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Cytopathology in Focus: Synergy in cytopathology and molecular microbiology

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Charles D. Sturgis, MD
Gary W. Procop, MD

August 2018—In today’s less-is-more world, health care consumers and providers often seek explicit and detailed information from minimally invasive procedures and tiny samples. Over are the days of “malignant cells present” and on to the next case. Cytopathologists and cytotechnologists are embracing and integrating novel techniques and applying new methods to the diagnosis and classification of essentially every imaginable form of neoplasia. The 2018 WHO publications confirm that 29 percent of deaths worldwide (more than 10 million people annually) are attributable to communicable diseases.1,2 This means the purpose of procuring many specimens is not to just rule out malignancy but also to diagnose infectious etiologies. Awareness of current and potential future synergies between traditional cytopathology practices and molecular microbiologic approaches may help pathologists and their patients sleep better at night.

When many physicians “think cytology” their minds turn immediately to concepts of cervical cancer prevention by Pap testing. No cancer screening test has contributed more to the well-being of humans than good old-fashioned exfoliative cervicovaginal cytology. Cotesting and reflex testing of liquid-based cervicovaginal cytology samples for human papillomavirus have become standard of care, and a burgeoning literature exists that evaluates and compares various commercially available and laboratory-developed techniques for detecting nucleic acids and proteins that are specific to certain strains of HPV.3,4 With the recent Food and Drug Administration approval of the first HPV molecular test for primary screening for cervical cancer, even the lay press (Time) has published articles covering the synergistic applications of molecular microbiologic techniques and liquid-based cytology samples.5,6

Non-morphologic and non-culture–based testing platforms have also emerged as the gold standard for diagnoses of other cervicovaginal infections, including Chlamydia trachomatis and Neisseria gonorrhoeae. These pathogens can be readily identified from PreservCyt liquid-based Pap samples.7,8 Some laboratories are also using commercially available, non-amplified nucleic acid probe-based tests on cervicovaginal cytology samples to identify the etiologic agents of vaginitis, including Candida species, Gardnerella vaginalis, and Trichomonas vaginalis.9,10 Molecular testing for HPV can also prove valuable in nongynecologic cytologic samples derived from anal carcinomas and squamous cell carcinomas of the head and neck.11,12

Molecular testing of cytology samples for oncogenic viruses is not limited to HPV. Other viruses such as Epstein-Barr are known to be carcinogenic, and confirmation of EBV in conditions such as certain B-cell lymphomas and undifferentiated nasopharyngeal carcinomas can definitely be achieved from cytology samples.13,14

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