Lower Anogenital Tract Squamous Terminology

This issue of Pathology Case Reviews describes and illustrates how the Lower Anogenital Squamous Terminology (LAST) terminology for the histopathologic reporting of human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract (LAT), jointly sponsored by the College of American Pathologists and the American Society of Colposcopy and Cervical Pathology (ASCCP), can be utilized in daily practice.1 Drs Teresa Darragh and David Wilbur, cochairs of the LAST Steering Committee, describe the rationale behind the introduction of a standardized terminology and recommendations for the use of specific biomarkers to clarify challenging histopathology in their commentary entitled, “Why LAST? Polishing the Gold Standard.” The underlying philosophy is similar to that of the Bethesda terminology for reporting cervical cytology, namely, the pathology report should be clear, concise, consistent, and relevant and use terminology that is evidence based and reproducible. The cornerstone of the LAST recommendations is that HPV-related squamous lesions of the LAT have a unified biology. Current evidence no longer supports the concept of intraepithelial neoplasia as a disease spectrum. Human papillomavirus causes a viral infection with little to no risk of malignant progression or a precancer that has a higher risk of progression to invasive carcinoma. This biology is reflected in the LAST-recommended 2-tiered terminology of low- and high-grade squamous intraepithelial lesion (SIL). The terminology change is expected to improve the reproducibility of histopathologic reporting aided by the judicious use of p16 immunohistochemistry and lead to overall improved patient management. Dr Castle’s commentary, “A LASTing Impression: Incorporating p16 Immunohistochemistry Into Routine Diagnosis of Cervical Neoplasia,” elaborates on the natural history of HPV infection of squamous epithelia of the LAT and its relationship to the terminology used for reporting its morphologic manifestations in squamous epithelia of the LAT. He discusses the pros and cons of utilizing the CIN2 reporting category and the role of p16 immunohistochemistry in grading the extent of histopathologic abnormality. The concerns that arose during the formulation of the LAST recommendations centered mostly on the impact of a 2-tiered terminology on management, and the potential for overuse of p16 by pathologists. Although LAST provides the option to include the relevant (-IN) terminology after low-grade SIL/high-grade SIL, Dr Castle discussed why this should be mandatory and not optional. As far as effective utilization of p16, many pathologists and practices are already routinely using p16 as an adjunct to routine hematoxylin-eosin–stained morphological assessment, so the LAST guidelines that delineate circumstances that warrant the use of p16 ancillary testing, and also those in which it should not be utilized, in fact should potentially decrease unnecessary usage of p16 testing. Drs Cox, Wilkinson, and O’Connor eloquently describe the historical variability of histopathology reporting terminology used for the LAT, largely based on physician specialty (general surgical pathologist, dermatologist/dermatopathologist, gynecologic pathologist, cytopathologist) and location (cutaneous versus mucosal). It is fascinating to read this review, which describes how our increasing understanding of HPV biology has improved our approach to management of HPV lesions. It also underscores the importance of the LAST project, which aims to decrease the lack of consistency and clarity with which pathologists have traditionally communicated these results to our clinical colleagues, leading to potential variation in management of lesions that had similar biologic potential. Drs Henry and Ioffe in their comprehensive article, “Squamous Premalignancy of the Cervix: Advantages of a 2-Tiered Versus a 3-tiered terminology,” describe the pros and cons of the proposed terminology change. Key aspects of the biology and morphology of HPV cervical disease and the application of biomarkers to aid in a 2-tiered classification are detailed and illustrated. The impact on patient management and the clinical concerns related to the LAST 2-tiered terminology are discussed. Because the ASCCP management guidelines published in 2007 promoted expectant management of CIN1 and CIN2 in young women, with the option to follow disease reported as CIN2/CIN3 but not CIN3, a 2-tiered terminology may result in those with CIN2 being overtreated if they were reported as high-grade SIL. The LAST publication and recently published ASCCP 2012 guidelines address this issue. The parenthetic use of CIN terminology in the reporting of disease in young women will facilitate expectant management. Drs Stoler and Wilbur cochaired the LAST work group that developed recommendations for the use of biomarkers in the diagnosis of HPV-related squamous lesions. Clinicians were, and many still are, under the false premise that the biopsy is the criterion standard and that all pathologists diagnose them in the same way. However, there are substantial published data to the contrary. We have data to show that the reproducibility of morphologic diagnoses using the current 3-tiered nomenclature (-IN1to -IN3) cannot be substantially improved by education of practitioners. On the other hand, limiting the number of reporting tiers and the use of objective biomarkers has been shown to reduce diagnostic variation in histopathologic diagnoses. Using a case-based approach, Drs Stoler and Wilbur detail the practical application of the LAST recommendations for and against the use of p16 immunohistochemistry as an adjunct to the hematoxylin-eosin morphologic assessment. They stress that appropriate usage of p16 has the potential to improve pathologist diagnostic accuracy/reproducibility and result in better patient care. In addition to addressing intraepithelial lesions, the LAST project also made recommendations for reporting superficially invasive squamous cell carcinoma. Drs Lytwyn, Zaino, Colgan, and Otis in their article entitled, “Superficially Invasive Squamous Cell Carcinoma of the Uterine Cervix: the Assessment of Key Parameters,” introduce the new terminology for invasive cervical carcinomas that can be managed conservatively. Superficially invasive squamous cell carcinoma of the cervix is defined as a grossly nonvisible carcinoma with no more than 3 mm of stromal invasion, no more than 7 mm of horizontal extent, and negative margins: In other words, a FIGO (International Federation of Gynecology and Obstetrics) stage 1A1 carcinoma. Although the LAST consensus development process supported this definition of superficially invasive squamous cell carcinoma, controversy and lack of consensus surrounding the measurement of horizontal extent and the impact the way in which LEEP, cone biopsies, and hysterectomies were sectioned had on the horizontal extent metric were acknowledged as an outstanding issue. In their article, the authors describe why the controversy exists and propose a method for measuring the horizontal extent metric. It is important for readers to note that the methodology represents the authors’ opinion and has not been officially endorsed by the College of American Pathologists or the ASCCP. Given the potential for the understaging of cervical carcinoma should inconsistency of horizontal extent measurement continue, this should be a future area of study, discussion, and consensus by the appropriate professional organizations. Using a case of multifocal early invasive squamous cell carcinoma of the vulva, Drs Heller, Colgan, and Allbritton review the application of the LAST recommendations to the vulva and vagina and highlight the difficulties associated with diagnosing these lesions. Technical aspects of measuring invasion, morphologic pitfalls, and management implications of this diagnosis are addressed by the authors. Drs Palefsky and Darragh report 3 cases of anal squamous premalignant disease to illustrate how the 2-tiered LAST terminology applies at this site. Their epidemiological data indicate anal cytology and biopsy are destined to become a larger part of our pathology practice. This timely review informs the reader of the prevention, diagnosis, and management of anal squamous intraepithelial lesions. As with any new set of recommendations or guidelines, implementation can take time and concerted educational efforts. The World Health Organization in conjunction with the International Society of Gynecologic Pathology are currently updating reporting histopathology terminology for the cervix, vulva, and vagina and will also likely propose a 2-tiered reporting terminology in the future. The 2012 ASCCP guidelines do not specifically address the use of LAST terminology; however, interim guidance is available,2,3 which states that when using 2012 LAST histopathology terminology, CIN1 is equivalent to histopathologic low-grade SIL, and CIN2,3 is equivalent to histopathologic high-grade SIL. It is emphasized that cytological low-grade SIL is not equivalent to histopathologic CIN1, and cytological high-grade SIL is not equivalent to histopathologic CIN2,3. Future ASCCP updates will further delineate management strategies using a 2-tiered histopathologic reporting terminology. Furthermore, with additional experience, subsequent revisions to the LAST recommendations if and when warranted will follow.FIGURE: Máire A. Duggan, MD, FRCPCFIGURE: Ritu Nayar, MD

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