Cytology Specimens: A Goldmine for Molecular Testing

Advances in targeted therapies and molecular diagnostics have revolutionized the field of pathology, with particular impact on the field of cytopathology. Cytopathology specimens have a major role in the diagnosis of patients with advanced diseases—a population where predictive molecular testing is now the standard of care for a growing number of tumor types. In addition, diagnostic molecular and cytogenetic applications are an extremely fertile field for cytology samples. Despite the many advances in molecular cytopathology, the suitability and utility of cytology samples in molecular testing of tumors is still frequently questioned, and it is common for clinical trials and commercial laboratories to exclude cytology samples from molecular testing. This is related, at least in part, to the lack of familiarity with cytologic preparations, as well as the lack of uniformity in preanalytical variables involved in preparation of cytologic specimens across institutions. Conversely, at some institutions, cytology specimens are fully integrated into the molecular testing pipelines, and are considered equivalent or superior to small biopsies for molecular testing. One of the greatest advantages of cytology samples in molecular testing is that a variety of cytologic preparations are non–formalin fixed (eg, cell block collected in non-formalin media, smears, liquid-based, etc) and thus provide a superior quality of nucleic acid, devoid of the damaging effects of formalin. On the flip side, incorporation of such specimens requires a separate validation of molecular tests on non–formalin-fixed material, as well as a more customized approach to specimen handling. We hope that this special section in the Archives will highlight some of the advantages afforded by cytology specimens, which justify extra effort of incorporating these samples into molecular testing workflows.This special section of the Archives is divided into 2 parts: part I is presented in this issue, and part II will appear in the December 2016 issue. In part I, we present 3 articles that describe practical experience with molecular testing of solid tumors using small samples at MD Anderson Cancer Center (by Roy-Chowdhuri and Stewart), Memorial Sloan Kettering Cancer Center (by Tian et al), and the University of Colorado (by Aisner et al), with an emphasis on the critical utility of cytology samples in achieving high success rates in molecular testing of tumors by conventional methods as well as next-generation sequencing. The articles highlight various adaptations of standard processes in pathology laboratories at these institutions to fulfill the mantra of doing more with less.In part II of this special section are 4 articles addressing practical, high-yield topics in molecular cytopathology. Saqi reviews the advantages and limitations of ancillary studies on cell blocks, and discusses the possible methods to optimize the results. Savic and Bubendorf discuss common fluorescence in situ hybridization (FISH) applications in cytology, emphasizing the essential role of targeted evaluation of the lesional cells for the success of FISH in cytologic preparations. Zhou and Moreira address issues of predictive biomarker testing in lung cytology and small biopsy samples by immunohistochemistry, emphasizing the impact of cytologic fixatives on several theranostic antibodies. Lastly, Zhang and Lin review the current state of the art in molecular testing of thyroid nodules—a rapidly evolving area, with a great potential to guide clinical management of patients with equivocal diagnoses in thyroid fine-needle aspirates.We hope that this special section in the Archives will highlight that cytology samples represent a goldmine for molecular studies, and will promote the greater integration of cytology samples into routine molecular testing of tumors.We would like to thank Philip T. Cagle, MD, for proposing and supporting this special section, and Katie Giesen, the Archives managing editor, for her outstanding administrative assistance.