Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of neck lymphadenopathy for the diagnosis of recurrent lymphoma.

OBJECTIVE: In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. DESIGN: Retrospective cohort study with stepwise forward logistic regression analysis of results. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. METHODS: On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. RESULTS: Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). CONCLUSION: This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded.

Internal Transport Barrier Broadening through Subdominant Mode Stabilization in Reversed Field Pinch Plasmas.

The reversed field pinch (RFP) device RFX-mod features strong internal transport barriers when the plasma accesses states with a single dominant helicity. Such transport barriers enclose a hot helical region with high confinement whose amplitude may vary from a tiny one to an amplitude encompassing an appreciable fraction of the available volume. The transition from narrow to wide thermal structures has been ascribed so far to the transport reduction that occurs when the dominant mode separatrix, which is a preferred location for the onset of stochastic field lines, disappears. In this Letter we show instead that the contribution from the separatrix disappearance, by itself, is marginal and the main role is instead played by the progressive stabilization of secondary modes. The position and the width of the stochastic boundary encompassing the thermal structures have been estimated by applying the concept of a 3D quasiseparatrix layer, developed in solar physics to treat reconnection phenomena without true separatrices and novel to toroidal laboratory plasmas. Considering the favorable scaling of secondary modes with the Lundquist number, these results open promising scenarios for RFP plasmas at temperatures higher than the presently achieved ones, where lower secondary modes and, consequently, larger thermal structures are expected. Furthermore, this first application of the quasiseparatrix layer to a toroidal plasma indicates that such a concept is ubiquitous in magnetic reconnection, independent of the system geometry under investigation.

An analysis of different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia: a single-centre experience.

CONTEXT: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of Cushing's syndrome (CS). A variety of in vivo tests to identify aberrant receptor expression have been proposed to guide medical treatment. Unilateral adrenalectomy (UA) may be effective in selected patients, but little is known about recurrence during follow-up. OBJECTIVE: To describe a series of patients with BMAH and CS treated by different approaches, with a particular focus on the benefit of UA. DESIGN AND PATIENTS: We retrospectively assessed 16 patients with BMAH and CS (11 females, five males), analysing the in vivo cortisol response to different provocative tests. Twelve of the 16 patients underwent UA and were monitored over the long term. RESULTS: Based on in vivo test results, octreotide LAR or propranolol was administered in one case of food-dependent CS and two patients with a positive postural test. A significant improvement in biochemical values was seen in all patients but with limited clinical response. UA was performed in 12 patients, producing long-term remission in three (106 ± 28 months; range: 80-135), recurrence in eight (after 54 ± 56 months; range 12-180) and persistence in one other. Four patients subsequently underwent contralateral adrenalectomy for overt CS, one received ketoconazole, and four other patients remain under observation for subclinical CS. CONCLUSIONS: Medical treatment based on cortisol response to provocative tests had a limited role in our patients, whereas UA was useful in some of them. Although recurrence is likely, the timing of onset is variable and close follow-up is mandatory to identify it.

Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication.

OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

Experimental observation of microtearing modes in a toroidal fusion plasma.

Experimental evidences of short wavelength electromagnetic modes are found in the reversed-field-pinch configuration device RFX-mod by means of in-vessel magnetic probes. The modes are revealed during the helical states of the plasma. Their amplitude is well correlated to the electron temperature gradient strength in the core. On the basis of linear gyrokinetic calculations we interpret these instabilities as microtearing modes.

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.

Fine needle aspiration of non-small cell lung cancer: current state and future perspective.

AThe emerging treatment revolution determined by the advent of new targeted therapies requires accurate tumour subtyping as a mandatory step in the clinical workup of patients with non-small cell lung carcinoma (NSCLC). As a result of advanced and inoperable disease or poor performance status, in many patients, minimally invasive procedures must be employed to obtain diagnostic material. Fine needle aspiration (FNA) is a valid and widely employed alternative to either tru-cut or open-sky biopsy. Indeed, cytological specimens are suitable for techniques such as immunocytochemistry, mutation and microRNA analysis, and may present advantages over small biopsies especially if cell blocks are prepared and attention is paid to cytomorphology and pre-analytic management of specimens at the time they are collected. These will allow the adequate stratification of patients into different diagnostic and prognostic classes.

Vanishing magnetic shear and electron transport barriers in the RFX-mod reversed field pinch.

We define the safety factor q for the helical plasmas of the experiment RFX-mod by accounting for the actual three-dimensional nature of the magnetic flux surfaces. Such a profile is not monotonic but goes through a maximum located in the vicinity of the electron transport barriers measured by a high resolution Thomson scattering diagnostic. Helical states with a single axis obtained in viscoresistive magnetohydrodynamic numerical simulations exhibit similar nonmonotonic q profiles provided that the final states are preceded by a magnetic island phase, like in the experiment.

Somatostatin receptor expression in adrenocortical tumors and effect of a new somatostatin analog SOM230 on hormone secretion in vitro and in ex vivo adrenal cells.

BACKGROUND: Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion, cell proliferation, and apoptosis by 5 somatostatin receptors (SSTR1-5). The inhibitory effects of somatostatin on tumor growth may be the result of its suppressing the synthesis and/or secretion of growth factors and growth-promoting hormones. AIM: Very little information is available on the effect of somatostatin analogs on adrenal tumors, so we examined SSTR expression in adrenocortical tumors and studied the effect of a somatostatin analog (SOM230) on hormone secretion and cell viability in adrenal cells. MATERIAL/SUBJECTS AND METHODS: SSTR expression was analyzed by real-time PCR in 13 adrenocortical carcinomas (ACC), 24 aldosterone-producing adenomas (APA), 11 cortisol-producing adenomas (CPA), and 7 normal adrenals (NA), and verified by immunohistochemistry (IHC) in 14 samples. The effect of SOM230 on cortisol or aldosterone secretion in H295R and primary cell cultures was determined by radioimmunoassay, and its effect on viability in H295R and SW13 using the MTT test. RESULTS: SSTR1 and SSTR2 mRNA was expressed in 100% of adrenal tumors. Compared to NA, ACC revealed an increase in almost all SSTR, while only some APA over-expressed SSTR3 and SSTR1. CPA expressed SSTR similar to NA. IHC confirmed the mRNA expression data. At nanomolar concentrations, SOM230 inhibited hormone secretion in primary adrenal cultures and H295R cells, but had no evident effect on cell viability. CONCLUSIONS: The evidence of SSTR over-expression (particularly in ACC) and of hormone secretion being inhibited by SOM230 suggests a potential therapeutic role for this broad-spectrum somatostatin analog in adrenal tumors.

Role and accuracy of rapid on-site evaluation of CT-guided fine needle aspiration cytology of lung nodules.

OBJECTIVE: To prospectively investigate the role of trans-thoracic fine needle aspiration cytology (FNA) and the value of rapid on-site evaluation (ROSE) in the clinical management of patients with pulmonary nodules/masses. Computed tomography (CT)-guided FNA is commonly employed for the diagnosis of lung lesions although its position in the diagnostic work-up is still a matter of debate. METHODS: We reviewed 311 patients (211 males and 100 females, mean age 69.5 years) admitted to the University of Padova from 2004 to 2008, correlating the results of cytology with the available histological findings obtained from biopsies, surgery or autopsy. RESULTS: Smears were adequate in 305 cases (98%) and inadequate in six (2%); a diagnosis of malignancy was achieved in 263 cases (86.2%); 39 cases (12.8%) were classified as non-malignant; and three cases (1%) were classified as suspect for malignancy. When correlated with histology, FNA with ROSE discriminated malignant versus non-malignant lesions (Cohen's kappa 0.78), with three false negatives (sensitivity 96.3%, specificity 100%). Moreover, a satisfactory overall agreement of 71.4% was achieved in differentiating the cancer histological types. Pneumothorax occurred in 13 cases, haemoptysis in four, and chest pain in three. A single aspiration was sufficient in 79.6% of patients; two aspirations were needed in 17.4% and three in 3%. The low complication rate was related to the limited number of aspirations needed due to ROSE. CONCLUSIONS: FNA with ROSE is a safe and useful tool in the diagnostic work-up of lung cancer patients, with no contraindications to its use as the first diagnostic procedure for all patients with peripheral lung lesions. FNA with ROSE should be reconsidered in the guidelines for diagnosing and managing lung cancer.

On combining the beam path of similar wavelength lasers for dual-laser Thomson scattering.

A novel method for the path combination of two lasers with very similar wavelengths has been implemented to enable the evaluation of a dual-laser calibration Thomson scattering (TS) technique. The first experimental test of this TS technique has been performed in a RFX-mod plasma device, where, due to experimental constraints, the combination of a Nd:YAG (λ = 1064 nm) and a Nd:YLF (λ = 1053 nm) laser system was the only viable choice available. The method requires that the beam path of both lasers be combined into a single path with the same polarization. This presents a unique challenge due to the small difference between the two laser wavelengths. In this paper, we describe two methods for beam combination: first via a prism, eventually dismissed as unpractical, and second via a polarizing beam splitter in reverse with a dual-wavelength waveplate. We detail the optical setup, waveplate design, and successful implementation of this second method.

Design of JT-60SA core Thomson scattering diagnostic system.

An incoherent Thomson scattering diagnostic will be installed in the JT-60SA tokamak to measure electron temperature and electron density profiles. The target radial spatial resolution is 25 mm with 46 spatial channels. The accuracy in electron temperature and density is a few percent at ne = 7.5 × 1019 m-3, which is the expected value in the plasma core. This paper presents the designs of collection optics, fibers with their alignment system, and polychromators. The collection optics overcomes unique issues for superconducting fusion devices, i.e., limited design space, high-temperature measurements, and harsh radiation condition. When in several years the more performing plasma will generate intense nuclear radiation, the lens materials of the optics can be replaced by radiation resistant glasses without major changes in the lens holder. It will prevent transmission degradation and keep stable measurement accuracy.

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.

CRISP: A compact RF ion source prototype for emittance scanner testing.

A movable Allison type emittance scanner is being developed to characterize the phase-space distribution of the beamlets of spectral phase interferometry for direct electric-field reconstruction, the prototype RF negative ion source of the ITER heating neutral beam injector. To test the electronics and verify the capability of the device to resolve nearby beamlets, a compact RF ion source prototype has been set up, capable of accelerating 1 mA of helium ions up to a voltage of 2 kV. A commercial 100 W RF generator creates a plasma inside a Pyrex tube, with a density between 1015 and 1016 m-3 and an electron temperature up to 15 eV. Three multi-aperture grids in accel-decel configuration extract and accelerate the ions, which are measured with a Faraday cup. We present in this paper the characterization of the ion source and its first operation, showing that it is suitable for the commissioning of the Allison scanner.

Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer.

Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22-0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer.

The role of breast FNAC in diagnosis and clinical management: a survey of current practice.

Most participating countries have now adopted a triple assessment approach, i.e. clinical,imaging and pathology, to breast diagnosis, with FNAC as the first-line pathological investigation in both screening and symptomatic populations, with the exception of microcalcifications. Pathologists specialized in cytopathology are best qualified to collect and interpret FNAC samples, but this is not always possible or practical. Radiologists involved in breast imaging should ensure that they have the necessary skills to carry out FNAC under all forms of image guidance. Best results are achieved by a combination of both techniques, as shown in the image-guided FNAC in the presence of the cytopathologist. The majority of European countries use similar reporting systems for breast FNAC (C1-C5), in keeping with European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis, although some still prefer descriptive reporting only. When triple assessment is concordant, final treatment may proceed on the basis of FNAC, without a tissue biopsy. ER and PR assessment can be done safely on FNAC material. However, not all institutions may have expertise in doing this. HER-2 protein expression on direct cytological preparations is insufficiently reliable for clinical use, although its use for FISH is possible, if expertise is available. The majority of participants practise a degree of one-stop diagnosis with a cytopathologist present in the out-patient clinic. Formal recognition of the importance of the time spent outside the laboratory, both for cytopathologist and cytotechnologist, is necessary in order to ensure appropriate resourcing. The use of core biopsy (CB) has increased, although not always for evidence-based reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC findings and malignancies where radiology cannot guarantee stromal invasion.

Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

Risedronate prevents the loss of microarchitecture in glucocorticoid-induced osteoporosis in rats.

UNLABELLED: Osteoporosis is a severe complication of glucocorticoid treatment. Bisphosphonates are a powerful therapeutic option to prevent osteoporotic fractures. The aims of this study were: a) to determine bone alterations induced by therapy with glucocorticoids (GC); b) to establish the efficacy of risedronate (Ris) in the prevention of these effects. We studied 40 female Sprague-Dawley rats randomly divided into 4 groups of treatment, administered 3 times a week sc: 1. CONTROL: vehicle of methylprednisolone (GC) + vehicle of Ris; 2. Ris: Ris 5 mug/kg body weight vehicle of GC; 3. GC: GC 7 mg/kg + vehicle of Ris; 4. GC+Ris: GC 7 mg/kg, Ris 5 microg/kg. Animals were treated for 30 days and then were sacrificed. Densitometry was performed at baseline and at the end of the treatment. Right tibiae were removed for histomorphometric analyses. The GC group showed a 7% decrease in bone density vs controls (p<0.05), while the GC+Ris group was associated with a 3.5% increase in bone density vs controls (p<0.05). In the GC group, histomorphometric evaluations showed reduced bone volume (BV/TV) and thinning of trabeculae (Tb.Th) vs controls (BV/TV: 31+/-1 vs 35+/-1%, p<0.05; Tb.Th: 43+/-2 vs 50+/-3 microm, p<0.01; Ac.f: 1.8+/-0.2 vs 1.6+/-0.3 N/yr). The GC+Ris group had increased BV/TV and Tb.Th, and reduced Ac.f vs the GC group. Ris also maintained trabecular microarchitecture. At the histological level, glucocorticoid-induced osteoporosis was characterized by decreased bone volume, reduced osteoblastic activity, and deterioration of microarchitecture. Ris counteracted these effects both by prolonging osteoblast activity, and by maintaining bone microarchitecture.