International Journal of Research and Reports in Dentistry

4(4): 29-34, 2021; Article [Link].71494

Proliferative Verrucous Leukoplakia: A Diagnostic

Perplexity
Nidhi Sinha1*, Meghanand T. Nayak2, Shreya Gupta3, Devangi Dwivedi1,
Neeti Swarup4 and Mansi Agarwal2
1
Department of Oral Pathology and Microbiology, College of dental sciences BBD University,
Lucknow, Uttar Pradesh, India.
2
Department of Oral Pathology and Microbiology, Teerthanker Mahaveer Dental College and
Research Centre, Teerthanker Mahaveer University, Mooradabad, Uttar Pradesh, India.
3
Oral Pathology and Microbiology, Content strategist, RELX India Pvt. Ltd, Gurgaon, Harayana, India.
4
Department of Oral Pathology and Microbiology, School of Dentistry, Seoul National University,
South Korea.

Authors’ contributions

This work was carried out in collaboration among all authors. All authors read and approved the final
manuscript.

Article Information

Editor(s):
(1) Dr. Roberta Gasparro, University of Naples Federico II, Italy.
Reviewers:
(1) Dharmashree Satyarup, Institute of Dental Sciences, Siksha ‘O’ Anusandhan University, India.
(2) Sania Sultana Ullah, Silchar Medical College and Hospital, India.
Complete Peer review History: [Link]

Received 25 May 2021

Accepted 30 July 2021
Case Report
Published 04 August 2021

ABSTRACT

Proliferative verrucous leukoplakia (PVL) is an uncommon pathological lesion which is defined as a

diffuse, white and smooth or papillary or wart-like exophytic growth of oral mucosa showing
capricious degrees of epithelial hyperplasia. Initially, the lesion shows focal clinical hyperkeratosis
that gradually becomes a comprehensive multifocal disease. In its primary stages, the lesion
clinically is bland that it is often diagnosed as frictional hyperkeratosis or hyperplastic candidiasis,
but with its descriptive natural features of chronic proliferation, copious occurrences, refractoriness
to treatment and high rate of malignant transformation, it can be positively diagnosed as oral
proliferative verrucous leukoplakia (OPVL).

Keywords: Exophytic growt; multifocal disease; refractoriness; malignant transformation.

_____________________________________________________________________________________________________

*Corresponding author: Email: [Link]@[Link];

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1. INTRODUCTION resembled hyperplastic candidiasis and

histopathologically as OPVL.
Oral leukoplakia is well-defined
defined by W.H.O as “A
white patch or plaque that cannot be 2. CASE REPORT
characterized clinically or pathologically as any
other diseases. PVL is a special high-risk
high form of
A 50 years old male patient reported to OPD with
leukoplakia which is characterized by the
a chief complaint of a white growth in the left side
development of multiple keratotic plaques with w
of the cheek region for 6 years. The patient gave
roughened surface projection [1] It is a prolonged
the history of a white patches in the lower
progressive condition, developing primarily as a
anterior region in relation to 41, 31 which slowly
white plaque of hyperkeratosis that eventually
extended towards the left buccal mucosa. The
becomes a multifocal disease with confluent,
patient also gave history of chewing the tobacco
exophytic and proliferative features [2] and
in the past 8 years.
behaves more aggressively
gressively and relentlessly than
other innocuous white oral lesions to which it
resemble clinically [3] A diagnostic criteria for this Intra oral examination revealed white patches
lesion was proposed by Cerero-Lapiedra
Lapiedra R et al.
a which was multifocal in nature. The patches
[2] well ahead modified by Carrard VC [4] [ Its rate being distributed throughout left buccal mucosa,
of malignant transformation
ation is enormously high. coleasing and extending from the left retromolar
According to the latest World Health area to the right gingival and the labial mucosa in
Organization nomenclature, OPVL fits into the relation to 41,31 crossing the midline and not
new terminology of “potentially malignant sparing the angle of the mouth, measuring about
disorders”, that it is neither a restricted lesion nor 6x3 cm in dimension(fig1&2). The surface of the
a condition [1] PVL was first described and lesion was rough with areas showing nodular
isolated
ed from other forms of leukoplakia by projections and corrugations (Fig.
Fig. 1).
1 The overall
Hansen et al. [5] Bagan concluded that PVL hygiene was poor. On palpation the lesion was
quickly becomes malignant, approximately within firm, non-tender, non-scrapable
scrapable with no tendency
4.7 years [6],, whereas Hansen reported an to bleed. On extra oral examinations no facial
average time to cancer of 6.1 years [7] Yet, asymmetry or any other malformation was noted.
Silverman and Gorsky reported a longer mean a Based on history and clinical findings differential
malignant process of 11.6 years [8] In the diagnosis of chronic hyperplastic candidiasis and
present article, we describe a case that clinically leukoplakia were considered.

Fig. [Link] intraoral photograph showing the Fig. 2. Intraoral photograph showing lesion
extent of the lesion with surface corrugations
corr extending from left buccal mucosa to
noted, involving left buccal mucosa and angle of anterior labial and gingival mucosa
mouth crossing the midline

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Fig. 4. Section shows

hyperkeratotic,hyperplastic stratisfied
squamous epithelium with keratin plugging
and dysplastic features such as broad
Fig. 3. Photomicrogaph shows section with bulbous retepegs , basilar hyperplasia,
yperplasia,
features of veruccous hyperplesia(Biopsy site-
site ,individual cell keratinization epithelial pearl,
labial mucosa) are observed(Biopsy site- buccal mucosa)

Incisional biopsies were done from lesioned Batsakis [Link] [11] reduced the number of
areas, both from the left buccal mucosa as well histologic stages to four with intermediates:
as anterior labial mucosa for histopathological
evaluation. H&E-stained
stained section showed Grade 0: Clinical flat leukoplakia without
hyperkeratotic stratified squamous epithelium dysplasia
with prominent hyperplasia. The rete ridges are Grade 2: Verrucous hyperplasia
long, broad and bulbous with basilar hyperplasia. Grade 4: Verrucous carcinoma
Features such as hyperchromatism, altered Grade 6: Conventional squamous cell
nuclear-cytoplasmic
lasmic ratio, pleomorphism, carcinoma with Intermediates
individual cell keratinization and keratin pearl (Issrani et al. [10])
formation were evident, suggestive of dysplasia
were evident. The connective tissue stroma Our case represented grade 4 on the left buccal
shows intense chronic inflammatory cell mucosa, grade 6 on the anterior labial mucosa
infiltrates chiefly of lymphocytes and plasma as described by Hansen et al. This explains
explain the
cells.
lls. Clinicopathologic correlation was spectrum of disease, showing different grades at
suggestive of proliferating verrucous leukoplakia. different sites at the same time. In our case,
The patient was referred to oral surgery for histologic picture of labial mucosa appears less
further management. aggressive with features suggestive of verrucous
hyperplasia whereas biopsy from left buccal
Histopathological findings associated with OPVL mucosa shows moderate dysplasia, features
are dependent on the stage of the disease and consistent with verrucous carcinoma, thus
adequacy of biopsy [9].. According to Hansen et encompassing changing stages of the disease at
al. [5] the histologic stages in OPVL are,
various areas of the lesion. Cerero
Cerero‑Lapiedra et
Grade 0: Normal mucosa al2 established the subsequent major and minor
Grade 2: Hyperkeratosis (clinical leukoplakia) criteria for the clinical diagnosis of OPVL,
Grade 4: Verrucous hyperplasia
Grade 6: Verrucous carcinoma 3. MAJOR CRITERIA
Grade 8: Papillary squamous cell carcinoma
carcinom
Grade 10: Less well‑differentiated
differentiated squamous cell a. A leukoplakia lesion with more than two
carcinoma (Issrani et al. [10]) different oral sites, which is most frequently

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seen in the gingiva, palate and alveolar vestibule), tongue, and buccal mucosa palatal
processes involvement is also seen in few cases. According
b. The existence of a verrucous area to Haley et al., the gingiva is the most likely site
c. That the lesions have spread or engrossed for the malignant transformation of PVL [14].
during development of the disease Baughman and Boland and Eversole have
d. That there has been a recurrence in a provided in-depth discussions on the clinical
previously treated area differential diagnosis for oral PVL, the late or
e. Histopathologically, there can be from advanced stages of PVL cannot be differentiated
simple epithelial hyperkeratosis to clinically from verrucous carcinoma or an
verrucous hyperplasia, verrucous exophytic papillary form of squamous cell
carcinoma or OSCC, whether in situ or carcinoma.1 No literature is available about the
infiltrating. role of immunodeficiency or any associated
syndrome for PVL. According to Bagan et al.
4. MINOR CRITERIA 2004 the proliferative effect of PVL was
explained on basis of the high rate of field
a. An OL lesion that occupies at least 3 cm cancerization existing in PVL patients [15,16].
when adding all the affected areas Histopathologically the lesion shows variable
b. That the patient is female appearances, in the early phase the lesion
c. That patient (male or female) be a exhibit benign hyperkeratosis in few cases the
non‑smoker lesion shows an interface lymphocytic infiltrate
d. A disease evolution higher than 5 years. that may have a pronounced lichenoid pattern,
with advancing time, the lesion progresses to a
The present case satisfies four major criteria’s papillary, exophytic proliferation (termed
except for (d) and three minor criteria’s except verrucous hyperplasia) [17,1]. ln later stages, this
(b), to reach at the confirmatory final diagnosis of papillary proliferation shows downgrowth of well-
OPVL. In contrast to previous reports, suggesting differentiated squamous epithelium with broad,
higher prevalence of PVL in females and no blunt rete ridges. This epithelium demonstrates
association between PVL and tobacco, we report invasion into the underlying lamina propria; at
a male patient with history of 8 years of chewing this stage, it is indistinguishable from verrucous
tobacco. carcinoma. In the final stages, the invading
epithelium becomes less differentiated,
5. DISCUSSION transforming into a full-fledged squamous cell
carcinoma [1]. Our case exhibited, variable
PVL is a unique type of oral leukoplakia, which histopathological picture of the same lesion but
begins as a simple hyperkeratosis and with time at different sites that varied from innocuous
spreads locally or to other sites to become verrucous hyperplasia to dysplastic epithelium
multifocal and proliferative [1]. PVL lesions are with features of verrucous carcinoma.
commonly slow-growing, persistent and
irreversible and with time become exophytic and Presently, apart from surgical excision, no other
wart-like, presenting verrucal projections with definite treatment modality has been found to be
regions of erythematous change within white effective in the management of the PVL.
patches, and also shows the appearance of However, complete removal may be challenging
verrucous and nodular leukoplakia [5] It presents because of its multifocal manifestation in the oral
specific characteristics, mainly a more cavity. Consequently, the patients with PVL need
aggressive biological behaviour than other forms multiple biopsies over the interval to detect the
of leukoplakia expressed by: a tendency towards histologic status of the lesion [18] The same was
multifocality; a high probability of recurrence; and followed in the present case.
a high rate of malignant transformation, which
can range between 40 and 100% in a follow-up 6. CONCLUSION
period of 4.4 to 11.6 years [2] The etiology of
PVL is unknown but tobacco use, trauma and Proliferative verrucous leukoplakia is an
alcohol abuse are doubted to be the commonest aggressive form of oral leukoplakia with higher
causes,1 the same etiology is seen in the rate of malignant transformation with unknown
present case too. Human papilloma virus, etiology. PVL if misdiagnosed as other white
subtype 16, may be suspected to be a cofactor in lesions of the oral cavity due to lack of exact
PVL [12,13]. The most common locations are the clinical diagnostic criteria, apparently becomes
gingiva or alveolar ridge (often extending into the more aggressive and may even shows malignant

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changes. There is significant importance for Hyperplasia of Palate Transforming Into

multiple biopsies as the lesion shows a Squamous Cell Carcinoma: A Diagnostic
continuum in the histological stages due to the Emergency. Journal of Dental Sciences.
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COMPETING INTERESTS
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