scholarly journals Practical Applications of Molecular Testing in the Cytologic Diagnosis of Pancreatic Cysts

2021 ◽  
Vol 2 (1) ◽  
pp. 11-22
Author(s):  
Mingjuan Lisa Zhang ◽  
Martha B. Pitman
Keyword(s):  
Preoperative Evaluation ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cysts ◽  
Molecular Testing ◽  
Cytological Diagnosis ◽  
Specific Test ◽  
Practical Applications ◽  
Molecular Alterations ◽  
High Risk Lesion ◽  
Mucinous Cyst

Mucinous pancreatic cysts are precursor lesions of ductal adenocarcinoma. Discoveries of the molecular alterations detectable in pancreatic cyst fluid (PCF) that help to define a mucinous cyst and its risk for malignancy have led to more routine molecular testing in the preoperative evaluation of these cysts. The differential diagnosis of pancreatic cysts is broad and ranges from non-neoplastic to premalignant to malignant cysts. Not all pancreatic cysts—including mucinous cysts—require surgical intervention, and it is the preoperative evaluation with imaging and PCF analysis that determines patient management. PCF analysis includes biochemical and molecular analysis, both of which are ancillary studies that add significant value to the final cytological diagnosis. While testing PCF for carcinoembryonic antigen (CEA) is a very specific test for a mucinous etiology, many mucinous cysts do not have an elevated CEA. In these cases, detection of a KRAS and/or GNAS mutation is highly specific for a mucinous etiology, with GNAS mutations supporting an intraductal papillary mucinous neoplasm. Late mutations in the progression to malignancy such as those found in TP53, p16/CDKN2A, and/or SMAD4 support a high-risk lesion. This review highlights PCF triage and analysis of pancreatic cysts for optimal cytological diagnosis.

scholarly journals The Tail Wagging the Dog (or the Challenges Faced When the Financing of Medicine Gets Ahead of the Science of Medicine)

2018 ◽  
Vol 56 (10) ◽  
Author(s):  
David W. Kimberlin
Keyword(s):  
Case Series ◽  
Molecular Testing ◽  
Labor Costs ◽  
Specific Test ◽  
Potential Harm ◽  
Viral Culture ◽  
Diagnostic Decision ◽  
Simplex Virus ◽  
Diagnostic Decision Making ◽  
Made In

ABSTRACTIn their article in this issue of theJournal of Clinical Microbiology, S. R. Dominguez et al. (J Clin Microbiol 56:e00632-18, 2018,https://doi.org/10.1128/JCM.00632-18) describe the performance of PCR detection of herpes simplex virus (HSV) DNA versus viral culture in skin and mucosal samples from 7 neonates with HSV disease. This is a significant contribution to our understanding of the optimal diagnostic approach in babies being evaluated for neonatal HSV disease. Many diagnostic laboratories already have made the change to molecular diagnostics for skin and mucosal swab testing, however, in large part due to the labor costs associated with viral cultures. Thus, important studies such as this one are being conducted to support a decision that has already been made in many locations on mostly economic grounds. This small case series supports the decision to use molecular testing for samples from skin and mucosal sites, but larger studies are needed to more fully define the performance characteristics of PCR in this population. Since a false-positive result would commit a baby to months of management that would be unnecessary and have potential harm, it is critical to base diagnostic decision making on data that support the use of a specific test.

Targeted therapies in cholangiocarcinoma: Assessment of US oncologist practice patterns.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 347-347
Author(s):  
Kinjal Parikh ◽  
Davecia Ragoonath Cameron ◽  
Tristin Abair ◽  
Patrick Kugel ◽  
Arndt Vogel
Keyword(s):  
Clinical Practice ◽  
Targeted Therapies ◽  
Progressive Disease ◽  
Community Setting ◽  
Molecular Testing ◽  
Learning Needs ◽  
Self Awareness ◽  
Multiple Choice Questions ◽  
Molecular Alterations ◽  
Practice Assessment

347 Background: Chemotherapy is a mainstay treatment modality for patients with advanced cholangiocarcinoma (CCA). Recent developments and new approvals have led to changing paradigms, incorporating the use of targeted therapies for patients with progressive disease. Given the need for a greater understanding of the molecular alterations, varying targets, and available and emerging therapies, education is needed to assess knowledge regarding these recent advances in unresectable CCA. The goal of this activity was to increase the knowledge of self-assess the learning needs of oncologists in treating patients with unresectable CCA. Methods: The education included 25 multiple choice questions in a continuing medical education (CME)-certified clinical practice assessment to assess practice gaps. The questions were designed to measure knowledge, competence, confidence, and attitudes of oncologists regarding clinical evidence, role of molecular testing, and place in the treatment paradigm for targeted therapies in unresectable CCA. The self-assessment was made available online to physicians as a learning tool to gain foundational knowledge, as well as receive feedback about their performance as compared to other test-takers, to improve self-awareness of their own personal educational gaps. The activity launched 6/24/20, and data are reported through 8/31/20. Results: A total of 1,009 learners, including 758 physicians, participated in the activity. Of the 104 oncologists that participated, a majority practiced in the community setting, saw patients with a range of cancers, and were not confident about using targeted therapies or recognizing targets for biomarker testing. Oncologists demonstrated the following gaps related to: NGS sequencing and biomarkers: 21% do not use; 32% use upon progressive disease; 35% did not realize that not all panels detect FGFR2 fusions; 20% do not test for biomarkers; 29% and 56% test for IDH or FGFR, respectively; 60% recognize the incidence of IDH1 mutations; Clinical trial (FIGHT202 and ClarIDHy): 45% were able to identify biomarker eligibility for pemigatinib; 9% were able to identify pemigatinib OS outcomes; 30% were able to recognize most common grade 3 AE of pemigatinib; 51% recognized the PFS endpoint with ivosidenib; 34% were able to identify eligibility for ivosidenib; 55% recognized most common AEs of ivosidenib. Conclusions: This CME-certified clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and use of targeted therapies and emerging data in patients with unresectable CCA. As new data emerges and the number of targets and targeted therapies expand, continued education remains important to continue to optimize patient care.

scholarly journals Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma

2019 ◽  
Vol 6 ◽  
pp. 237428951984835 ◽  
Author(s):  
MacLean P. Nasrallah ◽  
Zev A. Binder ◽  
Derek A. Oldridge ◽  
Jianhua Zhao ◽  
David B. Lieberman ◽  
...  
Keyword(s):  
Patient Care ◽  
Dna Methyltransferase ◽  
Improve Patient Care ◽  
Return Of Results ◽  
Molecular Testing ◽  
Methylguanine Dna Methyltransferase ◽  
Molecular Alterations ◽  
Molecular Abnormalities ◽  
Tissue Handling ◽  
Testing Algorithm

Molecular profiling of glioblastoma has revealed complex cytogenetic, epigenetic, and molecular abnormalities that are necessary for diagnosis, prognosis, and treatment. Our neuro-oncology group has developed a data-driven, institutional consensus guideline for efficient and optimal workup of glioblastomas based on our routine performance of molecular testing. We describe our institution’s testing algorithm, assay development, and genetic findings in glioblastoma, to illustrate current practices and challenges in neuropathology related to molecular and genetic testing. We have found that coordination of test requisition, tissue handling, and incorporation of results into the final pathologic diagnosis by the neuropathologist improve patient care. Here, we present analysis of O6-methylguanine-DNA-methyltransferase promoter methylation and next-generation sequencing results of 189 patients, obtained utilizing our internal processes led by the neuropathology team. Our institutional pathway for neuropathologist-driven molecular testing has streamlined the management of glioblastoma samples for efficient return of results for incorporation of genomic data into the pathological diagnosis and optimal patient care.

Primary Lung Cribriform Adenocarcinoma With Squamoid Morules Harboring Somatic CTNNB1 Mutation in a Never-Smoked Healthy Adolescent

2020 ◽  
Vol 23 (6) ◽  
pp. 472-475
Author(s):  
Hao Wu ◽  
Qiqi Ye ◽  
Dana Razzano ◽  
Oya Tugal ◽  
Jeremy Rosenblum ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Congenital Malformation ◽  
Pediatric Patients ◽  
Molecular Testing ◽  
Adolescent Female ◽  
Healthy Adolescent ◽  
Molecular Alterations ◽  
Tissue Of Origin ◽  
Lung Adenocarcinomas ◽  
Ctnnb1 Mutation

Primary lung adenocarcinomas are rare in pediatric patients, and even rarer in patients without precedent malignancy or congenital malformation. Here we present the first reported case of primary lung cribriform adenocarcinoma with squamoid morules in a previously healthy adolescent female. Molecular testing identified CTNNB1 mutation in the tumor and excluded other common mutations in lung adenocarcinoma. Our case suggests molecular alterations to the same signaling pathway can lead to similar histomorphology regardless of the tissue of origin.

scholarly journals Lung Adenocarcinoma during Pregnancy: 11-Year Follow-Up

2020 ◽  
Vol 13 (2) ◽  
pp. 892-895
Author(s):  
Angel Acosta Rojas ◽  
Ana Collazo-Lorduy ◽  
Jordi Remon ◽  
Ovidio Hernando Requejo ◽  
Beatriz Jiménez-Munarriz ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Young Women ◽  
Whole Brain Radiotherapy ◽  
High Rate ◽  
Molecular Testing ◽  
Molecular Alterations ◽  
Brain Radiotherapy ◽  
Alk Positive ◽  
Brain Radiation

The incidence of lung cancer during pregnancy is rising due to the high rate of smokers in young women and the late mean age of pregnancy; in addition, considering that the patients are young women with a higher incidence of molecular alterations, molecular testing in lung adenocarcinoma should always be performed, even in pregnancy. Here, we report the case of a lung adenocarcinoma diagnosed during pregnancy with a long survival who benefitted from brain radiotherapy, conventional chemotherapy, and ALK TKI-targeted treatment. It reveals the safety of whole brain radiotherapy during pregnancy and consideration of other brain radiation techniques even in palliative cases, which should be personalized and managed by a multidisciplinary team. However, upfront management of brain metastasis in ALK-positive patients remains unresolved.

scholarly journals The Role of Molecular Testing for the Indeterminate Thyroid FNA

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 736 ◽  
Author(s):  
Esther Diana Rossi ◽  
Liron Pantanowitz ◽  
William C. Faquin
Keyword(s):  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Adult Population ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
American Thyroid Association ◽  
Cytological Diagnosis ◽  
Fine Needle ◽  
Thyroid Fna

Thyroid nodules are common in the adult population where a majority are benign and only 4.0% to 6.5% are malignant. Fine needle aspiration (FNA) is a key method used in the early stages to evaluate and triage patients with thyroid nodules. While a definitive cytological diagnosis is provided in more than 70–75% of all thyroid FNA cases, the group of indeterminate lesions offers a challenge in terms of interpretation and clinical management. Molecular testing platforms have been developed, are recognized as an option by the 2015 American Thyroid Association Guidelines, and are frequently used in conjunction with FNA as an integral part of the cytologic evaluation. In this review, the utility of molecular testing options for nodules assigned to the group of indeterminate thyroid FNAs is described.

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.

Molecular testing (strand displacement assay) for identification of urethral gonorrhoea in men: can it replace culture as the gold standard?

2005 ◽  
Vol 16 (6) ◽  
pp. 430-432 ◽  
Author(s):  
H L Wheeler ◽  
C J Skinner ◽  
A Khunda ◽  
C Aitken ◽  
D Perpanthan ◽  
...  
Keyword(s):  
Predictive Value ◽  
Diagnostic Yield ◽  
Molecular Testing ◽  
Strand Displacement ◽  
Specific Test ◽  
Strand Displacement Amplification ◽  
Conventional Culture ◽  
Study Population ◽  
Displacement Assay ◽  
Sensitivity Specificity

The objective was to evaluate the performance of Becton Dickinson's BD Probe TecTM (BDPT) strand displacement amplification (SDA) test for the detection of Neisseria gonorrhoeae on urethral specimens from men with urethritis compared with conventional culture and to show that SDA improves the diagnostic yield of gonorrhoea infections (GC). Anonymized retrospective testing of stored urethral swab samples from men attending genitourinary services in East London was performed using SDA. The prevalence of GC culture positive infections in this sample was 20/152 (13%). The sensitivity, specificity, positive predictive value and negative predictive value for the BDPT-SDA system compared with culture were 100%, 95%, 77% and 100%, respectively. In this study population, the BDPT-SDA assay was a highly sensitive and specific test for the diagnosis of N. gonorrhoeae from urethral swabs in men. Therefore, SDA can be used to complement culture in the diagnosis of N. gonorrhoeae infection. No ethics committee approval was obtained as all samples were anonymized.

Analysis of pancreatobiliary adenocarcinoma (PBC) treatment response and resistance utilizing circulating tumor DNA (ctDNA).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 758-758
Author(s):  
Madhulika Banerjee ◽  
Alejandro Recio Boiles ◽  
Sumana Veeravelli ◽  
Jorge Andres Leiva ◽  
Kathylynn Saboda ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Target Genes ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Driver Mutations ◽  
Resistance Mutations ◽  
Kras Mutations ◽  
Molecular Alterations ◽  
Imaging Results ◽  
Therapeutic Decision Making

758 Background: Accurate disease monitoring in PBC is instrumental for optimal therapeutic decision-making. CA 19-9 is the most utilized biomarker, though it has limited sensitivity/specificity and cannot be used in CA 19-9 non-secretors (n-S). ctDNA is a potentially helpful monitoring aid and surrogate for PBC n-S. Serial ctDNA could identify emerging resistant driver mutations. Our study prospectively examined ctDNA in PBC patients receiving treatment and retrospectively correlated it with clinical response. Methods: We performed genomic testing of ctDNA from metastatic PBC patients’ plasma from 11/2016 to 08/2019. This included 77 patients, of those, 18 had >1 ctDNA measurement with 49 correlative data points in total. Demographics, serial CA 19-9 levels and imaging results were collected. ctDNA analysis by parallel sequencing of amplified target genes (74) using Guardant360 was obtained. We correlated imaging and CA 19-9 responses with molecular alterations in patients receiving systemic chemotherapy. Descriptive statistics and logistic regression of the data was performed. Results: Of those included, median age was 66 yo, 50% male, and 92% pancreatic ductal adenocarcinoma. Baseline ctDNA showed 103 mutations including TP53 12.6%, KRAS 9.7%, MET 6.8%, APC, ARID1A and NF1 4.8% each, and others < 3%. 44% of patients were n-S with 75% having both TP53 and KRAS mutations. APC, ARID1A, and NF1 were only present in n-S. 91% vs 90% KRAS and 84% vs 78% TP53 of n-S and secretors (S), respectively, had correlation between ctDNA levels and imaging response. S TP53 and KRAS mutations correlated to CA19-9 levels and scans in 78% and 70% responses. New TP53 subclonal variant mutations were the most common resistance mutations for all progressions (75%). A logistic regression model of imaging progression on change in CA19-9 secretion and TP53 or KRAS expression was not statistically significant. Conclusions: Baseline ctDNA level changes ( TP53 and KRAS) can potentially act as a biomarker of response in PBC, specifically in n-S. TP53 subclonal mutations were the most common resistant alterations at progression and can be explored as future targets. This is being explored in larger prospective trials.

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