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A. Fassina, R. Cappellesso, F. Simonato, C. Lanza, A. Marzari and M. Fassan Fine needle aspiration of non-small cell lung cancer: current state and future perspective The 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. [ABSTRACT FROM AUTHOR]

Background Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. Aims To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. Methods A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Results Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H . pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant ( P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. Conclusions In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H . pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies. [ABSTRACT FROM AUTHOR]

A. Fassina, M. Corradin, D. Zardo, R. Cappellesso, F. Corbetti and M. Fassan 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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the diagnosis of siderotic nodules (SNs) in liver.

A letter to the editor is presented regarding the incidence of tumour cells seeding after fine needle aspiration cytology (FNAC) in liver oncology.

Due to the COVID-19 crisis, many scheduled medical and surgical activities have been suspended. This interruption to the healthcare system can negatively affect the diagnosis and management of melanoma. Neglecting melanoma throughout the outbreak may be associated with increased rates of mortality, morbidity, and healthcare expenses. We performed a retrospective review of all dermatological and surgical activity performed in our Melanoma Skin Unit between 23 February 2020 and 21 May 2020 and compared these data with those from the same period in 2019. During the lockdown period, we observed a decrease in dermatologic follow-up (DFU) (-30.2%) and in surgical follow-up (SFU) (-37%), and no modification of melanoma diagnosis (-3%). Finally, surgical excisions (SE) (+ 31.7%) increased, but sentinel lymph node biopsy (SLNB) (-29%) and lymph node dissections(LND) (-64%) decreased compared to the same period in 2019. Our experience supports the continuation of surgical and diagnostic procedures in patients with melanoma during the COVID-19 pandemic. Surgical and follow-up procedures for the diagnosis and treatment of melanoma should not be postponed considering that the pandemic is lasting for an extended period., (© 2021 Wiley Periodicals LLC.)

The cytomorphologic evaluation of serous cavity specimens can quickly determine the cause of an effusion as well as the presence or absence of a neoplastic process. Ancillary tests such as immunohistochemistry and fluorescence in situ hybridization are frequently used to help to definitively identify malignant cells, determine a site of origin, and distinguish between malignant and reactive mesothelial proliferations. In recent years, microRNAs (miRNAs) have been increasingly evaluated in cytologic specimens, including those from serous cavities. The examination of miRNA is attractive because of the stability of miRNA in such specimens and data suggesting that miRNA can provide prognostic and therapeutic information in addition to its role in diagnosis. Furthermore, miRNAs exist within extracellular exosomes, and this allows for their analysis in specimens that contain only rare malignant cells, degenerated cells, or obscuring components. This review discusses the technical aspects of specimen processing for miRNA analysis, recent studies of miRNA expression in malignant serous cavity specimens, and the potential importance of miRNA expression analysis for serous cavity specimens in the near future., (© 2019 American Cancer Society.)

Background: Malignant pleural mesothelioma is a rare tumor with a dismal prognosis, usually presenting with recurrent effusions. However, the majority of malignant pleural effusions are due to lung adenocarcinoma (AdC). The distinction between these tumors has considerable therapeutic and medicolegal implications and can be very challenging both histologically and cytologically. Appropriate immunohistochemistry (IHC) is required to support the diagnosis. MicroRNA (miRNA) expression analysis could be a viable diagnostic tool for distinguishing between these tumors. The purpose of the current study was to assess the reliability of miRNAs as diagnostic markers to differentiate epithelioid malignant mesothelioma (MM) from lung AdC., Methods: Bioinformatic analysis of publicly searchable data sets regarding miRNA expression profiling was performed to select the most significant differentially expressed miRNAs. These were analyzed by quantitative polymerase chain reaction on histologic (41 MM cases and 40 lung AdC cases) and cytological (26 MM cases and 27 lung AdC cases) specimens and the diagnostic performances were assessed., Results: miR-130a, miR-193a, miR-675, miR-141, miR-205, and miR-375 were found to be the best distinguishing markers. Of these, only miR-130a was significantly overexpressed in MM compared with lung AdC (P =.029 in histologic and P =.014 in cytological samples). miR-130a demonstrated a sensitivity of 77%, a specificity of 67%, a positive predictive value of 69%, a negative predictive value of 75%, and an accuracy of 72% in identifying MM., Conclusions: The diagnostic performances of miR-130a expression analysis and IHC appear to be similar. miR-130a quantification could be used reliably as second-level diagnostic tool to differentiate MM from lung AdC in pleural effusion cytology, mainly in those cases with ambiguous or negative IHC. Further validation is needed. Cancer Cytopathol 2017;125:635-43. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Cytopathology is a noninvasive and cost-effective method for detecting cancer cells in pleural effusions (PEs), although in many cases, the diagnostic performance is hindered by the paucity of significant cells or the lack of clear morphological criteria. This study presents the results of an omics approach to improving the diagnostic performance of PE cytology., Methods: Metabolic profiling with proton nuclear magnetic resonance ( 1 H-NMR) was performed for 92 PEs (44 malignant cases of 8 different cancers and 48 benign cases of 7 nonneoplastic conditions). Light's criteria were used to further classify PEs as transudates or exudates, and 1 H-NMR spectroscopy was used to differentiate malignant pleural effusions (mPEs) from benign pleural effusions (bPEs)., Results: 1 H-NMR metabolic analysis showed clearly different spectra for mPEs and bPEs in the regions of the signals due to lipids, branched amino acids, and lactate, which were increased in mPEs. Transudates and exudates in bPEs were differentiated as well on the basis of the 1 H-NMR signals from lipids and lipoproteins, which were increased in exudates., Conclusions: Subject to validation in further larger studies, 1 H-NMR metabonomics could be an effective and reliable ancillary tool for PE investigations and diagnoses. Cancer Cytopathol 2017;125:341-348. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: In pleural effusion cytology, the distinction of malignant mesothelioma (MM) from reactive mesothelial cells (RMCs) may be challenging, even with the aid of immunocytochemistry or fluorescence in situ hybridization. It has been demonstrated that several microRNAs (miRNAs) are useful for this purpose in cell lines and histologic samples. In the current study, the authors evaluated the utility of an miRNA-based classifier as a complement to cytology., Methods: Quantitative reverse transcriptase-polymerase chain reaction analysis of 15 miRNAs was performed in mesothelial (MET-5A) and MM (H28 and H2052) cell lines. Significant miRNAs were validated in 51 MM and 40 nonneoplastic pleural histologic samples and then were tested in 29 MM and 24 RMC cytologic specimens. The performance of individual and combined miRNAs was assessed for their ability to differentiate between MM and RMCs., Results: MiRNA-19a (MiR-19a), miR-19b, miR-21, miR-25, and miR-126 were differentially expressed in cell lines and histologic samples. MiR-126 was down-regulated in MM surgical specimens compared with nonneoplastic specimens, whereas all of the other miRNAs were overexpressed. In cytologic specimens, all miRNAs except miR-25 were confirmed, exhibiting a sensitivity or a specificity higher than the threshold of 0.80, as recommended by the International Mesothelioma Interest Group. The best classifier resulted from the combination of miR-21 and miR-126, which achieved 0.86 sensitivity and 0.87 specificity., Conclusions: Subject to validation of the current results in further larger studies, miR-21 and miR-126 profiling could be an effective and reliable tool for the diagnosis of MM in pleural effusions complementary to cytology evaluation., (© 2016 American Cancer Society.)

Background & Aims: MicroRNAs (miRNAs) have been involved in hepatocarcinogenesis, but little is known on their role in the progression of chronic viral hepatitis. Aim of this study was to identify miRNA signatures associated with stages of disease progression in patients with chronic viral hepatitis., Methods: MiRNA expression profile was investigated in liver biopsies from patients with chronic viral hepatitis and correlated with clinical, virological and histopathological features. Relevant miRNAs were further investigated., Results: Most of the significant changes in miRNA expression were associated with liver fibrosis stages and included the significant up-regulation of a group of miRNAs that were demonstrated to target the master regulators of epithelial-mesenchymal transition ZEB1 and ZEB2 and involved in the preservation of epithelial cell differentiation, but also in cell proliferation and fibrogenesis. In agreement with miRNA data, immunostaining of liver biopsies showed that expression of the epithelial marker E-cadherin was maintained in severe fibrosis/cirrhosis while expression of ZEBs and other markers of epithelial-mesenchymal transition were low or absent. Severe liver fibrosis was also significantly associated with the down-regulation of miRNAs with antiproliferative and tumour suppressor activity. Similar changes in miRNA and target gene expression were demonstrated along with disease progression in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis, suggesting that they might represent a general response to liver injury., Conclusion: Chronic viral hepatitis progression is associated with the activation of miRNA pathways that promote cell proliferation and fibrogenesis, but preserve the differentiated hepatocyte phenotype., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Ovarian serous carcinoma (OSC) is a fatal gynecologic malignancy usually presenting with bilateral localization and malignant peritoneal effusion. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is directly controlled by microRNA-21 (miR-21). Exosomes are small cell-derived vesicles that participate in intercellular communication, delivering their cargo of molecules to specific cells. Exosomes are involved in several physiological and pathological processes including oncogenesis, immunomodulation, angiogenesis, and metastasis. The current study analyzed the expression of PDCD4 and miR-21 in resected OSC specimens and in cells and exosomes from OSC peritoneal effusions., Methods: PDCD4 was immunohistochemically examined in 14 normal ovaries, 14 serous cystadenoma (CA), and 14 OSC cases. Quantitative reverse transcriptase-polymerase chain reaction analysis of PDCD4 and miR-21 expression was performed in CA and OSC cases and in cells and exosomes obtained from 10 OSC and 10 nonneoplastic peritoneal effusions. miR-21 was also evaluated by in situ hybridization., Results: Immunohistochemistry demonstrated a gradual PDCD4 loss from normal ovaries to CA and OSC specimens. Quantitative reverse transcriptase-polymerase chain reaction displayed higher PDCD4 messenger RNA levels in CA specimens compared with OSC cases and highlighted miR-21 overexpression in OSC specimens. In situ hybridization detected miR-21 only in OSC cells. This PDCD4 and miR-21 inverse expression was also noted in cells and exosomes from OSC peritoneal effusions compared with nonneoplastic effusions., Conclusions: PDCD4 and miR-21 are involved in OSC oncogenesis. The transfer of miR-21 by exosomes could promote oncogenic transformation in target cells distant from the primary tumor without direct colonization by cancer cells and could be used as a diagnostic tool., (© 2014 American Cancer Society.)

Background: Anaplastic thyroid carcinoma (ATC) and primary thyroid lymphoma (PTL) are uncommon tumors of the thyroid gland with several overlapping clinical and pathologic features that may render their differentiation difficult in fine-needle aspiration (FNA) cytology. MicroRNA (miRNA) signatures have been recently reported as useful diagnostic tools applied to cytology specimens., Methods: Smears of 23 ATCs, 14 PTLs, and 20 non-neoplastic materials with multinodular goiter (MNG) were retrieved and classified based on their cytologic features and flow cytometric profiles. The ATC-related expression of hsa-miR-26a, hsa-miR-146b, hsa-miR-221, and hsa-miR-222 was quantified using quantitative reverse transcriptase-polymerase chain reaction analysis., Results: All miRNAs were remarkably up-regulated in ATC samples compared with PTL samples (P < .01). Moreover, expression levels of hsa-miR-146b, hsa-miR-221, and hsa-miR-222 were significantly higher in ATCs than in MNG samples (P < .01). Significant down-regulation of hsa-miR-26a was observed in PTLs compared with MNG samples, whereas hsa-miR-146b was overexpressed. Receiver operating characteristic analysis was used to determine the optimal cutoff for distinguishing ATC from PTL. The estimated receiver operating characteristic thresholds displayed a sensitivity level greater than 0.80 in achieving a diagnosis of PTL, allowing the correct identification of 13 of 14 PTL samples (93%)., Conclusions: Histotype-specific miRNA signatures can provide new insight into the molecular mechanisms of thyroid carcinogenesis. The tested 4-miRNA signature is a promising diagnostic tool for differentiating ATC from PTL and non-neoplastic MNG, even in the presence of scant material obtained from minimally invasive procedures., (© 2013 American Cancer Society.)

Background: In pediatric patients, a cutaneous nodule is usually diagnosed by performing an excisional biopsy, but fine-needle cytology (FNC) is a safer and noninvasive diagnostic method widely used to obtain diagnostic specimens with little stress to the patient. The authors compared the ability of FNC and biopsy to differentiate Langerhans cell histiocytosis (LCH) from juvenile xanthogranuloma (JXG)., Methods: Correlating cytological results with histological findings, the authors reviewed 27 patients (15 males and 12 females; mean age, 37 months; range, 1 month to 14 years) admitted to the University of Padua Department of Pediatrics from 1998 to 2010., Results: Cytology smears were adequate in all 27 (100%) patients: 14 (52%) were classified as having JXG, 12 (44%) as having LCH, and 1 (4%) as having a doubtful finding. A biopsy was also performed in 20 of these patients, and in all but 1, the 2 methods were completely concordant., Conclusions: FNC is safe and useful in the diagnostic workup of pediatric patients with cutaneous nodules and has no contraindications to its use as the initial diagnostic procedure., (Copyright © 2010 American Cancer Society.)