Clinicopathologic analysis of verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma as part of the clinicopathologic spectrum of oral proliferative verrucous leukoplakia: A literature review and analysis.

OBJECTIVE: Proliferative verrucous leukoplakia is classified as a potentially malignant disorder because of its high rate of malignant transformation. PVL progresses in a series of clinical stages where the early stage represents multiple, multifocal leukoplakias with a high recurrence rate. The intermediate and late stages are clinically exophytic lesion, diagnosed microscopically as verrucous hyperplasia that often progresses into verrucous carcinoma and/or squamous cell carcinoma. There is no single histologic definition and the diagnosis is retrospective following observed progression of the disorder. The goal of the current study was to conduct a literature review and analysis of PVL in the later stages to gain further knowledge on their clinicopathologic features. DATA SOURCES: Medline's PubMed and Google Scholar were searched for adequately documented cases from 1985 to 2018. References of published articles were searched for additional cases. REVIEW METHODS: Overall, 57 manuscripts were analyzed. 35/57 manuscripts provided adequate data on the clinicopathologic features in the premalignant and malignant stages. RESULTS: Malignant transformation rate was 50% (average of 57 months). Gingiva, palate and buccal mucosa were the most common locations. Clinicopathologic features included; well differentiated carcinoma (78%), perineural invasion (3%), lymph node metastasis (4%); distant metastasis (0%), average duration of illness (65 months), DOD-dead of disease (44%). Moderate dysplasia, severe dysplasia and carcinoma in situ were exceptionally uncommon in the premalignant stages (0.8%). CONCLUSION: Prognostic factors such as perineural invasion, lymph node metastasis and distant metastasis were uncommon occurrences which may have practical implications on treatment. Further studies are needed to substantiate our findings.

Vascularity as assessed by Doppler intraoral ultrasound around the invasion front of tongue cancer is a predictor of pathological grade of malignancy and cervical lymph node metastasis.

OBJECTIVES: To quantitatively evaluate the relationship of vascularity of tongue cancer as demonstrated on intraoral ultrasonography images and tumour thickness with pathological grade of malignancy and the presence of cervical lymph node metastases. METHODS: 18 patients with tongue cancer were enrolled in this retrospective study. Using Doppler ultrasonography images of the invasion front of the cancers along the length of their tumour boundaries, three vascular indexes were analysed quantitatively, namely ratio of blood flow signal area within the cancer to whole tumour area (BAR), blood flow signal number ratio (BNR) and blood flow signal width ratio (BWR). The associations between these three indexes and occurrence of cervical lymph node metastasis and pathological grade of malignancy [Yamamoto-Kohama (YK) classification] were assessed. Furthermore, the relationship between tumour thickness and occurrence of cervical lymph node metastasis was evaluated on B-mode intraoral ultrasonography images. RESULTS: There was no significant association between BAR and tumour thickness or occurrence of cervical lymph node metastasis. The BNRs and BWRs of patients with cervical lymph node metastasis were significantly higher than those of patients without nodal involvement. The BWRs of patients with high-grade malignancy (YK-4C) were significantly higher than those of patients with low-grade malignancy (YK-2 or 3). CONCLUSIONS: BNR and BWR on the invasion front of the tongue cancer are predictors of pathological grade of malignancy and cervical lymph node metastasis.

Susceptibility to oral cancers with CD95 and CD95L promoter SNPs may vary with the site and gender.

We investigated risk association of oral cancers (tongue and buccal mucosa cancers) with FAS (-1377G > A and FAS -670 A > G) and FASL (-844 T > C) SNPs, in males and females. A case-control study of 535 oral cancer and 525 control subjects was performed. SNPs were detected in the genomic DNA isolated from peripheral blood using PCR-RFLP. We report FASL -844 T > C SNPs increased risk for buccal mucosa cancer in females but not in males. On the other hand, FAS genotypes did not alter the risk of the cancers in both females and males. However, co-occurrence of FAS -1377 GA and -670 GG, FAS -1377 AA and -670 GG genotypes, and combined genotypes of FAS and FASL (FAS -1377 AA + FAS -670 GG + FASL -844 CC) alter male susceptibility towards tongue cancer. In females, combined genotypes of FAS (-1377GA and -670 AA) were found to be a risk factor of buccal mucosa cancer (OR = 3.27, CI = 1.28-8.36; P ≤ 0.01). FASL variants (GA and AA) increased tongue cancer risk in females who were tobacco users compared to non-tobacco users. In conclusion, SNPs of the FAS and FASL might alter risk of tongue and buccal mucosa cancers differentially, in a gender-dependent manner.

Verrucous carcinoma of the renal pelvis with a focus of conventional squamous cell carcinoma.

Verrucous carcinoma (VC) is a rare variant of squamous cell carcinoma (SCC) with an extremely well-differentiated microscopic appearance. It is able to show extensive local invasion, but practically never metastasizes. VCs mostly occur in the oral cavity, larynx, nasal cavity, esophagus, vulva, vagina, anorectal region, penis and skin. VCs sometimes coexist with conventional SCCs, and in these instances they are associated with a higher recurrence rate than pure VCs. The occurrence of VC in the renal pelvis is very rare and to date only 4 cases have been reported. We report here a case of VC with a focus of conventional SCC in the renal pelvis. The patient showed fistula formation by residual tumor in the follow-up period.

Combined ultrasound and magnetic resonance imaging findings on cervical verrucous carcinoma with endometrial invasion: a case report.

BACKGROUND: Cervical verrucous carcinoma is a rare form of cervical cancer. Very few reports present the correlation between diagnostic images and clinicopathologic findings. CASE: A 50-year-old woman was treated with laser ablation for cervical condyloma 6 years prior to her presentation with progressive vaginal bleeding and a foul-smelling discharge at our clinics in August 2004. Biopsy of the cervical mass was compatible with pathologic features of condyloma acuminata. Ultrasonography with color Doppler revealed a 5.9x4.1-cm, hyperechogenic mass with a honeycomb appearance in the lower uterine corpus and hypervascularization of the tumor with resistance indexes ranging from 0.41 to 0.47. Magnetic resonance imaging (MRI) showed that the tumor had a homogeneous intensity on T1-weighted images and heterogeneous intensity on T2-weighted images. After administration of contrast medium, the tumor exhibited a lower signal intensity than did the surrounding cervical stroma. A human papillomavirus test was positive for types 11 and 53. Combined with the clinicopathologic findings, verrucous carcinoma of the cervix, stage Ib2, was suspected and the patient underwent radical hysterectomy and bilateral pelvic lymph node dissection. The final pathology report proved the impression of malignancy. The patient had an uneventful postoperative course, and no disease recurred during 1 year of follow-up. CONCLUSION: The diagnosis of cervical verrucous carcinoma requires a good clinical and pathologic correlation. Nevertheless, detailed imaging studies, such as ultrasound and MRI, as in our case, may provide valuable presurgical information for treatment.

Acute visual loss in a head and neck cancer patient with ocular metastasis and sphenoid pyocele.

We report an extremely rare case of head and neck cancer patient with right acute visual loss by ocular metastasis after excluding compressive optic neuropathy by endoscopic decompression of the sphenoid pyocele. The ocular metastasis from head and neck cancer had been reported only once in English literatures. Besides, the patient combined with sphenoid pyocele increases the difficulty in differentiating the etiologies. In this article, we describe the history of this patient and discuss the possible cause of acute visual loss and the treatment strategy. Although to differentiate the etiology of acute visual loss between metastatic malignancy and compressive optic neuropathy remain difficult, treatment strategy should focus on rescuing visual acuity. Ocular metastases should always keep in mind when acute visual loss is encountered in patients with previously treated head and neck squamous cell carcinoma.

Synchronous advanced scrotal verrucous carcinoma with peripheral T-cell lymphoma.

Scrotal verrucous carcinoma is extremely rare. Classic cases have been suggested to be occupation related. We report on a 65-year-old male drifter, who had concomitant multiple condyloma acuminatum and advanced verrucous carcinoma of the right hemiscrotal skin with peripheral T-cell lymphoma and extensive lymphadenopathy. To our knowledge, it is the first case of synchronous verrucous carcinoma and peripheral T-cell lymphoma. The patient died of disseminated disease 2 months after undergoing wide excision of the tumor. A brief discussion of the diagnosis, treatment, and prognosis is presented.

The role of whole-body FDG-PET in preoperative assessment of tumor staging in oral cancers.

OBJECTIVE: The aim of this study is to clarify the clinical utility of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) in determining the TNM classification in patients with oral cancer. METHODS: Twenty-five consecutive patients (14 male and 11 female; age range, 40 yr to 86 yr) with oral cancer were included in this study. The diagnostic accuracy for detecting cervical lymph nodes was investigated by comparing the results of CT and/or MRI and physical findings. For the semi-quantitative analysis, the tumor standardized uptake value (SUV) and tumor to background SUV ratio (T/B ratio) were assessed in primary tumors and cervical lymph nodes. RESULTS: All primary lesions were visualized on FDG-PET images. Even though artifacts from dental materials near the lesion hampered the delineation of primary tumors on CT/MRI, the extent of primary tumors was accurately assessed by FDG-PET. The SUV and T/B ratio in the primary tumor classified in higher T grade (T3 and T4) was significantly higher than that in lower T grade (T1 and T2) (mean +/- SD of SUV; 8.32 +/- 2.99 vs. 5.15 +/- 3.77, p < 0.01, mean +/- SD of T/B ratio; 6.96 +/- 3.23 vs. 3.61 +/- 2.76, p < 0.01). The SUV and T/B ratio of metastatic lymph nodes were also significantly higher than those of normal lymph nodes (mean +/- SD of SUV; 3.39 +/- 1.69 vs. 1.55 +/- 0.57, p < 0.001, mean +/- SD of T/B ratio; 2.46 +/- 1.08 vs. 1.03 +/- 0.22, p < 0.001). Among these three methods, FDG-PET in conjunction with CT/MRI showed the highest accuracy of 92%, but there were no significant differences in diagnostic accuracy among the three methods. For the semi-quantitative analysis, a threshold SUV of 2.0 provided 100% sensitivity, 82% specificity, and 88% accuracy. Furthermore, a threshold T/B ratio of 1.5 provided 100% sensitivity, 100% specificity, and 100% accuracy. Regarding the detection of distant metastasis, there was one positive result in FDG-PET showing distant pulmonary metastasis. CONCLUSIONS: Whole-body FDG-PET is an effective and convenient diagnostic tool for the evaluation of tumor staging in patients with oral cancer. Tumor staging by whole-body FDG-PET may, in fact, supplement the conventional staging by means of CT/MRI and physical findings.

Penile hybrid verrucous-squamous carcinoma associated with a superficial inguinal lymph node metastasis.

A 62-year-old Japanese man who presented with penile carcinoma is reported. The initial exophytic neoplasm excised from the coronal sulcus and prepuce on the abdominal side of the penis was diagnosed histologically as verrucous carcinoma. Twenty-six months after the primary operation, an epithelial neoplasm recurred within the scar of the primary operation. The neoplasm histologically showed verrucous carcinoma and multiple invasive foci of conventional squamous cell carcinoma in the advancing edge of the tumor, as such representing a hybrid verrucous-squamous carcinoma. A lymph node metastasis in the left superficial inguinal lymph node occurred 4 months after the second operation. A total bilateral inguinal lymphadenectomy was performed and revealed no other lymph node metastases. The patient is alive without local recurrence or evidence of metastases in pelvic lymph nodes or visceral organs 2 years after the resection of the hybrid verrucous-squamous carcinoma. The initial verrucous carcinoma, recurrent hybrid verrucous-squamous carcinoma, and metastatic lymph node were negative for human papillomavirus DNA type 6, 11, 16, 18, and 33 sequences by dot blot hybridization of polymerase chain reaction products. The characteristics of hybrid verrucous-squamous carcinoma and importance of lymph node metastasis in penile carcinoma are discussed.

Angiogenesis in metastatic verrucous carcinoma of the uterine cervix.

A 65-year old woman operated on for verrucous carcinoma of the uterine cervix 13 years previously was found to have multiple small recurrent tumors in the retroperitoneal space. Tumor cell expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) was investigated at the second operation. Expression of VEGF was strongly positive in the tumor cells and expression of PD-ECGF was strongly positive in both the tumor cells and the interstitial cells.

Clinical implications of natural killer cytotoxicity in patients with squamous cell carcinoma of the penis.

Impairment of natural cytotoxicity mediated by natural killer (NK) cells may play a role in the pathogenesis of penile carcinoma. The aim of this study was to examine the NK activity profile and its prognostic significance in patients with squamous cell carcinoma of the penis. The NK activity was measured in peripheral blood mononuclear cells (PBMCs) from 39 patients diagnosed histologically as having invasive squamous cell penile carcinoma and 4 patients with verrucous carcinoma of the penis. Of 39 patients with invasive squamous cell carcinoma, 4 had undergone previous penile amputation. According to the prognosis, the patients with invasive squamous cell carcinoma were divided into two groups: with metastasis and without metastasis. The patients were evaluated in relation to clinicopathologic variables using univariate analyses. NK cell activity was significantly decreased in all patients with penile carcinoma when compared with the control groups (p < 0.0001). There was no statistically significant difference between the groups with and without metastasis. We conclude that there is a decrease in NK activity in PBMCs from patients with penile carcinoma and that the presence of advanced disease or metastatic involvement is not responsible for this reduction.

Outcome following radiotherapy in verrucous carcinoma of the larynx.

PURPOSE: To evaluate the outcome of patients with verrucous carcinoma of the larynx treated at the Princess Margaret Hospital with respect to control rates with radiotherapy, the salvage of local failure, the risk of regional lymph node metastasis following radiation therapy, and the risk of anaplastic transformation following radiotherapy. METHODS AND MATERIALS: Forty-eight patients underwent primary treatment for verrucous carcinoma of the larynx in the period between January 1961 and December 1990. This represented 1.1% of cases of laryngeal cancer seen in this time period. Forty-three received radiotherapy and 5 had surgery as the primary treatment. Several radiation dose-fractionation schedules were used, the most frequent being 50 Gy in 20 fractions in 4 weeks (31 cases), while eight patients were treated with 55 Gy over 5 weeks. RESULTS: The 5-year rate of local control was 59% for the 43 patients treated with radiotherapy. Surgical salvage was universally successful in all cases where it was attempted. The five cases treated with surgery alone did not experience relapse. Only one patient died of verrucous carcinoma. He had been medically unfit for surgical intervention at the time of initial treatment and at the time of relapse. He underwent a truncated course of radiotherapy (24 Gy in 3 fractions over three weeks in 1975). There was no evidence of increased neck relapse compared to other forms of laryngeal carcinoma following radiation treatment. No evidence to support anaplastic transformation of tumors treated with radiotherapy was evident in this series. CONCLUSIONS: Local control using radiation treatment is less successful than with ordinary invasive and in situ squamous carcinomas of the larynx. Nevertheless, the treatment is effective and provides an appropriate option for laryngeal conservation, especially in advanced lesions where total laryngectomy may be the only treatment alternative. Surgical salvage of radiation failures contributes to very high rates of cure for verrucous carcinoma of the larynx. Anaplastic transformation of cases treated with radiotherapy was not observed in any case in this series.