Molecular diagnostic testing of cytology specimens: current applications and future considerations

Molecular mechanisms of pathogenesis continue to be discovered, accelerating significant expansion of the spectrum of clinically useful molecular diagnostic tests and their incorporation into patient care algorithms. Currently, molecular assays facilitate identification of infectious processes, detection of specific constitutional and somatically acquired pathogenic mutations, guidance of therapy selection, and monitoring of treatment response and disease progression. The correlation of genomic test results with clinical, morphologic, and immunophenotypic findings has defined the practice of “precision medicine” with wide-reaching implications for health care. As novel promising techniques such as microarrays and next-generation sequencing are adopted by health care providers, new practice standards are being developed for incorporation into practice. Cytology specimens are good sources of high-quality nucleic acids. Although sometimes limited in quantity, in many cases such specimens are well suited for molecular diagnostic testing, which is capable of maximizing the number of tests from small amounts of sample. The pathologist continues to serve as a central resource for diagnostic testing and consultation regarding appropriate use of molecular tests. Understanding current methodologies, clinical utility of currently available nucleic acid tests, validation requirements for test implementation, quality assurance metrics, and future technology trends is essential to the practice of contemporary molecular pathology.