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Lepidic-Like Pattern of Metastasis in Solitary Pulmonary Nodules: A Systematic Review with Radiologic-Pathologic Correlation of a Deceptive Phenomenon [Meeting Abstract]

Amezcua, Jose Manuel Gutierrez; Zhou, Fang; Azour, Leah; Narula, Navneet; Moreira, Andre; Adler, Esther
ISI:000629694102301
ISSN: 0023-6837
CID: 4916742

Proteins Associated with Systemic Disease Are Detected in Clinically Unsuspected Isolated Amyloidosis in Atrial Appendages and Cardiac Valves [Meeting Abstract]

Amezcua, Jose Manuel Gutierrez; Zhou, Fang; Moreira, Andre; Narula, Navneet
ISI:000629694100153
ISSN: 0023-6837
CID: 4916732

Proteins Associated with Systemic Disease Are Detected in Clinically Unsuspected Isolated Amyloidosis in Atrial Appendages and Cardiac Valves [Meeting Abstract]

Amezcua, Jose Manuel Gutierrez; Zhou, Fang; Moreira, Andre; Narula, Navneet
ISI:000629690900153
ISSN: 0893-3952
CID: 4916712

Lepidic-Like Pattern of Metastasis in Solitary Pulmonary Nodules: A Systematic Review with Radiologic-Pathologic Correlation of a Deceptive Phenomenon [Meeting Abstract]

Amezcua, Jose Manuel Gutierrez; Zhou, Fang; Azour, Leah; Narula, Navneet; Moreira, Andre; Adler, Esther
ISI:000629690900928
ISSN: 0893-3952
CID: 4916722

Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models [PrePrint]

Yuin Ho, Jessica Sook; Wing-Yee Mok, Bobo; Campisi, Laura; Jordan, Tristan; Yildiz, Soner; Parameswaran, Sreeja; Wayman, Joseph A; Gaudreault, Natasha N; Meekins, David A; Indran, Sabarish V; Morozov, Igor; Trujillo, Jessie D; Fstkchyan, Yesai S; Rathnasinghe, Raveen; Zhu, Zeyu; Zheng, Simin; Zhao, Nan; White, Kris; Ray-Jones, Helen; Malysheva, Valeriya; Thiecke, Michiel J; Lau, Siu-Ying; Liu, Honglian; Junxia Zhang, Anna; Chak-Yiu Lee, Andrew; Liu, Wen-Chun; Aydillo, Teresa; Salom Melo, Betsaida; Guccione, Ernesto; Sebra, Robert; Shum, Elaine; Bakker, Jan; Kaufman, David A; Moreira, Andre L; Carossino, Mariano; Balasuriya, Udeni B R; Byun, Minji; Miraldi, Emily R; Albrecht, Randy A; Schotsaert, Michael; Garcia-Sastre, Adolfo; Chanda, Sumit K; Jeyasekharan, Anand D; TenOever, Benjamin R; Spivakov, Mikhail; Weirauch, Matthew T; Heinz, Sven; Chen, Honglin; Benner, Christopher; Richt, Juergen A; Marazzi, Ivan
The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of Topotecan (TPT), a FDA-approved Top1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as four days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of Top1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing Top1 inhibitors for COVID-19 in humans.
PMID: 33299999
ISSN: 2692-8205
CID: 4843582

Validation of PD-L1 clone 22C3 immunohistochemical stain on two Ventana DISCOVERY autostainer models: detailed protocols, test performance characteristics, and interobserver reliability analyses

Basu, Atreyee; Chiriboga, Luis; Narula, Navneet; Zhou, Fang; Moreira, Andre L
Immunohistochemical (IHC) stain for PD-L1 as a biomarker for immunotherapy is recommended in non-small cell lung cancer (NSCLC). Under the FDA, the selection of patients for pembrolizumab requires companion diagnostic testing using the Dako Agilent PD-L1 IHC 22C3 pharmDx kit performed on the Dako Autostainer Link 48 platform. However, because it is not widely available, there is need for cross-platform validation. Existing studies provide incomplete protocol detail. In our study, 73 lung tumors were stained using the FDA-approved test ('gold standard'). The same blocks were stained using two different models of the Ventana DISCOVERY platform (ULTRA, n = 73 and XT, n = 70) using different parameters, and interpreted by three pathologists. The ULTRA group met College of American Pathologists (CAP) validation criteria (concordance 91.8%) while the XT group did not (concordance 67.1%). Using tumor proportion score (TPS) ≥1% and TPS ≥50% as cut-offs, the ULTRA protocol had higher sensitivity (97.8% and 91.7%) than XT (73.3% and 60.9%) and similar specificity (ULTRA 88.9% and 100%, XT 88% and 100%). Discordance between ULTRA and XT was 27%, and in all these cases ULTRA was concordant with gold standard. Interobserver reliability was substantial for ULTRA and almost perfect for XT, providing evidence that staining rather than observer variability accounts for XT's inferior performance. Cross-validation of the clinically used 22C3 anti PD-L1 antibody test with substantial interobserver agreement is possible on the commonly used the Ventana DISCOVERY ULTRA automated instrument, while the validation failed on the XT. Cautious attention to detail must be paid when choosing cross-validation parameters.
PMID: 33245263
ISSN: 2046-0236
CID: 4681492

Increased early acute cellular rejection events in hepatitis C-positive heart transplantation

Gidea, Claudia G; Narula, Navneet; Reyentovich, Alex; Fargnoli, Anthony; Smith, Deane; Pavone, Jennifer; Lewis, Tyler; Karpe, Hannah; Stachel, Maxine; Rao, Shaline; Moreira, Andre; Saraon, Tajinderpal; Raimann, Jochen; Kon, Zachary; Moazami, Nader
BACKGROUND:Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs). METHODS:In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs. RESULTS:A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT- recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT- group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8-45) in the NAT+ group vs 65 (IQR: 44-84) days in the NAT-. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004). CONCLUSIONS:Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.
PMID: 32739334
ISSN: 1557-3117
CID: 4553482

A Grading system for invasive pulmonary adenocarcinoma: a proposal from the IASLC pathology committee

Moreira, Andre L; Ocampo, Paolo Ss; Xia, Yuhe; Zhong, Hua; Russell, Prudence A; Minami, Yuko; Cooper, Wendy A; Yoshida, Akihiko; Bubendorf, Lukas; Papotti, Mauro; Pelosi, Giuseppe; Lopez-Rios, Fernando; Kunitoki, Keiko; Ferrari-Light, Dana; Sholl, Lynette M; Beasley, Mary Beth; Borczuk, Alain; Botling, Johan; Brambilla, Elisabeth; Chen, Gang; Chou, Teh-Ying; Chung, Jin-Haeng; Dacic, Sanja; Jain, Deepali; Hirsch, Fred R; Hwang, David; Lantuejoul, Sylvie; Lin, Dongmei; Longshore, John W; Motoi, Noriko; Noguchi, Masayuki; Poleri, Claudia; Rekhtman, Natasha; Tsao, Ming-Sound; Thunnissen, Erik; Travis, William D; Yatabe, Yasushi; Roden, Anja C; Daigneault, Jillian B; Wistuba, Ignacio I; Kerr, Keith M; Pass, Harvey; Nicholson, Andrew G; Mino-Kenudson, Mari
INTRODUCTION/BACKGROUND:A grading system for pulmonary adenocarcinoma has not been established. The IASLC pathology panel evaluated a set of histological criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. DESIGN/METHODS:A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histological features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). ROC curve analysis was used to select the best model, which was validated (n=212) and tested (n=300, including Stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. RESULTS:The best model (AUC= 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histological pattern with a cut off of 20% for the latter. The model consists of: Grade 1: lepidic predominant tumor; Grade 2: acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and Grade 3: any tumor with 20% or more of high-grade patterns (solid, micropapillary and or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC of 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Inter-observer reproducibility showed good agreement (k=0.617). CONCLUSION/CONCLUSIONS:A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma. ACKNOWLEDGEMENT/UNASSIGNED:This project was supported by grants from the International Association for the study of Lung Cancer (IASLC), and NIH/NCI Early Detection Research Network 1U01CA214195-01 to HP used for biospecimen collection and salary support (DFL). We would like to thank the staff of the Center of Biospecimen Research and Development (CBRD) from the New York University for their help in digital pathology and histology for this project. CBRD is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.
PMID: 32562873
ISSN: 1556-1380
CID: 4514362

Round Robin Evaluation of MET Protein Expression in Lung Adenocarcinomas Improves Interobserver Concordance

Boyle, Theresa A; Khalil, Farah K; Mino-Kenudson, Mari; Sica, Gabriel L; Moreira, Andre L; Sholl, Lynette M; Knight, Mirna Z; Zhang, Liping; Saller, James; Varella-Garcia, Marileila; Berry, Lynne D; Chen, Heidi; Ellison, Kim E; Rivard, Christopher J; Kugler, Kelly; Wistuba, Ignacio I; Fujimoto, Junya; Kwiatkowski, David J; Bunn, Paul A; Kris, Mark G; Haura, Eric B; Hirsch, Fred R
INTRODUCTION/BACKGROUND:Overexpression of the mesenchymal-epithelial transition (MET) receptor, a receptor tyrosine kinase, can propel the growth of cancer cells and portends poor prognoses for patients with lung cancer. Evaluation of MET by immunohistochemistry is challenging, with MET protein overexpression varying from 20% to 80% between lung cancer cohorts. Clinical trials using MET protein expression to select patients have also reported a wide range of positivity rates and outcomes. MATERIALS AND METHODS/METHODS:To overcome this variability, the Lung Cancer Mutation Consortium Pathologist Panel endeavored to standardize the evaluation of MET protein expression with "Round Robin" conferences. This panel used randomly selected Aperio-scanned formalin-fixed paraffin-embedded lung cancer specimens stained by MET immunohistochemistry for the Lung Cancer Mutation Consortium 2.0 study (N=838). Seven pathologists in separate laboratories scored images of 5 initial cases and 2 subsequent rounds of 39 cases. The pathologists' scores were compared for consistency using the intraclass correlation coefficient. Issues affecting reproducibility were discussed in Round Robin conferences between rounds, and steps were taken to improve scoring consistency, such as sharing reference materials and example images. RESULTS:The overall group intraclass correlation coefficient comparing the consistency of scoring improved from 0.50 (95% confidence interval, 0.37-0.64) for the first scoring round to 0.74 (95% confidence interval, 0.64-0.83) for the second round. DISCUSSION/CONCLUSIONS:We found that the consistency of MET immunohistochemistry scoring is improved by continuous training and communication between pathologists.
PMID: 31876606
ISSN: 1533-4058
CID: 4244292

Evolution of guidelines for respiratory cytology by the Papanicolaou Society of Cytopathology

Moreira, Andre L
Cytology serves a fundamental role in the evaluation of the lower respiratory tract. Cytological specimens are often the first diagnostic attempt for the evaluation of radiographic alterations. The categorization of the pathological process as infectious, inflammatory or neoplastic is critical in guiding further clinical management of the affected patient. Therefore it is imperative that cytopathologists use a standardized approach to sample handling and reporting in order to establish clear communication with the treating physician. The Papanicolaou Society of cytopathology has been an active leader in this field and has proposed several guidelines for sampling, handling, and reporting of lower respiratory tract cytology. These guidelines have been updated to incorporate new emerging concepts and technologies in the field. Respiratory medicine is a fast growing area with constant new challenges, thus requiring an ever demanding adaptation from cytopathologists and cytology specific guidelines.
PMID: 32359109
ISSN: 1097-0339
CID: 4437052