Case report of rapidly progressive proliferative verrucous leukoplakia and a proposal for aetiology in mainland China
- Lin Ge†1,
- Yun Wu†1,
- Lan-yan Wu2,
- Lin Zhang1,
- Bing Xie1,
- Xin Zeng3,
- Mei Lin3Email author and
- Hong-mei Zhou3Email author
© Ge et al; licensee BioMed Central Ltd. 2011
Received: 22 November 2010
Accepted: 27 February 2011
Published: 27 February 2011
Proliferative verrucous leukoplakia (PVL) is a rare oral leukoplakia and has four features such as chronic proliferation, multiple occurrences, refractoriness to treatment and high rate of malignant transformation. As mentioned above, most PVL cases processed to malignancy over many years, sometimes 20 years. However, this report described a case of rapid progress, which had malignant transformation in a short period. Additionally, the aetiology of PVL was discussed and immunity was proposed as the possible cause.
Proliferative verrucous leukoplakia (PVL) is a rare oral leukoplakia, principally characterized by chronic proliferation, multiple occurrences, and refractoriness to treatment. Its rate of malignant transformation is extremely high . The characteristics of its clinical and pathological progress are considered vital bases for the diagnosis of PVL because there are no particular differences between the pathological changes of PVL and those of oral verrucous leukoplakia (OVL) .
PVL grows slowly and can take up to 7.8 years to become cancerous. The process is irreversible and usually progresses to cancer. According to the study by Bagan, PVL quickly becomes malignant, on average within 4.7 years , whereas Hansen reported an average time to cancer of 6.1 years . However, Silverman and Gorsky reported a longer mean malignant process of 11.6 years .
Recently, our department treated a patient with PVL that developed extremely rapidly, with only 16 months from the appearance of white patches to their cancerous transformation. Consequently, this case warrants attention. We describe this case with reference to the relevant literature, and confirm that this is the first report of PVL in mainland China.
A female patient, aged 52 years, attended the Department of Oral Medicine at West China Hospital of Stomatology, Sichuan University in June, 2006, with painless white patches over the right bucca and palate for over a year. One year earlier, the patient had discovered the white patches on her right bucca and palate, which felt coarse but were painless. The local hospital diagnosed them by biopsy as leukoplakia, but did not treat them.
General properties of PVL
PVL is a rare and specific disease that differs from OVL, and is often seen in middle-aged and elderly women, occurring predominantly on the bucca, palate, gingiva, and tongue. Hansen et al.  classified the pathological process of PVL into 10 grades, i.e., 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 by the adjacent even scores. Once PVL is confirmed, active therapy should be undertaken, such as surgery, laser management, photodynamic therapy, combined treatments, etc. [5–9]. However, PVL responds poorly to various therapeutic measures, and its recurrence rate is relatively high, even after its surgical removal.
Developmental process of PVL and related epidemiological investigation in China
PVL is usually chronic and progressive, and a patient often has a long history of leukoplakia before he/she attends a clinic [8, 10]. Most cases progress for 20-25 years. In contrast to most slow-growing PVL, the case described here became cancerous quite rapidly. 1) There was only a short history of leukoplakia; the duration of the disease preceding the patient's first visit was only one year, according to the patient. 2) There was no obvious growth process from single foci to multiple foci. 3) The lesions changed quickly; the disease was clearly more hyperplastic in the fourth month after the initial visit. 4) The period to malignancy was short; the whole process in this case took less than two years. The white patch over the palate was shown by biopsy to have undergone malignant transformation within about four months of the initial visit.
The disease reported here developed rapidly within four months of the patient's initial clinic visit. Therefore, we speculate that when PVL progresses to moderate dysplasia or malignancy, it is supposed to develop rapidly and not remain so chronic as its early stage. Furthermore, previous studies have primarily focused on Caucasian subjects, reflecting the growth status and properties of PVL only among these ethnic groups, so there is little knowledge of PVL in Asian or specifically Chinese populations . Therefore, it must be determined whether PVL has different features in these populations.
China undertook an epidemiological census of oral leukoplakia in 134,492 people between 1978 and 1979. The results showed that 14,076 of the subjects had oral leukoplakia, 287 of whom had warty lesions, constituting a large proportion (68.33%) of the 420 patients with heterogeneous leukoplakia . A longer observation period is required to establish a definite diagnosis of PVL, to allow its progression, because in its initial stages, PVL appears to be simple verrucous leukoplakia. Therefore, the incidence of PVL in China requires a long-term longitudinal study.
Aetiology of PVL
Until now, the aetiological factors of PVL have been unclear. However, the case reported here and those in the literature seem to implicate immune factors. As reported, our patient suffered from chronic superficial antral gastritis, which would affect nutrient absorption and further affect the immunity of the patient. Enhancing the patient's immunity and topical therapies had a positive effect at the first examination. The report of a patient with PVL after bone-marrow transplantation (BMT)  supports this impression. BMT involves an immunosuppressive step and oral squamous cell carcinoma (OSCC) is a malignancy that can occur after BMT. This indicates that immunity plays an important role in PVL, as in OSCC. Epidemiological data have demonstrated that there is a high incidence of PVL in elderly women, with no obvious association with cigarette smoking and alcohol consumption, which distinguishes PVL from other ordinary leukoplakias. Common sense tells us that women have lower immunity than that of men and that immunity decreases with age. This implies that immune factors, rather than external stimuli, play a major role in PVL. Moreover, PVL patients infected with human papillomavirus [7, 14] or Epstein-Barr virus  might be immunocompromised like human immunodeficiency virus -infected patients . If immunity plays an important role in PVL, enhancing the immune response is a critical intervention, especially in the early phase of the disease because some patients have shown resistance to such therapies in later stages.
Whether PVL progresses especially rapidly in Asian or Chinese populations requires further investigation. The health of these patients, especially their immune status, warrants examination for its contribution to the aetiology of PVL.
Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of her written consent is available for review by the Editor-in-Chief of this journal.
This research was supported by the grant from National Natural Science Foundation of China, 30872873
- Hansen LS, Olson JA, Silverman S: Proliferative verrucous leukoplakia: A long-term study of thirty patients. Oral Surg Oral Med Oral Pathol. 1985, 60: 285-298. 10.1016/0030-4220(85)90313-5.View ArticlePubMedGoogle Scholar
- Gale N, Pilch BZ, Sidransky D: Epithelial precursor lesions. Pathology and genetics of head and neck tumor. Edited by: Barnes L, Eveson JW, Reichart P, Sidransky D. 2005, Lyon, France: IARC Press, 177-179.Google Scholar
- Bagan JV, Jimenez Y, Sanchis JM, Poveda R, Milian MA, Murillo J, Scully C: Proliferative verrucous leukoplakia: high incidence of gingival squamous cell carcinoma. J Oral Pathol Med. 2003, 32 (7): 379-382. 10.1034/j.1600-0714.2003.00167.x.View ArticlePubMedGoogle Scholar
- Silverman S, Gorsky M: Proliferative verrucous leukoplakia: A follow-up study of 54 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997, 84: 154-157. 10.1016/S1079-2104(97)90062-7.View ArticlePubMedGoogle Scholar
- 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, 82: 396-401. 10.1016/S1079-2104(96)80303-9.View ArticlePubMedGoogle Scholar
- Schoelch ML, Sekandari N, Regezi JA, Silverman S: Laser management of oral leukoplakias: A follow-up study of 70 patients. Laryngoscope. 1999, 109: 949-953. 10.1097/00005537-199906000-00021.View ArticlePubMedGoogle Scholar
- Femiano F, Gombos F, Scully C: Oral proliferative verrucous leukoplakia (PVL), open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL. Int J Oral Maxillofac Surg. 2001, 30: 318-322. 10.1054/ijom.2001.0066.View ArticlePubMedGoogle Scholar
- Vigliante CE, Quinn PD, Alawi F: Proliferative verrucous leukoplakia: report of a case with characteristic long-term progression. J Oral Maxillofac Surg. 2003, 61: 626-631. 10.1053/joms.2003.50119.View ArticlePubMedGoogle Scholar
- Fettig A, Pogrel MA, Silverman S, Bramanti TE, Da Costa M, Regezi JA: Proliferative verrucous leukoplakia of the gingiva. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000, 90: 723-730. 10.1067/moe.2000.108950.View ArticlePubMedGoogle Scholar
- Shopper TP, Brannon RB, Stalker WH: Proliferative verrucous leukoplakia: an aggressive form of oral leukoplakia. J Dent Hyg. 2004, 78: 7-PubMedGoogle Scholar
- Ghazali N, Bakri MM, Zain RB: Aggressive, multifocal oral verrucous leukoplakia: proliferative verrucous leukoplakia or not?. J Oral Pathol Med. 2003, 32: 383-392. 10.1034/j.1600-0714.2003.00180.x.View ArticlePubMedGoogle Scholar
- Minwen L, Tingfa Z: National epidemiological survey report on OLK. Oral premalignant lesions: leukoplakia and lichen planus. Edited by: Guoqi X, Bingqi L, Huifeng L. 1992, Beijing: China Medical Technology Press, 8-20.Google Scholar
- Torres-Pereira C, Funke V, Giovanini AF, Lemos CA, Amenabar JM, Piazzetta CM: Oral proliferative verrucous leukoplakia (PVL) in a post-bone marrow transplant patient. Biol Blood Marrow Transplant. 2008, 14 (10): 1197-1199. 10.1016/j.bbmt.2008.07.012.View ArticlePubMedGoogle Scholar
- Palefsky JM, Silverman S, Abdel-Salaam M: Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16. J Oral Pathol Med. 1995, 24 (5): 193-197. 10.1111/j.1600-0714.1995.tb01165.x.View ArticlePubMedGoogle Scholar
- Bagan JV, Jimenez Y, Murillo J, Poveda R, Diaz JM, Gavalda C, Margaix M, Scully C, Alberola TM, Torres Puente M, Pérez Alonso M: Epstein-Barr virus in oral proliferative verrucous leukoplakia and squamous cell carcinoma: A preliminary study. Med Oral Patol Oral Cir Bucal. 2008, 13 (2): E110-113.PubMedGoogle Scholar
- Adler-Storthz K, Ficarra G, Woods KV, Gaglioti D, DiPietro M, Shillitoe EJ: Prevalence of Epstein-Barr virus and human papillomavirus in oral mucosa of HIV-infected patients. J Oral Pathol Med. 1992, 21 (4): 164-170. 10.1111/j.1600-0714.1992.tb00095.x.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.