Verrucous Carcinoma of the Foot: A Single Canadian Center Experience on Diagnosis, Management, and Outcomes.

INTRODUCTION: Verrucous carcinoma (VC) was first described in 1948 by Dr. Ackerman. It is a low-grade cutaneous squamous carcinoma that usually develops in the oral cavity, the anogenital region, and the plantar surface of the foot. Clinically, there is low suspicion for malignancy given the slow growth of VC lesions and their wart-like appearance. Diagnosis can be difficult because of the benign histological appearance with well-differentiated cells and absence of dysplasia. Surgical excision is the only satisfactory form of treatment for plantar VC; however, this becomes difficult given its benign clinical appearance and the pathologic misinterpretation of the lesion as a benign hyperplasia. While there are case reports and retrospective studies of patients with plantar VC in the literature, we present the largest case series of plantar VC within North America, with recurrence despite negative margins. METHODS: We report on all the plantar VC excised between 2014-2023. We report six cases of VC, their treatment, and their outcomes. RESULTS: Six patients obtained a diagnosis of plantar VC by incisional biopsy. All patients underwent excision of their lesions and had negative margins reported on the final pathology. All patients developed nonhealing wounds at the site of their lesion excision; therefore, biopsies were performed to confirm a recurrence. All patients had a recurrence of VC at the initial site. All patients underwent re-excision of the lesions. Despite negative margins again on final pathology, all patients had a subsequent second recurrence. Ultimately, all patients underwent an amputation as definitive management. Each patient had an average of 3 operations. There were 4 different surgeons and different pathologists reporting their findings. CONCLUSIONS: Our experience with plantar VC suggests that an aggressive approach to surgical management is needed. Furthermore, management is optimized with the combined expertise of an experienced dermatopathologist and surgeon. Despite negative margins and repeated excisions, VC lesions recur and invade local tissues to the extent that only amputation of the involved foot has resulted in cure.

Verrucous carcinoma presenting as recalcitrant verruca plantaris.

Verrucous carcinoma (VC) is a rare, low-grade variant of well-differentiated squamous cell carcinoma. Plantar verrucous carcinoma presents as a slow-growing, exophytic, verrucous plaque on weight bearing areas of the foot. Verrucous carcinomas have low metastatic potential, but are high risk for local invasion. We describe a patient with a 20-year history of a slowly growing, ulcerated, verrucous plaque on the sole of the left foot that was erroneously treated for years as verruca plantaris and was eventually diagnosed as invasive verrucous carcinoma. Verrucous carcinomas are a diagnostic challenge due to clinical and histopathologic mimicry of benign lesions. Mohs micrographic surgery should be employed to allow the ability to intraoperatively assess tumor margins while excising the minimal amount of necessary tissue. It is important for clinicians to recognize the characteristics and accurately diagnose verrucous carcinomas. Delays in treatment may require more extensive dissection or amputation.

Cutaneous Verrucous Carcinomas: A Review.

Verrucous carcinoma (VC) is a relatively rare locally aggressive, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential and is most frequent in the mucosa. Although rarely reported on the skin, cutaneous verrucous carcinomas (CVC) can appear anywhere, most commonly on the feet. However, clinical and pathologic diagnosis of CVC has been confusing and challenging. It can easily be mistaken for benign or more malignant conditions such as giant condyloma acuminata, keratoacanthoma, and pseudoepithelioma-like hyperplasia or squamous cell carcinoma, resulting in inappropriate management. In this review, we describe the different aspects associated with CVC, including its pathogenesis and clinicopathologic features. The available evidence for the differential diagnosis and treatment of CVC is discussed, and specific management recommendations are made. After the treatment, careful follow-up examinations of the excised area should be performed at regular intervals.

Clinical manifestations of oral proliferative verrucous leukoplakia: A systematic review.

OBJECTIVE: The aim of this systematic review was to gather the available evidence about proliferative verrucous leukoplakia. This systematic review was conducted to answer the question: "What are the main clinical features of PVL patients?". MATERIAL AND METHODS: A systematic review of the literature was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. An electronic research was carried out using different electronic databases; PubMed, and Scopus. Inclusion criteria were papers which reported at least 10 patients with proliferative verrucous leukoplakia and were published not more than 10 years ago. RESULTS: A total of 285 records were identified through databases, although only 6 of them were eligible. Most patients were women, above 60 years of age (67.4). Additionally, 28 of them were non-smokers (66.6%) and 24 were non-habitual drinkers (57.1%). The most common locations were gingiva (50.9%), buccal mucosa (44.9%), and tongue (40.6%) CONCLUSION: Level C can be established to conclude the proliferative verrucous leukoplakia demographic data, risk factors, malignant transformation, and location. A strict follow-up on these patients should be mandatory, even after surgical management since they have a high recurrence rate and a malignant transformation.

MCM-2 expression differentiates potentially malignant verrucous lesions from oral carcinomas.

BACKGROUND: Mcm-2 is a biomarker belonging to Mcm family of proteins which has rarely been used in oral potentially malignant and malignant lesions of the verrucous type. The objective of this study is to assess the expression of Mcm-2 in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC) and Oral Squamous Cell Carcinoma (OSCC) and compare it with the clinicopathological characteristics. METHODOLOGY: A total of 70 formalin fixed paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by using the SPSS software. RESULTS: There was a significant difference in Mcm-2 expression with quantitative analysis among all the groups (p < 0.05). There was a significant progressive increase in nuclear Labelling Indices (nLI) from NM (49.08%), VC (60.45%), VH with Dysplasia (64.10%), and OSCC (89.22%). CONCLUSION: The findings suggest that Mcm-2 may be a sensitive proliferation marker in oral potentially malignant and malignant lesions which may be useful for differentiating between VH with/ without dysplasia, VC and OSCC.

[Precancerous lesions of the buccal epithelium]. / Les lésions précancéreuses épithéliales buccales.

Squamous cell carcinomas of the oral cavity and lips consistently have a high incidence (they constitute the fifth most common form of cancer in France) and carry a heavy prognosis, particularly if diagnosed late. According to different studies, between 10 and 80% of such carcinomas occur in a pre-existing or precancerous lesion. The World Health Organisation (WHO) recommends the use of two terms for such lesions: precursor lesions, i.e. histological lesions associated with intraepithelial neoplasia (IEN) and verrucous hyperplasia (VH), frequently resulting clinically in leukoplakia or erythroplakia; "at risk" lesions, which include lichen planus, submucosal oral fibrosis and certain forms of genodermatosis.

Pyoderma Vegetans Misdiagnosed as Verrucous Carcinoma.

Pyoderma vegetans, a rare disorder of the skin, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. It is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. Here, the authors report the case of a 33-year-old man who was misdiagnosed as having verrucous carcinoma for 4 years.

A Rare Cause of Hoarseness: Laryngeal Verruca Vulgaris.

Verruca vulgaris is a cutaneous disease manifested with a single or multiple, small painless lesions that may involve keratinized or nonkeratinized epithelium. It can be localized at skin or mucosa. It is a benign lesion; however, it is of importance to discriminate from verrucous carcinoma to plan treatment, especially in those with laryngeal localization. Total excision is adequate in the management of verruca vulgaris; thus, accurate differential diagnosis is essential to avoid unnecessary surgical interventions. Here, the authors presented a patient with verruca vulgaris which was totally excised by cold-blade surgical excision.

Verrucous Carcinoma of the Vulva: A 20 Year Retrospective Study and Literature Review.

OBJECTIVE: The aim of the study was to assess the clinicopathological characteristics of patients with verrucous carcinoma (VC) of the vulva. MATERIALS AND METHODS: We reviewed data on the age, disease course, clinical manifestation, pathologic diagnosis, treatment, and follow-up of patients with vulvar VC who were treated at Tianjin Medical University General Hospital and cases that were reported in the Chinese and English literature during the past 20 years. RESULTS: Six cases were identified in Tianjin Medical University General Hospital, the mean age of patients was 55 years, and their mean disease course was 26 months. Primary symptoms were exophytic neoplasm with pruritus and/or pain. Surgical treatment included wide local excision, simple vulvectomy, and radical vulvectomy with or without lymph node dissection in the groin. Vulvar VC occurred simultaneously with vulvar intraepithelial neoplasia in 2 cases and well-differentiated squamous cell carcinoma in 2 cases. The mean follow-up was 16.8 months with no recurrence in those 6 cases. During the 20-year period, 20 and 41 cases were reported in Chinese and English literature, respectively. Three cases were misdiagnosed with giant condyloma acuminatum in China. One case (1/20) was reported with coexistent squamous carcinoma in Chinese literature and 8 cases (8/41) in the English literature. The recurrence rate was 12.5% (2/19) and 17.5% (7/40) in Chinese and English literature, respectively. CONCLUSIONS: Vulvar VC is a distinct type of slow-growing, nonmetastatic tumor with unclear etiology. These tumors should be distinguished from giant condyloma acuminatum and well-differentiated squamous cell carcinoma. Surgery is the most effective treatment.

Laser micro-dissection and qPCR for identifying specific HPV types responsible for malignancy in penile lesions.

The aim of the study was to identify specific human papillomavirus (HPV) type responsible for malignancy in penile tissue samples using laser micro-dissection and TaqMan quantitative real-time PCR (qPCR). The study was based on two pre-malignant and seven malignant penile tissue samples and laser micro-dissection was performed on all. Genotyping was performed on whole tissue sections and laser micro-dissection samples using qPCR. Two whole tissue section samples were HPV negative while seven were HPV positive. In four samples that were single HPV infections with whole tissue section PCR, identical HPV types were confirmed with laser micro-dissection PCR. Clearly confirming that the single HPV type detected is responsible for malignancy. In two samples that had multiple HPV infections with whole tissue section PCR, only one HPV type with the highest viral load was detected with laser micro-dissection PCR, suggesting that the HPV type with the highest viral load is most likely the cause of that particular lesion. HPV 11 and/or HPV 16 were the only types detected with laser micro-dissection PCR in these cases, compared to multiple HPV types (HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 35, and HPV 39) initially detected with whole tissue section PCR. HPV 11 was associated with verrucous lesions while HPV 16 was associated with squamous cell carcinoma and PIN 3 lesions. This study confirms that laser micro-dissection and qPCR are essential tools in identifying the HPV types responsible for malignancy in penile lesions, particularly in samples with multiple infections.

Salivary glyco-sialylation changes monitors oral carcinogenesis.

Alterations in cell membrane glycosylation play important role in oral carcinogenesis. The present study evaluated salivary sialylation changes i.e. total sialic acid (TSA), sialidase activity, linkage specific (α2-3 and α2-6) sialoproteins and sialyl transferase (ST) activity in controls, patients with oral precancerous conditions (OPC) and oral cancer. Subjects enrolled included 100 controls, 50 patients with OPC, 100 oral cancer patients, and 30 post treatment follow-ups. TSA was estimated by spectrophotometric method, sialidase activity by spectrofluorometric assay and linkage specific biotinylated lectins (α2-3: sambucus nigra agglutinin and α2-6: maackia amurensis agglutinin) were used to detect α-2,3 and α-2,6 STs and sialoproteins by ELISA and dot blot respectively. An increasing trend of salivary TSA/TP ratio, sialidase activity, α2-3 sialoproteins, α-2,3 and α-2,6 ST activities was observed from controls to patients with OPC to oral cancer patients and levels were significantly elevated in oral cancer patients as compared to the controls. Sialidase activity exhibited significant association with metastasis and infiltration. Sialidase activity, TSA/TP ratio, α-2,3 and α-2,6 ST activities were found to be higher in patients with metastasis as compared to patients without metastasis. A progressive increase in TSA/TP ratio, sialidase activity, α2-3 and α2-6 sialoproteins was observed from controls to early to advanced stage of the disease. Sialidase activity, α2-3 and α2-6 sialoproteins and ST activities were found to be decreased in complete responders; while levels were elevated in non-responders. The results documented utility of salivary sialylation endpoints, a non invasive tool in monitoring of oral carcinogenesis.

Endoscopic diagnosis and treatment of esophageal verrucous squamous cell cancer.

Verrucous squamous cell cancer (VSCC) of the esophagus is a variant of squamous cell carcinoma. This rare entity has been described in only a handful of case reports in the literature. We sought to evaluate the endoscopic features, treatment, and outcomes related to esophageal VSCC. The medical records of all patients with esophageal VSCC seen at our institution from January 1995 to December 2010 were reviewed retrospectively. A total of 11 patients (6 men; mean age 66 years [range 57-75 years]) were identified, with a mean follow up of 4 years (range 0.5-10 years) available in nine patients after diagnosis. About half the patients smoked or consumed alcohol on a regular basis. The median time interval from onset of symptoms to diagnosis of esophageal VSCC was 2.5 years (range 1-20 years), with dysphagia being present in all patients. The majority of tumors (8 of 11) exhibited a white, warty, plaque-like appearance with superimposed Candida at endoscopy, which led solely to a diagnosis of Candida esophagitis on initial presentation. The disease was either extensive (n = 5) throughout the esophagus or localized (n = 6) often by tumor nodules or projections, with the lower third of the esophagus being most commonly involved. Initial pinch biopsies were nondiagnostic in eight (73%) of the patients. Six patients underwent esophagectomy; neoadjuvant chemoradiation therapy was provided in two. In patients treated solely with surgery and who had a preoperative endoscopic ultrasound, the latter tended to overestimate staging of the lesion relative to surgical pathologic staging. Two patients were deemed to be poor operative candidates and received only chemoradiation treatment. One patient with a T2N0 tumor by endoscopic ultrasound staging was managed symptomatically with intermittent endoscopic dilation because of significant comorbidities that precluded surgery and oncologic therapy. There has been no evidence for residual or recurrent neoplastic disease in the eight patients who received treatment with surgery and/or chemoradiation therapy. Five of six patients who underwent surgery have required intermittent endoscopic dilation of anastomotic strictures during follow up. One of the two patients who received only chemoradiation therapy has required periodic endoscopic dilation for radiation-induced esophageal stricture. Two of the nine (22%) patients have died of causes unrelated to VSCC or its treatment at last follow up. In conclusion, a high index of suspicion for esophageal VSCC should be raised by the presence of long-standing symptoms coupled with white, warty esophageal lesions seen on endoscopic evaluation. Candida overgrowth can be expected to confound the diagnosis. Despite the long duration of symptoms, surgical resection typically shows relatively low-grade tumors, consistent with the rare propensity of this variant of esophageal squamous cell carcinoma to metastasize.

A verrucous presentation of mycosis fungoides.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma and can have a variety of clinical and histological manifestations, including erythrodermic, pustular, bullous, hypo/hyperpigmented, and verrucous forms. We describe a case of a 59-year-old woman who presented with verrucous hyperkeratotic plaques on her distal fingertips, dorsal feet, and areolae that were subsequently biopsied and shown to be mycosis fungoides. This case highlights one of the many atypical manifestations of MF and underscores the need to have a high clinical suspicion for the disease.