Education and training in cytology in Europe.

Education and training in cytology in Europe is hampered by the fact that there is no homogenous programme across Europe. This can be observed for (Cyto)Pathologists and Cytotechnologists. However, lack of workforce and lack of a pan-European Cytology diploma are decreasing motivation among junior staff to dedicate their professional interests to cytology. Cytology and histology are complementary approaches for the diagnosis or exclusion of disease in patients and there are many individual efforts of National Societies to maintain competencies in cytology by workshops, seminars, tutorials and congresses. Furthermore, professional organizations such as the European Federation of Cytology Societies (EFCS), the European Society of Pathology (ESP) and Union of European Medical Specialists (UEMS) - Section Pathology are working together in order to develop a pan-European Cytology diploma. The EFCS is part supported by EU funding in this endeavour. Activities are ongoing in the fields of training (Eurocytology) and examination (QUATE Aptitude Test - Quality Assurance, Training and Examination) or both (Cy-Test). Modern techniques such as Webatlas with teaching modules in cytology and Tele(cyto)pathology are more and more integrated in daily teaching activities resulting in standardization of cytology in Europe.

Training and practice of cytotechnologists: a discussion forum focused on Europe.

OBJECTIVES: To discuss the role and training of cytotechnologists (CTs) in Europe, to identify areas of good practice and to provide an informed opinion to those providing guidelines for training and practice in Europe. METHODS: All members of the Editorial Advisory Board of Cytopathology were invited to take part in a 'discussion forum' for which six topics were circulated in advance concerning the roles of CTs with regard to: (1) pre-screening slides; (2) 'signing out' reports; (3) carrying out ancillary techniques; (4) supervising laboratory staff; (5) taking part in rapid on-site evaluation (ROSE) of fine needle aspirates (FNAs); and (6) whether CTs were trained specifically in cytopathology or in general histopathology. Notes of the meeting were circulated by email and a final report was agreed by 22 participants from 17 predominantly European countries. RESULTS: Training for CTs throughout Europe was variable, especially for non-gynaecological cytology, which was inconsistent with the range of activities required. The participants recommended graduate entry, preliminary training in general laboratory technology, and subsequent training to take account of the probability and, in some centres, the reality of primary cervical cancer screening changing from cytology to human papillomavirus (HPV) testing. They further recommended that CTs should perform HPV tests and take part in ROSE for FNAs, and they supported the European Federation of Cytology Societies developing guidelines for training and practice. CONCLUSION: With CT training added to a university-based education in laboratory or biomedical science, a career in cytotechnology should be an attractive option involving a diverse range of laboratory and clinically based activities.

[Diagnosis of pulmonary tuberculosis using Ziehl-Neelsen stain and polymerase chain reaction]. / Diagnostik der Lungentuberkulose mit Ziehl-Neelsen-Färbung und Polymerasekettenreaktion.

BACKGROUND: Definitive diagnosis of unclear pulmonary lesions is mainly based on morphological methods. In addition to a neoplasm, inflammatory reactions, in particular tuberculosis (TB), have to be considered in most cases. Therefore, the aim of this work was to determine whether established methods used in general pathology can be efficiently used with cytological material. MATERIALS AND METHODS: An established polymerase chain reaction (PCR) protocol for the detection of Mycobacterium tuberculosis complex (Mtc) DNA in fixed specimens was conducted on fixed material available as an assay for liquid-based cytology (LBC). CytoLyt®-fixed material of 45 patients with clinically suspected TB or other mycobacteriosis were selected and were initially tested cytologically. In cases of absent tumor cells, PCR for detection of Mtc DNA and Ziehl-Neelsen stain (ZN) were performed. RESULTS: In 9 patients (20 %), Mtc DNA was found by PCR. The following methods were used to obtain material: catheter biopsy (5), needle biopsy (2), transbronchial needle aspiration (1), and bronchoalveolar lavage (1). Cytologically an inflammatory reaction was observed in all cases. In 2 patients, a history of TB, in 2 further cases either silicosis or a posttransplant situation was known. In cases with a positive PCR, 7 patients (78 %) were positive in ZN and 3 patients (33.3 %) in TB culture (15.5 % vs. 6.7 % of the total cohort); however, the material used for investigation was not always from identical sources, respectively. In 36 out of 45 patients, both PCR and ZN were negative for the detection of Mtc DNA. CONCLUSION: The material intended for LBC can be used for detection of TB with ZN and Mtc PCR.

The UEMS section/board of pathology, chapter 6: requirement for recognition of postgraduate training in pathology: a presentation of the paris document.

After more than five years discussion the UEMS Section/Board of Pathology agreed a specification of requirements for recognition of post-graduate training in pathology, which is the key to the future of our discipline. The document published here, subject to ratification by UEMS Council, was voted on and accepted by the Pathology Board at the UEMS Paris meeting of 9 June 2012. Cytopathology is regarded as integral part of pathology: in general, training in pathology takes five years and maintains a common trunk of four (minimum three) years where surgical pathology, autopsy pathology and basic knowledge of neuropathology, dermatopathology and cytopathology are adequately trained and assessed. Training in so-called 'areas of interests' covers the remaining 12-24 months. Certificates of 'advanced level of competence' remain within the authority of national boards. As senior members of its Executive Board, we believe that the European Federation of Cytology Societies (EFCS) should take responsibility for establishing 1) standards in the quality of cytopathology training, 2) training guidelines and qualification for advanced levels of competence in cytopathology, 3) manpower planning, 4) tutorials for pathologists and cytotechnologists and 4) standards of cytotechnologist training.

[Bethesda classification of fine needle punctures of the thyroid. Much ado about nothing really new?]. / Bethesda-Klassifikation der Feinnadelpunktion der Schilddrüse. Viel Lärm um wenig Neues?

The Bethesda system for reporting thyroid cytopathology was published in 2008 (Baloch et al. 2008, Cytojournal 5:6; Baloch et al. 2008, Diagn Cytopathol 36:425-437) offering a classification system which is closely related to clinical data. The aim was to ensure adequate terminology without risk of errors in understanding, to advise clinicians concerning therapeutic options in relationship to cytological diagnoses as well as to facilitate the comparison of cytology data at national and international levels. However, mainly due to specific US American (both medical and legal) demands, this classification system is not yet fully appreciated in most European countries. The reasons are various: (a) Criteria for representative material are much more restrictive than those commonly used and in Germany a higher number of (unnecessary) repunctures would be the consequence. (b) It remains doubtful whether the introduction of a new and rather heterogeneous category of "atypia of undetermined significance or follicular lesion of undetermined significance" would contribute to a substantial decrease of findings classified as "follicular neoplasia". Furthermore it is unlikely that clinicians would be willing to accept the recommended conservative approach with repuncture if a new diagnostic category is associated with a calculated risk of malignancy in 5-15% cases. (c) Until now an integration of new developments in molecular markers into the Bethesda system is missing. Thus, for experienced cytologists the Bethesda system for reporting thyroid cytopathology offers very limited benefits in comparison to the currently used, established and highly accepted classification systems. However, a positive argument remains the fact that an internationally accepted classification system may improve the comparability of the results of national and international studies on thyroid findings.

The placenta and gestational diabetes mellitus.

By its location between maternal and fetal bloodstreams the human placenta not only handles the materno-fetal transport of nutrients and gases, but may also be exposed to intrauterine conditions adversely affecting placental and fetal development. Such adverse conditions exist in pregnancies complicated by gestational diabetes mellitus (GDM), and have been associated with alterations in placental anatomy and physiology. These alterations are mainly based on changes on the micro-anatomical and/or even molecular level including aberrant villous vascularization, a disbalance of vasoactive molecules, and enhanced oxidative stress. The consequence thereof may be impaired fetal oxygenation and changes in transplacental nutrient supply. Although transplacental glucose flux is flow limited and independent of glucose transporter availability, transport of essential and nonessential amino acids and expression of genes involved in lipid transport and metabolism are significantly affected by GDM.

The Bethesda terminology for reporting thyroid cytopathology: from theory to practice in Europe.

OBJECTIVES: A 2007 conference held at the National Cancer Institute, Bethesda, Md., USA, proposed a new terminology for classifying the results of thyroid fine-needle aspiration (FNA) - The Bethesda System for Reporting Thyroid Cytology (TBSRTC). The need to standardize thyroid FNA terminology was emphasized during the 35th European Congress of Cytology in 2009. An interobserver review study to assess the new terminology for analyzing the results of thyroid FNA was organized by the scientific committee of the European Federation of Cytology Societies. STUDY DESIGN: Four experts in thyroid FNA examined and classified 116 FNAs according to the 6 levels of TBSRTC which are: nondiagnostic (ND); benign; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), with those of Hürthle cell type reported as follicular neoplasm, Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type (FNHCT/SFNHCT); suspicious (SUS), and malignant. RESULTS: The total consensus was 62.1%; the cytopathologists disagreed on 44 cases, including 8 cases of AUS/FLUS and 18 of FN/SFN; 59% of the cases had no consensus. They agreed on 73 and 80% of the cases classified as benign and malignant, respectively, and on 58.3% of the SUS cases. The percentage of no consensus for each expert was between 32 and 39%. CONCLUSIONS: Disagreement regarding the use of TBSRTC terminology for classifying the results of thyroid FNA mainly occurred in the most-often criticized categories of AUS/FLUS and FN/SFN.

Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009.

A European Federation of Cytology Societies (EFCS) working party of 28 members from 14 European countries met at the European Congress of Cytology in Lisbon in September 2009, with two observers from the USA, to discuss the need for standardising thyroid FNA nomenclature in the light of the National Institute of Cancer (NCI) recommendations resulting from the State of the Science conference in Bethesda in 2007. The data were obtained through two questionnaires sent by email and a transcript of the live discussion at the congress, which is presented in full. The surveys and discussion showed that there were currently no national terminologies for reporting thyroid FNA in the different European countries except in Italy and the UK. Personal, 'local', surgical pathology and descriptive terminologies were in use. All but one of the working party members agreed that thyroid FNA reporting should be standardised. Whilst almost a third would adopt the NCI Bethesda terminology, which offers the advantages of a 'risk of cancer' correlation and is linked to clinical recommendations, more than half favoured a translation of local terminology as the first step towards a unified nomenclature, as has been done recently in the UK. There was some disagreement about the use of: a) the six-tiered as opposed to four or five-tiered systems, b) the use of an indeterminate category and c) the 'follicular neoplasm' category, which was felt by some participants not to be different from the 'suspicious of malignancy' category. The conclusions will be passed to the different national societies of cytology for discussion, who will be asked to map their local terminologies to the Bethesda classification, observe its acceptance by clinicians and audit its correlation with outcome.

Esophageal sarcoidosis presenting as pseudodiverticulum.

Sarcoidosis is a multisystem granulomatous disorder that may involve many organs. However, the involvement of the gastrointestinal tract is very rare. This report describes an unusual case of esophageal sarcoidosis presenting as a pseudodiverticulum and reviews the world literature. Our case is also characterized by unusual progression of the esophageal involvement despite stable disease in other organs involved. Myotomy improved the pharyngoesophageal stenosis with no recurrence to date. Physicians should be aware of this rare manifestation, which should be suspected in any sarcoidosis patient complaining about dysphagia.

The future of cytopathology in Europe. Will the wider use of HPV testing have an impact on the provision of cervical screening?

The emphasis of the EFCS Congress held in Venice in October 2006 was on the future of Cytopathology in relation to events in Europe. Much of the discussion centred on the role of human papilloma virus testing and its impact on the provision of cervical screening. The following is a transcript of the discussion that took place at the Advisory Board Meeting for the journal Cytopathology, with some additional written comments received prior to the meeting. A brief summary has been provided as a conclusion by Dr A. Herbert.

[Bronchoalveolar lavage]. / Bronchoalveoläre Lavage.

Bronchoalveolar lavage (BAL) has become an established method for the diagnosis of infectious and interstitial lung diseases. Using a bronchoscope material from the peripheral airways and alveolar spaces can be obtained. When standard protocols are followed the procedure is generally well tolerated and in combination with clinical tests allows a reliable diagnosis in many cases. Certain clinical entities, e.g. alveolar proteinosis and Langerhans cell histiocytosis can be diagnosed by BAL alone without resorting to invasive diagnostic tests. In other diseases, BAL allows to narrow the range of the differential diagnosis. However, biopsies can often still not be avoided completely. A combination of both methods together with the clinical findings represents a powerful tool for diagnosis and research into the pathologic alterations in inflammatory and fibroising lung diseases.

Primary invasive aspergillosis of the digestive tract: report of two cases and review of the literature.

BACKGROUND: Disseminated aspergillosis is thought to occur as a result of vascular invasion from the lungs with subsequent bloodstream dissemination, and portals of entry other than sinuses and/or the respiratory tract remain speculative. METHODS: We report two cases of primary aspergillosis in the digestive tract and present a detailed review of eight of the 23 previously-published cases for which detailed data are available. RESULTS AND CONCLUSION: These ten cases presented with symptoms suggestive of typhlitis, with further peritonitis requiring laparotomy and small bowel segmental resection. All cases were characterized by the absence of pulmonary disease at the time of histologically-confirmed gastrointestinal involvement with vascular invasion by branched Aspergillus hyphae. These cases suggest that the digestive tract may represent a portal of entry for Aspergillus species in immunocompromised patients.

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

Time and tidal volume-dependent ventilator-induced lung injury in healthy rats.

BACKGROUND AND OBJECTIVE: We evaluated the effect of duration of mechanical ventilation with different tidal volumes (VT) on ventilator-induced lung injury in healthy rats. METHODS: Anaesthetized rats were ventilated with VT between 9 and 45 mL kg[-1] for 1 or 7 h with a positive end-expiratory pressure of 2.5 cmH2O. RESULTS: After 1 h, rats ventilated even with the highest applied VT (36 and 45 mL kg[minus sign]1, resulting in average peak airway pressures of 30 +/-3 and 37 +/- 4 cmH2O), had no detectable alterations in dynamic or static lung mechanics, gas exchange or pulmonary permeability, but a moderate degree of lung inflammation (neutrophil accumulation in broncho-alveolar lavage) observed in all groups. In contrast, after 3 h of ventilation, rats ventilated with the highest VT (36 and 45 mL kg[minus sign]1) died from progressive circulatory failure and high-permeability pulmonary oedema, manifested by hypoxaemia, an increased alveolar-arterial protein concentration ratio and a reduced static lung compliance (mortality rate at 7 h, 62.5% and 100%). Animals with lower VT all survived and presented no changes in the measured variables. CONCLUSION: These results in normal rats demonstrate the preponderant effect of the duration (>3 h) of 'aggressive' ventilation and the cut-off value of the level of VT applied (>27 mL kg[minus sign]1).

[Thyroid tumors]. / Tumoren der Schilddrüse.

The vast majority of thyroid tumours are epithelial. In contrast to thyroid adenoma, which is a common tumour, thyroid carcinomas make up only 1% of all human malignancies. Routine pathology is regularly confronted with a differential diagnosis involving thyroid adenoma and carcinoma, as well as particular variants of these tumours. This paper deals with the standardised gross and histological examination, as well as the impact of immunohistochemistry and intraoperative frozen sections on thyroid pathology.