Oral verrucous carcinoma: A retrospective analysis for clinicopathologic features.

AIM: To study the clinicopathological features of oral verrucous carcinoma (VC). METHODS: Archives of the department were retrieved for verrucous lesions. After thorough histopathologic examination, 10 cases were confirmed as VC. Age, sex, site, tobacco habit, clinical presentation, and histologically, the presence of dysplasia and koilocytic changes were studied. RESULTS: Oral VC showed a distinct male preponderance with male:female ratio of 8:2 and occurring predominantly in sixth and seventh decade. Tobacco association in the form of chewing (50%), smoking (40%) or both (10%) was found in all the cases. In chewers, the site of lesion corresponded to the site of tobacco placement that is gingivobuccal sulcus. In smokers, the posterior part of the oral cavity was affected, and the lesions were extensive. Painless, exophytic, cauliflower-like growth was the most common presentation with surrounding whitish (leukoplakic) mucosa. Fifty percentage of the cases showed human papilloma virus-induced changes in the epithelium. Dysplasia was seen in two cases. CONCLUSION: Oral VCs are invariably associated with tobacco habits. In smokers, the lesions are extensive, affecting the posterior parts of the oral cavity. Although evidence of viral infection was seen but its role as an etiological agent is still controversial. Site and depth of the biopsy along with thorough histopathological sampling is essential to avoid erroneous diagnosis.

Carcinoma cuniculatum in course of etanercept: blocking autoimmunity but propagation of carcinogenesis?

Carcinoma cuniculatum (CC) or verrucous squamous cell carcinoma is a rare variant of squamous cell carcinoma with low incidence of metastasis. It mainly affects men during the fifth-sixth decade of life, arising mostly on the weight-bearing surface of the foot, but it can also be found in other body areas. The favorable effects on the psoriatic, rheumatoid, juvenile polyarthritis as well as the ankylosing spondylitis after the application of Tumour Necrosis Factor (TNF)-alpha inhibitors, like etanercept, presume the availability of similarity between the etiopathogenetic mechanisms which are responsible for the generation of the inflammatory cascade. According to the latest studies, the sensitivity of the patients to TNF-alpha inhibitors could be genetically determined and may also be due to certain genetic polymorphisms of the NLP3 and CARD8 zones of the inflammasome. The blocking of the inflammatory reaction within the borderlines of the psoriatic arthritis could also be accepted as something of a double edged sword. There is a growing volume of literary data which informs us of the clinical manifestation, not only of skin, but also of other types of tumors after the application of TNF-alpha inhibitors. This inevitably generates the hypothesis that within a certain group of patients the TNF-alpha inhibitors have some additional, and currently obscure, effects on presumably key regulatory proteins of the so-called extrinsic apoptotic pathway. Other proteins of the human inflammasome could be also implicated in the regulation of the programmed cell death and the carcinogenesis - there are speculations, that the adapter protein, ASC/TMS1, could be one of these. The present study describes the case of a patient who developed a rare form of skin tumor - epithelioma cuniculatum - whilst undergoing etanercept therapy for psoriatic arthritis. Under discussion are the possible critical connections in the complex regulatory networks of the inflammatory processes, the programmed cell death (apoptosis) and the carcinogenesis which, in the near or distant future, could become the objects of a targeted therapy.

Verrucous carcinoma due to arsenic ingestion in a psoriasis patient.

BACKGROUND AND OBJECTIVE: Verrucous carcinoma is a rare clinicopathologic entity caused by multifactorial influences. We report here a 64-year-old male patient presenting with a large exophytic mass in the right leg. RESULTS AND CONCLUSION: The patient had a 19-year duration of psoriasis and received various treatments. In his last year of life, he had been taking an illegally produced folk drug with the hope of controlling his psoriasis. However, 6 months after the drug ingestion, many papules appeared on his right leg, which eventually developed into a large tumor in the next few months. The patient died of acute pulmonary embolism only a week after hospitalization, when his tumor was pathologically confirmed as verrucous carcinoma. Later, the folk drug was analyzed and found to contain arsenic. The causative relevance of the tumor with his daily arsenic intake is discussed.

Caustic ingestion and oesophageal cancer: intra- and peri-tumoral fibrosis is associated with a better prognosis.

OBJECTIVE: Oesophageal carcinoma is a well-known late complication of caustic ingestion, occurring in up to 7% of cases. We report a large series of patients with oesophageal scar cancer (SC), investigating the association between fibrosis and survival. METHODS: A total of 25 patients with a history of oesophageal SC (1979-2005) were retrospectively studied. The amount of intra- and peri-tumoral fibrotic tissue was measured with Azan-Mallory staining. A control group of patients with non-SC was used for comparison. RESULTS: Twenty-five patients (16 males:9 females, median age 59 years), presented with SC. The histotype was squamous cell carcinoma (SCC) in 20 (80%) patients, adenocarcinoma (AC) in three (12%) and verrucous carcinoma in two (8%). Oesophageal resection was performed in 17 of 25 (68%) patients; in eight (32%), only a palliative treatment (endoscopic/surgical) was possible. Mortality and morbidity rates were 4% and 40%, respectively. One-, 3- and 5-year overall actuarial survival rates for SC patients were 72%, 56% and 52%, respectively. The amount of fibrotic tissue around/within the tumour was significantly higher in SC patients (34.5% vs 5.9% non-SC, p=0.01); these patients had also a higher prevalence of tumours limited to the muscular wall (pT1-T2) (76% vs 28% non-SC, p<0.0001) and less lymph node metastases in T1-T2 cases (8% vs 34% non-SC, p=0.07). The 5-year survival was significantly better in SC patients: 71% versus 24% for resected cancers (p<0.0001), and 52% versus 15% for all observed patients (p=0.0001). CONCLUSIONS: The presence of fibrotic tissue around/within the tumour is associated with a better prognosis in SC. Fibrosis might offer a protection against both local spread and nodal dissemination.

Surgical outcome in patients with oral verrucous carcinoma: long-term follow-up in an endemic betel quid chewing area.

BACKGROUND/AIMS: To evaluate the clinical features and prognosis of patients with oral verrucous carcinoma (OVC) in an endemic betel quid chewing area. METHODS: A retrospective review was conducted in 39 patients with OVC treated surgically from 1991 to 2002. RESULTS: Thirty-seven patients (94.9%) were male. The median age at diagnosis was 53.8 years. All patients had been exposed to betel quid, cigarette smoking, and/or alcohol. The most common site of tumor origin was the buccal mucosa (64.1%). The tumor control rate was 97.4% after the first surgical procedure. Second/multiple primary tumors (SPTs/MPTs) were found in 21 patients. There were 13 deaths during the follow-up period, with SPTs/MPTs being the most common cause. The cancer-specific survival rate was 89.1% at 5 years, but continued to decrease thereafter. CONCLUSION: Surgery was effective for controlling OVC. However, long-term follow-up was necessary because of the high incidence of SPTs/MPTs and its impact on patient survival.

Clinical, pathological, cellular and molecular lesions caused by oral smokeless tobacco--a review.

While carcinogenicity of smokeless tobacco (ST) to humans is well established the oral lesions that precede development of cancer are less well characterized. The clinical appearances of ST-associated lesions are variable. Epidemiological studies show a strong significant association of risk with chronic daily use but population differences are noted because of various commercial products in use. Morphological features observed are some what different to oral lesions caused by smoking and oral dysplasia in ST-associated lesions is less common. Effects of ST on oral keratinocytes observed in vitro include alterations in cell proliferation, apoptosis and activation of inflammatory markers. Genetic aberrations caused by ST include activation of ras, uncommon in smokers but mutational hot spots in p53 encountered are similar to those in smokers.

Light-induced fluorescence spectroscopy: a potential diagnostic tool for oral neoplasia.

For the early detection of oral neoplasia, light-induced fluorescence spectroscopy was used to measure the fluorescence emission of malignant (squamous cell carcinoma & verrucous carcinoma) and premalignant (epithelial dysplasia, hyperkeratosis & lichen planus) oral tissues as well as normal oral mucosa ex vivo to assess the ability of this technique to distinguish neoplastic from normal oral tissues. The emission spectra of histologically normal and neoplastic oral tissues were obtained under excitation wavelengths varied from 270 nm to 400 nm at 10-nm intervals. At 300-nm excitation, the most intensely fluorescent peak occurred at 330-nm and 470 nm emission. At 330-nm emission, the spectrum of the malignant oral tissue was significantly stronger than that of the normal oral mucosal tissue after area normalization. However, at 470-nm emission, the spectrum of the malignant oral tissue was significantly weaker than that of the normal oral mucosal tissue. A diagnostic algorithm based on the ratio of relative intensities of 330 nm to 470 nm emission within the +/-5 nm peak area of each sample was calculated and paired. The histogram of ratios showed that histologically neoplastic oral tissues could be distinguished from normal oral mucosal tissues using the 300 nm excitation wavelength. The average ratio of malignant or premalignant oral samples was significantly greater than that of the normal oral mucosal samples (p < 0.001). This ex vivo study indicated that fluorescence spectroscopy may be useful in differentiating malignant or premalignant oral tissue from normal oral mucosa.

Chronic esophagitis evolving to verrucous squamous cell carcinoma: possible role of exogenous chemical carcinogens.

BACKGROUND & AIMS: A patient exposed to aerosolized lye and ingested kerosene was followed up for 16 years with chronic esophagitis before developing verrucous esophageal squamous carcinoma. The aim of this study was to elucidate the pathogenesis of the carcinoma. METHODS: Multiple biopsy specimens were graded according to the severity of esophagitis and dysplasia. Molecular biological techniques and immunocytological assay were used to look for human papillomavirus infection, p53 mutations, loss of heterozygosity for TP53 and chromosome 8 markers, and ras mutations. RESULTS: Morphological features of the chronic esophagitis in this patient were similar to the precancerous lesions from high-risk areas for esophageal squamous cancer and the precancerous lesions induced in rats by N-methyl-N-nitrosoaniline. Gastroesophageal acid reflux and human papillomavirus infection were ruled out. No loss of heterozygosity of p53 or for chromosome 8 markers was found. Mutations of the ras oncogene were not identified. By immunocytological assay overexpression of p53 was identified only in the invasive portion of the carcinoma. CONCLUSIONS: In this patient, verrucous squamous carcinoma evolved from chronic esophagitis, squamous papillary hyperplasia, and dysplasia. Although exogenous carcinogens may have been important, they probably did not act by causing loss of heterozygosity or ras mutations. p53 overexpression occurred late.