Laboratory Studies

Although no definitive role has been identified for human papillomavirus (HPV) infection, lesional polymerase chain reaction testing for HPV DNA may be performed. In addition, flow cytometric analysis of tissue may have a role in detecting lesions of proliferative verrucous leukoplakia (PVL) early in the course of disease. Furthermore, increased expression of Mcm-2 as detected by immunohistochemistry may be helpful in identifying areas of potential malignant transformation within lesions of proliferative verrucous leukoplakia.^{[24, 25]}A small 2016 study of salivary proteins has shown an association with low-expression levels of angiotensin and dipeptidyl peptidase 1 proteins in proliferative verrucous leukoplakia patients versus controls, suggesting that these could be used as potential biomarkers of disease in the future.^[26]

Procedures

Perform an oral biopsy using either a scalpel or a brush biopsy, and use computer-aided analytical techniques to detect dysplasia or carcinoma.

Histologic Findings

Histology findings can range from verrucous hyperplasia to verrucous carcinoma to less-differentiated carcinoma and can include any combination of these histologic features. Additionally, a lymphocytic lichenoid infiltrate without evidence of significant basilar vacuolization has been reported in some cases.^{[10, 20]}One or more of these histologic features may appear in a single biopsy specimen, multiple biopsies taken at the same time, or from serial biopsies over time.^[27]Because of this variability, the diagnosis of proliferative verrucous leukoplakia (PVL) is based mainly on clinical findings.^{[28, 29]}

Treatment & Management

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Bagan JV, Jimenez Y, Murillo J, et al. Epstein-Barr virus in oral proliferative verrucous leukoplakia and squamous cell carcinoma: A preliminary study. Med Oral Patol Oral Cir Bucal. 2008 Feb 1. 13(2):E110-3. [Medline].
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Kannan R, Bijur GN, Mallery SR, et al. Transforming growth factor-alpha overexpression in proliferative verrucous leukoplakia and oral squamous cell carcinoma: an immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Jul. 82(1):69-74. [Medline].
Kahn MA, Dockter ME, Hermann-Petrin JM. Proliferative verrucous leukoplakia. Four cases with flow cytometric analysis. Oral Surg Oral Med Oral Pathol. 1994 Oct. 78(4):469-75. [Medline].
Klanrit P, Sperandio M, Brown AL, et al. DNA ploidy in proliferative verrucous leukoplakia. Oral Oncol. 2007 Mar. 43(3):310-6. [Medline].
Hansen LS, Olson JA, Silverman S Jr. Proliferative verrucous leukoplakia. A long-term study of thirty patients. Oral Surg Oral Med Oral Pathol. 1985 Sep. 60(3):285-98. [Medline].
Bagan JV, Murillo J, Poveda R, Gavalda C, Jimenez Y, Scully C. Proliferative verrucous leukoplakia: unusual locations of oral squamous cell carcinomas, and field cancerization as shown by the appearance of multiple OSCCs. Oral Oncol. 2004 Apr. 40(4):440-3. [Medline].
Zakrzewska JM, Lopes V, Speight P, Hopper C. Proliferative verrucous leukoplakia: a report of ten cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Oct. 82(4):396-401. [Medline].
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Batsakis JG, Suarez P, el-Naggar AK. Proliferative verrucous leukoplakia and its related lesions. Oral Oncol. 1999 Jul. 35(4):354-9. [Medline].
Ghazali N, Bakri MM, Zain RB. Aggressive, multifocal oral verrucous leukoplakia: proliferative verrucous leukoplakia or not?. J Oral Pathol Med. 2003 Aug. 32(7):383-92. [Medline].
Bagan JV, Jiménez-Soriano Y, Diaz-Fernandez JM, Murillo-Cortés J, Sanchis-Bielsa JM, Poveda-Roda R, et al. Malignant transformation of proliferative verrucous leukoplakia to oral squamous cell carcinoma: a series of 55 cases. Oral Oncol. 2011 Aug. 47(8):732-5. [Medline].
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Bagan JV, Jimenez Y, Sanchis JM, et al. Proliferative verrucous leukoplakia: high incidence of gingival squamous cell carcinoma. J Oral Pathol Med. 2003 Aug. 32(7):379-82. [Medline].
Abadie WM, Partington EJ, Fowler CB, Schmalbach CE. Optimal Management of Proliferative Verrucous Leukoplakia: A Systematic Review of the Literature. Otolaryngol Head Neck Surg. 2015 Oct. 153 (4):504-11. [Medline].
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Media Gallery

A leukokeratotic plaque is seen in on the upper lip, along with an erythematous plaque on the left hard palate. The patient has a large right-palate defect from a prior surgical excision of a squamous cell carcinoma.

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Author

Rahat S Azfar, MD Clinical Instructor, Department of Dermatology, University of Pennsylvania Health System

Rahat S Azfar, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Fatima A Abdulla, MD Associated Staff Physician, Department of Dermatology, Cleveland Clinic Abu Dhabi, UAE

Fatima A Abdulla, MD is a member of the following medical societies: European Academy of Dermatology and Venereology, Jordan Medical Association, Jordanian Society of Dermatology and Venereology

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for MOHS Surgery, Association of Military Dermatologists, Phi Beta Kappa

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Jeff Burgess, DDS, MSD (Retired) Clinical Assistant Professor, Department of Oral Medicine, University of Washington School of Dental Medicine; (Retired) Attending in Pain Center, University of Washington Medical Center; (Retired) Private Practice in Hawaii and Washington; Director, Oral Care Research Associates

Disclosure: Nothing to disclose.

Additional Contributors

Jacek C Szepietowski, MD, PhD Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

Sections Proliferative Verrucous Leukoplakia
Overview
Presentation
DDx
Workup
Treatment
Medication
References

Proliferative Verrucous Leukoplakia Workup

Laboratory Studies

Procedures

Histologic Findings

References

Tables

Contributor Information and Disclosures

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