (21-G and 27-G) were used to evaluate the influence of these two cannula. Subsequently, 103 thyroid nodules were biopsied in vivo and compared the results with a preliminary series of the same physician. In the workup and evaluation of the cytology the ThinPrep® technology was used. RESULTS: In vitro the automatic microaspirator was superior to Cameco gun in both when using the 21-Gauge and the 27-Gauge needle. In terms of needle sizes a statistically significant difference at the 95% confidence level was evident for both comparisons in favor of 21-gauge needle. In vivo, 91% of punctures with the microaspirator were usable, while in the pre-series only 84% were usable (p>0.05). CONCLUSION: The automatic microaspirator is superior to the manual aspiration. Moreover, under sonographic control it is more convenient, to biopsy even very small nodules and lesiosn (down to 4 mm in diameter).