We wholeheartedly thank Philip T. Cagle, MD, editor-in-chief, and the editorial board of the Archives of Pathology & Laboratory Medicine for giving us the exceptional opportunity to publish this special section consisting of 10 articles from the Molecular Cytopathology Meeting: Focus on Next Generation Sequencing [NGS], which took place in Napoli, Italy, on October 18, 2016.
It is widely held that any molecular assay that has been developed on formalin-fixed, paraffin-embedded material can also be performed on any cytology sample with appropriate validation.1 However, the complexity of the preanalytical aspects, reflected by the wide range of preparations, fixation, and staining techniques adopted in different cytology laboratories; the need for a rigorous validation protocol; and the specific clinical applications requires a conscious and ongoing effort to fully exploit the vast potential offered by minimally invasive cytology samples.2 Thus, in order to engage in a timely update on the increasing number and variety of molecular tests performed on cytologic specimens, the University of Naples Federico II has been organizing an annual molecular cytopathology meeting since 2010. The meeting aims at both engaging pathologists with the clinical and therapeutic aspects of oncology and at engaging clinicians with the challenges of molecular testing on small tissue samples. Further, the meeting has also served as the launchpad for the Molecular Cytopathology Meeting Group, with a goal of developing collaborative projects across the globe. Performing interlaboratory ring trials with cytologic smears is difficult because these slides are not reproducible or replaceable, and therefore the molecular cytopathology literature primarily reflects single-institution studies rather than multicenter experiences. The Molecular Cytopathology Meeting Group3 has recently optimized quantitative cytologic molecular reference slides as a useful tool for monitoring the performance of a variety of multigene mutational assays, to achieve better standardization of molecular cytopathology methods.
The 10 articles in this 2-part special section on molecular cytopathology review the current literature summarizing the diagnostic experience of expert molecular cytopathologists and are specifically designed to be a practical and concise guide to the current clinical practice. In part I of this series, we present 4 articles, 3 of which focus on preanalytical issues of specimen handling, processing, and storage that impact downstream molecular testing. The article by Lozano et al focuses on routine cytologic smears as a suitable platform for lung cancer predictive biomarker testing, using rapid on-site evaluation (ROSE) of procured material. Martini et al highlight the use of liquid-based cytology as a valid alternative in situations where ROSE is not available or feasible. With the increasing use of cytologic material for molecular testing, the need for preserving and storing genomic material for future ancillary studies has also grown, and da Cunha Santos reviews the utility of Whatman Classic and Elute FTA cards as useful storage tools for molecular testing. In the last article of part I in this series, Fassan emphasizes the need for a strategic change in specimen handling and processing in pathology laboratories in order to triage and optimize cytologic samples not just for diagnosis, but also to preserve specimen biomolecular integrity for downstream ancillary studies. The second part of this special section includes an editorial by Salto-Tellez highlighting the role played by the cytopathologist in the multidisciplinary care of the cancer patient and the need to integrate molecular cytopathology in pathology residents' education and training. The article by Nishino and Nikiforova provides an update on molecular testing for cytologically indeterminate thyroid nodules to help cytopathologists select and interpret these tests in a clinically meaningful way. The demonstration of specific oncogenic mutations in pancreatic cytopathology can help stratify cases into high- and low-risk groups, and de Biase et al focus on the role of NGS in increasing the accuracy of preoperative cytologic diagnoses of pancreatic lesions. The unique technical and biological challenges of molecular testing in lung cancer patients progressing on targeted treatments specifically relating to NGS analyses of endobronchial ultrasound–guided needle aspiration are discussed by Guerini-Rocco et al. And finally, the 2 articles by Teixidó et al and Alì et al discuss RNA-based assays as part of comprehensive molecular diagnostics, indicating that both NGS and the nCounter system are promising methods for rapid detection of targetable gene fusions using minute amounts of RNA.
We hope that this special section in the Archives will highlight the role of the Molecular Cytopathology Meeting in educating and enabling the pathologist to effectively play a central role in the molecular analysis workflow of cytologic samples.
References
Giancarlo Troncone, MD, PhD, is full professor of anatomic pathology at the University Federico II in Naples, Italy. He is director of the cytopathology unit, the molecular pathology unit, and the master's degree program in predictive molecular pathology. He is the coordinator of the PhD course in public health and preventive medicine. He was trained in pathology at the Nuffield Department of Pathology, University of Oxford (Oxford, United Kingdom), and in cytopathology at the Department of Pathology and Laboratory Medicine, University of Pennsylvania (Philadelphia). His research interests include the development, validation, and quality assessment of a wide range of morpho-molecular techniques on cytopathologic specimens in the field of predictive pathology of solid tumors. He maintains an active cytodiagnostic practice, which includes lung, thyroid, lymph node, and breast samples.
Giancarlo Troncone, MD, PhD, is full professor of anatomic pathology at the University Federico II in Naples, Italy. He is director of the cytopathology unit, the molecular pathology unit, and the master's degree program in predictive molecular pathology. He is the coordinator of the PhD course in public health and preventive medicine. He was trained in pathology at the Nuffield Department of Pathology, University of Oxford (Oxford, United Kingdom), and in cytopathology at the Department of Pathology and Laboratory Medicine, University of Pennsylvania (Philadelphia). His research interests include the development, validation, and quality assessment of a wide range of morpho-molecular techniques on cytopathologic specimens in the field of predictive pathology of solid tumors. He maintains an active cytodiagnostic practice, which includes lung, thyroid, lymph node, and breast samples.
Sinchita Roy-Chowdhuri, MD, PhD, is assistant professor of pathology and the director of molecular cytopathology at the University of Texas MD Anderson Cancer Center (Houston). She received her medical degree from Calcutta National Medical College, Calcutta University, India, and her PhD degree from University of Illinois at Chicago. Dr Roy-Chowdhuri completed her residency training in anatomic pathology at the National Cancer Institute, National Institutes of Health (Bethesda, Maryland), followed by fellowships in cytopathology at the National Cancer Institute, National Institutes of Health (Bethesda, Maryland), and in molecular genetic pathology at Memorial Sloan Kettering Cancer Center (New York, New York). Her research interests include the application of molecular diagnostics in cytology samples and identifying preanalytic factors to improve molecular testing from limited-volume samples. Dr Roy-Chowdhuri currently serves as the associate editor in molecular cytopathology for the Archives of Pathology & Laboratory Medicine.
Sinchita Roy-Chowdhuri, MD, PhD, is assistant professor of pathology and the director of molecular cytopathology at the University of Texas MD Anderson Cancer Center (Houston). She received her medical degree from Calcutta National Medical College, Calcutta University, India, and her PhD degree from University of Illinois at Chicago. Dr Roy-Chowdhuri completed her residency training in anatomic pathology at the National Cancer Institute, National Institutes of Health (Bethesda, Maryland), followed by fellowships in cytopathology at the National Cancer Institute, National Institutes of Health (Bethesda, Maryland), and in molecular genetic pathology at Memorial Sloan Kettering Cancer Center (New York, New York). Her research interests include the application of molecular diagnostics in cytology samples and identifying preanalytic factors to improve molecular testing from limited-volume samples. Dr Roy-Chowdhuri currently serves as the associate editor in molecular cytopathology for the Archives of Pathology & Laboratory Medicine.