Alarice Cheng-Yi Lowe

All Publications

• Detection of effusion tumor cells under different storage and processing conditions. Cancer cytopathology Libert, D. M., Zhu, Y., Wang, A., Allard, G. M., Cheng-Yi Lowe, A. 2024

  Abstract

  Circulating tumor cells (CTCs) shed into blood provide prognostic and/or predictive information. Previously, the authors established an assay to detect carcinoma cells from pleural fluid, termed effusion tumor cells (ETCs), by employing an immunofluorescence-based CTC-identification platform (RareCyte) on air-dried unstained ThinPrep (TP) slides. To facilitate clinical integration, they evaluated different slide processing and storage conditions, hypothesizing that alternative comparable conditions for ETC detection exist.The authors enumerated ETCs on RareCyte, using morphology and mean fluorescence intensity (MFI) cutoffs of >100 arbitrary units (a.u.) for epithelial cellular adhesion molecule (EpCAM) and <100 a.u. for CD45. They analyzed malignant pleural fluid from three patients under seven processing and/or staining conditions, three patients after short-term storage under three conditions, and seven samples following long-term storage at -80°C. MFI values of 4',6-diamidino-2-phenylindol, cytokeratin, CD45, and EpCAM were compared.ETCs were detected in all conditions. Among the different processing conditions tested, the ethanol-fixed, unstained TP was most similar to the previously established air-dried, unstained TP protocol. All smears and Pap-stained TPs had significantly different marker MFIs from the established condition. After short-term storage, the established condition showed comparable results, but ethanol-fixed and Pap-stained slides showed significant differences. ETCs were detectable after long-term storage at -80°C in comparable numbers to freshly prepared slides, but most marker MFIs were significantly different.It is possible to detect ETCs under different processing and storage conditions, lending promise to the application of this method in broader settings. Because of decreased immunofluorescence-signature distinctions between cells, morphology may need to play a larger role.

  View details for DOI 10.1002/cncy.22803

  View details for PubMedID 38373107

• Immunofluorescent and molecular characterization of effusion tumor cells reveal cancer site‐of‐origin and disease‐driving mutations Cancer Cytopathology Zhu, Y., Wang, A., Allard, G. M., Nordberg, J. J., Nair, R. V., Kunder, C. A., Lowe, A. C. 2022

  View details for DOI 10.1002/cncy.22610

• Identification and characterization of effusion tumor cells (ETCs) from remnant pleural effusion specimens. Cancer cytopathology Zhu, Y., Allard, G. M., Ericson, N. G., George, T. C., Kunder, C. A., Lowe, A. C. 2021

  Abstract

  Cancer is a leading cause of death worldwide, and patients may have advanced disease when diagnosed. Targeted therapies guided by molecular subtyping of cancer can benefit patients significantly. Pleural effusions are frequently observed in patients with metastatic cancer and are routinely removed for therapeutic purposes; however, effusion specimens have not been recognized as typical substrates for clinical molecular testing because of frequent low tumor cellularity.Excess remnant pleural effusion samples (N = 25) from 21 patients with and without suspected malignancy were collected at Stanford Health Care between December 2019 and November 2020. Samples were processed into ThinPrep slides and underwent novel effusion tumor cell (ETC) analysis. The ETC results were compared with the original clinical diagnoses for accuracy. A subset of confirmed ETCs was further isolated and processed for molecular profiling to identify cancer driver mutations. All samples were obtained with Institutional Review Board approval.The authors established novel quantitative standards to identify ETCs and detected epithelial malignancy with 89.5% sensitivity and 100% specificity in the pleural effusion samples. Molecular profiling of confirmed ETCs (pools of 5 cells evaluated) revealed key pathogenic mutations consistent with clinical molecular findings.In this study, the authors developed a novel ETC-testing assay that detected epithelial malignancies in pleural effusions with high sensitivity and specificity. Molecular profiling of 5 ETCs showed promising concordance with the clinical molecular findings. To promote cancer subtyping and guide treatment, this ETC-testing assay will need to be validated in larger patient cohorts to facilitate integration into cytologic workflow.

  View details for DOI 10.1002/cncy.22483

  View details for PubMedID 34171181

• Science, Medicine, and Cytology: an educational program of the Diversity, Equity, and Inclusion Committee of the American Society of Cytopathology. Journal of the American Society of Cytopathology Gimenez, C., Balassanian, R., Banet, N., Barkan, G., DeRobbio, K., Henderson-Jackson, E., Jenkins, E., Kilic, A., Lai, L., Lura, T., Morgenstern, N., Mito, J., Reid, M. D., Rivera-Colon, G., Stewart, J. 3., Lowe, A. C. 2024

  Abstract

  INTRODUCTION: As our field of pathology continues to grow, our trainee numbers are on the decline. To combat this trend, the ASC Diversity, Equity, and Inclusion Committee established the Science, Medicine, and Cytology SumMer Certificate program to improve exposure to pathology/cytopathology with a focus on diversity, equity, and inclusion. Herein, we report our findings of the first 2 years of the program.MATERIALS AND METHODS: An online course was developed targeting students who are underrepresented in medicine at the high school and college level. It consisted of several didactic sessions, presenting the common procedures involving cytopathologists and cytologists. Interviews with cytopathologists were also included. Participants were surveyed for demographic information and provided course evaluations.RESULTS: In the first year of the program (2021), 34 participants completed the program, which increased to 103 in 2022. In both years there was a diversity in participant demographic backgrounds; however, only a minority of participants self-identified as being underrepresented in medicine. A vast majority (>85%) of participants in both years were high school or college students. In 2021, 100% of participants stated that the program format was effective and 94% thought the content was appropriate for their level of education; in 2022 the results were similar. In 2021, 66% considered health care as a potential career; this value increased in 2022 to 83%. In 2021 and 2022, 31% and 38%, respectively, considered cytology as a career.CONCLUSIONS: Evaluations were excellent, generating interest in cytopathology. Barriers in reaching underrepresented minorities exist and additional work is needed. Expansion to a wider audience may increase outreach.

  View details for DOI 10.1016/j.jasc.2024.04.002

  View details for PubMedID 38834386

• Success Rates for Molecular Testing with ThyroSeq v3 Genomic Classifier and Stanford's Solid Tumor Actionable Mutation Panel (STAMP) from Cytology Smears Nichols, T., Fakhari, M., Shiu, T., Dey, R., Phan, T., Lowe, A. ELSEVIER SCIENCE INC. 2024: S450-S451

  View details for Web of Science ID 001302363401087

• Multicancer screening test based on the detection of circulating non haematological proliferating atypical cells. Molecular cancer Malara, N., Coluccio, M. L., Grillo, F., Ferrazzo, T., Garo, N. C., Donato, G., Lavecchia, A., Fulciniti, F., Sapino, A., Cascardi, E., Pellegrini, A., Foxi, P., Furlanello, C., Negri, G., Fadda, G., Capitanio, A., Pullano, S., Garo, V. M., Ferrazzo, F., Lowe, A., Torsello, A., Candeloro, P., Gentile, F. 2024; 23 (1): 32

  Abstract

  BACKGROUND: the problem in early diagnosis of sporadic cancer is understanding the individual's risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation.METHODS: a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction.RESULTS: the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity.CONCLUSION: this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.

  View details for DOI 10.1186/s12943-024-01951-x

  View details for PubMedID 38350884

• Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer. JCO precision oncology Saylor, P. J., Otani, K., Balza, R., Ukleja, J., Pleskow, H., Fisher, R., Kusaka, E., Otani, Y. S., Badusi, P. O., Smith, M. R., Meneely, E., Olivier, K., Lowe, A. C., Toner, M., Maheswaran, S., Haber, D. A., Yeap, B. Y., Lee, R. J., Miyamoto, D. T. 2024; 8: e2300230

  Abstract

  Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity.Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction.The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS (P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase.Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

  View details for DOI 10.1200/PO.23.00230

  View details for PubMedID 38354328

• Comprehensive epithelial biomarker analysis of malignant mesothelioma: EpCAM positivity is a potential diagnostic pitfall. Cancer cytopathology Zhu, Y., Moore, S., Wang, A., George, E., Allard, G. M., Libert, D. M., Lowe, A. C. 2023

  Abstract

  Epithelial cell adhesion molecule (EpCAM) is frequently used to distinguish carcinoma from background mesothelial cells during cytologic examination of body cavity fluids. Previously, the authors identified one malignant mesothelioma case with strong and diffuse membranous EpCAM staining, making it indistinguishable from carcinoma.In this study, the authors evaluated all available effusion specimens from patients with malignant mesothelioma, including the above-mentioned index case, obtained at Stanford Health Care, from 2011 to 2021 (N = 17) as well as control cases (N = 5). Analyses included an immunohistochemistry (IHC) assay for EpCAM and claudin-4, a multiplexed immunofluorescent (IF) assay for EpCAM, and an RNA in situ hybridization assay targeting EpCAM.The authors detected EpCAM positivity of variable intensity and percentage in four malignant mesothelioma cases (23.5%; although only two showed positivity for the epithelial-specific IHC marker MOC31 in ≥40% of cells) and claudin-4 negativity in all cases, with two cases displaying focal and weak claudin-4 staining in <1% of cells. Multiplexed IF staining on the cases with EpCAM IHC positivity showed strong, membranous EpCAM staining in one of four cases. RNA in situ hybridization also was used to assess the correlation between EpCAM positivity by IHC/IF and RNA expression levels. Strong EpCAM RNA expression was detected in the three malignant mesothelioma cases.The current findings revealed that a subset of epithelioid malignant mesothelioma cases mimic or exhibit the immunophenotypic features of carcinoma when evaluating for EpCAM only. Additional biomarker testing, such as claudin-4, may help avoid this potential pitfall to yield accurate diagnoses.

  View details for DOI 10.1002/cncy.22706

  View details for PubMedID 37069606

• Single-cell Retrieval from Clinical Cytology Slides Under Morphologic Guidance Facilitates Future Comprehensive Genomic Profiling from Paucicellular Samples Zhu, Y., Aragon, A., Wang, A., Gonzalez-pena, V., Gawad, C., Lowe, A. ELSEVIER SCIENCE INC. 2023: S388

  View details for Web of Science ID 000990969800408

• Axial and Intra-Cranial Tumors Presenting as Extra-Cranial Soft Tissue Masses in the Head and Neck: Cytologic Features of 9 Cases Diagnosed on Fine Needle Aspiration (FNA) Ewais, M., Lowe, A., Reid, M., Birdsong, G., Ewaz, A. ELSEVIER SCIENCE INC. 2023: S294

  View details for Web of Science ID 000990969800314

• Fine Needle Aspiration with Rapid on-site Evaluation in Diagnosing Retroperitoneal Masses: A Clinicopathological Analysis of 63 Cases Liu, Y., Lowe, A., Qian, X. ELSEVIER SCIENCE INC. 2023: S331

  View details for Web of Science ID 000990969800354

• Detecting Effusion Tumor Cells (ETCs) Under Different Storage and Processing Conditions Libert, D., Zhu, Y., Wang, A., Lowe, A. ELSEVIER SCIENCE INC. 2023: S328-S329

  View details for Web of Science ID 000990969800352

• Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells. Nature communications Bhere, D., Choi, S. H., van de Donk, P., Hope, D., Gortzak, K., Kunnummal, A., Khalsa, J., Revai Lechtich, E., Reinshagen, C., Leon, V., Nissar, N., Bi, W. L., Feng, C., Li, H., Zhang, Y. S., Liang, S. H., Vasdev, N., Essayed, W. I., Quevedo, P. V., Golby, A., Banouni, N., Palagina, A., Abdi, R., Fury, B., Smirnakis, S., Lowe, A., Reeve, B., Hiller, A., Chiocca, E. A., Prestwich, G., Wakimoto, H., Bauer, G., Shah, K. 2022; 13 (1): 2810

  Abstract

  Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by thelack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment in GBM patients. In this study, we show the detection of cell surface death receptor (DR) target on CD146-enriched circulating tumor cells (CTC) captured from the blood of mice bearing GBM and patients diagnosed with GBM. Next, we developed allogeneic "off-the-shelf" clinical-grade bifunctional mesenchymal stem cells (MSCBif) expressing DR-targeted ligand and a safety kill switch. We show that biodegradable hydrogel encapsulated MSCBif (EnMSCBif) has a profound therapeutic efficacy in mice bearing patient-derived invasive, primary and recurrent GBM tumors following surgical resection. Activation of the kill switch enhances the efficacy of MSCBif and results in their elimination post-tumor treatment which can be tracked by positron emission tomography (PET) imaging. This study establishes a foundation towards a clinical trial of EnMSCBif in primary and recurrent GBM patients.

  View details for DOI 10.1038/s41467-022-30558-3

  View details for PubMedID 35589724

• Circulating tumor cell analysis in locally advanced and metastatic squamous cell carcinoma of the head and neck. Laryngoscope investigative otolaryngology Harris, E. J., Huang, J., Carroll, E., Lowe, A. C., Chau, N. G., Rabinowits, G., Haddad, R., Hanna, G. J., Haddad, T., Sanborn, M., Kacew, A., Lorch, J. 2020; 5 (6): 1063-1069

  Abstract

  Circulating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role.In this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the CellSearch System. Select cases also had sequential CTC evaluation. Presence of CTCs was correlated with patient characteristics and outcomes.Forty-eight patients enrolled, and 36 had evaluable clinical data and baseline CTC counts. Twenty-five patients had locally advanced disease (LAD) and 11 had metastatic disease. ≥1 CTCs were detected in six patients with LAD (24%) and four with metastatic disease (36%). On univariate analysis, smoking was associated with CTCs.CTCs are not associated with prognosis in patients with LAD and metastatic disease; however, they are present in this patient population, and ≥1 CTCs is associated with a history of smoking.1b; individual prospective cohort study.

  View details for DOI 10.1002/lio2.448

  View details for PubMedID 33364395

  View details for PubMedCentralID PMC7752061

• Circulating tumor cell analysis in locally advanced and metastatic squamous cell carcinoma of the head and neck LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY Harris, E. J., Huang, J., Carroll, E., Lowe, A. C., Chau, N. G., Rabinowits, G., Haddad, R., Hanna, G. J., Haddad, T., Sanborn, M., Kacew, A., Lorch, J. 2020

  View details for DOI 10.1002/lio2.448

  View details for Web of Science ID 000583937600001

• Multiplexed fluorescence in situ hybridization-based detection of circulating tumor cells: A novel liquid-based technology to facilitate accurate and early identification of non-small cell lung cancer patients. Cancer cytopathology Zhu, Y., Lowe, A. C. 2020

  View details for DOI 10.1002/cncy.22277

  View details for PubMedID 32320525

• A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC. Theranostics Lim, M., Park, J., Lowe, A. C., Jeong, H. O., Lee, S., Park, H. C., Lee, K., Kim, G. H., Kim, M. H., Cho, Y. K. 2020; 10 (12): 5181-5194

  Abstract

  Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy.

  View details for DOI 10.7150/thno.44693

  View details for PubMedID 32373206

  View details for PubMedCentralID PMC7196290

• A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC THERANOSTICS Lim, M., Park, J., Lowe, A. C., Jeong, H., Lee, S., Park, H., Lee, K., Kim, G., Kim, M., Cho, Y. 2020; 10 (12): 5181–94

  View details for DOI 10.7150/thno.44693

  View details for Web of Science ID 000526083000002

• Use of Deep Learning to Develop and Analyze Computational Hematoxylin and Eosin Staining of Prostate Core Biopsy Images for Tumor Diagnosis. JAMA network open Rana, A. n., Lowe, A. n., Lithgow, M. n., Horback, K. n., Janovitz, T. n., Da Silva, A. n., Tsai, H. n., Shanmugam, V. n., Bayat, A. n., Shah, P. n. 2020; 3 (5): e205111

  Abstract

  Histopathological diagnoses of tumors from tissue biopsy after hematoxylin and eosin (H&E) dye staining is the criterion standard for oncological care, but H&E staining requires trained operators, dyes and reagents, and precious tissue samples that cannot be reused.To use deep learning algorithms to develop models that perform accurate computational H&E staining of native nonstained prostate core biopsy images and to develop methods for interpretation of H&E staining deep learning models and analysis of computationally stained images by computer vision and clinical approaches.This cross-sectional study used hundreds of thousands of native nonstained RGB (red, green, and blue channel) whole slide image (WSI) patches of prostate core tissue biopsies obtained from excess tissue material from prostate core biopsies performed in the course of routine clinical care between January 7, 2014, and January 7, 2017, at Brigham and Women's Hospital, Boston, Massachusetts. Biopsies were registered with their H&E-stained versions. Conditional generative adversarial neural networks (cGANs) that automate conversion of native nonstained RGB WSI to computational H&E-stained images were then trained. Deidentified whole slide images of prostate core biopsy and medical record data were transferred to Massachusetts Institute of Technology, Cambridge, for computational research. Results were shared with physicians for clinical evaluations. Data were analyzed from July 2018 to February 2019.Methods for detailed computer vision image analytics, visualization of trained cGAN model outputs, and clinical evaluation of virtually stained images were developed. The main outcome was interpretable deep learning models and computational H&E-stained images that achieved high performance in these metrics.Among 38 patients who provided samples, single core biopsy images were extracted from each whole slide, resulting in 102 individual nonstained and H&E dye-stained image pairs that were compared with matched computationally stained and unstained images. Calculations showed high similarities between computationally and H&E dye-stained images, with a mean (SD) structural similarity index (SSIM) of 0.902 (0.026), Pearson correlation coefficient (PCC) of 0.962 (0.096), and peak signal to noise ratio (PSNR) of 22.821 (1.232) dB. A second cGAN performed accurate computational destaining of H&E-stained images back to their native nonstained form, with a mean (SD) SSIM of 0.900 (0.030), PCC of 0.963 (0.011), and PSNR of 25.646 (1.943) dB compared with native nonstained images. A single blind prospective study computed approximately 95% pixel-by-pixel overlap among prostate tumor annotations provided by 5 board certified pathologists on computationally stained images, compared with those on H&E dye-stained images. This study also used the first visualization and explanation of neural network kernel activation maps during H&E staining and destaining of RGB images by cGANs. High similarities between kernel activation maps of computationally and H&E-stained images (mean-squared errors <0.0005) provide additional mathematical and mechanistic validation of the staining system.These findings suggest that computational H&E staining of native unlabeled RGB images of prostate core biopsy could reproduce Gleason grade tumor signatures that were easily assessed and validated by clinicians. Methods for benchmarking, visualization, and clinical validation of deep learning models and virtually H&E-stained images communicated in this study have wide applications in clinical informatics and oncology research. Clinical researchers may use these systems for early indications of possible abnormalities in native nonstained tissue biopsies prior to histopathological workflows.

  View details for DOI 10.1001/jamanetworkopen.2020.5111

  View details for PubMedID 32432709

• Malignancy risk for solitary and multiple nodules in Hurthle cell-predominant thyroid fine-needle aspirations: A multi-institutional study CANCER CYTOPATHOLOGY Wong, K. S., Jo, V. Y., Lowe, A. C., Faquin, W. C., Renshaw, A. A., Shah, A. A., Roh, M. H., Stelow, E. B., Krane, J. F. 2019

  Abstract

  Hürthle cell metaplasia is common in hyperplastic nodules, particularly within the setting of lymphocytic thyroiditis (LT). The Bethesda System for Reporting Thyroid Cytopathology indicates that it is acceptable to classify Hürthle cell-predominant fine-needle aspiration (HC FNA) specimens as atypia of undetermined significance (AUS) rather than suspicious for a Hürthle cell neoplasm (HUR) within the setting of multiple nodules or known LT. The goal of the current study was to address whether this approach is justified.HC FNA specimens were identified and correlated with ultrasound and surgical pathology reports if available. Multinodularity was determined based on findings on macroscopic examination if imaging results were unavailable.A total of 698 HC FNA specimens were identified, including 576 resected nodules, 455 of which (79%) were benign. The overall risk of malignancy for HUR was 27%, whereas the risk of malignancy for AUS was 10%. The mean size of the benign nodules was 2.1 cm on surgical resection specimens, with multiple nodules noted in 293 cases (64%) and histologic LT noted in 116 cases (25%). The mean size of the malignant nodules was 2.8 cm, with multiple nodules and histologic LT noted in 74 cases (61%) and 22 cases (18%), respectively. The malignancy rate did not differ between solitary or multiple nodules (P = .52) or in the presence or absence of LT (P = .12). However, size did significantly differ between malignant and benign nodules (P < 0.01).The malignancy rate did not differ significantly in the presence of multiple nodules or LT, although the latter demonstrated a statistical trend. A diagnosis of AUS over HUR based solely on the presence of multinodularity is not warranted.

  View details for DOI 10.1002/cncy.22213

  View details for Web of Science ID 000497737300001

  View details for PubMedID 31751003

• Integration of rare cell capture technology into cytologic evaluation of cerebrospinal fluid specimens from patients with solid tumors and suspected leptomeningeal metastasis. Journal of the American Society of Cytopathology Torre, M., Lee, E. Q., Chukwueke, U. N., Nayak, L., Cibas, E. S., Lowe, A. C. 2019

  Abstract

  INTRODUCTION: Dissemination of tumor to the leptomeninges, subarachnoid space, and cerebrospinal fluid (CSF) is termed leptomeningeal metastasis (LM) and occurs in approximately 5% of patients with solid tumors. LM is associated with dismal clinical prognosis, and routine cytologic and radiologic methods for diagnosing LM have limited sensitivity. The CellSearch immunomagnetic rare cell capture assay is FDA-approved to detect circulating tumor cells (CTCs) in peripheral blood, but whether it may have a role in identifying CSF CTCs is still unclear.MATERIAL AND METHODS: CSF specimens from 20 patients with clinically suspected solid tumor LM collected from 2 institutions between October 2016 and January 2019 were evaluated with routine CSF cytology and underwent concurrent CTC testing with the CellSearch assay (Menarini-Silicon Biosystems, Huntingdon Valley, PA). The results of CTC testing were compared to routine CSF cytology and radiologic studies for detecting LM.RESULTS: The CellSearch assay achieved a sensitivity of 88.9% and specificity of 100% for detecting LM (using a threshold of 1 CTC/mL of CSF as the definition of a positive CTC result). One patient with negative CSF cytology but positive CTCs developed positive cytology 37 days later.CONCLUSIONS: In this proof-of-principle pilot study, we demonstrate that the CellSearch assay can be successfully integrated with the routine CSF cytologic workflow to aid in the diagnosis of solid tumor LM. Importantly, CTCs detected by this rare cell capture assay are found in a subset of patients with non-positive routine CSF cytology, which may have significant implications for patient management.

  View details for DOI 10.1016/j.jasc.2019.09.001

  View details for PubMedID 31606331