Case Report Proliferative Verrucous Leukoplakia of the Gingiva: An Early Lesion Refractory to Surgical Excision

Abstract

This report describes a case of proliferative verrucous leukoplakia (PVL) of the gingiva with no discernible aetiology, which presented in a 36-year-old female. The initial nonscrapable gingival lesion was treated with CO 2 laser ablation, and the histopathological evaluation was carried out. The presence of koilocytic cells in the superficial epithelium led to immunohistochemical investigations with p16 antibody, which showed strong nuclear positivity and slight cytoplasmic positivity in >50% of the cells with >25% confluency. However, it was not possible to confirm the presence of HPV infection with further investigations due to logistic reasons. The lesion recurred twice within a short time despite the surgical resection following the first recurrence. Thus, this paper presents a case of proliferative verrucous leukoplakia, which demonstrated a significant resistance to routine treatment protocols recommended in the management of such lesions.

Full text

Case Report
Proliferative Verrucous Leukoplakia of the Gingiva: An Early
Lesion Refractory to Surgical Excision
Dhanushka Leuke Bandara ,
1
Primali Rukmal Jayasooriya ,
2
and Ruwan Duminda Jayasinghe
1
1
Department of Oral Medicine & Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya 20400, Sri Lanka
2
Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya 20400, Sri Lanka
Correspondence should be addressed to Dhanushka Leuke Bandara; dhanulb@pdn.ac.lk
Received 12 May 2019; Revised 5 July 2019; Accepted 20 August 2019; Published 22 October 2019
Academic Editor: Rui Amaral Mendes
Copyright © 2019 Dhanushka Leuke Bandara et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work
is properly cited.
This report describes a case of proliferative verrucous leukoplakia (PVL) of the gingiva with no discernible aetiology, which presented
in a 36-year-old female. The initial nonscrapable gingival lesion was treated with CO
2
laser ablation, and the histopathological
evaluation was carried out. The presence of koilocytic cells in the superficial epithelium led to immunohistochemical
investigations with p16 antibody, which showed strong nuclear positivity and slight cytoplasmic positivity in >50% of the cells
with >25% confluency. However, it was not possible to confirm the presence of HPV infection with further investigations due to
logistic reasons. The lesion recurred twice within a short time despite the surgical resection following the first recurrence. Thus,
this paper presents a case of proliferative verrucous leukoplakia, which demonstrated a significant resistance to routine treatment
protocols recommended in the management of such lesions.
1. Introduction
White lesions in the oral cavity could represent a variety of
aetiological factors including increased or abnormal keratin
production in the oral epithelium, which is denoted by the
term “keratosis”[1].
In addition to keratotic lesions that occur due to tobacco
use, they may also occur due to frictional, chemical, or
thermal irritations as well as due to inflammation. Frictional
keratosis is usually seen in areas of recurring mild mechanical
trauma or irritation while chemical keratosis may occur as the
result of the compounds in smokeless tobacco, certain tooth-
pastes, inappropriately used acidic medications, and alkaline
liquids [2, 3]. Usually, keratotic lesions cannot be scrapped
offand may differ in texture depending on the cause [3].
Oral leukoplakia (OL) is defined as a “white plaque of
questionable risk having excluded (other) known diseases
or disorders that carry no increased risk for cancer”[4].
Proliferative verrucous leukoplakia (PVL) is a rare form of
oral leukoplakia with a malignant transformation rate of
70% [5]. It develops initially as a white plaque of hyperkerato-
sis that eventually becomes a multifocal disease with conflu-
ent, exophytic, and proliferative features showing different
degrees of dysplasia. PVL is more commonly a disease of the
elderly females which can develop in both tobacco users and
nontobacco users [5, 6].
Recently, Woo et al. have reported a subset of lesions,
with the majority clinically presenting as OL, harbouring
high-risk HPV subtypes and positive for p16 [7]. In addition,
clinicopathological spectrums of these lesions are similar
to tobacco-induced leukoplakia that occurs more often in
adult males on the tongue and floor of the mouth [7].
According to Barasch et al., when interpreting p16 positivity,
the presence of p16 positivity in >50% of cells with >25%
confluence or >70% positivity could be considered as the
threshold to determine a positive reaction [8].
Hindawi
Case Reports in Dentistry
Volume 2019, Article ID 5785060, 4 pages
https://doi.org/10.1155/2019/5785060

This case report describes a rare case of early stage of PVL
with no apparent aetiology that developed in a relatively
young patient.
2. Case Presentation
A 36-year-old female presented with an asymptomatic
whitish lesion, on the gingiva in relation to 13, 14, and 15.
The lesion had existed for more than one year in duration
which had initiated during her second pregnancy. She was
otherwise healthy except for having mild hypochromic
microcytic anaemia due to being a carrier for thalassemia
trait. However, her serum ferritin levels were within the nor-
mal range. Her plaque control measures revealed brushing
twice daily with a fluoridated toothpaste although supple-
mentary tools were not used. Furthermore, the patient did
not practice any risk habits such as betel chewing, smoking,
or alcohol consumption.
Intraoral examination revealed a linear, plaque-like whit-
ish lesion on the palatal and buccal free gingiva of 13, 14,
and 15 (Figure 1). No verrucous/papillary appearance was
evident, and the lesion was nonscrapable.
She had no other significant extraoral or intraoral
findings, and the radiological examination in relation to the
site was normal (Figure 2). As baseline investigations, an
incisional biopsy was performed together with the necessary
haematological investigations.
2.1. The Histological Findings. The histopathological analysis
revealed a hyperorthokeratinized stratified squamous epithe-
lium which showed cytological atypia in the lower part
amounting to mild epithelial dysplasia with numerous koilo-
cytes in the stratum spinosum (Figures 3 and 4).
Furthermore, due to the presence of koilocytosis, immu-
nohistochemical evaluation was carried out with p16 anti-
body which clearly revealed positivity in >50% of the cells
with >25% confluency (Figure 5). It is also worthwhile to
mention that in the present lesion, nuclear staining was
stronger compared to cytoplasmic staining.
Figure 1: Linear, plaque-like whitish lesion on the palatal and
buccal gingiva of 13, 14, and 15.
Figure 2: IOPA radiograph of 13–15 region.
Figure 3: Keratosis with mild epithelial dysplasia under H&E
staining.
Figure 4: Koilocytic cells under ×40 magnification.
Figure 5: Immunohistochemical assay with p16 showing positive
staining in >50% of the cells with >25% cell confluency.
2 Case Reports in Dentistry

However, as p16 is only a surrogate marker, it was not
possible to confirm the high-risk HPV infection as the
etiological factor for the present lesion due to the absence of
adequate amount of fresh tissue. Therefore, considering the
histological findings together with the clinical features, early
stage of PVL was derived as the possible diagnosis.
2.2. Management. Thus, following informing the patient
regarding the findings, she was referred for HIV and gyneco-
logical screening. The HIV test was negative, and she had no
abnormalities detected with the gynecology screening.
However, despite the thorough probing into the possible
causative factors including behavioural risk factors and
habits, no aetiological factor for this oral lesion was revealed,
except for p16 positivity, which could not be confirmed as
due to a high-risk HPV infection with further investigations.
For the management of the lesion, resection of the lesion
with adequate margins using CO
2
laser was carried out
following improving the oral hygiene. Nevertheless, the
lesion reappeared within few weeks at the same sites which
led to perform a surgical resection with an adequate margin
in the second attempt.
However, the lesion recurred similar to the initial presen-
tation showing its resistance to excision. Thus, within a
period of nearly six months, it recurred thrice despite electro-
surgical interventions. Considering the diagnosis of PVL,
currently, the patient is being followed up with short recall
intervals and the lesion remains same with no significant
change in size compared to the initial presentation.
3. Discussion
As the lesion described in the present report is a rare
occurrence, difficulties were encountered when naming the
lesion, especially with references to the terms “keratosis”
and “leukoplakia.”According to literature, similar lesions
have been named as linear gingival keratosis [3] as well as
linear gingival leukoplakia [9]. When linear gingival keratosi-
s/leukoplakia reported in literature [10] was compared with
the present lesion, it did not show bone erosion. In contrast
to lesions reported in literature [9, 10], the present lesion
showed dysplasia and p16 positivity. However, in this case,
the lesion was diagnosed as an early stage of PVL rather
than linear gingival keratosis, due to the fact that it occurred
in a female in the gingiva and also as it was refractory to
surgical management.
In frictional keratosis histology of the spinous layer often
demonstrate intraepithelial edema and occasional vacuolated
cells with pyknotic nuclei resembling koilocytes [3]. The
diagnosis of frictional keratosis typically consists of a detailed
clinical examination, considering the possible oral habits and
the agents that may involve in the chronic trauma of the oral
mucosa [10]. However, in the present case, no aetiological
factor was found indicating frictional irritation. Furthermore,
the patient did not reveal any possibility of chemical irrita-
tion. A minority of keratotic lesions show dysplastic changes
[1]. In this case, although the dysplastic changes were mainly
observed in the lower part of the epithelium, dyskeratosis and
koilocytosis were mainly observed in the upper layers of the
epithelium. Though, it was not possible to confirm the pres-
ence of high-risk HPV infection in the present lesion, it
would be worthwhile to explore the contribution of HPV in
future studies.
When considering the management, PVL is commonly
treated with conventional surgery, electrocautery, laser
ablation, and cryosurgery [11]. Except in conventional sur-
gery where resection of the lesion is targeted, in other
methods, the tissue destruction is obtained via intercellular
and extracellular freezing, denaturing lipid–protein com-
plexes, and cell dehydration. There are several advantages
of using CO
2
lasers for oral lesions, particularly less intraop-
erative bleeding, minimal damage to adjacent tissue, delayed
acute inflammatory reaction, and reduced myofibroblast
activity, leading to reduced wound contraction and scarring
[11]. In addition, though generally lesions that are diagnosed
as mild epithelial dysplasia are followed up [1, 4, 12], surgical
excision was planned due to aesthetic concerns of the patient.
PVL is a progressive disease and may not respond to tra-
ditional treatment [5] similar to the present case which
showed a high recurrence rate despite the early interventions
carried out in the management.
When there is no obvious aetiology for oral PVL, the
lesions may be considered as leukoplakia and managed
accordingly [12]. Furthermore, in the present case, histolog-
ical diagnosis of koilocytic dysplasia was not excluded
completely, though the lesion displayed histologic features
of HPV infection such as koilocytosis and multinucleated
keratinocytes.
4. Conclusion
The key feature in the case presented was the high recurrence
rate showed despite the various treatment methods. There-
fore, the patient should be followed up with close monitoring
to detect any further increase in dysplastic changes which
could follow with the presence of koilocytic cells and with
PVL lesions. In addition, occurrence of early PVL lesions as
gingival keratosis should be further explored.
Conflicts of Interest
The authors declare that there is no conflict of interest
regarding the publication of this paper.
Acknowledgments
We acknowledge the immense support given by the patient
and the clinical staffof the respective clinics during the
management.
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