scholarly journals Utility of molecular tests in cytopathology

CytoJournal ◽  
2014 ◽  
Vol 11 ◽  
pp. 5 ◽  
Author(s):  
Arthur David Somoza ◽  
F. Zahra Aly
Keyword(s):  
Molecular Analysis ◽  
Diagnostic Information ◽  
Classification Systems ◽  
Cervical Cytology ◽  
Pancreatic Cysts ◽  
Molecular Testing ◽  
Thyroid Cytology ◽  
Anaplastic Lymphoma ◽  
Molecular Tests ◽  
Test Kit

With the popularity of interventional radiology, diagnostic material obtained can be limited requiring critical decisions on making the best use of it. Molecular testing using nanogram amounts of tissue can add useful diagnostic information by improving sensitivity and/or specificity of the diagnosis. This review examines the use of molecular tests in cervical cytology, “indeterminate” thyroid cytology specimens, pancreatic cyst fluid, urinary tract and pulmonary adenocarcinoma cytologic material. Molecular human papillomavirus (HPV) testing combined with cervical cytology increases sensitivity of detection of high grade lesions. In cytologically negative cases, the HPV negative predictive value endorses longer screening intervals. With the high prevalence of benign thyroid nodules, cytology plays a vital role in screening. However, 10-40% of the specimens obtained are cytologically indeterminate. Molecular analysis of these specimens can predict the malignant risk in these cases. Increased detection of pancreatic cysts has necessitated accurate pre-operative diagnosis delineating non-mucinous from mucinous cysts, which have a potential for progression to adenocarcinoma. Multimodal diagnosis of pancreatic cysts and molecular analysis help to clarify neoplastic risk; and in cases of limited fluid, may be the only available diagnostic information. Urothelial carcinoma (UC) of the bladder, a common cancer with frequent recurrences, requires lifelong surveillance. The UroVysion ™ test kit can increase the sensitivity of detection of UC especially in cases of residual/recurrent carcinoma after therapy. Subsets of lung adenocarcinomas are now commonly targeted by therapies based on molecular mutation results of epidermal growth factor receptor, KRAS or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase re-arrangements. The move toward standardization of reporting of cytology specimens commencing with cervical smears and more recently, thyroid cytology specimens is also changing the practice of cytopathology. Combining the stringent cytology criteria with ancillary molecular testing is expected to yield more discrete and diagnostic categories for research and reporting. The profession is at an exciting point of implementing novel molecular markers to refine diagnostic criteria and create clinically relevant classification systems.

scholarly journals Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules

2018 ◽  
Vol 142 (4) ◽  
pp. 446-457 ◽  
Author(s):  
Michiya Nishino ◽  
Marina Nikiforova
Keyword(s):  
Fine Needle Aspiration ◽  
Test Performance ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
Fine Needle ◽  
Diagnostic Uncertainty ◽  
Thyroid Cytology ◽  
Molecular Tests ◽  
Pubmed Search

Context.— Approximately 15% to 30% of thyroid nodules that undergo fine-needle aspiration are classified as cytologically indeterminate, presenting management challenges for patients and clinicians alike. During the past several years, several molecular tests have been developed to reduce the diagnostic uncertainty of indeterminate thyroid fine-needle aspirations. Objective.— To review the methodology, clinical validation, and recent peer-reviewed literature for 4 molecular tests that are currently marketed for cytologically indeterminate thyroid fine-needle aspiration specimens: Afirma, ThyroSeq, ThyGenX/ThyraMIR, and RosettaGX Reveal. Data Sources.— Peer-reviewed literature retrieved from PubMed search, data provided by company websites and representatives, and authors' personal experiences. Conclusions.— The 4 commercially available molecular tests for thyroid cytology offer unique approaches to improve the risk stratification of thyroid nodules. Familiarity with data from the validation studies as well as the emerging literature about test performance in the postvalidation setting can help users to select and interpret these tests in a clinically meaningful way.

scholarly journals Genetic testing for indeterminate thyroid cytology: review and meta-analysis

2018 ◽  
Vol 25 (3) ◽  
pp. R163-R177 ◽  
Author(s):  
Sergio Vargas-Salas ◽  
José R Martínez ◽  
Soledad Urra ◽  
José Miguel Domínguez ◽  
Natalia Mena ◽  
...  
Keyword(s):  
Clinical Performance ◽  
Meta Analysis ◽  
Molecular Testing ◽  
Clinical Use ◽  
Thyroid Cytology ◽  
Molecular Tests ◽  
Indeterminate Nodule ◽  
Health Need ◽  
The Impact

Thyroid cancer is the most frequent endocrine malignancy, and its incidence is increasing. A current limitation of cytological evaluation of thyroid nodules is that 20–25% are reported as indeterminate. Therefore, an important challenge for clinicians is to determine whether an indeterminate nodule is malignant, and should undergo surgery, or benign, and should be recommended to follow-up. The emergence of precision medicine has offered a valuable solution for this problem, with four tests currently available for the molecular diagnosis of indeterminate cytologies. However, efforts to critically analyze the quality of the accumulated evidence are scarce. This systematic review and meta-analysis is aimed to contribute to a better knowledge about the four available molecular tests, their technical characteristics, clinical performance, and ultimately to help clinicians to make better decisions to provide the best care options possible. For this purpose, we address three critical topics: (i) the proper theoretical accuracy, considering the intended clinical use of the test (rule-in vs rule-out) and the impact on clinical decisions; (ii) the quality of the evidence reported for each test (iii) and how accurate and effective have the tests proved to be after their clinical use. Together with the upcoming evidence, this work provides significant and useful information for healthcare system decision-makers to consider the use of molecular testing as a public health need, avoiding unnecessary surgical risks and costs.

scholarly journals Computed Tomography-Guided Lung Biopsy for Molecular Tests: A Meta-Analysis

2021 ◽  
Author(s):  
Jian-Hua Zhang ◽  
Feng-Fei Xia ◽  
Xiao-Shan Yang ◽  
Yi-Bing Shi ◽  
Yu-Fei Fu ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Biopsy ◽  
Meta Analysis ◽  
Egfr Mutations ◽  
Cochrane Library ◽  
Molecular Testing ◽  
Ct Guided ◽  
Anaplastic Lymphoma ◽  
Molecular Tests ◽  
Positive Rate

Abstract Background To evaluate the potential clinical effectiveness of computed tomography (CT)-guided lung biopsy in the molecular tests. Materials and Methods We searched the related studies from the PubMed, Embase, and Cochrane Library until July 2021. The endpoints included adequacy rates for molecular tests, positive rates of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocation, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Results Initially, we were able to identify 1783 potentially relevant studies among which, only 12 were ultimately included in the present meta-analysis. All the studies were retrospective in nature. A total of 2559 patients underwent CT-guided lung biopsy and 1414 of them received molecular testing. We found that pooled adequacy rate for molecular tests, positive rate of EGFR mutations, and positive rate of ALK translocation were 95% (95% CI: 0.93–0.98), 49% (95% CI: 0.42–0.56), and 7% (95% CI: 0.04–0.09), respectively. Moreover, only 1 article reported the positive rate of KRAS mutation of 6% but a significant heterogeneity was detected in the endpoints of adequacy rate for molecular tests (I2 = 86.2%, P < 0.001) and positive rate of EGFR mutations (I2 = 77.7%, P < 0.001). While conducting a meta-regression analysis, we did not identify any variables that could significantly influence adequacy rate for molecular tests and positive rate of EGFR mutations. A high risk of publication bias was also found in the endpoint of adequacy rate for molecular tests (Egger test: P = 0.043). Conclusions CT-guided lung biopsy can serve as an effective method to provide sufficient lung cancer samples for molecular testing. EGFR gene was found to be the most frequently mutated during the analysis.

Role of Ancillary Techniques in Thyroid Cytology Specimens

2019 ◽  
Vol 64 (1-2) ◽  
pp. 40-51 ◽  
Author(s):  
Michiya Nishino ◽  
Jeffrey F. Krane
Keyword(s):  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
Copy Number Alterations ◽  
Preoperative Risk ◽  
Thyroid Cytology ◽  
Molecular Tests ◽  
Preoperative Risk Stratification ◽  
Gene Expression Alterations

Ancillary molecular testing has emerged as a promising way to refine the preoperative risk stratification of thyroid nodules with indeterminate fine needle aspiration (FNA) biopsy results. Commercially available molecular tests for thyroid FNAs include those that analyze samples for mutations and gene fusions, gene expression alterations, microRNA expression alterations, chromosomal copy number alterations, or a combination thereof. This review summarizes the performance characteristics of the most current iterations of three tests currently marketed for cytologically indeterminate thyroid nodules: ThyroSeq v3, ThyGeNEXT/ThyraMIR, and Afirma Gene Sequencing Classifier.

scholarly journals Trends in Thyroid Fine-Needle Aspiration Cytology Practices: Results From a College of American Pathologists 2016 Practice Survey

2019 ◽  
Vol 143 (11) ◽  
pp. 1364-1372 ◽  
Author(s):  
Daniel D. Mais ◽  
Barbara A. Crothers ◽  
Diane Davis Davey ◽  
Kristen E. Natale ◽  
Ritu Nayar ◽  
...  
Keyword(s):  
Fine Needle Aspiration ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Fine Needle ◽  
Thyroid Cytology ◽  
Molecular Tests ◽  
Thyroid Fine Needle Aspiration ◽  
Thyroid Fna

Context.— The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2016 survey concerning thyroid fine-needle aspiration (FNA). Objective.— To provide a cross-sectional survey of thyroid cytology practices in 2016. Design.— In 2016, a survey was sent to 2013 laboratories participating in the College of American Pathologists Non-Gynecologic Cytology Education Program (NGC-A) requesting data from 2015–2016 on several topics relating to thyroid FNA. Results.— A total of 878 laboratories (43.6% of 2013) replied to the survey. Radiologists performed the most thyroid FNA procedures in most laboratories (70%; 529 of 756), followed by endocrinologists (18.7%; 141 of 756), and most of these were performed under ultrasound guidance (92.1%; 699 of 759). A total of 32.6% of respondents (251 of 769) provided feedback on unsatisfactory rates for nonpathology providers who performed FNA. Intraprocedural adequacy assessment was primarily performed by attending pathologists (77.4%; 490 of 633) or cytotechnologists (28.4%; 180 of 633). Most laboratories used the Bethesda System for Reporting Thyroid Cytopathology (89.8%; 701 of 781) and performed molecular testing based on clinician request (68.1%; 184 of 270) rather than FNA diagnosis. Correlation of thyroid excisions with prior cytology results most often occurred retrospectively (38.4%; 283 of 737) and was used for pathologist interpretive quality assurance purposes. Conclusions.— These survey results offer a snapshot of national thyroid FNA cytology practices in 2016 and indicate that standardized cytology terminology is commonly used; pathologists perform most immediate adequacy assessments for thyroid FNA; laboratories use correlation statistics to evaluate pathologists' performance; and molecular tests are increasingly requested for indeterminate interpretations, but reflex molecular testing is rare.

What Every Neuropathologist Needs to Know: Practical Aspects and Pitfalls in Molecular Diagnosis of Brain Tumors

2021 ◽  
Author(s):  
J Stephen Nix ◽  
Cristiane M Ida
Keyword(s):  
Brain Tumors ◽  
Molecular Diagnosis ◽  
Genetic Alterations ◽  
Genetic Alteration ◽  
Molecular Testing ◽  
Test Results ◽  
Molecular Test ◽  
Molecular Tests ◽  
Clinically Significant ◽  
Selection Of

Abstract Molecular testing has become part of the routine diagnostic workup of brain tumors after the implementation of integrated histomolecular diagnoses in the 2016 WHO classification update. It is important for every neuropathologist to be aware of practical preanalytical, analytical, and postanalytical factors that impact the performance and interpretation of molecular tests. Prior to testing, optimizing tumor purity and tumor amount increases the ability of the molecular test to detect the genetic alteration of interest. Recognizing basic molecular testing platform analytical characteristics allows selection of the optimal platform for each clinicopathological scenario. Finally, postanalytical considerations to properly interpret molecular test results include understanding the clinical significance of the detected genetic alteration, recognizing that detected clinically significant genetic alterations are occasionally germline constitutional rather than somatic tumor-specific, and being cognizant that recommended and commonly used genetic nomenclature may differ. Potential pitfalls in brain tumor molecular diagnosis are also discussed.

scholarly journals Thyroid and Molecular Testing. Advances in Thyroid Molecular Cytopathology

2021 ◽  
Vol 2 (2) ◽  
pp. 77-92
Author(s):  
Esther Diana Rossi ◽  
Philippe Vielh
Keyword(s):  
Thyroid Nodules ◽  
Adult Population ◽  
Needle Aspiration ◽  
Common Finding ◽  
Molecular Testing ◽  
Additional Tool ◽  
Thyroid Cytology ◽  
Hürthle Cell ◽  
Cell Neoplasm ◽  
Undetermined Significance

Thyroid nodules are a common finding in the adult population including the fact that more than 50% of individuals, over the age of 60, have thyroid nodules. The majority have been mostly detected with ultrasonography and 10% by palpation. The majority of these nodules are benign, whereas 5–15% of them are malignant. The pre-operative diagnosis of cancer is a critical challenge in order to ensure that each patient can be treated with the best tailored management with a reduction of unnecessary surgery for benign lesions. Fine needle aspiration cytology (FNAC) represents the first and most important diagnostic tool for the evaluation of thyroid lesions. According to the literature, FNAC is able to render a conclusive diagnosis in up to 70–80% of all cases. For the remaining 20–30% of nodules, cytological diagnoses fall into the category of indeterminate lesions mostly due to the lack of specific morphological features. According to the Bethesda system for reporting thyroid cytopathology (TBSRTC), indeterminate lesions can be sub-stratified into three different subcategories including “atypia of undetermined significance/follicular lesion of undetermined significance-AUS/FLUS”; “follicular or Hürthle cell neoplasm/suspicious for follicular or Hürthle cell neoplasm-FN/SFN”; and “suspicious for malignancy-SFM”. Many of these indeterminate lesions undergo repetition or diagnostic lobectomy. Nonetheless, the majority of these cases will have a benign diagnosis due to the fact that the rate of cancer ranges between 6 and 30%. It stands to reason that the application of ancillary technique, mostly molecular testing, emerged as a critical additional tool for those thyroid indeterminate lesions. Since the early 1990s, material collected from cytological samples yields sufficient and adequate cells for the detection of point mutation or gene fusions. Nonetheless, the further availability of new sequencing technologies such as next-generation sequencing (NGS) has led to more comprehensive molecular applications adopted now in clinical use. The current review investigates the multiple advances in the field of molecular testing applied in thyroid cytology.

scholarly journals ALK-positive Histiocytosis of Umbilicus Subcutaneous with KIF5B-ALK Fusion: a Case Report

2021 ◽  
Author(s):  
Yili Zhu ◽  
Jun Fan ◽  
Bo Huang ◽  
Ying Wu ◽  
Heshui Shi ◽  
...  
Keyword(s):  
Pathological Examination ◽  
Older Children ◽  
Anaplastic Lymphoma ◽  
Molecular Tests ◽  
Spindle Cells ◽  
First Case ◽  
Alk Positive ◽  
Painless Mass ◽  
Lymphocytic Infiltrates

Abstract Background: Since the discovery of the first case of Anaplastic lymphoma kinase (ALK) -positive histiocytosis in 2008, originally described as a systemic, self-limiting disease in infants, the range of ALK-positive histiocytosis has recently been expanded to include localized diseases in older children and young adults. Case presentation: We present the case of an 18-year-old female with periumbilical painless mass for 5 months, who underwent a resection of the mass. Pathological examination showed the tumor consists predominantly of fascicular to storiform growth of nonatypical spindle cells, admixed with lymphocytic infiltrates. The tumor spindle cells were diffusely positive for CD68, CD163 and ALK. Further, molecular tests revealed ALK gene fusion: Kinesin Family Member 5B (KIF5B) (E24)-ALK (E20), confirmed ALK-positive histiocytosis. The tumor has not recurred one and a half years after resection by follow-up examination.Conclusion: ALK-positive histiocytosis in local lesion can achieve remission by complete resection and clinical follow-up showed a favorable prognosis.

scholarly journals EBUS in optimizing non-small cell lung cancer diagnosis and treatment

2020 ◽  
Author(s):  
Antonia Haranguș ◽  
Ioana Berindan-Neagoe ◽  
Lăcrămioara Toma ◽  
Ioan Șimon ◽  
Ovidiu Pop ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Analysis ◽  
Cancer Diagnosis ◽  
Predictive Value ◽  
Small Cell ◽  
Endobronchial Ultrasound ◽  
Mediastinal Lymphadenopathy ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Lung Cancer Diagnosis

Background. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly used minimally invasive method for the diagnosis and staging of lung cancer. In order to improve its diagnostic accuracy, rapid on-site cytologic evaluation (ROSE) is being utilized in some institutions. ROSE, performed by a cytopathologist in the examination room, allows the assessment of the adequacy of the collected samples, identifies malignant cells and sometimes establishes diagnosis on the spot, thus improving diagnostic sensitivity. As non-small cell lung carcinomas (NSCLC) require not only pathological subtyping, but also molecular characterization, obtaining the adequate amount of tissue is crucial. Only a limited number of studies have analyzed the suitability of EBUS-TBNA samples for assessment of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed death-ligand 1 (PD-L1) status. Aim. We intended to examine the diagnostic yield of ROSE in NSCLC and the results and feasibility of molecular analysis performed on EBUS-TBNA small samples. Methods. 100 patients with lung tumors and hilar and/or mediastinal lymphadenopathy on CT or PET/CT scans were retrospectively identified over a 3-year period, from a prospectively maintained EBUS-TBNA database. All examinations were accompanied by on-site cytological exam - ROSE, histopathological exam (HPE) and, in the case of NSCLC, molecular testing. After the sampling of the lymph nodes, specimens were Diff-Quik stained and a rapid preliminary diagnosis was established. Immunohistochemistry and mutational testing were performed using cell blocks. Results. Adenocarcinoma was the most frequent diagnosis in both ROSE (34%) and histopathology (53%). Overall sensitivity and positive predictive value of ROSE in NSCLC, considering HPE the gold standard, were 92.18% and 93.65%, respectively, with a specificity and negative predictive value of 75% and 70.58%, respectively. All samples that were tested for EGFR mutation and ALK rearrangement were adequate for analysis. The adequacy ratio for PD-L1 was 91.66%; 37.5% of patients showed a high PD-L1 expression level, with a tumor proportion score TPS≥50%. Conclusion. EBUS-TBNA is a valuable method for lung cancer diagnosis. ROSE proved to have a moderate prediction of the final diagnosis in NSCLC. Molecular analysis of EGFR, ALK and PD-L1 can be successfully accomplished on EBUS-TBNA small tissue samples.

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