Objective A meta-analysis has not been previously performed to evaluate critically the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solely pancreatic ductal adenocarcinoma and address factors that have an impact on variability of accuracy. The aim of this study was to determine whether the presence of a cytopathologist, variability of the reference standard and other sources of heterogeneity significantly impacts diagnostic accuracy. Methods We conducted a comprehensive search to identify studies, in which the pooled sensitivity, specificity, likelihood ratios for a positive or negative test (LR+, LR) and summary receiver-operating curves (SROC) could be determined for EUS-FNA of the pancreas for ductal adenocarcinoma using clinical follow-up, and/or surgical biopsy or excision as the reference standard. Results We included 34 distinct studies (3644 patients) in which EUS-FNA for a solid pancreatic mass was evaluated. The pooled sensitivity and specificity for EUS-FNA for pancreatic ductal adenocarcinoma was 88.6% [95% confidence interval (CI): 87.289.9] and 99.3% (95% CI: 98.799.7), respectively. The LR+ and LR were 33.46 (95% CI: 20.7653.91) and 0.11 (95% CI: 0.080.16), respectively. The meta-regression model showed rapid on-site evaluation (ROSE) (P=0.001) remained a significant determinant of EUS-FNA accuracy after correcting for study population number and reference standard. Conclusion EUS-FNA is an effective modality for diagnosing pancreatic ductal adencarcinoma in solid pancreatic lesions, with an increased diagnostic accuracy when using on-site cytopathology evaluation.
ObjectivesAssessment of proliferation by the Ki-67 labelling index (Ki67-LI) is an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on resection specimens. Ki67-LI values for grading are not fully established on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to determine the accuracy of Ki67-LI on EUS-FNA to predict a final grade of pNET and to analyse the relationship between cytological grading and progression-free survival (PFS). MethodsBetween 1996 and 2010, 46 pNETs (33 were resected) from 45 patients were diagnosed by EUS-FNA. Ki67-LI was evaluated on cytological and histological material for each tumour and classified according to the 2010 WHO grading system. ResultsA very good inter-observer agreement for Ki67-LI on EUS-FNA and surgical specimens, respectively, were obtained. Discrepancies were observed between histology and cytology, especially in grade 2 (G2) tumours, where cytology underestimated grading owing to tumour heterogeneity. Still, EUS-FNA was able to distinguish a poor prognostic group, as the actuarial PFS of cytological (c) G3 tumours was 104months versus 29 +/- 7 and 68 +/- 10 for cG2 and cG1 tumours, respectively (P<0.0001). ConclusionThis study attests the reproducibility of Ki67-LI of pNETs whether counted on cytology or histology with a very good inter-observer correlation. Determination of Ki67-LI on EUS-FNA of pNETs should be included systematically in their prognostic work-up.
Recently, a diagnostic classification system has been developed for salivary gland cytology. This system utilizing diagnostic categories is compared with an older approach based on specific diagnoses. Diagnostic accuracy and clinical implications of the two approaches are compared and contrasted.
We aimed to assess our practice using the recently developed standardised classification system designated The Milan System for Reporting Salivary Cytopathology ( MSRSGC ) and to ascertain the rates of malignancy for each category by means of a retrospective study. The MSRSGC appears to be a useful tool to guide clinical management and provide an indication of possible risk of malignancy.
This paper investigates the corresponding cytologic diagnoses, Gene Expression Classifier results and ultrasound features of thyroid nodules diagnosed as non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), as well as the histologic landscape of the background surgical resection specimens.
Mutation profiling can be successfully performed on residual material of thyroid LB‐FNA without any dedicated sample in a pathology lab. It is an easy way to improve diagnostic accuracy of LB‐FNA with indeterminate cytology in routine practice and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.
This study suggests that assigning AUS/FLUS cases to one of four sub‐categories ‐ nuclear atypia, architectural atypia, predominant oncocytic changes, both nuclear and architectural atypia ‐ might facilitate more appropriate risk stratification and better clinical management of this heterogeneous group. It also found that the AUS/FLUS category may carry a higher risk of malignancy than previously thought.
European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1 The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18:213-9). A woman with a high-grade cytological lesion, a repeated low-grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow-up for each woman seen. Reflex testing for high-risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow-up of low-grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC-H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow-up of special cases such as women who are pregnant, postmenopausal or immunocompromised.
V. Hofman, E. Long, M. Ilie, C. Bonnetaud, J. M. Vignaud, J. F. Fléjou, S. Lantuejoul, E. Piaton, N. Mourad, C. Butori, E. Selva, C. H. Marquette, M. Poudenx, S. Sibon, S. Kelhef, N. Vénissac, J. P. Jais, J. Mouroux, T. J. Molina, P. Vielh and P. Hofman Morphological analysis of circulating tumour cells in patients undergoing surgery for non‐small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method Background and objective: Recurrence rates after surgery for non‐small cell lung cancer (NSCLC) range from 25 to 50% and 5‐year survival is only 60–70%. Because no biomarkers are predictive of recurrence or the onset of metastasis, pathological TNM (pTNM) staging is currently the best prognostic factor. Consequently, the preoperative detection of circulating tumour cells (CTCs) might be useful in tailoring therapy. The aim of this study was to characterize morphologically any circulating non‐haematological cells (CNHCs) in patients undergoing surgery for NSCLC using the isolation by size of epithelial tumour cell (ISET) method. Methods: Of 299 blood samples tested, 250 were from patients with resectable NSCLC and 59 from healthy controls. The presence of CNHCs was assessed blindly and independently by 10 cytopathologists on May‐Grünwald–Giemsa stained filters and the cells classified into three groups: (i) malignant cells, (ii) uncertain malignant cells, and (iii) benign cells. We assessed interobserver agreement using Kappa (κ) analysis as the measure of agreement. Results: A total of 123 out of 250 (49%) patients showed CNHCs corresponding to malignant, uncertain malignant and benign cells, in 102/250 (41%), 15/250 (6%) and 6/250 (2%) cases, respectively. No CNHCs were detected in the blood of healthy subjects. Interobserver diagnostic variability was absent for CNHCs, low for malignant cells and limited for uncertain malignant and benign cells. Conclusion: Identification of CTCs in resectable NSCLC patients, using ISET technology and according to cytopathological criteria of malignancy, appears to be a new and promising field of cytopathology with potential relevance to lung oncology.
A review of combined FNA cytology‐flow cytometry reporting for lymphoid lesions of the head and neck found high accuracy (99.3%) for NHL s. Rare false negative and false positives were identified, mainly with Hodgkin Lymphoma and large cell lymphomas. Specimens collected with rapid on‐site evaluation showed significantly lower inadequate rates and higher sensitivity and negative predictive value for NHL s.
In this study, atypical urine cytology samples were reclassified according to the recently published ‘The Paris System’ (TPS) criteria. The reclassified cases were subsequently correlated with histology and UroVysion fluorescence in situ hybridisation results. This is the first study examining the usefulness of UroVysion in the setting of TPS classification. Furthermore, the study highlights the utility of TPS in objectively stratifying urine cytology specimens and its strength in identifying high grade urothelial carcinoma.
ObjectiveWe studied whether atypical, non-superficial urothelial cells (AUC) could be separated into new subcategories including AUC of undetermined significance' (AUC-US) and cannot exclude high grade'' (AUC-H) in order to help to standardize urine cytopathology reports, as it is widely accepted in the Bethesda system for gynaecological cytopathology. MethodsWe investigated whether AUC-US and AUC-H, defined by distinctive cytological criteria, might be separated with statistical significance according to actual diagnosis and follow-up data. A series of 534 cyto-histological comparisons taken in 139 patients, including 221 AUC at various steps of their clinical history was studied. There were 513 (96.1%) postcystoscopy and 469 (87.8%) ThinPrep (R) liquid-based specimens (95.9% and 89.1% of AUC cases, respectively). Patients viewed between 1999 and 2011 had histological control in a 0- to 6-months delay and were followed-up during an additional 5.99.2 (0- to 56-) months period. ResultsThe 221 AUC represented 0.8-2% of the specimens viewed during the study period. Among AUC-H cases, 70 out of 185 (37.8%) matched with high-grade lesions, compared with 3 of 38 (8.3%) of AUC-US cases (P=0.0003). Conservatively treated patients with AUC-H more frequently developed high-grade lesions than those with AUC-US (54.1% versus 16.7%, P=0.0007) with a 17.6-months mean delay. Nuclear hyperchromasia, a nuclear to cytoplasm (N/C) ratio>0.7 and the combination of both were the more informative diagnostic criteria, all with P<0.01. ConclusionWe conclude that the new subcategories could help to standardize urine cytopathology reports and contribute to the patient's management, provided it is validated by multicentric studies.
The main objective of this study was to assess the diagnostic accuracy of salivary gland fine needle aspirations (FNA) within the framework of the Milan System and evaluate the Milan System for Reporting Salivary Gland Cytopathology as a tool for risk assessment. We document our institutional experience with salivary gland FNAs over an 8‐year period, retrospectively applying Milan System categorizations to cytologic diagnoses, comparing pre‐ and post‐operative diagnoses, and determining risks of neoplasm and malignancy.
We have investigated the presence of malignant cells in gastric lavage ( GL 1) of gastric cancer ( GC ) patients using cytopathologic analysis in order to find novel information on the pathobiology of this tumor. Our results showed that GL 1 was associated with advanced disease, predicted aggressive tumor behavior and was a multivariate independent prognostic factor for poor overall survival and progression‐free survival. The clinical adoption of our test could ameliorate staging and treatment selection of GC patients.
A study on 125 cytology cases of upper urinary tract with associated histologic specimens from 74 patients found that The use of the Paris system in evaluating upper urinary tract cytology specimens was specific and sensitive in identifying patients with high grade urothelial carcinoma by histology.
Non‐invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP), an indolent tumor, differs from its malignant counterpart follicular variant of papillary thyroid carcinoma (FVPTC) and papillary thyroid carcinoma with predominant follicular pattern (PTC‐FP) in prognosis and required management although it mimics them in architectural pattern. The feasibility of distinguishing between these differentials cytologically was evaluated, and it was found that while NIFTP and FVPTC cannot be separated out on cytology, PTC‐FP can usually be diagnosed correctly.
A novel approach showing that cyto‐morphologic features of signet ring cells, nuclear grooves, and nucleolar shapes can help triage cytology and biopsy samples for appropriate molecular testing of primary ALK (+) lung cancer.
Extramedullary hematopoiesis is a rare finding in a lymph node aspirate. It can be seen in various hematological conditions compromising the bone marrow milieu. Though it is a benign condition, it may be misdiagnosed as it may mimic some hematological malignancies.