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Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting

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Abstract

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as “corrugated ortho(para)hyperkeratotic lesion, not reactive” and “SCC” (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the “Bulky hyperkeratotic epithelial proliferation, not reactive” category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) “corrugated ortho(para)hyperkeratotic lesion, not reactive;” (2) “bulky hyperkeratotic epithelial proliferation, not reactive;” and (3) “suspicious for,” or “squamous cell carcinoma.” Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

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Acknowledgements

Statistical analysis of inter-rater agreement was provided by Sijia Yue, MS at the University of Florida College of Public Health and Health Professions Department of Biostatistics.

Funding

No external funding was obtained for this study, with support from institutional review boards and the sponsoring societies.

Author information

Author notes

  1. Lester D. R. Thompson and Sarah G. Fitzpatrick share equal authorship contribution.

Authors and Affiliations

  1. Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, 5601 De Soto Avenue Woodland Hills, CA, 91364, Woodland Hills, USA

    Lester D. R. Thompson

  2. Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA

    Sarah G. Fitzpatrick, Indraneel Bhattacharyya, Mohammed N. Islam & Donald M. Cohen

  3. Atlanta Oral Pathology, Emory University School of Medicine, Decatur, GA, USA

    Susan Müller

  4. Oral Health and Diagnostic Sciences, University of Connecticut Health, Farmington, CT, USA

    Ellen Eisenberg

  5. Section of Diagnostic Sciences, Department of Applied Dental Medicine, Southern Illinois University School of Dental Medicine, Alton, IL, USA

    Jasbir D. Upadhyaya

  6. Department of Pathology, University of Chicago Medicine, Chicago, IL, USA

    Mark W. Lingen

  7. Department of Diagnostic and Biomedical Sciences, University of Texas School of Dentistry at Houston, Houston, TX, USA

    Nadarajah Vigneswaran

  8. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA

    Sook-Bin Woo

  9. Department of Diagnostic Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA

    Elizabeth A. Bilodeau

  10. Centro Clínico de Cabeza y Cuello, Patología División, Guatemala City, Guatemala

    Roman Carlos

  11. Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA

    Marino E. Leon

  12. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

    James S. Lewis Jr. & Mitra Mehrad

  13. Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Kelly R. Magliocca

  14. Department of Pathology, Inova Fairfax Hospital, Falls Church, VA, USA

    Haresh Mani

  15. Department of Pathology, University of Ottawa, Ottawa, Ontario, Canada

    Bibianna Purgina

  16. Department of Pathology, MUSC Health-University Medical Center, Charleston, SC, USA

    Mary Richardson

  17. Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA

    Bruce M. Wenig

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  1. Lester D. R. Thompson
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Correspondence to Lester D. R. Thompson.

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Thompson, L.D.R., Fitzpatrick, S.G., Müller, S. et al. Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting. Head and Neck Pathol 15, 572–587 (2021). https://doi.org/10.1007/s12105-020-01262-9

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