Proliferative Verrucous Leukoplakia of the Gingiva: A Rare Palatal Presentation

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1 CASE REPORT Proliferative Verrucous Leukoplakia of the Gingiva: A Rare Palatal Presentation M. Shaurya*, S. Ravindra, Sarvani Murthy *Post Graduate Student, Professor and Head, Department of Periodontics, Professor and Head, Department of Oral Pathology, Sri Hasanamba Dental College and Hospital, Hassan, Karnataka, India ABSTRACT Proliferative verrucous leukoplakia (PVL), distinct clinical form of oral leukoplakia, is a rare potentially malignant oral mucosal disorder with a high rate of progression to oral squamous cell carcinoma (SCC) and verrucous carcinoma (VC). It frequently involves periodontal sites. PVL is characterized by a high recurrence rate. The condition develops initially as focal clinical hyperkeratosis that progressively becomes a wide multifocal disease with gross exophytic features. Multiple oral sites such as buccal mucosa, gingiva, alveolar ridges and tongue are affected, but gingiva is one of the most frequently involved site. A clinically distinctive form of PVL, called PVL of the gingiva, was proposed by some investigators to identify a subset of patients with only gingival involvement. This paper attempts to describe a case of PVL with a rare palatal presentation with periodontal involvement. Keywords: Oral mucosal lesions, Periodontal diseases, Oral pathology INTRODUCTION Proliferative Verrucous Leukoplakia (PVL) is described by the World Health Oraganisation (WHO) as a rare, but distinctive, high risk clinical form of oral precancerous lesions, without a single pathognomonic criterion but with characteristic combined histologic and clinical features and behavior. [1] Recently, it was classified among the potentially malignant disorders of the oral cavity. [2] The progression rate to oral cancer in conventional leukoplakia ranges from 0.13% to 17.5% over an extended follow up; PVL is a chronic, slow growing lesion that seems to have a higher malignant Serial Listing: Print-ISSN ( ) Online-ISSN ( ) Formerly Known as Journal of Advanced Dental Research Bibliographic Listing: Indian National Medical Library, Index Copernicus, EBSCO Publishing Database, Proquest, Open J-Gate. Quick Response Code: Access this article online Website: DOI: ***** transformation rate. The gingiva and tongue are the most common sites of transformation observed in PVL. [1,3] However, this report describes a case of rapid progression of the lesion of PVL with unique exophytic appearance, but uniquely had stable features clinically and histopathologically in the follow up period. CASE REPORT A female patient aged 45 years reported to Department of Periodontology, Sri Hasanamba Dental College and Hospital, Hassan district with chief complaint of swelling on the inner side of the upper front teeth region which increased in size since one month. Seven months back swelling was of a smaller size for which patient tried meddling with it by pin pricking the lesion, and reported the lesion reached the present size of dimension 1 1 cm over 1 month, which bled spontaneously. No other associated symptoms were present. No relevant past dental/medical or family history was reported. Personal history revealed patient consumed mixed diet and had deleterious habit of chewing tobacco powder wrapped in betel leaves since 35 years. Intra-oral examination revealed the oral hygiene status was poor. Periodontal status revealed generalized Address for correspondence: M. Shaurya, Department of Oral Pathology, Sri Hasanamba Dental College and Hospital, Hassan, Karnataka, India. shauryamanjunath@gmail.com 35

2 gingival inflammation and bleeding on probing, presence of generalized periodontal pockets, gingival recession and tooth mobility. Local examination of the lesion revealed an overgrowth on the palatal gingiva, measuring about 1 1 cm dimension between the tooth 12 and 13 with extension into the rugae area [Figure 1]. 13 presented with Miller s Class II recession [Figure 2]. The surface of the exophytic growth was characteristically wart like, roughened and lobulated with white areas on it. It was soft in consistency which had tendency to bleed spontaneously or on slight provocation. Other soft tissue examination revealed irregular, non-scrapable white lesion about 3 2 cm dimension with rough texture on the left buccal mucosa, adjacent to retro-molar area at line of occlusion with interspersed orange-reddish keratotic patches in it. On extra-oral examination, no gross facial asymmetries were detected, right and left submandibular lymph nodes were palpable, slightly tender, firm in consistency and mobile [Figure 3]. Based on the history and clinical findings, the case was provisionally diagnosed as- Leukoplakia of left buccal mucosa with pyogenic granuloma in relation to right lateral incisor and canine (12 and 13). The treatment plan proceeded as follows: 1) Patient was counseled and educated about the deleterious effects of tobacco and motivated to quit chewing tobacco. 2) Oral hygiene instructions were given and Phase I therapy (scaling) was performed. 3) A week later excisional biopsy of the lesion was done under local anaesthesia inclusive of the surrounding normal tissue and the patient was prescribed systemic antibiotics and antiseptic mouth wash. 4) Oral multivitamins were given. The biopsy specimen was sent for histopathological examination. The patient was recalled after a week for reevaluation. Re-evaluation after 1 week showed uneventful wound healing. Figure 3: Photograph showing leukoplakia of the left buccal mucosa with interspersed orange-red pigmentations Figure 1: Photograph showing gingival overgrowth on the palate between right lateral incisor and canine (12 & 13) Figure 2: Patient s labial view showing recession in relation to 13. Figure 4: H & E section showing Hyperkeratosis, bulbous rete ridges (under 4 magnifi cation) 36

3 Histopathology Histopathological examination revealed stratified squamous epithelium which was hyperkeratotic in nature. The rete ridges were bulbous/drop shaped, with basilar hyperplasia. Acanthosis, individual cell keratinisation could be appreciated in few areas of epithelium, which suggested features of dysplastic epithelium. Dysplasia was of moderate degree; Grade 4 on the palatal gingival and Grade 2 on left buccal mucosa as described by Hansen. The underlying connective tissue was cellular, composed of dense chronic inflammatory infiltrate with few bundles of collagen. There were abundant blood vessels and areas of haemorrhage could be appreciated. By combining the characteristics of the oral lesions and histopathological changes, a primary diagnosis of Proliferative Verrucous Leukoplakia was drawn [Figures 5 and 6]. DISCUSSION White lesions are relatively frequent in the oral cavity with a prevalence of approximately 24.8%. Leukoplakia is by far the most common oral potentially malignant disorder representing 85% of such lesions. Oral leukoplakia (leuko = white; plakia = patch) is defined by the World Health Organization (WHO) as A white patch or plaque that cannot be characterized clinically or pathologically as any other disease. [4,5] Barely a few decades ago, a rare form of oral leukoplakia known as proliferative verrucous leukoplakia (PVL) was described, first by Hansen et al. in [6] It presents specific characteristics, mainly a more aggressive biological behaviour than other forms of leukoplakia expressed by: a tendency towards multifocality; a high probability of recurrence; and a high rate of malignant transformation, which can range between 40 and 100% in a follow-up period of 4.4 to 11.6 years. [7] PVL is a progressive condition which develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. The lesions are slow-growing yet persistent, as well as irreversible and resistant to all forms of treatment with a high recurrence rate. [8] Throughout its development, it is common to find erythematous and/or verrucous areas that occasionally progress to verrucous carcinoma or squamous cell carcinoma (SCC). [3,6] According to case series presented regarding PVL patients who develop oral cancers were more commonly females [9] and non-smokers. [10] The mean age at the time of diagnosis is over 60 years. Tobacco use does not seem to have a significant influence on the disease given that PVL occurs both in smokers and non-smokers. [7] There is probably no racial predilection [Figure 4]. [11] A number of the reported cases have initially presented as a solitary, otherwise inconspicuous flat homogenous leukoplakia, while others present with multiple involved sites at time of diagnosis. Initial presentation may vary but recurrence after treatment is very often. It was noticed that after first treatment the lesions recur, not only at the previous site but also at new sites too. The gingiva is most commonly affected (Silverman et al. 1997, Fettig et al and Bagan et al. 2003) and hence the term Proliferative Verrucous Leukoplakia of the Gingiva (PVLG) was introduced. [12] But because of the absence of a specific description or reference and Figure 5: H & E section showing Keratin Deposition (under 40 magnification) Figure 6: H & E section showing Basilar hyperplasia, Hyperchromatic nuclei (under 40 magnifi cation 37

4 as a compromise for comparing the past literature to the present case which involved the palatal gingiva partly with extensions partly into the anterior palatal rugae, it has been assumed that the use of the term gingiva does not differentiate tissues with functionally or anatomically specific features, so it should be used only to refer to keratinized tissue around teeth. [13] The etiology of PVL is still not known. The proliferative effect of PVL was explained on basis of the high rate of field cancerization existing in PVL patients (Bagan et al. 2004). [14] It was noted that there is usually a time lag between the appearances of new tumors in the same patient [12] ; which is suggestive of an infectious etiology. Although several authors have suggested that HPV (Human Papilloma Virus) might have a role in the pathogenesis of PVL, [15,16] Bagan et al. in 2007 [17] suggested that there is no association of PVL with HPV. In 2008 Bagan et al. [18] detected the presence of EBV in a large percent of their patient group suggesting an etiologic role in the pathogenesis and recurrence of PVL. Several others have reported that genetic factors and immunologic factors should be implicated in the malignant transformation of PVL more than local factors. It should be noted that in cases of multifocality, not all lesions are at the same stage of evolution. While one lesion may be simple hyperkeratosis, another one located elsewhere may already have developed into a carcinoma. PVL as described by Hansen develops through a histopathological continuum encompassing 10 stages from - normal oral mucosa (0), homogeneous leukoplakia (2), verrucous hyperplasia (4), verrucous carcinoma (6), papillary squamous cell carcinoma (8), and poorly differentiated carcinoma (10), in which the odd scores refer to a status intermediate between those referred to a status intermediate between those referred to by the adjacent even scores. [6] Batsakis et al. reduced the number of histologic stages to 4 with intermediates: Grade 0: Clinical flat leukoplakia without dysplasia. Grade 2: Verrucous hyperplasia Grade 4: Verrucous carcinoma Grade 6: Conventional squamous cell carcinoma with intermediates. [19] The present study confirmed part of the previously reported data: the higher prevalence of PVL in females and the age of occurrence around the fifth to seventh decade. In contrast to previous reports suggesting no association between PVL and tobacco, the patient described here gave a chronic history of 35 years of chewing tobacco. PVL is usually chronic and progressive and a patient often has a long history of leukoplakia before he/she attends a clinic. [20] Most cases progress for years. In contrast to most slow growing PVL which usually appear as rough textured extensive white patches with multiple peaks, the case described here progressed quite rapidly over a period of 6 months as patient states and assumed a verrucous exophytic growth mimicking a papilloma or verrucous carcinoma. Another unique aspect to this case was despite rapid progression in size of the lesion, clinically and radiographically there was neither sign of erosion nor the related teeth showed signs of mobility which infers there was no transition to malignancy. Histopathological report revealed moderate dysplasia. Also patient did not report complaints regarding presence of other associated symptoms (like fever, malaise due to secondary bacterial infection) when she reported to the outpatient or during the follow up period which questions the viral (Human Papilloma virus) etiology implicated as causative of PVL. An overall physical examination revealed no malignant tumor elsewhere in the body. Intraoral examination over a follow up period of 6 months showed no signs of disease progression. Also, histopathological analysis done at the end of 6 months confirmed the same. Thus, although on one hand the entity of a recurrent, progressive verrucal lesion cannot be questioned, it is not correct to include several lesions as mentioned by Hansen et al. in one category as PVL. [12] CONCLUSION Proliferative verrucous leukoplakia is a rare but highly aggressive form of oral leukoplakia. The high frequency of gingival involvement and the high transformation rate on masticatory mucosa without reliable predictive parameters emphasizes the importance of PVL awareness for clinicians. It is an unknown disease in which no etiological factor has been proven until today. Although various set of diagnostic criteria have been proposed; lack of exact diagnostic criteria is a prime reason due to which patients of PVL do not get correct treatment on time. Many patients are diagnosed many years after the first presentation of the disease, mostly retrospectively. All recurrent white lesions, with multifocal appearance should be suspected and early aggressive intervention should be started. Continued 38

5 biopsy of old and new lesions is mandatory. Various treatment modalities are proposed for management of lesions of PVL which include complete removal accomplished by conventional surgery, radiotherapy, cryotherapy, vitamin A therapy, antiviral therapy, or recent techniques by carbon dioxide laser surgery and photodynamic therapy. Long term follow up after removal is extremely important because recurrences are frequent and because additional leukoplakias may develop. [4] The possible complication is the high rate of malignant transformation, the lack of a successful treatment, and the number of recurrences after management. REFERENCES 1. Gandolfo S, Castellani R, Pentenero M. Proliferative verrucous leukoplakia: A potentially malignant disorder involving periodontal sites. J Periodontol 2009;80: Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007;36: Silverman S Jr, Gorsky M. Proliferative verrucous leukoplakia: A follow-up study of 54 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84: Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3 rd ed. St. Louis: Saunders; p , Kramer IR, Lucas RB, Pindborg JJ, Sobin LH. Definition of leukoplakia and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46: Hansen LS, Olson JA, Silverman S Jr. Proliferative verrucous leukoplakia. A long-term study of thirty patients. Oral Surg Oral Med Oral Pathol 1985;60: Cerero-Lapiedra R, Baladé-Martínez D, Moreno-López LA, Esparza-Gómez G, Bagán JV. Proliferative verrucous leukoplakia: A proposal for diagnostic criteria. Med Oral Patol Oral Cir Bucal 2010;15:e Bagan J, Scully C, Jimenez Y, Martorell M. Proliferative verrucous leukoplakia: A concise update. Oral Dis 2010;16: Cabay RJ, Morton TH Jr, Epstein JB. Proliferative verrucous leukoplakia and its progression to oral carcinoma: A review of the literature. J Oral Pathol Med 2007;36: 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;47: Ghazali N, Bakri MM, Zain RB. Aggressive, multifocal oral verrucous leukoplakia: Proliferative verrucous leukoplakia or not? J Oral Pathol Med 2003;32: Bishen KA, Sethi A. Proliferative verrucous leukoplakia Diagnostic pitfalls and suggestions. Med Oral Patol Oral Cir Bucal 2009;14:E American Academy of Periodontology. Glossary of Periodontal Terms. 4 th ed. Chicago: American Academy of Periodontology; p Bagán JV, Murillo J, Poveda R, Gavaldá C, Jiménez 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;40: Palefsky JM, Silverman S Jr, Abdel-Salaam M, Daniels TE, Greenspan JS. Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16. J Oral Pathol Med 1995;24: Eversole LR. Papillary lesions of the oral cavity: Relationship to human papillomaviruses. J Calif Dent Assoc 2000;28: Bagan JV, Jimenez Y, Murillo J, Gavaldá C, Poveda R, Scully C, et al. Lack of association between proliferative verrucous leukoplakia and human papillomavirus infection. J Oral Maxillofac Surg 2007;65: Bagan JV, Jiménez Y, Murillo J, Poveda R, Díaz JM, Gavaldá C, et al. Epstein-Barr virus in oral proliferative verrucous leukoplakia and squamous cell carcinoma: A preliminary study. Med Oral Patol Oral Cir Bucal 2008;13:E Batsakis JG, Suarez P, el-naggar AK. Proliferative verrucous leukoplakia and its related lesions. Oral Oncol 1999;35: Vigliante CE, Quinn PD, Alawi F. Proliferative verrucous leukoplakia: Report of a case with characteristic long-term progression. J Oral Maxillofac Surg 2003;61: Cite this article as: Citation will be included before issue gets online*** Source of Support: Nil. Conflict of Interest: None delcared. 39