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.

Epidemiological, clinical and oncological outcomes of laryngeal verrucous carcinomas: a systematic review.

OBJECTIVE: To investigate epidemiological, clinical and oncological outcomes of patients with laryngeal verrucous carcinomas (LVC). METHODS: Two independent authors investigated PubMed, Scopus and Cochrane Library for studies dedicated to epidemiological, clinical and oncological outcomes of patients with LVC. The following outcomes were investigated with PRISMA criteria: age; gender; tobacco/alcohol consumption; HPV infection; anatomical, pathological, therapeutic and survival outcomes. Studies were analyzed for bias through a validated clinical tool. RESULTS: Of the 212 identified articles, 15 retrospective studies and one prospective uncontrolled study met our inclusion criteria. Three studies reported findings from national databases. The males/females ratio is 9/1. Mean age was 60.3 years, which was younger compared to other laryngeal malignancies. The alcohol, cigarette overuse and the HPV status of patients were lacking in most studies. Glottis and supraglottis were the most common anatomical locations, corresponding to 78.7% and 12.4% of cases, respectively. The main therapeutic approaches consisted of surgery, radiotherapy, surgery followed by radiotherapy. Treatments reported 5-year overall survival and disease-specific survival of 86.3 and 90.8, respectively. The 5- and 10-year local control rate were 83.6 and 72.6, respectively. The 10-year disease-specific survival was 80.2. Heterogeneity between studies was found for inclusion criteria, comorbidity data, and treatments. CONCLUSION: LVC is a rare laryngeal cancer associated with better survival and recurrence outcomes than laryngeal squamous cell carcinoma. The role of radiotherapy in the treatment regimen needs to be investigated in future prospective controlled studies.

Epithelioma Cuniculatum (Plantar Verrucous Carcinoma): A Systematic Review of Treatment Options.

Epithelioma cuniculatum (EC) is a subtype of verrucous carcinoma (VC) that affects the feet. Treatment involves complete tumor removal by wide local excision (WLE) or Mohs micrographic surgery (MMS). Extensive local destruction may require amputation. We sought to compare reported treatment methods for EC and determine their efficacy by assessing for tumor recurrence and treatment-associated complications. A systematic review of the literature spanning multiple databases was performed. To date, surgical excision is recommended as the standard of care for treatment of EC, with amputation considered in more advanced cases. Mohs micrographic surgery appears to be a promising treatment modality for EC and may have lower recurrence rates than WLE but requires further investigation.

Optimal treatment for penile verrucous carcinoma: a systematic literature review.

BACKGROUND: Verrucous carcinoma, a rare low-grade well-differentiated squamous cell carcinoma, is known for its favorable biological behavior and lack of metastatic potential. However, aggressive resection is problematic in terms of compromised function and aesthetics. Hence, more conservative treatments are needed. METHODS: To identify the up-to-date general biological behavior, diagnosis, and treatment trends, we searched PubMed using the keyword "penile verrucous carcinoma" without restrictions on publication date. RESULTS: Current treatments for penile verrucous carcinoma include wide surgical excision, seldom preventive lymphadenectomy, and conservative chemotherapy without surgery or local excision with safe margins. Despite the advent of partial penectomy to minimally impact function and aesthetics, affected patients experience psychosexual problems. Local excision can be used to save the penile shaft and glans penis without preventive lymphadenectomy or adjuvant therapy and can achieve good clinical prognosis with rare recurrence. CONCLUSIONS: To preserve the functional and cosmetic aspects, we recommend local excision, especially for tumors measuring < 3 cm and classified as stage T1 according to the 2016 tumor node metastasis clinical and pathological classification for penile cancer.

Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis.

BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.

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.

Oral human papilloma virus infection: an overview of clinical-laboratory diagnosis and treatment.

OBJECTIVE: The aim of this review is to describe the "hot points" of current clinical governance for oral HPV comprising the use of new diagnostic molecular procedures, namely, Pyrosequencing and Next Generation Sequencing. MATERIALS AND METHODS: The data on oral HPV was collected through two levels of research. First for all, we used the canonical medical search engines, PubMed, and Medline, followed by the study of current commercial tools for HPV diagnosis, particularly within commercial companies involved in the molecular procedures for HPV detecting and genotyping. RESULTS: Different medical procedures are now described and used throughout the world in HPV diagnosis and treatment. However, the laboratory methods are often validated and used for genital infections, and, in these cases, data are missing in the literature as regards the clinical approach for oral lesions. CONCLUSIONS: Dental care units are often the front line for a clinical evaluation of a possible HPV lesion in the oral cavity, which means that correct clinical governance could avoid a viral neoplastic progression of this disease with great advantages for the patient. In this case, the problem is due to the difficulty in lesion recognition but also and more especially the absence of correct laboratory diagnosis and subsequent treatment in the clinical course.

[Diagnostic and treatment pitfalls and guidelines for variants of squamous cell carcinomas of the head and neck: on behalf of the REFCOR]. / Variants des carcinomes épidermoïdes dans les voies aérodigestives supérieures (VADS), implications pour le diagnostic et la prise en charge, selon les référentiels du REFCOR.

Among the 20,000 new cases of head and neck neoplasms in France each year, squamous cell carcinomas (HNSCC) represent about 90 % of the cases. Among these, variants of conventional squamous cell carcinomas represent between 5% and 10% of cases. Patient history and risk factors are often similar from those of conventional HSNCC. Variants may, however, be misdiagnosed, which can lead to therapeutic mismanagement due to confusion with sarcomas, glandular tumors or even benign tumors. Diagnostic workup needs to be more cautionary or to include additional exams not to omit their most aggressive component in the case of composite tumors or to under stage the tumor. Immunohistochemistry and specific molecular analyses may be required for proper diagnosis. Central pathological review may also be essential for some of these variants. In addition, some variants are radioresistant and, conversely, others are radiosensitive. An update of the REFCOR 2008 standards was carried out in the light of the international literature and the 2017 WHO/IARC classification for the seven main variants of HNSCC, verrucous, acantholytic (to be named adenoid carcinomas), basaloid, papillary, spindle cell (incorrectly named sarcomatoid), adenosquamous and lymphoepithelial carcinomas.

Epidemiology and survival outcomes of sinonasal verrucous carcinoma in the United States.

INTRODUCTION: Verrucous carcinoma (VC) is a rare, variant of squamous cell carcinoma with benign cytohistopathologic features and a generally favorable prognosis. Epidemiologic and clinical outcomes data are lacking as a result of limited cases of sinonasal VC. OBJECTIVE: To describe the incidence and determinants of survival of patients with verrucous carcinoma of the sinonasal tract between the years of 1973 to 2014 using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The SEER registry was utilized to calculate survival trends for patients with verrucous carcinoma of the sinonasal tract between 1973 and 2014. Patient data then was analyzed with respect to age, sex, race, and treatment modalities (surgery and radiation therapy). Overall survival (OS) and disease-specific survival (DSS) were calculated. RESULTS: A total of 86 cases of VC of the sinonasal tract were identified. The cohort was comprised of 69.8% males. The mean age at diagnosis was 67.4 years. The nasal cavity was the most common primary site (51.2%), followed by the maxillary sinus (40.7%) and nasopharynx (5.8%). The median OS was 97.6 months. 89.5% of cases underwent surgery and 20.9% received both surgery and radiation therapy. Overall survival at 2, 5, and 10 years was 73%, 59%, and 36%, respectively. On multivariate analysis, advanced age (P < 0.05) and primary site (P < 0.05) were associated with worse OS and DSS, respectively. Primary nasopharyngeal tumor site was associated with reduced DSS (P < 0.05). Surgery improved OS (P < 0.001) and DSS (P < 0.001). CONCLUSION: Verrucous carcinoma of the sinonasal tract is associated with a generally favorable prognosis. Age, primary site, and surgical therapy are independent predictors of OS and DSS, respectively. We present the first population-based analysis of sinonasal VC, thus clarifying the prognosis and reinforcing the management of this malignancy. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:651-656, 2017.

Laryngeal Verrucous Carcinoma.

Objective Laryngeal verrucous carcinoma (LVC) is a rare, locally invasive neoplasm comprising 1% to 3.4% of laryngeal carcinomas. Management strategies are a topic of ongoing conversation, and no definitive treatment protocol based on T stage and presentation exists. This review examines characteristics, treatment modalities, and patient outcomes of LVC. Data Sources PubMed, MEDLINE, EMBASE, and Web of Science. Methods Databases were searched through October 29, 2015, for literature detailing individual patient cases of LVC. Variables analyzed included patient demographics, tumor characteristics, tumor size, treatment, and outcomes. Results Thirty-seven articles with 369 cases were included. LVC was found more commonly in males (13.8:1), at an average age of 58.7 years, and located in the glottis (74.0%). Most patients had local disease at presentation (94.9%). The most common presenting symptom was hoarseness (92.3%). The most common primary treatment was surgery alone (72.3%), with local excision as the most common technique (56.8%). In patients with data available on both surgical modality and T stage, most patients who presented as T1 and were managed surgically underwent local excision (79.2%). Surgical treatment alone led to high rates of disease-free survival at follow-up (86.8%). A large number of patients presenting with T1 disease were disease free at follow-up (88.6%). Overall survival was 80.3%. Conclusion LVC is most often managed surgically. The extent of surgical resection may be guided by T stage, with smaller tumors resected via local excision and larger tumors via partial or total laryngectomy. Regardless of T stage or therapy, LVC has a good posttreatment prognosis.

Malignant Transformation of a Site of Prior Diabetic Foot Ulceration to Verrucous Carcinoma: A Case Report.

The case of a 62-year-old Caucasian man with type 1 diabetes who developed malignant transformation of an area of prior diabetic foot ulceration (DFU) is reported. He had significant hallux valgus deformity, multiple episodes of healing and breakdown, and eventual transformation to verrucous carcinoma (VC). This case report highlights the malignant transformation of a site of previous DFU to VC, which, to the best of the authors' knowledge, has not yet been described in the literature. There has been little research performed that examines VC in the diabetic population. This case report also highlights the importance of clinical suspicion for malignant transformation as well as the use of subsequent biopsy when necessary.

[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.

Recurrent verrucous carcinoma of the urinary bladder after transurethral resection followed by intravesical mitomycin, and a review of the literature.

Verrucous carcinoma (VC) is a locally invasive, non-metastasising well differentiated variant of squamous cell carcinoma. It is very rare in the urinary bladder and mostly associated with schistosomiasis. It has a characteristic multilobular appearance with small surface projections on contrast cystogram. Owing to its bland cytology, it is a challenging diagnosis. We report a case of VC of the bladder-unrelated to schistosomiasis and involving the prostate-that recurred after transurethral resection of the tumour and prostate followed by six doses of intravesical mitomycin. To the best of our knowledge, no such case has been reported from Pakistan.

Rare tumors of esophageal squamous mucosa.

In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study provides an introduction to these and presents a brief review of the literature, including the diagnostic and prognostic importance of each variant.

Oral verrucous carcinoma: From multifactorial etiology to diverse treatment regimens (Review).

Oral verrucous carcinoma (OVC) is a verrucous variant of oral squamous cell carcinoma (OSCC), which accounts for 2-12% of all oral carcinomas with a 5-year survival rate of only approximately 50%. Enormous effort has been dedicated to this cancer, and the past decades have witnessed significant advances in relevant diagnostic and therapeutic approaches. Currently, there exist three challenges from primary sub-fields of research and clinical practice of the cancer, namely multifactorial etiology, complex molecular mechanism, and deficient treatment. This study reviews the existing literature on the cancer, encompassing its etiology, clinical manifestations and pathology, molecular mechanism, diagnosis and differential diagnosis, and treatment. For improved treatment of OVC, multifactorial etiology analysis, incorporation of effective biomarkers for mechanism illustration, and integration of multidisciplinary modalities are expounded, in an attempt to resolve the challenges and to provide a useful guide for future research in the field.

Radioprotectant and Cytotoxic Effects of Spirulina in Relapsed Verrucous Vulvar Cancer: A Case Report.

CONTEXT: The treatment of relapsed verrucous vulvar cancer (VVC) is difficult. When vulvar cancer relapses, the treatment response is low for second-line treatments. Conversely, toxicity is high. Therefore, scientists need to identify different treatment methods. OBJECTIVES: The case study was intended to examine the benefits of combining treatment with microalgae and metronidazole with radiotherapy to increase the response to treatment. SETTING: The study took place in the Department of Radiation Oncology at Bezmialem Vakif University, in Istanbul, Turkey. PARTICIPANT: The case study involved an 81-y-old female patient whose vulvar tumor was excised and who came to the research team's radiation oncology service for postoperative radiation. She had 2 comorbid disorders: Alzheimer's disease and cardiovascular disease. INTERVENTION: A relapse had occurred in the 15-d postoperative period. Because of the patient's age and comorbid disorders, the research team decided to treat the new tumor only with concurrent radiochemotherapy and a weekly dose of cisplatin that contained chemoradiotherapy, for a total of 25 mg. At the 52.2 Gy dose level, grade 3 radiation skin toxicity occurred in the radiated area, although the research team had obtained an 80% response to the radiochemotherapy. The treatment was interrupted because of toxicity but also due to a deterioration in the patient's general health. Progression of the tumor continued, and the tumor's diameter increased to 7 cm after a 4-mo period. The research team then initiated radiotherapy again, combining it with spirulina in a 750 mg/dose at 2 doses/d and metronidazole in a 500 mg/dose at 3 doses/d, to decrease radiation toxicity and increase radiosensitivity. Radiotherapy was applied at 200 cGy per fraction with a total dose of 2400 cGy, with only 1 anterior local-tumor field. RESULTS: The patient showed a complete response to radiotherapy, and the tumor disappeared at the 2400 cGy radiation dose. No toxicity occurred related to the skin or the woman's general health. Her Karnofsky performance score increased to 90% from 50%, which was the initial score of the second treatment.

Oral verrucous carcinoma complicating a repetitive injury by the dental prosthesis: a case report.

Verrucous carcinoma (VC) is an unusual, well differentiated, and low-grade type of squamous cell carcinoma, characterized by benign histology and cytology but markedly invasive clinical behavior. They have a predilection for squamous mucosae, particularly those of the head and neck region. Many factors have been associated with its pathogenesis, including the presence of previous skin lesions; VC arising from a prosthesis injury is rare. Here we reported a case of VC of oral cavity a particularly very aggressive, arising from prosthesis injury. Regardless of the treatment modality, given new insights into the possible aggressivity of this tumor, radiotherapy associated to chemotherapy may be a more appropriate primary treatment compared with the significant local morbidity associated with surgery.

Oral squamous cell carcinoma associated with proliferative verrucous leukoplakia compared with conventional squamous cell carcinoma--a clinical, histologic and immunohistochemical study.

OBJECTIVE: Proliferative verrucous leukoplakia (PVL), a potentially malignant disorder, often undergoes malignant transformation to oral squamous cell carcinoma. The aim of our study was to document and compare the histologic, immunohistochemical, and clinical features and the survival rates of carcinoma arising in patients with PVL (p-scca) with conventional squamous cell carcinoma (c-scca) in order to determine if p-scca should be categorized as a separate clinical entity. MATERIALS AND METHODS: A retrospective review of 11 patients with PVL, 38 with p-scca tumors and 49 with c-scca tumors: buccal mucosa (n = 28) and gingiva or palate (n = 21). Immunohistochemistry was performed by using antibodies directed against p16, p53, and ki67. RESULTS: P-scca had lower clinical stage (P = .0001), smaller tumor size (P = .0033), no lymph node metastasis (P = .0002) or distant metastasis (P = .05), and better short term (P = .03), but not long term (P = .12) survival. Microscopically, p-scca tumor thickness was significantly less (P = .0001). P-53 overexpression was more common in p-scca (P = .0043) but not ki67 or p16 overexpression. CONCLUSIONS: P-scca, compared with c-scca, presented with significantly better prognostic factors and short-term survival rates and longer duration of disease. Our results suggest that p-scca may represent a distinct entity, which may have practical implications when deciding on treatment. Further studies on a larger cohort of patients are recommended.

Rapid-onset postchemoradiotherapy rhabdomyosarcoma of the maxillofacial region.

Radiation-induced sarcomas of the head and neck are rare and tend to occur decades after treatment. We report a case of rapid-onset postchemoradiotherapy rhabdomyosarcoma of the maxillofacial region and briefly review the literature.