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Proliferative Verrucous Leukoplakia Presenting as
a Ring Around the Collar and Cancer: A Case
Report
Valentin Vergier , Katarzyna Czarny , Jean-Jacques Brau , François Le Pelletier , Ihsène Taihi
1. Department of Dentistry, Faculty of Health, Université Paris Cité, Montrouge, FRA 2. Department of Dentistry,
Charles Foix Hospital, Assistance Publique-Hôpitaux de Paris, Ivry-sur-Seine, FRA 3. Orofacial Pathologies, Imaging,
and Biotherapies Laboratory (URP 2496 BRIO), Université Paris Cité, Montrouge, FRA 4. Department of Maxillo-facial
Plastic Surgery and Stomatology, Gonesse Hospital, Gonesse, FRA 5. Odontology and Maxillofacial Prosthesis Unit,
Department of Cervicofacial Cancerology, Gustave Roussy Cancer Center, Villejuif, FRA 6. Department of Pathology,
Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, FRA 7. Department of Oral Surgery,
Rothschild Hospital, Assistance Publique-Hôpitaux de Paris, Paris, FRA
Corresponding author: Valentin Vergier, valentin.vergier@aphp.fr
Abstract
Proliferative verrucous leukoplakia (PVL) is an oral mucosa lesion with a high rate of malignant
transformation. The diagnosis is often difficult, especially when the initial lesion is a simple homogeneous
white leukoplakia, and when located only on the gingiva or palate. Moreover, the anatomopathological
analysis is non-specific in the initial stages. The gingival PVL localisation (gPVL) is described as the most
aggressive form with the highest rate of malignant transformation. Cases with a unique gingival localisation
are rare, described with a “ring around the collar” clinical form. Considering the difficulty of early diagnosis
of gPVL, we report the case of a 72-year-old woman, who presented “white lesions on her gingiva” with a
slight discomfort in February 2019. The lesion was initially limited to the buccal part of the mandibular right
gingiva, but rapidly extended to all the lingual and buccal mandibular gingiva during follow-up, leading to a
diagnosis of gPVL. Two biopsies were performed, which concluded a verrucous hyperplasia and papilloma
with a lichenoid part. The diagnosis of gPVL was made after a six-month follow-up based on clinical and
anatomopathological factors. The gPVL transformed into a squamous cell carcinoma (SCC) after 18 months
of follow-up. A surgical right mandibular bone excision with an autologous left fibula graft associated with
radiotherapy was performed. Three years after the surgery, the patient remains under monitoring, with
several gPVL and SCC recurrences treated. This case highlights that gPVL is a rare and aggressive form of
PVL, with a high risk of fast malignant transformation. Knowledge about its aetiology, anatomic pathology,
and biological markers is highly needed to speed up the diagnosis and develop specific follow-up and
treatment.
Categories: Pathology, Oral Medicine, Oncology
Keywords: oral dermatology, attached gingiva, verrucous leukoplakia, oral cancers, squamous cell carcinoma
Introduction
Proliferative verrucous leukoplakia (PVL) is a white oral mucosa lesion and a potentially malignant disorder.
It was first described in 1985 by Hansen et al. [1], who described the lesion as “a simple hyperkeratosis but
tends to extend and become multifocal over varying periods of time. The lesions are slow-growing,
persistent, irreversible, and frequently developed erythematous components. Some areas later become
exophytic and wart-like and transform into lesions that are clinically and microscopically identical to
verrucous carcinoma (VC) and squamous cell carcinoma (SCC). In addition, they are resistant to different
treatments.”
A five patterns and 10 grades scale simplified later to a four patterns and five grades scale has been proposed
[2]. The grades range from normal mucosa (grade 0) to hyperkeratosis (grade 1), verrucous hyperplasia
(grade 2), verrucous carcinoma (grade 3), and, lastly, invasive SCC (grade 4).
The diagnosis of PVL is often difficult and needs a close follow-up to control the lesion’s evolution. Indeed,
in the few cases described in the literature, the diagnosis was made after several months of follow-up
because of the challenging diagnosis of the lesion, especially at early stages. Although several diagnostic
criteria have been described, they are often unclear and difficult to assess. The most recent and easy to
assess are those from Cerero-Lapiedra et al. in 2010 [3]. They classified the criteria as major or minor. For a
diagnosis of PVL, the lesion needs to meet three major criteria (the histology criteria among them) or two
major and two minor criteria.
Although the majority of reported oral PVL lesions are often multifocal, gingival-only forms have been
recently described [4]. The gingival localisation is one of the most frequent and seems to have a higher
malignant transformation rate than other localisations [5]. However, very few cases have been described in
1, 2, 3 1, 4 5 6 1, 3, 7
Open Access Case
Report DOI: 10.7759/cureus.56077
How to cite this article
Vergier V, Czarny K, Brau J, et al. (March 13, 2024) Proliferative Verrucous Leukoplakia Presenting as a Ring Around the Collar and Cancer: A
Case Report. Cureus 16(3): e56077. DOI 10.7759/cureus.56077
the literature, especially when the lesion is limited to the gingiva, which makes the diagnosis more difficult.
Based on this observation, we report the case of a woman presenting a gingival-only PVL (gPVL) with a
rapid malignant transformation.
This case was previously presented as a poster at the 2021 annual French Society of Oral Surgery Congress
on September 10, 2021.
Case Presentation
A 72-year-old woman presented at an oral surgery consultation in February 2019, referred by her dentist for
“white lesions on her gingiva” with slight discomfort. No history of tobacco or alcoholic intoxication was
reported by the patient.
The patient reported a history of balanced hypertension, hypothyroidism, and osteoporosis treated with
alendronate. She was followed by a dermatologist for a facial basal cell carcinoma two years ago, treated by
photodynamic therapy at that time. Her father and grandfather had carcinomas.
Clinical examination showed about 1 cm2 of gingival linear keratotic plaques with undefined limits and
erythematous borders, limited to the attached gingiva, located on the buccal side of the first left mandibular
premolar which continued to the first right mandibular molar (Figure 1, Panels A, B). The lesion was
attached to the gingiva, and no bleeding on probing, nodules, lymphadenopathy, or ulceration was noted.
FIGURE 1: The gingival-only proliferative verrucous leukoplakia case
reported before malignant transformation.
A: The lesion noted seven days after the firs t biopsy in February 2019. The specific aspect of a “ring around the
collar” leukoplakia can be noticed.
B: The lesion noted six months later. It had extended to the lingual mandibular gingiva.
C: Hematoxylin-eosin colouration of the second biopsy. The papillomatous aspect with a lichenoid part can be
noticed but without any malignant cells.
At this stage of examination, the possible differential diagnoses were hyperplastic oral lichen planus, PVL,
drug-induced leukoplakia, chronic candidiasis, idiopathic leukoplakia, verrucous carcinoma, or SCC.
A biopsy of the gingival papilla was performed in the incisors region. The anatomopathological examination
showed papillomatous epithelial hyperplasia and non-specific fibrous reshaping. An idiopathic leukoplakia
was diagnosed and a six-month follow-up was established.
During this period, the lesion extended all over the buccal mandibular gingiva and thickened on the lingual
side. The lesion grew in thickness at the biopsy site. The patient still did not experience any pain, ulceration,
nodules or lymphadenopathy. A second biopsy was performed in March 2020 on the lingual gingival papilla
in the incisors region, which concluded verrucous hyperplasia and papilloma with a lichenoid part, without
any malignant cells (Figure 1C). The detection of a verrucous part in that biopsy compared to the first biopsy
was the major evolution.
Given the histopathological findings and the clinical evolution of the lesion, the gPVL diagnosis was made.
At this stage, the patient met four major criteria proposed by Cerero-Lapiedra et al. [3] (Table 1). A
leukoplakia lesion with more than two different oral sites (buccal marginal gingiva in incisors and molars
regions), the lesions had spread or engrossed during the development of the disease (at the incisors’ lingual
marginal gingiva), recurrence in a previously treated area (recurrence after the biopsy), and compatible
histopathology with verrucous hyperplasia. The patient also met two minor criteria, i.e., the patient was
female and a non-smoker.
2024 Vergier et al. Cureus 16(3): e56077. DOI 10.7759/cureus.56077 2 of 7
Major criteria Minor criteria
AA leukoplakia lesion with more than two different oral sites, which is most frequently
found in the gingiva, alveolar processes, and palate a
An oral leukoplakia lesion that occupies
at least 3 cm when adding all the affected
areas
B The existence of a verrucous area b A female patient
C The lesions have spread or engrossed during the development of the disease c A non-smoker patient (male or female)
D There has been a recurrence in a previously treated area d A disease evolution higher than 5 years
E
Histopathologically, ranging from simple epithelial hyperkeratosis to verrucous
hyperplasia, verrucous carcinoma, or oral squamous cell carcinoma, whether in situ or
infiltrating
TABLE 1: The diagnostic criteria for proliferative verrucous leukoplakia.
These criteria were proposed by Cerero-Lapiedra et al. in 2010 [3].
The positive diagnosis is made if the patient meets either three major criteria (histopathological criteria among them) or two major criteria
(histopathological criteria among them) and two minor criteria.
The variation of the histological description by the pathologists was due to the similarity of lichenoid lesions
and papilloma with PVL at early stages.
Because of the localisation of the lesion as a “ring around the collar” of all the mandibular teeth [4], a total
excision could not be performed, despite the high risk of malignant transformation. Thus, a three-month
control interval was established to diagnose the malignant transformation as soon as possible.
Between the controls, she was prescribed antibiotics by her generalist due to “stinks in her mouth.” The
patient started to experience slight pain but did not report it to her generalist. The clinical examination
showed a gingival swelling in the right mandibular premolars and probing of 15 mm but without any signs of
general alteration as nodules or facial swelling. This suggested a periodontal abscess. She underwent an
ultrasonic scaling in the Periodontology Department in July 2020, along with a seven-day course of
amoxicillin and clavulanic acid.
Due to the COVID-19 pandemic, the patient did not come back for three months, although the swelling
started to extend to the mandibular molar region. During this period, the patient had a basal cell carcinoma
on the nose, which was excised by her dermatologist and analysed.
The patient came back in October 2020 with a right mandibular facial swelling. Intraoral examination
showed suppurative swelling limited to the buccal gingiva regarding the lower right premolars and molars
and a second swelling on the lingual side in the lower left incisors (Figures 2A, 2B). This was associated with
a right submandibular lymphadenopathy. Given these findings, biopsies were performed and confirmed the
diagnosis of SCC (Figures 2C , 2D). The patient was referred to the Cervico-facial Carcinology Department
(Gustave Roussy Cancer Center Villejuif, France). After a complete assessment using positron emission
tomography scanning (Figure 2E) and local and general radiological analyses, the multidisciplinary
consultation staff decided on a surgical right mandibular bone excision with an autologous left fibula graft
associated with radiotherapy (Figure 3A). Nine months later, the graft was a success and the patient could
drink with her mouth. She continued to eat with gastrostomy for a year and a half after the surgery. She also
still had gPVL growing at the left mandibular canine collar, even after the surgery and radiotherapy (Figures
3B, 3C). Two years after surgery, a new SCC was diagnosed on the left mandibular gingiva. The patient was
treated for that new lesion with a new autologous right fibula graft, along with radiotherapy. Three years
after the first SCC, the patient had a left lymph node recurrence, which was treated with surgery. The patient
remains in close monitoring every three months to diagnose every recurrence as soon as possible.
2024 Vergier et al. Cureus 16(3): e56077. DOI 10.7759/cureus.56077 3 of 7
FIGURE 2: The gingival-only proliferative verrucous leukoplakia case
reported during the malignant transformation.
A: The lesion in September 2020. Swelling in the vestibular part of the tumefaction in regard to the second right
mandibular premolar and second right mandibular molar.
B: The lesion in September 2020. Second localization in the lingual gingiva between the second right mandibular
incisor and right mandibular canine.
C: Biopsies in October 2020. Vestibular biopsy between the second right mandibular premolar and first right
mandibular molar: in situ squamous cell carcinoma (SCC) characterised by architectural disorganisation and
cytonuclear atypia/mitosis (white arrows) found throughout the epithelium.
D: Biopsies in October 2020. Immunohistochemistry DAB anti-Ki67 in the 42-43 site showing hyperplasia with
hyperkeratosis but without dysplasia. The site needed a second biopsy to confirm the in situ SCC, which was
performed under general anaesthesia at Gustave Roussy Institute.
E: Positron emission tomography scan showing the important SCC invasion in the mandibular tissues (Siemens
©
Biograph Camera, 245 MBq of fludeoxyglucose F18, maximum standardized uptake value = 15.7).
2024 Vergier et al. Cureus 16(3): e56077. DOI 10.7759/cureus.56077 4 of 7
FIGURE 3: The first malignant transformation treatment.
A: Patient’s panoramic radiograph one month after the surgery.
B and C: Patient’s intrabuccal view nine months after the surgery. The gingival-only proliferative verrucous
leukoplakia persisted even after the surgery and radiotherapy.
Discussion
Since gPVL was first described by Hansen et al. in 1985 [1], a few cases have been reported in the literature.
This localisation is, however, the most frequent, as 50.9% of PVL cases have at least a gingival localisation
[6]. It is important to consider this diagnosis when a verrucous form of marginal linear leukoplakia, evolving
rapidly, forming a “ring around the collar” of the teeth appears [4]. It is the first and only case of gPVL we
observed in our department, which made the diagnosis even more challenging.
This form of leukoplakia appears mostly in women more than 65 years old, as they represent 67.1% of the
PVL cases [6]. Likewise, smoking is not a PVL risk factor, as there is one smoker for two non-smokers in PVL
cases [7]. The patient presented here confirms these observations.
Regarding malignant transformation, PVL has a high transformation rate, as 45.8% of PVL cases transform
to verrucous carcinoma or SCC [7]. Our patient had a very fast malignant transformation, as it appeared only
a year and a half after the first appointment, much faster than the mean follow-up duration of 4.1 years
before a malignant transformation, as reported by Palaia et al. [7].
Fortunately, the cancers developed on PVL seem to be less aggressive than other oral SCCs, as only 17.1% of
the patients died during follow-up [7-9]. This is also the case of the patient presented here, as she is still
alive at the time of this report, three years after the malignant transformation.
The patient presented here also had multiple melanomas before the SCC, in addition to her parents. This
could be a sign of inherited genetic factors. To date, there is no evidence of candidate biomarkers which
could be predictive of PVL malignant transformation [9]. To our knowledge, the genetic factors have been
explored and can be a good area for further studies.
The human papillomavirus (HPV) 16 infection is often evoked as a potential factor for PVL and malignant
transformation [10]. As several studies have found no association between viral infection and the
appearance of the lesion [4,11], we did not perform an HPV infection analysis for our patient.
2024 Vergier et al. Cureus 16(3): e56077. DOI 10.7759/cureus.56077 5 of 7
The case presented here highlights the difficulty in diagnosing PVL, especially when it is an exclusively
gingival localization. Indeed, in the early stages, gPVL is often confused with other oral leukoplakias, such
as traumatic or smoking leukoplakias, or drug-induced leukoplakias [2]. The histopathological analysis is
also confusing, as it often shows hyperkeratosis or verrucous hyperplasia at the initial stage, as shown in the
reported case. Verrucous hyperplasia is characterised by epithelial thickening, which induces a slight lifting
of the hyperkeratotic surfaces, with in-depth accentuation of the epithelial basal layer.
Our patient highlights the evolving process of the gPVL and the importance of a close follow-up with regular
biopsies in case of extension or change in the clinical presentation.
In our case, the second biopsy diagnosed a papilloma associated with a lichenoid reaction. This was
disturbing because of our clinical impression of the gPVL diagnosis. This was recently described in a study
that analysed multiple slides labelled as PVL or lichenoid lesions, with 5% of specimens exhibiting both
lichenoid lesion and PVL characteristics. This mainly concerned lesions of the same site analysed at
different times. This may be due to discrepancies between the diagnoses or changes in the lesion.
Consequently, the hypothesis of a continuum between oral lichenoid lesions and PVL, particularly on the
same site, should be considered [12]. Indeed, the characteristics of lichenoid lesions are common to the
verrucous hyperkeratosis of PVL and verrucous carcinoma; it may, therefore, be a non-specific inflammatory
response to dysplasia or malignancy rather than concomitant lichenoid disease [13].
Conclusions
The diagnosis of gPVL can be quite challenging because of the non-specific histology and clinical aspects.
The rapid evolution and the particular form of leukoplakia evolving as a “ring around the collar” on the
attached gingiva are key to diagnosing this specific form of PVL. Follow-up and repeated biopsies are very
important for PVL, as it can rapidly transform to SCC or verrucous carcinoma with around 50% risk of
malignant transformation. Because of very few cases reported in the literature, the knowledge about the
aetiology, anatomopathological, or genetic markers of gPVL is very poor. This knowledge can help predict
malignant transformation and improve gPVL follow-up to adapt the therapeutic procedures available.
Additional Information
Author Contributions
All authors have reviewed the final version to be published and agreed to be accountable for all aspects of the
work.
Concept and design: Valentin Vergier, Ihsène Taihi
Acquisition, analysis, or interpretation of data: Valentin Vergier, Katarzyna Czarny, Jean-Jacques Brau,
François Le Pelletier, Ihsène Taihi
Drafting of the manuscript: Valentin Vergier, Ihsène Taihi
Critical review of the manuscript for important intellectual content: Valentin Vergier, Katarzyna
Czarny, Jean-Jacques Brau, François Le Pelletier, Ihsène Taihi
Supervision: Ihsène Taihi
Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In
compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services
info: All authors have declared that no financial support was received from any organization for the
submitted work. Financial relationships: All authors have declared that they have no financial
relationships at present or within the previous three years with any organizations that might have an
interest in the submitted work. Other relationships: All authors have declared that there are no other
relationships or activities that could appear to have influenced the submitted work.
Acknowledgements
The authors are grateful to Dr De Kermadec and Dr Honart for the patient follow-up at the Cervico-facial
Carcinology Department (Gustave Roussy Cancer Center, Villejuif ).
References
1. Hansen LS, Olson JA, Silverman S Jr: Proliferative verrucous leukoplakia. A long-term study of thirty
patients. Oral Surg Oral Med Oral Pathol. 1985, 60:285-98. 10.1016/0030-4220(85)90313-5
2. Czarny K, Le Pelletier F, Vergier V, Taihi I: [Proliferative verrucous leukoplakia]. Ann Dermatol Venereol.
2024 Vergier et al. Cureus 16(3): e56077. DOI 10.7759/cureus.56077 6 of 7
2022, 2:124-34. 10.1016/j.fander.2021.06.010
3. 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:e839-45.
10.4317/medoral.15.e839
4. Upadhyaya JD, Fitzpatrick SG, Islam MN, Bhattacharyya I, Narayana N, Cohen DM: Marginal linear gingival
leukoplakia progressing to "ring around the collar"-an ominous sign of proliferative verrucous leukoplakia. J
Periodontol. 2021, 92:273-85. 10.1002/JPER.19-0621
5. Alabdulaaly L, Villa A, Chen T, et al.: Characterization of initial/early histologic features of proliferative
leukoplakia and correlation with malignant transformation: a multicenter study. Mod Pathol. 2022, 35:1034-
44. 10.1038/s41379-022-01021-x
6. Torrejon-Moya A, Jané-Salas E, López-López J: Clinical manifestations of oral proliferative verrucous
leukoplakia: a systematic review. J Oral Pathol Med. 2020, 49:404-8. 10.1111/jop.12999
7. Palaia G, Bellisario A, Pampena R, Pippi R, Romeo U: Oral proliferative verrucous leukoplakia: progression
to malignancy and clinical implications. Systematic review and meta-analysis. Cancers (Basel). 2021,
13:4085. 10.3390/cancers13164085
8. González-Moles MÁ, Warnakulasuriya S, González-Ruiz I, et al.: Clinicopathological and prognostic
characteristics of oral squamous cell carcinomas arising in patients with oral lichen planus: a systematic
review and a comprehensive meta-analysis. Oral Oncol. 2020, 106:104688.
10.1016/j.oraloncology.2020.104688
9. Faustino IS, de Pauli Paglioni M, de Almeida Mariz BA, et al.: Prognostic outcomes of oral squamous cell
carcinoma derived from proliferative verrucous leukoplakia: a systematic review. Oral Dis. 2023, 29:1416-31.
10.1111/odi.14171
10. 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, 24:193-7.
10.1111/j.1600-0714.1995.tb01165.x
11. Fettig A, Pogrel MA, Silverman S Jr, Bramanti TE, Da Costa M, Regezi JA: Proliferative verrucous leukoplakia
of the gingiva. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000, 90:723-30.
10.1067/moe.2000.108950
12. Thomson PJ, Goodson ML, Smith DR: Potentially malignant disorders revisited-the lichenoid
lesion/proliferative verrucous leukoplakia conundrum. J Oral Pathol Med. 2018, 47:557-65.
10.1111/jop.12716
13. Davidova LA, Fitzpatrick SG, Bhattacharyya I, Cohen DM, Islam MN: Lichenoid characteristics in
premalignant verrucous lesions and verrucous carcinoma of the oral cavity. Head Neck Pathol. 2019,
13:573-9. 10.1007/s12105-019-01006-4
2024 Vergier et al. Cureus 16(3): e56077. DOI 10.7759/cureus.56077 7 of 7
