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。     

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.     

Treatment of verrucous hyperplasia and verrucous carcinoma by shave excision and simple cryosurgery

Wide excision and skin or mucosa grafting has been the primary form of therapy for verrucous hyperplasia and verrucous carcinoma. But those with wide involvement often make the procedures complicated. A simple management, shave excision followed by simple cryosurgery, is presented. The treatment modality described is simple, and less traumatic. It can be performed under local anaesthesia, and requires no hospitalization. It has been easily used to treat 26 lesions in 20 patients with satisfactory results.     

Detection of human papillomavirus-genomic DNA in oral epithelial dysplasias, oral smokeless tobacco-associated leukoplakias, and epithelial malignancies

Human papillomavirus (HPV) is an infectious agent that is increasingly associated with mucosal cancers, in particular cancer of the cervix. The present investigation was undertaken in an attempt to determine whether HPV could be easily detected in biopsies of oral tissues, specifically oral squamous cell carcinomas, oral epithelial dysplasias, smokeless tobacco keratoses, verrucous hyperplasia, and verrucous carcinoma. In situ DNA hybridization methods were used to isolate specific HPV genomes. Among 100 instances of benign leukoplakia, only 4% of non-tobacco-related and 10% of smokeless tobacco-related lesions harbored viral sequences. We were able to detect viral sequences in dysplastic lesions 3% of the time. Alternatively, 17% and 20% of the verrucous hyperplasias and verrucous carcinomas were positive for viral nucleic acids. Six percent of the squamous cell carcinomas harbored HPV. On the basis of these findings, it is concluded that HPV of known genotype can be identified in oral premalignant and malignant neoplasms.     

Verrucous carcinoma, hyperplasia and leukoplakia of the oral mucosa: a clinico-histopathological and histometric study

Thirteen cases of verrucous leucoplakia (VL), 3 of verrucous hyperplasia (VH) and 19 of verrucous carcinoma (VC) were evaluated by means of 4 clinical features, 12 microscopic parameters and 6 epithelial histometric measurements. No significant clinical differences were detected, but histologic data showed that orthokeratinization was more frequent in VL and VH, while parakeratinization proved more common in VC. Sharp epithelial projections predominated in all three lesion types, though lymphoplasmatic infiltration and Russell bodies were more frequent in VH. Histometrically, there were statistical differences between VL or VH vs VC in three parameters, namely connective tissue-epithelial interface (Ice), epithelial height (He) and connective tissue-epithelial interface plus verrucous epithelial surface (Ice + Sve). To conclude, in this series, VH failed to exhibit significant clinical or histologic differences vs VL or VC, but histometric analysis was able to detect epithelial differences between both premalignant lesions and VC.     

Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: a follow-up study based in a Taiwanese hospital

BACKGROUND: It is generally accepted that the development of cancer in the oral mucosa is preceded by an identifiable non-invasive precursor lesion. The aim of this follow-up study was to estimate the rate and the time to transformation in a group of patients from southern Taiwan with potentially malignant oral epithelial lesions. METHODS: The follow-up time is defined as the duration between the onset of the initial diagnosis and the occurrence of confirmed oral cancer. A total of 1458 patients with histological diagnoses of various pre-malignant oral lesions were followed up between 1991 and 2001. The average age at initial diagnosis was 47.5 years. The histological diagnoses were divided into six categories: epithelial dysplasia with hyperkeratosis/epithelial hyperplasia (8.85%); epithelial dysplasia with submucous fibrosis (2.54%); submucous fibrosis (27.57%); hyperkeratosis/epithelial hyperplasia (29.01%); lichen planus (9.80%) and verrucous hyperplasia (22.22%). RESULTS: Within the cohort of 1458 patients, 44 patients progressed to oral cancer in the same site as the initial lesions with an overall transformation rate of 3.02% and a mean follow-up time of 42.64 months. Eight of the 166 patients with dysplastic lesions and 15 of 423 patients with hyperkeratosis/epithelial hyperplasia progressed to malignancy. The other patients with malignant transformation originated from various pre-cancerous oral lesions and conditions (submucous fibrosis, eight of 402; lichen planus, three of 143; verrucous hyperplasia, 10 of 324). CONCLUSION: These results indicate that patients with pre-malignant oral lesions need long-term follow up.     

Immunohistochemical demonstration of epithelial glutathione S-transferase isoenzymes in normal, benign, premalignant and malignant human oral mucosa

The expression and localization of glutathione S-transferase (GST) isoenzymes in the epithelium of normal oral mucosa ( n = 9), overlying reactive fibrous hyperplasia ( n =9), and of potentially malignant [leukoplakia ( n =25), submucous fibrosis ( n =12), verrucous hyperplasia ( n =16)] and malignant [squamous cell carcinoma ( n =36), verrucous carcinoma ( n =13)] oral lesions were examined immunohistochemically using polyclonal antibodies raised against GST isoenzymes (alpha, mu and pi) with the standard avidin-biotin-peroxidase complex (ABC) method. GST alpha, mu and pi were almost completely absent in the epithelium of normal oral mucosa and overlying benign fibrous tissues. GST alpha staining was cytoplasmic and focally positive, while GST mu staining was similar to but weaker than that seen for GST alpha. GST pi showed both cytoplasmic and nuclear staining and was expressed in 60% of leukoplakias with mild dysplasia ( n =15), 80% of leukoplakias with moderate to severe dysplasia ( n =10). 75% of submucous fibrosis samples ( n =12), 75% of verrucous hyperplasias ( n =16), 77% of verrucous carcinomas ( n =13), 81% of well-differentiated squamous cell carcinomas ( n = 26) and 70% of moderate- to poorly-differentiated squamous cell carcinomas ( n =10). In addition, GST pi expression was independent of the state of differentiation of oral cancers. Since GST pi was significantly over-expressed in the oral premalignant and malignant lesions, the kinetics of GST pi-positive cells and the value of GST pi as a tumor marker in oral carcinogenesis need further investigation.     

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。     

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.     

In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus.

Twenty-one papillomas, 23 ordinary benign keratoses, 13 smokeless tobacco keratoses, 10 verrucous hyperplasias, 10 verrucous carcinomas, 17 squamous cell carcinomas, 3 epithelial dysplasias, and 6 lichen planus lesions were evaluated for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/35, with biotinylated double-stranded DNA probes by in situ hybridization. Sixty-two percent (13/21) of oral squamous papillomas were positive for HPV DNA. HPV DNA types 6 and 11 demonstrated the strongest reactivity. Of the 13 cases, 10 also showed some reactivity with HPV-16/18 and -31/33/35. None of the cases of keratoses, epithelial dysplasia, squamous cell carcinoma, verrucous hyperplasia, verrucous carcinoma, or lichen planus were positive for HPV DNA. This study confirms the consistent and frequent finding of HPV DNA in oral squamous cell papillomas and the inconsistency of being able to identify HPV DNA in keratotic, premalignant, or cancerous lesions of the oral mucous membranes.     

Leukoplakia of the labial commissure

A white lesion located in the labial commissure can pose problems for both the clinician and the pathologist. The clinician may be limited in his surgical treatment because of aesthetic reasons, whilst the pathologist may be confronted with a lesion with or without candidal involvement, showing the histological features of hyperplastic candidiasis, verrucous hyperplasia, verrucous carcinoma, epithelial dysplasia, carcinoma-in-situ and, occasionally, squamous cell carcinoma. A retrospective study was undertaken of 10 patients with leukoplakic commissural lesions, who visited the Department of Oral Surgery in the Teaching Hospital of the Free University, Amsterdam in the period between 1973-1986. The clinical and histopathological findings are presented. Although a carcinoma in this particular region is rather rare, alertness remains necessary as one patient with the clinical appearance typical of leukoplakia, showed on biopsy the presence of a squamous cell carcinoma at this first visit. In another two patients the areas of leukoplakic change were shown histologically to be based on verrucous carcinoma. In one patient a squamous cell carcinoma developed after several years, in spite of treatment. In view of the small number of patients under discussion and also the somewhat debatable diagnosis of verrucous carcinoma, we do not feel justified in drawing any firm conclusions from our findings with regard to the malignant potential of leukoplakia of the oral commissures.     

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.     

Verrucous carcinoma of the mouth

This paper describes a survey of 198 cases of oral verrucous carcinoma reported in the literature and a study of a further 15 personally-observed cases. Elderly Caucasoid males are most frequently affected, although in the South African group there were 10 females and 5 males. The lesion, which classically has a verrucous surface, may be small or more extensive. The cheek mucosa and the alveolar mucosa/gingiva are the sites most commonly involved. Sometimes more than one area is affected in the same patient and the tumor may be associated with other lesions such as leukoplakia, pseudo-epitheliomatous hyperplasia and frank carcinoma. The etiology is uncertain but tobacco usage in any form appears to be implicated. The tumor is locally invasive and 6 of our series of 15 recurred after surgical removal. It does not metastasize unless it undergoes anaplastic transformation, which it frequently does if treated with radiotherapy. The correct treatment is therefore wide surgical excision. Histologically, there is a typical abrupt margin. The tumor has surface papillary projections and infiltrating broad, blunt rete pegs which form a "pushing margin". The epithelium is generally well-differentiated but there may be a high mitotic index and there may be an appearance of epithelial atypia if the epithelium is inflamed. Keratin is usually present on the surface and in the crevices of the deep invaginations but may be absent from tumors involving non-keratinizing surfaces.     

Detection of human papillomavirus DNA by in situ DNA hybridization and polymerase chain reaction in premalignant and malignant oral lesions.

The sensitivity of detection of human papillomavirus (HPV) DNA in premalignant and malignant oral lesions by in situ hybridization (ISH) and polymerase chain reaction (PCR) were compared. With both methods HPV DNA was found in 4 of 24 cases of epithelial dysplasia, 4 of 14 cases of verrucous hyperplasia, and 1 of 10 cases of squamous cell carcinoma. The 10 cases of smokeless tobacco keratoses and 3 cases of verrucous carcinoma that we examined were all negative for HPV DNA. The PCR for the E6 open reading frame of HPV-16 correctly identified all cases that were positive by ISH. Only a single case that was positive by PCR was negative by ISH for HPV DNA. However, the PCR demonstrated the presence of HPV-16 infection in one case, which had hybridized most intensely with the probe for types 31/33/35 in the ISH. This discrepancy probably is due to the high degree of cross-hybridization in the ISH assay. PCR appears to be an effective technique for identifying HPV-16 DNA sequences in biopsy material from premalignant and malignant oral lesions.     

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.     

Papillary lesions of the oral cavity: relationship to human papillomaviruses

Human papillomaviruses are a group of genetically related organisms that infect stratified squamous epithelium. Unlike many other viruses that infect oral epithelium and induce lysis of the cells they penetrate, HPVs induce proliferative changes in these cells that result in both benign and malignant tumors. The common skin wart (verruca vulgaris) is induced by HPV 2 and 4. Genital warts (condylomas) and the common solitary oral papilloma are associated with HPV 6 and 11. Either HPV 13 or 32 causes focal epithelial hyperplasia. All of these wart-like lesions are benign growths of the stratified squamous lining of the oral cavity and lips and can be treated by surgical excision or laser ablation. HPV 16 and other less frequently encountered genotypes are associated with uterine cervix cancer in 95 percent to 98 percent of cases, and the evidence for a causal role is robust. There are emerging data that implicate HPV in certain subsets of oral cancer, particularly those that arise in the oropharynx/tonsillar region. Some instances of the various histologic subtypes subsumed under proliferative verrucous leukoplakia and verrucous carcinoma also harbor HPV.     

Successful treatment of an extensive verrucous carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy

Our recent study found that a new topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) protocol composed of multiple 3-min fractionated irradiations with a light emitting diode (LED) red light at 635 +/- 5 nm for a total of 1000 s (fluence rate: 100 mW/cm(2); light exposure dose: 100 J/cm(2)) after topical application of 20% ALA for 1.5 or 2 h can be used successfully for the treatment of oral verrucous hyperplasia. In this case report, we tested the efficacy of this new treatment protocol of ALA-PDT for an extraoral verrucous carcinoma (VC) lesion at the right mouth angle and an intraoral VC lesion at the right buccal mucosa of a 56-year-old male areca quid chewer and smoker. The extraoral tumor was cleared after six treatments of topical ALA-PDT and the intraoral tumor showed complete regression after 22 treatments of topical ALA-PDT. No recurrence of the VC lesion was found after a follow-up period of 6 months. We suggest that PDT using a topical application of 20% ALA followed by multiple 3-min fractionated irradiations with an LED red light is also an effective and successful treatment modality for VC.     

Evaluation of Versatility and Effectiveness of Pedicled Buccal Fat Pad Used in the Reconstruction of Intra Oral Defects

Introduction

The use of buccal fat pad as a grafting source in the closure of intraoral defects has gained popularity in the last quarter of this century. Because of the ease of access and rich blood supply, its use in oral defects is an attractive concept.

Methodology

The study comprised of 8 patients with oral submucous fibrosis, 1 patient with oroantral fistula, 1 patient with verrucous hyperplasia. The acquired oral defects following resection of pathology in the oral cavity, were reconstructed with pedicled buccal fat pad. The Post operative follow up at the intervals of 1st, 7th and 15th day, followed by 1st month, 2nd month and 3rd month was done.

Results

The procedure was successful in all the patients. Healing was satisfactory with no breakdown or liquefaction necrosis post operatively. All the patients had definitive colour change at the end of 1st post operative month owing to the epithelialisation. Residual defect was present in one patient diagnosed of verrucous hyperplasia on the 1st and the 7th post operative day which subsequently healed. In 8 patients with oral submucous fibrosis post operative mouth opening was measured in and was observed to be in the range of 12–26 mm on the 1st post operative day and 34–42 mm during 3rd month post operatively.

Conclusion

The results of this study support the view that the use of buccal fat pad is a simple, convenient and reliable method for the reconstruction of small to medium sized intra oral defects.     

Repair of oral mucosal defects with cryopreserved human amniotic membrane grafts: prospective clinical study

The aim of this study was to evaluate the clinical outcome of the surgical repair of oral mucosal defects using cryopreserved human amniotic membrane (HAM) as a graft material. Thirty-four patients with precancerous lesions such as leukoplakia, erythroplakia, and verrucous hyperplasia were included. Fresh amniotic membrane was obtained from women undergoing elective caesarean section; the membrane was cleaned, prepared in antibiotic solutions, and preserved at −80 °C. Results suggested that HAM promotes healing and epithelialization without specific complications. Thus we conclude that the use of HAM gives promising results in the repair of post-surgical oral mucosal defects.