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Background Verrucous carcinoma is a rare mucocutaneous malignancy characterized by slow, relentless growth and a low metastasis rate. Objective Herein we summarize surgical success rates and review newer approaches to the treatment of verrucous carcinomas.Methods & Materials: PubMed electronic searches were performed by B.F. and C.V. using combinations of the following terms: ''verrucous carcinoma,'' ''Ackerman tumor,'' ''Buschke Lowenstein,'' ''epithelioma cuniculatum,'' ''carcinoma cuniculatum,'' ''papillomatosis cutis,'' ''treatment,'' ''therapeutics,'' ''management,'' ''mohs surgery,'' and ''excision.'' A systematic review was conducted on 49 articles in accordance with PRISMA guidelines. Results Surgical management remains first-line therapy. Wide local excision is most commonly utilized, with highly variable margins (0.5-3.0 cm) and recurrence rates (4.6-75.0%). Mohs Micrographic Surgery has also been used, especially for recurrent tumors, with an overall recurrence rate of 12.9%. Conclusion Surgery is the treatment of choice, either by Mohs Micrographic Surgery or wide local excision. However, surgical recurrence rates are high, and tissue-sparing therapies are desirable given the sensitive locations involved. Ultimately, randomized control trials are needed to develop evidence-based guidelines for the management of VCs.

Objective Oral verrucous squamous cell carcinoma or oral verrucous carcinoma (OVC) is a rare verrucous variant of oral squamous cell carcinoma (OSCC), which accounts for 2 to 12% of all oral carcinomas. Oral verrucous hyperplasia (OVH) is clinically similar to OVC and has been proposed to be a precursor lesion of OVC. Etiopathogenesis of both lesions is still inconspicuous. Oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV) have been reported to be associated with some cases of OSCC, and we hypothesized that it may act as a causative agent of these verrucous lesions. This study aimed to investigate frequency of HPV and EBV infections in OVC and OVH. Material and Methods Using polymerase chain reaction (PCR), a total of 35 formalin-fixed paraffin-embedded (FFPE) tissue samples, including 27 OVC samples and 8 OVH samples, were investigated for HPV and EBV infection. HeLa and B95-8 cell lines were used as positive controls of HPV and EBV PCR, respectively. Results All OVC and OVH samples show a positivity to GAPDH, whereas neither HPV nor EBV PCR products was detected in both OVC and OVH samples. Conclusions In summary, our study demonstrated that HPV and EBV are not involved in pathogenesis of OVC and OVH. Other etiologic factors contributing to OVC and OVH need to be further clarified.

Buschke-Lowenstein (B-L) tumors or giant condylomata are large fungating lesions that are caused by human papillomavirus (HPV) and develop in the anogenital region. Although uncommon, physicians and surgeons who treat sexually transmitted diseases or other diseases involving the anogenital area will encounter these patients. The purpose of this study is to review the current literature regarding these lesions. We evaluated every published study in PubMed and Embase from 1925 to 2020, concentrating on the clinical data included in each report, such as presentation and treatment. We also evaluated each work for any definition used and found that there is no accepted definition for these lesions. As such, we provide an inclusive, workable definition. In addition, there are many misconceptions about B-L that continue to be propogated as more case reports are published every year. After evaluating every published case, we refute the fact that these lesions have a high mortality or a high malignancy rate. Furthermore, we refute that these lesions are synonymous with verrucous carcinoma. In addition to a definition, we also propose a simple grading system that we hope can be used to assist in the study and management of these patients moving forward. Although the literature is very heterogenous regarding B-L, they are caused by HPV and are distinct from verrucous carcinoma. Because of the majority of information is based on case reports, the literature concentrates on treatment, but more work is clearly needed to delineate the association with specific HPV types and optimal management of this disease.

Vulvar Verrucous Carcinoma (VVC) is a rare lesion, with few described cases. It has low metastatic potential with high morbidity due to the necessity of extensive resections, although. Previously, VVC was considered a synonym to the Buschke-Lowenstein Tumor (BLT) or Giant Condyloma Acuminatum (GCA). Lichen Sclerosus (LS) is associated with Vulvar Intraepithelial Neoplasia (VIN) and Vulvar Squamous-cell carcinoma (SCC); association with VVC is also described. The case of a 60-year-old menopausal woman is reported; she had chronic itching and an extensive verrucous lesion in vulva, initially diagnosed and treated as condyloma acuminatum; there was recurrence as verrucous carcinoma associated to LS. Excision with margins was performed and clobetasol and imiquimod were used. Patient had complete remission with no further recurrences. Distinction between VVC and BLT can be difficult; current literature considers them different entities. Human papillomavirus (HPV) infection and the presence of LS play a controversial role in these injuries.

Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1–T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1–T3 lesions treated with surgery or radiotherapy (p = 0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

Head and neck reconstruction poses unique challenges in rehabilitating surgical defects in terms of integrity, function, and form. The radial forearm free flap (RFFF) has been widely used for defect coverage, especially in the head and neck area, but its versatility allows it to be used for soft-tissue reconstruction in various parts of the body. The vascular features of the flap are quite constant and reliable. Nevertheless, abnormalities of the forearm vascular tree have been described over the decades. We report a case of intraoral reconstruction after verrucous carcinoma recurrence in a 74-year-old woman with an unusual forearm flap, which we called the median forearm free flap, based on a median branch of the radial artery that was preoperatively detected using handheld Doppler ultrasonography. The distally located skin paddle was predominantly supplied by the aberrant median vessel with its perforators. The flap was thus safely harvested with this atypical pedicle. Successful reconstruction of the intraoral defect was achieved, with an uneventful postoperative course.

Introduction: Verrucous carcinoma is a non-metastatic variant of squamous cell carcinoma. It was first reported by Ackerman in 1948. It is a verrucous exophytic tumor and, although it is a rare lesion, it mainly affects the oral cavity, with slow growth and can be locally invasive. Objective: To report a case and present an observational and retrospective analysis of medical records containing biopsy data from patients diagnosed with oral verrucous carcinoma (OVC) in an oral diagnostic referral service for a period of 24 years. Material and methods: The following data were collected: age, sex, ethnicity, anatomical location and management. Result: Eight cases of OVC were found, all in Caucasian patients (n = 8, 100%), aged between 57 and 102 years. 62% of the injuries affected women. The most affected region was the jugal mucosa (n = 4, 50%). In addition, Smoking patients were not found. In all cases, incisional biopsy was performed and referral to the head and neck surgeon. Conclusion: Caucasian women in the sixth and seventh decades of life were the most affected by OVC. The absence of smoking patients corroborates the literature, which reports that cigarettes appear to be unrelated to this injury. The dentist's role is to recognize the disease early, diagnose it and refer it for medical treatment.

To the Editor: Cutaneous warts are seen in as many as a quarter of immunosuppressed patients. 1 Cell-mediated immunodeficiency, as seen in HIV, is correlated with increased rates of palmoplantar warts. 2 These warts often cause discomfort, and can progress to verrucous carcinoma. As they can be resistant to traditional treatments like cryotherapy, patients must resort to more aggressive and invasive measures like intralesional bleomycin. In this case report, we present an immunocompromised patient with HIV successfully treated for his palmoplantar human papilloma virus (HPV) warts using the nonavalent HPV vaccine (Gardasil 9TM, Merck Inc, Kenilworth, NJ, USA) after only marginal improvement with six treatments of bleomycin.

Meng Jia, Feng-Zeng Li, Qian Ye, Ke-Jun Chen, Sheng Fang Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Sheng FangDepartment of Dermatology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaEmail fangshengderm@163.comBackground: Heat shock proteins (HSPs), a group of heat stress proteins, are characterized by highly conserved properties. Malignant transformation is a cellular stress, and the expression of HSPs may be affected during this process. Heat shock protein 105 (HSP105) is a protective protein that has long been observed in many cancer types, but little attention has been given to cutaneous squamous cell carcinoma (CSCC). As such, the objectives of this study were to observe the expression of HSP105 on CSCC and evaluate its correlation with clinicopathological characteristics.Methods: This retrospective study enrolled 60 patients with CSCC. The patients’ clinical data, including sex, age, tumor location, tumor type, and degree of pathological differentiation, were collected. The expression of HSP105 was measured by Western blot and immunohistochemical staining.Results: HSP105 expression was decreased in CSCC (HSCORE=0.65 (0.30, 1.98)) compared with normal skin (HSCORE=2.20 (1.50, 2.80)) (P< 0.001). These results were consistent with the Western blot analysis. HSP105 immunostaining of Bowen disease (HSCORE=1.28 (1.08, 2.40)) revealed higher expression than in verrucous carcinoma (HSCORE=0.30 (0.23, 0.85)), keratoacanthoma (HSCORE=0.53 (0.29, 0.93)) and acantholytic squamous cell carcinoma (HSCORE=0.53 (0.41, 0.68) (P< 0.01)). Poorly differentiated CSCC showed significantly higher expression of HSP105.Conclusion: Our study reveals for the first time that the expression of HSP105 is decreased in CSCC. We suggest that the molecular mechanisms underlying the differential expression of HSP deserve a more rigorous future study, the results of which might explain its role in carcinogenesis and its potential as a target for selective tumor therapy.Keywords: heat shock protein 105, cutaneous, squamous cell carcinoma, expression

Cutaneous horn is a protuberance constituted by compact keratinous material, with a hard consistence similar to a horn, which occurs more frequently in photoexposed areas. The authors describe a case of cutaneous horn on the glans considered a rare location. Verrucous carcinoma was the histopathological diagnosis of the base of the horn and lichen sclerosis, the precursor lesion.

Verrucous carcinoma is classically considered a variant of squamous cell carcinoma, most commonly occurring in the oral cavity in association with snuff and chewed tobacco. However, the association between verrucous carcinoma of the foot and diabetes is less well known. This study presents a systematic review of all articles containing the search term “verrucous carcinoma” and “diabetic foot ulcer” in the abstract or title that have been published in PubMed before September 2020. The requirement for inclusion in our report were that the patient data had been documented in a case‐related manner and the patient diagnosed with verrucous carcinoma secondary to diabetic foot lesion. Seven descriptions of verrucous carcinoma presenting in patients with diabetic foot ulcers were presented across six case reports, and clinical case descriptions are collected here along with treatment outcomes, where available, and discussion of common mimics of verrucous carcinoma of the foot. Due to treatability and potential for extensive invasion of local structures requiring resection with wide margins, verrucous carcinoma should be carefully considered in the differential diagnosis of a warty foot lesion in the setting of the diabetic foot.

Proliferative verrucous leukoplakia (PVL) is a chronic, aggressive oral mucosal condition with a poor long-term prognosis. It has no specific, defining microscopic characteristics and is a clinical rather than histological diagnosis. PVL may appear clinicopathologically innocuous in its early stages, but there are clues that can alert the histopathologist to a dangerous condition, such as the recognition of hyperkeratoses which, though apparently benign, are inconsistent with well-defined reactive entities. The intermediate stages may show a constellation of histological appearances, and although terminology remains unsatisfactory verrucous hyperplasia, verrucous carcinoma and papillary squamous cell carcinoma are diagnoses which have stood the test of time. The temptation to use unconventional, individual and subjective terms which are descriptions rather than diagnoses should be resisted where possible. The aim of this article is to review the histopathology of PVL, describe its early microscopic indicators and discuss differential diagnoses.

Oral Carcinoma cuniculatum(OCC) is rare variant of squamous cell carcinoma. The histopathological features of this type of carcinoma makes it special in the literature of Pathology. The appearance of deep invading epithelial islands with pool of keratin cores very similar to rabbit burrows gives the term cuniculatum to the carcinoma. Here we present a case of OCC on the lateral surface of the tongue. Early diagnosis of such case is very important to distinguish it distinctly from the other entities of squamous cell carcinoma like verrucous carcinoma. The knowledge of existence of such entity of squamous cell carcinoma occurring in the oral cavity is very important to facilitate correct treatment planning and management.

Summary: An increasing amount of evidence from clinical and experimental studies suggests that biopsies, thought to assist with definitive diagnoses, may aggravate tumor progression. We present a case of fast-growing giant verrucous squamous cell carcinoma, observed two weeks following biopsy. A 38-year-old man presented with a nose tumor that recurred two weeks after a biopsy and debridement to remove a lesion that was thought to be an abscess. Wide excision was performed on the tumor, frozen sectioned; the defect was reconstructed with a two-step forehead flap. The rapid tumor growth observed in this case raises the question of whether biopsies or other interventions may accelerate the growth of malignant tumors. Verrucous squamous cell carcinoma is slow-growing with a predilection for oral and nasal mucosa and rarely metastasizes. The patient presented here is an unusual case, with a tumor rapidly growing within fifteen days. A two-staged paramedian forehead flap is the workhorse of nasal reconstruction. Even though the benefit of doing biopsies overall outweighs the potential side effects, further research is required to determine whether biopsies affect the progression of the tumor. Early differential diagnosis is also crucial, as it may affect the patient's plan of treatment and prognosis. Giant tumors on the facial area may cause a functional and cosmetic disturbance. A two-step forehead flap produces a satisfactory cosmetic appearance for the patient one-year post-procedure.

Verrucous carcinoma, a very well differentiated malignant tumour of the oral cavity which has capacity to invade the underlying tissues very quickly. Very invasive as name suggests, this tumour is warty often misleads the oral physician to come upto a clear cut diagnosis. Encountering a patient of Verrucous carcinoma is often accidental as the awe astonishing fact for this tumour is that the subject would never report the chief complaint in maximum number if cases. Verrucous hyperplasia, a very common variant or antecedent of Verrucous carcinoma has almost similar biological potential as the former. This warty appearing tumour aggravates quickly in patients who have constant habit of tobacco chewing and areca nut chewing, thus its termed as Snuff Dippers Cancer. Verrucous carcinoma (also known as Ackerman tumor) is an uncommon exophytic low-grade well differentiated variant of squamous cell carcinoma. This neoplasm typically involves the oral cavity, larynx, genitalia, skin, and esophagus. Often the ‘bad kind’ of squamous cell carcinoma, the troubling and problematic diagnosis of this cancer makes it a physician dilemma both clinically and histopathologically. Keywords: Verrucous carcinoma, Cancer, Invasive, Ulceroproliferative, Retromolar trigone area.

Summary Hemorrhoidectomy specimens serve as an excellent resource for study of incidental anal pathology. Detection of most incidental findings is quite rare, although diagnosing clinically significant lesions can have profound impact on the clinical follow-ups. While there are many case reports of incidental findings in hemorrhoidectomy specimens, there are few large studies focused on this topic. The aim of this study was to describe the spectrum and likelihood of detecting incidental findings in hemorrhoidectomy specimens. We reviewed all hemorrhoidectomy specimens that showed incidental clinically significant diagnoses over a 16-year period (2003–2019) for this study. Patient's age, sex, and significant clinical history (Human Immunodeficiency Virus (HIV) status, precursor lesions, other malignancy) were recorded from clinical notes. We identified incidental clinically significant findings in 72 of 1612 (4.5%) specimens. We identified 7 incidental malignancies (squamous cell carcinoma, verrucous carcinoma, adenocarcinoma, mixed adenocarcinoma and neuroendocrine carcinoma, poorly differentiated neuroendocrine carcinoma, melanoma), 54 anal intraepithelial neoplasias (AINs), and 11 benign findings (melanocytic lesions, colorectal polyps, angiokeratoma, infectious/inflammatory). Within the AIN group, the detection of low-grade squamous intraepithelial lesions (LSILs) remained steady; there was a recent, sustained rise in detection of high-grade squamous intraepithelial lesions (HSILs), with more cases showing HSILs (2.6%) than only LSILs (0.7%). In 72.2% of patients, the incidental secondary finding represented a first diagnosis for that entity in the anal canal. Thirty seven percent of patients with anal dysplasia in the hemorrhoidectomy specimen had a prior diagnosis of squamous dysplasia in the anogenital tract. Overall, significant incidental findings were detected in 4.5% (72/1612) of hemorrhoidectomies, supporting routine histological examination of these specimens.

Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral mucosal leukoplakia of unknown origin, characterized by high rates of malignant transformation. Different diagnostic criteria, terminologies, and therapeutic approaches have been proposed since the first report in 1985. There remains no general agreement regarding the clinical and histological diagnosis, prevention, and correct management of this disease. This retrospective study investigated 48 patients affected by PVL showing at least one malignant transformation and followed up at 2-month intervals. Twenty-five were female (52.1%) and 23 (47.9%) were male; their median age was 67 years (range 40-93 years). Follow-up ranged from 18 to 240 months. Clinical examination included the use of Lugol's solution to prevent clinical underestimation of the margins and toluidine blue for suspicious areas. Surgical excision by scalpel was the preferred treatment for suspicious lesions, with only five carcinomas surgically removed by diode laser and two by CO2 laser. All specimens were accurately mapped after formalin fixation. Fifteen patients (31.3%; 10 female, five male) developed one oral carcinoma, while 33 (68.7%) developed two or more primary tumours (range 3-12). Only four patients (8.3%), who developed between 2 and 8 oral squamous cell carcinomas (OSCCs), died of tumour-related causes. The pre-surgical clinical workup, subsequent surgical treatment, and follow-up are key to success for patients affected by PVL with malignant transformation into stage 1 OSCC and/or verrucous carcinoma, leading to a high overall survival rate.

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

This paper seeks to present surgical procedures, results and complications of treatment of verrucous carcinoma (VC) of the vulva treated at the clinics for gynecology and obstetrics within the Faculty of Medicine, University of Novi Sad (Serbia), as well as a literature review of surgical treatment of VC. During a period of 15 years (2005?2019), we performed 76 surgeries of vulvar cancer, nine (11.8%) due to VC of the vulva. In surgical treatment of vulva VC, we performed complete surgical excision of the tumor (three), complete surgical excision of the tumor with defect coverage using VY fasciocutaneous skin flap (two), simplex vulvectomy (two), radical hemivulvectomy (one), and radical vulvectomy (one). We came across two main complications (22.2%): suture bleeding within 12 hours after excision in one patient (11.1%) and lower extremity lymphoedema after inguinofemoral lymphadenectomy with ligation of the great saphenous vein in one patient (11.1%). Out of the total number of nine treated patients, survival rate was 88.8% (eight patients) with death rate of 11.1% (one patient) within 12 months after surgery. In three patients (33.3%), the disease returned after surgery: one residual tumor after surgery, one relapse on the other side one year after surgery, one newly developed invasive squamous cell carcinoma 10 years after primary surgery.

We report two cases of histologically documented pseudoepitheliomatous keratotic and micaceous balanitis in middle-aged male patients, which showed positivity for low-risk serotype human papillomavirus DNA. To our knowledge, only one other case has been documented. Further immunohistochemical proliferative markers were performed and compared to literature findings in penile epithelial proliferations. Evolution to invasive verrucous carcinoma has been associated with absence of HPV DNA. Thus, if confirmed by further studies, HPV testing should be included in pseudoepitheliomatous keratotic and micaceous balanitis assessment to address prognosis, and management.

Introduction: Verrucous lesions present as cauliflower like, slowly growing masses, which may be single, multiple or diffuse involving the broad areas of skin or mucosal surfaces. Clinically these lesions are diagnostic challenges. Histopathology remains the gold standard in diagnosing this diverse group of verrucous lesions. The aim of this study was to understand the microscopy of clinically verrucous lesions. Material and Methods: This is a retrospective data of clinically verrucous lesions over the past five years. Clinical details were obtained from the archives and diagnosis was noted from the pathology records. A total of 116 clinically verrucous lesions were included. Results: Majority of the cases were Verruca vulgaris (37 cases), followed by 33 cases of Seborrheic keratosis. There were 12 cases of verrucous carcinoma, seven cases of tuberculosis verrucosa cutis, six cases of verrucous nevus and one case of verrucous hemangioma. The other cases were of varied histology, inspite of clinically verrucous appearance. All the cases were diagnosed purely based on histopathology findings, which show characteristic morphological features, which help the pathologist in the correct diagnosis. Conclusions: Histopathologic confirmation helps in alleviating the anxiety of the patients and helps us to arrive at a correct diagnosis. Keywords: Carcinoma, Papillomatosis, Seborrheic keratosis, Verrucous, Wart.

Background: Verneuil’s disease is a rare suppurative pathology of apocrine glands and pilosebaceous system of the inguinal-pelvis and perianal region with a multifactorial aetiology. The disease produces skin fistulas, draining a serum-purulent material on the skin, and finally with spontaneous healing. Verneuil’s disease can be complicated by recurrence, and unfortunately, by squamous carcinoma. We have found in literature, just 2 cases of Hidradenitis Suppurativa, complicated by Verrucous Carcinoma. Main Observation: we describe a patient F, 34-year-old, comes to our observation at 4th gestational month, with suppurative sinus pilonidalis diagnosis and with the absolute indication of the gynaecologist to the abortion. We decided to continue the pregnancy. The patient gives birth with C. to 9 months; the new-born baby was perfectly healthy and after the maternal milk analysis, the baby also nursed for about 2 months. Finally, we decided to perform a wide excision biopsy and after a controversial histology (first Warty Carcinoma, then after a “second view” Suppurative Hidradenitis), we started a series of medical treatments, including biological therapy with Infliximab, but unfortunately with fleeting results. The patient did not answer substantially. Therefore, the last chance appears a combined demolitive and plastic surgical treatment. The histology described a Verrucous squamous cell carcinoma maximum diameter of 38 x 26 cm, with lateral deep margins free of neoplastic involvement. Conclusion: This very advanced clinical behaviour of the Hidradenitis Suppurativa can present in pregnancy, therefore, motivating the interruption of the same one. Our experience contributes to underlining the possibility to bring to term the pregnancy. This case report shows how the hormonal activity can anyway influence the development of the hidradenitis and an interesting hypothesis could consider the hormonal activity of the pregnancy and the HPV promoting gene regulation (RB) from inflammatory pathology to neoplastic pathology in VC like a model to study.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words “verruciform” and “verrucous” were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.

Background Potentially malignant lesions of the gingiva may frequently present as well-demarcated white lesions confined to the marginal gingiva. These lesions often become thick and verrucoid and spread along the marginal gingiva to encircle the tooth. Some cases of marginal gingival leukoplakia, over time, progress to extensively involve the gingiva fulfilling the criteria for proliferative verrucous leukoplakia (PVL). The objective of this study is to raise awareness of this pattern of leukoplakia by reporting a series of cases of marginal gingival leukoplakia. Methods An IRB approved retrospective search of UF and UNMC oral biopsy services was performed for all gingival biopsies. Inclusion criteria included cases (a) exhibiting marginal gingival leukoplakia, and (b) with accompanying clinical images. Results A total of 30 cases of marginal gingival leukoplakia were included. All cases presented as well-demarcated leukoplakias, either on the buccal or lingual gingival margin, or circumferentially forming a "ring around the collar" of single or multiple teeth. Eight patients had recurrent lesions and twelve had multifocal involvement. Six of the 12 patients with multifocal involvement presented with a "ring around the collar". The histopathologic diagnoses were representative of benign lesions in 7 cases, premalignant in 13, and malignant or suggestive of malignancy in 10 cases. Seven patients had carcinoma at the time of first biopsy, whereas 6 cases showed progression at time of follow-up. Conclusion This study aims to raise awareness that marginal gingival leukoplakia may represent potentially malignant lesions, and if circumferential and/or thick, may be the first manifestation of PVL. This article is protected by copyright. All rights reserved.

Verrucous carcinomas are a rare variant of squamous cell carcinoma. Vulval verrucous carcinoma comprises only 1% of vulval malignancies. This case report discusses the successful management of aggressive recurrent vulval verrucous carcinoma with acitretin, an oral synthetic retinoid used to manage severe psoriasis, after multiple surgical interventions and radiotherapy had failed. This is the first reported case in which verrucous carcinoma had recurred in a musculocutaneous graft. To manage the recurrence, the patient underwent radiotherapy, which did not resolve the condition. The patient was then administered acitretin 25 mg once daily, which successfully resolved the condition, and the patient has been symptom free for 6 months. This report aims to propose the use of acitretin as a management option for recurrent verrucous carcinomas.

Enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 that catalyzes trimethylation of H3K27 (H3K27me3), has been shown to promote tumor development and progression. Expression of EZH2 is associated with cell cycle regulation and cell proliferation in various neoplasms. Oral verrucous hyperplasia (OVH) and Oral verrucous carcinoma (OVC) are rare entities and share several clinical and histopathologic features. Problems distinguishing these lesions are added by a lack of adjacent normal tissue of the biopsy samples and poorly oriented tissue sections. The aim of this study was to investigate the expression of EZH2 and H3K27me3 in OVH and OVC and comparing the expression with normal oral mucosa and oral squamous cell carcinoma (OSCC). Seventy-eight samples, including 25 cases of OVC, 8 cases of OVH, 35 cases of OSCC and 10 cases of normal oral mucosa, were retrieved and submitted for immunohistochemical staining. The results demonstrated that the mean labeling indices (LIs) of EZH2 and H3K27me3 expression were highest in OSCC, followed by the OVC, OVH, and normal mucosa. Statistical differences in EZH2 LI were observed among these lesions whereas H3K27me3 LI was significantly different among OSCC, OVH and normal mucosa. EZH2 LI was found to have a sensitivity of 72.00% and specificity of 87.50% in distinguishing OVH from OVC, and a sensitivity of 57.14% and specificity of 84.00% in distinguishing OVC from OSCC. A positive correlation between EZH2 and H3K27me3 expression was significantly found in OVC but not in OVH and OSCC. These findings highlight the involvement of epigenetic regulation by EZH2-mediated H3K27me3 in the pathogenesis of OVH and OVC, and EZH2 expression indicates disease progression of these verrucous lesions. Diagnostic test analysis further suggests that EZH2 may be used as an additional test for differentiating OVH from OVC in questionable cases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12105-020-01209-0) contains supplementary material, which is available to authorized users.

Objectives: This cross-sectional study was designed to determine the prevalence of potentially malignant lesions and oral cancer among smokers. Methods: The current observational cross-sectional study was conducted in the Clinics of Oral Medicine and Periodontology department and the Diagnostic center, Faculty of Dentistry - Cairo University in Cairo- Egypt. Smokers from all age groups and both genders who agreed to sign the informed consent were included in the study. Detailed history of tobacco consumption, different forms of tobacco use, drugs, alcohol consumption and quitting trials were recorded and followed by clinical examination and histopathological assessment of suspicious lesions. Results: Among the 1664 enrolled participants, 3.54% had leukoplakia, 2.88% had oral lichen planus, 1.5% had oral squamous cell carcinoma and 0.12% had verrucous carcinoma. Conclusion: leukoplakia was the most frequently encountered lesion followed by oral lichen planus. Dentists must be aware of the risk of smoking on oral mucosa and the early signs of developing premalignant or malignant lesions.

Verruka vulgaris HPV ile ilişkili sık görülen bir deri lezyonudur. Larinkste nadir görülür. Larinkste görülen verruka vulgaris, deride görülen verruka vulgaris ile histolojik olarak benzer özelliklere sahiptir. Benign bir lezyondur ve malign bir lezyon olan verruköz karsinomdan ayrımı tedavi açısından önem taşımaktadır. Biz burada ses kısıklığı şikâyeti ile gelen 59 yaşındaki erkek hastayı sunduk. Lezyon cerrahi olarak çıkarıldıktan sonra patoloji sonucu verruka vulgaris olarak tespit edildi.

Background Early detection of dysplastic changes within oral potentially malignant disorders is the mainstay to prevent oral cancer. Ki-67 is one of the most useful antigens in this purpose. Aims The study aims were to recognize and mutually compare the proliferative status of idiopathic oral leukoplakia (OL) patches, which presented through different forms of dysplasia and carcinoma. Settings and Design In 4 years of observation, cumulatively 140 OL lesions were included for examination. The wholesome Ki-67 labeling scores in each of the subgroups were calculated. Subjects and Methods The World Health Organization recommended histopathological classification was used to categorize the dysplastic and malignant lesions. Paraffin-embedded tissue sections were processed for Ki-67 immunostaining. The labeling indices (LIs) were quantified semiquantitatively at the site of maximal reactive cells on tissue sections. Statistical Analysis The statistical comparison was performed by means of the SPSS software (Version 16.0 SPSS Inc.). A p-value < 0.05 was considered as the benchmark for statistical significance. Results A steady and significant increment in Ki-67 expression was discovered from dysplastic to malignant OL patches compared with normal mucosa. The labeling differences were significant between normal mucosa and mild dysplasia, as well as between mild, moderate, and severe dysplasia. However, the expression did not differ significantly with the severity of oral cancers. Conclusions Ki-67 is a useful molecular marker of carcinogenesis in OL. It also serves worthwhile in separating marginally dysplastic lesions, such as mild dysplasia or verrucous carcinoma from their benign epigones.

OBJECTIVES To investigate the clinical characteristics of patients with penile cancer in Japan using the nationwide hospital-based cancer registry database. METHODS Using hospital-based cancer registry data, we described the distribution of age, pathology, tumor-node-metastases classification, and first-course treatment in patients treated between 2012 and 2015. We compared the patterns of first-line treatment between elderly and non-elderly patients. RESULTS A total of 1012 patients were diagnosed with squamous cell carcinoma among 1773 patients with penile tumors who registered under topography code C60. The median age at diagnosis was 74 years, and 85.9% of patients were aged >60 years. The most common pathology was usual-type squamous cell carcinoma (91.9%), followed by verrucous carcinoma (5.0%), sarcomatoid carcinoma (1.1%), papillary carcinoma (0.7%), basaloid carcinoma (0.6%), adenosquamous carcinoma (0.4%), warty carcinoma (0.2%) and mixed carcinoma (0.1%). A total of 61.3% of patients were diagnosed with localized disease. In contrast, the proportions of patients with lymph node and distant metastases were 27.5% and 2.1% at diagnosis, respectively. The proportion of patients who were treated with chemotherapy as the first-course treatment was significantly lower among elderly patients (≥80 years) with clinical stage III (27.6% vs 7.1%, P = 0.0312) and clinical stage IV (53.2% vs 14.3%, P = 0.0086). CONCLUSIONS Most penile cancer patients in Japan are diagnosed with usual-type squamous cell carcinoma, and those with human papilloma virus-related squamous cell carcinomas are

Background Crohn’s disease (CD) is a chronic inflammatory disorder which leads to anorectal fistulas. In rare cases, patients develop anal squamous cell carcinoma (ASCC) within these lesions. There is limited literature regarding ASCC in patients with CD. Here, we report on a unique case of advanced verrucous carcinoma (VC), a rare variant of squamous cell carcinoma, developing on the grounds of extensive chronic anorectal fistulas in CD. Methods and results A 54-year-old male patient with a 20-year history of CD presented with a large inflammatory tumor at the perineal region with multiple discharging perianal fistulas. Histopathological analysis of the perineal mass revealed a VC. Subsequent surgery with radical tumor resection and terminal colostomy resulted in a large perineal cavity and a partially exposed sacrum. The defect extended to a total of 35 × 25 × 25 cm. Reconstruction was achieved through a two-step approach. A first surgical step established an arteriovenous (AV) loop in the upper thigh. Subsequently, a free latissimus dorsi (LD) myocutaneous flap was harvested and anastomosed with the AV loop, allowing for satisfactory closure of the defect and reconstruction of the perianal and perineal region. Conclusion Radical surgical excision with negative margins is the therapy of choice for VC. This case report demonstrates a curative treatment option with special emphasis on the reconstructive possibilities of a unique case of extended perianal and perineal VC associated with chronic anorectal fistulas in CD.

Biological tissues (including oral mucosa) can absorb and re-emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as "autofluorescence" (AF). Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope® system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer.

Cystic squamous cell carcinomas (SCCs) of the jaws, including carcinoma cuniculatum, are rare, slow growing, and relentlessly invasive. The aim of this article is to present 12 cases, 4 of which were designated as carcinoma cuniculatum on the basis of deeply endophytic, anastomosing channels of cystic stratified squamous epithelium and keratin microabscesses. The other 8 were also cystic, but more heterogeneous morphologically and were diagnosed as well differentiated SCCs. Six patients were female, 6 were male (mean age = 74.0 years, range = 50-94 years). Six tumors affected the mandible, 6 the maxillary alveolus with or without extension into the hard palate. All patients underwent primary resection with neck dissection and were staged as T4a N0 M0. In 4 patients, diagnosis was delayed as a result of superficial biopsies and/or confusing histopathology. Cystic SCCs of the jaws can be difficult to diagnose and clinicoradiological correlation is essential. Long-term follow-up is mandatory.

Background Verrucous carcinoma is an extremely rare form of cancer in the esophagus. Case presentation A 56-year-old woman presented with dysphagia in 2007. Endoscopic examination revealed an irregular protruding circumferential erosion in the lower thoracic esophagus, but because pathological examination of the biopsy specimen showed no evidence of malignancy, the status of the erosion was followed up by an upper gastrointestinal endoscopic examination every 3 months. A year later, polypoid lesions and fungal infection were observed in the eroded area, but no evidence of malignancy was detected in the biopsy specimen at the time. Eighteen months later, the polypoid lesions had increased in size, and the biopsy specimen was diagnosed as highly suspicious of well-differentiated squamous cell carcinoma. Because the patient’s condition deteriorated due to worsening of the dysphagia and weight loss, we performed a thoracoscopic esophagectomy with lymph node dissection and reconstructed the alimentary tract with a gastric tube via the posterior mediastinal route. Macroscopic examination of the resected specimen showed a white protruding lesion with an irregular surface, and histopathological examination led to a diagnosis of esophageal verrucous carcinoma without lymph node metastasis. No signs of recurrence have been observed in the 8 years since surgery. Conclusion We have reported a long-term follow-up case of verrucous carcinoma of the esophagus that was difficult to diagnose before surgery.

Background: Squamous cell carcinoma antigen (SCCA) is used as a prognostic marker for recurrence of squamous cell carcinoma in various sites, including head and neck. Studies suggest that its high serum levels are correlated to some clinical features, such as nodal metastasis. However, it is still unknown if high SCCA in patients with SCCA tissue expression in tumor cells are related to peripheral T-lymphocytes. Therefore, we did this study to evaluate SCCA expression in squamous cell carcinoma and verrucous carcinoma and to compare it with normal oral mucosa, also investigating the correlation between serum-based and tissue-based antigen levels. Methodology: In this study, the immunohistochemistry (IHC) technique was used to determine the SCCA1 expression pattern in 81 specimens divided into 3 groups, including oral squamous cell carcinoma, verrucous carcinoma, and normal oral mucosa. Serum-based and tissue-based antigen levels of 20 oral squamous cell carcinoma cases were compared by the western blot assay. SCCA expression was also evaluated and compared in both tumor cells and peripheral T-lymphocytes by the immunofluorescence assay. Results: Our results showed that the SCCA levels in SCC specimens were significantly lower than in verrucous carcinoma and normal and hyperplastic oral mucosa specimens. We found no correlation between the IHC expression of SCCA and serum levels. SCCA was well expressed in both tumor cells and peripheral T-lymphocytes. Conclusion: Decreasing SCCA in SCC specimens suggested that SCC tumor cells may affect more than the serum levels of SCCA in some patients. In addition, expression of SCCA in peripheral T-lymphocytes showed that both tumor cells and T-lymphocytes may cause serum SCCA.

Oral cancer is a significant cause of morbidity and mortality worldwide. In this article we present two cases of potentially innocuous looking lesions, initially thought to be traumatic in origin, but later diagnosed as cancer. The first patient presented with a persistent laceration thought to be caused by an accidental shaving injury, which was subsequently diagnosed as squamous cell carcinoma. The second patient presented with a hyperplastic mucosal lesion, suspected as forming due to denture-clasp irritation, which was subsequently diagnosed as proliferative verrucous carcinoma. The importance of early detection and palpation of suspicious lesions is emphasised in this article.

Scrotal verrucous carcinoma is a rare entity. It is rarely metastatic especially in lymph nodes. Imaging is important for local extension in order to guide the surgical procedure. The diagnostic is histological. The treatment is based on surgical excision. The prognosis is relatively good, but local recurrences are frequent. We report a case of scrotal verrucous carcinoma in a 49-year-old man evolving for 1 year.

Purpose This study aims to provide an overview of the literature on carcinoma arising from giant perianal condyloma acuminatum. Methods We present a new case of squamous cell carcinoma arising from giant perianal condyloma acuminatum. We also conducted a systematic search of the medical literature using PubMed, Medline, Google, and Google Scholar related to carcinoma arising from giant perianal condyloma acuminatum. The following search terms were used in various combinations: condyloma acuminatum, giant condyloma acuminatum, Buschke-Lowenstein tumor, squamous cell carcinoma, and verrucous carcinoma. The search included articles published before in the English language November 2020. Results A total of 55 article concerning 97 patients with carcinoma (squamous cell carcinoma, verrucous carcinoma, basaloid cell carcinoma, carcinoma insitu) arising from giant perianal condyloma acuminatum meeting the aforementioned criteria were included. The patients were aged from 24 to 82 years (median: 49.6, IQR: 21); 20 were female (median age: 52.5, IQR: 20.5), and 75 were male (median age: 53, IQR: 17.5). The gender data of the remaining two patients could not be obtained. The histopathological features of tumors arising from giant condyloma acuminatum are as follows: squamous cell carcinoma (n = 56), squamous cell carcinoma in situ (n = 16), verrucous carcinoma (n = 19) and basaloid cell carcinoma (n = 1), squamous cell carcinoma + verrucous carcinoma (n = 1), squamous cell carcinoma + squamous cell carcinoma in situ (n = 1), squamous cell carcinoma + basaloid cell carcinoma (n = 1) and malignant behavior (n = 2). Conclusion Giant condyloma acuminatum is a rare variant of anogenital warts. It is known that this tumor, which is mostly thought to be benign, has a high potential for local recurrence and transformation into invasive cancer. Therefore, it is vital that the tumor is resected with clean surgical margins, even if it looks benign, and that aggressive treatment options are not avoided when necessary.

A transgender female in her 40s with history of HIV and testicular cancer status post-genital X-irradiation presented with a perianal mass and pruritic rash across her chest. Physical examination revealed a bulky, verrucous tumor protruding outward from the anus involving the medial buttocks. Examination of the chest and arms showed numerous guttate, pink, flat-topped papules coalescing into plaques. Clinically and histologically the lesions were consistent with Buschke-Lowenstein condyloma (BLC) and acquired epidermodysplasia verruciformis (AEDV). Buschke-Lowenstein condyloma incisional biopsy tested negative for common low- and high-risk human papillomavirus (HPV) subtypes, including 6, 11, 16, and 18, possibly implicating beta HPV subtype or a less common pathogenic subtype. The patient underwent abdominoperineal resection of the BLC, which tested positive for low-risk HPV subtypes, suggesting the possibility of multiple implicated HPV subtypes in the same tumor. This case demonstrates a possible role of beta HPV or rarer HPV subtypes in the pathogenesis of verrucous carcinoma, particularly in the setting of immunosuppression.

Simple Summary Proliferative verrucous leukoplakia (PVL) was recognized in 2005 by the World Health Organization as a rare subtype of true oral leukoplakia, with unknown etiology. Since its first description in 1985, several diagnostic criteria have been proposed over the years. The aim of this systematic review is to investigate the percentage of patients diagnosed with proliferative verrucous leukoplakia who progressed to oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC). Abstract Aim: The aim of the present systematic review was to investigate the risk of malignant transformation of proliferative verrucous leukoplakia (PVL). Materials and Methods: the search was carried out using a combination of terms (leukoplakia OR leucoplakia) AND (multifocal OR proliferative) on the following databases: PubMed, Scopus, Web of Science (WOS Core Collection), Cochrane Library, selecting only articles published since 1985 and in the English language. Demographic, disease-related, and follow-up data extracted from the studies included in the qualitative synthesis were combined. Weighted means ± standard deviations were calculated for continuous variables, while categorical variables were reported as frequencies and percentages. Dichotomous outcomes were expressed as odd ratios (ORs) with 95% confidence intervals (CIs). Odd ratios for individual studies were combined using a random-effects meta-analysis, conducted using Review Manager 5.4 Software (Cochrane Community, Oxford, England). Results: twenty-two articles were included, with a total of 699 PVL patients, undergoing a mean follow-up of 7.2 years. Sixty-six percent of patients were females, with a mean age of 70.2 years, and 33.3% were males, with a mean age of 59.6 years. Most patients were non-smokers and non-alcohol users, and the gingiva/alveolar ridge mucosa was the most involved anatomical site by both PVL appearance and malignant transformation. A total of 320 PVL patients developed oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC) because of malignant transformation of PVL lesions (45.8%). A statistically significant 3.8-fold higher risk of progression to conventional OSCC was found compared to OVC in PVL patients, with women being 1.7 times more likely to develop oral cancer than men, as a consequence of PVL progression. Moreover, a statistically significant higher likelihood of developing conventional OSCC in female PVL patients than in males was found. In 46.5% of patients with PVL malignant transformation, multiple carcinomas, in different oral sites, occurred during follow-up. Conclusions: PVL is an aggressive lesion, which, in a high percentage of cases (almost 50%), undergoes malignant transformation, mainly toward OSCC. The female gender is most affected, especially in the elderly, with a negative history for alcohol and tobacco consumption.

Erythroplasia of Queyrat is a rare squamous cell carcinoma that occurs in middle-aged, uncircumcised men, and usually involves the glans. The cause of this disease is still unclear, although it may be related to a redundant prepuce, phimosis, and human papillomavirus infection, and may develop into squamous cell carcinoma. A case of Erythroplasia of Queyrat, complicated by verrucous carcinoma, is reported in this paper.