Bridging the gap: Cytopathology at the threshold of personalized medicine

The discipline of Anatomic Pathology has experienced a number of technical innovations significantly changing how physicians practice the art and science of pathology and view their professional responsibilities. Initially, pathology was the study of gross morbid anatomy. The application of light microscopy to the study of disease produced the discipline of histopathology and gave birth to modern Surgical Pathology as practiced by Arthur Purdy Stout and Lauren V. Akerman among others. Cytopathology as championed by Papanicolaou had its major impact on patient screening for early detection of neoplastic disease and monitoring for disease recurrence. The development of electron microscopy and immunohistochemistry significantly improved the pathologist’s ability to determine a neoplasm’s direction of differentiation and more accurately predict a given neoplasm’s biopotential and the patient’s response to therapy. For years the Papanicolaou Society of Cytopathology (PSC) has dedicated itself to ‘‘bridging the gap between cytopathology and surgical pathology’’, contributing to the convergence between fine needle aspiration (FNA) and core needle biopsy (CNB), now performed and interpreted seamlessly. From a number of PSC guidelines for the handling of samples from different body sites, to its current monograph series, entitled ‘‘Cytohistology of Small Tissue Samples’’ the PSC has kept its focus on generating diagnostic, prognostic, and therapeutic information, in a noninvasive manner. The present symposium issue of Diagnostic Cytopathology explores recent advances in diagnostic techniques including molecular diagnosis, digital imaging, flow cytometry, and immunohistochemistry. These technical advances allow pathologists to study tissue specimens in new and exciting ways. More precisely directed therapies (currently falling within the rubric of ‘‘personalized medicine’’) will require pathologists to evaluate tissue specimens for key mutations or amplifications which are predictive of response to specific targeted therapies. Appropriate use of molecular diagnostic tests will help guide oncologists to the most appropriate and specific ‘‘targeted therapy’’ or treatment protocol available. As many of the tests will be performed on cytologic specimens, cytopathologists must be knowledgeable about appropriate molecular testing and the type and amount of tissue required for analysis. Cytopathologists should play a consultative role in test selection to optimize testing protocols and the utilization of the limited amount of tissue available. Optimally, guidance from Anatomic Pathologists will help focus testing to appropriate modalities and control testing costs in an increasingly resource limited environment. The development of digital imaging and telepathology/ cytology may allow increased ease in obtaining consultations from distant sites and improve the utilization of cytopathologists’ and cytotechnologists’ time. Although digital pathology may improve quality and timeliness of pathologic diagnoses, potential downsides exist for ‘‘telepathology. ’’ Telepathology systems may unexpectedly increase costs owing to equipment expense and the cost of ongoing maintenance and technical support. Other adverse outcomes could include an increasing centralization of expertise in cytopathology with loss of community-based practitioners and the dominance of a few large commercial providers or even distant outsourcing of professional services. A number of neoplasms demonstrate lineage specific mutations helpful in their recognition on biopsy material. Synovial sarcoma, the Ewing’s family of neoplasms and gastrointestinal stromal tumors are three examples of such malignancies. A variety of molecular techniques can be used to demonstrate the associated genetic changes. Fluorescence in situ hybridization (FISH) is useful for the University of Utah, Surgical Pathology, Salt Lake City, Utah, USA Received 16 March 2012; Accepted 16 March 2012 DOI 10.1002/dc.22868 Published online in Wiley Online Library (wileyonlinelibrary.com).