Abstract 579: Ensartinib (X-396), a novel ALK TKI, in Chinese ALK-positive non-small cell lung cancer: A phase I, dose-escalation and expansion study

Ensartinib (X-396) is a novel ALK inhibitor with high activity against a broad range of crizotinib-resistant ALK mutations (such as G1269A, F1174, C1156Y, and T1151) and CNS metastases. This Phase I study (NCT02959619) determined the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D), investigated the safety and PK, and explored the clinical efficiency for the compound as monotherapy in Chinese ALK+ NSCLC patients.Patients with advanced ALK+ NSCLC were treated with oral ensartinib (150, 200, 225, or 250 mg once daily) using a conventional 3+3 dose escalation design. The dose-escalation evaluated patients in 28-day cycles. In the dose-expansion phase, ensartinib was given at the recommended dose to further explore PK and clinical efficacy. Treatment was continued until disease progression, or unacceptable toxicity. The study finds ensartinib was well tolerated in Chinese ALK-positive NSCLC patients with high antitumor activity. RP2D was established at 225 mg QD. Ensartini..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-579

Authors: Hongyun Zhao, Yuxiang Ma, Yang Zhang, Shaodong Hong, Wenfeng Fang, Yunpeng Yang, Jianjin Huang, Jing Zhao, Yan Huang, Lieming Ding, Li Mao, Giovanni Selvaggi, Li Zhang

Clinical TrialsKirk SmithAugust 1, 2020Ensartinib, X-396, ALK inhibitor, crizotinib, CNS, Chinese, antitumor activity

Abstract 2997: Longitudinal circulating tumor DNA (ctDNA) analysis predicts response and reveals the resistance mechanisms of ensartinib in ALK+ NSCLC patients (pts) progressed on crizotinib

Consistent with previous reports, ensartinib showed high clinical efficacy. Longitudinal ctDNA analysis
could be a powerful tool in predicting treatment outcomes and revealing resistant mechanisms of
ensartinib. We observed G1269A, G1202R and E1210K as the major resistant mutations to ensartinib. READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-2997

Authors: Yunpeng Yang, Jie Huang, Tao Wang, Jianya Zhou, Jing Zheng, Jifeng Feng, Wu Zhuang, Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Yunpeng Liu, Zhendong Zheng, Gaofeng Li, Ning Wu, Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Li Mao, Giovanni Selvaggi, Larry Zhu, Shanshan Xiao, Li Zhang

Clinical TrialsKirk SmithAugust 1, 2020Ensartinib, X-396, ALK inhibitor, post-crizotinib

Immune exhaustion of tumor microenvironment mediates crizotinib resistance in ALK rearranged advanced non small cell lung cancer

Previous study showed the correlation between immune tumor microenvironment and the efficacy of checkpoint inhibitor in non-small cell lung cancer (NSCLC). This study evaluated whether biomarkers for immune tumor microenvironment including programmed death ligand 1 (PD-L1), cluster of differentiation 8 (CD8), Granzyme B (GZMB) and T cell receptor (TCR) could predict the treatment response to the first-line crizotinib of patients with ALK-rearranged non-small cell lung cancer (NSCLC).We retrospectively evaluated patients with advanced NSCLC who received crizotinib at Hunan Cancer Hospital between January 2016 and December 2018.his study revealed immune exhaustion for tumor microenvironment as a poor predictive marker in first-line crizotinib-treated ALK-rearranged non-small cell lung cancer. The findings indicate the reshaping of an inflamed immune phenotype characterized by PD-L1, CD8, GZMB, and TCR expression and suggest potential therapeutic sensitivity to PD-1 blockade. READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-4479

Authors: Yongchang Zhang

Abstract 1865: Phosphoproteomic analyses identify EGFR as a critical cooperative kinase for ALK

In order to interrogate the contribution of EGFR to downstream signaling under ALK inhibition, we conducted phosphoproteomics for two ALK-driven cell lines, DFCI032 and H3122, using the ALK inhibitor crizotinib or in combination with the EGFR inhibitor gefitinib. Kinase-Substrate Enrichment Analysis (KSEA) and Phosphoproteomics Dissection Using Networks (PHOTON) analysis were used to identify whether a signaling node was functionally regulated based on substrate phosphorylation or on protein-protein interaction partner phosphorylation, respectively. Strikingly, both methods showed that EGFR was functionally downregulated by ALK inhibition. ALK was also considered functionally more downregulated under EGFR/ALK dual inhibition compared to ALK inhibition alone by KSEA analysis. These data suggest ALK and EGFR engage in overlapping signaling pathways. Collectively, EGFR and ALK dual inhibition can significantly delay or prevent the emergence of ALK TKI resistance by suppressing critical overlapping signaling pathways and promotes signaling reprogramming in cancer cells. READ ARTICLE

AACR abstract DOI: 10.1158/1538-7445.AM2020-1865

Authors: Nan Chen, Anh T. Le, Andrea E. Doak, Guolin Zhang, Bin Fang, Eric B. Haura and Robert C. Doebele

Pre-ClinicalKirk SmithAugust 1, 2020ALK, EGFR, proteomics

Investigation on the prognostic impact of concurrent genomic alterations in crizotinib-treated EML4-ALK-rearranged advanced non-small cell lung cancer patients

Background: ... In our study, we investigated concurrent molecular factors that could contribute to the heterogeneity of their clinical outcomes to crizotinib therapy... Conclusion: Our study revealed that concurrent deleterious mutations, particularly copy number amplifications in oncogenic genes have prognostic implications in patients with EML4-ALK-rearranged NSCLC receiving crizotinib therapy. These observations advance the understanding of the heterogeneity of treatment responses among patients with EML4-ALK-rearranged tumors. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.05.026

Authors: Jing Zheng, Yanping Zhu, Ke Sun, Qian Shen, Yuehong Wang, He Cao, Analyn Lizaso, Bing Yu, Jing Lin, Songan Chen, Jianya Zhou, Jianying Zhou

Case StudyKirk SmithAugust 1, 2020ALK fusion, ALK rearrangements, EML4-ALK, Crizotinib, Lung cancer

Enrichment of kinase fusions in ESR1 wild-type, metastatic breast cancer revealed by a systematic analysis of 4854 patients

Background: Kinase fusions are rare and poorly characterized in breast cancer (BC). We aimed to characterize kinase fusions within a large cohort of advanced BC... Results: Twenty-seven of 4854 (0.6%) patients harbored fusions: 11 FGFR (five FGFR2, three FGFR3, three FGFR1), five BRAF, four NTRK1, two RET, two ROS1, one ALK, one ERBB2, and one MET... Conclusion: Kinase fusions in BC are extremely rare, and appear to be enriched in hormone-resistant, metastatic carcinomas and mutually exclusive with ESR1 mutations. The present study expands the spectrum of genetic alterations activating mitogen-activated protein kinase (MAPK) signaling that can substitute for ESR1 mutations in this setting. Molecular testing at progression after endocrine therapy should include fusion testing, particularly in the absence of ESR1 hotspot alterations, in an effort to identify additional therapeutic options which may provide substantial clinical benefit. READ ARTICLE

Annals of Oncology DOI:10.1016/j.annonc.2020.04.008

Authors: D. S. Ross, B. Liu, A. M. Schram, P. Razavi, S. M. Lagana, Y. Zhang, M. Scaltriti, J. F. Bromberg, M. Ladanyi, D. M. Hyman, A. Drilon, A. Zehir, R. Benayed, S. Chandarlapaty, J. F. Hechtman

Review PaperKirk SmithAugust 1, 2020Breast cancer, endocrine therapy, kinase fusion, larotrectinib, resistance

ALK-rearranged lung adenocarcinoma transformation into high-grade large cell neuroendocrine carcinoma: Clinical and molecular description of two cases

Highlights: • First two cases of ALK-rearranged LUAD that transformed to high-grade LCNEC after ALK-TKI treatment. • Development of on-target ALK G1202R mutation, showing unique dual mechanisms of resistance in both cases. • Different RB1 status in both cases, with worse outcome in the case with RB1 loss. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.06.005

Authors: Aline F. Fares, Benjamin H. Lok, Tong Zhang, Michael Cabanero, Sally C. M. Lau, Tracy Stockley, Devalben Patel, Penelope A. Bradbury, Adrian Sacher, Kazuhiro Yasufuku, Barbara A. Morash, Peter J. B. Sabatini, Lananhn N. Nguyen, Natasha B. Leighl, Ming-Sound Tsao, Frances A. Shepherd, Geoffrey Liu, Sebastiao N. Martins-Filho, Prodipto Pal

BRAF V600E mutation and MET amplification as resistance pathways of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in lung cancer

Background: Anaplastic lymphoma kinase (ALK) targeted therapies have demonstrated remarkable efficacy in ALK-positive lung adenocarcinomas. However, patients inevitably develop resistance to such therapies. To investigate novel mechanisms of resistance to second generation ALK inhibitors, we characterized and modeled ALK inhibitor resistance of ALK-positive patient-derived xenograft (PDX) models established from advanced-stage lung adenocarcinoma patients who have progressed on one or more ALK inhibitors. Conclusions: Bypass signaling pathway through c-MET and BRAF are independent mechanisms of resistance to alectinib. Individualized intervention against these resistance pathways could be viable therapeutic options in alectinib-refractory lung adenocarcinoma. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.05.018

Authors: Ruoshi Shi, Sebastiao N. Martins Filho, Ming Li, Aline Fares, Jessica Weiss, Nhu-An Pham, Olga Ludkovski, Vibha Raghavan, Quan Li, Deepti Ravi, Michael Cabanero, Nadeem Moghal, Natasha B. Leighl, Penelope Bradbury, Adrian Sacher, Frances A. Shepherd, Kazuhiro Yasufuku, Ming-Sound Tsao, Geoffrey Liu

Strong biological bias for ALK intron 19 breakpoints in NSCLC

EML4-ALK translocations are detected in 4-8 % of non-small cell lung cancer (NSCLC). While different EML4-ALK variants are defined by different breakpoints in the EML4 gene, most frequently located in intron 6 or 13, ALK breakpoint is almost invariably in intron 19. Rare reports describe EML4-ALK translocations with breakpoints in intron 17 or intron 18 of the ALK gene. Despite all these ALK breakpoints potentially generate oncogenic fusions, the reasons of this strong imbalance toward intron 19 (exon 20) breakpoints in ALK positive NSCLC are currently unknown. The aim of this study is to investigate the mechanisms that underlie ALK translocation in NSCLC. Our data show that all EML4-ALK fusion variants were equally oncogenic when overexpressed. In contrast, when EML4-ALK variants were generated from the endogenous loci there was a strong selection bias toward ALK fusions originating in intron 19 suggesting that intron 19 variants have the strongest oncogenic potential in lung epitheli..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-2400

Authors: Giulia C. Leonardi, Taek-Chin Cheong, Chiara Ambrogio, Tao Chen, Wei-Tien Tai, Elif Karaca, Ines Mota, Massimo Libra, Mark M. Awad, Rafael Blasco-Patino and Roberto Chiarle

Kirk SmithAugust 1, 2020

Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay

Detection of genomic rearrangements like ALK fusions are of great interest in non-small cell lung cancer (NSCLC) as those alterations can be targeted by an increasing number of drugs. To overcome tissue limitations, detection of these alterations from liquid biopsies is an unmet need, despite the development of novel NGS-based tests. To allow the detection of ALK rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel RT-PCR based assay and compared the results to tissue-based testing using immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH).The prototype cobas ALK/RET/ROS1 Fusion Panel assay was able to detect ALK fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression. Limited sensitivity could be explained by biological factors influencing nucleic acid shedding by tumours, as well as the presence of fusions not covered by the assay. However, the assay demonstrated high specificity. T..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-5299

Authors: Simon Heeke, Marius Ilié, Maryline Allegra, Audrey Vallée, Carole Salacroup, Virginie Tanga, Véronique Hofman, Jaya Rajamani, Michael Lee, Ellen Ordinario, Marc G. Denis and Paul Hofman

Conference PaperKirk SmithAugust 1, 2020ALK, non-small cell lung cancer, NSCLC, cobas, RET, ROS1

$TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors$

TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors

Anaplastic lymphoma kinase (ALK) gene rearrangements occur in up to 7% of patients with non-small cell lung cancer (NSCLC) with the majority as EML4-ALK fusions. Crizotinib (first generation ALK inhibitor) was the first approved ALK inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer. However, development of resistance to crizotinib caused by secondary kinase domain mutations, bypass signaling, or morphology changes occurs. Second generation ALK inhibitors alectinib, ceritinib, and brigatinib were able to overcome the majority of ALK resistant mutations (L1196M, G1269A and F1174L) acquired with crizotinib. The solvent front mutation (SFM) G1202R is a common resistant mutation to crizotinib and the second generation ALK inhibitors. Lorlatinib, a third generation ALK inhibitor, can overcome G1202R resistance with moderate IC50 values of 40 - 60 nM in cell-based assays. Although, compound mutations such as ones with both gatekeeper and solvent front mutations..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-5226

Authors: J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee and Brion Murray

Conference PaperKirk SmithAugust 1, 2020ALK, EML4-ALK fusions, NSCLC, ALK positive, TPX-0131

Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

The treatment of advanced non–small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade. Molecular characterization of the disease has led to the rapid development of personalized medicine and swift delivery of targeted therapies to patients. The discovery of the anaplastic lymphoma kinase (ALK) gene in patients with NSCLC has resulted in rapid bench–bedside transition of several active drugs, with several others currently in clinical trials. After the first-generation ALK inhibitor crizotinib, next-generation ALK inhibitors have entered clinical applications for ALK-rearranged NSCLC. Ceritinib, alectinib, and brigatinib have all received approval for ALK-positive patients who have failed prior crizotinib, as well as first-line therapy in treatment-naïve patients based on favorable efficacy. Most recently, lorlatinib, a potent, newer-generation ALK inhibitor, has been approved as second- or third-line treatment. These advances have led to better patient outcomes,..... READ ARTICLE

Cancer Management and Research DOI:10.2147/CMAR.S260274

Authors: Abhay Singh, Hongbin Chen

Lung Adenocarcinoma during Pregnancy: 11-Year Follow-Up

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. READ ARTICLE

Case Reports in Oncology DOI:10.1159/000508360

Authors: Acosta Rojas A., Collazo-Lorduy A., Remon J., Hernando Requejo O., Jiménez-Munarriz B., Rubio Rodríguez M.C., De Castro J.

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Data are sparse concerning the sequential use of multiple anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).This study investigated sequencing and outcomes among patients receiving multiple ALK inhibitors.This study provides initial information on real-world treatment patterns following the introduction of new ALK inhibitors, and supports the use of sequential ALK therapies. READ ARTICLE

Drugs - Real World Outcomes DOI:10.1007/s40801-020-00207-6

Authors: David M. Waterhouse, Janet L. Espirito, Marc D. Chioda, Bismark Baidoo, Jack Mardekian, Nicholas J. Robert, Elizabeth T. Masters

Novel MRPL13-ALK and PPP1CB-ALK Double Fusion As a Potential Mechanism of Acquired Resistance to First-Line Osimertinib in EGFR-Mutant HighGrade Neuroendocrine Tumor of the Lung

To our knowledge, this is the first report to state that that EGFR L858R and ALK double fusion were found in a high-grade neuroendocrine tumor of the lung. The rare ALK double fusion may be the potential reason for osimertinib resistance. Serine/threonine-PPP1CB (PPP1CBALK) fusion has already been reported in individual cases in glioma of infancy and leiomyosarcoma, but none in lung cancer. MRPL13-ALK is a novel fusion, which has never been reported yet. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2020.100079

Authors: Yuyan Jiao, MM, Ming Liu, MM, Ningning Luo, MS, Hao Guo, PhD, Jianzhe Li, PhD

Case StudyKirk SmithJuly 23, 2020osimertinib, EGFR, yrosine kinase inhibitor, NSCLC, ALK

Genome-Scale CRISPR Screening reveals novel factors regulating Wnt-dependent regeneration of mouse gastric organoids

An ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding of the underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features of in vivo stem cell-driven epithelial regeneration, providing an excellent ex vivo platform for interrogation of key regulatory mechanisms. Here, we employed a Genome-Scale CRISPR Knock-Out (GeCKO) screening assay using mouse gastric epithelial organoids to identify novel modulators of Wnt-driven stem cell-dependent epithelial regeneration in the gastric mucosa. In addition to known Wnt pathway regulators such as Apc, we found that knock-out (KO) of Alk, Bclaf3 or Prkra supports the Wnt independent self-renewal of gastric epithelial cells ex vivo. In adult mice, expression of these factors is predominantly restricted to non Lgr5-expressing stem cell zones above the gland base, implicating a critical..... READ ARTICLE

BioRxiv DOI:10.1101/2020.07.17.208496

Authors: Kazuhiro Murakami, Yumi Terakado, Kikue Saito, Yoshie Jomen, Haruna Takeda, Masanobu Oshima, Nick Barker

The Relationship Between Primary Tumor Localization and Driver Mutation in Lung Cancer

Driver mutations are detected in 30–35% of metastatic non-small cell lung cancer (NSCLC) patients, andmutation discordance may occur between biopsies. Therefore, false negative results for a driver mutation are reportedin some patients who may need rebiopsy. We aim to determine a clinicopathological feature (especially tumor localization), other than smoking and gender, that predicts driver mutation in metastatic non-squamous NSCLC.Methods: A total of 75 patients with driver mutation reports were included in the study. The age, gender, smokingstatus, pathology, primary tumor location, and mutation of each patient were evaluated. The relationship between theclinicopathological features and driver mutations was analyzed.Results: The median age of the patients was 66 (range: 36–85); 55 (73%) of the patients were male. A driver mutationwas detected in 23 (30.7%) patients. The rates of EGFR, ALK, and ROS1 were 22.7%, 6.7%, and 1.3%, respectively. Drivermutations were more commonly found in ..... READ ARTICLE

EJMO DOI:10.14744/ejmo.2020.13543

Authors: Cengiz Karacin, Tulay Eren, Goksen Inanc Imamoglu, Sema Turker, Fevzi Coskun Sokmen, Mustafa Altinbas

Real-World OutcomesKirk SmithJuly 16, 2020ALK-positive, smoking, non-smoking

Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure–activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties. READ ARTICLE

Acta Pharmaceutica Sinica B DOI: 10.1016/j.apsb.2020.07.010

Authors: Zhendong Song, Meijing Wang, Yang Ge, Xue-Ping Chen, Ziyang Xu, Yang Sun, Xiao-Feng Xiong

Review PaperKirk SmithJuly 15, 2020SHP2, Phosphatase, Selectivity, Allosteric inhibitor, Tumor therapy

Clinicopathological and Prognostic Significance of the EML4-ALK Translocation and IGFR1, TTF1, Napsin A Expression in Patients with Lung Adenocarcinoma

Objective: Patients with lung adenocarcinoma who harbor ALK gene rearrangements can demonstrate significant clinical benefit with ALK tyrosine kinase inhibitors. Insulin-like growth factor receptor 1 (IGFR1) is a cellular membrane receptor that is overexpressed in many tumors. It plays an important role in cancer progression and is associated with increased postoperative recurrence and poorer disease-free survival. The aim of this study was to determine the EML4-ALK mutation and IGFR1 expression in lung adenocarcinoma and analyze their prognostic value. Conclusion: A solid signet-ring cell pattern or mucinous cribriform pattern was present at least focally in all ALK-positive tumors, consistently with the literature. In addition, IGFR1 expression levels showed an increase in the EML4-ALK-mutated cases in our series, but the clinical significance of this finding should be supported by larger series and survival analysis. Our findings show that IGFR1 expression may be useful as a poor p..... READ ARTICLE

Turkish Journal of Pathology DOI:10.5146/tjpath.2020.01503

Authors: Pınar Bulutay, Nalan AkyÜrek, Leyla MemiŞ

Real-World OutcomesKirk SmithJuly 13, 2020EML4-ALK, IGFR1, TTF1, Napsin A

Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion

Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial prolifer..... READ ARTICLE

Head and Neck Pathology DOI:10.1007/s12105-020-01198-0

Authors: Lisa M. Rooper, Lester D. R. Thompson, Jeffrey Gagan, Bahram R. Oliai, Ilan Weinreb & Justin A. Bishop