Oral verrucous carcinoma

Verrucous carcinoma is a well-defined variant of the squamous cell carcinoma. Although it is reported to be rare in the Scandinavian countries, 16 cases have been diagnosed in the Southern part of Norway from 1975 to 1982. The clinical and histological characteristics were investigated. The most common site of occurrence was the mandibular alveolar ridge. The average age was 71 years, and unlike most other series of verrucous carcinoma, there was a female predominance and use of tobacco seemed to be the exception. The patients mainly complained of ill-fitting dentures. Adequate surgical excision appears to be the treatment of choice.     

Proliferative verrucous leukoplakia of the gingiva

OBJECTIVE: The purpose of this study was to describe the clinical-pathologic features of what appears to be a gingival form of proliferative verrucous leukoplakia. STUDY DESIGN: Ten adult patients with recurrent and histologically progressive gingival leukoplakias who were diagnosed and treated at the University of California, San Francisco between 1994 and 1999, comprised the subject group for this investigation. Clinical and microscopic features were reviewed. Proliferation indices and p53 expression were evaluated immunohistochemically, and the presence of human papillomavirus (HPV) DNA was determined by using polymerase chain reaction (PCR) amplification. RESULTS: Lesions presented as solitary or regional flat/papillary/verrucal leukoplakias of the free and attached gingiva (tooth-bearing areas only). With time, flat lesions developed a papillary or verruciform profile. Although lesions were recurrent, they were confined to the gingiva, and multiple lesions did not develop. Half the patients used tobacco, and HPV could not be detected by using PCR. Microscopically, 6 cases began as hyperkeratotic lesions, and 4 initially exhibited a psoriasiform pattern with a marked inflammatory component. With recurrences, the lesions became progressively atypical histologically. The proliferation indices for these lesions showed modest increases over normal epithelium, and positive p53 staining was evident in 4 of 10 cases, indicating a disruption of the keratinocyte cell cycle in these lesions. The mechanism associated with the positive p53 staining (protein binding to wild type p53 versus mutation of the p53 gene) was not determined. Lesions recurred after conservative scalpel or laser excision, and many developed into verrucous or squamous cell carcinoma. CONCLUSIONS: Proliferative verrucous leukoplakia of the gingiva (PVLG) appears to be a subset of oral proliferative verrucous leukoplakia. It can be characterized as a solitary, recurring, progressive white patch that develops a verruciform architecture and may not be associated with HPV. PVLG has an unpredictable course and is at risk for development into verrucous or squamous cell carcinoma. Currently, there is no way to determine or predict which gingival white lesions will follow the clinical course described for this group of patients with PVLG.     

Proliferative verrucous leukoplakia: a concise update

Oral Diseases (2010) 16 , 328–332 Proliferative verrucous leukoplakia (PVL) is of uncertain etiology but may be associated with human papillomavirus (HPV) infection. Proliferative verrucous leukoplakia is seen mainly in older women, beginning as a simple slow‐growing, persistent leukoplakia that tends to spread and become multifocal and affect the gingival frequently. In time, PVL develops exophytic, wart‐like or erythroplakic areas that become squamous carcinomas. Proliferative verrucous leukoplakia appears to resist to all attempts at therapy and often recurs.     

Oral verrucous carcinoma. An analysis of 37 cases

37 cases of oral verrucous carcinoma, occurring over a period of six years from 1981-1986, were analysed in respect of the clinical, radiological and histological findings. A delineation of the clinical presentation of this tumour, and the relation of habits to the occurrence of the lesion, has been clarified. The connotation of the term verrucous hyperplasia and its differences from verrucous carcinoma, have been discussed. Surgery and radiotherapy both seem to give good results as methods of treatment, especially when coupled with adequate nutrition and cessation of harmful habits.     

Intraosseous verrucous carcinoma originating from an odontogenic cyst: a case report

Carcinoma originating in bone is uncommon; most of them apparently arise in odontogenic cysts. In this paper, we report an extremely rare case in which, verrucous carcinoma originated from an odontogenic cyst. This lesion was firm and non-tender on palpation and had a white-pink appearance. It was encased in the anterior aspect of the maxilla and exhibited microscopic features of verrucous carcinoma of the oral mucosa. After surgical enucleation, no recurrence or metastasis has been observed up to now. It is mandatory to correlate the clinical and histopathologic findings to establish a true diagnosis.     

口腔疣状癌的误诊研究

目的 研究口腔疣状癌误诊的原因，以提高其临床治疗效果。方法 对20例口腔疣状癌的首次诊断及诊疗过程进行回顾性研究。结果 口腔疣状癌首次临床诊断符合率为35％，首次病理诊断符合率为85％。常易被误诊为疣状增生、乳头状瘤、牙源性囊肿、牙周炎、慢性唇炎。结论 加强对口腔疣状癌生物学行为多样性的认识，掌握不同类型口腔疣状癌的生物学行为特征是提高诊断水平的关键。     

Increased expression of inducible nitric oxide synthase for human oral submucous fibrosis,verrucous hyperplasia,and verrucous carcinoma

Three isoforms of nitric oxide synthase (NOS), endothelial, neuronal and inducible NOS (iNOS), have been identified in humans. Enhanced expression of iNOS protein has been previously reported for human oral epithelial dysplasias, a human oral premalignant epithelial lesion; however, this expression has not been demonstrated for other premalignant epithelial lesions, namely, oral submucous fibrosis (SF) and verrucous hyperplasia (VH). On the other hand, iNOS protein expression has not been reported in human oral verrucous carcinoma (VCa). The aim of this current study was to determine whether iNOS protein also occurs for oral SF, VH and VCa lesions. We found that membranous stainings were observed chiefly in oral SF lesions (17/20, 85%), whereas cytoplasmic stainings were mainly found in the VH variants (16/20, 80%). By contrast, cytoplasmic and/or nuclear stainings were observed in the specimens of verrucous carcinoma (17/20, 85%). Since no iNOS activity could be detected for any of our specimens of normal buccal mucosa in the present immunohistochemical study, this suggests that an NOS-dependent mechanism may be involved in the malignant transformation of these two premalignant oral epithelial lesions.     

Odontogenic cyst with verrucous proliferation

An unusual case of an odontogenic cyst with verrucous proliferation is described in a 13-year-old girl. This histologically distinctive odontogenic cyst variant does not appear to have been reported previously. The cyst was characterised by a series of verrucous projections in the lumen with hypergranulosis and cells resembling koilocytes, raising the possibility of a viral aetiology. However, no evidence of human papillomavirus (HPV) was found using immunohistochemistry and polymerase chain reaction (PCR) amplification.     

A clinicopathological study on verrucous hyperplasia and verrucous carcinoma of the oral mucosa

J Oral Pathol Med (2012) 41 : 131–135 Background: Oral verrucous hyperplasia (VH) and verrucous carcinoma (VC) are two clinicopathologically distinctive oral verrucous lesions. The objective of this study was to investigate the clinicopathological features of the two verrucous lesions and estimate their relationship from China. Methods: Retrospective review of two series of patients with histologically confirmed VH (n = 121) and VC (n = 56) between 1996 and 2009 in our hospital were conducted. Results: The average age of VH was 58.5 years (ratio male:female = 1.37) with the tongue being the predominant site. The average age of VC was 64.3 years (ratio male:female = 1.15) with the lower lip being the predominant site. Multivariate analysis revealed that the elderly patient with verrucous lesion (≥60 years) was associated with 3.06‐fold (P = 0.007) increased carcinoma risk compared with the non‐elderly patient. The lesion located on lower lip was associated with 13.54‐fold (P < 0.001) increased carcinoma risk compared with other sites. Conclusion: Clinicopathological features of VH and VC in China were elucidated. Elderly patient with oral verrucous lesion located on the lower lip correlates with higher risk of carcinoma.     

口腔疣状癌超微结构特征研究

目的：探讨口腔疣状癌超微结构特征，对疣状癌提出分型。方法：取正常口腔黏膜，口腔疣状癌，口腔高分化鳞癌及低分化鳞癌石蜡标本各8例，常规电镜制样，H-600型透射电镜检测。结果：口腔疣状癌超微结构可归纳为3种类型：Ⅰ型：癌上皮细胞分化较好，形态规则，细胞间隙略窄，细胞间有丰富且形态规则的桥粒，胞浆内线粒体少，但粗面内质网丰富，胞浆内未见桥粒。上皮问可见角化珠。Ⅱ型癌上皮细胞分化很差，细胞异形性明显，细胞间桥粒散在，细胞内桥粒丰富，包裹成团，粗面内质网少。Ⅲ型：癌上皮细胞瘦长，核浆浓缩，细胞间隙较高分化鳞癌宽，细胞间桥粒瘦长且丰富。结论：口腔疣状癌超微结构变化是其临床生物学行为多样性的基础，由此推测疣状痛自身可能存在不同的亚型和分化潜能。     

口腔疣状癌临床诊治专家共识

口腔疣状癌(oral verrucous carcinoma, OVC)是一种具有独特组织学改变和生物学行为,有别于口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)的恶性肿瘤,发病原因目前尚不明确。研究发现,其首次临床诊断符合率仅为35%,常被误诊为疣状增生、牙源性角化囊肿、侵袭性牙周炎和慢性颌骨骨髓炎等疾病。OVC的治疗手段和预后与OSCC不尽相同,误诊和误治严重影响患者的生存质量。制定OVC临床诊治专家共识的目的,是希望减少OVC误诊误治,提高早期诊断率、患者生存率和生活质量。     

Proliferative verrucous leukoplakia: a case report

Proliferative verrucous leukoplakia (PVL) is a particularly aggressive form of oral leukoplakia that is resistant to treatment and presents a high risk of recurrence and malignant transformation. This article describes the microscopic and clinical characteristics of one case of PVL, which initially presented as hyperkeratosis with mild dysplasia and posteriorly developed multifocal areas and verrucous carcinoma despite treatment.     

Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria

Since its introduction in the literature in 1985, the term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Widespread or multifocal occurrence of oral leukoplakia is not just synonymous to PVL. In the present treatise the proposal is made to require the involvement of more than two oral oral subsites, a total added seizeof the leukoplakic areas of at least 3 centimeters, and a well documented period of at least five years of disease evolution being characterized by spreading and the occurrence of one or more recurrences in a previously treated area. Key words:Oral premalignant lesions, leukoplakia, verrucous leukoplakia.     

Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL

Proliferative verrucous leukoplakia (PVL) is a unique oral white lesion in which human papillomavirus (HPV) may play a role. PVL behaves far more aggressively than other forms of leukoplakia with a high rate of recurrence after surgical excision, and relentless progression to verrucous hyperplasia and to verrucous or squamous cell carcinomas. The treatment of PVL is usually by surgery, but there is often early recurrence. This study was an open trial of surgery in 25 patients with oral HPV-positive PVL, compared with combined therapy using surgery and methisoprinol in another group of 25 patients with oral PVL. Six months postoperatively there was a significant difference, with 18 recurrences in the patients treated by surgery alone compared to only two recurrences in the patients treated also with methisoprinol (isoprinosine or inosine pranobex), a synthetic agent with immunomodulatory properties and some antiviral activity against HPV. Eighteen months postoperatively there were no further recurrences in the patients treated by surgery alone but another two recurrences in the patients treated with methisoprinol. Overall, by 18 months follow-up, there were 18 recurrences in the group treated by surgery alone, compared with four in those also receiving methisoprinol. The use of this antiviral agent appeared to offer a significant enhancement to the surgical management of PVL.     

Salivary and serum interleukin-6 levels in proliferative verrucous leukoplakia

Background

Cytokines and chemokines have been analysed in patients with oral squamous cell carcinoma and potentially malignant disorders. We selected interleukin-6 (IL-6) because it is a multifunctional interleukin reported to be altered in potentially malignant oral disorders and in malignant lesions. To date, this has not been evaluated or tested in proliferative verrucous leukoplakia (PVL), however.

Objectives

This study aimed to analyse the differences in serum and saliva IL-6 levels among patients with PVL, oral squamous cell carcinoma (OSCC) and healthy controls and to examine the relationship between salivary IL-6 levels and the extent of the verrucous area.

Methods

Using an enzyme-linked immunosorbent assay, we determined the serum and saliva IL-6 levels in three groups: 20 patients with PVL, 20 with OSCC and 20 healthy controls.

Results

There were significant (p?<?0.01) differences in the serum and saliva IL-6 levels among the three groups and among the three grades of extent of the verrucous areas (p?=?0.01). In the OSCC group, there was a significant difference in the saliva IL-6 levels between patients with and without lymph node metastasis at diagnosis (p?=?0.02).

Conclusions

We found that patients with OSCC had the highest salivary and serum IL-6 levels, while PVL had lower values than OSCC, but higher than the controls, and these altered levels were associated with the extent of the verrucous areas.

Clinical relevance

Salivary and plasma IL-6 are altered in patients with PVL, with more extensive verrucous areas being associated to the highest IL-6 levels. This could be a significant tool for monitoring patients with PVL, their progression to more advances stages and their recurrences.

     

Nevus unius lateris and intraoral verrucous nevi

A case of nevus unius lateris and two cases with similar intraoral lesions but no evidence of cutaneous involvement are described. The terminology of papillary intraoral epithelial nevi is discussed, and it is suggested that lesions of this type, confined solely to the mouth, should be called verrucous nevi.     

Proliferative verrucous leukoplakia: a clinicopathological comparative study

A retrospective clinicopathological analysis was performed to compare 35 proliferative verrucous leukoplakia (PVL), 40 leukoplakia without dysplasia (LK), 48 oral lichen planus (OLP)/oral lichenoid lesions (OLL), and 11 verrucous carcinoma (VC) (N = 134). The PVL group comprised 24 female and 11 male patients (mean age 66.5 years), with two to six sites involved (mean 3.1 sites) and multiple biopsies over time (mean 7.1/case). All PVL cases developed malignancy: 77.1% squamous cell and 40% verrucous carcinoma; 68.6% had multiple sites of malignancy. None showed local or distant metastatic spread. Five-year disease-specific survival was 88.6%. In LK and OLP/OLL, malignant transformation was significantly lower than in PVL (2.5% and 2.1%, respectively). Invasive squamous cell carcinoma was not reported in any conventional VC. Immunohistochemical histomorphometric analysis for p53, COX-2, and podoplanin showed no significant differences between the groups. PVL may overlap with LK, OLP/OLL, and VC, but has a persistent aggressive behaviour and high malignant transformation rate. The overlapping features may delay recognition as PVL. The results emphasize the need for a detailed clinicopathological definition of PVL, and long-term close monitoring to ensure progression to PVL and malignancy are recognized in time. The management of this persistent aggressive condition is challenging.     

Diagnostic criteria in proliferative verrucous leukoplakia: Evaluation

Objectives: to evaluate the ability of the diagnostic criteria proposed by Cerero et al in 2010 to perform an early diagnose in patients with proliferative verrucous leukoplakia. Study Design: retrospective study with patients diagnosed with leukoplakia at Oral Medicine Service at Oral Medicine and Surgery Department at Dentistry Faculty at Universidad Complutense of Madrid. Results: the criteria were applied in 116 patients, turning positive in 40 cases. Out of these, 24 (60%) had been previously diagnosed with PVL. Most frequent criteria were major criteria A and E, concerning lesion’s site and histopathology, and minor criteria b and c, concerning sex and smoking habit. Conclusions: diagnostic criteria developed by Cerero et al can be a useful tool for an early diagnose of PVL, as in 60% of the cases, the criteria would have allowed to make an early diagnose of the disease. Key words:Proliferative verrucous leukoplakia, criteria, diagnose, early.     

Cyclin B1 overexpression in conventional oral squamous cell carcinoma and verrucous carcinoma-A correlation with clinicopathological features

Background: Nuclear localization of cyclin B1 is an indicator for cells undergoing mitotic division, and the overexpression has shown promising results as a good prognostic predictor for patients of squamous cell carcinoma (SCC). Cyclin B1 overexpression among histological grades of conventional oral squamous cell carcinoma (COSCC), as well as comparison with verrucous carcinoma (VC) has been less investigated. Study Design: Immunohistochemical expression of cyclin B1 was compared with various clinicopathological features in 30 primary COSCC and 31 primary VC cases. Result: Cyclin B1 showed significant overexpression for some clinical features for both the variants of oral squamous cell carcinoma. In histopathological variants, statistical significance was observed among grades of COSCC, as well as COSCC and its grades with VC. The concomitant increase in cyclin B1 overexpression from VC to grades COSCC was observed. Conclusion: Our study findings draw attention to cyclin B1 overexpression is involved in early carcinogenesis, cell differentiation and tumor proliferation. Key words:Cyclin B1, oral squamous cell carcinoma, verrucous carcinoma, head and neck cancer.     

Malignant transformation of oral proliferative verrucous leukoplakia: a series of 48 patients with suggestions for management

Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral mucosal leukoplakia of unknown origin, characterized by high rates of malignant transformation. Different diagnostic criteria, terminologies, and therapeutic approaches have been proposed since the first report in 1985. There remains no general agreement regarding the clinical and histological diagnosis, prevention, and correct management of this disease. This retrospective study investigated 48 patients affected by PVL showing at least one malignant transformation and followed up at 2-month intervals. Twenty-five were female (52.1%) and 23 (47.9%) were male; their median age was 67 years (range 40–93 years). Follow-up ranged from 18 to 240 months. Clinical examination included the use of Lugol’s solution to prevent clinical underestimation of the margins and toluidine blue for suspicious areas. Surgical excision by scalpel was the preferred treatment for suspicious lesions, with only five carcinomas surgically removed by diode laser and two by CO₂ laser. All specimens were accurately mapped after formalin fixation. Fifteen patients (31.3%; 10 female, five male) developed one oral carcinoma, while 33 (68.7%) developed two or more primary tumours (range 3–12). Only four patients (8.3%), who developed between 2 and 8 oral squamous cell carcinomas (OSCCs), died of tumour-related causes. The pre-surgical clinical workup, subsequent surgical treatment, and follow-up are key to success for patients affected by PVL with malignant transformation into stage 1 OSCC and/or verrucous carcinoma, leading to a high overall survival rate.